Evidence for control of mercury accumulation rates in Canadian High Arctic lake sediments by variations of aquatic primary productivity.

PubMed

Outridge, P M; Sanei, L H; Stern, G A; Hamilton, P B; Goodarzi, F

2007-08-01

Climate warming in the 20th Century has had profound effects on the limnology of High Arctic lakes, including substantial increases in autochthonous primary productivity (APP). Here, we report organic carbon and Hg core profiles from two lakes which support the hypothesis that 20th Century increases in sedimentary Hg at these latitudes were largely driven by APP increases, via Hg scavenging by algae and/or suspended detrital algal matter. Hydrocarbons quantitatively released by thermal cracking of algal-derived organic matter ("S2" carbon) were used to reconstruct past APP. Variation of S2 flux accounted for 87-91% of the variance in total Hg flux in the study lakes since 1854. Mercury and S2 carbon were also associated during the pre-Industrial Period, co-varying by as much as 30% during past warm/cool periods. As a test of the hypothesis, predicted values for 20th Century [Hg] were derived from pre-1900 Hg-S2 relationships. Measured 20th Century [Hg] was on average only 6-11% higher than that predicted in one lake, and 33% higher in the other. S2-normalization of [Hg] in the latter lake suggested that 78% of the average increase in 20th Century [Hg] could be explained by scavenging. These findings suggest that the atmospheric contribution of long-range anthropogenic Hg to High Arctic lakes may have been overestimated by several-fold because of this climate-driven process, and was responsible for no more than 22% of the 20th Century [Hg] increase in the study lakes.

Amyloid precursor protein-induced axonopathies are independent of amyloid-beta peptides.

PubMed

Stokin, Gorazd B; Almenar-Queralt, Angels; Gunawardena, Shermali; Rodrigues, Elizabeth M; Falzone, Tomás; Kim, Jungsu; Lillo, Concepción; Mount, Stephanie L; Roberts, Elizabeth A; McGowan, Eileen; Williams, David S; Goldstein, Lawrence S B

2008-11-15

Overexpression of amyloid precursor protein (APP), as well as mutations in the APP and presenilin genes, causes rare forms of Alzheimer's disease (AD). These genetic changes have been proposed to cause AD by elevating levels of amyloid-beta peptides (Abeta), which are thought to be neurotoxic. Since overexpression of APP also causes defects in axonal transport, we tested whether defects in axonal transport were the result of Abeta poisoning of the axonal transport machinery. Because directly varying APP levels also alters APP domains in addition to Abeta, we perturbed Abeta generation selectively by combining APP transgenes in Drosophila and mice with presenilin-1 (PS1) transgenes harboring mutations that cause familial AD (FAD). We found that combining FAD mutant PS1 with FAD mutant APP increased Abeta42/Abeta40 ratios and enhanced amyloid deposition as previously reported. Surprisingly, however, this combination suppressed rather than increased APP-induced axonal transport defects in both Drosophila and mice. In addition, neuronal apoptosis induced by expression of FAD mutant human APP in Drosophila was suppressed by co-expressing FAD mutant PS1. We also observed that directly elevating Abeta with fusions to the Familial British and Danish Dementia-related BRI protein did not enhance axonal transport phenotypes in APP transgenic mice. Finally, we observed that perturbing Abeta ratios in the mouse by combining FAD mutant PS1 with FAD mutant APP did not enhance APP-induced behavioral defects. A potential mechanism to explain these findings was suggested by direct analysis of axonal transport in the mouse, which revealed that axonal transport or entry of APP into axons is reduced by FAD mutant PS1. Thus, we suggest that APP-induced axonal defects are not caused by Abeta.

Patterns and severity of vascular amyloid in Alzheimer's disease associated with duplications and missense mutations in APP gene, Down syndrome and sporadic Alzheimer's disease.

PubMed

Mann, David M A; Davidson, Yvonne S; Robinson, Andrew C; Allen, Nancy; Hashimoto, Tadafumi; Richardson, Anna; Jones, Matthew; Snowden, Julie S; Pendleton, Neil; Potier, Marie-Claude; Laquerrière, Annie; Prasher, Vee; Iwatsubo, Takeshi; Strydom, Andre

2018-05-16

In this study, we have compared the severity of amyloid plaque formation and cerebral amyloid angiopathy (CAA), and the subtype pattern of CAA pathology itself, between APP genetic causes of AD (APPdup, APP mutations), older individuals with Down syndrome (DS) showing the pathology of Alzheimer's disease (AD) and individuals with sporadic (early and late onset) AD (sEOAD and sLOAD, respectively). The aim of this was to elucidate important group differences and to provide mechanistic insights related to clinical and neuropathological phenotypes. Since lipid and cholesterol metabolism is implicated in AD as well as vascular disease, we additionally aimed to explore the role of APOE genotype in CAA severity and subtypes. Plaque formation was greater in DS and missense APP mutations than in APPdup, sEOAD and sLOAD cases. Conversely, CAA was more severe in APPdup and missense APP mutations, and in DS, compared to sEOAD and sLOAD. When stratified by CAA subtype from 1 to 4, there were no differences in plaque scores between the groups, though in patients with APPdup, APP mutations and sEOAD, types 2 and 3 CAA were more common than type 1. Conversely, in DS, sLOAD and controls, type 1 CAA was more common than types 2 and 3. APOE ε4 allele frequency was greater in sEOAD and sLOAD compared to APPdup, missense APP mutations, DS and controls, and varied between each of the CAA phenotypes with APOE ε4 homozygosity being more commonly associated with type 3 CAA than types 1 and 2 CAA in sLOAD and sEOAD. The differing patterns in CAA within individuals of each group could be a reflection of variations in the efficiency of perivascular drainage, this being less effective in types 2 and 3 CAA leading to a greater burden of CAA in parenchymal arteries and capillaries. Alternatively, as suggested by immunostaining using carboxy-terminal specific antibodies, it may relate to the relative tissue burdens of the two major forms of Aβ, with higher levels of Aβ 40 promoting a more 'aggressive' form of CAA, and higher levels of Aβ 42(3) favouring a greater plaque burden. Possession of APOE ε4 allele, especially ε4 homozygosity, favours development of CAA generally, and as type 3 particularly, in sEOAD and sLOAD.

Different Hippocampus Functional Connectivity Patterns in Healthy Young Adults with Mutations of APP/Presenilin-1/2 and APOEε4.

PubMed

Zheng, Li Juan; Su, Yun Yan; Wang, Yun Fei; Schoepf, U Joseph; Varga-Szemes, Akos; Pannell, Jonathan; Liang, Xue; Zheng, Gang; Lu, Guang Ming; Yang, Gui Fen; Zhang, Long Jiang

2018-04-01

This study aims to explore the hippocampus-based functional connectivity patterns in young, healthy APP and/or presenilin-1/2 mutation carriers and APOE ε4 subjects. Seventy-eight healthy young adults (33 male, mean age 24.0 ± 2.2 years; 18 APP and/or presenilin1/2 mutation carriers [APP/presenilin-1/2 group], 30 APOE ε4 subjects [APOE ε4 group], and 30 subjects without the above-mentioned genes [control group]) underwent resting-state functional MR imaging and neuropsychological assessments. Bilateral hippocampus functional connectivity patterns were compared among three groups. The brain regions with statistical differences were then extracted, and correlation analyses were performed between Z values of the brain regions and neuropsychological results. Compared with control group, both APOE ε4 group and APP/presenilin-1/2 group showed increased functional connectivity in medial prefrontal cortex and precuneus for the seeds of bilateral hippocampi. The APOE ε4 group displayed increased functional connectivity from bilateral hippocampi to the left middle temporal gyrus compared with the control group. Moreover, compared with the APP/presenilin-1/2 group, the APOE ε4 group also had markedly increased functional connectivity in right hippocampus-left middle temporal gyrus. The Z values of right hippocampus-left middle temporal gyrus correlated with various neuropsychological results across all the subjects, as well as in APOE ε4 group. Young healthy adults carrying APOE ε4 and APP/presenilin-1/2 displayed different hippocampus functional connectivity patterns, which may underlie the discrepant mechanisms of gene-modulated cognitive dysfunction in Alzheimer's disease.

APP transgenic mice for modelling behavioral and psychological symptoms of dementia (BPSD)

PubMed Central

Lalonde, R.; Fukuchi, K.; Strazielle, C.

2012-01-01

The discovery of gene mutations responsible for autosomal dominant Alzheimer's disease has enabled researchers to reproduce in transgenic mice several hallmarks of this disorder, notably Aβ accumulation, though in most cases without neurofibrillary tangles. Mice expressing mutated and wild-type APP as well as C-terminal fragments of APP exhibit variations in exploratory activity reminiscent of behavioral and psychological symptoms of Alzeimer dementia (BPSD). In particular, open-field, spontaneous alternation, and elevated plus-maze tasks as well as aggression are modified in several APP transgenic mice relative to non-transgenic controls. However, depending on the precise murine models, changes in open-field and elevated plus-maze exploration occur in either direction, either increased or decreased relative to controls. It remains to be determined which neurotransmitter changes are responsible for this variability, in particular with respect to GABA, 5HT, and dopamine. PMID:22373961

Glycines from the APP GXXXG/GXXXA Transmembrane Motifs Promote Formation of Pathogenic Aβ Oligomers in Cells

PubMed Central

Decock, Marie; Stanga, Serena; Octave, Jean-Noël; Dewachter, Ilse; Smith, Steven O.; Constantinescu, Stefan N.; Kienlen-Campard, Pascal

2016-01-01

Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by progressive cognitive decline leading to dementia. The amyloid precursor protein (APP) is a ubiquitous type I transmembrane (TM) protein sequentially processed to generate the β-amyloid peptide (Aβ), the major constituent of senile plaques that are typical AD lesions. There is a growing body of evidence that soluble Aβ oligomers correlate with clinical symptoms associated with the disease. The Aβ sequence begins in the extracellular juxtamembrane region of APP and includes roughly half of the TM domain. This region contains GXXXG and GXXXA motifs, which are critical for both TM protein interactions and fibrillogenic properties of peptides derived from TM α-helices. Glycine-to-leucine mutations of these motifs were previously shown to affect APP processing and Aβ production in cells. However, the detailed contribution of these motifs to APP dimerization, their relation to processing, and the conformational changes they can induce within Aβ species remains undefined. Here, we describe highly resistant Aβ42 oligomers that are produced in cellular membrane compartments. They are formed in cells by processing of the APP amyloidogenic C-terminal fragment (C99), or by direct expression of a peptide corresponding to Aβ42, but not to Aβ40. By a point-mutation approach, we demonstrate that glycine-to-leucine mutations in the G29XXXG33 and G38XXXA42 motifs dramatically affect the Aβ oligomerization process. G33 and G38 in these motifs are specifically involved in Aβ oligomerization; the G33L mutation strongly promotes oligomerization, while G38L blocks it with a dominant effect on G33 residue modification. Finally, we report that the secreted Aβ42 oligomers display pathological properties consistent with their suggested role in AD, but do not induce toxicity in survival assays with neuronal cells. Exposure of neurons to these Aβ42 oligomers dramatically affects neuronal differentiation and, consequently, neuronal network maturation. PMID:27242518

[Mutations of amyloid precursor protein in early-onset familial Alzheimer's disease].

PubMed

Naruse, S; Tsuji, S; Miyatake, T

1992-09-01

Genetic linkage studies of familial Alzheimer's disease (FAD) have suggested that some form of early-onset FAD is linked to proximal long arm of chromosome 21. It has been also suggested that some form of late-onset FAD is linked to long arm of chromosome 19. Goate et al have identified a mis-sense mutation (Val to Ile) in exon 17 of the amyloid precursor protein (APP) gene in 2 of 16 early-onset FAD families, and have shown that the FAD locus in an FAD family is tightly linked to the mis-sense mutation. To determine if the mis-sense mutation is observed in different ethnic origine, we have studied some early-onset FAD families. Two early-onset FAD families showed the existence of the mutation. As the mutation has been identified in different ethnic origine and the mutation has not been observed in normal individuals, it strengthen hypothesis that the mutation is pathogenic. Recently, Val to Phe and Val to Gly mutations have been also identified at the same codon (Codon 717) of the APP gene.

The Ames dwarf mutation attenuates Alzheimer's disease phenotype of APP/PS1 mice.

PubMed

Puig, Kendra L; Kulas, Joshua A; Franklin, Whitney; Rakoczy, Sharlene G; Taglialatela, Giulio; Brown-Borg, Holly M; Combs, Colin K

2016-04-01

APP/PS1 double transgenic mice expressing human mutant amyloid precursor protein (APP) and presenilin-1 (PS1) demonstrate robust brain amyloid beta (Aβ) peptide containing plaque deposition, increased markers of oxidative stress, behavioral dysfunction, and proinflammatory gliosis. On the other hand, lack of growth hormone, prolactin, and thyroid-stimulating hormone due to a recessive mutation in the Prop 1 gene (Prop1df) in Ames dwarf mice results in a phenotype characterized by potentiated antioxidant mechanisms, improved learning and memory, and significantly increased longevity in homozygous mice. Based on this, we hypothesized that a similar hormone deficiency might attenuate disease changes in the brains of APP/PS1 mice. To test this idea, APP/PS1 mice were crossed to the Ames dwarf mouse line. APP/PS1, wild-type, df/+, df/df, df/+/APP/PS1, and df/df/APP/PS1 mice were compared at 6 months of age through behavioral testing and assessing amyloid burden, reactive gliosis, and brain cytokine levels. df/df mice demonstrated lower brain growth hormone and insulin-like growth factor 1 concentrations. This correlated with decreased astrogliosis and microgliosis in the df/df/APP/PS1 mice and, surprisingly, reduced Aβ plaque deposition and Aβ 1-40 and Aβ 1-42 concentrations. The df/df/APP/PS1 mice also demonstrated significantly elevated brain levels of multiple cytokines in spite of the attenuated gliosis. These data indicate that the df/df/APP/PS1 line is a unique resource in which to study aging and resistance to disease and suggest that the affected pituitary hormones may have a role in regulating disease progression. Copyright © 2016 Elsevier Inc. All rights reserved.

Multisite tyrosine phosphorylation of the N-terminus of Mint1/X11α by Src kinase regulates the trafficking of amyloid precursor protein.

PubMed

Dunning, Christopher J R; Black, Hannah L; Andrews, Katie L; Davenport, Elizabeth C; Conboy, Michael; Chawla, Sangeeta; Dowle, Adam A; Ashford, David; Thomas, Jerry R; Evans, Gareth J O

2016-05-01

Mint/X11 is one of the four neuronal trafficking adaptors that interact with amyloid precursor protein (APP) and are linked with its cleavage to generate β-amyloid peptide, a key player in the pathology of Alzheimer's disease. How APP switches between adaptors at different stages of the secretory pathway is poorly understood. Here, we show that tyrosine phosphorylation of Mint1 regulates the destination of APP. A canonical SH2-binding motif ((202) YEEI) was identified in the N-terminus of Mint1 that is phosphorylated on tyrosine by C-Src and recruits the active kinase for sequential phosphorylation of further tyrosines (Y191 and Y187). A single Y202F mutation in the Mint1 N-terminus inhibits C-Src binding and tyrosine phosphorylation. Previous studies observed that co-expression of wild-type Mint1 and APP causes accumulation of APP in the trans-Golgi. Unphosphorylatable Mint1 (Y202F) or pharmacological inhibition of Src reduced the accumulation of APP in the trans-Golgi of heterologous cells. A similar result was observed in cultured rat hippocampal neurons where Mint1(Y202F) permitted the trafficking of APP to more distal neurites than the wild-type protein. These data underline the importance of the tyrosine phosphorylation of Mint1 as a critical switch for determining the destination of APP. The regulation of amyloid precursor protein (APP) trafficking is poorly understood. We have discovered that the APP adapter, Mint1, is phosphorylated by C-Src kinase. Mint1 causes APP accumulation in the trans-Golgi network, whereas inhibition of Src or mutation of Mint1-Y202 permits APP recycling. The phosphorylation status of Mint1 could impact on the pathological trafficking of APP in Alzheimer's disease. © 2016 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

New Insights to Clathrin and Adaptor Protein 2 for the Design and Development of Therapeutic Strategies

PubMed Central

Poulsen, Ebbe Toftgaard; Larsen, Agnete; Zollo, Alen; Jørgensen, Arne L.; Sanggaard, Kristian W.; Enghild, Jan J.; Matrone, Carmela

2015-01-01

The Amyloid Precursor Protein (APP) has been extensively studied for its role as the precursor of the β-amyloid protein (Aβ) in Alzheimer’s disease (AD). However, our understanding of the normal function of APP is still patchy. Emerging evidence indicates that a dysfunction in APP trafficking and degradation can be responsible for neuronal deficits and progressive degeneration in humans. We recently reported that the Y682 mutation in the 682YENPTY687 domain of APP affects its binding to specific adaptor proteins and leads to its anomalous trafficking, to defects in the autophagy machinery and to neuronal degeneration. In order to identify adaptors that influence APP function, we performed pull-down experiments followed by quantitative mass spectrometry (MS) on hippocampal tissue extracts of three month-old mice incubated with either the 682YENPTY687 peptide, its mutated form, 682GENPTY687 or its phosphorylated form, 682pYENPTY687. Our experiments resulted in the identification of two proteins involved in APP internalization and trafficking: Clathrin heavy chain (hc) and its Adaptor Protein 2 (AP-2). Overall our results consolidate and refine the importance of Y682 in APP normal functions from an animal model of premature aging and dementia. Additionally, they open the perspective to consider Clathrin hc and AP-2 as potential targets for the design and development of new therapeutic strategies. PMID:26690411

The Fate of Nascent APP in Hippocampal Neurons: A Live Cell Imaging Study.

PubMed

DelBove, Claire E; Deng, Xian-Zhen; Zhang, Qi

2018-06-21

Amyloid precursor protein (APP) is closely associated with Alzheimer's disease (AD) because its proteolytic products form amyloid plaques and its mutations are linked to familial AD patients. As a membrane protein, APP is involved in neuronal development and plasticity. However, it remains unclear how nascent APP is distributed and transported to designated membrane compartments to execute its diverse functions. Here, we employed a dual-tagged APP fusion protein in combination with a synaptic vesicle marker to study the surface trafficking and cleavage of APP in hippocampal neurons immediately after its synthesis. Using long-term time-lapse imaging, we found that a considerable amount of nascent APP was directly transported to the somatodendritic surface, from which it propagates to distal neurites. Some APP in the plasma membrane was endocytosed and some was cleaved by α-secretase. Hence, we conclude that surface transportation of APP is a major step preceding its proteolytic processing and neuritic distribution.

NMR structure of the Arctic mutation of the Alzheimer's Aβ(1-40) peptide docked to SDS micelles

NASA Astrophysics Data System (ADS)

Usachev, K. S.; Filippov, A. V.; Khairutdinov, B. I.; Antzutkin, O. N.; Klochkov, V. V.

2014-11-01

The “Arctic” point mutation of the Alzheimer's amyloid β-peptide is a rare mutation leading to an early onset of Alzheimer's disease. The peptide may interact with neuronal membranes, where it can provide its toxic effects. We used 2D NMR spectroscopy to investigate the conformation of the “Arctic” mutant of Aβ1-40 Alzheimer's amyloid peptide in sodium dodecyl sulfate micelle solutions, which are the type of amphiphilic structures mimicking some properties of biomembranes. The study showed that the Arctic mutant of Aβ1-40 interacts with the surface of SDS micelles mainly through the Leu17-Asn27 310-helical region, while the Ile31-Val40 region is buried in the hydrophobic interior of the micelle. In contrast, wild-type Aβ1-40 interacts with SDS micelles through the Lys16-Asp23 α-helical region and Gly29-Met35. Both the Arctic mutant and the wild-type Aβ1-40 peptides interactions with SDS micelles are hydrophobic in nature. Aβ peptides are thought to be capable of forming pores in biomembranes that can cause changes in neuronal and endothelial cell membrane permeability. It has also been shown that Aβ peptides containing the “Arctic” mutation are more neurotoxic and aggregate more readily than the wild-type Aβ peptides at physiological conditions. Here, we propose that the extension of the helical structure of Leu17-Asn27 and a high aliphaticity (neutrality) of the C-terminal region in the Arctic Aβ peptides are consistent with the idea that formation of ion-permeable pores by Aβ oligomers may be one of prevailing mechanisms of a larger neuronal toxicity of the Arctic Aβ compared to the wild-type Aβ peptides, independent of oxidative damage and lipid peroxidation.

ADAM10 Missense Mutations Potentiate β-Amyloid Accumulation by Impairing Prodomain Chaperone Function

PubMed Central

Suh, Jaehong; Choi, Se Hoon; Romano, Donna M.; Gannon, Moira A.; Lesinski, Andrea N.; Kim, Doo Yeon; Tanzi, Rudolph E.

2014-01-01

SUMMARY The generation of Aβ, the main component of senile plaques in Alzheimer’s disease (AD), is precluded by α-secretase cleavage within the Aβ domain of the amyloid precursor protein (APP). We identified two rare mutations (Q170H and R181G) in the prodomain of the metalloprotease, ADAM10, that co-segregate with late-onset AD (LOAD). Here, we addressed the pathogenicity of these mutations in transgenic mice expressing human ADAM10 in brain. In Tg2576 AD mice, both mutations attenuated α-secretase activity of ADAM10 and shifted APP processing toward β-secretase-mediated cleavage, while enhancing Aβ plaque load and reactive gliosis. We also demonstrated ADAM10 expression potentiates adult hippocampal neurogenesis, which is reduced by the LOAD mutations. Mechanistically, both LOAD mutations impaired the molecular chaperone activity of ADAM10 prodomain. Collectively, these findings suggest that diminished α-secretase activity, owing to LOAD ADAM10 prodomain mutations, leads to AD-related pathology, strongly supporting ADAM10 as a promising therapeutic target for this devastating disease. PMID:24055016

ADAM10 missense mutations potentiate β-amyloid accumulation by impairing prodomain chaperone function.

PubMed

Suh, Jaehong; Choi, Se Hoon; Romano, Donna M; Gannon, Moira A; Lesinski, Andrea N; Kim, Doo Yeon; Tanzi, Rudolph E

2013-10-16

The generation of Aβ, the main component of senile plaques in Alzheimer's disease (AD), is precluded by α-secretase cleavage within the Aβ domain of the amyloid precursor protein (APP). We identified two rare mutations (Q170H and R181G) in the prodomain of the metalloprotease, ADAM10, that cosegregate with late-onset AD (LOAD). Here, we addressed the pathogenicity of these mutations in transgenic mice expressing human ADAM10 in brain. In Tg2576 AD mice, both mutations attenuated α-secretase activity of ADAM10 and shifted APP processing toward β-secretase-mediated cleavage, while enhancing Aβ plaque load and reactive gliosis. We also demonstrated ADAM10 expression potentiates adult hippocampal neurogenesis, which is reduced by the LOAD mutations. Mechanistically, both LOAD mutations impaired the molecular chaperone activity of ADAM10 prodomain. Collectively, these findings suggest that diminished α-secretase activity, owing to LOAD ADAM10 prodomain mutations, leads to AD-related pathology, strongly supporting ADAM10 as a promising therapeutic target for this devastating disease. Copyright © 2013 Elsevier Inc. All rights reserved.

An iPhone Application Intervention to Promote Surveillance Among Women with a BRCA Mutation: Pre-intervention Data.

PubMed

Cohen, Stephanie A; Scherr, Courtney Lynam; Nixon, Dawn M

2018-04-01

Women with BRCA mutations, at significantly increased risk for breast and ovarian cancer, do not consistently adhere to management guidelines due to lack of awareness and challenges tracking appointments. We developed an iPhone application (app) to help BRCA carriers manage their surveillance. We explored baseline awareness and adherence to surveillance guidelines and analytic data from 21 months of app use. Descriptive statistics were calculated on responses (N = 86) to a survey about surveillance awareness and practices. The majority were aware of breast surveillance guidelines, but only one third were aware of ovarian surveillance guidelines. In practice, the majority reported a clinical breast exam within 6 months, just over half reported a mammogram and breast MRI in the last year, and under half reported ovarian surveillance in the last year. Nearly 50% reported difficulty remembering appointments. Although only 69 received access codes, 284 unique users attempted to enter the app, which was visible in the iTunes store but only available to those with a study code. Evaluation of analytic data demonstrated user engagement with study participants accessing the app 427 times over the 21-month time period (range 2-57; mean = 6.28). Results indicate participants were more likely to know screening guidelines than practice them. There was interest in the app and users were engaged, suggesting app value. We will send a follow-up survey after 18 months of app use for additional evaluation and feedback.

An Intracellular Threonine of Amyloid-β Precursor Protein Mediates Synaptic Plasticity Deficits and Memory Loss

PubMed Central

Lombino, Franco; Biundo, Fabrizio; Tamayev, Robert; Arancio, Ottavio; D’Adamio, Luciano

2013-01-01

Mutations in Amyloid-ß Precursor Protein (APP) and BRI2/ITM2b genes cause Familial Alzheimer and Danish Dementias (FAD/FDD), respectively. APP processing by BACE1, which is inhibited by BRI2, yields sAPPß and ß-CTF. ß-CTF is cleaved by gamma-secretase to produce Aß. A knock-in mouse model of FDD, called FDDKI, shows deficits in memory and synaptic plasticity, which can be attributed to sAPPß/ß-CTF but not Aß. We have investigated further the pathogenic function of ß-CTF focusing on Thr668 of ß-CTF because phosphorylation of Thr668 is increased in AD cases. We created a knock-in mouse bearing a Thr668Ala mutation (APPTA mice) that prevents phosphorylation at this site. This mutation prevents the development of memory and synaptic plasticity deficits in FDDKI mice. These data are consistent with a role for the carboxyl-terminal APP domain in the pathogenesis of dementia and suggest that averting the noxious role of Thr668 is a viable therapeutic strategy for human dementias. PMID:23451158

SMART precision cancer medicine: a FHIR-based app to provide genomic information at the point of care.

PubMed

Warner, Jeremy L; Rioth, Matthew J; Mandl, Kenneth D; Mandel, Joshua C; Kreda, David A; Kohane, Isaac S; Carbone, Daniel; Oreto, Ross; Wang, Lucy; Zhu, Shilin; Yao, Heming; Alterovitz, Gil

2016-07-01

Precision cancer medicine (PCM) will require ready access to genomic data within the clinical workflow and tools to assist clinical interpretation and enable decisions. Since most electronic health record (EHR) systems do not yet provide such functionality, we developed an EHR-agnostic, clinico-genomic mobile app to demonstrate several features that will be needed for point-of-care conversations. Our prototype, called Substitutable Medical Applications and Reusable Technology (SMART)® PCM, visualizes genomic information in real time, comparing a patient's diagnosis-specific somatic gene mutations detected by PCR-based hotspot testing to a population-level set of comparable data. The initial prototype works for patient specimens with 0 or 1 detected mutation. Genomics extensions were created for the Health Level Seven® Fast Healthcare Interoperability Resources (FHIR)® standard; otherwise, the prototype is a normal SMART on FHIR app. The PCM prototype can rapidly present a visualization that compares a patient's somatic genomic alterations against a distribution built from more than 3000 patients, along with context-specific links to external knowledge bases. Initial evaluation by oncologists provided important feedback about the prototype's strengths and weaknesses. We added several requested enhancements and successfully demonstrated the app at the inaugural American Society of Clinical Oncology Interoperability Demonstration; we have also begun to expand visualization capabilities to include cancer specimens with multiple mutations. PCM is open-source software for clinicians to present the individual patient within the population-level spectrum of cancer somatic mutations. The app can be implemented on any SMART on FHIR-enabled EHRs, and future versions of PCM should be able to evolve in parallel with external knowledge bases. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

An Alzheimer Disease-linked Rare Mutation Potentiates Netrin Receptor Uncoordinated-5C-induced Signaling That Merges with Amyloid β Precursor Protein Signaling.

PubMed

Hashimoto, Yuichi; Toyama, Yuka; Kusakari, Shinya; Nawa, Mikiro; Matsuoka, Masaaki

2016-06-03

A missense mutation (T835M) in the uncoordinated-5C (UNC5C) netrin receptor gene increases the risk of late-onset Alzheimer disease (AD) and also the vulnerability of neurons harboring the mutation to various insults. The molecular mechanisms underlying T835M-UNC5C-induced death remain to be elucidated. In this study, we show that overexpression of wild-type UNC5C causes low-grade death, which is intensified by an AD-linked mutation T835M. An AD-linked survival factor, calmodulin-like skin protein (CLSP), and a natural ligand of UNC5C, netrin1, inhibit this death. T835M-UNC5C-induced neuronal cell death is mediated by an intracellular death-signaling cascade, consisting of death-associated protein kinase 1/protein kinase D/apoptosis signal-regulating kinase 1 (ASK1)/JNK/NADPH oxidase/caspases, which merges at ASK1 with a death-signaling cascade, mediated by amyloid β precursor protein (APP). Notably, netrin1 also binds to APP and partially inhibits the death-signaling cascade, induced by APP. These results may provide new insight into the amyloid β-independent pathomechanism of AD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Increased production of 4 kDa amyloid beta peptide in serum deprived human primary neuron cultures: possible involvement of apoptosis.

PubMed

LeBlanc, A

1995-12-01

The etiology of the amyloid beta peptide in sporadic Alzheimer's disease (AD) is not known. Amyloid beta peptide (A beta), a proteolytic product of the amyloid precursor protein (APP), is deposited in the senile plaques and cerebrovascular tissues of individuals with either sporadic or familial AD (FAD). Increased A beta production from mutant APPs in FAD fosters the hypothesis that overexpression of A beta plays a primary role in the pathogenesis of AD. The absence of APP mutations in sporadic AD which displays identical pathological features than FAD such as synapse and neuronal loss, senile plaques and neurofibrillary tangles, suggests other causes for overexpression and/or deposition of A beta. To investigate the effect of neuronal death on APP metabolism and A beta secretion, human primary neuron cultures were induced to undergo apoptosis by serum deprivation. Serum deprived neurons display shrunken and rounded morphology, contain condensed chromatine and fragmented DNA, which are characteristic of apoptosis. In serum deprived neurons, metabolism of APP through the nonamyloidogenic secretory pathway is decreased to 20% from 40% in control cultures whereas 4kDa A beta is increased three- to fourfold. The results suggest that human neurons undergoing apoptosis generate excess A beta and indicates a possible mechanism for increased A beta in the absence of APP mutations.

Screening for Small Molecule Inhibitors of Statin-Induced APP C-terminal Toxic Fragment Production

PubMed Central

Poksay, Karen S.; Sheffler, Douglas J.; Spilman, Patricia; Campagna, Jesus; Jagodzinska, Barbara; Descamps, Olivier; Gorostiza, Olivia; Matalis, Alex; Mullenix, Michael; Bredesen, Dale E.; Cosford, Nicholas D. P.; John, Varghese

2017-01-01

Alzheimer’s disease (AD) is characterized by neuronal and synaptic loss. One process that could contribute to this loss is the intracellular caspase cleavage of the amyloid precursor protein (APP) resulting in release of the toxic C-terminal 31-amino acid peptide APP-C31 along with the production of APPΔC31, full-length APP minus the C-terminal 31 amino acids. We previously found that a mutation in APP that prevents this caspase cleavage ameliorated synaptic loss and cognitive impairment in a murine AD model. Thus, inhibition of this cleavage is a reasonable target for new therapeutic development. In order to identify small molecules that inhibit the generation of APP-C31, we first used an APPΔC31 cleavage site-specific antibody to develop an AlphaLISA to screen several chemical compound libraries for the level of N-terminal fragment production. This antibody was also used to develop an ELISA for validation studies. In both high throughput screening (HTS) and validation testing, the ability of compounds to inhibit simvastatin- (HTS) or cerivastatin- (validation studies) induced caspase cleavage at the APP-D720 cleavage site was determined in Chinese hamster ovary (CHO) cells stably transfected with wildtype (wt) human APP (CHO-7W). Several compounds, as well as control pan-caspase inhibitor Q-VD-OPh, inhibited APPΔC31 production (measured fragment) and rescued cell death in a dose-dependent manner. The effective compounds fell into several classes including SERCA inhibitors, inhibitors of Wnt signaling, and calcium channel antagonists. Further studies are underway to evaluate the efficacy of lead compounds – identified here using cells and tissues expressing wt human APP – in mouse models of AD expressing mutated human APP, as well as to identify additional compounds and determine the mechanisms by which they exert their effects. PMID:28261092

Visualizing APP and BACE-1 approximation in neurons yields insight into the amyloidogenic pathway.

PubMed

Das, Utpal; Wang, Lina; Ganguly, Archan; Saikia, Junmi M; Wagner, Steven L; Koo, Edward H; Roy, Subhojit

2016-01-01

Cleavage of amyloid precursor protein (APP) by BACE-1 (β-site APP cleaving enzyme-1) is the rate-limiting step in amyloid-β (Aβ) production and a neuropathologic hallmark of Alzheimer's disease; thus, physical approximation of this substrate-enzyme pair is a crucial event with broad biological and therapeutic implications. Despite much research, neuronal locales of APP and BACE-1 convergence and APP cleavage remain unclear. Here we report an optical assay, based on fluorescence complementation, for visualizing in cellulo APP-BACE-1 interactions as a simple on/off signal. Combining this with other assays tracking the fate of internalized APP in hippocampal neurons, we found that APP and BACE-1 interacted in both biosynthetic and endocytic compartments, particularly along recycling microdomains such as dendritic spines and presynaptic boutons. In axons, APP and BACE-1 were cotransported, and they also interacted during transit. Finally, our assay revealed that the Alzheimer's disease-protective 'Icelandic' mutation greatly attenuates APP-BACE-1 interactions, suggesting a mechanistic basis for protection. Collectively, the data challenge canonical models and provide concrete insights into long-standing controversies in the field.

Clinical features of early onset, familial Alzheimer`s disease linked to chromosome 14

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mullan, M.; Bennett, C.; Figueredo, C.

1995-02-27

Early onset familial Alzheimer`s disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the {beta}-amyloid precursor protein ({beta}APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with {beta}APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val {r_arrow} Ile) or a valine to glycine (Val {r_arrow} Gly) change. More recently, a second locus for very early onsetmore » disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the {beta}APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the {beta}APP717 Val {r_arrow} Ile and {beta}APP717 Val {r_arrow} Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or {beta}APP codon 717 mutated families except mean age of onset. 52 refs., 2 figs., 5 tabs.« less

Amyloid protein-mediated differential DNA methylation status regulates gene expression in Alzheimer's disease model cell line

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sung, Hye Youn; Choi, Eun Nam; Ahn Jo, Sangmee

2011-11-04

Highlights: Black-Right-Pointing-Pointer Genome-wide DNA methylation pattern in Alzheimer's disease model cell line. Black-Right-Pointing-Pointer Integrated analysis of CpG methylation and mRNA expression profiles. Black-Right-Pointing-Pointer Identify three Swedish mutant target genes; CTIF, NXT2 and DDR2 gene. Black-Right-Pointing-Pointer The effect of Swedish mutation on alteration of DNA methylation and gene expression. -- Abstract: The Swedish mutation of amyloid precursor protein (APP-sw) has been reported to dramatically increase beta amyloid production through aberrant cleavage at the beta secretase site, causing early-onset Alzheimer's disease (AD). DNA methylation has been reported to be associated with AD pathogenesis, but the underlying molecular mechanism of APP-sw-mediated epigenetic alterationsmore » in AD pathogenesis remains largely unknown. We analyzed genome-wide interplay between promoter CpG DNA methylation and gene expression in an APP-sw-expressing AD model cell line. To identify genes whose expression was regulated by DNA methylation status, we performed integrated analysis of CpG methylation and mRNA expression profiles, and identified three target genes of the APP-sw mutant; hypomethylated CTIF (CBP80/CBP20-dependent translation initiation factor) and NXT2 (nuclear exporting factor 2), and hypermethylated DDR2 (discoidin domain receptor 2). Treatment with the demethylating agent 5-aza-2 Prime -deoxycytidine restored mRNA expression of these three genes, implying methylation-dependent transcriptional regulation. The profound alteration in the methylation status was detected at the -435, -295, and -271 CpG sites of CTIF, and at the -505 to -341 region in the promoter of DDR2. In the promoter region of NXT2, only one CpG site located at -432 was differentially unmethylated in APP-sw cells. Thus, we demonstrated the effect of the APP-sw mutation on alteration of DNA methylation and subsequent gene expression. This epigenetic regulatory mechanism may contribute to the pathogenesis of AD.« less

APP metabolism regulates tau proteostasis in human cerebral cortex neurons.

PubMed

Moore, Steven; Evans, Lewis D B; Andersson, Therese; Portelius, Erik; Smith, James; Dias, Tatyana B; Saurat, Nathalie; McGlade, Amelia; Kirwan, Peter; Blennow, Kaj; Hardy, John; Zetterberg, Henrik; Livesey, Frederick J

2015-05-05

Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer's disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families.

PubMed

Cruchaga, Carlos; Haller, Gabe; Chakraverty, Sumitra; Mayo, Kevin; Vallania, Francesco L M; Mitra, Robi D; Faber, Kelley; Williamson, Jennifer; Bird, Tom; Diaz-Arrastia, Ramon; Foroud, Tatiana M; Boeve, Bradley F; Graff-Radford, Neill R; St Jean, Pamela; Lawson, Michael; Ehm, Margaret G; Mayeux, Richard; Goate, Alison M

2012-01-01

Pathogenic mutations in APP, PSEN1, PSEN2, MAPT and GRN have previously been linked to familial early onset forms of dementia. Mutation screening in these genes has been performed in either very small series or in single families with late onset AD (LOAD). Similarly, studies in single families have reported mutations in MAPT and GRN associated with clinical AD but no systematic screen of a large dataset has been performed to determine how frequently this occurs. We report sequence data for 439 probands from late-onset AD families with a history of four or more affected individuals. Sixty sequenced individuals (13.7%) carried a novel or pathogenic mutation. Eight pathogenic variants, (one each in APP and MAPT, two in PSEN1 and four in GRN) three of which are novel, were found in 14 samples. Thirteen additional variants, present in 23 families, did not segregate with disease, but the frequency of these variants is higher in AD cases than controls, indicating that these variants may also modify risk for disease. The frequency of rare variants in these genes in this series is significantly higher than in the 1,000 genome project (p = 5.09 × 10⁻⁵; OR = 2.21; 95%CI = 1.49-3.28) or an unselected population of 12,481 samples (p = 6.82 × 10⁻⁵; OR = 2.19; 95%CI = 1.347-3.26). Rare coding variants in APP, PSEN1 and PSEN2, increase risk for or cause late onset AD. The presence of variants in these genes in LOAD and early-onset AD demonstrates that factors other than the mutation can impact the age at onset and penetrance of at least some variants associated with AD. MAPT and GRN mutations can be found in clinical series of AD most likely due to misdiagnosis. This study clearly demonstrates that rare variants in these genes could explain an important proportion of genetic heritability of AD, which is not detected by GWAS.

GeoMapApp as a platform for visualizing marine data from Polar Regions

NASA Astrophysics Data System (ADS)

Nitsche, F. O.; Ryan, W. B.; Carbotte, S. M.; Ferrini, V.; Goodwillie, A. M.; O'hara, S. H.; Weissel, R.; McLain, K.; Chinhong, C.; Arko, R. A.; Chan, S.; Morton, J. J.; Pomeroy, D.

2012-12-01

To maximize the investment in expensive fieldwork the resulting data should be re-used as much as possible. In addition, unnecessary duplication of data collection effort should be avoided. This becomes even more important if access to field areas is as difficult and expensive as it is in Polar Regions. Making existing data discoverable in an easy to use platform is key to improve re-use and avoid duplication. A common obstacle is that use of existing data is often limited to specialists who know of the data existence and also have the right tools to view and analyze these data. GeoMapApp is a free, interactive, map based tool that allows users to discover, visualize, and analyze a large number of data sets. In addition to a global view, it provides polar map projections for displaying data in Arctic and Antarctic areas. Data that have currently been added to the system include Arctic swath bathymetry data collected from the USCG icebreaker Healy. These data are collected almost continuously including from cruises where bathymetry is not the main objective and for which existence of the acquired data may not be well known. In contrast, existence of seismic data from the Antarctic continental margin is well known in the seismic community. They are archived at and can be accessed through the Antarctic Seismic Data Library System (SDLS). Incorporating these data into GeoMapApp makes an even broader community aware of these data and the custom interface, which includes capabilities to visualize and explore these data, allows users without specific software or knowledge of the underlying data format to access the data. In addition to investigating these datasets, GeoMapApp provides links to the actual data sources to allow specialists the opportunity to re-use the original data. Important identification of data sources and data references are achieved on different levels. For access to the actual Antarctic seismic data GeoMapApp links to the SDLS site, where users have to register before downloading the data and where they are informed about data owners. For the swath bathymetry data GeoMapApp links to an IEDA/MGDS web page for each cruise containing detailed information about investigators and surveys.

Deficits in working memory and motor performance in the APP/PS1ki mouse model for Alzheimer's disease.

PubMed

Wirths, Oliver; Breyhan, Henning; Schäfer, Stephanie; Roth, Christian; Bayer, Thomas A

2008-06-01

The APP/PS1ki mouse model for Alzheimer's disease (AD) exhibits robust brain and spinal cord axonal degeneration and hippocampal CA1 neuron loss starting at 6 months of age. It expresses human mutant APP751 with the Swedish and London mutations together with two FAD-linked knocked-in mutations (PS1 M233T and PS1 L235P) in the murine PS1 gene. The present report covers a phenotypical analysis of this model using either behavioral tests for working memory and motor performance, as well as an analysis of weight development and body shape. At the age of 6 months, a dramatic, age-dependent change in all of these properties and characteristics was observed, accompanied by a significantly reduced ability to perform working memory and motor tasks. The APP/PS1ki mice were smaller and showed development of a thoracolumbar kyphosis, together with an incremental loss of body weight. While 2-month-old APP/PS1ki mice were inconspicuous in all of these tasks and properties, there is a massive age-related impairment in all tested behavioral paradigms. We have previously reported robust axonal degeneration in brain and spinal cord, as well as abundant hippocampal CA1 neuron loss starting at 6 months of age in the APP/PS1ki mouse model, which coincides with the onset of motor and memory deficits described in the present report.

The Alzheimer Disease Protective Mutation A2T Modulates Kinetic and Thermodynamic Properties of Amyloid-β (Aβ) Aggregation*

PubMed Central

Benilova, Iryna; Gallardo, Rodrigo; Ungureanu, Andreea-Alexandra; Castillo Cano, Virginia; Snellinx, An; Ramakers, Meine; Bartic, Carmen; Rousseau, Frederic; Schymkowitz, Joost; De Strooper, Bart

2014-01-01

Missense mutations in alanine 673 of the amyloid precursor protein (APP), which corresponds to the second alanine of the amyloid β (Aβ) sequence, have dramatic impact on the risk for Alzheimer disease; A2V is causative, and A2T is protective. Assuming a crucial role of amyloid-Aβ in neurodegeneration, we hypothesized that both A2V and A2T mutations cause distinct changes in Aβ properties that may at least partially explain these completely different phenotypes. Using human APP-overexpressing primary neurons, we observed significantly decreased Aβ production in the A2T mutant along with an enhanced Aβ generation in the A2V mutant confirming earlier data from non-neuronal cell lines. More importantly, thioflavin T fluorescence assays revealed that the mutations, while having little effect on Aβ42 peptide aggregation, dramatically change the properties of the Aβ40 pool with A2V accelerating and A2T delaying aggregation of the Aβ peptides. In line with the kinetic data, Aβ A2T demonstrated an increase in the solubility at equilibrium, an effect that was also observed in all mixtures of the A2T mutant with the wild type Aβ40. We propose that in addition to the reduced β-secretase cleavage of APP, the impaired propensity to aggregate may be part of the protective effect conferred by A2T substitution. The interpretation of the protective effect of this mutation is thus much more complicated than proposed previously. PMID:25253695

Molecular determinants and thermodynamics of the amyloid precursor protein transmembrane domain implicated in Alzheimer's disease

PubMed Central

Wang, Hao; Barreyro, Laura; Provasi, Davide; Djemil, Imane; Torres-Arancivia, Celia; Filizola, Marta; Ubarretxena-Belandia, Iban

2011-01-01

The deposition of toxic amyloid-β peptide (Aβ) aggregates in the brain is a hallmark of Alzheimer's disease. The intramembrane proteolysis by γ-secretase of the amyloid precursor protein carboxy-terminal fragment (APP-βCTF) constitutes the final step in the production of Aβs. Mounting evidence suggests that APP-βCTF is a transmembrane domain (TMD) dimer, and that dimerization might modulate the production of Aβ species that are prone to aggregation, and therefore most toxic. We combined experimental and computational approaches to study the molecular determinants and thermodynamics of APP-βCTF dimerization, and produced a unifying structural model that reconciles much of the published data. Using a cell assay, which exploits a dimerization-dependent activator of transcription, we identified specific dimerization-disrupting mutations located mostly at the N-terminus of the TMD of APP-βCTF. The ability of selected mutants to disrupt the dimerization of full length APP-βCTF was confirmed by fluorescence resonance energy transfer experiments. Free-energy estimates of wild-type (WT) and mutants of the TMD of APP-βCTF derived from enhanced molecular dynamics simulations showed that the dimeric state is comprised of different arrangements, in which either 709GXXXA713 or 700GXXXG704GXXXG708 interaction motifs can engage in symmetric or asymmetric associations. Mutations along the TMD of APP-βCTF were found to modulate the relative free energy of the dimeric configurations, and to differently affect the distribution of interfaces within the dimeric state. This observation might have important biological implications, since dimers with a different arrangement of the transmembrane helices are likely to be recognized differently by γ-secretase and lead to a variation of Aβ levels. PMID:21440556

Visualization of APP and BACE-1 approximation in neurons: new insights into the amyloidogenic pathway

PubMed Central

Das, Utpal; Wang, Lina; Ganguly, Archan; Saikia, Junmi M.; Wagner, Steven L.; Koo, Edward H.; Roy, Subhojit

2016-01-01

Cleavage of APP (amyloid precursor protein) by BACE-1 (β-site APP cleaving enzyme-1) is the rate-limiting step in amyloid-beta (Aβ) production and a neuropathologic hallmark of Alzheimer's disease (AD); thus physical approximation of this substrate-enzyme pair is a critical event with broad biological and therapeutic implications. Despite much research, neuronal locales of APP/BACE-1 convergence and APP-cleavage remain unclear. Here we report an optical assay – based on fluorescence complementation – to visualize in-cellulo APP/BACE-1 interactions as a simple on/off signal. Combined with other assays tracking the fate of internalized APP in hippocampal neurons, we found that APP/BACE-1 interact in both biosynthetic and endocytic compartments; particularly along recycling-microdomains such as dendritic spines and presynaptic boutons. In axons, APP and BACE-1 are co-transported, and also interact during transit. Finally, our assay reveals that the AD-protective “Icelandic” mutation greatly attenuates APP/BACE-1 interactions, suggesting a mechanistic basis for protection. Collectively, the data challenge canonical models and provide concrete insights into long-standing controversies in the field. PMID:26642089

In vivo effects on photosynthesis gene expression of base pair exchanges in the gene encoding the light-responsive BLUF domain of AppA in Rhodobacter sphaeroides.

PubMed

Metz, Sebastian; Hendriks, Johnny; Jäger, Andreas; Hellingwerf, Klaas; Klug, Gabriele

2010-01-01

The Rhodobacter sphaeroides protein AppA has the unique quality of sensing and transmitting light and redox signals. By acting as antirepressor to the PpsR protein, it acts as a major regulator in photosynthesis gene expression. In this study, we show that by introducing amino acid exchanges into the AppA protein, the in vivo activity as an antirepressor can be greatly altered. The tryptophan 104 to phenylalanine (W104F) base exchange greatly diminished blue-light sensitivity of the BLUF domain. From the obtained in vivo data, the difference in thermal recovery rate of the signaling state of the BLUF domain between the wild type and mutated protein was calculated, predicting an about 10-fold faster recovery in the mutant, which is consistent with in vitro data. Introduction of a tyrosine 21 to phenylalanine (Y21F) or to cysteine (Y21C) mutation led to a complete loss of AppA antirepressor activity, while additionally leading to an increase of photosynthesis gene expression after illumination with high blue-light quantities. Interestingly, this effect is not visible in a W104F/Y21F double mutant that again shows a wild-type-like behavior of the BLUF domain after blue-light illumination, thus restoring the activity of AppA.

Molecular population genetics of the melanic plumage polymorphism in Arctic skuas (Stercorarius parasiticus): evidence for divergent selection on plumage colour.

PubMed

Janssen, Kirstin; Mundy, Nicholas I

2013-09-01

The Arctic skua (Stercorarius parasiticus) is a classic example of an avian plumage polymorphism, with variation in melanin-based ventral plumage coloration defining pale, intermediate and dark morphs in adults of both sexes. However, despite several decades of field research, there is an incomplete understanding of how the polymorphism in ventral plumage colour is maintained and the selective forces involved. Here, we investigate selection on a locus (MC1R) that is strongly associated with plumage colour variation in Arctic skuas using patterns of nucleotide variation and comparison to neutral loci (nuclear introns and mtDNA). We find that three linked nonsynonymous mutations in MC1R, including the single mutation described previously, are associated with plumage colour in the Arctic skua. The position of nonsynonymous mutations on a MC1R haplotype network implies that divergent selection drove the initial evolution of the colour morphs. Comparisons of F(ST)s of MC1R vs. nuclear introns among five skua populations differing in proportion of dark morphs along an approximate north-south cline reveal a signature of divergent selection on MC1R. In contrast, we find limited evidence for balancing selection on MC1R within populations, although the power is low. Our results provide strong evidence for both past and ongoing selection on MC1R, and, by implication, plumage colour in Arctic skuas. The results suggest that a fruitful avenue for future ecological studies will be analysis of selection on morphs in colonies at the extremes along the morph ratio cline. © 2013 John Wiley & Sons Ltd.

An Aberrant Phosphorylation of Amyloid Precursor Protein Tyrosine Regulates Its Trafficking and the Binding to the Clathrin Endocytic Complex in Neural Stem Cells of Alzheimer's Disease Patients

PubMed Central

Poulsen, Ebbe T.; Iannuzzi, Filomena; Rasmussen, Helle F.; Maier, Thorsten J.; Enghild, Jan J.; Jørgensen, Arne L.; Matrone, Carmela

2017-01-01

Alzheimer's disease (AD) is the most common cause of dementia and is likely caused by defective amyloid precursor protein (APP) trafficking and processing in neurons leading to amyloid plaques containing the amyloid-β (Aβ) APP peptide byproducts. Understanding how APP is targeted to selected destinations inside neurons and identifying the mechanisms responsible for the generation of Aβ are thus the keys for the advancement of new therapies. We previously developed a mouse model with a mutation at tyrosine (Tyr) 682 in the C-terminus of APP. This residue is needed for APP to bind to the coating protein Clathrin and to the Clathrin adaptor protein AP2 as well as for the correct APP trafficking and sorting in neurons. By extending these findings to humans, we found that APP binding to Clathrin is decreased in neural stem cells from AD sufferers. Increased APP Tyr phosphorylation alters APP trafficking in AD neurons and it is associated to Fyn Tyr kinase activation. We show that compounds affecting Tyr kinase activity and counteracting defects in AD neurons can control APP location and compartmentalization. APP Tyr phosphorylation is thus a potential therapeutic target for AD. PMID:28360834

A canine model of Alzheimer's disease generated by overexpressing a mutated human amyloid precursor protein.

PubMed

Lee, Geun-Shik; Jeong, Yeon Woo; Kim, Joung Joo; Park, Sun Woo; Ko, Kyeong Hee; Kang, Mina; Kim, Yu Kyung; Jung, Eui-Man; Moon, Changjong; Hyun, Sang Hwan; Hwang, Kyu-Chan; Kim, Nam-Hyung; Shin, Taeyoung; Jeung, Eui-Bae; Hwang, Woo Suk

2014-04-01

Canines are considered the most authentic model for studying multifactorial human diseases, as these animals typically share a common environment with man. Somatic cell nuclear transfer (SCNT) technology along with genetic engineering of nuclear donor cells provides a unique opportunity for examining human diseases using transgenic canines. In the present study, we generated transgenic canines that overexpressed the human amyloid precursor protein (APP) gene containing well-characterized familial Alzheimer's disease (AD) mutations. We successfully obtained five out of six live puppies by SCNT. This was confirmed by observing the expression of green fluorescence protein in the body as a visual transgenic marker and the overexpression of the mutated APP gene in the brain. The transgenic canines developed AD-like symptoms, such as enlarged ventricles, an atrophied hippocampus, and β-amyloid plaques in the brain. Thus, the transgenic canines we created can serve as a novel animal model for studying human AD.

The amyloid precursor protein and postnatal neurogenesis/neuroregeneration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Yanan; Tang, Bor Luen

2006-03-03

The amyloid precursor protein (APP) is the source of amyloid-beta (A{beta}) peptide, produced via its sequential cleavage {beta}- and {gamma}-secretases. Various biophysical forms of A{beta} (and the mutations of APP which results in their elevated levels) have been implicated in the etiology and early onset of Alzheimer's disease. APP's evolutionary conservation and the existence of APP-like isoforms (APLP1 and APLP2) which lack the A{beta} sequence, however, suggest that these might have important physiological functions that are unrelated to A{beta} production. Soluble N-terminal fragments of APP have been known to be neuroprotective, and the interaction of its cytoplasmic C-terminus with amore » myriad of proteins associates it with diverse processes such as axonal transport and transcriptional regulation. The notion for an essential postnatal function of APP has been demonstrated genetically, as mice deficient in both APP and APLP2 or all three APP isoforms exhibit early postnatal lethality and neuroanatomical abnormalities. Recent findings have also brought to light two possible functions of the APP family in Brain-regulation of neural progenitor cell proliferation and axonal outgrowth after injury. Interestingly, these two apparently related neurogenic/neuroregenerative functions of APP involve two separate domains of the molecule.« less

β- but not γ-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia.

PubMed

Tamayev, Robert; Matsuda, Shuji; Arancio, Ottavio; D'Adamio, Luciano

2012-03-01

A mutation in the BRI2/ITM2b gene causes loss of BRI2 protein leading to familial Danish dementia (FDD). BRI2 deficiency of FDD provokes an increase in amyloid-β precursor protein (APP) processing since BRI2 is an inhibitor of APP proteolysis, and APP mediates the synaptic/memory deficits in FDD. APP processing is linked to Alzheimer disease (AD) pathogenesis, which is consistent with a common mechanism involving toxic APP metabolites in both dementias. We show that inhibition of APP cleavage by β-secretase rescues synaptic/memory deficits in a mouse model of FDD. β-cleavage of APP yields amino-terminal-soluble APPβ (sAPPβ) and β-carboxyl-terminal fragments (β-CTF). Processing of β-CTF by γ-secretase releases amyloid-β (Aβ), which is assumed to cause AD. However, inhibition of γ-secretase did not ameliorate synaptic/memory deficits of FDD mice. These results suggest that sAPPβ and/or β-CTF, rather than Aβ, are the toxic species causing dementia, and indicate that reducing β-cleavage of APP is an appropriate therapeutic approach to treating human dementias. Our data and the failures of anti-Aβ therapies in humans advise against targeting γ-secretase cleavage of APP and/or Aβ. Copyright © 2012 EMBO Molecular Medicine.

β- but not γ-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia

PubMed Central

Tamayev, Robert; Matsuda, Shuji; Arancio, Ottavio; D'Adamio, Luciano

2012-01-01

A mutation in the BRI2/ITM2b gene causes loss of BRI2 protein leading to familial Danish dementia (FDD). BRI2 deficiency of FDD provokes an increase in amyloid-β precursor protein (APP) processing since BRI2 is an inhibitor of APP proteolysis, and APP mediates the synaptic/memory deficits in FDD. APP processing is linked to Alzheimer disease (AD) pathogenesis, which is consistent with a common mechanism involving toxic APP metabolites in both dementias. We show that inhibition of APP cleavage by β-secretase rescues synaptic/memory deficits in a mouse model of FDD. β-cleavage of APP yields amino-terminal-soluble APPβ (sAPPβ) and β-carboxyl-terminal fragments (β-CTF). Processing of β-CTF by γ-secretase releases amyloid-β (Aβ), which is assumed to cause AD. However, inhibition of γ-secretase did not ameliorate synaptic/memory deficits of FDD mice. These results suggest that sAPPβ and/or β-CTF, rather than Aβ, are the toxic species causing dementia, and indicate that reducing β-cleavage of APP is an appropriate therapeutic approach to treating human dementias. Our data and the failures of anti-Aβ therapies in humans advise against targeting γ-secretase cleavage of APP and/or Aβ. PMID:22170863

Occurrence of different Canine distemper virus lineages in Italian dogs.

PubMed

Balboni, Andrea; De Lorenzo Dandola, Giorgia; Scagliarini, Alessandra; Prosperi, Santino; Battilani, Mara

2014-01-01

This study describes the sequence analysis of the H gene of 7 Canine distemper virus (CDV) strains identified in dogs in Italy between years 2002-2012. The phylogenetic analysis showed that the CDV strains belonged to 2 clusters: 6 viruses were identified as Arctic-like lineage and 1 as Europe 1 lineage. These data show a considerable prevalence of Arctic-like-CDVs in the analysed dogs. The dogs and the 3 viruses more recently identified showed 4 distinctive amino acid mutations compared to all other Arctic CDVs.

Amyloid Precursor Protein Haploinsufficiency Preferentially Mediates Brain Iron Accumulation in Mice Transgenic for The Huntington's Disease Mutation.

PubMed

Berggren, Kiersten; Agrawal, Sonal; Fox, Julia A; Hildenbrand, Justin; Nelson, Ryan; Bush, Ashley I; Fox, Jonathan H

2017-01-01

Huntington's disease (HD) is an autosomal dominant disorder caused by a CAG expansion in the huntingtin gene that results in expression of mutant huntingtin protein. Iron accumulates in HD brain neurons. Amyloid precursor protein (APP) promotes neuronal iron export. However, the role of APP in brain iron accumulation in HD is unclear. To determine the effects of APP insufficiency on HD in YAC128 mice. We crossed APP hemizygous mice (APP+/-) with YAC128 mice that are transgenic (Tg) for human mutant huntingtin (hmHTT) to generate APP+/+ hmHTT-/-, APP+/- hmHTT-/-, APP+/+ hmHTT+/- and APP+/- hmHTT+/- progeny. Mice were evaluated for behavioral, biochemical and neuropathology HD outcomes at 2-12 months of age. APP heterozygosity decreased cortical APP 25% and 60% in non-Tg and Tg mice, respectively. Cerebral and striatal iron levels were increased by APP knockdown in Tg mice only. Nest-building behavior was decreased in Tg mice; APP knockdown decreased nest building in non-Tg but not Tg mice. Rota-rod endurance was decreased in Tg mice. APP+/- hHTT+/- mice demonstrated additional decreases in rota-rod endurance from 4-10 months of age. Tg mice had smaller striatal volumes and fewer striatal neurons but were not affected by APP knockdown. APP heterozygosity results in greater decreases of cortical APP in Tg versus non-Tg mice. Mutant huntingtin transgenic mice develop brain iron accumulation as a result of greater suppression of APP levels. Elevated brain iron in Tg mice was associated with a decline in motor endurance consistent with a disease promoting effect of iron in the YAC128 model of human HD.

Tyrosine Binding Protein Sites Regulate the Intracellular Trafficking and Processing of Amyloid Precursor Protein through a Novel Lysosome-Directed Pathway

PubMed Central

Tam, Joshua H. K.; Cobb, M. Rebecca; Seah, Claudia; Pasternak, Stephen H.

2016-01-01

The amyloid hypothesis posits that the production of β-amyloid (Aβ) aggregates leads to neurodegeneration and cognitive decline associated with AD. Aβ is produced by sequential cleavage of the amyloid precursor protein (APP) by β- and γ-secretase. While nascent APP is well known to transit to the endosomal/ lysosomal system via the cell surface, we have recently shown that APP can also traffic to lysosomes intracellularly via its interaction with AP-3. Because AP-3 interacts with cargo protein via interaction with tyrosine motifs, we mutated the three tyrosines motif in the cytoplasmic tail of APP. Here, we show that the YTSI motif interacts with AP-3, and phosphorylation of the serine in this motif disrupts the interaction and decreases APP trafficking to lysosomes. Furthermore, we show that phosphorylation at this motif can decrease the production of neurotoxic Aβ 42. This demonstrates that reducing APP trafficking to lysosomes may be a strategy to reduce Aβ 42 in Alzheimer’s disease. PMID:27776132

Tyrosine Binding Protein Sites Regulate the Intracellular Trafficking and Processing of Amyloid Precursor Protein through a Novel Lysosome-Directed Pathway.

PubMed

Tam, Joshua H K; Cobb, M Rebecca; Seah, Claudia; Pasternak, Stephen H

2016-01-01

The amyloid hypothesis posits that the production of β-amyloid (Aβ) aggregates leads to neurodegeneration and cognitive decline associated with AD. Aβ is produced by sequential cleavage of the amyloid precursor protein (APP) by β- and γ-secretase. While nascent APP is well known to transit to the endosomal/ lysosomal system via the cell surface, we have recently shown that APP can also traffic to lysosomes intracellularly via its interaction with AP-3. Because AP-3 interacts with cargo protein via interaction with tyrosine motifs, we mutated the three tyrosines motif in the cytoplasmic tail of APP. Here, we show that the YTSI motif interacts with AP-3, and phosphorylation of the serine in this motif disrupts the interaction and decreases APP trafficking to lysosomes. Furthermore, we show that phosphorylation at this motif can decrease the production of neurotoxic Aβ 42. This demonstrates that reducing APP trafficking to lysosomes may be a strategy to reduce Aβ 42 in Alzheimer's disease.

A molecular dynamics study of the binary complexes of APP, JIP1, and the cargo binding domain of KLC.

PubMed

Taylor, Cooper A; Miller, Bill R; Shah, Soleil S; Parish, Carol A

2017-02-01

Mutations in the amyloid precursor protein (APP) are responsible for the formation of amyloid-β peptides. These peptides play a role in Alzheimer's and other dementia-related diseases. The cargo binding domain of the kinesin-1 light chain motor protein (KLC1) may be responsible for transporting APP either directly or via interaction with C-jun N-terminal kinase-interacting protein 1 (JIP1). However, to date there has been no direct experimental or computational assessment of such binding at the atomistic level. We used molecular dynamics and free energy estimations to gauge the affinity for the binary complexes of KLC1, APP, and JIP1. We find that all binary complexes (KLC1:APP, KLC1:JIP1, and APP:JIP1) contain conformations with favorable binding free energies. For KLC1:APP the inclusion of approximate entropies reduces the favorability. This is likely due to the flexibility of the 42-residue APP protein. In all cases we analyze atomistic/residue driving forces for favorable interactions. Proteins 2017; 85:221-234. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Toward the treatment and prevention of Alzheimer's disease: rational strategies and recent progress.

PubMed

Gandy, Sam; DeKosky, Steven T

2013-01-01

Alzheimer's disease (AD) is the major cause of late-life brain failure. In the past 25 years, autosomal dominant forms of AD were found to be primariy attributable to mutations in one of two presenilins, polytopic proteins that contain the catalytic site of the γ-secretase protease that releases the amyloid beta (Aβ) peptide. Some familial AD is also due to mutations in the amyloid precursor protein (APP), but recently a mutation in APP was discovered that reduces Aβ generation and is protective against AD, further implicating amyloid metabolism. Prion-like seeding of amyloid fibrils and neurofibrillary tangles has been invoked to explain the stereotypical spread of AD within the brain. Treatment trials with anti-Aβ antibodies have shown target engagement, if not significant treatment effects. Attention is increasingly focused on presymptomatic intervention, because Aβ mismetabolism begins up to 25 years before symptoms begin. AD trials deriving from new biological information involve extraordinary international collaboration and may hold the best hope for success in the fight against AD.

Effects of Curculigoside on Memory Impairment and Bone Loss via Anti-Oxidative Character in APP/PS1 Mutated Transgenic Mice.

PubMed

Zhao, Lu; Liu, Sha; Wang, Yin; Zhang, Qiaoyan; Zhao, Wenjuan; Wang, Zejian; Yin, Ming

2015-01-01

Alzheimer's disease (AD) and osteoporosis are two closely related multifactorial progressively degenerative diseases that predominantly affect aged people. These two diseases share many common risk factors, including old age, being female, smoking, excessive drinking, low estrogen, and vitamin D3 levels. Additionally, oxidative damage and the dysfunction of the antioxidant system play important roles in the pathogenesis of osteoporosis and AD. Aβ not only leads to impaired memory but also plays a crucial role in the demineralization process of bone tissues of older people and women with menopause. Curculigoside can promote calcium deposition and increase the levels of ALP and Runx2 in osteoblasts under oxidative stress via anti-oxidative character. Therefore, we investigated the effects of CUR on the spatial learning and memory by the Morris water maze and brain immunohistochemistry, and bone microstructure and material properties of femurs by micro-computed tomography and mechanical testing in APP/PS1 mutated transgenic mice. Oral administration of CUR can significantly enhance learning performance and ameliorate bone loss in APP/PS1 mutated transgenic mice, and the mechanism may be related to its antioxidant effect. Based on these results, CUR has real potential as a new natural resource for developing medicines or dietary supplements for the prevention and treatment of the two closely linked multifactorial progressive degenerative disorders, AD and osteoporosis.

Genetic dissection of Alzheimer disease, a heterogeneous disorder.

PubMed

Schellenberg, G D

1995-09-12

The genetics of Alzheimer disease (AD) are complex and not completely understood. Mutations in the amyloid precursor protein gene (APP) can cause early-onset autosomal dominant AD. In vitro studies indicate that cells expressing mutant APPs overproduce pathogenic forms of the A beta peptide, the major component of AD amyloid. However, mutations in the APP gene are responsible for 5% or less of all early-onset familial AD. A locus on chromosome 14 is responsible for AD in other early-onset AD families and represents the most severe form of the disease in terms of age of onset and rate of decline. Attempts to identify the AD3 gene by positional cloning methods are underway. At least one additional early-onset AD locus remains to be located. In late-onset AD, the apolipoprotein E gene allele epsilon 4 is a risk factor for AD. This allele appears to act as a dose-dependent age-of-onset modifier. The epsilon 2 allele of this gene may be protective. Other late-onset susceptibility factors remain to be identified.

Polymorphism of prion protein gene in Arctic fox (Vulpes lagopus).

PubMed

Wan, Jiayu; Bai, Xue; Liu, Wensen; Xu, Jing; Xu, Ming; Gao, Hongwei

2009-07-01

Prion diseases are fatal neurodegenerative disorders of humans and certain other mammals. Prion protein gene (Prnp) is associated with susceptibility and species barrier to prion diseases. No natural and experimental prion diseases have been documented to date in Arctic fox. In the present study, coding region of Prnp from 135 Arctic foxes were cloned and screened for polymorphisms. Our results indicated that the Arctic fox Prnp open reading frame (ORF) contains 771 nucleotides encoding 257 amino acids. Four single nucleotide polymorphisms (SNPs) (G312C, A337G, C541T, and A723G) were identified. SNPs G312C and A723G produced silent mutations, but SNPs A337G and C541T resulted in a M-V change at codon 113 and R-C at codon 181, respectively. The Arctic fox Prnp amino acid sequence was similar to that of the dog (XM 542906). In short, this study provides preliminary information about genotypes of Prnp in Arctic fox.

Familial Alzheimer’s mutations within APPTM increase Aβ42 production by enhancing accessibility of ɛ-cleavage site

NASA Astrophysics Data System (ADS)

Chen, Wen; Gamache, Eric; Rosenman, David J.; Xie, Jian; Lopez, Maria M.; Li, Yue-Ming; Wang, Chunyu

2014-01-01

The high Aβ42/Aβ40 production ratio is a hallmark of familial Alzheimer’s disease, which can be caused by mutations in the amyloid precursor protein (APP). The C-terminus of Aβ is generated by γ-secretase cleavage within the transmembrane domain of APP (APPTM), a process that is primed by an initial ɛ-cleavage at either T48 or L49, resulting in subsequent production of Aβ42 or Aβ40, respectively. Here we solve the dimer structures of wild-type APPTM (AAPTM WT) and mutant APPTM (FAD mutants V44M) with solution NMR. The right-handed APPTM helical dimer is mediated by GXXXA motif. From the NMR structural and dynamic data, we show that the V44M and V44A mutations can selectively expose the T48 site by weakening helical hydrogen bonds and increasing hydrogen-deuterium exchange rate (kex). We propose a structural model in which FAD mutations (V44M and V44A) can open the T48 site γ-secretase for the initial ɛ-cleavage, and consequently shift cleavage preference towards Aβ42.

Generation and initial characterization of FDD knock in mice.

PubMed

Giliberto, Luca; Matsuda, Shuji; Vidal, Ruben; D'Adamio, Luciano

2009-11-18

Mutations in the integral membrane protein 2B, also known as BRI(2), a type II trans-membrane domain protein cause two autosomal dominant neurodegenerative diseases, Familial British and Danish Dementia. In these conditions, accumulation of a C-terminal peptide (ABri and ADan) cleaved off from the mutated precursor protein by the pro-protein convertase furin, leads to amyloid deposition in the walls of blood vessels and parenchyma of the brain. Recent advances in the understanding of the generation of amyloid in Alzheimer's disease has lead to the finding that BRI(2) interacts with the Amyloid Precursor Protein (APP), decreasing the efficiency of APP processing to generate Abeta. The interaction between the two precursors, APP and BRI(2), and possibly between Abeta and ABri or ADan, could be important in influencing the rate of amyloid production or the tendency of these peptides to aggregate. We have generated the first BRI(2) Danish Knock-In (FDD(KI)) murine model of FDD, expressing the pathogenic decamer duplication in exon 6 of the BRI(2) gene. FDD(KI) mice do not show any evident abnormal phenotype, with normal brain histology and no detectable amyloid deposition in blood vessel walls or parenchyma. This new murine mouse model will be important to further understand the interaction between APP and BRI(2), and to provide insights into the molecular basis of FDD.

Neurodegeneration in Alzheimer disease: role of amyloid precursor protein and presenilin 1 intracellular signaling.

PubMed

Nizzari, Mario; Thellung, Stefano; Corsaro, Alessandro; Villa, Valentina; Pagano, Aldo; Porcile, Carola; Russo, Claudio; Florio, Tullio

2012-01-01

Alzheimer disease (AD) is a heterogeneous neurodegenerative disorder characterized by (1) progressive loss of synapses and neurons, (2) intracellular neurofibrillary tangles, composed of hyperphosphorylated Tau protein, and (3) amyloid plaques. Genetically, AD is linked to mutations in few proteins amyloid precursor protein (APP) and presenilin 1 and 2 (PS1 and PS2). The molecular mechanisms underlying neurodegeneration in AD as well as the physiological function of APP are not yet known. A recent theory has proposed that APP and PS1 modulate intracellular signals to induce cell-cycle abnormalities responsible for neuronal death and possibly amyloid deposition. This hypothesis is supported by the presence of a complex network of proteins, clearly involved in the regulation of signal transduction mechanisms that interact with both APP and PS1. In this review we discuss the significance of novel finding related to cell-signaling events modulated by APP and PS1 in the development of neurodegeneration.

Apolipoprotein E-mimetics inhibit neurodegeneration and restore cognitive functions in a transgenic Drosophila model of Alzheimer's disease.

PubMed

Sarantseva, Svetlana; Timoshenko, Svetlana; Bolshakova, Olga; Karaseva, Eugenia; Rodin, Dmitry; Schwarzman, Alexander L; Vitek, Michael P

2009-12-07

Mutations of the amyloid precursor protein gene (APP) are found in familial forms of Alzheimer's disease (AD) and some lead to the elevated production of amyloid-beta-protein (Abeta). While Abeta has been implicated in the causation of AD, the exact role played by Abeta and its APP precursor are still unclear. In our study, Drosophila melanogaster transgenics were established as a model to analyze AD-like pathology caused by APP overexpression. We demonstrated that age related changes in the levels and pattern of synaptic proteins accompanied progressive neurodegeneration and impairment of cognitive functions in APP transgenic flies, but that these changes may be independent from the generation of Abeta. Using novel peptide mimetics of Apolipoprotein-E, COG112 or COG133 proved to be neuroprotective and significantly improved the learning and memory of APP transgenic flies. The development of neurodegeneration and cognitive deficits was corrected by injections of COG112 or COG133, novel mimetics of apolipoprotein-E (apoE) with neuroprotective activities.

Genomics of Alzheimer Disease: A Review.

PubMed

Rosenberg, Roger N; Lambracht-Washington, Doris; Yu, Gang; Xia, Weiming

2016-07-01

To provide a comprehensive review of knowledge of the genomics of Alzheimer disease (AD) and DNA amyloid β 42 (Aβ42) vaccination as a potential therapy. Genotype-phenotype correlations of AD are presented to provide a comprehensive appreciation of the spectrum of disease causation. Alzheimer disease is caused in part by the overproduction and lack of clearance of Aβ protein. Oligomer Aβ, the most toxic species of Aβ, causes direct injury to neurons, accompanied by enhanced neuroinflammation, astrocytosis and gliosis, and eventually neuronal loss. The strongest genetic evidence supporting this hypothesis derives from mutations in the amyloid precursor protein (APP) gene. A detrimental APP mutation at the β-secretase cleavage site linked to early-onset AD found in a Swedish pedigree enhances Aβ production, in contrast to a beneficial mutation 2 residues away in APP that reduces Aβ production and protects against the onset of sporadic AD. A number of common variants associated with late-onset AD have been identified including apolipoprotein E, BIN1, ABC7, PICALM, MS4A4E/MS4A6A, CD2Ap, CD33, EPHA1, CLU, CR1, and SORL1. One or 2 copies of the apolipoprotein E ε4 allele are a major risk factor for late-onset AD. With DNA Aβ42 vaccination, a Th2-type noninflammatory immune response was achieved with a downregulation of Aβ42-specific effector (Th1, Th17, and Th2) cell responses at later immunization times. DNA Aβ42 vaccination upregulated T regulator cells (CD4+, CD25+, and FoxP3+) and its cytokine interleukin 10, resulting in downregulation of T effectors. Mutations in APP and PS-1 and PS-2 genes that are associated with early-onset, autosomal, dominantly inherited AD, in addition to the at-risk gene polymorphisms responsible for late-onset AD, all indicate a direct and early role of Aβ in the pathogenesis of AD. A translational result of genomic research has been Aβ-reducing therapies including DNA Aβ42 vaccination as a promising approach to delay or prevent this disease.

Defects in Mitochondrial Dynamics and Metabolomic Signatures of Evolving Energetic Stress in Mouse Models of Familial Alzheimer's Disease

PubMed Central

Trushina, Eugenia; Nemutlu, Emirhan; Zhang, Song; Christensen, Trace; Camp, Jon; Mesa, Janny; Siddiqui, Ammar; Tamura, Yasushi; Sesaki, Hiromi; Wengenack, Thomas M.; Dzeja, Petras P.; Poduslo, Joseph F.

2012-01-01

Background The identification of early mechanisms underlying Alzheimer's Disease (AD) and associated biomarkers could advance development of new therapies and improve monitoring and predicting of AD progression. Mitochondrial dysfunction has been suggested to underlie AD pathophysiology, however, no comprehensive study exists that evaluates the effect of different familial AD (FAD) mutations on mitochondrial function, dynamics, and brain energetics. Methods and Findings We characterized early mitochondrial dysfunction and metabolomic signatures of energetic stress in three commonly used transgenic mouse models of FAD. Assessment of mitochondrial motility, distribution, dynamics, morphology, and metabolomic profiling revealed the specific effect of each FAD mutation on the development of mitochondrial stress and dysfunction. Inhibition of mitochondrial trafficking was characteristic for embryonic neurons from mice expressing mutant human presenilin 1, PS1(M146L) and the double mutation of human amyloid precursor protein APP(Tg2576) and PS1(M146L) contributing to the increased susceptibility of neurons to excitotoxic cell death. Significant changes in mitochondrial morphology were detected in APP and APP/PS1 mice. All three FAD models demonstrated a loss of the integrity of synaptic mitochondria and energy production. Metabolomic profiling revealed mutation-specific changes in the levels of metabolites reflecting altered energy metabolism and mitochondrial dysfunction in brains of FAD mice. Metabolic biomarkers adequately reflected gender differences similar to that reported for AD patients and correlated well with the biomarkers currently used for diagnosis in humans. Conclusions Mutation-specific alterations in mitochondrial dynamics, morphology and function in FAD mice occurred prior to the onset of memory and neurological phenotype and before the formation of amyloid deposits. Metabolomic signatures of mitochondrial stress and altered energy metabolism indicated alterations in nucleotide, Krebs cycle, energy transfer, carbohydrate, neurotransmitter, and amino acid metabolic pathways. Mitochondrial dysfunction, therefore, is an underlying event in AD progression, and FAD mouse models provide valuable tools to study early molecular mechanisms implicated in AD. PMID:22393443

APP is cleaved by Bace1 in pre-synaptic vesicles and establishes a pre-synaptic interactome, via its intracellular domain, with molecular complexes that regulate pre-synaptic vesicles functions.

PubMed

Del Prete, Dolores; Lombino, Franco; Liu, Xinran; D'Adamio, Luciano

2014-01-01

Amyloid Precursor Protein (APP) is a type I membrane protein that undergoes extensive processing by secretases, including BACE1. Although mutations in APP and genes that regulate processing of APP, such as PSENs and BRI2/ITM2B, cause dementias, the normal function of APP in synaptic transmission, synaptic plasticity and memory formation is poorly understood. To grasp the biochemical mechanisms underlying the function of APP in the central nervous system, it is important to first define the sub-cellular localization of APP in synapses and the synaptic interactome of APP. Using biochemical and electron microscopy approaches, we have found that APP is localized in pre-synaptic vesicles, where it is processed by Bace1. By means of a proteomic approach, we have characterized the synaptic interactome of the APP intracellular domain. We focused on this region of APP because in vivo data underline the central functional and pathological role of the intracellular domain of APP. Consistent with the expression of APP in pre-synaptic vesicles, the synaptic APP intracellular domain interactome is predominantly constituted by pre-synaptic, rather than post-synaptic, proteins. This pre-synaptic interactome of the APP intracellular domain includes proteins expressed on pre-synaptic vesicles such as the vesicular SNARE Vamp2/Vamp1 and the Ca2+ sensors Synaptotagmin-1/Synaptotagmin-2, and non-vesicular pre-synaptic proteins that regulate exocytosis, endocytosis and recycling of pre-synaptic vesicles, such as target-membrane-SNAREs (Syntaxin-1b, Syntaxin-1a, Snap25 and Snap47), Munc-18, Nsf, α/β/γ-Snaps and complexin. These data are consistent with a functional role for APP, via its carboxyl-terminal domain, in exocytosis, endocytosis and/or recycling of pre-synaptic vesicles.

Arctic Submarine Slope Stability

NASA Astrophysics Data System (ADS)

Winkelmann, D.; Geissler, W.

2010-12-01

Submarine landsliding represents aside submarine earthquakes major natural hazard to coastal and sea-floor infrastructure as well as to coastal communities due to their ability to generate large-scale tsunamis with their socio-economic consequences. The investigation of submarine landslides, their conditions and trigger mechanisms, recurrence rates and potential impact remains an important task for the evaluation of risks in coastal management and offshore industrial activities. In the light of a changing globe with warming oceans and rising sea-level accompanied by increasing human population along coasts and enhanced near- and offshore activities, slope stability issues gain more importance than ever before. The Arctic exhibits the most rapid and drastic changes and is predicted to change even faster. Aside rising air temperatures, enhanced inflow of less cooled Atlantic water into the Arctic Ocean reduces sea-ice cover and warms the surroundings. Slope stability is challenged considering large areas of permafrost and hydrates. The Hinlopen/Yermak Megaslide (HYM) north of Svalbard is the first and so far only reported large-scale submarine landslide in the Arctic Ocean. The HYM exhibits the highest headwalls that have been found on siliciclastic margins. With more than 10.000 square kilometer areal extent and app. 2.400 cubic kilometer of involved sedimentary material, it is one of the largest exposed submarine slides worldwide. Geometry and age put this slide in a special position in discussing submarine slope stability on glaciated continental margins. The HYM occurred 30 ka ago, when the global sea-level dropped by app. 50 m within less than one millennium due to rapid onset of global glaciation. It probably caused a tsunami with circum-Arctic impact and wave heights exceeding 130 meters. The HYM affected the slope stability field in its neighbourhood by removal of support. Post-megaslide slope instability as expressed in creeping and smaller-scaled slides are the consequence. Its geometrical configuration and timing is different from submarine slides on other glaciated continental margins. Thus, it raises the question whether slope stability within the Arctic Ocean is governed by processes specific to this environment. The extraordinary thick slabs (up to 1600 m) that were moved translationally during sliding rise the question on the nature of the weak layers associated with this process. Especially theories involving higher pore pressure are being challenged by this observation, because either extreme pore pressures or alternative explanations (e.g. mineralogical and/or textural) can be considered. To assess the actual submarine slope stability and failure potential in the Arctic Ocean, we propose to drill and recover weak layer material of the HYM from the adjacent intact strata by deep drilling under the framework of Integrated Ocean Drilling Program. This is the only method to recover weak layer material from the HYM, because the strata are too thick. We further propose to drill into the adjacent deforming slope to identify material properties of the layers acting as detachment and monitor the deformation.

Preserved Fronto-Striatal Plasticity and Enhanced Procedural Learning in a Transgenic Mouse Model of Alzheimer's Disease Overexpressing Mutant "hAPPswe"

ERIC Educational Resources Information Center

Middei, Silvia; Geracitano, Raffaella; Caprioli, Antonio; Mercuri, Nicola; Ammassari-Teule, Martine

2004-01-01

Mutations in the amyloid precursor protein (APP) gene inducing abnormal processing and deposition of [beta]-amyloid protein in the brain have been implicated in the pathogenesis of Alzheimer's disease (AD). Although Tg2576 mice with the Swedish mutation ("hAPPswe") exhibit age-related [Alpha][beta]-plaque formation in brain regions like the…

MicroRNA-153 Physiologically Inhibits Expression of Amyloid-β Precursor Protein in Cultured Human Fetal Brain Cells and Is Dysregulated in a Subset of Alzheimer Disease Patients*

PubMed Central

Long, Justin M.; Ray, Balmiki; Lahiri, Debomoy K.

2012-01-01

Regulation of amyloid-β (Aβ) precursor protein (APP) expression is complex. MicroRNAs (miRNAs) are expected to participate in the molecular network that controls this process. The composition of this network is, however, still undefined. Elucidating the complement of miRNAs that regulate APP expression should reveal novel drug targets capable of modulating Aβ production in AD. Here, we investigated the contribution of miR-153 to this regulatory network. A miR-153 target site within the APP 3′-untranslated region (3′-UTR) was predicted by several bioinformatic algorithms. We found that miR-153 significantly reduced reporter expression when co-transfected with an APP 3′-UTR reporter construct. Mutation of the predicted miR-153 target site eliminated this reporter response. miR-153 delivery in both HeLa cells and primary human fetal brain cultures significantly reduced APP expression. Delivery of a miR-153 antisense inhibitor to human fetal brain cultures significantly elevated APP expression. miR-153 delivery also reduced expression of the APP paralog APLP2. High functional redundancy between APP and APLP2 suggests that miR-153 may target biological pathways in which they both function. Interestingly, in a subset of human AD brain specimens with moderate AD pathology, miR-153 levels were reduced. This same subset also exhibited elevated APP levels relative to control specimens. Therefore, endogenous miR-153 inhibits expression of APP in human neurons by specifically interacting with the APP 3′-UTR. This regulatory interaction may have relevance to AD etiology, where low miR-153 levels may drive increased APP expression in a subset of AD patients. PMID:22733824

Cholinergic neurodegeneration in an Alzheimer mouse model overexpressing amyloid-precursor protein with the Swedish-Dutch-Iowa mutations.

PubMed

Foidl, Bettina Maria; Do-Dinh, Patricia; Hutter-Schmid, Bianca; Bliem, Harald R; Humpel, Christian

2016-12-01

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is mainly characterized by beta-amyloid (Aβ) plaque deposition, Tau pathology and dysfunction of the cholinergic system causing memory impairment. The aim of the present study was to examine (1) anxiety and cognition, (2) Aβ plaque deposition and (3) degeneration of cholinergic neurons in the nucleus basalis of Meynert (nbM) and cortical cholinergic innervation in an Alzheimer mouse model (APP_SweDI; overexpressing amyloid precursor protein (APP) with the Swedish K670N/M671L, Dutch E693Q, and Iowa D694N mutations). Our results show that 12-month-old APP_SweDI mice were more anxious and had more memory impairment. A large number of Aβ plaques were already visible at the age of 6 months and increased with age. A significant decrease in cholinergic neurons was seen in the transgenic mouse model in comparison to the wild-type mice, identified by immunohistochemistry against choline acetyltransferase (ChAT) and p75 neurotrophin receptor as well as by in situ hybridization. Moreover, a significant decrease in cortical cholinergic fiber density was found in the transgenic mice as compared to the wild-type. In the cerebral cortex of APP_SweDI mice, swollen cholinergic varicosities were seen in the vicinity of Aβ plaques. In conclusion, the present study shows that in an AD mouse model (APP_SweDI mice) a high Aβ plaque load in the cortex causes damage to cholinergic axons in the cortex, followed by subsequent retrograde-induced cell death of cholinergic neurons and some forms of compensatory processes. This degeneration was accompanied by enhanced anxiety and impaired cognition. Copyright © 2016 Elsevier Inc. All rights reserved.

A single amino acid difference between the intracellular domains of amyloid precursor protein and amyloid-like precursor protein 2 enables induction of synaptic depression and block of long-term potentiation.

PubMed

Trillaud-Doppia, Emilie; Paradis-Isler, Nicolas; Boehm, Jannic

2016-07-01

Alzheimer disease (AD) is initially characterized as a disease of the synapse that affects synaptic transmission and synaptic plasticity. While amyloid-beta and tau have been traditionally implicated in causing AD, recent studies suggest that other factors, such as the intracellular domain of the amyloid-precursor protein (APP-ICD), can also play a role in the development of AD. Here, we show that the expression of APP-ICD induces synaptic depression, while the intracellular domain of its homolog amyloid-like precursor protein 2 (APLP2-ICD) does not. We are able to show that this effect by APP-ICD is due to a single alanine vs. proline difference between APP-ICD and APLP2-ICD. The alanine in APP-ICD and the proline in APLP2-ICD lie directly behind a conserved caspase cleavage site. Inhibition of caspase cleavage of APP-ICD prevents the induction of synaptic depression. Finally, we show that the expression of APP-ICD increases and facilitates long-term depression and blocks induction of long-term potentiation. The block in long-term potentiation can be overcome by mutating the aforementioned alanine in APP-ICD to the proline of APLP2. Based on our results, we propose the emergence of a new APP critical domain for the regulation of synaptic plasticity and in consequence for the development of AD. Copyright © 2016 Elsevier Inc. All rights reserved.

Generation and Initial Characterization of FDD Knock In Mice

PubMed Central

Giliberto, Luca; Matsuda, Shuji; Vidal, Ruben; D'Adamio, Luciano

2009-01-01

Background Mutations in the integral membrane protein 2B [1], also known as BRI2 [2], a type II trans-membrane domain protein cause two autosomal dominant neurodegenerative diseases, Familial British and Danish Dementia [3]. In these conditions, accumulation of a C-terminal peptide (ABri and ADan) cleaved off from the mutated precursor protein by the pro-protein convertase furin [4], leads to amyloid deposition in the walls of blood vessels and parenchyma of the brain. Recent advances in the understanding of the generation of amyloid in Alzheimer's disease has lead to the finding that BRI2 interacts with the Amyloid Precursor Protein (APP), decreasing the efficiency of APP processing to generate Aβ [5], [6], [7]. The interaction between the two precursors, APP and BRI2, and possibly between Aβ and ABri or ADan, could be important in influencing the rate of amyloid production or the tendency of these peptides to aggregate. Methodology/Principal Findings We have generated the first BRI2 Danish Knock-In (FDDKI) murine model of FDD, expressing the pathogenic decamer duplication in exon 6 of the BRI2 gene. FDDKI mice do not show any evident abnormal phenotype, with normal brain histology and no detectable amyloid deposition in blood vessel walls or parenchyma. Conclusions/Significance This new murine mouse model will be important to further understand the interaction between APP and BRI2, and to provide insights into the molecular basis of FDD. PMID:19924302

ADP-Ribosylation Factor 6 and a Functional PIX/p95-APP1 Complex Are Required for Rac1B-mediated Neurite Outgrowth

PubMed Central

Albertinazzi, Chiara; Za, Lorena; Paris, Simona; de Curtis, Ivan

2003-01-01

The mechanisms coordinating adhesion, actin organization, and membrane traffic during growth cone migration are poorly understood. Neuritogenesis and branching from retinal neurons are regulated by the Rac1B/Rac3 GTPase. We have identified a functional connection between ADP-ribosylation factor (Arf) 6 and p95-APP1 during the regulation of Rac1B-mediated neuritogenesis. P95-APP1 is an ADP-ribosylation factor GTPase-activating protein (ArfGAP) of the GIT family expressed in the developing nervous system. We show that Arf6 has a predominant role in neurite extension compared with Arf1 and Arf5. Cotransfection experiments indicate a specific and cooperative potentiation of neurite extension by Arf6 and the carboxy-terminal portion of p95-APP1. Localization studies in neurons expressing different p95-derived constructs show a codistribution of p95-APP1 with Arf6, but not Arf1. Moreover, p95-APP1–derived proteins with a mutated or deleted ArfGAP domain prevent Rac1B-induced neuritogenesis, leading to PIX-mediated accumulation at large Rab11-positive endocytic vesicles. Our data support a role of p95-APP1 as a specific regulator of Arf6 in the control of membrane trafficking during neuritogenesis. PMID:12686588

The E2 Domains of APP and APLP1 Share a Conserved Mode of Dimerization

DOE Office of Scientific and Technical Information (OSTI.GOV)

S Lee; Y Xue; J Hulbert

2011-12-31

Amyloid precursor protein (APP) is genetically linked to Alzheimer's disease. APP is a type I membrane protein, and its oligomeric structure is potentially important because this property may play a role in its function or affect the processing of the precursor by the secretases to generate amyloid {beta}-peptide. Several independent studies have shown that APP can form dimers in the cell, but how it dimerizes remains controversial. At least three regions of the precursor, including a centrally located and conserved domain called E2, have been proposed to contribute to dimerization. Here we report two new crystal structures of E2, onemore » from APP and the other from APLP1, a mammalian APP homologue. Comparison with an earlier APP structure, which was determined in a different space group, shows that the E2 domains share a conserved and antiparallel mode of dimerization. Biophysical measurements in solution show that heparin binding induces E2 dimerization. The 2.1 {angstrom} resolution electron density map also reveals phosphate ions that are bound to the protein surface. Mutational analysis shows that protein residues interacting with the phosphate ions are also involved in heparin binding. The locations of two of these residues, Arg-369 and His-433, at the dimeric interface suggest a mechanism for heparin-induced protein dimerization.« less

[Genetic counseling and testing for families with Alzheimer's disease].

PubMed

Kowalska, Anna

2004-01-01

With the identification of the genes responsible for autosomal dominant early-onset familial Alzheimer's disease (FAD genes), there is a considerable interest in the application of this genetic information in medical practice through genetic testing and counseling. Pathogenic mutations in the PSEN1 and PSEN2 genes encoding presenilin-1 and -2, and the APP gene encoding amyloid b precursor protein, account for 18-50% of familial EOAD cases with autosomal dominant pattern of inheritance. A clinical algorithm of genetic testing and counseling proposed for families with AD has been presented here. A screening for mutations in the APP, PSEN1, and PSEN2 genes is available to individuals with AD symptoms and at-risk children or siblings of patients with early-onset disease determined by a known mutation. In an early-onset family, a known mutation in an affected patient puts the siblings and children at a 50% risk of inheriting the same mutation. The goal of genetic testing is to identify at-risk individuals in order to facilitate early and effective treatments in the symptomatic person based on an individual's genotype and strategies to delay the onset of disease in the presymptomatic mutation carriers. However, there are several arguments against the use of genetic testing both presymptomatically (unpredictable psychological consequences of information about a genetic defect for family members) and as a diagnostic tool for the differential diagnosis of dementia in general practice (a risk of errors in an interpretation of mutation penetrance and its secondary effects on family members, especially for novel mutations; the possibility of coexistence of another form of dementia at the presence of a mutation). Currently, APOE genotyping for presymptomatic individuals with a family history of late-onset disease is not recommended. The APOE4 allele may only confer greater risk for disease, but its presence is not conclusive for the development of AD.

APP intracellular domain derived from amyloidogenic β- and γ-secretase cleavage regulates neprilysin expression

PubMed Central

Grimm, Marcus O. W.; Mett, Janine; Stahlmann, Christoph P.; Grösgen, Sven; Haupenthal, Viola J.; Blümel, Tamara; Hundsdörfer, Benjamin; Zimmer, Valerie C.; Mylonas, Nadine T.; Tanila, Heikki; Müller, Ulrike; Grimm, Heike S.; Hartmann, Tobias

2015-01-01

Alzheimer's disease (AD) is characterized by an accumulation of Amyloid-β (Aβ), released by sequential proteolytic processing of the amyloid precursor protein (APP) by β - and γ-secretase. Aβ peptides can aggregate, leading to toxic Aβ oligomers and amyloid plaque formation. Aβ accumulation is not only dependent on de novo synthesis but also on Aβ degradation. Neprilysin (NEP) is one of the major enzymes involved in Aβ degradation. Here we investigate the molecular mechanism of NEP regulation, which is up to now controversially discussed to be affected by APP processing itself. We found that NEP expression is highly dependent on the APP intracellular domain (AICD), released by APP processing. Mouse embryonic fibroblasts devoid of APP processing, either by the lack of the catalytically active subunit of the γ-secretase complex [presenilin (PS) 1/2] or by the lack of APP and the APP-like protein 2 (APLP2), showed a decreased NEP expression, activity and protein level. Similar results were obtained by utilizing cells lacking a functional AICD domain (APPΔCT15) or expressing mutations in the genes encoding for PS1. AICD supplementation or retransfection with an AICD encoding plasmid could rescue the down-regulation of NEP further strengthening the link between AICD and transcriptional NEP regulation, in which Fe65 acts as an important adaptor protein. Especially AICD generated by the amyloidogenic pathway seems to be more involved in the regulation of NEP expression. In line, analysis of NEP gene expression in vivo in six transgenic AD mouse models (APP and APLP2 single knock-outs, APP/APLP2 double knock-out, APP-swedish, APP-swedish/PS1Δexon9, and APPΔCT15) confirmed the results obtained in cell culture. In summary, in the present study we clearly demonstrate an AICD-dependent regulation of the Aβ-degrading enzyme NEP in vitro and in vivo and elucidate the underlying mechanisms that might be beneficial to develop new therapeutic strategies for the treatment of AD. PMID:26074811

Genetic cathepsin B deficiency reduces beta-amyloid in transgenic mice expressing human wild-type amyloid precursor protein.

PubMed

Hook, Vivian Y H; Kindy, Mark; Reinheckel, Thomas; Peters, Christoph; Hook, Gregory

2009-08-21

Neurotoxic beta-amyloid (Abeta) peptides participate in Alzheimer's disease (AD); therefore, reduction of Abeta generated from APP may provide a therapeutic approach for AD. Gene knockout studies in transgenic mice producing human Abeta may identify targets for reducing Abeta. This study shows that knockout of the cathepsin B gene in mice expressing human wild-type APP (hAPPwt) results in substantial decreases in brain Abeta40 and Abeta42 by 67% and decreases in levels of the C-terminal beta-secretase fragment (CTFbeta) derived from APP. In contrast, knockout of cathepsin B in mice expressing hAPP with the rare Swedish (Swe) and Indiana (Ind) mutations had no effect on Abeta. The difference in reduction of Abeta in hAPPwt mice, but not in hAPPSwe/Ind mice, shows that the transgenic model can affect cathepsin B gene knockout results. Since most AD patients express hAPPwt, these data validate cathepsin B as a target for development of inhibitors to lower Abeta in AD.

Modeling the complex pathology of Alzheimer’s disease in Drosophila

PubMed Central

Fernandez-Funez, Pedro; de Mena, Lorena; Rincon-Limas, Diego E.

2015-01-01

Alzheimer’s disease (AD) is the leading cause of dementia and the most common neurodegenerative disorder. AD is mostly a sporadic disorder and its main risk factor is age, but mutations in three genes that promote the accumulation of the amyloid-β (Aβ42) peptide revealed the critical role of Amyloid precursor protein (APP) processing in AD. Neurofibrillary tangles enriched in tau are the other pathological hallmark of AD, but the lack of causative tau mutations still puzzles researchers. Here, we describe the contribution of a powerful invertebrate model, the fruit fly Drosophila melanogaster, to uncovering the function and pathogenesis of human APP, Aβ42, and tau. APP and tau participate in many complex cellular processes, although their main function is microtubule stabilization and the to-and-fro transport of axonal vesicles. Additionally, expression of secreted Aβ42 induces prominent neuronal death in Drosophila, a critical feature of AD, making this model a popular choice for identifying intrinsic and extrinsic factors mediating Aβ42 neurotoxicity. Overall, Drosophila has made significant contributions to better understand the complex pathology of AD, although additional insight can be expected from combining multiple transgenes, performing genome-wide loss-of-function screens, and testing anti-tau therapies alone or in combination with Aβ42. PMID:26024860

Vascular and parenchymal amyloid pathology in an Alzheimer disease knock-in mouse model: interplay with cerebral blood flow.

PubMed

Li, Hongmei; Guo, Qinxi; Inoue, Taeko; Polito, Vinicia A; Tabuchi, Katsuhiko; Hammer, Robert E; Pautler, Robia G; Taffet, George E; Zheng, Hui

2014-08-09

Accumulation and deposition of β-amyloid peptides (Aβ) in the brain is a central event in the pathogenesis of Alzheimer's disease (AD). Besides the parenchymal pathology, Aβ is known to undergo active transport across the blood-brain barrier and cerebral amyloid angiopathy (CAA) is a prominent feature in the majority of AD. Although impaired cerebral blood flow (CBF) has been implicated in faulty Aβ transport and clearance, and cerebral hypoperfusion can exist in the pre-clinical phase of Alzheimer's disease (AD), it is still unclear whether it is one of the causal factors for AD pathogenesis, or an early consequence of a multi-factor condition that would lead to AD at late stage. To study the potential interaction between faulty CBF and amyloid accumulation in clinical-relevant situation, we generated a new amyloid precursor protein (APP) knock-in allele that expresses humanized Aβ and a Dutch mutation in addition to Swedish/London mutations and compared this line with an equivalent knock-in line but in the absence of the Dutch mutation, both crossed onto the PS1M146V knock-in background. Introduction of the Dutch mutation results in robust CAA and parenchymal Aβ pathology, age-dependent reduction of spatial learning and memory deficits, and CBF reduction as detected by fMRI. Direct manipulation of CBF by transverse aortic constriction surgery on the left common carotid artery caused differential changes in CBF in the anterior and middle region of the cortex, where it is reduced on the left side and increased on the right side. However these perturbations in CBF resulted in the same effect: both significantly exacerbate CAA and amyloid pathology. Our study reveals a direct and positive link between vascular and parenchymal Aβ; both can be modulated by CBF. The new APP knock-in mouse model recapitulates many symptoms of AD including progressive vascular and parenchymal Aβ pathology and behavioral deficits in the absence of APP overexpression.

Studies on the control of development: isolation of Bacillus subtilis mutants blocked early in sporulation and defective in synthesis of highly phosphorylated nucleotides.

PubMed

Rhaese, H J; Hoch, J A; Groscurth, R

1977-03-01

To test our model on the mechanism of initiation of differentiation in Bacillus subtilis, we tested early blocked (stage 0) sporulation mutants for their ability to synthesize highly phosphorylated nucleotides. We also isolated early blocked asporogenous mutants with the aid of the intercalating drug tilorone. Among all mutants tested we found that the spo0F-bearing strain was unable to synthesize adenosine 3'(2')-triphosphate 5'-triphosphate, pppAppp. A revertant of this mutant regained the ability to both sporulate and synthesize pppAppp. Ribosomes of the asporogenous mutant isolated at T2 (2 hr after the end of logarithmic growth) of sporulation, in contrast to the wild type, do not synthesize adenosine 3'(2')-diphosphate 5'-diphosphate, ppApp, or adenosine 3'(2')-diphosphate 5'-triphosphate, pppApp, but synthesize guanosine 3'(2')-diphosphate 5'-diphosphate, ppGpp, and guanosine 3'(2')-diphosphate 5'-triphosphate, pppGpp. This behavior is characteristic of ribosomes from vegetative, not sporulating, cells. Ribosomes from the sporogenous revertant behave like those of the wild type. The results suggest that the spo0F mutation may be a mutation in the structural gene for pppAppp synthetase. The inability to synthesize pppAppp in this strain also prevents the formation of "sporulation-specific ribosomes," i.e., ribosomes that synthetize ppApp and pppApp. The present experiments suggest that the nucleotide pppAppp participates in the initiation of sporulation by triggering a sequencies of events required for the production of heat-resistant spores.

Inhibition of γ-secretase worsens memory deficits in a genetically congruous mouse model of Danish dementia

PubMed Central

2012-01-01

Background A mutation in the BRI2/ITM2b gene causes familial Danish dementia (FDD). BRI2 is an inhibitor of amyloid-β precursor protein (APP) processing, which is genetically linked to Alzheimer’s disease (AD) pathogenesis. The FDD mutation leads to a loss of BRI2 protein and to increased APP processing. APP haplodeficiency and inhibition of APP cleavage by β-secretase rescue synaptic/memory deficits of a genetically congruous mouse model of FDD (FDDKI). β-cleavage of APP yields the β-carboxyl-terminal (β-CTF) and the amino-terminal-soluble APPβ (sAPPβ) fragments. γ-secretase processing of β-CTF generates Aβ, which is considered the main cause of AD. However, inhibiting Aβ production did not rescue the deficits of FDDKI mice, suggesting that sAPPβ/β-CTF, and not Aβ, are the toxic species causing memory loss. Results Here, we have further analyzed the effect of γ-secretase inhibition. We show that treatment with a γ-secretase inhibitor (GSI) results in a worsening of the memory deficits of FDDKI mice. This deleterious effect on memory correlates with increased levels of the β/α-CTFs APP fragments in synaptic fractions isolated from hippocampi of FDDKI mice, which is consistent with inhibition of γ-secretase activity. Conclusion This harmful effect of the GSI is in sharp contrast with a pathogenic role for Aβ, and suggests that the worsening of memory deficits may be due to accumulation of synaptic-toxic β/α-CTFs caused by GSI treatment. However, γ-secretase cleaves more than 40 proteins; thus, the noxious effect of GSI on memory may be dependent on inhibition of cleavage of one or more of these other γ-secretase substrates. These two possibilities do not need to be mutually exclusive. Our results are consistent with the outcome of a clinical trial with the GSI Semagacestat, which caused a worsening of cognition, and advise against targeting γ-secretase in the therapy of AD. Overall, the data also indicate that FDDKI is a valuable mouse model to study AD pathogenesis and predict the clinical outcome of therapeutic agents for AD. PMID:22537414

Inhibition of γ-secretase worsens memory deficits in a genetically congruous mouse model of Danish dementia.

PubMed

Tamayev, Robert; D'Adamio, Luciano

2012-04-26

A mutation in the BRI2/ITM2b gene causes familial Danish dementia (FDD). BRI2 is an inhibitor of amyloid-β precursor protein (APP) processing, which is genetically linked to Alzheimer's disease (AD) pathogenesis. The FDD mutation leads to a loss of BRI2 protein and to increased APP processing. APP haplodeficiency and inhibition of APP cleavage by β-secretase rescue synaptic/memory deficits of a genetically congruous mouse model of FDD (FDDKI). β-cleavage of APP yields the β-carboxyl-terminal (β-CTF) and the amino-terminal-soluble APPβ (sAPPβ) fragments. γ-secretase processing of β-CTF generates Aβ, which is considered the main cause of AD. However, inhibiting Aβ production did not rescue the deficits of FDDKI mice, suggesting that sAPPβ/β-CTF, and not Aβ, are the toxic species causing memory loss. Here, we have further analyzed the effect of γ-secretase inhibition. We show that treatment with a γ-secretase inhibitor (GSI) results in a worsening of the memory deficits of FDDKI mice. This deleterious effect on memory correlates with increased levels of the β/α-CTFs APP fragments in synaptic fractions isolated from hippocampi of FDDKI mice, which is consistent with inhibition of γ-secretase activity. This harmful effect of the GSI is in sharp contrast with a pathogenic role for Aβ, and suggests that the worsening of memory deficits may be due to accumulation of synaptic-toxic β/α-CTFs caused by GSI treatment. However, γ-secretase cleaves more than 40 proteins; thus, the noxious effect of GSI on memory may be dependent on inhibition of cleavage of one or more of these other γ-secretase substrates. These two possibilities do not need to be mutually exclusive. Our results are consistent with the outcome of a clinical trial with the GSI Semagacestat, which caused a worsening of cognition, and advise against targeting γ-secretase in the therapy of AD. Overall, the data also indicate that FDDKI is a valuable mouse model to study AD pathogenesis and predict the clinical outcome of therapeutic agents for AD.

The Amyloid Precursor Protein is rapidly transported from the Golgi apparatus to the lysosome and where it is processed into beta-amyloid

PubMed Central

2014-01-01

Background Alzheimer’s disease (AD) is characterized by cerebral deposition of β-amyloid peptide (Aβ). Aβ is produced by sequential cleavage of the Amyloid Precursor Protein (APP) by β- and γ-secretases. Many studies have demonstrated that the internalization of APP from the cell surface can regulate Aβ production, although the exact organelle in which Aβ is produced remains contentious. A number of recent studies suggest that intracellular trafficking also plays a role in regulating Aβ production, but these pathways are relatively under-studied. The goal of this study was to elucidate the intracellular trafficking of APP, and to examine the site of intracellular APP processing. Results We have tagged APP on its C-terminal cytoplasmic tail with photoactivatable Green Fluorescent Protein (paGFP). By photoactivating APP-paGFP in the Golgi, using the Golgi marker Galactosyltranferase fused to Cyan Fluorescent Protein (GalT-CFP) as a target, we are able to follow a population of nascent APP molecules from the Golgi to downstream compartments identified with compartment markers tagged with red fluorescent protein (mRFP or mCherry); including rab5 (early endosomes) rab9 (late endosomes) and LAMP1 (lysosomes). Because γ-cleavage of APP releases the cytoplasmic tail of APP including the photoactivated GFP, resulting in loss of fluorescence, we are able to visualize the cleavage of APP in these compartments. Using APP-paGFP, we show that APP is rapidly trafficked from the Golgi apparatus to the lysosome; where it is rapidly cleared. Chloroquine and the highly selective γ-secretase inhibitor, L685, 458, cause the accumulation of APP in lysosomes implying that APP is being cleaved by secretases in the lysosome. The Swedish mutation dramatically increases the rate of lysosomal APP processing, which is also inhibited by chloroquine and L685, 458. By knocking down adaptor protein 3 (AP-3; a heterotetrameric protein complex required for trafficking many proteins to the lysosome) using siRNA, we are able to reduce this lysosomal transport. Blocking lysosomal transport of APP reduces Aβ production by more than a third. Conclusion These data suggests that AP-3 mediates rapid delivery of APP to lysosomes, and that the lysosome is a likely site of Aβ production. PMID:25085554

Leptin and leptin receptor gene polymorphisms are correlated with production performance in the Arctic fox.

PubMed

Zhang, M; Bai, X J

2015-05-25

The polymerase chain reaction-single-strand conformation polymorphism technique was employed to measure mononucleotide diversity in the coding region of the leptin and leptin receptor genes in the Arctic fox. The relationships between specific genetic mutations and reproductive performance in Arctic foxes were determined to im-prove breeding strategies. We found that a leptin gene polymorphism was significantly associated with body weight (P < 0.01), abdominal circumference (P < 0.01), and fur length (P < 0.01). Furthermore, a polymorphism in the leptin receptor gene was associated with carcass weight and guard hair length (P < 0.01). Leptin and leptin receptor gene combinatorial genotypes were significantly associated with abdominal circumference, fur length (P < 0.01), and body weight (P < 0.05). The leptin gene is thus a key gene affecting body weight, abdominal circumference, and fur length in Arctic foxes, whereas variations in the leptin receptor mainly affect carcass weight and guard hair. The marker loci identified in this study can be used to assist in the selection of Arctic foxes for breeding to raise the production performance of this species.

X11/Mint Genes Control Polarized Localization of Axonal Membrane Proteins in Vivo

PubMed Central

Gross, Garrett G.; Lone, G. Mohiddin; Leung, Lok Kwan; Hartenstein, Volker

2013-01-01

Mislocalization of axonal proteins can result in misassembly and/or miswiring of neural circuits, causing disease. To date, only a handful of genes that control polarized localization of axonal membrane proteins have been identified. Here we report that Drosophila X11/Mint proteins are required for targeting several proteins, including human amyloid precursor protein (APP) and Drosophila APP-like protein (APPL), to axonal membranes and for their exclusion from dendrites of the mushroom body in Drosophila, a brain structure involved in learning and memory. Axonal localization of APP is mediated by an endocytic motif, and loss of X11/Mint results in a dramatic increase in cell-surface levels of APPL, especially on dendrites. Mutations in genes required for endocytosis show similar mislocalization of these proteins to dendrites, and strongly enhance defects seen in X11/Mint mutants. These results suggest that X11/Mint-dependent endocytosis in dendrites may serve to promote the axonal localization of membrane proteins. Since X11/Mint binds to APP, and abnormal trafficking of APP contributes to Alzheimer's disease, deregulation of X11/Mint may be important for Alzheimer's disease pathogenesis. PMID:23658195

Amyloid Precursor Protein and Proinflammatory Changes Are Regulated in Brain and Adipose Tissue in a Murine Model of High Fat Diet-Induced Obesity

PubMed Central

Puig, Kendra L.; Floden, Angela M.; Adhikari, Ramchandra; Golovko, Mikhail Y.; Combs, Colin K.

2012-01-01

Background Middle age obesity is recognized as a risk factor for Alzheimer's disease (AD) although a mechanistic linkage remains unclear. Based upon the fact that obese adipose tissue and AD brains are both areas of proinflammatory change, a possible common event is chronic inflammation. Since an autosomal dominant form of AD is associated with mutations in the gene coding for the ubiquitously expressed transmembrane protein, amyloid precursor protein (APP) and recent evidence demonstrates increased APP levels in adipose tissue during obesity it is feasible that APP serves some function in both disease conditions. Methodology/Principal Findings To determine whether diet-induced obesity produced proinflammatory changes and altered APP expression in brain versus adipose tissue, 6 week old C57BL6/J mice were maintained on a control or high fat diet for 22 weeks. Protein levels and cell-specific APP expression along with markers of inflammation and immune cell activation were compared between hippocampus, abdominal subcutaneous fat and visceral pericardial fat. APP stimulation-dependent changes in macrophage and adipocyte culture phenotype were examined for comparison to the in vivo changes. Conclusions/Significance Adipose tissue and brain from high fat diet fed animals demonstrated increased TNF-α and microglial and macrophage activation. Both brains and adipose tissue also had elevated APP levels localizing to neurons and macrophage/adipocytes, respectively. APP agonist antibody stimulation of macrophage cultures increased specific cytokine secretion with no obvious effects on adipocyte culture phenotype. These data support the hypothesis that high fat diet-dependent obesity results in concomitant pro-inflammatory changes in brain and adipose tissue that is characterized, in part, by increased levels of APP that may be contributing specifically to inflammatory changes that occur. PMID:22276186

Hippocampal mutant APP and amyloid beta-induced cognitive decline, dendritic spine loss, defective autophagy, mitophagy and mitochondrial abnormalities in a mouse model of Alzheimer's disease.

PubMed

Manczak, Maria; Kandimalla, Ramesh; Yin, Xiangling; Reddy, P Hemachandra

2018-04-15

The purpose of our study was to determine the toxic effects of hippocampal mutant APP and amyloid beta (Aβ) in 12-month-old APP transgenic mice. Using rotarod and Morris water maze tests, immunoblotting and immunofluorescence, Golgi-cox staining and transmission electron microscopy, we assessed cognitive behavior, protein levels of synaptic, autophagy, mitophagy, mitochondrial dynamics, biogenesis, dendritic protein MAP2 and quantified dendritic spines and mitochondrial number and length in 12-month-old APP mice that express Swedish mutation. Mitochondrial function was assessed by measuring the levels of hydrogen peroxide, lipid peroxidation, cytochrome c oxidase activity and mitochondrial ATP. Morris water maze and rotarod tests revealed that hippocampal learning and memory and motor learning and coordination were impaired in APP mice relative to wild-type (WT) mice. Increased levels of mitochondrial fission proteins, Drp1 and Fis1 and decreased levels of fusion (Mfn1, Mfn2 and Opa1) biogenesis (PGC1α, NRF1, NRF2 and TFAM), autophagy (ATG5 and LC3BI, LC3BII), mitophagy (PINK1 and TERT), synaptic (synaptophysin and PSD95) and dendritic (MAP2) proteins were found in 12-month-old APP mice relative to age-matched non-transgenic WT mice. Golgi-cox staining analysis revealed that dendritic spines are significantly reduced. Transmission electron microscopy revealed significantly increased mitochondrial numbers and reduced mitochondrial length in APP mice. These findings suggest that hippocampal accumulation of mutant APP and Aβ is responsible for abnormal mitochondrial dynamics and defective biogenesis, reduced MAP2, autophagy, mitophagy and synaptic proteins and reduced dendritic spines and hippocampal-based learning and memory impairments, and mitochondrial structural and functional changes in 12-month-old APP mice.

Phosphorylation of amyloid precursor protein at threonine 668 is essential for its copper-responsive trafficking in SH-SY5Y neuroblastoma cells.

PubMed

Acevedo, Karla M; Opazo, Carlos M; Norrish, David; Challis, Leesa M; Li, Qiao-Xin; White, Anthony R; Bush, Ashley I; Camakaris, James

2014-04-18

Amyloid precursor protein (APP) undergoes post-translational modification, including O- and N-glycosylation, ubiquitination, and phosphorylation as it traffics through the secretory pathway. We have previously reported that copper promotes a change in the cellular localization of APP. We now report that copper increases the phosphorylation of endogenous APP at threonine 668 (Thr-668) in SH-SY5Y neuronal cells. The level of APPT668-p (detected using a phospho-site-specific antibody) exhibited a copper-dependent increase. Using confocal microscopy imaging we demonstrate that the phospho-deficient mutant, Thr-668 to alanine (T668A), does not exhibit detectable copper-responsive APP trafficking. In contrast, mutating a serine to an alanine at residue 655 does not affect copper-responsive trafficking. We further investigated the importance of the Thr-668 residue in copper-responsive trafficking by treating SH-SY5Y cells with inhibitors for glycogen synthase kinase 3-β (GSK3β) and cyclin-dependent kinases (Cdk), the main kinases that phosphorylate APP at Thr-668 in neurons. Our results show that the GSK3β kinase inhibitors LiCl, SB 216763, and SB 415286 prevent copper-responsive APP trafficking. In contrast, the Cdk inhibitors Purvalanol A and B had no significant effect on copper-responsive trafficking in SH-SY5Y cells. In cultured primary hippocampal neurons, copper promoted APP re-localization to the axon, and this effect was inhibited by the addition of LiCl, indicating that a lithium-sensitive kinase(s) is involved in copper-responsive trafficking in hippocampal neurons. This is consistent with APP axonal transport to the synapse, where APP is involved in a number of functions. We conclude that copper promotes APP trafficking by promoting a GSK3β-dependent phosphorylation in SH-SY5Y cells.

Phosphorylation of Amyloid Precursor Protein at Threonine 668 Is Essential for Its Copper-responsive Trafficking in SH-SY5Y Neuroblastoma Cells*

PubMed Central

Acevedo, Karla M.; Opazo, Carlos M.; Norrish, David; Challis, Leesa M.; Li, Qiao-Xin; White, Anthony R.; Bush, Ashley I.; Camakaris, James

2014-01-01

Amyloid precursor protein (APP) undergoes post-translational modification, including O- and N-glycosylation, ubiquitination, and phosphorylation as it traffics through the secretory pathway. We have previously reported that copper promotes a change in the cellular localization of APP. We now report that copper increases the phosphorylation of endogenous APP at threonine 668 (Thr-668) in SH-SY5Y neuronal cells. The level of APPT668-p (detected using a phospho-site-specific antibody) exhibited a copper-dependent increase. Using confocal microscopy imaging we demonstrate that the phospho-deficient mutant, Thr-668 to alanine (T668A), does not exhibit detectable copper-responsive APP trafficking. In contrast, mutating a serine to an alanine at residue 655 does not affect copper-responsive trafficking. We further investigated the importance of the Thr-668 residue in copper-responsive trafficking by treating SH-SY5Y cells with inhibitors for glycogen synthase kinase 3-β (GSK3β) and cyclin-dependent kinases (Cdk), the main kinases that phosphorylate APP at Thr-668 in neurons. Our results show that the GSK3β kinase inhibitors LiCl, SB 216763, and SB 415286 prevent copper-responsive APP trafficking. In contrast, the Cdk inhibitors Purvalanol A and B had no significant effect on copper-responsive trafficking in SH-SY5Y cells. In cultured primary hippocampal neurons, copper promoted APP re-localization to the axon, and this effect was inhibited by the addition of LiCl, indicating that a lithium-sensitive kinase(s) is involved in copper-responsive trafficking in hippocampal neurons. This is consistent with APP axonal transport to the synapse, where APP is involved in a number of functions. We conclude that copper promotes APP trafficking by promoting a GSK3β-dependent phosphorylation in SH-SY5Y cells. PMID:24610780

Mutant APP and Amyloid beta-induced defective autophagy, mitophagy, mitochondrial structural and functional changes and synaptic damage in hippocampal neurons from Alzheimer's disease.

PubMed

Reddy, P Hemachandra; Yin, XiangLin; Manczak, Maria; Kumar, Subodh; Jangampalli Adi, Pradeepkiran; Vijayan, Murali; Reddy, Arubala P

2018-04-25

The purpose of our study was to determine the toxic effects of hippocampal mutant APP and amyloid beta (Aβ) in human mutant APP (mAPP) cDNA transfected with primary mouse hippocampal neurons (HT22). Hippocampal tissues are the best source of studying learning and memory functions in patients with Alzheimer's disease (AD) and healthy controls. However, investigating immortalized hippocampal neurons that express AD proteins provide an excellent opportunity for drug testing. Using quantitative RT-PCR, immunoblotting & immunofluorescence, and transmission electron microscopy, we assessed mRNA and protein levels of synaptic, autophagy, mitophagy, mitochondrial dynamics, biogenesis, dendritic protein MAP2, and assessed mitochondrial number and length in mAPP-HT22 cells that express Swedish/Indiana mutations. Mitochondrial function was assessed by measuring the levels of hydrogen peroxide, lipid peroxidation, cytochrome c oxidase activity and mitochondrial ATP. Increased levels of mRNA and protein levels of mitochondrial fission genes, Drp1 and Fis1 and decreased levels fusion (Mfn1, Mfn2 and Opa1) biogenesis (PGC1α, NRF1, NRF2 & TFAM), autophagy (ATG5 & LC3BI, LC3BII), mitophagy (PINK1 & TERT, BCL2 & BNIPBL), synaptic (synaptophysin & PSD95) and dendritic (MAP2) genes were found in mAPP-HT22 cells relative to WT-HT22 cells. Cell survival was significantly reduced mAPP-HT22 cells. GTPase-Dp1 enzymatic activity was increased in mAPP-HT22 cells. Transmission electron microscopy revealed significantly increased mitochondrial numbers and reduced mitochondrial length in mAPP-HT22 cells. These findings suggest that hippocampal accumulation of mutant APP and Aβ is responsible for abnormal mitochondrial dynamics and defective biogenesis, reduced MAP2, autophagy, mitophagy and synaptic proteins & reduced dendritic spines and mitochondrial structural and functional changes in mutant APP hippocampal cells. These observations strongly suggest that accumulation of mAPP and Aβ causes mitochondrial, synaptic and autophagy/mitophagy abnormalities in hippocampal neurons, leading to neuronal dysfunction.

GENETIC CATHEPSIN B DEFICIENCY REDUCES β-AMYLOID IN TRANSGENIC MICE EXPRESSING HUMAN WILD-TYPE AMYLOID PRECURSOR PROTEIN

PubMed Central

Hook, Vivian Y. H.; Kindy, Mark; Reinheckel, Thomas; Peters, Christoph; Hook, Gregory

2009-01-01

Neurotoxic β-amyloid (Aβ) peptides participate in Alzheimer’s disease (AD); therefore, reduction of Aβ generated from APP may provide a therapeutic approach for AD. Gene knockout studies in transgenic mice producing human Aβ may identify targets for reducing Aβ. This study shows that knockout of the cathepsin B gene in mice expressing human wild-type APP (hAPPwt) results in substantial decrease of Aβ40 and Aβ42 by 67% in brain, and decreases levels of the C-terminal β-secretase fragment (CTFβ) derived from APP. In contrast, knockout of cathepsin B in mice expressing hAPP with the rare Swedish (Swe) and Indiana (Ind) mutations had no effect on Aβ. The difference in reduction of Aβ in hAPPwt mice, but not in hAPPSwe/Ind mice, shows that the transgenic model can affect cathepsin B gene knockout results. Since most AD patients express hAPPwt, these data validate cathepsin B as a target for development of inhibitors to lower Aβ in AD. PMID:19501042

Alzheimer Abeta peptide induces chromosome mis-segregation and aneuploidy, including trisomy 21: requirement for tau and APP.

PubMed

Granic, Antoneta; Padmanabhan, Jaya; Norden, Michelle; Potter, Huntington

2010-02-15

Both sporadic and familial Alzheimer's disease (AD) patients exhibit increased chromosome aneuploidy, particularly trisomy 21, in neurons and other cells. Significantly, trisomy 21/Down syndrome patients develop early onset AD pathology. We investigated the mechanism underlying mosaic chromosome aneuploidy in AD and report that FAD mutations in the Alzheimer Amyloid Precursor Protein gene, APP, induce chromosome mis-segregation and aneuploidy in transgenic mice and in transfected cells. Furthermore, adding synthetic Abeta peptide, the pathogenic product of APP, to cultured cells causes rapid and robust chromosome mis-segregation leading to aneuploid, including trisomy 21, daughters, which is prevented by LiCl addition or Ca(2+) chelation and is replicated in tau KO cells, implicating GSK-3beta, calpain, and Tau-dependent microtubule transport in the aneugenic activity of Abeta. Furthermore, APP KO cells are resistant to the aneugenic activity of Abeta, as they have been shown previously to be resistant to Abeta-induced tau phosphorylation and cell toxicity. These results indicate that Abeta-induced microtubule dysfunction leads to aneuploid neurons and may thereby contribute to the pathogenesis of AD.

Pharmacological activation of LXRs decreases amyloid-β levels in Niemann-Pick type C model cells.

PubMed

Stefulj, Jasminka; Peric, Maja; Malnar, Martina; Kosicek, Marko; Schweinzer, Cornelia; Zivkovic, Jelena; Scholler, Monika; Panzenboeck, Ute; Hecimovic, Silva

2013-01-01

Niemann-Pick type C disease (NPC) is an inherited disorder mainly caused by loss-of-function mutations in the NPC1 gene, that lead to intracellular cholesterol accumulation and disturbed cholesterol homeostasis. Similarly to Alzheimer's disease (AD), NPC is associated with progressive neurodegeneration and altered metabolism of amyloid precursor protein (APP). Liver X receptors (LXRs), the key transcriptional regulators of cholesterol homeostasis, were reported to play neuroprotective roles in NPC mice. We investigated the impacts of LXRs on APP metabolism in mutant CHO cells lacking the NPC1 gene (-NPC1 cells). Pharmacological activation of LXRs in -NPC1 cells tended to reduce the ratio of total secreted APP (sAPP) to full length APP (flAPP) levels and sAPPβ levels as well as to increase the ratio of APP Cterminal fragments to flAPP levels, resulting in decreased levels of amyloid β (Aβ) peptides. -NPC1 cells treated with LXR agonist TO901317 (TO90) displayed a modest increase in cholesterol efflux to apolipoprotein A-I (apoA-I) but not to HDL3, or in the absence of extracellular cholesterol acceptors. The observed similar reduction of Aβ levels upon TO90 treatment in the presence or in the absence of extracellular apoA-I indicated a cholesterol-efflux independent effect of TO90 on Aβ levels. Furthermore, TO90 had no effect on the cholesterol synthesis rate in -NPC1 cells, while it reduced the rate of cholesterol esterification. The obtained results indicate that LXR activation may decrease Aβ levels in NPC1- deficient conditions. The underlying mechanism of this action does not appear to be related to effects on cholesterol efflux or synthesis rates.

Adaptor protein 2–mediated endocytosis of the β-secretase BACE1 is dispensable for amyloid precursor protein processing

PubMed Central

Prabhu, Yogikala; Burgos, Patricia V.; Schindler, Christina; Farías, Ginny G.; Magadár, Javier G.; Bonifacino, Juan S.

2012-01-01

The β-site amyloid precursor protein (APP)–cleaving enzyme 1 (BACE1) is a transmembrane aspartyl protease that catalyzes the proteolytic processing of APP and other plasma membrane protein precursors. BACE1 cycles between the trans-Golgi network (TGN), the plasma membrane, and endosomes by virtue of signals contained within its cytosolic C-terminal domain. One of these signals is the DXXLL-motif sequence DISLL, which controls transport between the TGN and endosomes via interaction with GGA proteins. Here we show that the DISLL sequence is embedded within a longer [DE]XXXL[LI]-motif sequence, DDISLL, which mediates internalization from the plasma membrane by interaction with the clathrin-associated, heterotetrameric adaptor protein 2 (AP-2) complex. Mutation of this signal or knockdown of either AP-2 or clathrin decreases endosomal localization and increases plasma membrane localization of BACE1. Remarkably, internalization-defective BACE1 is able to cleave an APP mutant that itself cannot be delivered to endosomes. The drug brefeldin A reversibly prevents BACE1-catalyzed APP cleavage, ruling out that this reaction occurs in the endoplasmic reticulum (ER) or ER–Golgi intermediate compartment. Taken together, these observations support the notion that BACE1 is capable of cleaving APP in late compartments of the secretory pathway. PMID:22553349

Proteomic Changes in Cerebrospinal Fluid of Presymptomatic and Affected Persons Carrying Familial Alzheimer Disease Mutations

PubMed Central

Ringman, John M.; Schulman, Howard; Becker, Chris; Jones, Ted; Bai, Yuchen; Immermann, Fred; Cole, Gregory; Sokolow, Sophie; Gylys, Karen; Geschwind, Daniel H.; Cummings, Jeffrey L.; Wan, Hong I.

2013-01-01

Objective To identify cerebrospinal fluid (CSF) protein changes in persons who will develop familial Alzheimer disease (FAD) due to PSEN1 and APP mutations, using unbiased proteomics. Design We compared proteomic profiles of CSF from individuals with FAD who were mutation carriers (MCs) and related noncarriers (NCs). Abundant proteins were depleted and samples were analyzed using liquid chromatography– electrospray ionization–mass spectrometry on a high-resolution time-of-flight instrument. Tryptic peptides were identified by tandem mass spectrometry. Proteins differing in concentration between the MCs and NCs were identified. Setting A tertiary dementia referral center and a proteomic biomarker discovery laboratory. Participants Fourteen FAD MCs (mean age, 34.2 years; 10 are asymptomatic, 12 have presenilin-1 [PSEN1] gene mutations, and 2 have amyloid precursor protein [APP] gene mutations) and 5 related NCs (mean age, 37.6 years). Results Fifty-six proteins were identified, represented by multiple tryptic peptides showing significant differences between MCs and NCs (46 upregulated and 10 downregulated); 40 of these proteins differed when the analysis was restricted to asymptomatic individuals. Fourteen proteins have been reported in prior proteomic studies in late-onset AD, including amyloid precursor protein, transferrin, α1β-glycoprotein, complement components, afamin precursor, spondin 1, plasminogen, hemopexin, and neuronal pentraxin receptor. Many other proteins were unique to our study, including calsyntenin 3, AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) 4 glutamate receptor, CD99 antigen, di-N-acetyl-chitobiase, and secreted phosphoprotein 1. Conclusions We found much overlap in CSF protein changes between individuals with presymptomatic and symptomatic FAD and those with late-onset AD. Our results are consistent with inflammation and synaptic loss early in FAD and suggest new presymptomatic biomarkers of potential usefulness in drug development. PMID:22232349

Novel PSEN1 G209A mutation in early-onset Alzheimer dementia supported by structural prediction.

PubMed

An, Seong Soo A; Bagyinszky, Eva; Kim, Hye Ryoun; Seok, Ju-Won; Shin, Hae-Won; Bae, SeunOh; Kim, SangYun; Youn, Young Chul

2016-05-20

Three main genes are described as causative genes for early-onset Alzheimer dementia (EOAD): APP, PSEN1 and PSEN2. We describe a woman with EOAD had a novel PSEN1 mutation. A 54-year-old right-handed woman presented 12-year history of progressive memory decline. She was clinically diagnosed as familial Alzheimer's disease due to a PSEN1 mutation. One of two daughters also has the same mutation, G209A in the TM-IV of PS1 protein. Her mother had unspecified dementia that began at the age of 40s. PolyPhen2 and SIFT prediction suggested that G209A might be a damaging variant with high scores. 3D modeling revealed that G209A exchange could result significant changes in the PS1 protein. We report a case of EOAD having probable novel PSEN1 (G209A) mutation verified with structural prediction.

Amyloid Precursor Protein (APP) May Act as a Substrate and a Recognition Unit for CRL4CRBN and Stub1 E3 Ligases Facilitating Ubiquitination of Proteins Involved in Presynaptic Functions and Neurodegeneration.

PubMed

Del Prete, Dolores; Rice, Richard C; Rajadhyaksha, Anjali M; D'Adamio, Luciano

2016-08-12

The amyloid precursor protein (APP), whose mutations cause Alzheimer disease, plays an important in vivo role and facilitates transmitter release. Because the APP cytosolic region (ACR) is essential for these functions, we have characterized its brain interactome. We found that the ACR interacts with proteins that regulate the ubiquitin-proteasome system, predominantly with the E3 ubiquitin-protein ligases Stub1, which binds the NH2 terminus of the ACR, and CRL4(CRBN), which is formed by Cul4a/b, Ddb1, and Crbn, and interacts with the COOH terminus of the ACR via Crbn. APP shares essential functions with APP-like protein-2 (APLP2) but not APP-like protein-1 (APLP1). Noteworthy, APLP2, but not APLP1, interacts with Stub1 and CRL4(CRBN), pointing to a functional pathway shared only by APP and APLP2. In vitro ubiquitination/ubiquitome analysis indicates that these E3 ligases are enzymatically active and ubiquitinate the ACR residues Lys(649/650/651/676/688) Deletion of Crbn reduces ubiquitination of Lys(676) suggesting that Lys(676) is physiologically ubiquitinated by CRL4(CRBN) The ACR facilitated in vitro ubiquitination of presynaptic proteins that regulate exocytosis, suggesting a mechanism by which APP tunes transmitter release. Other dementia-related proteins, namely Tau and apoE, interact with and are ubiquitinated via the ACR in vitro This, and the evidence that CRBN and CUL4B are linked to intellectual disability, prompts us to hypothesize a pathogenic mechanism, in which APP acts as a modulator of E3 ubiquitin-protein ligase(s), shared by distinct neuronal disorders. The well described accumulation of ubiquitinated protein inclusions in neurodegenerative diseases and the link between the ubiquitin-proteasome system and neurodegeneration make this concept plausible. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Engaging informal audiences in learning about and responding to climate change through a portfolio of innovative approaches

NASA Astrophysics Data System (ADS)

Pfirman, S. L.; Brunacini, J.; Orlove, B. S.; Bachrach, E.; Hamilton, L.

2017-12-01

Informal learners have many different backgrounds, experiences, and perspectives. How can informal educators effectively reach such diverse audiences, meeting people where they are with regard to climate change? The Polar Learning and Responding: PoLAR Climate Change Education Partnership, supported by NSF, employs surveys, resource development, and research to develop innovative, evidence-based approaches that engage lifelong learners. General-public surveys on climate change yield insights on the knowledge and perceptions that informal learners bring to the table. That helps guide the creation of new tools for effective communication. For example, many people are unsure what causes sea level to rise. The Polar Explorer: Sea Level app uses a data and question-based approach guiding people through interactive maps to learn about melting land ice. In addition, people also tend to believe that climate impacts will happen in the future. Polar Voices podcasts feature Arctic Indigenous communities sharing first-hand experiences with climate change. Prior knowledge can be harnessed to enhance learning. Arctic SMARTIC engages people in role-playing negotiations with others to create a marine management plan. Climate game jams provide collaborative, creative spaces where participants learn as they interact with others. In each case participants, with all their knowledge and experience, are brought into group problem-solving. Understanding whom people trust for climate-change information offers insights that help them become climate communicators. Even those who are concerned about climate often do not discuss it with family and friends (Maibach et al. 2016), yet our research shows that family and friends are second only to scientists as trusted sources of climate information (Hamilton 2016). Fun and novel educational tools such as the EcoChains card game and the EcoKoin social networking app serve as conversation starters.

Distinct amyloid precursor protein processing machineries of the olfactory system.

PubMed

Kim, Jae Yeon; Rasheed, Ameer; Yoo, Seung-Jun; Kim, So Yeun; Cho, Bongki; Son, Gowoon; Yu, Seong-Woon; Chang, Keun-A; Suh, Yoo-Hun; Moon, Cheil

2018-01-01

Processing of amyloid precursor protein (APP) occurs through sequential cleavages first by β-secretase and then by the γ-secretase complex. However, abnormal processing of APP leads to excessive production of β-amyloid (Aβ) in the central nervous system (CNS), an event which is regarded as a primary cause of Alzheimer's disease (AD). In particular, gene mutations of the γ-secretase complex-which contains presenilin 1 or 2 as the catalytic core-could trigger marked Aβ accumulation. Olfactory dysfunction usually occurs before the onset of typical AD-related symptoms (eg, memory loss or muscle retardation), suggesting that the olfactory system may be one of the most vulnerable regions to AD. To date however, little is known about why the olfactory system is affected so early by AD prior to other regions. Thus, we examined the distribution of secretases and levels of APP processing in the olfactory system under either healthy or pathological conditions. Here, we show that the olfactory system has distinct APP processing machineries. In particular, we identified higher expressions levels and activity of γ-secretase in the olfactory epithelium (OE) than other regions of the brain. Moreover, APP c-terminal fragments (CTF) are markedly detected. During AD progression, we note increased expression of presenilin2 of γ-secretases in the OE, not in the OB, and show that neurotoxic Aβ*56 accumulates more quickly in the OE. Taken together, these results suggest that the olfactory system has distinct APP processing machineries under healthy and pathological conditions. This finding may provide a crucial understanding of the unique APP-processing mechanisms in the olfactory system, and further highlights the correlation between olfactory deficits and AD symptoms. Copyright © 2017 Elsevier Inc. All rights reserved.

Circadian and Brain State Modulation of Network Hyperexcitability in Alzheimer's Disease.

PubMed

Brown, Rosalind; Lam, Alice D; Gonzalez-Sulser, Alfredo; Ying, Andrew; Jones, Mary; Chou, Robert Chang-Chih; Tzioras, Makis; Jordan, Crispin Y; Jedrasiak-Cape, Izabela; Hemonnot, Anne-Laure; Abou Jaoude, Maurice; Cole, Andrew J; Cash, Sydney S; Saito, Takashi; Saido, Takaomi; Ribchester, Richard R; Hashemi, Kevan; Oren, Iris

2018-01-01

Network hyperexcitability is a feature of Alzheimer' disease (AD) as well as numerous transgenic mouse models of AD. While hyperexcitability in AD patients and AD animal models share certain features, the mechanistic overlap remains to be established. We aimed to identify features of network hyperexcitability in AD models that can be related to epileptiform activity signatures in AD patients. We studied network hyperexcitability in mice expressing amyloid precursor protein (APP) with mutations that cause familial AD, and compared a transgenic model that overexpresses human APP (hAPP) (J20), to a knock-in model expressing APP at physiological levels (APP NL/F ). We recorded continuous long-term electrocorticogram (ECoG) activity from mice, and studied modulation by circadian cycle, behavioral, and brain state. We report that while J20s exhibit frequent interictal spikes (IISs), APP NL/F mice do not. In J20 mice, IISs were most prevalent during daylight hours and the circadian modulation was associated with sleep. Further analysis of brain state revealed that IIS in J20s are associated with features of rapid eye movement (REM) sleep. We found no evidence of cholinergic changes that may contribute to IIS-circadian coupling in J20s. In contrast to J20s, intracranial recordings capturing IIS in AD patients demonstrated frequent IIS in non-REM (NREM) sleep. The salient differences in sleep-stage coupling of IIS in APP overexpressing mice and AD patients suggests that different mechanisms may underlie network hyperexcitability in mice and humans. We posit that sleep-stage coupling of IIS should be an important consideration in identifying mouse AD models that most closely recapitulate network hyperexcitability in human AD.

Glycogen Synthase Kinase 3 Inhibition Promotes Lysosomal Biogenesis and Autophagic Degradation of the Amyloid-β Precursor Protein

PubMed Central

Parr, Callum; Carzaniga, Raffaela; Gentleman, Steve M.; Van Leuven, Fred; Walter, Jochen

2012-01-01

Alzheimer's disease (AD) has been associated with altered activity of glycogen synthase kinase 3 (GSK3) isozymes, which are proposed to contribute to both neurofibrillary tangles and amyloid plaque formation. However, the molecular basis by which GSK3 affects the formation of Aβ remains unknown. Our aim was to identify the underlying mechanisms of GSK3-dependent effects on the processing of amyloid precursor protein (APP). For this purpose, N2a cells stably expressing APP carrying the Swedish mutation were treated with specific GSK3 inhibitors or transfected with GSK3α/β short interfering RNA. We show that inhibition of GSK3 leads to decreased expression of APP by enhancing its degradation via an increase in the number of lysosomes. This induction of the lysosomal/autophagy pathway was associated with nuclear translocation of transcription factor EB (TFEB), a master regulator of lysosomal biogenesis. Our data indicate that GSK3 inhibition reduces Aβ through an increase of the degradation of APP and its carboxy-terminal fragment (CTF) by activation of the lysosomal/autophagy pathway. These results suggest that an increased propensity toward autophagic/lysosomal alterations in AD patients could have consequences for neuronal function. PMID:22927642

Deletion of the γ-secretase subunits Aph1B/C impairs memory and worsens the deficits of knock-in mice modeling the Alzheimer-like familial Danish dementia

PubMed Central

Biundo, Fabrizio; Ishiwari, Keita; Del Prete, Dolores; D'Adamio, Luciano

2016-01-01

Mutations in BRI2/ITM2b genes cause Familial British and Danish Dementias (FBD and FDD), which are pathogenically similar to Familial Alzheimer Disease (FAD). BRI2 inhibits processing of Amyloid precursor protein (APP), a protein involved in FAD pathogenesis. Accumulation of a carboxyl-terminal APP metabolite –β-CTF- causes memory deficits in a knock-in mouse model of FDD, called FDDKI. We have investigated further the pathogenic function of β-CTF studying the effect of Aph1B/C deletion on FDDKI mice. This strategy is based on the evidence that deletion of Aph1B/C proteins, which are components of the γ-secretase that cleaves β-CTF, results in stabilization of β-CTF and a reduction of Aβ. We found that both the FDD mutation and the Aph1B/C deficiency mildly interfered with spatial long term memory, spatial working/short-term memory and long-term contextual fear memory. In addition, the Aph1BC deficiency induced deficits in long-term cued fear memory. Moreover, the two mutations have additive adverse effects as they compromise the accuracy of spatial long-term memory and induce spatial memory retention deficits in young mice. Overall, the data are consistent with a role for β-CTF in the genesis of memory deficits. PMID:26942869

Deletion of the γ-secretase subunits Aph1B/C impairs memory and worsens the deficits of knock-in mice modeling the Alzheimer-like familial Danish dementia.

PubMed

Biundo, Fabrizio; Ishiwari, Keita; Del Prete, Dolores; D'Adamio, Luciano

2016-03-15

Mutations in BRI2/ITM2b genes cause Familial British and Danish Dementias (FBD and FDD), which are pathogenically similar to Familial Alzheimer Disease (FAD). BRI2 inhibits processing of Amyloid precursor protein (APP), a protein involved in FAD pathogenesis. Accumulation of a carboxyl-terminal APP metabolite -ß-CTF- causes memory deficits in a knock-in mouse model of FDD, called FDDKI.We have investigated further the pathogenic function of ß-CTF studying the effect of Aph1B/C deletion on FDDKI mice. This strategy is based on the evidence that deletion of Aph1B/C proteins, which are components of the γ-secretase that cleaves ß-CTF, results in stabilization of ß-CTF and a reduction of Aβ. We found that both the FDD mutation and the Aph1B/C deficiency mildly interfered with spatial long term memory, spatial working/short-term memory and long-term contextual fear memory. In addition, the Aph1BC deficiency induced deficits in long-term cued fear memory. Moreover, the two mutations have additive adverse effects as they compromise the accuracy of spatial long-term memory and induce spatial memory retention deficits in young mice. Overall, the data are consistent with a role for β-CTF in the genesis of memory deficits.

The amyloid precursor protein locus and very-late-onset Alzheimer disease.

PubMed

Olson, J M; Goddard, K A; Dudek, D M

2001-10-01

Although mutations in the amyloid-beta precursor protein (APP) gene are known to confer high risk of Alzheimer disease (AD) to a small percentage of families in which it has early onset, convincing evidence of a major role for the APP locus in late-onset AD has not been forthcoming. In this report, we have used a covariate-based affected-sib-pair linkage method to analyze the chromosome 21 clinical and genetic data obtained on affected sibships by the National Institute of Mental Health Alzheimer Disease Genetics Initiative. The baseline model (without covariates) gave a LOD score of 0.02, which increases to 1.43 when covariates representing the additive effects of E2 and E4 are added. Larger increases in LOD scores were found when age at last examination/death (LOD score 5.54; P=.000002) or age at onset plus disease duration (LOD score 5.63; P=.000006) were included in the linkage model. We conclude that the APP locus may predispose to AD in the very elderly.

A comparative analysis of MC4R gene sequence, polymorphism, and chromosomal localization in Chinese raccoon dog and Arctic fox.

PubMed

Skorczyk, Anna; Flisikowski, Krzysztof; Switonski, Marek

2012-05-01

Numerous mutations of the human melanocortin receptor type 4 (MC4R) gene are responsible for monogenic obesity, and some of them appear to be associated with predisposition or resistance to polygenic obesity. Thus, this gene is considered a functional candidate for fat tissue accumulation and body weight in domestic mammals. The aim of the study was comparative analysis of chromosome localization, nucleotide sequence, and polymorphism of the MC4R gene in two farmed species of the Canidae family, namely the Chinese raccoon dog (Nycterutes procyonoides procyonoides) and the arctic fox (Alopex lagopus). The whole coding sequence, including fragments of 3'UTR and 5'UTR, shows 89% similarity between the arctic fox (1276 bp) and Chinese raccoon dog (1213 bp). Altogether, 30 farmed Chinese raccoon dogs and 30 farmed arctic foxes were searched for polymorphisms. In the Chinese raccoon dog, only one silent substitution in the coding sequence was identified; whereas in the arctic fox, four InDels and two single-nucleotide polymorphisms (SNPs) in the 5'UTR and six silent SNPs in the exon were found. The studied gene was mapped by FISH to the Chinese raccoon dog chromosome 9 (NPP9q1.2) and arctic fox chromosome 24 (ALA24q1.2-1.3). The obtained results are discussed in terms of genome evolution of species belonging to the family Canidae and their potential use in animal breeding.

Genomic Footprints in Selected and Unselected Beef Cattle Breeds in Korea.

PubMed

Lim, Dajeong; Strucken, Eva M; Choi, Bong Hwan; Chai, Han Ha; Cho, Yong Min; Jang, Gul Won; Kim, Tae-Hun; Gondro, Cedric; Lee, Seung Hwan

2016-01-01

Korean Hanwoo cattle have been subjected to intensive artificial selection over the past four decades to improve meat production traits. Another three cattle varieties very closely related to Hanwoo reside in Korea (Jeju Black and Brindle) and in China (Yanbian). These breeds have not been part of a breeding scheme to improve production traits. Here, we compare the selected Hanwoo against these similar but presumed to be unselected populations to identify genomic regions that have been under recent selection pressure due to the breeding program. Rsb statistics were used to contrast the genomes of Hanwoo versus a pooled sample of the three unselected population (UN). We identified 37 significant SNPs (FDR corrected) in the HW/UN comparison and 21 known protein coding genes were within 1 MB to the identified SNPs. These genes were previously reported to affect traits important for meat production (14 genes), reproduction including mammary gland development (3 genes), coat color (2 genes), and genes affecting behavioral traits in a broader sense (2 genes). We subsequently sequenced (Illumina HiSeq 2000 platform) 10 individuals of the brown Hanwoo and the Chinese Yanbian to identify SNPs within the candidate genomic regions. Based on allele frequency differences, haplotype structures, and literature research, we singled out one non-synonymous SNP in the APP gene (APP: c.569C>T, Ala199Val) and predicted the mutational effect on the protein structure. We found that protein-protein interactions might be impaired due to increased exposed hydrophobic surfaces of the mutated protein. The APP gene has also been reported to affect meat tenderness in pigs and obesity in humans. Meat tenderness has been linked to intramuscular fat content, which is one of the main breeding goals for brown Hanwoo, potentially supporting a causal influence of the herein described nsSNP in the APP gene.

Systematic analysis of mutation distribution in three dimensional protein structures identifies cancer driver genes.

PubMed

Fujimoto, Akihiro; Okada, Yukinori; Boroevich, Keith A; Tsunoda, Tatsuhiko; Taniguchi, Hiroaki; Nakagawa, Hidewaki

2016-05-26

Protein tertiary structure determines molecular function, interaction, and stability of the protein, therefore distribution of mutation in the tertiary structure can facilitate the identification of new driver genes in cancer. To analyze mutation distribution in protein tertiary structures, we applied a novel three dimensional permutation test to the mutation positions. We analyzed somatic mutation datasets of 21 types of cancers obtained from exome sequencing conducted by the TCGA project. Of the 3,622 genes that had ≥3 mutations in the regions with tertiary structure data, 106 genes showed significant skew in mutation distribution. Known tumor suppressors and oncogenes were significantly enriched in these identified cancer gene sets. Physical distances between mutations in known oncogenes were significantly smaller than those of tumor suppressors. Twenty-three genes were detected in multiple cancers. Candidate genes with significant skew of the 3D mutation distribution included kinases (MAPK1, EPHA5, ERBB3, and ERBB4), an apoptosis related gene (APP), an RNA splicing factor (SF1), a miRNA processing factor (DICER1), an E3 ubiquitin ligase (CUL1) and transcription factors (KLF5 and EEF1B2). Our study suggests that systematic analysis of mutation distribution in the tertiary protein structure can help identify cancer driver genes.

Systematic analysis of mutation distribution in three dimensional protein structures identifies cancer driver genes

PubMed Central

Fujimoto, Akihiro; Okada, Yukinori; Boroevich, Keith A.; Tsunoda, Tatsuhiko; Taniguchi, Hiroaki; Nakagawa, Hidewaki

2016-01-01

Protein tertiary structure determines molecular function, interaction, and stability of the protein, therefore distribution of mutation in the tertiary structure can facilitate the identification of new driver genes in cancer. To analyze mutation distribution in protein tertiary structures, we applied a novel three dimensional permutation test to the mutation positions. We analyzed somatic mutation datasets of 21 types of cancers obtained from exome sequencing conducted by the TCGA project. Of the 3,622 genes that had ≥3 mutations in the regions with tertiary structure data, 106 genes showed significant skew in mutation distribution. Known tumor suppressors and oncogenes were significantly enriched in these identified cancer gene sets. Physical distances between mutations in known oncogenes were significantly smaller than those of tumor suppressors. Twenty-three genes were detected in multiple cancers. Candidate genes with significant skew of the 3D mutation distribution included kinases (MAPK1, EPHA5, ERBB3, and ERBB4), an apoptosis related gene (APP), an RNA splicing factor (SF1), a miRNA processing factor (DICER1), an E3 ubiquitin ligase (CUL1) and transcription factors (KLF5 and EEF1B2). Our study suggests that systematic analysis of mutation distribution in the tertiary protein structure can help identify cancer driver genes. PMID:27225414

α-Secretase-derived Fragment of Cellular Prion, N1, Protects against Monomeric and Oligomeric Amyloid β (Aβ)-associated Cell Death*

PubMed Central

Guillot-Sestier, Marie-Victoire; Sunyach, Claire; Ferreira, Sergio T.; Marzolo, Maria-Paz; Bauer, Charlotte; Thevenet, Aurélie; Checler, Frédéric

2012-01-01

In physiological conditions, both β-amyloid precursor protein (βAPP) and cellular prion (PrPc) undergo similar disintegrin-mediated α-secretase cleavage yielding N-terminal secreted products referred to as soluble amyloid precursor protein-α (sAPPα) and N1, respectively. We recently demonstrated that N1 displays neuroprotective properties by reducing p53-dependent cell death both in vitro and in vivo. In this study, we examined the potential of N1 as a neuroprotector against amyloid β (Aβ)-mediated toxicity. We first show that both recombinant sAPPα and N1, but not its inactive parent fragment N2, reduce staurosporine-stimulated caspase-3 activation and TUNEL-positive cell death by lowering p53 promoter transactivation and activity in human cells. We demonstrate that N1 also lowers toxicity, cell death, and p53 pathway exacerbation triggered by Swedish mutated βAPP overexpression in human cells. We designed a CHO cell line overexpressing the London mutated βAPP (APPLDN) that yields Aβ oligomers. N1 protected primary cultured neurons against toxicity and cell death triggered by oligomer-enriched APPLDN-derived conditioned medium. Finally, we establish that N1 also protects neurons against oligomers extracted from Alzheimer disease-affected brain tissues. Overall, our data indicate that a cellular prion catabolite could interfere with Aβ-associated toxicity and that its production could be seen as a cellular protective mechanism aimed at compensating for an sAPPα deficit taking place at the early asymptomatic phase of Alzheimer disease. PMID:22184125

Aβ-Induced Inflammatory Processes in Microglia Cells of APP23 Transgenic Mice

PubMed Central

Bornemann, Klaus D.; Wiederhold, Karl-Heinz; Pauli, Chantal; Ermini, Florian; Stalder, Martina; Schnell, Lisa; Sommer, Bernd; Jucker, Mathias; Staufenbiel, Matthias

2001-01-01

A microglial response is part of the inflammatory processes in Alzheimer’s disease (AD). We have used APP23 transgenic mice overexpressing human amyloid precursor protein with the Swedish mutation to characterize this microglia response to amyloid deposits in aged mice. Analyses with MAC-1 and F4/80 antibodies as well as in vivo labeling with bromodeoxyuridine demonstrate that microglia in the plaque vicinity are in an activated state and that proliferation contributes to their accumulation at the plaque periphery. The amyloid-induced microglia activation may be mediated by scavenger receptor A, which is generally elevated, whereas the increased immunostaining of the receptor for advanced glycation end products is more restricted. Although components of the phagocytic machinery such as macrosialin and Fc receptors are increased in activated microglia, efficient clearance of amyloid is missing seemingly because of the lack of amyloid-bound autoantibodies. Similarly, although up-regulation of major histocompatibility complex class II (IA) points toward an intact antigen-presenting function of microglia, lack of T and B lymphocytes does not indicate a cell-mediated immune response in the brains of APP23 mice. The similar characteristics of microglia in the APP23 mice and in AD render the mouse model suitable to study the role of inflammatory processes during AD pathogenesis. PMID:11141480

Bulkiness or aromatic nature of tyrosine-143 of actin is important for the weak binding between F-actin and myosin-ADP-phosphate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gomibuchi, Yuki; Uyeda, Taro Q.P.; Wakabayashi, Takeyuki, E-mail: tw007@nasu.bio.teikyo-u.ac.jp

2013-11-29

Highlights: •The effect of mutation of Tyr143 that becomes more exposed on assembly was examined. •Mutation of tyrosine-143 of Dictyostelium actin changed actin polymerizability. •The bulkiness or aromatic nature of Tyr143 is important for the weak binding. •The weak interaction between myosin and actin strengthened by Tyr143Trp mutation. -- Abstract: Actin filaments (F-actin) interact with myosin and activate its ATPase to support force generation. By comparing crystal structures of G-actin and the quasi-atomic model of F-actin based on high-resolution cryo-electron microscopy, the tyrosine-143 was found to be exposed more than 60 Å{sup 2} to the solvent in F-actin. Because tyrosine-143more » flanks the hydrophobic cleft near the hydrophobic helix that binds to myosin, the mutant actins, of which the tyrosine-143 was replaced with tryptophan, phenylalanine, or isoleucine, were generated using the Dictyostelium expression system. It polymerized significantly poorly when induced by NaCl, but almost normally by KCl. In the presence of phalloidin and KCl, the extents of the polymerization of all the mutant actins were comparable to that of the wild-type actin so that the actin-activated myosin ATPase activity could be reliably compared. The affinity of skeletal heavy meromyosin to F-actin and the maximum ATPase activity (V{sub max}) were estimated by a double reciprocal plot. The Tyr143Trp-actin showed the higher affinity (smaller K{sub app}) than that of the wild-type actin, with the V{sub max} being almost unchanged. The K{sub app} and V{sub max} of the Tyr143Phe-actin were similar to those of the wild-type actin. However, the activation by Tyr143Ile-actin was much smaller than the wild-type actin and the accurate determination of K{sub app} was difficult. Comparison of the myosin ATPase activated by the various mutant actins at the same concentration of F-actin showed that the extent of activation correlates well with the solvent-accessible surface areas (ASA) of the replaced amino acid molecule. Because 1/K{sub app} reflects the affinity of F-actin for the myosin–ADP-phosphate intermediate (M.ADP.Pi) through the weak binding, these data suggest that the bulkiness or the aromatic nature of the tyrosin-143 is important for the initial binding of the M.ADP.Pi intermediate with F-actin but not for later processes such as the phosphate release.« less

Subjects harboring presenilin familial Alzheimer’s disease mutations exhibit diverse white matter biochemistry alterations

PubMed Central

Roher, Alex E; Maarouf, Chera L; Malek-Ahmadi, Michael; Wilson, Jeffrey; Kokjohn, Tyler A; Daugs, Ian D; Whiteside, Charisse M; Kalback, Walter M; Macias, MiMi P; Jacobson, Sandra A; Sabbagh, Marwan N; Ghetti, Bernardino; Beach, Thomas G

2013-01-01

Alzheimer’s disease (AD) dementia impacts all facets of higher order cognitive function and is characterized by the presence of distinctive pathological lesions in the gray matter (GM). The profound alterations in GM structure and function have fostered the view that AD impacts are primarily a consequence of GM damage. However, the white matter (WM) represents about 50% of the cerebrum and this area of the brain is substantially atrophied and profoundly abnormal in both sporadic AD (SAD) and familial AD (FAD). We examined the WM biochemistry by ELISA and Western blot analyses of key proteins in 10 FAD cases harboring mutations in the presenilin genes PSEN1 and PSEN2 as well as in 4 non-demented control (NDC) individuals and 4 subjects with SAD. The molecules examined were direct substrates of PSEN1 such as Notch-1 and amyloid precursor protein (APP). In addition, apolipoproteins, axonal transport molecules, cytoskeletal and structural proteins, neurotrophic factors and synaptic proteins were examined. PSEN-FAD subjects had, on average, higher amounts of WM amyloid-beta (Aβ) peptides compared to SAD, which may play a role in the devastating dysfunction of the brain. However, the PSEN-FAD mutations we examined did not produce uniform increases in the relative proportions of Aβ42 and exhibited substantial variability in total Aβ levels. These observations suggest that neurodegeneration and dementia do not depend solely on enhanced Aβ42 levels. Our data revealed additional complexities in PSEN-FAD individuals. Some direct substrates of γ-secretase, such as Notch, N-cadherin, Erb-B4 and APP, deviated substantially from the NDC group baseline for some, but not all, mutation types. Proteins that were not direct γ-secretase substrates, but play key structural and functional roles in the WM, likewise exhibited varied concentrations in the distinct PSEN mutation backgrounds. Detailing the diverse biochemical pathology spectrum of PSEN mutations may offer valuable insights into dementia progression and the design of effective therapeutic interventions for both SAD and FAD. PMID:24093083

A Two-Phase Approach to Developing SNAP: an iPhone Application to Support Appointment Scheduling and Management for Women with a BRCA Mutation.

PubMed

Scherr, Courtney Lynam; Feuston, Jessica L; Nixon, Dawn M; Cohen, Stephanie A

2018-04-01

Professional organizations provide surveillance guidelines for BRCA1 and BRCA2 (BRCA) carriers with intact breasts and/or ovaries to facilitate early cancer detection. However, literature indicates adherence to surveillance guidelines is inconsistent at best. Using the Messaging Model for Health Communication Campaigns framework, we undertook a two-phase formative research approach to develop an intervention to promote adherence to surveillance guidelines. Discussion groups identified preferred intervention format and function in phase I. Findings indicated carriers desired a phone application (app) to assist with surveillance management and appointment tracking. Thus, an iPhone app for carriers to track appointments based on published surveillance guidelines was developed. In phase II, we obtained feedback from BRCA carriers via a survey during a prototype demonstration at a regional conference. Participants in phase II wanted reminder capabilities and the ability to add and modify information fields. This feedback informed intervention modifications, resulting in the Scheduling Necessary Advised Procedures (SNAP) iPhone app currently being pilot tested by BRCA carriers throughout the USA.

Evidence that the C-terminus of Human Presenilin 1 is Located in the Extra-cytoplasmic Space

PubMed Central

James Turner, R.

2005-01-01

The polytopic membrane protein presenilin 1 (PS1) is a component of the γ-secretase complex that is responsible for the intramembranous cleavage of a number of type I transmembrane proteins including the β-amyloid precursor protein (APP). Mutations of PS1, apparently leading to aberrant processing of APP, have been genetically linked to early-onset familial Alzheimer's disease. PS1 contains ten hydrophobic regions (HRs) sufficiently long to be α-helical membrane spanning segments. Most topology models for PS1 place its C-terminal ∼40 amino acids, which include the 10th HR, in the cytosolic space. However, several recent observations suggest that HR 10 may be integrated into the membrane and involved in the interaction between PS1 and APP. We have applied three independent methodologies to investigate the location of HR 10 and the extreme C-terminus of PS1. The results from these methods indicate that HR 10 spans the membrane and that the C-terminal amino acids of PS1 lie in the extra-cytoplasmic space. PMID:15843437

Amyloid precursor protein and endosomal-lysosomal dysfunction in Alzheimer's disease: inseparable partners in a multifactorial disease.

PubMed

Nixon, Ralph A

2017-07-01

Abnormalities of the endosomal-lysosomal network (ELN) are a signature feature of Alzheimer's disease (AD). These include the earliest known cytopathology that is specific to AD and that affects endosomes and induces the progressive failure of lysosomes, each of which are directly linked by distinct mechanisms to neurodegeneration. The origins of ELN dysfunction and β-amyloidogenesis closely overlap, which reflects their common genetic basis, the established early involvement of endosomes and lysosomes in amyloid precursor protein (APP) processing and clearance, and the pathologic effect of certain APP metabolites on ELN functions. Genes that promote β-amyloidogenesis in AD (APP, PSEN1/2, and APOE4) have primary effects on ELN function. The importance of primary ELN dysfunction to pathogenesis is underscored by the mutations in more than 35 ELN-related genes that, thus far, are known to cause familial neurodegenerative diseases even though different pathogenic proteins may be involved. In this article, I discuss growing evidence that implicates AD gene-driven ELN disruptions as not only the antecedent pathobiology that underlies β-amyloidogenesis but also as the essential partner with APP and its metabolites that drive the development of AD, including tauopathy, synaptic dysfunction, and neurodegeneration. The striking amelioration of diverse deficits in animal AD models by remediating ELN dysfunction further supports a need to integrate APP and ELN relationships, including the role of amyloid-β, into a broader conceptual framework of how AD arises, progresses, and may be effectively therapeutically targeted.-Nixon, R. A. Amyloid precursor protein and endosomal-lysosomal dysfunction in Alzheimer's disease: inseparable partners in a multifactorial disease. © FASEB.

Properties and mutation studies of a bacteriophage-derived chimeric recombinant staphylolytic protein P128

PubMed Central

Saravanan, Sanjeev Rajagopalan; Paul, Vivek Daniel; George, Shilpa; Sundarrajan, Sudarson; Kumar, Nirmal; Hebbur, Madhavi; Kumar, Naveen; Veena, Ananda; Maheshwari, Uma; Appaiah, Chemira Biddappa; Chidambaran, Muralidharan; Bhat, Anuradha Gopal; Hariharan, Sukumar; Padmanabhan, Sriram

2013-01-01

P128 is a chimeric anti-staphylococcal protein having a catalytic domain from a Staphylococcus bacteriophage K tail associated structural protein and a cell wall targeting domain from the Staphylococcus bacteriocin-lysostaphin. In this study, we disclose additional properties of P128 and compared the same with lysostaphin. While lysostaphin was found to get inactivated by heat and was inactive on its parent strain S. simulans biovar staphylolyticus, P128 was thermostable and was lytic towards S. simulans biovar staphylolyticus demonstrating a difference in their mechanism of action. Selected mutation studies of the catalytic domain of P128 showed that arginine and cysteine, at 40th and 76th positions respectively, are critical for the staphylolytic activity of P128, although these amino acids are not conserved residues. In comparison to native P128, only the R40S mutant (P301) was catalytically active on zymogram gel and had a similar secondary structure, as assessed by circular dichroism analysis and in silico modeling with similar cell binding properties. Mutation of the arginine residue at 40th position of the P128 molecule caused dramatic reduction in the Vmax (∆OD600 [mg/min]) value (nearly 270 fold) and the recombinant lysostaphin also showed lesser Vmax value (nearly 1.5 fold) in comparison to the unmodified P128 protein. The kinetic parameters such as apparent Km (Km APP) and apparent Kcat (KcatAPP) of the native P128 protein also showed significant differences in comparison to the values observed for P301 and lysostaphin. PMID:24251076

Frontier Scientists use Modern Media

NASA Astrophysics Data System (ADS)

O'connell, E. A.

2013-12-01

Engaging Americans and the international community in the excitement and value of Alaskan Arctic discovery is the goal of Frontier Scientists. With a changing climate, resources of polar regions are being eyed by many nations. Frontier Scientists brings the stories of field scientists in the Far North to the public. With a website, an app, short videos, and social media channels; FS is a model for making connections between the public and field scientists. FS will demonstrate how academia, web content, online communities, evaluation and marketing are brought together in a 21st century multi-media platform, how scientists can maintain their integrity while engaging in outreach, and how new forms of media such as short videos can entertain as well as inspire.

Alternations of central insulin-like growth factor-1 sensitivity in APP/PS1 transgenic mice and neuronal models.

PubMed

Zhang, Bing; Tang, Xi Can; Zhang, Hai Yan

2013-05-01

Although many post-mortem studies have found evidence of central insulin resistance in Alzheimer's disease (AD) patients, results on changes of central insulin-like growth factor-1 (IGF-1) signaling in the pathological process of AD remain controversial. In the present study, we observed the activation states of IGF-1 downstream signaling in brain slices of transgenic mice carrying APPswe/PS1dE9 mutations (APP/PS1 mice) at both early and late stages (ex vivo) and further investigated the involvement of oligomeric β-amyloid (Aβ) and Aβ-enriched culture medium (CM) on IGF-1 sensitivity employing neuronal models (in vitro). In 6- and 18-month-old APP/PS1 mice, the phosphorylations of IGF-1 receptor (IGF-1R) and Akt in response to IGF-1 stimulation were significantly reduced in the hippocampal and cortical slices, whereas IGF-1R protein expression and mRNA levels of IGF-1 and IGF-1R in the hippocampal slices were significantly higher than that in wild-type mice. In agreement with these results, reduced IGF-1 sensitivity was verified in APP and PS1 double stably transfected CHO cells; moreover, IGF-1 stimulated phosphorylations of IGF-1R and Akt were also markedly weakened by oligomeric Aβ or Aβ-enriched CM posttreatment in CHO cells without APP/PS1-transfected (K1 cells) and primary hippocampal neurons. These observations indicate that the impaired central IGF-1 sensitivity at early and late stages of APP/PS1 transgenic mice might be attributable, at least partially, to the overproduced Aβ, especially the oligomeric Aβ. These findings may shed new light on the mechanisms underlying the defective IGF-1 signaling in AD pathogenesis and provide important clues for AD drug discovery. Copyright © 2013 Wiley Periodicals, Inc.

Cilostazol Upregulates Autophagy via SIRT1 Activation: Reducing Amyloid-β Peptide and APP-CTFβ Levels in Neuronal Cells.

PubMed

Lee, Hye Rin; Shin, Hwa Kyoung; Park, So Youn; Kim, Hye Young; Bae, Sun Sik; Lee, Won Suk; Rhim, Byung Yong; Hong, Ki Whan; Kim, Chi Dae

2015-01-01

Autophagy is a vital pathway for the removal of β-amyloid peptide (Aβ) and the aggregated proteins that cause Alzheimer's disease (AD). We previously found that cilostazol induced SIRT1 expression and its activity in neuronal cells, and thus, we hypothesized that cilostazol might stimulate clearances of Aβ and C-terminal APP fragment β subunit (APP-CTFβ) by up-regulating autophagy.When N2a cells were exposed to soluble Aβ1-42, protein levels of beclin-1, autophagy-related protein5 (Atg5), and SIRT1 decreased significantly. Pretreatment with cilostazol (10-30 μM) or resveratrol (20 μM) prevented these Aβ1-42 evoked suppressions. LC3-II (a marker of mammalian autophagy) levels were significantly increased by cilostazol, and this increase was reduced by 3-methyladenine. To evoke endogenous Aβ overproduction, N2aSwe cells (N2a cells stably expressing human APP containing the Swedish mutation) were cultured in medium with or without tetracycline (Tet+ for 48 h and then placed in Tet- condition). Aβ and APP-CTFβ expressions were increased after 12~24 h in Tet- condition, and these increased expressions were significantly reduced by pretreating cilostazol. Cilostazol-induced reductions in the expressions of Aβ and APP-CTFβ were blocked by bafilomycin A1 (a blocker of autophagosome to lysosome fusion). After knockdown of the SIRT1 gene (to ~40% in SIRT1 protein), cilostazol failed to elevate the expressions of beclin-1, Atg5, and LC3-II, indicating that cilostazol increases these expressions by up-regulating SIRT1. Further, decreased cell viability induced by Aβ was prevented by cilostazol, and this inhibition was reversed by 3-methyladenine, indicating that the protective effect of cilostazol against Aβ induced neurotoxicity is, in part, ascribable to the induction of autophagy. In conclusion, cilostazol modulates autophagy by increasing the activation of SIRT1, and thereby enhances Aβ clearance and increases cell viability.

Interaction of ApoE3 and ApoE4 isoforms with an ITM2b/BRI2 mutation linked to the Alzheimer disease-like Danish dementia: Effects on learning and memory

PubMed Central

Biundo, Fabrizio; Ishiwari, Keita; Del Prete, Dolores; D’Adamio, Luciano

2015-01-01

Mutations in Amyloid β Precursor Protein (APP) and in genes that regulate APP processing – such as PSEN1/2 and ITM2b/BRI2 – cause familial dementia, such Familial Alzheimer disease (FAD), Familial Danish (FDD) and British (FBD) dementias. The ApoE gene is the major genetic risk factor for sporadic AD. Three major variants of ApoE exist in humans (ApoE2, ApoE3, and ApoE4), with the ApoE4 allele being strongly associated with AD. ITM2b/BRI2 is also a candidate regulatory node genes predicted to mediate the common patterns of gene expression shared by healthy ApoE4 carriers and late-onset AD patients not carrying ApoE4. This evidence provides a direct link between ITM2b/BRI2 and ApoE4. To test whether ApoE4 and pathogenic ITM2b/BRI2 interact to modulate learning and memory, we crossed a mouse carrying the ITM2b/BRI2 mutations that causes FDD knocked-in the endogenous mouse Itm2b/Bri2 gene (FDDKI mice) with human ApoE3 and ApoE4 targeted replacement mice. The resultant ApoE3, FDDKI/ApoE3, ApoE4, FDDKI/ApoE4 male mice were assessed longitudinally for learning and memory at 4, 6, 12, and 16– 17 months of age. The results showed that ApoE4-carrying mice displayed spatial working/short-term memory deficits relative to ApoE3-carrying mice starting in early middle age, while long-term spatial memory of ApoE4 mice was not adversely affected even at 16–17 months, and that the FDD mutation impaired working/short-term spatial memory in ApoE3-carrying mice and produced impaired long-term spatial memory in ApoE4-carrying mice in middle age. The present results suggest that the FDD mutation may differentially affect learning and memory in ApoE4 carriers and non-carriers. PMID:26528887

Interaction of ApoE3 and ApoE4 isoforms with an ITM2b/BRI2 mutation linked to the Alzheimer disease-like Danish dementia: Effects on learning and memory.

PubMed

Biundo, Fabrizio; Ishiwari, Keita; Del Prete, Dolores; D'Adamio, Luciano

2015-12-01

Mutations in Amyloid β Precursor Protein (APP) and in genes that regulate APP processing--such as PSEN1/2 and ITM2b/BRI2--cause familial dementia, such Familial Alzheimer disease (FAD), Familial Danish (FDD) and British (FBD) dementias. The ApoE gene is the major genetic risk factor for sporadic AD. Three major variants of ApoE exist in humans (ApoE2, ApoE3, and ApoE4), with the ApoE4 allele being strongly associated with AD. ITM2b/BRI2 is also a candidate regulatory node genes predicted to mediate the common patterns of gene expression shared by healthy ApoE4 carriers and late-onset AD patients not carrying ApoE4. This evidence provides a direct link between ITM2b/BRI2 and ApoE4. To test whether ApoE4 and pathogenic ITM2b/BRI2 interact to modulate learning and memory, we crossed a mouse carrying the ITM2b/BRI2 mutations that causes FDD knocked-in the endogenous mouse Itm2b/Bri2 gene (FDDKI mice) with human ApoE3 and ApoE4 targeted replacement mice. The resultant ApoE3, FDDKI/ApoE3, ApoE4, FDDKI/ApoE4 male mice were assessed longitudinally for learning and memory at 4, 6, 12, and 16-17 months of age. The results showed that ApoE4-carrying mice displayed spatial working/short-term memory deficits relative to ApoE3-carrying mice starting in early middle age, while long-term spatial memory of ApoE4 mice was not adversely affected even at 16-17 months, and that the FDD mutation impaired working/short-term spatial memory in ApoE3-carrying mice and produced impaired long-term spatial memory in ApoE4-carrying mice in middle age. The present results suggest that the FDD mutation may differentially affect learning and memory in ApoE4 carriers and non-carriers. Copyright © 2015 Elsevier Inc. All rights reserved.

Identification of a Novel Aminopeptidase P-Like Gene (OnAPP) Possibly Involved in Bt Toxicity and Resistance in a Major Corn Pest (Ostrinia nubilalis)

PubMed Central

Khajuria, Chitvan; Buschman, Lawrent L.; Chen, Ming-Shun; Siegfried, Blair D.; Zhu, Kun Yan

2011-01-01

Studies to understand the Bacillus thuringiensis (Bt) resistance mechanism in European corn borer (ECB, Ostrinia nubilalis) suggest that resistance may be due to changes in the midgut-specific Bt toxin receptor. In this study, we identified 10 aminopeptidase-like genes, which have previously been identified as putative Bt toxin receptors in other insects and examined their expression in relation to Cry1Ab toxicity and resistance. Expression analysis for the 10 aminopeptidase-like genes revealed that most of these genes were expressed predominantly in the larval midgut, but there was no difference in the expression of these genes in Cry1Ab resistant and susceptible strains. This suggested that altered expression of these genes was unlikely to be responsible for resistance in these ECB strains. However, we found that there were changes in two amino acid residues of the aminopeptidase-P like gene (OnAPP) involving Glu305 to Lys305 and Arg307 to Leu307 in the two Cry1Ab-resistant strains as compared with three Cry1Ab-susceptible strains. The mature OnAPP contains 682 amino acid residues and has a putative signal peptide at the N-terminus, a predicted glycosylphosphatidyl-inositol (GPI)-anchor signal at the C-terminal, three predicted N-glycosylation sites at residues N178, N278 and N417, and an O-glycosylation site at residue T653. We used a feeding based-RNA interference assay to examine the role of the OnAPP gene in Cry1Ab toxicity and resistance. Bioassays of Cry1Ab in larvae fed diet containing OnAPP dsRNA resulted in a 38% reduction in the transcript level of OnAPP and a 25% reduction in the susceptibility to Cry1Ab as compared with larvae fed GFP dsRNA or water. These results strongly suggest that the OnAPP gene could be involved in binding the Cry1Ab toxin in the ECB larval midgut and that mutations in this gene may be associated with Bt resistance in these two ECB strains. PMID:21887358

[From physiopathology to treatment of Alzheimer's disease].

PubMed

Delacourte, A

2006-10-01

The natural and molecular history of familial or sporadic Alzheimer's disease (AD) shows that APP (amyloid protein precursor) dysfunction is a consensual central etiological factor in Alzheimer's disease (AD). This is demonstrated by 1) genetic defects involving APP gene or APP dysfunction (such as PS1 or PS2), leading to the formation of neocortical amyloid plaques in familial AD; 2) transgenic mice with these mutated genes that develop plaques; 3) both sporadic and familial AD develop plaques. But two alternatives to explain the physiopathology can be proposed: a gain of toxic function of AB peptide (reflected by the amyloid cascade hypothesis) or a loss of function of APP, a ubiquitous and well conserved protein with numerous possible neurotrophic activities. On the other hand, AD is also characterized by another inescapable degenerating process: tauopathy, an intraneuronal aggregation of tau proteins into neurofibrillary tangles. Remarkably enough, progression of tauopathy in neocortical areas fully explains the progressive clinical deficits of AD, from memory loss to aphasia, apraxia, agnosia. Also one has to bare in mind that most demented patients and most dementing neurodegenerative disorders have a tauopathy. From that, it is concluded that APP an Tau are solid therapeutic targets. But if we know that APP and Tau dysfunctions interact to boost neurodegeneration in AD, we still do no know what are the intraneuronal signaling pathways to activate or to inhibit to stop the degenerating process. There are many hypotheses and many possible approaches: the inhibition of toxicity of plaque, of AB protofibrils, or of AB oligomers inside or outside the neuron, using vaccination or ligands (Alzhemed). On the other hand, modulation of secretases that cleave APP by inhibiting those involved in the amyloidogenic pathway or by stimulating those of the non-amyloidogenic pathway, is a major route of research. Also modulation of kinases or phosphatases possibly involved in the aggregation of tau is also investigated. Because animal models are not perfectly relevant, at the end of the long and costly pathway of drug discovery, therapeutic trials are the only way to test these different hypotheses.

Activation of PPARδ prevents endothelial dysfunction induced by overexpression of amyloid-β precursor protein

PubMed Central

d'Uscio, Livius V.; Das, Pritam; Santhanam, Anantha V.R.; He, Tongrong; Younkin, Steven G.; Katusic, Zvonimir S.

2012-01-01

Aims Existing evidence suggests that amyloid-β precursor protein (APP) causes endothelial dysfunction and contributes to pathogenesis of atherosclerosis. In the present study, experiments were designed to: (1) determine the mechanisms underlying endothelial dysfunction and (2) define the effects of peroxisome proliferator-activated receptor delta (PPARδ) ligand on endothelial function in transgenic Tg2576 mice overexpressing mutated human APP. Methods and results Confocal microscopy and western blot analyses of wild-type mice aortas provided evidence that APP protein is mainly present in endothelial cells. Overexpression of APP significantly impaired endothelium-dependent relaxations to acetylcholine and phosphorylation of endothelial nitric oxide synthase at Ser1177 in aortas. HPLC analysis revealed that tetrahydrobiopterin (BH4) levels were reduced in Tg2576 mice aortas. This was caused by increased oxidation of BH4 and reduced expression and activity of GTP-cyclohydrolase I. Furthermore, gp91phox protein expression and superoxide anion production were increased in aortas of Tg2576 mice. This augmented superoxide formation was completely prevented by the NADPH oxidase inhibitor VAS2870. Expression of copper-/zinc-superoxide dismutase (Cu/ZnSOD) and extracellular SOD was downregulated. Treatment with PPARδ ligand GW501516 (2 mg/kg/day) for 14 days significantly increased BH4 bioavailability and improved endothelium-dependent relaxations in Tg2576 mice aortas. GW501516 also normalized protein expression of gp91phox and SODs, thereby reducing production of superoxide anion in the aortas. Conclusion Our results suggest that in APP transgenic mice loss of nitric oxide and increased oxidative stress are the major causes of endothelial dysfunction. The vascular protective effects of GW501516 in Tg2576 mice appear to be critically dependent on prevention of superoxide anion production. PMID:22886847

Activation of PPARδ prevents endothelial dysfunction induced by overexpression of amyloid-β precursor protein.

PubMed

d'Uscio, Livius V; Das, Pritam; Santhanam, Anantha V R; He, Tongrong; Younkin, Steven G; Katusic, Zvonimir S

2012-12-01

Existing evidence suggests that amyloid-β precursor protein (APP) causes endothelial dysfunction and contributes to pathogenesis of atherosclerosis. In the present study, experiments were designed to: (1) determine the mechanisms underlying endothelial dysfunction and (2) define the effects of peroxisome proliferator-activated receptor delta (PPARδ) ligand on endothelial function in transgenic Tg2576 mice overexpressing mutated human APP. Confocal microscopy and western blot analyses of wild-type mice aortas provided evidence that APP protein is mainly present in endothelial cells. Overexpression of APP significantly impaired endothelium-dependent relaxations to acetylcholine and phosphorylation of endothelial nitric oxide synthase at Ser(1177) in aortas. HPLC analysis revealed that tetrahydrobiopterin (BH(4)) levels were reduced in Tg2576 mice aortas. This was caused by increased oxidation of BH(4) and reduced expression and activity of GTP-cyclohydrolase I. Furthermore, gp91phox protein expression and superoxide anion production were increased in aortas of Tg2576 mice. This augmented superoxide formation was completely prevented by the NADPH oxidase inhibitor VAS2870. Expression of copper-/zinc-superoxide dismutase (Cu/ZnSOD) and extracellular SOD was downregulated. Treatment with PPARδ ligand GW501516 (2 mg/kg/day) for 14 days significantly increased BH(4) bioavailability and improved endothelium-dependent relaxations in Tg2576 mice aortas. GW501516 also normalized protein expression of gp91(phox) and SODs, thereby reducing production of superoxide anion in the aortas. Our results suggest that in APP transgenic mice loss of nitric oxide and increased oxidative stress are the major causes of endothelial dysfunction. The vascular protective effects of GW501516 in Tg2576 mice appear to be critically dependent on prevention of superoxide anion production.

Circadian and Brain State Modulation of Network Hyperexcitability in Alzheimer’s Disease

PubMed Central

Ying, Andrew; Jones, Mary; Chou, Robert Chang-Chih; Jordan, Crispin Y.; Jedrasiak-Cape, Izabela; Abou Jaoude, Maurice; Hashemi, Kevan

2018-01-01

Abstract Network hyperexcitability is a feature of Alzheimer’ disease (AD) as well as numerous transgenic mouse models of AD. While hyperexcitability in AD patients and AD animal models share certain features, the mechanistic overlap remains to be established. We aimed to identify features of network hyperexcitability in AD models that can be related to epileptiform activity signatures in AD patients. We studied network hyperexcitability in mice expressing amyloid precursor protein (APP) with mutations that cause familial AD, and compared a transgenic model that overexpresses human APP (hAPP) (J20), to a knock-in model expressing APP at physiological levels (APPNL/F). We recorded continuous long-term electrocorticogram (ECoG) activity from mice, and studied modulation by circadian cycle, behavioral, and brain state. We report that while J20s exhibit frequent interictal spikes (IISs), APPNL/F mice do not. In J20 mice, IISs were most prevalent during daylight hours and the circadian modulation was associated with sleep. Further analysis of brain state revealed that IIS in J20s are associated with features of rapid eye movement (REM) sleep. We found no evidence of cholinergic changes that may contribute to IIS-circadian coupling in J20s. In contrast to J20s, intracranial recordings capturing IIS in AD patients demonstrated frequent IIS in non-REM (NREM) sleep. The salient differences in sleep-stage coupling of IIS in APP overexpressing mice and AD patients suggests that different mechanisms may underlie network hyperexcitability in mice and humans. We posit that sleep-stage coupling of IIS should be an important consideration in identifying mouse AD models that most closely recapitulate network hyperexcitability in human AD. PMID:29780880

Molecular genetics of Alzheimer disease.

PubMed

St George-Hyslop, P H

1999-01-01

Epidemiological and individual case studies indicate that genetic factors play a significant role in the genesis of Alzheimer Disease (AD). To date, molecular genetic studies in families multiply affected with AD have identified three genes (Presenilin 1-PS1, Presenilin 2-PS2, and beta-amyloid precursor protein--betaAPP) associated with highly penetrant early onset AD, and one gene (Apolipoprotein E) associated with late onset AD. A fifth potential AD susceptibility locus has been mapped to a broad region of chromosome 12, but the responsible gene defect has not yet been identified. Case-control studies comparing the frequency of alleles in numerous other candidate genes have identified a number of additional potential AD genes. However, methodological difficulties and conflicting results in follow-up studies, make it unclear whether allelic variations in these genes are truly pathogenic. Nevertheless, analysis of the biochemical effects of mutations in PS1, PS2, betaAPP at least, suggest a common biochemical effect-namely disturbances in the processing of betaAPP protein. In addition to utility in defining potential therapeutic targets, in some circumstances these genes can also potentially be used as adjunctives in clinical presymptomatic, symptomatic or pharmacogenomic diagnosis.

Regional distribution of synaptic markers and APP correlate with distinct clinicopathological features in sporadic and familial Alzheimer’s disease

PubMed Central

Shinohara, Mitsuru; Fujioka, Shinsuke; Murray, Melissa E.; Wojtas, Aleksandra; Baker, Matthew; Rovelet-Lecrux, Anne; Rademakers, Rosa; Das, Pritam; Parisi, Joseph E.; Graff-Radford, Neill R.; Petersen, Ronald C.; Dickson, Dennis W.

2014-01-01

Recent studies suggest that subcortical structures, including striatum, are vulnerable to amyloid-β accumulation and other neuropathological features in familial Alzheimer’s disease due to autosomal dominant mutations. We explored differences between familial and sporadic Alzheimer’s disease that might shed light on their respective pathogenic mechanisms. To this end, we analysed 12 brain regions, including neocortical, limbic and subcortical areas, from post-mortem brains of familial Alzheimer’s disease (n = 10; age at death: 50.0 ± 8.6 years) with mutations in amyloid precursor protein (APP) or presenilin 1 (PSEN1), sporadic Alzheimer’s disease (n = 19; age at death: 84.7 ± 7.8 years), neurologically normal elderly without amyloid-β accumulation (normal ageing; n = 13, age at death: 82.9 ± 10.8 years) and neurologically normal elderly with extensive cortical amyloid-β deposits (pathological ageing; n = 15; age at death: 92.7 ± 5.9 years). The levels of amyloid-β40, amyloid-β42, APP, apolipoprotein E, the synaptic marker PSD95 (now known as DLG4), the astrocyte marker GFAP, other molecules related to amyloid-β metabolism, and tau were determined by enzyme-linked immunosorbent assays. We observed that familial Alzheimer’s disease had disproportionate amyloid-β42 accumulation in subcortical areas compared with sporadic Alzheimer’s disease, whereas sporadic Alzheimer’s disease had disproportionate amyloid-β42 accumulation in cortical areas compared to familial Alzheimer’s disease. Compared with normal ageing, the levels of several proteins involved in amyloid-β metabolism were significantly altered in both sporadic and familial Alzheimer’s disease; however, such changes were not present in pathological ageing. Among molecules related to amyloid-β metabolism, the regional distribution of PSD95 strongly correlated with the regional pattern of amyloid-β42 accumulation in sporadic Alzheimer’s disease and pathological ageing, whereas the regional distribution of APP as well as β-C-terminal fragment of APP were strongly associated with the regional pattern of amyloid-β42 accumulation in familial Alzheimer’s disease. Apolipoprotein E and GFAP showed negative regional association with amyloid-β (especially amyloid-β40) accumulation in both sporadic and familial Alzheimer’s disease. Familial Alzheimer’s disease had greater striatal tau pathology than sporadic Alzheimer’s disease. In a retrospective medical record review, atypical signs and symptoms were more frequent in familial Alzheimer’s disease compared with sporadic Alzheimer’s disease. These results suggest that disproportionate amyloid-β42 accumulation in cortical areas in sporadic Alzheimer’s disease may be mediated by synaptic processes, whereas disproportionate amyloid-β42 accumulation in subcortical areas in familial Alzheimer’s disease may be driven by APP and its processing. Region-specific amyloid-β42 accumulation might account for differences in the relative amounts of tau pathology and clinical symptoms in familial and sporadic Alzheimer’s disease. PMID:24625695

Decreased platelet APP isoform ratios in autosomal dominant Alzheimer's disease: baseline data from a DIAN cohort subset.

PubMed

Chatterjee, Pratishtha; Gupta, Veer B; Fagan, Anne M; Jasielec, Mateusz S; Xiong, Chengjie; Sohrabi, Hamid R; Dhaliwal, Satvinder; Taddei, Kevin; Bourgeat, Pierrick; Brown, Belinda M; Benzinger, Tammie; Bateman, Randall J; Morris, John C; Martins, Ralph N

2015-01-01

This study examines platelet amyloid precursor protein (APP) isoform ratios of 120KDa to 110KDa (APPr) between mutation carriers (MC) carrying a mutation for autosomal dominant Alzheimer's disease (ADAD) and non-carriers (NC). Two previous studies reported no significant difference in APPr between ADAD MC and NC, which may have been due to the small sample size in both studies. The current study examines APPr in MC versus NC in a larger sample. In addition, it investigated whether APPr correlate with neuroimaging data, neuropsychological data and cerebrospinal fluid biomarkers in a cohort subset derived from the Dominantly Inherited Alzheimer Network (DIAN) study. APPr were quantified by western blotting. Fifteen MC (symptomatic and asymptomatic) were compared against twelve NC using univariate general linear model. All participants underwent neuroimaging and neuropsychological testing which were correlated with APPr using Pearson's correlation coefficient (r). APPr were lower in MC compared to NC (p=0.003) while Mini-Mental State Examination (MMSE) scores were not significantly different (p>0.1). Furthermore, APPr inversely correlated with amyloid imaging in the Caudate Nucleus (r=-0.505; p<0.05) and Precuneus (r=-0.510; p<0.05). APPr are lower in ADAD MC compared to NC, and inversely correlated with brain amyloid load prior to significant differences in cognitive health. However, the use of APPr as a biomarker needs to be explored further.

A Climate-Data Record (CDR) of the "Clear Sky" Surface Temperature of the Greenland Ice Sheet

NASA Technical Reports Server (NTRS)

Hall, Dorothy K.; Comiso, J. C.; DiGirolamo, N. E.; Shuman, C. A.

2011-01-01

To quantify the ice-surface temperature (IST) we are developing a climate-data record (CDR) of monthly IST of the Greenland ice sheet, from 1982 to the present using Advanced Very High Resolution Radiometer (AVHRR) and Moderate-Resolution Imaging Spectroradiometer (MODIS) data at 5-km resolution. "Clear-sky" surface temperature increases have been measured from the early 1980s to the early 2000s in the Arctic using AVHRR data, showing increases ranging from 0.57-0.02 (Wang and Key, 2005) to 0.72 0.10 deg C per decade (Comiso, 2006). Arctic warming has implications for ice-sheet mass balance because much of the periphery of the ice sheet is near 0 deg C in the melt season and is thus vulnerable to more extensive melting (Hanna et al., 2008). The algorithm used for this work has a long history of measuring IST in the Arctic with AVHRR (Key and Haefliger, 1992). The data are currently available from 1981 to 2004 in the AVHRR Polar Pathfinder (APP) dataset (Fowler et al., 2000). J. Key1NOAA modified the AVHRR algorithm for use with MODIS (Hall et al., 2004). The MODIS algorithm is now being processed over Greenland. Issues being addressed in the production of the CDR are: time-series bias caused by cloud cover, and cross-calibration between AVHRR and MODIS instruments. Because of uncertainties, time series of satellite ISTs do not necessarily correspond with actual surface temperatures. The CDR will be validated by comparing results with in-situ (see Koenig and Hall, in press) and automatic-weather station data (e.g., Shuman et al., 2001).

Positive evolutionary selection of an HD motif on Alzheimer precursor protein orthologues suggests a functional role.

PubMed

Miklós, István; Zádori, Zoltán

2012-02-01

HD amino acid duplex has been found in the active center of many different enzymes. The dyad plays remarkably different roles in their catalytic processes that usually involve metal coordination. An HD motif is positioned directly on the amyloid beta fragment (Aβ) and on the carboxy-terminal region of the extracellular domain (CAED) of the human amyloid precursor protein (APP) and a taxonomically well defined group of APP orthologues (APPOs). In human Aβ HD is part of a presumed, RGD-like integrin-binding motif RHD; however, neither RHD nor RXD demonstrates reasonable conservation in APPOs. The sequences of CAEDs and the position of the HD are not particularly conserved either, yet we show with a novel statistical method using evolutionary modeling that the presence of HD on CAEDs cannot be the result of neutral evolutionary forces (p<0.0001). The motif is positively selected along the evolutionary process in the majority of APPOs, despite the fact that HD motif is underrepresented in the proteomes of all species of the animal kingdom. Position migration can be explained by high probability occurrence of multiple copies of HD on intermediate sequences, from which only one is kept by selective evolutionary forces, in a similar way as in the case of the "transcription binding site turnover." CAED of all APP orthologues and homologues are predicted to bind metal ions including Amyloid-like protein 1 (APLP1) and Amyloid-like protein 2 (APLP2). Our results suggest that HDs on the CAEDs are most probably key components of metal-binding domains, which facilitate and/or regulate inter- or intra-molecular interactions in a metal ion-dependent or metal ion concentration-dependent manner. The involvement of naturally occurring mutations of HD (Tottori (D7N) and English (H6R) mutations) in early onset Alzheimer's disease gives additional support to our finding that HD has an evolutionary preserved function on APPOs.

Positive Evolutionary Selection of an HD Motif on Alzheimer Precursor Protein Orthologues Suggests a Functional Role

PubMed Central

Miklós, István; Zádori, Zoltán

2012-01-01

HD amino acid duplex has been found in the active center of many different enzymes. The dyad plays remarkably different roles in their catalytic processes that usually involve metal coordination. An HD motif is positioned directly on the amyloid beta fragment (Aβ) and on the carboxy-terminal region of the extracellular domain (CAED) of the human amyloid precursor protein (APP) and a taxonomically well defined group of APP orthologues (APPOs). In human Aβ HD is part of a presumed, RGD-like integrin-binding motif RHD; however, neither RHD nor RXD demonstrates reasonable conservation in APPOs. The sequences of CAEDs and the position of the HD are not particularly conserved either, yet we show with a novel statistical method using evolutionary modeling that the presence of HD on CAEDs cannot be the result of neutral evolutionary forces (p<0.0001). The motif is positively selected along the evolutionary process in the majority of APPOs, despite the fact that HD motif is underrepresented in the proteomes of all species of the animal kingdom. Position migration can be explained by high probability occurrence of multiple copies of HD on intermediate sequences, from which only one is kept by selective evolutionary forces, in a similar way as in the case of the “transcription binding site turnover.” CAED of all APP orthologues and homologues are predicted to bind metal ions including Amyloid-like protein 1 (APLP1) and Amyloid-like protein 2 (APLP2). Our results suggest that HDs on the CAEDs are most probably key components of metal-binding domains, which facilitate and/or regulate inter- or intra-molecular interactions in a metal ion-dependent or metal ion concentration-dependent manner. The involvement of naturally occurring mutations of HD (Tottori (D7N) and English (H6R) mutations) in early onset Alzheimer's disease gives additional support to our finding that HD has an evolutionary preserved function on APPOs. PMID:22319430

Macroautophagy-generated increase of lysosomal amyloid β-protein mediates oxidant-induced apoptosis of cultured neuroblastoma cells

PubMed Central

Terman, Alexei; Hallbeck, Martin; Dehvari, Nodi; Cowburn, Richard F.; Benedikz, Eirikur; Kågedal, Katarina; Cedazo-Minguez, Angel; Marcusson, Jan

2011-01-01

Increasing evidence suggests the toxicity of intracellular amyloid β-protein (Aβ) to neurons, as well as the involvement of oxidative stress in Alzheimer disease (AD). Here we show that normobaric hyperoxia (exposure of cells to 40% oxygen for five days), and consequent activation of macroautophagy and accumulation of Aβ within lysosomes, induced apoptosis in differentiated SH-SY5Y neuroblastoma cells. Cells under hyperoxia showed: (1) increased numbers of autophagic vacuoles that contained amyloid precursor protein (APP) as well as Aβ monomers and oligomers, (2) increased reactive oxygen species production, and (3) enhanced apoptosis. Oxidant-induced apoptosis positively correlated with cellular Aβ production, being the highest in cells that were stably transfected with APP Swedish KM670/671NL double mutation. Inhibition of γ-secretase, prior and/or in parallel to hyperoxia, suggested that the increase of lysosomal Aβ resulted mainly from its autophagic uptake, but also from APP processing within autophagic vacuoles. The oxidative stress-mediated effects were prevented by macroautophagy inhibition using 3-methyladenine or ATG5 downregulation. Our results suggest that upregulation of macroautophagy and resulting lysosomal Aβ accumulation are essential for oxidant-induced apoptosis in cultured neuroblastoma cells and provide additional support for the interactive role of oxidative stress and the lysosomal system in AD-related neurodegeneration. PMID:22108004

MicroRNA-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion

PubMed Central

Chen, Xin; Jiang, Xue-Mei; Zhao, Lin-Jing; Sun, Lin-Lin; Yan, Mei-Ling; Tian, You; Zhang, Shuai; Duan, Ming-Jing; Zhao, Hong-Mei; Li, Wen-Rui; Hao, Yang-Yang; Wang, Li-Bo; Xiong, Qiao-Jie; Ai, Jing

2017-01-01

Impaired synaptic plasticity and neuron loss are hallmarks of Alzheimer’s disease and vascular dementia. Here, we found that chronic brain hypoperfusion (CBH) by bilateral common carotid artery occlusion (2VO) decreased the total length, numbers and crossings of dendrites and caused neuron death in rat hippocampi and cortices. It also led to increase in N-terminal β-amyloid precursor protein (N-APP) and death receptor-6 (DR6) protein levels and in the activation of caspase-3 and caspase-6. Further study showed that DR6 protein was downregulated by miR-195 overexpression, upregulated by miR-195 inhibition, and unchanged by binding-site mutation and miR-masks. Knockdown of endogenous miR-195 by lentiviral vector-mediated overexpression of its antisense molecule (lenti-pre-AMO-miR-195) decreased the total length, numbers and crossings of dendrites and neuron death, upregulated N-APP and DR6 levels, and elevated cleaved caspase-3 and caspase-6 levels. Overexpression of miR-195 using lenti-pre-miR-195 prevented these changes triggered by 2VO. We conclude that miR-195 is involved in CBH-induced dendritic degeneration and neuron death through activation of the N-APP/DR6/caspase pathway. PMID:28569780

Huperzine A activates Wnt/β-catenin signaling and enhances the nonamyloidogenic pathway in an Alzheimer transgenic mouse model.

PubMed

Wang, Chun-Yan; Zheng, Wei; Wang, Tao; Xie, Jing-Wei; Wang, Si-Ling; Zhao, Bao-Lu; Teng, Wei-Ping; Wang, Zhan-You

2011-04-01

Huperzine A (HupA) is a reversible and selective inhibitor of acetylcholinesterase (AChE), and it has multiple targets when used for Alzheimer's disease (AD) therapy. In this study, we searched for new mechanisms by which HupA could activate Wnt signaling and reduce amyloidosis in AD brain. A nasal gel containing HupA was prepared. No obvious toxicity of intranasal administration of HupA was found in mice. HupA was administered intranasally to β-amyloid (Aβ) precursor protein and presenilin-1 double-transgenic mice for 4 months. We observed an increase in ADAM10 and a decrease in BACE1 and APP695 protein levels and, subsequently, a reduction in Aβ levels and Aβ burden were present in HupA-treated mouse brain, suggesting that HupA enhances the nonamyloidogenic APP cleavage pathway. Importantly, our results further showed that HupA inhibited GSK3α/β activity, and enhanced the β-catenin level in the transgenic mouse brain and in SH-SY5Y cells overexpressing Swedish mutation APP, suggesting that the neuroprotective effect of HupA is not related simply to its AChE inhibition and antioxidation, but also involves other mechanisms, including targeting of the Wnt/β-catenin signaling pathway in AD brain.

Huperzine A Activates Wnt/β-Catenin Signaling and Enhances the Nonamyloidogenic Pathway in an Alzheimer Transgenic Mouse Model

PubMed Central

Wang, Chun-Yan; Zheng, Wei; Wang, Tao; Xie, Jing-Wei; Wang, Si-Ling; Zhao, Bao-Lu; Teng, Wei-Ping; Wang, Zhan-You

2011-01-01

Huperzine A (HupA) is a reversible and selective inhibitor of acetylcholinesterase (AChE), and it has multiple targets when used for Alzheimer's disease (AD) therapy. In this study, we searched for new mechanisms by which HupA could activate Wnt signaling and reduce amyloidosis in AD brain. A nasal gel containing HupA was prepared. No obvious toxicity of intranasal administration of HupA was found in mice. HupA was administered intranasally to β-amyloid (Aβ) precursor protein and presenilin-1 double-transgenic mice for 4 months. We observed an increase in ADAM10 and a decrease in BACE1 and APP695 protein levels and, subsequently, a reduction in Aβ levels and Aβ burden were present in HupA-treated mouse brain, suggesting that HupA enhances the nonamyloidogenic APP cleavage pathway. Importantly, our results further showed that HupA inhibited GSK3α/β activity, and enhanced the β-catenin level in the transgenic mouse brain and in SH-SY5Y cells overexpressing Swedish mutation APP, suggesting that the neuroprotective effect of HupA is not related simply to its AChE inhibition and antioxidation, but also involves other mechanisms, including targeting of the Wnt/β-catenin signaling pathway in AD brain. PMID:21289607

Direct imaging of APP proteolysis in living cells.

PubMed

Parenti, Niccoló; Del Grosso, Ambra; Antoni, Claudia; Cecchini, Marco; Corradetti, Renato; Pavone, Francesco S; Calamai, Martino

2017-01-01

Alzheimer's disease is a multifactorial disorder caused by the interaction of genetic, epigenetic and environmental factors. The formation of cytotoxic oligomers consisting of A β peptide is widely accepted as being one of the main key events triggering the development of Alzheimer's disease. A β peptide production results from the specific proteolytic processing of the amyloid precursor protein (APP). Deciphering the factors governing the activity of the secretases responsible for the cleavage of APP is still a critical issue. Kits available commercially measure the enzymatic activity of the secretases from cells lysates, in vitro . By contrast, we have developed a prototypal rapid bioassay that provides visible information on the proteolytic processing of APP directly in living cells. APP was fused to a monomeric variant of the green fluorescent protein and a monomeric variant of the red fluorescent protein at the C-terminal and N-terminal (mChAPPmGFP), respectively. Changes in the proteolytic processing rate in transfected human neuroblastoma and rat neuronal cells were imaged with confocal microscopy as changes in the red/green fluorescence intensity ratio. The significant decrease in the mean red/green ratio observed in cells over-expressing the β -secretase BACE1, or the α -secretase ADAM10, fused to a monomeric blue fluorescent protein confirms that the proteolytic site is still accessible. Specific siRNA was used to evaluate the contribution of endogenous BACE1. Interestingly, we found that the degree of proteolytic processing of APP is not completely homogeneous within the same single cell, and that there is a high degree of variability between cells of the same type. We were also able to follow with a fluorescence spectrometer the changes in the red emission intensity of the extracellular medium when BACE1 was overexpressed. This represents a complementary approach to fluorescence microscopy for rapidly detecting changes in the proteolytic processing of APP in real time. In order to allow the discrimination between the α - and the β -secretase activity, we have created a variant of mChAPPmGFP with a mutation that inhibits the α -secretase cleavage without perturbing the β -secretase processing. Moreover, we obtained a quantitatively robust estimate of the changes in the red/green ratio for the above conditions by using a flow cytometer able to simultaneously excite and measure the red and green fluorescence. Our novel approach lay the foundation for a bioassay suitable to study the effect of drugs or particular conditions, to investigate in an unbiased way the the proteolytic processing of APP in single living cells in order, and to elucidate the causes of the variability and the factors driving the processing of APP.

Wild-type presenilin 1 protects against Alzheimer disease mutation-induced amyloid pathology.

PubMed

Wang, Runsheng; Wang, Baiping; He, Wanxia; Zheng, Hui

2006-06-02

Mutations in presenilin 1 (PS1) lead to dominant inheritance of early onset familial Alzheimer disease (FAD). These mutations are known to alter the gamma-secretase cleavage of the amyloid precursor protein, resulting in increased ratio of Abeta42/Abeta40 and accelerated amyloid plaque pathology in transgenic mouse models. To investigate the factors that drive the Abeta42/Abeta40 ratio and amyloid pathogenesis and to investigate the possible interactions between wild-type and FAD mutant PS1, which are co-expressed in transgenic animals, we expressed the PS1 M146V knock-in allele either on wild-type PS1 (PS1M146V/+) or PS1 null (PS1M146V/-) background and crossed these alleles with the Tg2576 APP transgenic mice. Introduction of the PS1 M146V mutation on Tg2576 background resulted in earlier onset of plaque pathology. Surprisingly, removing the wild-type PS1 in the presence of the PS1 M146V mutation (PS1M146V/-) greatly exacerbated the amyloid burden; and this was attributed to a reduction of gamma-secretase activity rather than an increase in Abeta42. Our findings establish a protective role of the wild-type PS1 against the FAD mutation-induced amyloid pathology through a partial loss-of-function mechanism.

Evaluation of Cu(i) binding to the E2 domain of the amyloid precursor protein - a lesson in quantification of metal binding to proteins via ligand competition.

PubMed

Young, Tessa R; Wedd, Anthony G; Xiao, Zhiguang

2018-01-24

The extracellular domain E2 of the amyloid precursor protein (APP) features a His-rich metal-binding site (denoted as the M1 site). In conjunction with surrounding basic residues, the site participates in interactions with components of the extracellular matrix including heparins, a class of negatively charged polysaccharide molecules of varying length. This work studied the chemistry of Cu(i) binding to APP E2 with the probe ligands Bcs, Bca, Fz and Fs. APP E2 forms a stable Cu(i)-mediated ternary complex with each of these anionic ligands. The complex with Bca was selected for isolation and characterization and was demonstrated, by native ESI-MS analysis, to have the stoichiometry E2 : Cu(i) : Bca = 1 : 1 : 1. Formation of these ternary complexes is specific for the APP E2 domain and requires Cu(i) coordination to the M1 site. Mutation of the M1 site was consistent with the His ligands being part of the E2 ligand set. It is likely that interactions between the negatively charged probe ligands and a positively charged patch on the surface of APP E2 are one aspect of the generation of the stable ternary complexes. Their formation prevented meaningful quantification of the affinity of Cu(i) binding to the M1 site with these probe ligands. However, the ternary complexes are disrupted by heparin, allowing reliable determination of a picomolar Cu(i) affinity for the E2/heparin complex with the Fz or Bca probe ligands. This is the first documented example of the formation of stable ternary complexes between a Cu(i) binding protein and a probe ligand. The ready disruption of the complexes by heparin identified clear 'tell-tale' signs for diagnosis of ternary complex formation and allowed a systematic review of conditions and criteria for reliable determination of affinities for metal binding via ligand competition. This study also provides new insights into a potential correlation of APP functions regulated by copper binding and heparin interaction.

Mutations, associated with early-onset Alzheimer’s disease, discovered in Asian countries

PubMed Central

Bagyinszky, Eva; Youn, Young Chul; An, Seong Soo A; Kim, SangYun

2016-01-01

Alzheimer’s disease (AD), the most common form of senile dementia, is a genetically complex disorder. In most Asian countries, the population and the number of AD patients are growing rapidly, and the genetics of AD has been extensively studied, except in Japan. However, recent studies have been started to investigate the genes and mutations associated with AD in Korea, the People’s Republic of China, and Malaysia. This review describes all of the known mutations in three early-onset AD (EOAD) causative genes (APP, PSEN1, and PSEN2) that were discovered in Asian countries. Most of the EOAD-associated mutations have been detected in PSEN1, and several novel PSEN1 mutations were recently identified in patients from various parts of the world, including Asia. Until 2014, no PSEN2 mutations were found in Asian patients; however, emerging studies from Korea and the People’s Republic of China discovered probably pathogenic PSEN2 mutations. Since several novel mutations were discovered in these three genes, we also discuss the predictions on their pathogenic nature. This review briefly summarizes genome-wide association studies of late-onset AD and the genes that might be associated with AD in Asian countries. Standard sequencing is a widely used method, but it has limitations in terms of time, cost, and efficacy. Next-generation sequencing strategies could facilitate genetic analysis and association studies. Genetic testing is important for the accurate diagnosis and for understanding disease-associated pathways and might also improve disease therapy and prevention. PMID:27799753

Caspase-6 Activation in Familial Alzheimer Disease Brains Carrying Amyloid Precursor Protein, Presenilin I or Presenilin II Mutations

PubMed Central

Albrecht, Steffen; Bogdanovic, Nenad; Ghetti, Bernardino; Winblad, Bengt; LeBlanc, Andréa C.

2010-01-01

We previously demonstrated the activation of Caspase-6 in the hippocampus and cortex in cases of mild, moderate, severe and very severe Alzheimer disease (AD). To determine whether Caspase-6 is also activated in familial AD, we performed an immunohistochemical analysis of active Caspase-6 and Tau cleaved by Caspase-6 in temporal cortex and hippocampal tissue sections from cases of familial AD. The cases included 5 carrying the amyloid precursor protein K670N, M671L Swedish mutation, 1 carrying the amyloid precursor protein E693G Arctic mutation, 2 each carrying the Presenilin I M146V, F105L, A431E, V261F, Y115C mutations, and 1 with the Presenilin II N141I mutation. Active Caspase-6 immunoreactivity was found in all cases. Caspase-6 immunoreactivity was observed in neuritic plaques or cotton wool plaques in some cases, neuropil threads and neurofibrillary tangles. These results indicate that Caspase-6 is activated in familial forms of AD, as previously observed in sporadic forms. Since sporadic and familial AD cases have similar pathological features, these results support a fundamental role of Caspase-6 in the pathophysiology of both familial and sporadic AD. PMID:19915487

Efficient introduction of specific homozygous and heterozygous mutations using CRISPR/Cas9.

PubMed

Paquet, Dominik; Kwart, Dylan; Chen, Antonia; Sproul, Andrew; Jacob, Samson; Teo, Shaun; Olsen, Kimberly Moore; Gregg, Andrew; Noggle, Scott; Tessier-Lavigne, Marc

2016-05-05

The bacterial CRISPR/Cas9 system allows sequence-specific gene editing in many organisms and holds promise as a tool to generate models of human diseases, for example, in human pluripotent stem cells. CRISPR/Cas9 introduces targeted double-stranded breaks (DSBs) with high efficiency, which are typically repaired by non-homologous end-joining (NHEJ) resulting in nonspecific insertions, deletions or other mutations (indels). DSBs may also be repaired by homology-directed repair (HDR) using a DNA repair template, such as an introduced single-stranded oligo DNA nucleotide (ssODN), allowing knock-in of specific mutations. Although CRISPR/Cas9 is used extensively to engineer gene knockouts through NHEJ, editing by HDR remains inefficient and can be corrupted by additional indels, preventing its widespread use for modelling genetic disorders through introducing disease-associated mutations. Furthermore, targeted mutational knock-in at single alleles to model diseases caused by heterozygous mutations has not been reported. Here we describe a CRISPR/Cas9-based genome-editing framework that allows selective introduction of mono- and bi-allelic sequence changes with high efficiency and accuracy. We show that HDR accuracy is increased dramatically by incorporating silent CRISPR/Cas-blocking mutations along with pathogenic mutations, and establish a method termed 'CORRECT' for scarless genome editing. By characterizing and exploiting a stereotyped inverse relationship between a mutation's incorporation rate and its distance to the DSB, we achieve predictable control of zygosity. Homozygous introduction requires a guide RNA targeting close to the intended mutation, whereas heterozygous introduction can be accomplished by distance-dependent suboptimal mutation incorporation or by use of mixed repair templates. Using this approach, we generated human induced pluripotent stem cells with heterozygous and homozygous dominant early onset Alzheimer's disease-causing mutations in amyloid precursor protein (APP(Swe)) and presenilin 1 (PSEN1(M146V)) and derived cortical neurons, which displayed genotype-dependent disease-associated phenotypes. Our findings enable efficient introduction of specific sequence changes with CRISPR/Cas9, facilitating study of human disease.

Characterization of a sensitive mouse Aβ40 PD biomarker assay for Alzheimer's disease drug development in wild-type mice.

PubMed

Lu, Yanmei; Hoyte, Kwame; Montgomery, William H; Luk, Wilman; He, Dongping; Meilandt, William J; Zuchero, Y Joy Yu; Atwal, Jasvinder K; Scearce-Levie, Kimberly; Watts, Ryan J; DeForge, Laura E

2016-05-01

Transgenic mice that overexpress human amyloid precursor protein with Swedish or London (APPswe or APPlon) mutations have been widely used for preclinical Alzheimer's disease (AD) drug development. AD patients, however, rarely possess these mutations or overexpress APP. We developed a sensitive ELISA that specifically and accurately measures low levels of endogenous Aβ40 in mouse plasma, brain and CSF. In wild-type mice treated with a bispecific anti-TfR/BACE1 antibody, significant Aβ reductions were observed in the periphery and the brain. APPlon transgenic mice showed a slightly less reduction, whereas APPswe mice did not have any decrease. This sensitive and well-characterized mouse Aβ40 assay enables the use of wild-type mice for preclinical PK/PD and efficacy studies of potential AD therapeutics.

Total flavonoid extract from Dracoephalum moldavica L. attenuates β-amyloid-induced toxicity through anti-amyloidogenesic and neurotrophic pathways.

PubMed

Liu, Qing-Shan; Jiang, Hai-Lun; Wang, Yu; Wang, Lin-Lin; Zhang, Jun-Xia; He, Cheng-Hui; Shao, Shuai; Zhang, Tian-Tai; Xing, Jian-Guo; Liu, Rui

2018-01-15

Alzheimer's disease (AD) is an incurable neurodegenerative disorder characterized by global cognitive impairment that involves accumulation of amyloid-beta peptides (Aβ) in the brain. Herbal approaches can be used as alternative medicines to slow the progression of AD. This study aimed to determine the beneficial effects and potential underlying mechanisms of total flavonoid extract from Dracoephalum moldavica L. (TFDM) for attenuating Alzheimer-related deficits induced by Aβ. We used amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mice and copper-injured APP Swedish mutation overexpressing SH-SY5Y cells to evaluate the beneficial effects of TFDM. Further, identifying the mechanisms of action was conducted on anti-amyloidogenic and neurotrophic transductions. Our results indicated that TFDM treatment ameliorated cognitive impairments and neurodegeneration and improved the antioxidant defense system in APP/PS1 mice. TFDM also reduced Aβ burden by relieving Aβ deposition, decreasing insoluble Aβ levels, and inhibiting β-amyloidogenic processing pathway involving downregulation of β-secretase and β-C-terminal fragment in the brain. In the in vitro model of AD, TFDM treatment protected injured cells, and combined with the beneficial effects of decreasing APP levels, lowered Aβ 1-42 and regulated the redox imbalance. Moreover, TFDM preserved the extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor pathway both in vitro and in vivo. In conclusion, TFDM clearly demonstrated neuroprotective effects by restoring the anti-amyloidogenic and neurotrophic transductions in the context of AD-associated deficits. These findings indicate the potential use of herb-based substances as supplements or potential alternative supplements for attenuating the progression of AD. Copyright © 2017. Published by Elsevier Inc.

A novel presenilin 1 mutation (Ala275Val) as cause of early-onset familial Alzheimer disease.

PubMed

Luedecke, Daniel; Becktepe, Jos S; Lehmbeck, Jan T; Finckh, Ulrich; Yamamoto, Raina; Jahn, Holger; Boelmans, Kai

2014-04-30

Mutations in the presenilin 1 (PS1) gene (PSEN1) are associated with familial Alzheimer disease (FAD). Here, we report on a 50-year-old patient presenting with progressive deterioration of his short-term memory and a family history of early-onset dementia. Diagnostic workup included a neuropsychological examination, structural magnetic resonance (MR) imaging, cerebrospinal fluid (CSF) biomarkers including total tau, phosphorylated tau, and Aβ42 levels, as well as sequencing relevant fragments of the genes PSEN1, PSEN2, and APP. Additionally, we were able to obtain archival paraffin-embedded cerebellar tissue from the patient's father for cosegregation analysis. Clinical, neuropsychological and MR imaging data were indicative of early-onset Alzheimer disease. Furthermore, CSF biomarkers showed a typical pattern for Alzheimer disease. DNA sequencing revealed a heterozygous nucleotide transition (c.824C>T) in exon 8 of PSEN1, leading to an amino acid change from alanine to valine at codon 275 (Ala275Val). The same mutation was found in an archival brain specimen of the patient's demented father, but not in a blood sample of the non-demented mother. This mutation alters a conserved residue in the large hydrophilic loop of PS1, suggesting pathogenic relevance. Cosegregegation analysis and the structural as well as the presumed functional role of the mutated and highly conserved residue suggest FAD causing characteristics of the novel PSEN1 mutation Ala275Val. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Impaired default network functional connectivity in autosomal dominant Alzheimer disease

PubMed Central

Chhatwal, Jasmeer P.; Schultz, Aaron P.; Johnson, Keith; Benzinger, Tammie L.S.; Jack, Clifford; Ances, Beau M.; Sullivan, Caroline A.; Salloway, Stephen P.; Ringman, John M.; Koeppe, Robert A.; Marcus, Daniel S.; Thompson, Paul; Saykin, Andrew J.; Correia, Stephen; Schofield, Peter R.; Rowe, Christopher C.; Fox, Nick C.; Brickman, Adam M.; Mayeux, Richard; McDade, Eric; Bateman, Randall; Fagan, Anne M.; Goate, Allison M.; Xiong, Chengjie; Buckles, Virginia D.; Morris, John C.

2013-01-01

Objective: To investigate default mode network (DMN) functional connectivity MRI (fcMRI) in a large cross-sectional cohort of subjects from families harboring pathogenic presenilin-1 (PSEN1), presenilin-2 (PSEN2), and amyloid precursor protein (APP) mutations participating in the Dominantly Inherited Alzheimer Network. Methods: Eighty-three mutation carriers and 37 asymptomatic noncarriers from the same families underwent fMRI during resting state at 8 centers in the United States, United Kingdom, and Australia. Using group-independent component analysis, fcMRI was compared using mutation status and Clinical Dementia Rating to stratify groups, and related to each participant's estimated years from expected symptom onset (eYO). Results: We observed significantly decreased DMN fcMRI in mutation carriers with increasing Clinical Dementia Rating, most evident in the precuneus/posterior cingulate and parietal cortices (p < 0.001). Comparison of asymptomatic mutation carriers with noncarriers demonstrated decreased fcMRI in the precuneus/posterior cingulate (p = 0.014) and right parietal cortex (p = 0.0016). We observed a significant interaction between mutation carrier status and eYO, with decreases in DMN fcMRI observed as mutation carriers approached and surpassed their eYO. Conclusion: Functional disruption of the DMN occurs early in the course of autosomal dominant Alzheimer disease, beginning before clinically evident symptoms, and worsening with increased impairment. These findings suggest that DMN fcMRI may prove useful as a biomarker across a wide spectrum of disease, and support the feasibility of DMN fcMRI as a secondary endpoint in upcoming multicenter clinical trials in Alzheimer disease. PMID:23884042

Modeling Alzheimer’s disease: from past to future

PubMed Central

Saraceno, Claudia; Musardo, Stefano; Marcello, Elena; Pelucchi, Silvia; Di Luca, Monica

2013-01-01

Alzheimer’s disease (AD) is emerging as the most prevalent and socially disruptive illness of aging populations, as more people live long enough to become affected. Although AD is placing a considerable and increasing burden on society, it represents the largest unmet medical need in neurology, because current drugs improve symptoms, but do not have profound disease-modifying effects. Although AD pathogenesis is multifaceted and difficult to pinpoint, genetic and cell biological studies led to the amyloid hypothesis, which posits that amyloid β (Aβ) plays a pivotal role in AD pathogenesis. Amyloid precursor protein (APP), as well as β- and γ-secretases are the principal players involved in Aβ production, while α-secretase cleavage on APP prevents Aβ deposition. The association of early onset familial AD with mutations in the APP and γ-secretase components provided a potential tool of generating animal models of the disease. However, a model that recapitulates all the aspects of AD has not yet been produced. Here, we face the problem of modeling AD pathology describing several models, which have played a major role in defining critical disease-related mechanisms and in exploring novel potential therapeutic approaches. In particular, we will provide an extensive overview on the distinct features and pros and contras of different AD models, ranging from invertebrate to rodent models and finally dealing with computational models and induced pluripotent stem cells. PMID:23801962

Neuropathology of Autosomal Dominant Alzheimer Disease in the National Alzheimer Coordinating Center Database.

PubMed

Ringman, John M; Monsell, Sarah; Ng, Denise W; Zhou, Yan; Nguyen, Andy; Coppola, Giovanni; Van Berlo, Victoria; Mendez, Mario F; Tung, Spencer; Weintraub, Sandra; Mesulam, Marek-Marsel; Bigio, Eileen H; Gitelman, Darren R; Fisher-Hubbard, Amanda O; Albin, Roger L; Vinters, Harry V

2016-03-01

Alzheimer disease (AD) represents a genetically heterogeneous entity. To elucidate neuropathologic features of autosomal dominant AD ([ADAD] due to PSEN1, APP, or PSEN2 mutations), we compared hallmark AD pathologic findings in 60 cases of ADAD and 120 cases of sporadic AD matched for sex, race, ethnicity, and disease duration. Greater degrees of neuritic plaque and neurofibrillary tangle formation and cerebral amyloid angiopathy (CAA) were found in ADAD (p values < 0.01). Moderate to severe CAA was more prevalent in ADAD (63.3% vs. 39.2%, p = 0.003), and persons with PSEN1 mutations beyond codon 200 had higher average Braak scores and severity and prevalence of CAA than those with mutations before codon 200. Lewy body pathology was less extensive in ADAD but was present in 27.1% of cases. We also describe a novel pathogenic PSEN1 mutation (P267A). The finding of more severe neurofibrillary pathology and CAA in ADAD, particularly in carriers of PSEN1 mutations beyond codon 200, warrants consideration when designing trials to treat or prevent ADAD. The finding of Lewy body pathology in a substantial minority of ADAD cases supports the assertion that development of Lewy bodies may be in part driven by abnormal β-amyloid protein precursor processing. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

Population genomics reveal recent speciation and rapid evolutionary adaptation in polar bears.

PubMed

Liu, Shiping; Lorenzen, Eline D; Fumagalli, Matteo; Li, Bo; Harris, Kelley; Xiong, Zijun; Zhou, Long; Korneliussen, Thorfinn Sand; Somel, Mehmet; Babbitt, Courtney; Wray, Greg; Li, Jianwen; He, Weiming; Wang, Zhuo; Fu, Wenjing; Xiang, Xueyan; Morgan, Claire C; Doherty, Aoife; O'Connell, Mary J; McInerney, James O; Born, Erik W; Dalén, Love; Dietz, Rune; Orlando, Ludovic; Sonne, Christian; Zhang, Guojie; Nielsen, Rasmus; Willerslev, Eske; Wang, Jun

2014-05-08

Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyper-lipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479-343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization of the cardiovascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk of heart disease in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

POPULATION GENOMICS REVEAL RECENT SPECIATION AND RAPID EVOLUTIONARY ADAPTATION IN POLAR BEARS

PubMed Central

Liu, Shiping; Lorenzen, Eline D.; Fumagalli, Matteo; Li, Bo; Harris, Kelley; Xiong, Zijun; Zhou, Long; Korneliussen, Thorfinn Sand; Somel, Mehmet; Babbitt, Courtney; Wray, Greg; Li, Jianwen; He, Weiming; Wang, Zhuo; Fu, Wenjing; Xiang, Xueyan; Morgan, Claire C.; Doherty, Aoife; O’Connell, Mary J.; McInerney, James O.; Born, Erik W.; Dalén, Love; Dietz, Rune; Orlando, Ludovic; Sonne, Christian; Zhang, Guojie; Nielsen, Rasmus; Willerslev, Eske; Wang, Jun

2014-01-01

SUMMARY Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyperlipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479–343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization of the cardio-vascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk of heart disease in humans. PMID:24813606

A Neuroprotective Brain-penetrating Endopeptidase Fusion Protein Ameliorates Alzheimer Disease Pathology and Restores Neurogenesis*

PubMed Central

Spencer, Brian; Verma, Inder; Desplats, Paula; Morvinski, Dinorah; Rockenstein, Ed; Adame, Anthony; Masliah, Eliezer

2014-01-01

Alzheimer disease (AD) is characterized by widespread neurodegeneration throughout the association cortex and limbic system, deposition of amyloid-β peptide (Aβ) in the neuropil and around the blood vessels, and formation of neurofibrillary tangles. The endopeptidase neprilysin has been successfully used to reduce the accumulation of Aβ following intracranial viral vector delivery or ex vivo manipulated intracranial delivery. These therapies have relied on direct injections into the brain, whereas a clinically desirable therapy would involve i.v. infusion of a recombinant enzyme. We previously characterized a recombinant neprilysin that contained a 38-amino acid brain-targeting domain. Recombinant cell lines have been generated expressing this brain-targeted enzyme (ASN12). In this report, we characterize the ASN12 recombinant protein for pharmacology in a mouse as well as efficacy in two APPtg mouse models of AD. The recombinant ASN12 transited to the brain with a t½ of 24 h and accumulated to 1.7% of injected dose at 24 h following i.v. delivery. We examined pharmacodynamics in the tg2576 APPtg mouse with the prion promoter APP695 SWE mutation and in the Line41 mThy1 APP751 mutation mouse. Treatment of either APPtg mouse resulted in reduced Aβ, increased neuronal synapses, and improved learning and memory. In addition, the Line41 APPtg mice showed increased levels of C-terminal neuropeptide Y fragments and increased neurogenesis. These results suggest that the recombinant brain-targeted neprilysin, ASN12, may be an effective treatment for AD and warrant further investigation in clinical trials. PMID:24825898

Mechanisms of AD neurodegeneration may be independent of Aβ and its derivatives.

PubMed

Robakis, Nikolaos K

2011-03-01

Alzheimer's disease (AD) is the most common cause of dementia in the aged population. Most cases are sporadic although a small percent are familial (FAD) linked to genetic mutations. AD is caused by severe neurodegeneration in the hippocampus and neocortical regions of the brain but the cause of this neuronal loss is unclear. A widely discussed theory posits that amyloid depositions of Aβ peptides or their soluble forms are the causative agents of AD. Extensive research in the last 20 years however, failed to produce convincing evidence that brain amyloid is the main cause of AD neurodegeneration. Moreover, a number of observations, including absence of correlations between amyloid deposits and cognition, detection in normal individuals of amyloid loads similar to AD, and animal models with behavioral abnormalities independent of amyloid, are inconsistent with this theory. Other theories propose soluble Aβ peptides or their oligomers as agents that promote AD. These peptides, however, are normal components of human CSF and serum and there is little evidence of disease-associated increases in soluble Aβ and oligomers. That mutants of amyloid precursor protein (APP) and presenilin (PS) promote FAD suggests these proteins play crucial roles in neuronal function and survival. Accordingly, PS regulates production of signaling peptides and cell survival pathways while APP functions in cell death and may promote endosomal abnormalities. Evidence that FAD mutations inhibit the biological functions of PS combined with absence of haploinsufficiency mutants, support a model of allelic interference where inactive FAD mutant alleles promote autosomal dominant neurodegeneration by also inhibiting the functions of wild type alleles. Copyright © 2011 Elsevier Inc. All rights reserved.

Development of a Smartphone App for a Genetics Website: The Amyotrophic Lateral Sclerosis Online Genetics Database (ALSoD)

PubMed Central

Abel, Olubunmi; Shatunov, Aleksey; Jones, Ashley R; Andersen, Peter M; Powell, John F

2013-01-01

Background The ALS Online Genetics Database (ALSoD) website holds mutation, geographical, and phenotype data on genes implicated in amyotrophic lateral sclerosis (ALS) and links to bioinformatics resources, publications, and tools for analysis. On average, there are 300 unique visits per day, suggesting a high demand from the research community. To enable wider access, we developed a mobile-friendly version of the website and a smartphone app. Objective We sought to compare data traffic before and after implementation of a mobile version of the website to assess utility. Methods We identified the most frequently viewed pages using Google Analytics and our in-house analytic monitoring. For these, we optimized the content layout of the screen, reduced image sizes, and summarized available information. We used the Microsoft .NET framework mobile detection property (HttpRequest.IsMobileDevice in the Request.Browser object in conjunction with HttpRequest.UserAgent), which returns a true value if the browser is a recognized mobile device. For app development, we used the Eclipse integrated development environment with Android plug-ins. We wrapped the mobile website version with the WebView object in Android. Simulators were downloaded to test and debug the applications. Results The website automatically detects access from a mobile phone and redirects pages to fit the smaller screen. Because the amount of data stored on ALSoD is very large, the available information for display using smartphone access is deliberately restricted to improve usability. Visits to the website increased from 2231 to 2820, yielding a 26% increase from the pre-mobile to post-mobile period and an increase from 103 to 340 visits (230%) using mobile devices (including tablets). The smartphone app is currently available on BlackBerry and Android devices and will be available shortly on iOS as well. Conclusions Further development of the ALSoD website has allowed access through smartphones and tablets, either through the website or directly through a mobile app, making genetic data stored on the database readily accessible to researchers and patients across multiple devices. PMID:25098641

Development of a Smartphone App for a Genetics Website: The Amyotrophic Lateral Sclerosis Online Genetics Database (ALSoD).

PubMed

Abel, Olubunmi; Shatunov, Aleksey; Jones, Ashley R; Andersen, Peter M; Powell, John F; Al-Chalabi, Ammar

2013-09-04

The ALS Online Genetics Database (ALSoD) website holds mutation, geographical, and phenotype data on genes implicated in amyotrophic lateral sclerosis (ALS) and links to bioinformatics resources, publications, and tools for analysis. On average, there are 300 unique visits per day, suggesting a high demand from the research community. To enable wider access, we developed a mobile-friendly version of the website and a smartphone app. We sought to compare data traffic before and after implementation of a mobile version of the website to assess utility. We identified the most frequently viewed pages using Google Analytics and our in-house analytic monitoring. For these, we optimized the content layout of the screen, reduced image sizes, and summarized available information. We used the Microsoft .NET framework mobile detection property (HttpRequest.IsMobileDevice in the Request.Browser object in conjunction with HttpRequest.UserAgent), which returns a true value if the browser is a recognized mobile device. For app development, we used the Eclipse integrated development environment with Android plug-ins. We wrapped the mobile website version with the WebView object in Android. Simulators were downloaded to test and debug the applications. The website automatically detects access from a mobile phone and redirects pages to fit the smaller screen. Because the amount of data stored on ALSoD is very large, the available information for display using smartphone access is deliberately restricted to improve usability. Visits to the website increased from 2231 to 2820, yielding a 26% increase from the pre-mobile to post-mobile period and an increase from 103 to 340 visits (230%) using mobile devices (including tablets). The smartphone app is currently available on BlackBerry and Android devices and will be available shortly on iOS as well. Further development of the ALSoD website has allowed access through smartphones and tablets, either through the website or directly through a mobile app, making genetic data stored on the database readily accessible to researchers and patients across multiple devices.

Comparison of Monthly Mean Cloud Fraction and Cloud Optical depth Determined from Surface Cloud Radar, TOVS, AVHRR, and MODIS over Barrow, Alaska

NASA Technical Reports Server (NTRS)

Uttal, Taneil; Frisch, Shelby; Wang, Xuan-Ji; Key, Jeff; Schweiger, Axel; Sun-Mack, Sunny; Minnis, Patrick

2005-01-01

A one year comparison is made of mean monthly values of cloud fraction and cloud optical depth over Barrow, Alaska (71 deg 19.378 min North, 156 deg 36.934 min West) between 35 GHz radar-based retrievals, the TOVS Pathfinder Path-P product, the AVHRR APP-X product, and a MODIS based cloud retrieval product from the CERES-Team. The data sets represent largely disparate spatial and temporal scales, however, in this paper, the focus is to provide a preliminary analysis of how the mean monthly values derived from these different data sets compare, and determine how they can best be used separately, and in combination to provide reliable estimates of long-term trends of changing cloud properties. The radar and satellite data sets described here incorporate Arctic specific modifications that account for cloud detection challenges specific to the Arctic environment. The year 2000 was chosen for this initial comparison because the cloud radar data was particularly continuous and reliable that year, and all of the satellite retrievals of interest were also available for the year 2000. Cloud fraction was chosen as a comparison variable as accurate detection of cloud is the primary product that is necessary for any other cloud property retrievals. Cloud optical depth was additionally selected as it is likely the single cloud property that is most closely correlated to cloud influences on surface radiation budgets.

The ACAT inhibitor CP-113,818 markedly reduces amyloid pathology in a mouse model of Alzheimer's disease.

PubMed

Hutter-Paier, Birgit; Huttunen, Henri J; Puglielli, Luigi; Eckman, Christopher B; Kim, Doo Yeon; Hofmeister, Alexander; Moir, Robert D; Domnitz, Sarah B; Frosch, Matthew P; Windisch, Manfred; Kovacs, Dora M

2004-10-14

Amyloid beta-peptide (Abeta) accumulation in specific brain regions is a pathological hallmark of Alzheimer's disease (AD). We have previously reported that a well-characterized acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitor, CP-113,818, inhibits Abeta production in cell-based experiments. Here, we assessed the efficacy of CP-113,818 in reducing AD-like pathology in the brains of transgenic mice expressing human APP(751) containing the London (V717I) and Swedish (K670M/N671L) mutations. Two months of treatment with CP-113,818 reduced the accumulation of amyloid plaques by 88%-99% and membrane/insoluble Abeta levels by 83%-96%, while also decreasing brain cholesteryl-esters by 86%. Additionally, soluble Abeta(42) was reduced by 34% in brain homogenates. Spatial learning was slightly improved and correlated with decreased Abeta levels. In nontransgenic littermates, CP-113,818 also reduced ectodomain shedding of endogenous APP in the brain. Our results suggest that ACAT inhibition may be effective in the prevention and treatment of AD by inhibiting generation of the Abeta peptide.

BRI2 (ITM2b) Inhibits Aβ Deposition in Vivo

PubMed Central

Kim, Jungsu; Miller, Victor M.; Levites, Yona; West, Karen Jansen; Zwizinski, Craig W.; Moore, Brenda D.; Troendle, Fredrick J.; Bann, Maralyssa; Verbeeck, Christophe; Price, Robert W.; Smithson, Lisa; Sonoda, Leilani; Wagg, Kayleigh; Rangachari, Vijayaraghavan; Zou, Fanggeng; Younkin, Steven G.; Graff-Radford, Neill; Dickson, Dennis; Rosenberry, Terrone; Golde, Todd E.

2008-01-01

Analyses of the biologic effects of mutations in the BRI2 (ITM2b) and the amyloid β precursor protein (APP) genes support the hypothesis that cerebral accumulation of amyloidogenic peptides in familial British and familial Danish dementias and Alzheimer’s disease (AD) is associated with neurodegeneration. We have used somatic brain transgenic technology to express the BRI2 and BRI2-Aβ1-40 transgenes in amyloid β protein precursor (APP) mouse models. Expression of BRI2-Aβ1-40 mimics the suppressive effect previously observed using conventional transgenic methods, further validating the somatic brain transgenic methodology. Unexpectedly, we also find that expression of wild type human BRI2 reduces cerebral Aβ deposition in an AD mouse model. Additional data indicate that the 23 amino acid peptide, Bri23, released from BRI2 by normal processing is present in human cerebrospinal fluid (CSF), inhibits Aβ aggregation in vitro, and mediates its anti-amyloidogenic effect in vivo. These studies demonstrate that BRI2 is a novel mediator of Aβ deposition in vivo. PMID:18524908

Presenilin-Based Genetic Screens in Drosophila melanogaster Identify Novel Notch Pathway Modifiers

PubMed Central

Mahoney, Matt B.; Parks, Annette L.; Ruddy, David A.; Tiong, Stanley Y. K.; Esengil, Hanife; Phan, Alexander C.; Philandrinos, Panos; Winter, Christopher G.; Chatterjee, Runa; Huppert, Kari; Fisher, William W.; L'Archeveque, Lynn; Mapa, Felipa A.; Woo, Wendy; Ellis, Michael C.; Curtis, Daniel

2006-01-01

Presenilin is the enzymatic component of γ-secretase, a multisubunit intramembrane protease that processes several transmembrane receptors, such as the amyloid precursor protein (APP). Mutations in human Presenilins lead to altered APP cleavage and early-onset Alzheimer's disease. Presenilins also play an essential role in Notch receptor cleavage and signaling. The Notch pathway is a highly conserved signaling pathway that functions during the development of multicellular organisms, including vertebrates, Drosophila, and C. elegans. Recent studies have shown that Notch signaling is sensitive to perturbations in subcellular trafficking, although the specific mechanisms are largely unknown. To identify genes that regulate Notch pathway function, we have performed two genetic screens in Drosophila for modifiers of Presenilin-dependent Notch phenotypes. We describe here the cloning and identification of 19 modifiers, including nicastrin and several genes with previously undescribed involvement in Notch biology. The predicted functions of these newly identified genes are consistent with extracellular matrix and vesicular trafficking mechanisms in Presenilin and Notch pathway regulation and suggest a novel role for γ-tubulin in the pathway. PMID:16415372

Presenilin-based genetic screens in Drosophila melanogaster identify novel notch pathway modifiers.

PubMed

Mahoney, Matt B; Parks, Annette L; Ruddy, David A; Tiong, Stanley Y K; Esengil, Hanife; Phan, Alexander C; Philandrinos, Panos; Winter, Christopher G; Chatterjee, Runa; Huppert, Kari; Fisher, William W; L'Archeveque, Lynn; Mapa, Felipa A; Woo, Wendy; Ellis, Michael C; Curtis, Daniel

2006-04-01

Presenilin is the enzymatic component of gamma-secretase, a multisubunit intramembrane protease that processes several transmembrane receptors, such as the amyloid precursor protein (APP). Mutations in human Presenilins lead to altered APP cleavage and early-onset Alzheimer's disease. Presenilins also play an essential role in Notch receptor cleavage and signaling. The Notch pathway is a highly conserved signaling pathway that functions during the development of multicellular organisms, including vertebrates, Drosophila, and C. elegans. Recent studies have shown that Notch signaling is sensitive to perturbations in subcellular trafficking, although the specific mechanisms are largely unknown. To identify genes that regulate Notch pathway function, we have performed two genetic screens in Drosophila for modifiers of Presenilin-dependent Notch phenotypes. We describe here the cloning and identification of 19 modifiers, including nicastrin and several genes with previously undescribed involvement in Notch biology. The predicted functions of these newly identified genes are consistent with extracellular matrix and vesicular trafficking mechanisms in Presenilin and Notch pathway regulation and suggest a novel role for gamma-tubulin in the pathway.

SIRT3 activator Honokiol attenuates β-Amyloid by modulating amyloidogenic pathway

PubMed Central

Lynd, Tyler; Briggs, Gwyneth; Adamek, Danielle; Jones, Ellery; Heiner, Jake; Majrashi, Mohammed; Moore, Timothy; Amin, Rajesh; Suppiramaniam, Vishnu

2018-01-01

Honokiol (poly-phenolic lignan from Magnolia grandiflora) is a Sirtuin-3 (SIRT3) activator which exhibit antioxidant activity and augment mitochondrial functions in several experimental models. Modern evidence suggests the critical role of SIRT3 in the progression of several metabolic and neurodegenerative diseases. Amyloid beta (Aβ), the precursor to extracellular senile plaques, accumulates in the brains of patients with Alzheimer’s disease (AD) and is related to the development of cognitive impairment and neuronal cell death. Aβ is generated from amyloid-β precursor protein (APP) through sequential cleavages, first by β-secretase and then by γ-secretase. Drugs modulating this pathway are believed to be one of the most promising strategies for AD treatment. In the present study, we found that Honokiol significantly enhanced SIRT3 expression, reduced reactive oxygen species generation and lipid peroxidation, enhanced antioxidant activities, and mitochondrial function thereby reducing Aβ and sAPPβ levels in Chinese Hamster Ovarian (CHO) cells (carrying the amyloid precursor protein-APP and Presenilin PS1 mutation). Mechanistic studies revealed that Honokiol affects neither protein levels of APP nor α-secretase activity. In contrast, Honokiol increased the expression of AMPK, CREB, and PGC-1α, thereby inhibiting β-secretase activity leading to reduced Aβ levels. These results suggest that Honokiol is an activator of SIRT3 capable of improving antioxidant activity, mitochondrial energy regulation, while decreasing Aβ, thereby indicating it to be a lead compound for AD drug development. PMID:29324783

Amyloid β production is regulated by β2-adrenergic signaling-mediated post-translational modifications of the ryanodine receptor.

PubMed

Bussiere, Renaud; Lacampagne, Alain; Reiken, Steven; Liu, Xiaoping; Scheuerman, Valerie; Zalk, Ran; Martin, Cécile; Checler, Frederic; Marks, Andrew R; Chami, Mounia

2017-06-16

Alteration of ryanodine receptor (RyR)-mediated calcium (Ca 2+ ) signaling has been reported in Alzheimer disease (AD) models. However, the molecular mechanisms underlying altered RyR-mediated intracellular Ca 2+ release in AD remain to be fully elucidated. We report here that RyR2 undergoes post-translational modifications (phosphorylation, oxidation, and nitrosylation) in SH-SY5Y neuroblastoma cells expressing the β-amyloid precursor protein (βAPP) harboring the familial double Swedish mutations (APPswe). RyR2 macromolecular complex remodeling, characterized by depletion of the regulatory protein calstabin2, resulted in increased cytosolic Ca 2+ levels and mitochondrial oxidative stress. We also report a functional interplay between amyloid β (Aβ), β-adrenergic signaling, and altered Ca 2+ signaling via leaky RyR2 channels. Thus, post-translational modifications of RyR occur downstream of Aβ through a β2-adrenergic signaling cascade that activates PKA. RyR2 remodeling in turn enhances βAPP processing. Importantly, pharmacological stabilization of the binding of calstabin2 to RyR2 channels, which prevents Ca 2+ leakage, or blocking the β2-adrenergic signaling cascade reduced βAPP processing and the production of Aβ in APPswe-expressing SH-SY5Y cells. We conclude that targeting RyR-mediated Ca 2+ leakage may be a therapeutic approach to treat AD. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Genome-editing applications of CRISPR–Cas9 to promote in vitro studies of Alzheimer’s disease

PubMed Central

Shim, Kyu Hwan; Bagyinszky, Eva

2018-01-01

Genetic variations play an important role in the clinical presentation and progression of Alzheimer’s disease (AD), especially early-onset Alzheimer’s disease. Hundreds of mutations have been reported with the majority resulting from alterations in β-amyloid precursor protein (APP), presenilin 1 (PSEN1), or presenilin 2 (PSEN2) genes. The roles of these mutations in the pathogenesis of AD have been classically confirmed or refuted through functional studies, where the mutations are cloned, inserted into cell lines, and monitored for changes in various properties including cell survival, amyloid production, or Aβ42/40 ratio. However, these verification studies tend to be expensive, time consuming, and inconsistent. Recently, the clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 (CRISPR–Cas9) system was developed, which improves sequence-specific gene editing in cell lines, organs, and animals. CRISPR–Cas9 is a promising tool for the generation of models of human genetic diseases and could facilitate the establishment of new animal AD models and the observation of dynamic bioprocesses in AD. Here, we recapitulated the history of CRISPR technology, recent progress, and, especially, its potential applications in AD-related genetic, animal modeling, and functional studies. PMID:29445268

Gain-of-function somatic mutations contribute to inflammation and blood vessel damage that lead to Alzheimer dementia: a hypothesis.

PubMed

Marchesi, Vincent T

2016-02-01

Amyloid deposits are a characteristic feature of advanced Alzheimer dementia (AD), but whether they initiate the disease or are a consequence of it remains an unsettled question. To explore an alternative pathogenic mechanism, I propose that the triggering events that begin the pathogenic cascade are not amyloid deposits but damaged blood vessels caused by inflammatory reactions that lead to ischemia, amyloid accumulation, axonal degeneration, synaptic loss, and eventually irreversible neuronal cell death. Inflammation and blood vessel damage are well recognized complications of AD, but what causes them and why the cerebral microvasculature is affected have never been adequately addressed. Because heritable autosomal dominant mutations of NLRP3, APP, TREX1, NOTCH3, and Col4A1 are known to provoke inflammatory reactions and damage the brain in a wide variety of diseases, I propose that one or more low abundant, gain-of-function somatic mutations of the same 5 gene families damage the microvasculature of the brain that leads to dementia. This implies that the pathogenic triggers that lead to AD are derived not from external invaders or amyloid but from oxidative damage of our own genes. © FASEB.

Protein expression of targets of the FMRP regulon is altered in brains of subjects with schizophrenia and mood disorders

PubMed Central

Folsom, Timothy D.; Thuras, Paul D.; Fatemi, S. Hossein

2016-01-01

Fragile X mental retardation protein (FMRP) is an RNA binding protein with 842 target mRNAs in mammalian brain. Silencing of the fragile X mental retardation 1 (FMR1) gene leads to loss of expression of FMRP and upregulated metabotropic glutamate receptor 5 (mGluR5) signaling resulting in the multiple physical and cognitive deficits associated with fragile X syndrome (FXS). Reduced FMRP expression has been identified in subjects with autism, schizophrenia, bipolar disorder, and major depression who do not carry the mutation for FMR1. Our laboratory has recently demonstrated altered expression of four downstream targets of FMRP-mGluR5 signaling in brains of subjects with autism: homer 1, amyloid beta A4 precursor protein (APP), ras-related C3 botulinum toxin substrate 1 (RAC1), and striatal-enriched protein tyrosine phosphatase (STEP). In the current study we investigated the expression of the same four proteins in lateral cerebella of subjects with schizophrenia, bipolar disorder, and major depression and in frontal cortex of subjects with schizophrenia and bipolar disorder. In frontal cortex we observed: 1) reduced expression of 120 kDa form of APP in subjects with schizophrenia and bipolar disorder; 2) reduced expression of 61 kDa and 33 kDa forms of STEP in subjects with schizophrenia; 3) reduced expression of 88 kDa form of APP in subjects with bipolar disorder; and 3) trends for reduced expression of 88 kDa form of APP and homer 1 in subjects with schizophrenia and bipolar disorder, respectively. In lateral cerebella there was no group difference, however we observed increased expression of RAC1 in subjects with bipolar disorder, and trends for increased RAC1 in subjects with schizophrenia and major depression. Our results provide further evidence that proteins involved in the FMRP-mGluR5 signaling pathway are altered in schizophrenia and mood disorders. PMID:25956630

Protein expression of targets of the FMRP regulon is altered in brains of subjects with schizophrenia and mood disorders.

PubMed

Folsom, Timothy D; Thuras, Paul D; Fatemi, S Hossein

2015-07-01

Fragile X mental retardation protein (FMRP) is an RNA binding protein with 842 target mRNAs in mammalian brain. Silencing of the fragile X mental retardation 1 (FMR1) gene leads to loss of expression of FMRP and upregulated metabotropic glutamate receptor 5 (mGluR5) signaling resulting in the multiple physical and cognitive deficits associated with fragile X syndrome (FXS). Reduced FMRP expression has been identified in subjects with autism, schizophrenia, bipolar disorder, and major depression who do not carry the mutation for FMR1. Our laboratory has recently demonstrated altered expression of four downstream targets of FMRP-mGluR5 signaling in brains of subjects with autism: homer 1, amyloid beta A4 precursor protein (APP), ras-related C3 botulinum toxin substrate 1 (RAC1), and striatal-enriched protein tyrosine phosphatase (STEP). In the current study we investigated the expression of the same four proteins in lateral cerebella of subjects with schizophrenia, bipolar disorder, and major depression and in frontal cortex of subjects with schizophrenia and bipolar disorder. In frontal cortex we observed: 1) reduced expression of 120 kDa form of APP in subjects with schizophrenia and bipolar disorder; 2) reduced expression of 61 kDa and 33k Da forms of STEP in subjects with schizophrenia; 3) reduced expression of 88 kDa form of APP in subjects with bipolar disorder; and 3) trends for reduced expression of 88 kDa form of APP and homer 1 in subjects with schizophrenia and bipolar disorder, respectively. In lateral cerebella there was no group difference, however we observed increased expression of RAC1 in subjects with bipolar disorder, and trends for increased RAC1 in subjects with schizophrenia and major depression. Our results provide further evidence that proteins involved in the FMRP-mGluR5 signaling pathway are altered in schizophrenia and mood disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

A neuroprotective brain-penetrating endopeptidase fusion protein ameliorates Alzheimer disease pathology and restores neurogenesis.

PubMed

Spencer, Brian; Verma, Inder; Desplats, Paula; Morvinski, Dinorah; Rockenstein, Ed; Adame, Anthony; Masliah, Eliezer

2014-06-20

Alzheimer disease (AD) is characterized by widespread neurodegeneration throughout the association cortex and limbic system, deposition of amyloid-β peptide (Aβ) in the neuropil and around the blood vessels, and formation of neurofibrillary tangles. The endopeptidase neprilysin has been successfully used to reduce the accumulation of Aβ following intracranial viral vector delivery or ex vivo manipulated intracranial delivery. These therapies have relied on direct injections into the brain, whereas a clinically desirable therapy would involve i.v. infusion of a recombinant enzyme. We previously characterized a recombinant neprilysin that contained a 38-amino acid brain-targeting domain. Recombinant cell lines have been generated expressing this brain-targeted enzyme (ASN12). In this report, we characterize the ASN12 recombinant protein for pharmacology in a mouse as well as efficacy in two APPtg mouse models of AD. The recombinant ASN12 transited to the brain with a t½ of 24 h and accumulated to 1.7% of injected dose at 24 h following i.v. delivery. We examined pharmacodynamics in the tg2576 APPtg mouse with the prion promoter APP695 SWE mutation and in the Line41 mThy1 APP751 mutation mouse. Treatment of either APPtg mouse resulted in reduced Aβ, increased neuronal synapses, and improved learning and memory. In addition, the Line41 APPtg mice showed increased levels of C-terminal neuropeptide Y fragments and increased neurogenesis. These results suggest that the recombinant brain-targeted neprilysin, ASN12, may be an effective treatment for AD and warrant further investigation in clinical trials. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Dysregulation of cellular calcium homeostasis in Alzheimer's disease: bad genes and bad habits.

PubMed

Mattson, M P; Chan, S L

2001-10-01

Calcium is one of the most important intracellular messengers in the brain, being essential for neuronal development, synaptic transmission and plasticity, and the regulation of various metabolic pathways. The findings reviewed in the present article suggest that calcium also plays a prominent role in the pathogenesis of Alzheimer's disease (AD). Associations between the pathological hallmarks ofAD (neurofibrillary tangles [NFT] and amyloid plaques) and perturbed cellular calcium homeostasis have been established in studies of patients, and in animal and cell culture models of AD. Studies of the effects of mutations in the beta-amyloid precursor protein (APP) and presenilins on neuronal plasticity and survival have provided insight into the molecular cascades that result in synaptic dysfunction and neuronal degeneration in AD. Central to the neurodegenerative process is the inability of neurons to properly regulate intracellular calcium levels. Increased levels of amyloid beta-peptide (Abeta) induce oxidative stress, which impairs cellular ion homeostasis and energy metabolism and renders neurons vulnerable to apoptosis and excitotoxicity. Subtoxic levels of Abeta may induce synaptic dysfunction by impairing multiple signal transduction pathways. Presenilin mutations perturb calcium homeostasis in the endoplasmic reticulum in a way that sensitizes neurons to apoptosis and excitotoxicity; links between aberrant calcium regulation and altered APP processing are emerging. Environmental risk factors for AD are being identified and may include high calorie diets, folic acid insufficiency, and a low level of intellectual activity (bad habits); in each case, the environmental factor impacts on neuronal calcium homeostasis. Low calorie diets and intellectual activity may guard against AD by stimulating production of neurotrophic factors and chaperone proteins. The emerging picture of the cell and molecular biology of AD is revealing novel preventative and therapeutic strategies for eradicating this growing epidemic of the elderly.

Pathways Impacted by Genomic Alterations in Pulmonary Carcinoid Tumors.

PubMed

Asiedu, Michael K; Thomas, Charles F; Dong, Jie; Schulte, Sandra C; Khadka, Prasidda; Sun, Zhifu; Kosari, Farhad; Jen, Jin; Molina, Julian; Vasmatzis, George; Kuang, Ray; Aubry, Marie Christine; Yang, Ping; Wigle, Dennis A

2018-04-01

Purpose: Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, comprise 30% of all carcinoid malignancies, and are defined histologically as typical carcinoid (TC) and atypical carcinoid (AC) tumors. The role of specific genomic alterations in the pathogenesis of pulmonary carcinoid tumors remains poorly understood. We sought to identify genomic alterations and pathways that are deregulated in these tumors to find novel therapeutic targets for pulmonary carcinoid tumors. Experimental Design: We performed integrated genomic analysis of carcinoid tumors comprising whole genome and exome sequencing, mRNA expression profiling and SNP genotyping of specimens from normal lung, TC and AC, and small cell lung carcinoma (SCLC) to fully represent the lung neuroendocrine tumor spectrum. Results: Analysis of sequencing data found recurrent mutations in cancer genes including ATP1A2, CNNM1, MACF1, RAB38, NF1, RAD51C, TAF1L, EPHB2, POLR3B , and AGFG1 The mutated genes are involved in biological processes including cellular metabolism, cell division cycle, cell death, apoptosis, and immune regulation. The top most significantly mutated genes were TMEM41B, DEFB127, WDYHV1, and TBPL1 Pathway analysis of significantly mutated and cancer driver genes implicated MAPK/ERK and amyloid beta precursor protein (APP) pathways whereas analysis of CNV and gene expression data suggested deregulation of the NF-κB and MAPK/ERK pathways. The mutation signature was predominantly C>T and T>C transitions with a minor contribution of T>G transversions. Conclusions: This study identified mutated genes affecting cancer relevant pathways and biological processes that could provide opportunities for developing targeted therapies for pulmonary carcinoid tumors. Clin Cancer Res; 24(7); 1691-704. ©2018 AACR . ©2018 American Association for Cancer Research.

A Selective Sweep on a Deleterious Mutation in CPT1A in Arctic Populations

PubMed Central

Clemente, Florian J.; Cardona, Alexia; Inchley, Charlotte E.; Peter, Benjamin M.; Jacobs, Guy; Pagani, Luca; Lawson, Daniel J.; Antão, Tiago; Vicente, Mário; Mitt, Mario; DeGiorgio, Michael; Faltyskova, Zuzana; Xue, Yali; Ayub, Qasim; Szpak, Michal; Mägi, Reedik; Eriksson, Anders; Manica, Andrea; Raghavan, Maanasa; Rasmussen, Morten; Rasmussen, Simon; Willerslev, Eske; Vidal-Puig, Antonio; Tyler-Smith, Chris; Villems, Richard; Nielsen, Rasmus; Metspalu, Mait; Malyarchuk, Boris; Derenko, Miroslava; Kivisild, Toomas

2014-01-01

Arctic populations live in an environment characterized by extreme cold and the absence of plant foods for much of the year and are likely to have undergone genetic adaptations to these environmental conditions in the time they have been living there. Genome-wide selection scans based on genotype data from native Siberians have previously highlighted a 3 Mb chromosome 11 region containing 79 protein-coding genes as the strongest candidates for positive selection in Northeast Siberians. However, it was not possible to determine which of the genes might be driving the selection signal. Here, using whole-genome high-coverage sequence data, we identified the most likely causative variant as a nonsynonymous G>A transition (rs80356779; c.1436C>T [p.Pro479Leu] on the reverse strand) in CPT1A, a key regulator of mitochondrial long-chain fatty-acid oxidation. Remarkably, the derived allele is associated with hypoketotic hypoglycemia and high infant mortality yet occurs at high frequency in Canadian and Greenland Inuits and was also found at 68% frequency in our Northeast Siberian sample. We provide evidence of one of the strongest selective sweeps reported in humans; this sweep has driven this variant to high frequency in circum-Arctic populations within the last 6–23 ka despite associated deleterious consequences, possibly as a result of the selective advantage it originally provided to either a high-fat diet or a cold environment. PMID:25449608

The genetics of Alzheimer's disease.

PubMed

Bertram, Lars; Tanzi, Rudolph E

2012-01-01

Genetic factors play a major role in determining a person's risk to develop Alzheimer's disease (AD). Rare mutations transmitted in a Mendelian fashion within affected families, for example, APP, PSEN1, and PSEN2, cause AD. In the absence of mutations in these genes, disease risk is largely determined by common polymorphisms that, in concert with each other and nongenetic risk factors, modestly impact risk for AD (e.g., the ε4-allele in APOE). Recent genome-wide screening approaches have revealed several additional AD susceptibility loci and more are likely to be discovered over the coming years. In this chapter, we review the current state of AD genetics research with a particular focus on loci that now can be considered established disease genes. In addition to reviewing the potential pathogenic relevance of these genes, we provide an outlook into the future of AD genetics research based on recent advances in high-throughput sequencing technologies. Copyright © 2012 Elsevier Inc. All rights reserved.

Linkage of familial Alzheimer disease to chromosome 14 in two large early-onset pedigrees: effects of marker allele frequencies on lod scores.

PubMed

Nechiporuk, A; Fain, P; Kort, E; Nee, L E; Frommelt, E; Polinsky, R J; Korenberg, J R; Pulst, S M

1993-05-01

Alzheimer disease (AD) is a devastating neurodegenerative disease leading to global dementia. In addition to sporadic forms of AD, familial forms (FAD) have been recognized. Mutations in the amyloid precursor protein (APP) gene on chromosome (CHR) 21 have been shown to cause early-onset AD in a small number of pedigrees. Recently, linkage to markers on CHR 14 has been established in several early-onset FAD pedigrees. We now report lod scores for CHR 14 markers in two large early-onset FAD pedigrees. Pairwise linkage analysis suggested that in these pedigrees the mutation is tightly linked to the loci D14S43 and D14S53. However, assumptions regarding marker allele frequencies had a major and often unpredictable effect on calculated lod scores. Therefore, caution needs to be exercised when single pedigrees are analyzed with marker allele frequencies determined from the literature or from a pool of spouses.

Screening of dementia genes by whole-exome sequencing in early-onset Alzheimer disease: input and lessons.

PubMed

Nicolas, Gaël; Wallon, David; Charbonnier, Camille; Quenez, Olivier; Rousseau, Stéphane; Richard, Anne-Claire; Rovelet-Lecrux, Anne; Coutant, Sophie; Le Guennec, Kilan; Bacq, Delphine; Garnier, Jean-Guillaume; Olaso, Robert; Boland, Anne; Meyer, Vincent; Deleuze, Jean-François; Munter, Hans Markus; Bourque, Guillaume; Auld, Daniel; Montpetit, Alexandre; Lathrop, Mark; Guyant-Maréchal, Lucie; Martinaud, Olivier; Pariente, Jérémie; Rollin-Sillaire, Adeline; Pasquier, Florence; Le Ber, Isabelle; Sarazin, Marie; Croisile, Bernard; Boutoleau-Bretonnière, Claire; Thomas-Antérion, Catherine; Paquet, Claire; Sauvée, Mathilde; Moreaud, Olivier; Gabelle, Audrey; Sellal, François; Ceccaldi, Mathieu; Chamard, Ludivine; Blanc, Frédéric; Frebourg, Thierry; Campion, Dominique; Hannequin, Didier

2016-05-01

Causative variants in APP, PSEN1 or PSEN2 account for a majority of cases of autosomal dominant early-onset Alzheimer disease (ADEOAD, onset before 65 years). Variant detection rates in other EOAD patients, that is, with family history of late-onset AD (LOAD) (and no incidence of EOAD) and sporadic cases might be much lower. We analyzed the genomes from 264 patients using whole-exome sequencing (WES) with high depth of coverage: 90 EOAD patients with family history of LOAD and no incidence of EOAD in the family and 174 patients with sporadic AD starting between 51 and 65 years. We found three PSEN1 and one PSEN2 causative, probably or possibly causative variants in four patients (1.5%). Given the absence of PSEN1, PSEN2 and APP causative variants, we investigated whether these 260 patients might be burdened with protein-modifying variants in 20 genes that were previously shown to cause other types of dementia when mutated. For this analysis, we included an additional set of 160 patients who were previously shown to be free of causative variants in PSEN1, PSEN2 and APP: 107 ADEOAD patients and 53 sporadic EOAD patients with an age of onset before 51 years. In these 420 patients, we detected no variant that might modify the function of the 20 dementia-causing genes. We conclude that EOAD patients with family history of LOAD and no incidence of EOAD in the family or patients with sporadic AD starting between 51 and 65 years have a low variant-detection rate in AD genes.

Regulation of neuronal APL-1 expression by cholesterol starvation.

PubMed

Wiese, Mary; Antebi, Adam; Zheng, Hui

2012-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of β-amyloid plaques composed primarily of the amyloid-β peptide, a cleavage product of amyloid precursor protein (APP). While mutations in APP lead to the development of Familial Alzheimer's Disease (FAD), sporadic AD has only one clear genetic modifier: the ε4 allele of the apolipoprotein E (ApoE) gene. Cholesterol starvation in Caenorhabditis elegans leads to molting and arrest phenotypes similar to loss-of-function mutants of the APP ortholog, apl-1 (amyloid precursor-like protein 1), and lrp-1 (lipoprotein receptor-related protein 1), suggesting a potential interaction between apl-1 and cholesterol metabolism. Previously, we found that RNAi knock-down of apl-1 leads to aldicarb hypersensitivity, indicating a defect in synaptic function. Here we find the same defect is recapitulated during lrp-1 knock-down and by cholesterol starvation. A cholesterol-free diet or loss of lrp-1 directly affects APL-1 levels as both lead to loss of APL-1::GFP fluorescence in neurons. However, loss of cholesterol does not affect global transcription or protein levels as seen by qPCR and Western blot. Our results show that cholesterol and lrp-1 are involved in the regulation of synaptic transmission, similar to apl-1. Both are able to modulate APL-1 protein levels in neurons, however cholesterol changes do not affect global apl-1 transcription or APL-1 protein indicating the changes are specific to neurons. Thus, regulation of synaptic transmission and molting by LRP-1 and cholesterol may be mediated by their ability to control APL-1 neuronal protein expression.

Evaluating the Dietary and Nutritional Apps in the Google Play Store.

PubMed

Schumer, Harleigh; Amadi, Chioma; Joshi, Ashish

2018-01-01

The objective of this study was to evaluate the features of diet and nutrition apps available in the Google Play Store. A search was conducted in August 2017 using the Google Play Store database to identify apps related to diet and nutrition. Terms entered into the app search engine included 'diet apps' and 'nutrition apps'. The first 50 apps resulting from each search term was assessed. Duplicates were removed, and a comparative analysis was performed on the remaining diet and nutrition apps. A total of 86 diet and nutrition apps were identified. One hundred percent (n = 86) of the apps retrieved were freely available. More than half of the apps were applicable to a target user group of all ages (94%, n = 81). Stratified analysis across unique diet and nutrition apps (total, n = 72) showed a higher average rating for the diet apps (4.4) in comparison to that for the nutrition apps (4.3). Diet apps were more likely to be recently updated than the nutrition apps (72% vs. 66%), and diet apps were more likely to feature app purchase than nutrition apps (36% vs. 19%). The average rating was slightly higher for diet apps not featuring in-app purchases, but ratings were similar for the nutrition apps. A centralized resource is needed that can provide information on health-related apps to allow for systematic evaluation of their effectiveness. Further research needs to examine improved methods of designing app-store platforms and presenting the available apps to properly guide users in app selection.

Early-Onset Network Hyperexcitability in Presymptomatic Alzheimer’s Disease Transgenic Mice Is Suppressed by Passive Immunization with Anti-Human APP/Aβ Antibody and by mGluR5 Blockade

PubMed Central

Kazim, Syed F.; Chuang, Shih-Chieh; Zhao, Wangfa; Wong, Robert K. S.; Bianchi, Riccardo; Iqbal, Khalid

2017-01-01

Cortical and hippocampal network hyperexcitability appears to be an early event in Alzheimer’s disease (AD) pathogenesis, and may contribute to memory impairment. It remains unclear if network hyperexcitability precedes memory impairment in mouse models of AD and what are the underlying cellular mechanisms. We thus evaluated seizure susceptibility and hippocampal network hyperexcitability at ~3 weeks of age [prior to amyloid beta (Aβ) plaque deposition, neurofibrillary pathology, and cognitive impairment] in a triple transgenic mouse model of familial AD (3xTg-AD mouse) that harbors mutated human Aβ precursor protein (APP), tau and presenilin 1 (PS1) genes. Audiogenic seizures were elicited in a higher proportion of 3xTg-AD mice compared with wild type (WT) controls. Seizure susceptibility in 3xTg-AD mice was attenuated either by passive immunization with anti-human APP/Aβ antibody (6E10) or by blockade of metabotropic glutamate receptor 5 (mGluR5) with the selective antagonist, 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP). In in vitro hippocampal slices, suppression of synaptic inhibition with the GABAA receptor antagonist, bicuculline, induced prolonged epileptiform (>1.5 s in duration) ictal-like discharges in the CA3 neuronal network in the majority of the slices from 3xTg-AD mice. In contrast, only short epileptiform (<1.5 s in duration) interictal-like discharges were observed following bicuculline application in the CA3 region of WT slices. The ictal-like activity in CA3 region of the hippocampus was significantly reduced in the 6E10-immunized compared to the saline-treated 3xTg-AD mice. MPEP acutely suppressed the ictal-like discharges in 3xTg-AD slices. Remarkably, epileptiform discharge duration positively correlated with intraneuronal human (transgenic) APP/Aβ expression in the CA3 region of the hippocampus. Our data suggest that in a mouse model of familial AD, hypersynchronous network activity underlying seizure susceptibility precedes Aβ plaque pathology and memory impairment. This early-onset network hyperexcitability can be suppressed by passive immunization with an anti-human APP/Aβ antibody and by mGluR5 blockade in 3xTg-AD mice. PMID:28392767

Cleavage of amyloid precursor protein by an archaeal presenilin homologue PSH

PubMed Central

Dang, Shangyu; Wu, Shenjie; Wang, Jiawei; Li, Hongbo; Huang, Min; He, Wei; Li, Yue-Ming; Wong, Catherine C. L.; Shi, Yigong

2015-01-01

Aberrant cleavage of amyloid precursor protein (APP) by γ-secretase contributes to the development of Alzheimer’s disease. More than 200 disease-derived mutations have been identified in presenilin (the catalytic subunit of γ-secretase), making modulation of γ-secretase activity a potentially attractive therapeutic opportunity. Unfortunately, the technical challenges in dealing with intact γ-secretase have hindered discovery of modulators and demand a convenient substitute approach. Here we report that, similar to γ-secretase, the archaeal presenilin homolog PSH faithfully processes the substrate APP C99 into Aβ42, Aβ40, and Aβ38. The molar ratio of the cleavage products Aβ42 over Aβ40 by PSH is nearly identical to that by γ-secretase. The proteolytic activity of PSH is specifically suppressed by presenilin-specific inhibitors. Known modulators of γ-secretase also modulate PSH similarly in terms of the Aβ42/Aβ40 ratio. Structural analysis reveals association of a known γ-secretase inhibitor with PSH between its two catalytic aspartate residues. These findings identify PSH as a surrogate protease for the screening of agents that may regulate the protease activity and the cleavage preference of γ-secretase. PMID:25733893

Erratum: Erratum to: "Numerical simulation of the two-phase flow produced by spraying a liquid by a nozzle"

NASA Astrophysics Data System (ADS)

Simakov, N. N.

2018-04-01

Page 1010, left column, line 4 from bottom should read "radius R APP" instead of "diameter D APP" Page 1010, right column, before the formula (19) should read " R APP" instead of " D APP" Page 1010, in the caption to Fig. 5 should read "radius R APP" instead of "diameter D APP" Page 1011, in the caption to Fig. 6 should read "radius R APP" instead of "diameter D APP" Page 1011, left column, second paragraph after Fig. 6, line 4 from top should read "radius R APP" instead of "diameter D APP" Page 1011, the same paragraph, lines 1, 2 from bottom, in the expression for Qm and after it should read "radius R APP" instead of "diameter D APP" Page 1011, left column, paragraph 3 after Fig. 6, last two lines should read " R APP =" instead of " D APP =" Page 1011, Fig. 7, the notation on the abscissa axis should read " R APP" instead of " D APP" Page 1011, in the caption to Fig. 7 should read "radius R APP" instead of "diameter D APP" Page 1011, in caption to Fig. 8 should read "for both radii R APP" instead of "for both diameters D APP" Page 1012, in caption to Fig. 9 should read "for both radii R APP" instead of "for both diameters D APP"

Serum neurofilament light in familial Alzheimer disease: A marker of early neurodegeneration.

PubMed

Weston, Philip S J; Poole, Teresa; Ryan, Natalie S; Nair, Akshay; Liang, Yuying; Macpherson, Kirsty; Druyeh, Ronald; Malone, Ian B; Ahsan, R Laila; Pemberton, Hugh; Klimova, Jana; Mead, Simon; Blennow, Kaj; Rossor, Martin N; Schott, Jonathan M; Zetterberg, Henrik; Fox, Nick C

2017-11-21

To investigate whether serum neurofilament light (NfL) concentration is increased in familial Alzheimer disease (FAD), both pre and post symptom onset, and whether it is associated with markers of disease stage and severity. We recruited 48 individuals from families with PSEN1 or APP mutations to a cross-sectional study: 18 had symptomatic Alzheimer disease (AD) and 30 were asymptomatic but at 50% risk of carrying a mutation. Serum NfL was measured using an ultrasensitive immunoassay on the single molecule array (Simoa) platform. Cognitive testing and MRI were performed; 33 participants had serial MRI, allowing calculation of atrophy rates. Genetic testing established mutation status. A generalized least squares regression model was used to compare serum NfL among symptomatic mutation carriers, presymptomatic carriers, and noncarriers, adjusting for age and sex. Spearman coefficients assessed associations between serum NfL and (1) estimated years to/from symptom onset (EYO), (2) cognitive measures, and (3) MRI measures of atrophy. Nineteen of the asymptomatic participants were mutation carriers (mean EYO -9.6); 11 were noncarriers. Compared with noncarriers, serum NfL concentration was higher in both symptomatic ( p < 0.0001) and presymptomatic mutation carriers ( p = 0.007). Across all mutation carriers, serum NfL correlated with EYO (ρ = 0.81, p < 0.0001) and multiple cognitive and imaging measures, including Mini-Mental State Examination (ρ = -0.62, p = 0.0001), Clinical Dementia Rating Scale sum of boxes (ρ = 0.79, p < 0.0001), baseline brain volume (ρ = -0.62, p = 0.0002), and whole-brain atrophy rate (ρ = 0.53, p = 0.01). Serum NfL concentration is increased in FAD prior to symptom onset and correlates with measures of disease stage and severity. Serum NfL may thus be a feasible biomarker of early AD-related neurodegeneration. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

[Animal models of neurodegenerative diseases].

PubMed

Langui, Dominique; Lachapelle, François; Duyckaerts, Charles

2007-02-01

Numerous evidences indicate that the phenotype of a neurodegenerative disease and its pathogenetic mechanism are only loosely linked. The phenotype is directly related to the topography of the lesions and is reproduced whatever the mechanism as soon as the same neurons are destroyed or deficient: the symptoms of Parkinson disease are mimicked by any destruction of the neurons of the substantia nigra, caused for instance by the toxin MPTP. This does not mean that idiopathic Parkinson disease is due to MPTP. In the same way, mouse lines such as Reeler, Weaver and Staggerer in which ataxia occurs spontaneously does not help to understand human ataxias: now that mutations responsible for these phenotypes have been identified, it appears that one is responsible for lissencephaly (mutation of the reelin gene) and the other two have no equivalent in man. Therapeutic attempts, however, rely on the understanding of the pathogenetic mechanisms. Introducing a mutated human transgene in the genome of an animal has, in many instances, significantly improved this understanding. Transgenic mice have proven useful in reproducing lesions seen in neurodegenerative disease such as the plaques of Alzheimer disease (in the APP mouse which has integrated the mutated gene of the amyloid protein precursor), the tau glial and neuronal accumulation (seen in cases of frontotemporal dementias due to tau mutation), the nuclear inclusions caused by CAG triplet expansion (seen in the mutation of Huntington disease and autosomal dominant spinocerebellar ataxias). These recent advances have fostered numerous therapeutic attempts. Transgenesis in drosophila and in the worm Caenorhabditis elegans have opened new possibilities in the screening of protein partners, modifier genes, and potential therapeutic molecules. However, it is also becoming clear that introducing a human mutated gene in an animal does not necessarily trigger pathogenetic cascades identical to those seen in the human disease. Human diseases have to be studied in parallel with their animal models to ensure that the model mimic at least a few original mechanisms, on which new therapeutics may be tested.

Evaluating the Dietary and Nutritional Apps in the Google Play Store

PubMed Central

Schumer, Harleigh; Amadi, Chioma

2018-01-01

Objectives The objective of this study was to evaluate the features of diet and nutrition apps available in the Google Play Store. Methods A search was conducted in August 2017 using the Google Play Store database to identify apps related to diet and nutrition. Terms entered into the app search engine included ‘diet apps’ and ‘nutrition apps’. The first 50 apps resulting from each search term was assessed. Duplicates were removed, and a comparative analysis was performed on the remaining diet and nutrition apps. Results A total of 86 diet and nutrition apps were identified. One hundred percent (n = 86) of the apps retrieved were freely available. More than half of the apps were applicable to a target user group of all ages (94%, n = 81). Stratified analysis across unique diet and nutrition apps (total, n = 72) showed a higher average rating for the diet apps (4.4) in comparison to that for the nutrition apps (4.3). Diet apps were more likely to be recently updated than the nutrition apps (72% vs. 66%), and diet apps were more likely to feature app purchase than nutrition apps (36% vs. 19%). The average rating was slightly higher for diet apps not featuring in-app purchases, but ratings were similar for the nutrition apps. Conclusions A centralized resource is needed that can provide information on health-related apps to allow for systematic evaluation of their effectiveness. Further research needs to examine improved methods of designing app-store platforms and presenting the available apps to properly guide users in app selection. PMID:29503751

Medical applications: a database and characterization of apps in Apple iOS and Android platforms.

PubMed

Seabrook, Heather J; Stromer, Julie N; Shevkenek, Cole; Bharwani, Aleem; de Grood, Jill; Ghali, William A

2014-08-27

Medical applications (apps) for smart phones and tablet computers are growing in number and are commonly used in healthcare. In this context, there is a need for a diverse community of app users, medical researchers, and app developers to better understand the app landscape. In mid-2012, we undertook an environmental scan and classification of the medical app landscape in the two dominant platforms by searching the medical category of the Apple iTunes and Google Play app download sites. We identified target audiences, functions, costs and content themes using app descriptions and captured these data in a database. We only included apps released or updated between October 1, 2011 and May 31, 2012, with a primary "medical" app store categorization, in English, that contained health or medical content. Our sample of Android apps was limited to the most popular apps in the medical category. Our final sample of Apple iOS (n = 4561) and Android (n = 293) apps illustrate a diverse medical app landscape. The proportion of Apple iOS apps for the public (35%) and for physicians (36%) is similar. Few Apple iOS apps specifically target nurses (3%). Within the Android apps, those targeting the public dominated in our sample (51%). The distribution of app functions is similar in both platforms with reference being the most common function. Most app functions and content themes vary considerably by target audience. Social media apps are more common for patients and the public, while conference apps target physicians. We characterized existing medical apps and illustrated their diversity in terms of target audience, main functions, cost and healthcare topic. The resulting app database is a resource for app users, app developers and health informatics researchers.

“Let’s get Wasted!” and Other Apps: Characteristics, Acceptability, and Use of Alcohol-Related Smartphone Applications

PubMed Central

Weaver, Emma R; Horyniak, Danielle R; Jenkinson, Rebecca; Dietze, Paul

2013-01-01

Background Smartphone applications (“apps”) offer a number of possibilities for health promotion activities. However, young people may also be exposed to apps with incorrect or poor quality information, since, like the Internet, apps are mostly unregulated. Little is known about the quality of alcohol-related apps or what influence they may have on young people’s behavior. Objective To critically review popular alcohol-related smartphone apps and to explore young people’s opinions of these apps, their acceptability, and use for alcohol-related health promotion. Methods First, a content analysis of 500 smartphone apps available via Apple iTunes and Android Google Play stores was conducted. Second, all available blood alcohol concentration (BAC) apps were tested against four individual case profiles of known BAC from a previous study. Third, two focus group discussions explored how young people use alcohol-related apps, particularly BAC apps. Results 384 apps were included; 50% (192) were entertainment apps, 39% (148) were BAC apps, and 11% (44) were health promotion and/or stop drinking–related apps. When testing the BAC apps, there was wide variation in results, with apps tending to overestimate BAC scores compared with recorded scores. Participants were skeptical of the accuracy of BAC apps, and there was an overall concern that these apps would be used as a form of entertainment, further encouraging young people to drink, rather than reduce their drinking and risk taking. Conclusions The majority of popular alcohol-related apps encouraged alcohol consumption. Apps estimating blood alcohol concentration were widely available but were highly unreliable. Health departments and prominent health organizations need to endorse alcohol smartphone apps that are accurate and evidence-based to give specific apps credibility in the ever-expanding market of unregulated apps. PMID:25100681

Review of infectious diseases applications for iPhone/iPad and Android: from pocket to patient.

PubMed

Moodley, Amaran; Mangino, Julie E; Goff, Debra A

2013-10-01

The explosion of medical applications (apps) in the Apple and Google Play app stores has made it increasingly difficult to find relevant and reliable infectious diseases (ID) apps. Apple created a section called "Apps for Healthcare Professionals"; however, several ID apps are missing. Google Play's ID category has several non-ID apps. Many apps involve diagnosis and patient management, creating a need for regulations and oversight by the US Food and Drug Administration. There are no standards to guide accuracy or reliability of medical apps' content. We searched Apple and Google Play app stores to identify new ID apps. Over 1200 apps were identified. We applied several exclusion criteria to identify adult/pediatric apps with data from trustworthy sources that were not reviewed within the last year. Twelve new ID apps were identified with a comprehensive list of 24 ID apps to assist healthcare professionals at the point of care.

Mobile Apps for the Dietary Approaches to Stop Hypertension (DASH): App Quality Evaluation.

PubMed

DiFilippo, Kristen Nicole; Huang, Wen-Hao David; Chapman-Novakofski, Karen M

2018-03-08

To identify the availability and quality of apps supporting Dietary Approaches to Stop Hypertension (DASH) education. The researchers identified DASH apps over 1 month in the Apple App Store. Five registered dietitians used the App Quality Evaluation (AQEL) to evaluate app quality on 7 domains. Interrater reliability was tested using intraclass correlations. One paid and 3 free DASH apps were evaluated. Interrater reliability (n = 5) was good for 3 apps and fair for 1 app. Only the paid app scored high (>8 of 10) on most AQEL quality domains. Based on lower quality found among the included free apps, further development of free apps is warranted. Whereas the paid app may be useful in supporting DASH education, future research should determine whether improvements in clinical outcomes are found and whether this app should be improved to address AQEL domains better. Copyright © 2018 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

AppVis: Enabling data-rich apps in app inventor

NASA Astrophysics Data System (ADS)

Harunani, Farzeen

MIT App Inventor has enabled middle school students to learn computing while creating their own apps--including apps that serve community needs. However, few resources exist for building apps that gather and share data. There is a need for new tools and an instructional materials for students to build data-enabled, community-focused apps. We developed an extension for App Inventor, called AppVis, which allows app-makers to publish and retrieve data from iSENSE, our existing web-based collaborative data visualization platform. We used AppVis and supporting instructional materials in two one-week summer camps attended by a total of 33 middle school students. Based on student interview data and analysis of their final apps, our approach was broadly accessible to a diverse population of students. Students were motivated to build apps that could be used by their own communities. This thesis presents the design of AppVis and results from students' work in summer camps.

mHealthApps: A Repository and Database of Mobile Health Apps.

PubMed

Xu, Wenlong; Liu, Yin

2015-03-18

The market of mobile health (mHealth) apps has rapidly evolved in the past decade. With more than 100,000 mHealth apps currently available, there is no centralized resource that collects information on these health-related apps for researchers in this field to effectively evaluate the strength and weakness of these apps. The objective of this study was to create a centralized mHealth app repository. We expect the analysis of information in this repository to provide insights for future mHealth research developments. We focused on apps from the two most established app stores, the Apple App Store and the Google Play Store. We extracted detailed information of each health-related app from these two app stores via our python crawling program, and then stored the information in both a user-friendly array format and a standard JavaScript Object Notation (JSON) format. We have developed a centralized resource that provides detailed information of more than 60,000 health-related apps from the Apple App Store and the Google Play Store. Using this information resource, we analyzed thousands of apps systematically and provide an overview of the trends for mHealth apps. This unique database allows the meta-analysis of health-related apps and provides guidance for research designs of future apps in the mHealth field.

Qualitative evaluation of mobile cancer apps with particular attention to the target group, content, and advertising.

PubMed

Böhme, Cathleen; von Osthoff, Marc Baron; Frey, Katrin; Hübner, Jutta

2018-01-01

Medical apps are gaining importance rapidly. Also in the field of cancer care, apps are offered. Yet, so far little is known with respect to their quality. In a pilot phase we developed a rating tool based on formal and content-related criteria for the assessment of cancer apps. We used this instrument on cancer apps available in the App Store (iOS) concerning breast, prostate and colorectal cancer. The results were stratified according to target group, content and advertising. We assessed 41 mobile cancer apps. Six apps (14.63%) scored very high, fifteen apps (36.59%) high, seventeen apps (41.46%) were deficient, and three apps (7.32%) were insufficient. The largest group of apps represents those apps with the "deficient" rating. The very good to good apps had reliable sources, a concrete intent/ purpose in their app description, and a strict distinction of scientific content and advertisement. Apps with the predicates "deficient" or "insufficient" had particularly poor ratings, e.g. in the subscales "information on sources" and "data protection". Almost half of the tested apps were deficient or insufficient. In order to improve safety of patients using apps, some regulation seems mandatory. Putting apps under the legislation for medical products might be one way to better regulate and control quality. Second, efforts should focus on the development of checklists that make it easier for patients to search for suitable cancer apps.

Mobile Phone Apps to Improve Medication Adherence: A Systematic Stepwise Process to Identify High-Quality Apps.

PubMed

Santo, Karla; Richtering, Sarah S; Chalmers, John; Thiagalingam, Aravinda; Chow, Clara K; Redfern, Julie

2016-12-02

There are a growing number of mobile phone apps available to support people in taking their medications and to improve medication adherence. However, little is known about how these apps differ in terms of features, quality, and effectiveness. We aimed to systematically review the medication reminder apps available in the Australian iTunes store and Google Play to assess their features and their quality in order to identify high-quality apps. This review was conducted in a similar manner to a systematic review by using a stepwise approach that included (1) a search strategy; (2) eligibility assessment; (3) app selection process through an initial screening of all retrieved apps and full app review of the included apps; (4) data extraction using a predefined set of features considered important or desirable in medication reminder apps; (5) analysis by classifying the apps as basic and advanced medication reminder apps and scoring and ranking them; and (6) a quality assessment by using the Mobile App Rating Scale (MARS), a reliable tool to assess mobile health apps. We identified 272 medication reminder apps, of which 152 were found only in Google Play, 87 only in iTunes, and 33 in both app stores. Apps found in Google Play had more customer reviews, higher star ratings, and lower cost compared with apps in iTunes. Only 109 apps were available for free and 124 were recently updated in 2015 or 2016. Overall, the median number of features per app was 3.0 (interquartile range 4.0) and only 18 apps had ≥9 of the 17 desirable features. The most common features were flexible scheduling that was present in 56.3% (153/272) of the included apps, medication tracking history in 54.8% (149/272), snooze option in 34.9% (95/272), and visual aids in 32.4% (88/272). We classified 54.8% (149/272) of the included apps as advanced medication reminder apps and 45.2% (123/272) as basic medication reminder apps. The advanced apps had a higher number of features per app compared with the basic apps. Using the MARS instrument, we were able to identify high-quality apps that were rated as being very interesting and entertaining, highly interactive and customizable, intuitive, and easy to use and to navigate as well as having a high level of visual appeal and good-quality information. Many medication reminder apps are available in the app stores; however, the majority of them did not have many of the desirable features and were, therefore, considered low quality. Through a systematic stepwise process, we were able to identify high-quality apps to be tested in a future study that will provide evidence on the use of medication reminder apps to improve medication adherence. ©Karla Santo, Sarah S Richtering, John Chalmers, Aravinda Thiagalingam, Clara K Chow, Julie Redfern. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 02.12.2016.

Mobile Phone Apps to Improve Medication Adherence: A Systematic Stepwise Process to Identify High-Quality Apps

PubMed Central

Richtering, Sarah S; Chalmers, John; Thiagalingam, Aravinda; Chow, Clara K; Redfern, Julie

2016-01-01

Background There are a growing number of mobile phone apps available to support people in taking their medications and to improve medication adherence. However, little is known about how these apps differ in terms of features, quality, and effectiveness. Objective We aimed to systematically review the medication reminder apps available in the Australian iTunes store and Google Play to assess their features and their quality in order to identify high-quality apps. Methods This review was conducted in a similar manner to a systematic review by using a stepwise approach that included (1) a search strategy; (2) eligibility assessment; (3) app selection process through an initial screening of all retrieved apps and full app review of the included apps; (4) data extraction using a predefined set of features considered important or desirable in medication reminder apps; (5) analysis by classifying the apps as basic and advanced medication reminder apps and scoring and ranking them; and (6) a quality assessment by using the Mobile App Rating Scale (MARS), a reliable tool to assess mobile health apps. Results We identified 272 medication reminder apps, of which 152 were found only in Google Play, 87 only in iTunes, and 33 in both app stores. Apps found in Google Play had more customer reviews, higher star ratings, and lower cost compared with apps in iTunes. Only 109 apps were available for free and 124 were recently updated in 2015 or 2016. Overall, the median number of features per app was 3.0 (interquartile range 4.0) and only 18 apps had ≥9 of the 17 desirable features. The most common features were flexible scheduling that was present in 56.3% (153/272) of the included apps, medication tracking history in 54.8% (149/272), snooze option in 34.9% (95/272), and visual aids in 32.4% (88/272). We classified 54.8% (149/272) of the included apps as advanced medication reminder apps and 45.2% (123/272) as basic medication reminder apps. The advanced apps had a higher number of features per app compared with the basic apps. Using the MARS instrument, we were able to identify high-quality apps that were rated as being very interesting and entertaining, highly interactive and customizable, intuitive, and easy to use and to navigate as well as having a high level of visual appeal and good-quality information. Conclusions Many medication reminder apps are available in the app stores; however, the majority of them did not have many of the desirable features and were, therefore, considered low quality. Through a systematic stepwise process, we were able to identify high-quality apps to be tested in a future study that will provide evidence on the use of medication reminder apps to improve medication adherence. PMID:27913373

Users’ Adoption of Mental Health Apps: Examining the Impact of Information Cues

PubMed Central

Huang, Hsiao-Ying

2017-01-01

Background Numerous mental health apps have been developed and made available to users on the current app market. Users may find it difficult and overwhelming to select apps from the hundreds of choices that are available in the app marketplace. Clarifying what information cues may impact a user’s selection and adoption of mental health apps is now a critical and pressing issue. Objective The aim of this study was to investigate the impact of information cues on users’ adoption of anxiety apps using observational data from the Android app market. Methods A systematic search of anxiety apps was conducted on the Android app store by using keywords search. The title and metadata information of a total of 274 apps that met our criteria were collected and analyzed. Three trained researchers recorded the app rankings from the search results page on different dates and Web browsers. Results Our results show that ratings (r=.56, P<.001) and reviews (r=.39, P<.001) have significant positive correlations with the number of installs, and app prices have significant negative correlations with installs (r=−.36). The results also reveal that lower-priced apps have higher ratings (r=−.23, P<.001) and a greater number of app permission requests (r=.18, P=.002) from the device. For app titles, we found that apps with titles related to symptoms have significantly lower installs than apps with titles that are not related to symptoms (P<.001). Conclusions This study revealed a relationship between information cues and users’ adoption of mental health apps by analyzing observational data. As the first of its kind, we found impactful indicators for mental health app adoptions. We also discovered a labeling effect of app titles that could hinder mental health app adoptions and which may provide insight for future designs of mental health apps and their search mechanisms. PMID:28659256

mHealth in Urology: A Review of Experts' Involvement in App Development.

PubMed

Pereira-Azevedo, Nuno; Carrasquinho, Eduardo; Cardoso de Oliveira, Eduardo; Cavadas, Vitor; Osório, Luís; Fraga, Avelino; Castelo-Branco, Miguel; Roobol, Monique J

2015-01-01

Smartphones are increasingly playing a role in healthcare and previous studies assessing medical applications (apps) have raised concerns about lack of expert involvement and low content accuracy. However, there are no such studies in Urology. We reviewed Urology apps with the aim of assessing the level of participation of healthcare professionals (HCP) and scientific Urology associations in their development. A systematic search was performed on PubMed, Apple's App Store and Google's Play Store, for Urology apps, available in English. Apps were reviewed by three graders to determine the app's platform, target customer, developer, app type, app category, price and the participation of a HCP or a scientific Urology association in the development. The search yielded 372 apps, of which 150 were specific for Urology. A fifth of all apps had no HCP involvement (20.7%) and only a third had been developed with a scientific Urology association (34.7%). The lowest percentage of HCP (13.4%) and urological association (1.9%) involvement was in apps designed for the general population. Furthermore, there was no contribution from an Urology society in "Electronic Medical Record" nor in "Patient Information" apps. A limitation of the study is that only Android and iOS apps were reviewed. Despite the increasing Mobile Health (mHealth) market, this is the first study that demonstrates the lack of expert participation in the design of Urology apps, particularly in apps designed for the general public. Until clear regulation is enforced, the urological community should help regulate app development. Maintaining a register of certified apps or issuing an official scientific seal of approval could improve overall app quality. We propose that urologists become stakeholders in mHealth, shaping future app design and promoting peer-review app validation.

Pro-smoking apps: where, how and who are most at risk.

PubMed

BinDhim, Nasser F; Freeman, Becky; Trevena, Lyndal

2015-03-01

Pro-smoking applications (app) provide information about brands of tobacco products, where to buy them, and encourage their use. It is unclear in which countries these apps are being downloaded, or whether app stores play a role in promoting or regulating these apps, particularly those that appear to target children. The lifetime popularity of 107 pro-smoking apps was investigated, using a third-party app metrics service that aggregates data from app stores about app download popularity by country. Apps were deemed popular if at any time in their lifespan they achieved a top 25 ranking overall across all apps, or a top 25 ranking in any particular category of apps, such as 'educational games'. Fifty-eight pro-smoking apps reached 'popularity' status in Apple and Android stores in one or more of 49 countries, particularly Italy, Egypt, Germany, Belgium and the USA. The daily downloads in each country ranged from approximately 2000 to 80 000. The Apple store featured five of the pro-smoking apps in various categories, and two apps were featured by the Android market. Two pro-smoking apps in the Apple store were extremely popular in the 'Educational Games' and 'Kids' Games' categories. Pro-smoking apps were popular in many countries. Most apps were assigned to entertainment and games categories, with some apps specifically targeting children through placement in categories directed at children. App stores that feature pro-smoking apps may be in violation of tobacco control laws. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Smartphone applications in burns.

PubMed

Wurzer, Paul; Parvizi, Daryousch; Lumenta, David B; Giretzlehner, Michael; Branski, Ludwik K; Finnerty, Celeste C; Herndon, David N; Tuca, Alexandru; Rappl, Thomas; Smolle, Christian; Kamolz, Lars P

2015-08-01

Since the introduction of applications (apps) for smartphones, the popularity of medical apps has been rising. The aim of this review was to demonstrate the current availability of apps related to burns on Google's Android and Apple's iOS store as well as to include a review of their developers, features, and costs. A systematic online review of Google Play Store and Apple's App Store was performed by using the following search terms: "burn," "burns," "thermal," and the German word "Verbrennung." All apps that were programmed for use as medical apps for burns were included. The review was performed from 25 February until 1 March 2014. A closer look at the free and paid calculation apps including a standardized patient was performed. Four types of apps were identified: calculators, information apps, book/journal apps, and games. In Google Play Store, 31 apps were related to burns, of which 20 were calculation apps (eight for estimating the total body surface area (TBSA) and nine for total fluid requirement (TFR)). In Apple's App Store, under the category of medicine, 39 apps were related to burns, of which 21 were calculation apps (19 for estimating the TBSA and 17 for calculating the TFR). In 19 out of 32 available calculation apps, our study showed a correlation of the calculated TFR compared to our standardized patient. The review demonstrated that many apps for medical burns are available in both common app stores. Even free available calculation apps may provide a more objective and reproducible procedure compared to manual/subjective estimations, although there is still a lack of data security especially in personal data entered in calculation apps. Further clinical studies including smartphone apps for burns should be performed. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Smartphone apps to support hospital prescribing and pharmacology education: a review of current provision

PubMed Central

Haffey, Faye; Brady, Richard R W; Maxwell, Simon

2014-01-01

Junior doctors write the majority of hospital prescriptions but many indicate they feel underprepared to assume this responsibility and around 10% of prescriptions contain errors. Medical smartphone apps are now widely used in clinical practice and present an opportunity to provide support to inexperienced prescribers. This study assesses the contemporary range of smartphone apps with prescribing or related content. Six smartphone app stores were searched for apps aimed at the healthcare professional with drug, pharmacology or prescribing content. Three hundred and six apps were identified. 34% appeared to be for use within the clinical environment in order to aid prescribing, 14% out with the clinical setting and 51% of apps were deemed appropriate for both clinical and non-clinical use. Apps with drug reference material, such as textbooks, manuals or medical apps with drug information were the commonest apps found (51%), followed by apps offering drug or infusion rate dose calculation (26%). 68% of apps charged for download, with a mean price of £14.25 per app and a range of £0.62–101.90. A diverse range of pharmacology-themed apps are available and there is further potential for the development of contemporary apps to improve prescribing performance. Personalized app stores may help universities/healthcare organizations offer high quality apps to students to aid in pharmacology education. Users of prescribing apps must be aware of the lack of information regarding the medical expertise of app developers. This will enable them to make informed choices about the use of such apps in their clinical practice. PMID:23488599

Smartphone apps for orthopaedic sports medicine - a smart move?

PubMed

Wong, Seng Juong; Robertson, Greg A; Connor, Katie L; Brady, Richard R; Wood, Alexander M

2015-01-01

With the advent of smartphones together with their downloadable applications (apps), there is increasing opportunities for doctors, including orthopaedic sports surgeons, to integrate such technology into clinical practice. However, the clinical reliability of these medical apps remains questionable. We reviewed available apps themed specifically towards Orthopaedic Sports Medicine and related conditions and assessed the level of medical professional involvement in their design and content, along with a review of these apps. The most popular smartphone app stores (Android, Apple, Blackberry, Windows, Samsung, Nokia) were searched for Orthopaedic Sports medicine themed apps, using the search terms; Orthopaedic Sports Medicine, Orthopaedics, Sports medicine, Knee Injury, Shoulder Injury, Anterior Cruciate Ligament Tear, Medial Collateral Ligament Tear, Rotator Cuff Tear, Meniscal Tear, Tennis Elbow. All English language apps related to orthopaedic sports medicine were included. A total of 76 individual Orthopaedic Sports Medicine themed apps were identified. According to app store classifications, there were 45 (59 %) medical themed apps, 28 (37 %) health and fitness themed apps, 1 (1 %) business app, 1 (1 %) reference app and 1 (1 %) sports app. Forty-nine (64 %) apps were available for download free of charge. For those that charged access, the prices ranged from £0.69 to £69.99. Only 51 % of sports medicine apps had customer satisfaction ratings and 39 % had named medical professional involvement in their development or content. We found the majority of Orthopaedic Sports Medicine apps had no named medical professional involvement, raising concerns over their content and evidence-base. We recommend increased regulation of such apps to improve the accountability of app content.

Smartphone apps to support hospital prescribing and pharmacology education: a review of current provision.

PubMed

Haffey, Faye; Brady, Richard R W; Maxwell, Simon

2014-01-01

Junior doctors write the majority of hospital prescriptions but many indicate they feel underprepared to assume this responsibility and around 10% of prescriptions contain errors. Medical smartphone apps are now widely used in clinical practice and present an opportunity to provide support to inexperienced prescribers. This study assesses the contemporary range of smartphone apps with prescribing or related content. Six smartphone app stores were searched for apps aimed at the healthcare professional with drug, pharmacology or prescribing content. Three hundred and six apps were identified. 34% appeared to be for use within the clinical environment in order to aid prescribing, 14% out with the clinical setting and 51% of apps were deemed appropriate for both clinical and non-clinical use. Apps with drug reference material, such as textbooks, manuals or medical apps with drug information were the commonest apps found (51%), followed by apps offering drug or infusion rate dose calculation (26%). 68% of apps charged for download, with a mean price of £14.25 per app and a range of £0.62-101.90. A diverse range of pharmacology-themed apps are available and there is further potential for the development of contemporary apps to improve prescribing performance. Personalized app stores may help universities/healthcare organizations offer high quality apps to students to aid in pharmacology education. Users of prescribing apps must be aware of the lack of information regarding the medical expertise of app developers. This will enable them to make informed choices about the use of such apps in their clinical practice. © 2013 The British Pharmacological Society.

Pro-smoking apps for smartphones: the latest vehicle for the tobacco industry?

PubMed

BinDhim, Nasser F; Freeman, Becky; Trevena, Lyndal

2014-01-01

Smartphone use is growing exponentially and will soon become the only mobile phone handset for about 6 billion users. Smartphones are ideal marketing targets as consumers can be reached anytime, anywhere. Smartphone application (app) stores are global shops that sell apps to users all around the world. Although smartphone stores have a wide collection of health-related apps they also have a wide set of harmful apps. In this study, the availability of 'pro-smoking' apps in two of the largest smartphone app stores (Apple App store and Android Market) was examined. In February 2012, we searched the Apple App Store and Android Market for pro-smoking apps, using the keywords Smoke, Cigarette, Cigar, Smoking and Tobacco. We excluded apps that were not tobacco-related and then assessed the tobacco-related apps against our inclusion criteria. 107 pro-smoking apps were identified and classified into six categories based on functionality.42 of these apps were from the Android Market and downloaded by over 6 million users. Some apps have explicit images of cigarette brands. Tobacco products are being promoted in the new 'smartphone app' medium which has global reach, a huge consumer base of various age groups and underdeveloped regulation. The paper also provides two examples of app store responses to country-specific laws and regulations that could be used to control the harmful contents in the app stores for individual countries.

Free smoking cessation mobile apps available in Australia: a quality review and content analysis.

PubMed

Thornton, Louise; Quinn, Catherine; Birrell, Louise; Guillaumier, Ashleigh; Shaw, Brad; Forbes, Erin; Deady, Mark; Kay-Lambkin, Frances

2017-12-01

This review aimed to identify free, high-quality, smoking cessation mobile applications (apps) that adhere to Australian smoking cessation treatment guidelines. A systematic search of smoking cessation apps was conducted using Google. The technical quality of relevant apps was rated using the Mobile Application Rating Scale. The content of apps identified as high quality was assessed for adherence to smoking cessation treatment guidelines. 112 relevant apps were identified. The majority were of poor technical quality and only six 'high-quality' apps were identified. These apps adhered to Australian treatment guidelines in part. The efficacy of two apps had been previously evaluated. In lieu of more substantial research in this area, it is suggested that the high-quality apps identified in this review may be more likely than other available apps to encourage smoking cessation. Implications for public health: Smoking cessation apps have the potential to address many barriers that prevent smoking cessation support being provided; however few high-quality smoking cessation apps are currently available in Australia, very few have been evaluated and the app market is extremely volatile. More research to evaluate smoking cessation apps, and sustained funding for evidence-based apps, is needed. © 2017 The Authors.

Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

PubMed

Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

2015-02-01

Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

APP/Aβ structural diversity and Alzheimer's disease pathogenesis.

PubMed

Roher, Alex E; Kokjohn, Tyler A; Clarke, Steven G; Sierks, Michael R; Maarouf, Chera L; Serrano, Geidy E; Sabbagh, Marwan S; Beach, Thomas G

2017-11-01

The amyloid cascade hypothesis of Alzheimer's disease (AD) proposes amyloid- β (Aβ) is a chief pathological element of dementia. AD therapies have targeted monomeric and oligomeric Aβ 1-40 and 1-42 peptides. However, alternative APP proteolytic processing produces a complex roster of Aβ species. In addition, Aβ peptides are subject to extensive posttranslational modification (PTM). We propose that amplified production of some APP/Aβ species, perhaps exacerbated by differential gene expression and reduced peptide degradation, creates a diverse spectrum of modified species which disrupt brain homeostasis and accelerate AD neurodegeneration. We surveyed the literature to catalog Aβ PTM including species with isoAsp at positions 7 and 23 which may phenocopy the Tottori and Iowa Aβ mutations that result in early onset AD. We speculate that accumulation of these alterations induce changes in secondary and tertiary structure of Aβ that favor increased toxicity, and seeding and propagation in sporadic AD. Additionally, amyloid-β peptides with a pyroglutamate modification at position 3 and oxidation of Met35 make up a substantial portion of sporadic AD amyloid deposits. The intrinsic physical properties of these species, including resistance to degradation, an enhanced aggregation rate, increased neurotoxicity, and association with behavioral deficits, suggest their emergence is linked to dementia. The generation of specific 3D-molecular conformations of Aβ impart unique biophysical properties and a capacity to seed the prion-like global transmission of amyloid through the brain. The accumulation of rogue Aβ ultimately contributes to the destruction of vascular walls, neurons and glial cells culminating in dementia. A systematic examination of Aβ PTM and the analysis of the toxicity that they induced may help create essential biomarkers to more precisely stage AD pathology, design countermeasures and gauge the impacts of interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Apps of Steel: Are Exercise Apps Providing Consumers with Realistic Expectations?: A Content Analysis of Exercise Apps for Presence of Behavior Change Theory

ERIC Educational Resources Information Center

Cowan, Logan T.; Van Wagenen, Sarah A.; Brown, Brittany A.; Hedin, Riley J.; Seino-Stephan, Yukiko; Hall, P. Cougar; West, Joshua H.

2013-01-01

Objective. To quantify the presence of health behavior theory constructs in iPhone apps targeting physical activity. Methods. This study used a content analysis of 127 apps from Apple's (App Store) "Health & Fitness" category. Coders downloaded the apps and then used an established theory-based instrument to rate each app's inclusion of…

Diet and Physical Activity Apps: Perceived Effectiveness by App Users

PubMed Central

Egelandsdal, Bjørg; Amdam, Gro V; Almli, Valerie L; Oostindjer, Marije

2016-01-01

Background Diet and physical activity apps are two types of health apps that aim to promote healthy eating and energy expenditure through monitoring of dietary intake and physical activity. No clear evidence showing the effectiveness of using these apps to promote healthy eating and physical activity has been previously reported. Objective This study aimed to identify how diet and physical activity (PA) apps affected their users. It also investigated if using apps was associated with changes in diet and PA. Methods First, 3 semi-structured focus group discussions concerning app usability were conducted (15 app users and 8 nonusers; mean age 24.2 years, SD 6.4), including outcome measures such as motivations, experiences, opinions, and adherence. Results from the discussions were used to develop a questionnaire. The questionnaire, which contained questions about behavior changes, app usage, perceived effectiveness, and opinions of app usability, was answered by 500 Norwegians, with a mean age of 25.8 years (SD 5.1). Results App users found diet and PA apps effective in promoting healthy eating and exercising. These apps affected their actions, health consciousness, and self-education about nutrition and PA; and were also a part of their social lives. Over half of the users perceived that apps were effective in assisting them to eat healthily and to exercise more. Diet apps were more effective when they were frequently used and over a long period of time, compared to infrequent or short-term use (P=.01 and P=.02, respectively). Users who used diet and PA apps, perceived apps as more effective than users who only used one type of app (all P<.05). App users were better at maintaining diet and PA behaviors than nonusers (all P<.05). Young adults found apps fun to use, but sometimes time consuming. They wanted apps to be designed to meet their personal expectations. Conclusions App usage influenced action, consciousness, self-education about nutrition and PA, and social life. It facilitated maintaining a healthy diet and exercising more. Diet and PA apps of the future can be further strengthened by being tailored to meet personal needs. PMID:27056639

Should We Recommend Renal Diet-Related Apps to Our Patients? An Evaluation of the Quality and Health Literacy Demand of Renal Diet-Related Mobile Applications.

PubMed

Lambert, Kelly; Mullan, Judy; Mansfield, Kylie; Owen, Paris

2017-11-01

Mobile phone applications (apps) are increasingly being used by patients with chronic kidney disease (CKD). We sought to describe the main purpose of commonly available renal diet apps and to quantify the accuracy of information, technical quality, and health literacy demand of renal diet apps. The design was content analysis. All eligible renal diet apps in the Australian Apple App Store, Google Play, Windows Phone, and Blackberry App World were evaluated. Eligible apps were in English and were related to kidney disease in humans (of any type or stage). Exclusion criteria included apps which were prohibited because of password protection. Renal diet information in the apps was compared with evidence-based guidelines for the management of kidney disease to quantify information accuracy. App information was evaluated using the Silberg Scale. Technical quality and health literacy demand were evaluated using the Mobile Application Rating Scale. A total of 21 apps were eligible for evaluation. The main purpose of these apps was to provide food and nutrition information (57.1%) or for educative purposes for CKD patients (38.1%). Only 47.6% (10/21) of apps contained accurate evidence-based information. Overall, app technical quality was considered acceptable (mean Mobile Application Rating Scale score 3.19 ± 0.35 out of 5), with 80.9% of apps scoring acceptable or greater for app technical quality. Scores for health literacy demand also indicated that most apps (15/21, 71.4%) were acceptable. A range of apps currently exist that may provide individuals with CKD with useful food and nutrition information or increase their knowledge of the renal diet. These apps are also mainly of acceptable technical quality and health literacy demand. However, caution is required when using renal diet apps because more than half of the apps evaluated were not accurate and evidence based. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The Exosome Secretory Pathway Transports Amyloid Precursor Protein Carboxyl-terminal Fragments from the Cell into the Brain Extracellular Space*

PubMed Central

Perez-Gonzalez, Rocio; Gauthier, Sebastien A.; Kumar, Asok; Levy, Efrat

2012-01-01

In vitro studies have shown that neuronal cell cultures secrete exosomes containing amyloid-β precursor protein (APP) and the APP-processing products, C-terminal fragments (CTFs) and amyloid-β (Aβ). We investigated the secretion of full-length APP (flAPP) and APP CTFs via the exosome secretory pathway in vivo. To this end, we developed a novel protocol designed to isolate exosomes secreted into mouse brain extracellular space. Exosomes with typical morphology were isolated from freshly removed mouse brains and from frozen mouse and human brain tissues, demonstrating that exosomes can be isolated from post-mortem tissue frozen for long periods of time. flAPP, APP CTFs, and enzymes that cleave both flAPP and APP CTFs were identified in brain exosomes. Although higher levels of both flAPP and APP CTFs were observed in exosomes isolated from the brains of transgenic mice overexpressing human APP (Tg2576) compared with wild-type control mice, there was no difference in the number of secreted brain exosomes. These data indicate that the levels of flAPP and APP CTFs associated with exosomes mirror the cellular levels of flAPP and APP CTFs. Interestingly, exosomes isolated from the brains of both Tg2576 and wild-type mice are enriched with APP CTFs relative to flAPP. Thus, we hypothesize that the exosome secretory pathway plays a pleiotropic role in the brain: exosome secretion is beneficial to the cell, acting as a specific releasing system of neurotoxic APP CTFs and Aβ, but the secretion of exosomes enriched with APP CTFs, neurotoxic proteins that are also a source of secreted Aβ, is harmful to the brain. PMID:23129776

mHealth in Urology: A Review of Experts’ Involvement in App Development

PubMed Central

Pereira-Azevedo, Nuno; Carrasquinho, Eduardo; Cardoso de Oliveira, Eduardo; Cavadas, Vitor; Osório, Luís; Fraga, Avelino; Castelo-Branco, Miguel; Roobol, Monique J.

2015-01-01

Introduction Smartphones are increasingly playing a role in healthcare and previous studies assessing medical applications (apps) have raised concerns about lack of expert involvement and low content accuracy. However, there are no such studies in Urology. We reviewed Urology apps with the aim of assessing the level of participation of healthcare professionals (HCP) and scientific Urology associations in their development. Material and Methods A systematic search was performed on PubMed, Apple's App Store and Google's Play Store, for Urology apps, available in English. Apps were reviewed by three graders to determine the app’s platform, target customer, developer, app type, app category, price and the participation of a HCP or a scientific Urology association in the development. Results The search yielded 372 apps, of which 150 were specific for Urology. A fifth of all apps had no HCP involvement (20.7%) and only a third had been developed with a scientific Urology association (34.7%). The lowest percentage of HCP (13.4%) and urological association (1.9%) involvement was in apps designed for the general population. Furthermore, there was no contribution from an Urology society in "Electronic Medical Record" nor in "Patient Information" apps. A limitation of the study is that only Android and iOS apps were reviewed. Conclusions Despite the increasing Mobile Health (mHealth) market, this is the first study that demonstrates the lack of expert participation in the design of Urology apps, particularly in apps designed for the general public. Until clear regulation is enforced, the urological community should help regulate app development. Maintaining a register of certified apps or issuing an official scientific seal of approval could improve overall app quality. We propose that urologists become stakeholders in mHealth, shaping future app design and promoting peer-review app validation. PMID:25984916

Apps for People With Rheumatoid Arthritis to Monitor Their Disease Activity: A Review of Apps for Best Practice and Quality

PubMed Central

Townsley, Hermaleigh; White, Bonnie; Langlotz, Tobias; Taylor, William J

2017-01-01

Background Rheumatoid arthritis (RA) is a chronic inflammatory arthritis requiring long-term treatment with regular monitoring by a rheumatologist to achieve good health outcomes. Since people with RA may wish to monitor their own disease activity with a smartphone app, it is important to understand the functions and quality of apps for this purpose. Objective The aim of our study was to assess the features and quality of apps to assist people to monitor their RA disease activity by (1) summarizing the available apps, particularly the instruments used for measurement of RA disease activity; (2) comparing the app features with American College of Rheumatology and European League against Rheumatism (ACR and EULAR) guidelines for monitoring of RA disease activity; and (3) rating app quality with the Mobile App Rating Scale (MARS). Methods Systematic searches of the New Zealand iTunes and Google Play app stores were used to identify all apps for monitoring of RA disease activity that could be used by people with RA. The apps were described by both key metadata and app functionality. App adherence with recommendations for monitoring of RA disease activity in clinical practice was evaluated by identifying whether apps included calculation of a validated composite disease activity measure and recorded results for future retrieval. App quality was assessed by 2 independent reviewers using the MARS. Results The search identified 721 apps in the Google Play store and 216 in the iTunes store, of which 19 unique apps met criteria for inclusion (8 from both app stores, 8 iTunes, and 3 Google Play). In total, 14 apps included at least one validated instrument measuring RA disease activity; 7 of 11 apps that allowed users to enter a joint count used the standard 28 swollen and tender joint count; 8 apps included at least one ACR and EULAR-recommended RA composite disease activity (CDA) measure; and 10 apps included data storage and retrieval. Only 1 app, Arthritis Power, included both an RA CDA measure and tracked data, but this app did not include the standard 28 tender and swollen joint count. The median overall MARS score for apps was 3.41/5. Of the 6 apps that scored ≥4/5 on the overall MARS rating, only 1 included a CDA score endorsed by ACR and EULAR; however, this app did not have a data tracking function. Conclusions This review found a lack of high-quality apps for longitudinal assessment of RA disease activity. Current apps fall into two categories: simple calculators primarily for rheumatologists and data tracking tools for people with RA. The latter do not uniformly collect data using validated instruments or composite disease activity measures. There is a need for appropriate, high-quality apps for use by rheumatologists and patients together in co-management of RA. PMID:28223263

A systematic review of smartphone applications for smoking cessation.

PubMed

Haskins, Brianna L; Lesperance, Donna; Gibbons, Patric; Boudreaux, Edwin D

2017-06-01

Tobacco use is the leading cause of preventable disease and death in the USA. However, limited data exists regarding smoking cessation mobile app quality and intervention effectiveness. Innovative and scalable interventions are needed to further alleviate the public health implications of tobacco addiction. The proliferation of the smartphone and the advent of mobile phone health interventions have made treatment more accessible than ever. The purpose of this review was to examine the relation between published scientific literature and available commercial smartphone health apps for smoking cessation to identify the percentage of scientifically supported apps that were commercially available to consumers and to determine how many of the top commercially available apps for smoking cessation were supported by the published scientific literature. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, apps were reviewed in four phases: (1) identified apps from the scientific literature, (2) searched app stores for apps identified in the literature, (3) identified top apps available in leading app stores, and (4) determined which top apps available in stores had scientific support. Seven articles identified six apps with some level of scientific support, three (50%) were available in at least one app store. Conversely, among the top 50 apps suggested by each of the leading app stores, only two (4%) had any scientific support. While half of the scientifically vetted apps remain available to consumers, they are difficult to find among the many apps that are identified through app store searches.

App Chronic Disease Checklist: Protocol to Evaluate Mobile Apps for Chronic Disease Self-Management

PubMed Central

Anderson, Kevin; Burford, Oksana

2016-01-01

Background The availability of mobile health apps for self-care continues to increase. While little evidence of their clinical impact has been published, there is general agreement among health authorities and authors that consumers’ use of health apps assist in self-management and potentially clinical decision making. A consumer’s sustained engagement with a health app is dependent on the usability and functionality of the app. While numerous studies have attempted to evaluate health apps, there is a paucity of published methods that adequately recognize client experiences in the academic evaluation of apps for chronic conditions. Objective This paper reports (1) a protocol to shortlist health apps for academic evaluation, (2) synthesis of a checklist to screen health apps for quality and reliability, and (3) a proposed method to theoretically evaluate usability of health apps, with a view towards identifying one or more apps suitable for clinical assessment. Methods A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram was developed to guide the selection of the apps to be assessed. The screening checklist was thematically synthesized with reference to recurring constructs in published checklists and related materials for the assessment of health apps. The checklist was evaluated by the authors for face and construct validity. The proposed method for evaluation of health apps required the design of procedures for raters of apps, dummy data entry to test the apps, and analysis of raters’ scores. Results The PRISMA flow diagram comprises 5 steps: filtering of duplicate apps; eliminating non-English apps; removing apps requiring purchase, filtering apps not updated within the past year; and separation of apps into their core functionality. The screening checklist to evaluate the selected apps was named the App Chronic Disease Checklist, and comprises 4 sections with 6 questions in each section. The validity check verified classification of, and ambiguity in, wording of questions within constructs. The proposed method to evaluate shortlisted and downloaded apps comprises instructions to attempt set-up of a dummy user profile, and dummy data entry to represent in-range and out-of-range clinical measures simulating a range of user behaviors. A minimum score of 80% by consensus (using the Intraclass Correlation Coefficient) between raters is proposed to identify apps suitable for clinical trials. Conclusions The flow diagram allows researchers to shortlist health apps that are potentially suitable for formal evaluation. The evaluation checklist enables quantitative comparison of shortlisted apps based on constructs reported in the literature. The use of multiple raters, and comparison of their scores, is proposed to manage inherent subjectivity in assessing user experiences. Initial trial of the combined protocol is planned for apps pertaining to the self-monitoring of asthma; these results will be reported elsewhere. PMID:27815233

RNAi-mediated knock-down of Dab and Numb attenuate Aβ levels via γ-secretase mediated APP processing.

PubMed

Xie, Zhongcong; Dong, Yuanlin; Maeda, Uta; Xia, Weiming; Tanzi, Rudolph E

2012-03-22

Amyloid-β-protein (Aβ), the key component of senile plaques in Alzheimer's disease (AD) brain, is produced from amyloid precursor protein (APP) by cleavage of β-secretase and then γ-secretase. APP adaptor proteins with phosphotyrosine-binding (PTB) domains, including Dab (gene: DAB) and Numb (gene: NUMB), can bind to and interact with the conserved YENPTY-motif in the APP C-terminus. Here we describe, for the first time, the effects of RNAi knock-down of Dab and Numb expression on APP processing and Aβ production. RNAi knock-down of Dab and Numb in H4 human neuroglioma cells stably transfected to express either FL-APP (H4-FL-APP cells) or APP-C99 (H4-APP-C99 cells) increased levels of APP-C-terminal fragments (APP-CTFs) and lowered Aβ levels in both cell lines by inhibiting γ-secretase cleavage of APP. Finally, RNAi knock-down of APP also reduced levels of Numb in H4-APP cells. These findings suggest that pharmacologically blocking interaction of APP with Dab and Numb may provide novel therapeutic strategies of AD. The notion of attenuating γ-secretase cleavage of APP via the APP adaptor proteins, Dab and Numb, is particularly attractive with regard to therapeutic potential, given that side effects of γ-secretase inhibition owing to impaired proteolysis of other γ-secretase substrates, e.g. Notch, might be avoided.

Development of a Rating Tool for Mobile Cancer Apps: Information Analysis and Formal and Content-Related Evaluation of Selected Cancer Apps.

PubMed

Böhme, Cathleen; von Osthoff, Marc Baron; Frey, Katrin; Hübner, Jutta

2017-08-17

Mobile apps are offered in large numbers and have different qualities. The aim of this article was to develop a rating tool based on formal and content-related criteria for the assessment of cancer apps and to test its applicability on apps. After a thorough analysis of the literature, we developed a specific rating tool for cancer apps based on the MARS (mobile app rating system) and a rating tool for cancer websites. This instrument was applied to apps freely available in stores and focusing on some cancer topic. Ten apps were rated on the basis of 22 criteria. Sixty percent of the apps (6/10) were rated poor and insufficient. The rating by different scientists was homogenous. The good apps had reliable sources were regularly updated and had a concrete intent/purpose in their app description. In contrast, the apps that were rated poor had no distinction of scientific content and advertisement. In some cases, there was no imprint to identify the provider. As apps of poor quality can give misinformation and lead to wrong treatment decisions, efforts have to be made to increase usage of high-quality apps. Certification would help cancer patients to identify reliable apps, yet acceptance of a certification system must be backed up.

The Top Chinese Mobile Health Apps: A Systematic Investigation.

PubMed

Hsu, Jeffrey; Liu, Di; Yu, Ya Min; Zhao, Hui Tong; Chen, Zhi Rou; Li, Jiao; Chen, Wei

2016-08-29

China's mHealth market is on track to become a global leader by industry size. The Chinese mobile app market and health care system have peculiarities that distinguish them from other app markets. To date, Chinese mHealth apps have not been systematically investigated. The objective of this study was to provide an overview of Chinese mHealth apps as of December 2015. We identified and investigated the most downloaded apps from the iOS and Android platforms. For each app, we analyzed and recorded its main service offered, mHealth initiative, disease and specialty focus, app cost, target user, Web app availability, and emphasis on information security. Standard descriptive statistics were used. A total of 234 apps met the inclusion criteria and were investigated. The apps targeting nonhealth care professionals focused on providing telemedicine and appointment-making services. The apps targeting health care professionals focused on education and peer reviewed articles. The most common disease-specific apps focused primarily on diabetes, hypertension, and hepatitis management. Most apps were free and available on both iOS and Android platforms. The primary mHealth initiatives targeted by the apps reflect Chinese patients' demand for access to medical care. Disease-specific apps are also representative of disease prevalence in China. Government press releases suggest that new policies on the horizon may shift the industry.

Smartphone apps for snoring.

PubMed

Camacho, M; Robertson, M; Abdullatif, J; Certal, V; Kram, Y A; Ruoff, C M; Brietzke, S E; Capasso, R

2015-10-01

To identify and systematically evaluate user-friendly smartphone snoring apps. The Apple iTunes app store was searched for snoring apps that allow recording and playback. Snoring apps were downloaded, evaluated and rated independently by four authors. Two patients underwent polysomnography, and the data were compared with simultaneous snoring app recordings, and one patient used the snoring app at home. Of 126 snoring apps, 13 met the inclusion and exclusion criteria. The most critical app feature was the ability to graphically display the snoring events. The Quit Snoring app received the highest overall rating. When this app's recordings were compared with in-laboratory polysomnography data, app snoring sensitivities ranged from 64 to 96 per cent, and snoring positive predictive values ranged from 93 to 96 per cent. A chronic snorer used the app nightly for one month and tracked medical interventions. Snoring decreased from 200 to 10 snores per hour, and bed partner snoring complaint scores decreased from 9 to 2 (on a 0-10 scale). Select smartphone apps are user-friendly for recording and playing back snoring sounds. Preliminary comparison of more than 1500 individual snores demonstrates the potential clinical utility of such apps; however, further validation testing is recommended.

Quantifying App Store Dynamics: Longitudinal Tracking of Mental Health Apps

PubMed Central

Nicholas, Jennifer; Christensen, Helen

2016-01-01

Background For many mental health conditions, mobile health apps offer the ability to deliver information, support, and intervention outside the clinical setting. However, there are difficulties with the use of a commercial app store to distribute health care resources, including turnover of apps, irrelevance of apps, and discordance with evidence-based practice. Objective The primary aim of this study was to quantify the longevity and rate of turnover of mental health apps within the official Android and iOS app stores. The secondary aim was to quantify the proportion of apps that were clinically relevant and assess whether the longevity of these apps differed from clinically nonrelevant apps. The tertiary aim was to establish the proportion of clinically relevant apps that included claims of clinical effectiveness. We performed additional subgroup analyses using additional data from the app stores, including search result ranking, user ratings, and number of downloads. Methods We searched iTunes (iOS) and the Google Play (Android) app stores each day over a 9-month period for apps related to depression, bipolar disorder, and suicide. We performed additional app-specific searches if an app no longer appeared within the main search Results On the Android platform, 50% of the search results changed after 130 days (depression), 195 days (bipolar disorder), and 115 days (suicide). Search results were more stable on the iOS platform, with 50% of the search results remaining at the end of the study period. Approximately 75% of Android and 90% of iOS apps were still available to download at the end of the study. We identified only 35.3% (347/982) of apps as being clinically relevant for depression, of which 9 (2.6%) claimed clinical effectiveness. Only 3 included a full citation to a published study. Conclusions The mental health app environment is volatile, with a clinically relevant app for depression becoming unavailable to download every 2.9 days. This poses challenges for consumers and clinicians seeking relevant and long-term apps, as well as for researchers seeking to evaluate the evidence base for publicly available apps. PMID:27507641

Emergency Preparedness and Disaster Response: There's An App for That.

PubMed

Bachmann, Daniel J; Jamison, Nathan K; Martin, Andrew; Delgado, Jose; Kman, Nicholas E

2015-10-01

Smartphone applications (or apps) are becoming increasingly popular with emergency responders and health care providers, as well as the public as a whole. There are thousands of medical apps available for Smartphones and tablet computers, with more added each day. These include apps to view textbooks, guidelines, medication databases, medical calculators, and radiology images. Hypothesis/Problem With an ever expanding catalog of apps that relate to disaster medicine, it is hard for both the lay public and responders to know where to turn for effective Smartphone apps. A systematic review of these apps was conducted. A search of the Apple iTunes store (Version 12; Apple Inc.; Cupertino, California USA) was performed using the following terms obtained from the PubMed Medical Subject Headings Database: Emergency Preparedness, Emergency Responders, Disaster, Disaster Planning, Disaster Medicine, Bioterrorism, Chemical Terrorism, Hazardous Materials (HazMat), and the Federal Emergency Management Agency (FEMA). After excluding any unrelated apps, a working list of apps was formed and categorized based on topics. Apps were grouped based on applicability to responders, the lay public, or regional preparedness, and were then ranked based on iTunes user reviews, value, relevance to audience, and user interface. This search revealed 683 applications and was narrowed to 219 based on relevance to the field. After grouping the apps as described above, and subsequently ranking them, the highest quality apps were determined from each group. The Community Emergency Response Teams and FEMA had the best apps for National Disaster Medical System responders. The Centers for Disease Control and Prevention (CDC) had high-quality apps for emergency responders in a variety of fields. The National Library of Medicine's Wireless Information System for Emergency Responders (WISER) app was an excellent app for HazMat responders. The American Red Cross had the most useful apps for natural disasters. Numerous valuable apps for public use, including alert apps, educational apps, and a well-made regional app, were also identified. Smartphone applications are fast becoming essential to emergency responders and the lay public. Many high-quality apps existing in various price ranges and serving different populations were identified. This field is changing rapidly and it deserves continued analysis as more apps are developed.

Mobile medical and health apps: state of the art, concerns, regulatory control and certification

PubMed Central

Boulos, Maged N. Kamel; Brewer, Ann C.; Karimkhani, Chante; Buller, David B.; Dellavalle, Robert P.

2014-01-01

This paper examines the state of the art in mobile clinical and health-related apps. A 2012 estimate puts the number of health-related apps at no fewer than 40,000, as healthcare professionals and consumers continue to express concerns about the quality of many apps, calling for some form of app regulatory control or certification to be put in place. We describe the range of apps on offer as of 2013, and then present a brief survey of evaluation studies of medical and health-related apps that have been conducted to date, covering a range of clinical disciplines and topics. Our survey includes studies that highlighted risks, negative issues and worrying deficiencies in existing apps. We discuss the concept of ‘apps as a medical device’ and the relevant regulatory controls that apply in USA and Europe, offering examples of apps that have been formally approved using these mechanisms. We describe the online Health Apps Library run by the National Health Service in England and the calls for a vetted medical and health app store. We discuss the ingredients for successful apps beyond the rather narrow definition of ‘apps as a medical device’. These ingredients cover app content quality, usability, the need to match apps to consumers’ general and health literacy levels, device connectivity standards (for apps that connect to glucometers, blood pressure monitors, etc.), as well as app security and user privacy. ‘Happtique Health App Certification Program’ (HACP), a voluntary app certification scheme, successfully captures most of these desiderata, but is solely focused on apps targeting the US market. HACP, while very welcome, is in ways reminiscent of the early days of the Web, when many “similar” quality benchmarking tools and codes of conduct for information publishers were proposed to appraise and rate online medical and health information. It is probably impossible to rate and police every app on offer today, much like in those early days of the Web, when people quickly realised the same regarding informational Web pages. The best first line of defence was, is, and will always be to educate consumers regarding the potentially harmful content of (some) apps. PMID:24683442

Arctic and Arctic-like rabies viruses: distribution, phylogeny and evolutionary history

PubMed Central

KUZMIN, I. V.; HUGHES, G. J.; BOTVINKIN, A. D.; GRIBENCHA, S. G.; RUPPRECHT, C. E.

2008-01-01

SUMMARY Forty-one newly sequenced isolates of Arctic and Arctic-like rabies viruses, were genetically compared to each other and to those available from GenBank. Four phylogenetic lineages of Arctic viruses were identified. Arctic-1 viruses circulate in Ontario, Arctic-2 viruses circulate in Siberia and Alaska, Arctic-3 viruses circulate circumpolarly, and a newly described lineage Arctic-4 circulates locally in Alaska. The oldest available isolates from Siberia (between 1950 and 1960) belong to the Arctic-2 and Arctic-3 lineages and share 98·6–99·2% N gene identity with contemporary viruses. Two lineages of Arctic-like viruses were identified in southern Asia and the Middle East (Arctic-like-1) and eastern Asia (Arctic-like-2). A time-scaled tree demonstrates that the time of the most recent common ancestor (TMRCA) of Arctic and Arctic-like viruses is dated between 1255 and 1786. Evolution of the Arctic viruses has occurred through a northerly spread. The Arctic-like-2 lineage diverged first, whereas Arctic viruses share a TMRCA with Arctic-like-1 viruses. PMID:17599781

Arctic and Arctic-like rabies viruses: distribution, phylogeny and evolutionary history.

PubMed

Kuzmin, I V; Hughes, G J; Botvinkin, A D; Gribencha, S G; Rupprecht, C E

2008-04-01

Forty-one newly sequenced isolates of Arctic and Arctic-like rabies viruses, were genetically compared to each other and to those available from GenBank. Four phylogenetic lineages of Arctic viruses were identified. Arctic-1 viruses circulate in Ontario, Arctic-2 viruses circulate in Siberia and Alaska, Arctic-3 viruses circulate circumpolarly, and a newly described lineage Arctic-4 circulates locally in Alaska. The oldest available isolates from Siberia (between 1950 and 1960) belong to the Arctic-2 and Arctic-3 lineages and share 98.6-99.2% N gene identity with contemporary viruses. Two lineages of Arctic-like viruses were identified in southern Asia and the Middle East (Arctic-like-1) and eastern Asia (Arctic-like-2). A time-scaled tree demonstrates that the time of the most recent common ancestor (TMRCA) of Arctic and Arctic-like viruses is dated between 1255 and 1786. Evolution of the Arctic viruses has occurred through a northerly spread. The Arctic-like-2 lineage diverged first, whereas Arctic viruses share a TMRCA with Arctic-like-1 viruses.

Adherence to evidence-based guidelines among diabetes self-management apps.

PubMed

Breland, Jessica Y; Yeh, Vivian M; Yu, Jessica

2013-09-01

Smartphone apps can provide real-time, interactive self-management aid to individuals with diabetes. It is currently unclear whether existing diabetes self-management apps follow evidence-based guidelines. The purpose of this study was to evaluate the extent to which existing diabetes self-management apps address the seven self-management behaviors recommended by the American Association of Diabetes Educators (the AADE7™). The term "diabetes" identified relevant self-management apps via the Apple App Store search engine in March 2012. Ratings were based on app descriptions and downloads. Chi-square analyses assessed differences in apps based on developer type. Apps promoted a median of two AADE7™ skills. Overall reliability between description and download ratings was good (kappa = .66). Reliability of individual skills was variable (kappa = .25 to .91). Most diabetes apps do not conform to evidence-based recommendations, and future app reviews would benefit from testing app performance. Future apps may also benefit from theory-based designs.

Quality Assessment of Medical Apps that Target Medication-Related Problems.

PubMed

Loy, John Shiguang; Ali, Eskinder Eshetu; Yap, Kevin Yi-Lwern

2016-10-01

The advent of smartphones has enabled a plethora of medical apps for disease management. As of 2012, there are 40,000 health care-related mobile apps available in the market. Since most of these medical apps do not go through any stringent quality assessment, there is a risk of consumers being misinformed or misled by unreliable information. In this regard, apps that target medication-related problems (MRPs) are not an exception. There is little information on what constitutes quality in apps that target MRPs and how good the existing apps are. To develop a quality assessment tool for evaluating apps that target MRPs and assess the quality of such apps available in the major mobile app stores (iTunes and Google Play). The top 100 free and paid apps in the medical categories of iTunes and Google Play stores (total of 400 apps) were screened for inclusion in the final analysis. English language apps that targeted MRPs were downloaded on test devices to evaluate their quality. Apps intended for clinicians, patients, or both were eligible for evaluation. The quality assessment tool consisted of 4 sections (appropriateness, reliability, usability, privacy), which determined the overall quality of the apps. Apps that fulfilled the inclusion criteria were classified based on the presence of any 1 or more of the 5 features considered important for apps targeting MRPs (monitoring, interaction checker, dose calculator, medication information, medication record). Descriptive statistics and Mann-Whitney tests were used for analysis. Final analysis was based on 59 apps that fulfilled the study inclusion criteria. Apps with interaction checker (66.9%) and monitoring features (54.8%) had the highest and lowest overall qualities. Paid apps generally scored higher for usability than free apps (P = 0.006) but lower for privacy (P = 0.003). Half of the interaction checker apps were unable to detect interactions with herbal medications. Blood pressure and heart rate monitoring apps had the highest overall quality scores (67.7%), while apps that monitored visual, hearing, and temperature changes scored the lowest (35.5%). A quality assessment tool for evaluating medical apps targeting MRPs has been developed. Clinicians can use this tool to guide their assessments of medical apps that are appropriate for use in the health care setting. Although potentially useful apps were identified, many apps were found to have deficiencies in quality, among which was poor reliability scores for most of the apps. Continued assessments of the quality of apps targeting MRPs are recommended to ensure their usefulness for clinicians and patients. No outside funding supported this study. The authors have no conflicts of interests directly related to this study. Study concept and design were contributed by Loy and Yap. Loy collected the data and took the lead in data interpretation, along with Ali and Yap. The manuscript was primarily written by Loy, along with Yap, and revised primarily by Ali, along with Yap.

Mobile Application Use Among Obstetrics and Gynecology Residents.

PubMed

Perry, Rachel; Burns, Roshan M; Simon, Rebecca; Youm, Julie

2017-10-01

Mobile applications (apps) are increasingly used in clinical settings, particularly among resident physicians. Apps available to patients and physicians are rapidly expanding. We aimed to describe obstetrics and gynecology (ob-gyn) residents' use of and attitudes toward ob-gyn-related mobile apps. We conducted a cross-sectional survey of residents at all 19 California ob-gyn programs using a web-based questionnaire. Responses were analyzed using descriptive and chi-square statistics. Of 386 residents contacted, 197 (51%) completed the survey. All respondents owned mobile devices (100% smartphone, 74% tablet), and 93% used apps in the clinical setting. Commonly used ob-gyn-related apps were pregnancy wheels (84%), cervical cancer screening algorithms (68%), and contraceptive eligibility guidelines (47%). Only 53% of respondents recommended apps to patients, with many reporting not being aware of appropriate apps. Sixty-two percent of respondents used apps for learning, but only 3 ob-gyn-specific apps were mentioned. Most chose apps based on recommendations from other residents. Residents viewed mobile technology as an important clinical tool (92%) that improves efficiency (89%). App use did not differ by gender, age, or postgraduate year. Mobile technology and ob-gyn-related app use are widely used among California ob-gyn residents, who feel that apps enhance their ability to care for patients. Context of app use varies, with most residents using apps during clinical care, but only half recommending apps to patients. Recommendations from other residents are the common resource for discovering new apps, suggesting a need for more formal guidance on finding and evaluating apps.

Smartphone apps for spinal surgery: is technology good or evil?

PubMed

Robertson, Greg A J; Wong, Seng Juong; Brady, Richard R; Subramanian, Ashok S

2016-05-01

The increased utilization of smartphones together with their downloadable applications (apps) provides opportunity for doctors, including spinal surgeons, to integrate such technology into clinical practice. However, the clinical reliability of the medical app sector remains questionable. We reviewed available apps themed specifically towards spinal surgery and related conditions and assessed the level of medical professional involvement in their design and content. The most popular smartphone app stores (Android, Apple, Blackberry, Windows, Samsung, Nokia) were searched for spinal surgery-themed apps, using the disease terms Spinal Surgery, Back Surgery, Spine, Disc Prolapse, Sciatica, Radiculopathy, Spinal Stenosis, Scoliosis, Spinal Fracture and Spondylolisthesis. A total of 78 individual spinal surgery themed apps were identified, of which there were six duplicates (N = 72). According to app store classifications, there were 57 (79 %) medical themed apps, 11 (15 %) health and fitness themed apps, 1 (1 %) business and 3 (4 %) education themed apps. Forty-five (63 %) apps were available for download free of charge. For those that charged access, the prices ranged from £0.62 to £47.99. Only 44 % of spinal surgery apps had customer satisfaction ratings and 56 % had named medical professional involvement in their development or content. This is the first study to specifically address the characteristics of apps related to spinal surgery. We found that nearly half of spinal surgery apps had no named medical professional involvement, raising concerns over app content and evidence base for their use. We recommend increased regulation of spinal surgical apps to improve the accountability of app content.

Congenital sucrase-isomaltase deficiency: identification of a common Inuit founder mutation.

PubMed

Marcadier, Julien L; Boland, Margaret; Scott, C Ronald; Issa, Kheirie; Wu, Zaining; McIntyre, Adam D; Hegele, Robert A; Geraghty, Michael T; Lines, Matthew A

2015-02-03

Congenital sucrase-isomaltase deficiency is a rare hereditary cause of chronic diarrhea in children. People with this condition lack the intestinal brush-border enzyme required for digestion of di- and oligosaccharides, including sucrose and isomaltose, leading to malabsorption. Although the condition is known to be highly prevalent (about 5%-10%) in several Inuit populations, the genetic basis for this has not been described. We sought to identify a common mutation for congenital sucrase-isomaltase deficiency in the Inuit population. We sequenced the sucrase-isomaltase gene, SI, in a single Inuit proband with congenital sucrase-isomaltase deficiency who had severe fermentative diarrhea and failure to thrive. We then genotyped a further 128 anonymized Inuit controls from a variety of locales in the Canadian Arctic to assess for a possible founder effect. In the proband, we identified a novel, homozygous frameshift mutation, c.273_274delAG (p.Gly92Leufs*8), predicted to result in complete absence of a functional protein product. This change was very common among the Inuit controls, with an observed allele frequency of 17.2% (95% confidence interval [CI] 12.6%-21.8%). The predicted Hardy-Weinberg prevalence of congenital sucrase-isomaltase deficiency in Inuit people, based on this single founder allele, is 3.0% (95% CI 1.4%-4.5%), which is comparable with previous estimates. We found a common mutation, SI c.273_274delAG, to be responsible for the high prevalence of congenital sucrase-isomaltase deficiency among Inuit people. Targeted mutation testing for this allele should afford a simple and minimally invasive means of diagnosing this condition in Inuit patients with chronic diarrhea. © 2015 Canadian Medical Association or its licensors.

Use of and Beliefs About Mobile Phone Apps for Diabetes Self-Management: Surveys of People in a Hospital Diabetes Clinic and Diabetes Health Professionals in New Zealand.

PubMed

Boyle, Leah; Grainger, Rebecca; Hall, Rosemary M; Krebs, Jeremy D

2017-06-30

People with diabetes mellitus (DM) are using mobile phone apps to support self-management. The numerous apps available to assist with diabetes management have a variety of functions. Some functions, like insulin dose calculators, have significant potential for harm. The study aimed to establish (1) whether people with DM in Wellington, New Zealand, use apps for DM self-management and evaluate desirable features of apps and (2) whether health professionals (HPs) in New Zealand treating people with DM recommend apps to patients, the features HPs regard as important, and their confidence with recommending apps. A survey of patients seen at a hospital diabetes clinic over 12 months (N=539) assessed current app use and desirable features. A second survey of HPs attending a diabetes conference (n=286) assessed their confidence with app recommendations and perceived usefulness. Of the 189 responders (35.0% response rate) to the patient survey, 19.6% (37/189) had used a diabetes app. App users were younger and in comparison to other forms of diabetes mellitus, users prominently had type 1 DM. The most favored feature of the app users was a glucose diary (87%, 32/37), and an insulin calculator was the most desirable function for a future app (46%, 17/37). In non-app users, the most desirable feature for a future app was a glucose diary (64.4%, 98/152). Of the 115 responders (40.2% response rate) to the HPs survey, 60.1% (68/113) had recommended a diabetes app. Diaries for blood glucose levels and carbohydrate counting were considered the most useful app features and the features HPs felt most confident to recommend. HPs were least confident in recommending insulin calculation apps. The use of apps to record blood glucose was the most favored function in apps used by people with diabetes, with interest in insulin dose calculating function. HPs do not feel confident in recommending insulin dose calculators. There is an urgent need for an app assessment process to give confidence in the quality and safety of diabetes management apps to people with diabetes (potential app users) and HPs (potential app prescribers). ©Leah Boyle, Rebecca Grainger, Rosemary M Hall, Jeremy D Krebs. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 30.06.2017.

RNAi-mediated knock-down of Dab and Numb attenuate Aβ levels via γ-secretase mediated APP processing

PubMed Central

2012-01-01

Amyloid-β-protein (Aβ), the key component of senile plaques in Alzheimer's disease (AD) brain, is produced from amyloid precursor protein (APP) by cleavage of β-secretase and then γ-secretase. APP adaptor proteins with phosphotyrosine-binding (PTB) domains, including Dab (gene: DAB) and Numb (gene: NUMB), can bind to and interact with the conserved YENPTY-motif in the APP C-terminus. Here we describe, for the first time, the effects of RNAi knock-down of Dab and Numb expression on APP processing and Aβ production. RNAi knock-down of Dab and Numb in H4 human neuroglioma cells stably transfected to express either FL-APP (H4-FL-APP cells) or APP-C99 (H4-APP-C99 cells) increased levels of APP-C-terminal fragments (APP-CTFs) and lowered Aβ levels in both cell lines by inhibiting γ-secretase cleavage of APP. Finally, RNAi knock-down of APP also reduced levels of Numb in H4-APP cells. These findings suggest that pharmacologically blocking interaction of APP with Dab and Numb may provide novel therapeutic strategies of AD. The notion of attenuating γ-secretase cleavage of APP via the APP adaptor proteins, Dab and Numb, is particularly attractive with regard to therapeutic potential, given that side effects of γ-secretase inhibition owing to impaired proteolysis of other γ-secretase substrates, e.g. Notch, might be avoided. PMID:23211096

Smartphone use in neurosurgery? APP-solutely!

PubMed

Zaki, Michael; Drazin, Doniel

2014-01-01

A number of smartphone medical apps have recently emerged that may be helpful for the neurosurgical patient, practitioner, and trainee. This study aims to review the current neurosurgery-focused apps available for the iPhone, iPad, and Android platforms as of December 2013. Two of the most popular smartphone app stores (Apple Store and Android Google Play Store) were surveyed for neurosurgery-focused apps in December 2013. Search results were categorized based on their description page. Data were collected on price, rating, app release date, target audience, and medical professional involvement in app design. A review of the top apps in each category was performed. The search resulted in 111 unique apps, divided into these 7 categories: 16 (14%) clinical tools, 17 (15%) conference adjunct, 27 (24%) education, 18 (16%) literature, 15 (14%) marketing, 10 (9%) patient information, and 8 (7%) reference. The average cost of paid apps was $23.06 (range: $0.99-89.99). Out of the 111 apps, 71 (64%) were free, 48 (43%) had reviews, and 14 (13%) had more than 10 reviews. Seventy-three (66%) apps showed evidence of medical professional involvement. The number of apps being released every year has been increasing since 2009. There are a number of neurosurgery-themed apps available to all audiences. There was a lack of patient information apps for nonspinal procedures. Most apps did not have enough reviews to evaluate their quality. There was also a lack of oversight to validate the accuracy of medical information provided in these apps.

Integrated approach reveals diet, APOE genotype and sex affect immune response in APP mice.

PubMed

Nam, Kyong Nyon; Wolfe, Cody M; Fitz, Nicholas F; Letronne, Florent; Castranio, Emilie L; Mounier, Anais; Schug, Jonathan; Lefterov, Iliya; Koldamova, Radosveta

2018-01-01

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that is influenced by genetic and environmental risk factors, such as inheritance of ε4 allele of APOE (APOE4), sex and diet. Here, we examined the effect of high fat diet (HFD) on amyloid pathology and expression profile in brains of AD model mice expressing human APOE isoforms (APP/E3 and APP/E4 mice). APP/E3 and APP/E4 mice were fed HFD or Normal diet for 3months. We found that HFD significantly increased amyloid plaques in male and female APP/E4, but not in APP/E3 mice. To identify differentially expressed genes and gene-networks correlated to diet, APOE isoform and sex, we performed RNA sequencing and applied Weighted Gene Co-expression Network Analysis. We determined that the immune response network with major hubs Tyrobp/DAP12, Csf1r, Tlr2, C1qc and Laptm5 correlated significantly and positively to the phenotype of female APP/E4-HFD mice. Correspondingly, we found that in female APP/E4-HFD mice, microglia coverage around plaques, particularly of larger size, was significantly reduced. This suggests altered containment of the plaque growth and sex-dependent vulnerability in response to diet. The results of our study show concurrent impact of diet, APOE isoform and sex on the brain transcriptome and AD-like phenotype. Copyright © 2017 Elsevier B.V. All rights reserved.

The Quality and Accuracy of Mobile Apps to Prevent Driving After Drinking Alcohol.

PubMed

Wilson, Hollie; Stoyanov, Stoyan R; Gandabhai, Shailen; Baldwin, Alexander

2016-08-08

Driving after the consumption of alcohol represents a significant problem globally. Individual prevention countermeasures such as personalized mobile app aimed at preventing such behavior are widespread, but there is little research on their accuracy and evidence base. There has been no known assessment investigating the quality of such apps. This study aimed to determine the quality and accuracy of apps for drink driving prevention by conducting a review and evaluation of relevant mobile apps. A systematic app search was conducted following PRISMA guidelines. App quality was assessed using the Mobile App Rating Scale (MARS). Apps providing blood alcohol calculators (hereafter "calculators") were reviewed against current alcohol advice for accuracy. A total of 58 apps (30 iOS and 28 Android) met inclusion criteria and were included in the final analysis. Drink driving prevention apps had significantly lower engagement and overall quality scores than alcohol management apps. Most calculators provided conservative blood alcohol content (BAC) time until sober calculations. None of the apps had been evaluated to determine their efficacy in changing either drinking or driving behaviors. This novel study demonstrates that most drink driving prevention apps are not engaging and lack accuracy. They could be improved by increasing engagement features, such as gamification. Further research should examine the context and motivations for using apps to prevent driving after drinking in at-risk populations. Development of drink driving prevention apps should incorporate evidence-based information and guidance, lacking in current apps.

The Quality and Accuracy of Mobile Apps to Prevent Driving After Drinking Alcohol

PubMed Central

Stoyanov, Stoyan R; Gandabhai, Shailen; Baldwin, Alexander

2016-01-01

Background Driving after the consumption of alcohol represents a significant problem globally. Individual prevention countermeasures such as personalized mobile apps aimed at preventing such behavior are widespread, but there is little research on their accuracy and evidence base. There has been no known assessment investigating the quality of such apps. Objective This study aimed to determine the quality and accuracy of apps for drink driving prevention by conducting a review and evaluation of relevant mobile apps. Methods A systematic app search was conducted following PRISMA guidelines. App quality was assessed using the Mobile App Rating Scale (MARS). Apps providing blood alcohol calculators (hereafter “calculators”) were reviewed against current alcohol advice for accuracy. Results A total of 58 apps (30 iOS and 28 Android) met inclusion criteria and were included in the final analysis. Drink driving prevention apps had significantly lower engagement and overall quality scores than alcohol management apps. Most calculators provided conservative blood alcohol content (BAC) time until sober calculations. None of the apps had been evaluated to determine their efficacy in changing either drinking or driving behaviors. Conclusions This novel study demonstrates that most drink driving prevention apps are not engaging and lack accuracy. They could be improved by increasing engagement features, such as gamification. Further research should examine the context and motivations for using apps to prevent driving after drinking in at-risk populations. Development of drink driving prevention apps should incorporate evidence-based information and guidance, lacking in current apps. PMID:27502956

App Chronic Disease Checklist: Protocol to Evaluate Mobile Apps for Chronic Disease Self-Management.

PubMed

Anderson, Kevin; Burford, Oksana; Emmerton, Lynne

2016-11-04

The availability of mobile health apps for self-care continues to increase. While little evidence of their clinical impact has been published, there is general agreement among health authorities and authors that consumers' use of health apps assist in self-management and potentially clinical decision making. A consumer's sustained engagement with a health app is dependent on the usability and functionality of the app. While numerous studies have attempted to evaluate health apps, there is a paucity of published methods that adequately recognize client experiences in the academic evaluation of apps for chronic conditions. This paper reports (1) a protocol to shortlist health apps for academic evaluation, (2) synthesis of a checklist to screen health apps for quality and reliability, and (3) a proposed method to theoretically evaluate usability of health apps, with a view towards identifying one or more apps suitable for clinical assessment. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram was developed to guide the selection of the apps to be assessed. The screening checklist was thematically synthesized with reference to recurring constructs in published checklists and related materials for the assessment of health apps. The checklist was evaluated by the authors for face and construct validity. The proposed method for evaluation of health apps required the design of procedures for raters of apps, dummy data entry to test the apps, and analysis of raters' scores. The PRISMA flow diagram comprises 5 steps: filtering of duplicate apps; eliminating non-English apps; removing apps requiring purchase, filtering apps not updated within the past year; and separation of apps into their core functionality. The screening checklist to evaluate the selected apps was named the App Chronic Disease Checklist, and comprises 4 sections with 6 questions in each section. The validity check verified classification of, and ambiguity in, wording of questions within constructs. The proposed method to evaluate shortlisted and downloaded apps comprises instructions to attempt set-up of a dummy user profile, and dummy data entry to represent in-range and out-of-range clinical measures simulating a range of user behaviors. A minimum score of 80% by consensus (using the Intraclass Correlation Coefficient) between raters is proposed to identify apps suitable for clinical trials. The flow diagram allows researchers to shortlist health apps that are potentially suitable for formal evaluation. The evaluation checklist enables quantitative comparison of shortlisted apps based on constructs reported in the literature. The use of multiple raters, and comparison of their scores, is proposed to manage inherent subjectivity in assessing user experiences. Initial trial of the combined protocol is planned for apps pertaining to the self-monitoring of asthma; these results will be reported elsewhere. ©Kevin Anderson, Oksana Burford, Lynne Emmerton. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 04.11.2016.

Overview of smartphone applications for sleep analysis.

PubMed

Ong, Adrian A; Gillespie, M Boyd

2016-03-01

To review and assess the current selection of sleep analysis smartphone applications (apps) available for download. The iOS and Google Play mobile app store were searched for sleep analysis apps targeted for consumer use. Alarm clock, sleep-aid, snoring and sleep-talking recorder, fitness tracker apps, and apps geared towards health professionals were excluded. App information and features were obtained from in-store descriptions, and the app developer website. A total of 51 unique sleep apps in both iOS and Google Play stores were included. The apps were rated 3.8/5 in both stores, and had an average price of $1.12 in the iOS store and $0.58 in the Google Play store. >65% of sleep apps report on sleep structure, including duration, time awake, and time in light/deep sleep, while reporting of REM was limited. The availability of extra features was variable, ranging from 4% to 73% of apps. There are a variety of sleep analysis apps with a range of functionality. The apps with the most reviews from the each store are featured. Many apps provide data on sleep structure; however the algorithms are not validated by scientific literature or studies. Since patients may inquire about their sleep habits from these apps, it is necessary for physicians to be aware of the most common apps and the features offered and their limitations in order to properly counsel patients.

The Top Chinese Mobile Health Apps: A Systematic Investigation

PubMed Central

Hsu, Jeffrey; Liu, Di; Yu, Ya Min; Zhao, Hui Tong; Chen, Zhi Rou; Li, Jiao

2016-01-01

Background China’s mHealth market is on track to become a global leader by industry size. The Chinese mobile app market and health care system have peculiarities that distinguish them from other app markets. To date, Chinese mHealth apps have not been systematically investigated. Objective The objective of this study was to provide an overview of Chinese mHealth apps as of December 2015. Methods We identified and investigated the most downloaded apps from the iOS and Android platforms. For each app, we analyzed and recorded its main service offered, mHealth initiative, disease and specialty focus, app cost, target user, Web app availability, and emphasis on information security. Standard descriptive statistics were used. Results A total of 234 apps met the inclusion criteria and were investigated. The apps targeting nonhealth care professionals focused on providing telemedicine and appointment-making services. The apps targeting health care professionals focused on education and peer reviewed articles. The most common disease-specific apps focused primarily on diabetes, hypertension, and hepatitis management. Most apps were free and available on both iOS and Android platforms. Conclusions The primary mHealth initiatives targeted by the apps reflect Chinese patients’ demand for access to medical care. Disease-specific apps are also representative of disease prevalence in China. Government press releases suggest that new policies on the horizon may shift the industry. PMID:27573724

Client-Focused Security Assessment of mHealth Apps and Recommended Practices to Prevent or Mitigate Transport Security Issues

PubMed Central

Müthing, Jannis; Jäschke, Thomas

2017-01-01

Background Mobile health (mHealth) apps show a growing importance for patients and health care professionals. Apps in this category are diverse. Some display important information (ie, drug interactions), whereas others help patients to keep track of their health. However, insufficient transport security can lead to confidentiality issues for patients and medical professionals, as well as safety issues regarding data integrity. mHealth apps should therefore deploy intensified vigilance to protect their data and integrity. This paper analyzes the state of security in mHealth apps. Objective The objectives of this study were as follows: (1) identification of relevant transport issues in mHealth apps, (2) development of a platform for test purposes, and (3) recommendation of practices to mitigate them. Methods Security characteristics relevant to the transport security of mHealth apps were assessed, presented, and discussed. These characteristics were used in the development of a prototypical platform facilitating streamlined tests of apps. For the tests, six lists of the 10 most downloaded free apps from three countries and two stores were selected. As some apps were part of these top 10 lists in more than one country, 53 unique apps were tested. Results Out of the 53 apps tested from three European App Stores for Android and iOS, 21/53 (40%) showed critical results. All 21 apps failed to guarantee the integrity of data displayed. A total of 18 apps leaked private data or were observable in a way that compromised confidentiality between apps and their servers; 17 apps used unprotected connections; and two apps failed to validate certificates correctly. None of the apps tested utilized certificate pinning. Many apps employed analytics or ad providers, undermining user privacy. Conclusions The tests show that many mHealth apps do not apply sufficient transport security measures. The most common security issue was the use of any kind of unprotected connection. Some apps used secure connections only for selected tasks, leaving all other traffic vulnerable. PMID:29046271

Client-Focused Security Assessment of mHealth Apps and Recommended Practices to Prevent or Mitigate Transport Security Issues.

PubMed

Müthing, Jannis; Jäschke, Thomas; Friedrich, Christoph M

2017-10-18

Mobile health (mHealth) apps show a growing importance for patients and health care professionals. Apps in this category are diverse. Some display important information (ie, drug interactions), whereas others help patients to keep track of their health. However, insufficient transport security can lead to confidentiality issues for patients and medical professionals, as well as safety issues regarding data integrity. mHealth apps should therefore deploy intensified vigilance to protect their data and integrity. This paper analyzes the state of security in mHealth apps. The objectives of this study were as follows: (1) identification of relevant transport issues in mHealth apps, (2) development of a platform for test purposes, and (3) recommendation of practices to mitigate them. Security characteristics relevant to the transport security of mHealth apps were assessed, presented, and discussed. These characteristics were used in the development of a prototypical platform facilitating streamlined tests of apps. For the tests, six lists of the 10 most downloaded free apps from three countries and two stores were selected. As some apps were part of these top 10 lists in more than one country, 53 unique apps were tested. Out of the 53 apps tested from three European App Stores for Android and iOS, 21/53 (40%) showed critical results. All 21 apps failed to guarantee the integrity of data displayed. A total of 18 apps leaked private data or were observable in a way that compromised confidentiality between apps and their servers; 17 apps used unprotected connections; and two apps failed to validate certificates correctly. None of the apps tested utilized certificate pinning. Many apps employed analytics or ad providers, undermining user privacy. The tests show that many mHealth apps do not apply sufficient transport security measures. The most common security issue was the use of any kind of unprotected connection. Some apps used secure connections only for selected tasks, leaving all other traffic vulnerable. ©Jannis Müthing, Thomas Jäschke, Christoph M Friedrich. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 18.10.2017.

Commercially available mobile phone headache diary apps: a systematic review.

PubMed

Hundert, Amos S; Huguet, Anna; McGrath, Patrick J; Stinson, Jennifer N; Wheaton, Mike

2014-08-19

Headache diaries are often used by headache sufferers to self-monitor headaches. With advances in mobile technology, mobile electronic diary apps are becoming increasingly common. This review aims to identify and evaluate all commercially available mobile headache diary apps for the two most popular mobile phone platforms, iOS and Android. The authors developed a priori a set of 7 criteria that define an ideal headache diary app intended to help headache sufferers better understand and manage their headaches, while providing relevant data to health professionals. The app criteria were intended as minimum requirements for an acceptable headache diary app that could be prescribed by health care professionals. Each app was evaluated and scored against each criterion. Of the 38 apps identified, none of the apps met all 7 app criteria. The 3 highest scoring apps, meeting 5 of the app criteria, were iHeadache (developed by Better QOL), ecoHeadache (developed by ecoTouchMedia), and Headache Diary Pro (developed by Froggyware). Only 18% of the apps were created with scientific or clinical headache expertise and none of the apps reported on psychometric properties. Despite the growing market and demand, there is a concerning lack of scientific expertise and evidence base associated with headache diary apps.

Commercially Available Mobile Phone Headache Diary Apps: A Systematic Review

PubMed Central

Huguet, Anna; McGrath, Patrick J; Stinson, Jennifer N; Wheaton, Mike

2014-01-01

Background Headache diaries are often used by headache sufferers to self-monitor headaches. With advances in mobile technology, mobile electronic diary apps are becoming increasingly common. Objective This review aims to identify and evaluate all commercially available mobile headache diary apps for the two most popular mobile phone platforms, iOS and Android. Methods The authors developed a priori a set of 7 criteria that define an ideal headache diary app intended to help headache sufferers better understand and manage their headaches, while providing relevant data to health professionals. The app criteria were intended as minimum requirements for an acceptable headache diary app that could be prescribed by health care professionals. Each app was evaluated and scored against each criterion. Results Of the 38 apps identified, none of the apps met all 7 app criteria. The 3 highest scoring apps, meeting 5 of the app criteria, were iHeadache (developed by Better QOL), ecoHeadache (developed by ecoTouchMedia), and Headache Diary Pro (developed by Froggyware). Only 18% of the apps were created with scientific or clinical headache expertise and none of the apps reported on psychometric properties. Conclusions Despite the growing market and demand, there is a concerning lack of scientific expertise and evidence base associated with headache diary apps. PMID:25138438

The Rise and Need for Mobile Apps for Maternal and Child Health Care in China: Survey Based on App Markets.

PubMed

Zhang, Puhong; Dong, Le; Chen, Huan; Chai, Yanling; Liu, Jianbo

2018-06-08

Mobile health services are thriving in the field of maternal and child health in China due to expansions in the field of electronic health and the introduction of the two-child policy. There are numerous maternal and child health apps in computer stores, but the exact number of apps, number of downloads, and features of these apps is not known. This study aimed to explore the use of maternal and child health apps in Android and iOS app stores and to describe the key functional features of the most popular apps, with the purpose of providing insight into further research and development of maternal and child health mobile health products. The researchers conducted a search in the 3 most popular Android app stores (Tencent MyApp, Baidu Mobile Assistant, and 360 Mobile Assistant) and the iTunes App Store in China. All apps regarding family planning (contraception and preparing for pregnancy), pregnancy and perinatal care, neonatal care and health, and development for children under 6 years were included in the initial analysis. Maternal and child health mobile apps with predominant features of product marketing, children's songs, animation, or games were excluded from the study. The 50 most frequently used apps in each of the Android stores as well as the iTunes store (a total of 78 deduplicated apps) were selected and downloaded for an in-depth analysis. A total of 5276 Android apps and 877 iOS apps developed for maternal and child health care were identified. Of the 78 most frequently used apps, 43 (55%) apps focused on one stage of MCH care, mainly targeting child care (25 apps) and before pregnancy care (11 apps), whereas 35 (45%) of the apps covered 2 or more stages, most of which (32 apps) included both pregnancy and child care services. The app features that were commonly adopted by the popular apps were health education, communication, health status self-monitoring, a diary, reminders, and counseling. Within the app feature of "health status self-monitoring," the researchers found 47 specific tools supporting activities such as pregnancy preparation, fetal heart monitoring, blood glucose and blood pressure monitoring, and doctor visits. A few apps were equipped with external devices (n=3) or sensors. No app with intelligent decision-support features to support disease management for conditions such as gestational diabetes and pregnancy-induced hypertension was found. A small number of apps (n=5) had a Web connection with hospital information systems to support appointment making, payments, hospital service guidance, or checking of laboratory results. There are thousands of maternal and child health apps in the Chinese market. Child care, pregnancy, and before pregnancy were the mostly covered maternal and child health stages, in that order. Various app features and tools were adopted by maternal and child health apps, but the use of internal or external sensors, intelligent decision support, and tethering with existing hospital information systems was rare and these features need more research and development. ©Puhong Zhang, Le Dong, Huan Chen, Yanling Chai, Jianbo Liu. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 08.06.2018.

Uptake and Usage of IntelliCare: A Publicly Available Suite of Mental Health and Well-Being Apps.

PubMed

Lattie, Emily G; Schueller, Stephen M; Sargent, Elizabeth; Stiles-Shields, Colleen; Tomasino, Kathryn Noth; Corden, Marya E; Begale, Mark; Karr, Chris J; Mohr, David C

2016-05-01

Treatments for depression and anxiety have several behavioral and psychological targets and rely on varied strategies. Digital mental health treatments often employ feature-rich approaches addressing several targets and strategies. These treatments, often optimized for desktop computer use, are at odds with the ways people use smartphone applications. Smartphone use tends to focus on singular functions with easy navigation to desired tools. The IntelliCare suite of apps was developed to address the discrepancy between need for diverse behavioral strategies and constraints imposed by typical app use. Each app focuses on one strategy for a limited subset of clinical aims all pertinent to depression and anxiety. This study presents the uptake and usage of apps from the IntelliCare suite following an open deployment on a large app marketplace. Thirteen lightweight apps, including 12 interactive apps and one Hub app that coordinates use across those interactive apps, were developed and made free to download on the Google Play store. De-identified app usage data from the first year of IntelliCare suite deployment were analyzed for this study. In the first year of public availability, 5,210 individuals downloaded one or more of the IntelliCare apps, for a total of 10,131 downloads. Nearly a third of these individuals (31.8%) downloaded more than one of these apps. The modal number of launches for each of the apps was 1, however the mean number of app launches per app ranged from 3.10 to 16.98, reflecting considerable variability in the use of each app. The use rate of the IntelliCare suite of apps is higher than public deployments of other comparable digital resources. Our findings suggest that people will use multiple apps and provides support for the concept of app suites as a useful strategy for providing diverse behavioral strategies.

Safe Sex Messages Within Dating and Entertainment Smartphone Apps: A Review

PubMed Central

Williams, Henrietta; Hocking, Jane S; Lim, Megan SC

2016-01-01

Background Smartphone apps provide a new platform for entertainment, information distribution, and health promotion activities, as well as for dating and casual sexual encounters. Previous research has shown high acceptability of sexual health interventions via smartphone apps; however, sexual health promotion apps were infrequently downloaded and underused. Integrating sexual health promotion into established apps might be a more effective method. Objective The objective of our study was to critically review popular sex-related apps and dating apps, in order to ascertain whether they contain any sexual health content. Methods Part 1: In January 2015, we used the term “sexual” to search for free apps in the Apple iTunes store and Android Google Play store, and categorized the sexual health content of the 137 apps identified. Part 2: We used the term “dating” to search for free geosocial-networking apps in the Apple iTunes and Android Google Play stores. The apps were downloaded to test functionality and to determine whether they included sexual health content. Results Part 1: Of the 137 apps identified, 15 (11.0%) had sexual health content and 15 (11.0%) contained messages about sexual assault or violence. The majority of the apps did not contain any sexual health content. Part 2: We reviewed 60 dating apps: 44 (73%) targeting heterosexual users, 9 (15%) targeting men who have sex with men (MSM), 3 (5%) targeting lesbian women, and 4 (7%) for group dating. Only 9 dating apps contained sexual health content, of which 7 targeted MSM. Conclusions The majority of sex-related apps and dating apps contained no sexual health content that could educate users about and remind them of their sexual risks. Sexual health practitioners and public health departments will need to work with app developers to promote sexual health within existing popular apps. For those apps that already contain sexual health messages, further study to investigate the effectiveness of the content is needed. PMID:27826133

Assessment of medication adherence app features, functionality, and health literacy level and the creation of a searchable Web-based adherence app resource for health care professionals and patients.

PubMed

Heldenbrand, Seth; Martin, Bradley C; Gubbins, Paul O; Hadden, Kristie; Renna, Catherine; Shilling, Rebecca; Dayer, Lindsey

2016-01-01

To assess the features and level of health literacy (HL) of available medication adherence apps and to create a searchable website to assist health care providers (HCP) and patients identify quality adherence apps. Medication nonadherence continues to be a significant problem and leads to poor health outcomes and avoidable health care expense. The average adherence rate for chronic medications, regardless of disease state, is approximately 50% leaving significant room for improvement. Smartphone adherence apps are a novel resource to address medication nonadherence. With widespread smartphone use and the growing number of adherence apps, both HCP and patients should be able to identify quality adherence apps to maximize potential benefits. Assess the features, functionality and level of HL of available adherence apps and create a searchable website to help both HCP and patients identify quality adherence apps. Online marketplaces (iTunes, Google Play, Blackberry) were searched in June of 2014 to identify available adherence apps. Online descriptions were recorded and scored based on 28 author-identified features across 4 domains. The 100 highest-scoring apps were user-tested with a standardized regimen to evaluate their functionality and level of HL. 461 adherence apps were identified. 367 unique apps were evaluated after removing "Lite/Trial" versions. The median initial score based on descriptions was 15 (max of 68; range: 3 to 47). Only 77 apps of the top 100 highest-scoring apps completed user-testing and HL evaluations. The median overall user-testing score was 30 (max of 73; range: 16 to 55). App design, functionality, and level of HL varies widely among adherence apps. While no app is perfect, several apps scored highly across all domains. The website www.medappfinder.com is a searchable tool that helps HCP and patients identify quality apps in a crowded marketplace. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

MedAd-AppQ: A quality assessment tool for medication adherence apps on iOS and android platforms.

PubMed

Ali, Eskinder Eshetu; Teo, Amanda Kai Sin; Goh, Sherlyn Xue Lin; Chew, Lita; Yap, Kevin Yi-Lwern

2018-02-02

With the recent proliferation of smartphone medication adherence applications (apps), it is increasingly more difficult for patients and clinicians to identify the most useful app. To develop a quality assessment tool for medication adherence apps, and evaluate the quality of such apps from the major app stores. In this study, a Medication Adherence App Quality assessment tool (MedAd-AppQ) was developed and two evaluators independently assessed apps that fulfilled the following criteria: availability in English, had at least a medication reminder feature, non-specific to certain disease conditions (generic apps), free of technical malfunctions and availability on both the iPhone Operating System (iOS) and Android platforms. Descriptive statistics, Mann-Whitney U test, Pearson product moment correlation and Spearman rank-order correlation were used for statistical analysis. MedAd-AppQ was designed to have 24 items (total 43 points) categorized under three sections: content reliability (11 points), feature usefulness (29 points) and feature convenience (3 points). The three sections of MedAd-AppQ were found to have inter-rater correlation coefficients of 0.801 (p-value < .001) or higher. Based on analysis of 52 apps (27 iOS and 25 Android), quality scores ranged between 7/43 (16.3%) and 28/43 (65.1%). There was no significant difference between the quality scores of the Android and iOS versions. None of the apps had features for self-management of side effects. Only two apps in each platform provided disease-related and/or medication information. MedAd-AppQ can be used to reliably assess the quality of adherence apps. Clinicians can use the tool in selecting apps for use by patients. Developers of adherence apps should consider features that provide therapy-related information and help patients in medications and side-effects management. Copyright © 2018 Elsevier Inc. All rights reserved.

Quality of Publicly Available Physical Activity Apps: Review and Content Analysis

PubMed Central

Alkhaldi, Ghadah; Slee, April; Hamilton, Fiona L; Murray, Elizabeth

2018-01-01

Background Within the new digital health landscape, the rise of health apps creates novel prospects for health promotion. The market is saturated with apps that aim to increase physical activity (PA). Despite the wide distribution and popularity of PA apps, there are limited data on their effectiveness, user experience, and safety of personal data. Objective The purpose of this review and content analysis was to evaluate the quality of the most popular PA apps on the market using health care quality indicators. Methods The top-ranked 400 free and paid apps from iTunes and Google Play stores were screened. Apps were included if the primary behavior targeted was PA, targeted users were adults, and the apps had stand-alone functionality. The apps were downloaded on mobile phones and assessed by 2 reviewers against the following quality assessment criteria: (1) users’ data privacy and security, (2) presence of behavior change techniques (BCTs) and quality of the development and evaluation processes, and (3) user ratings and usability. Results Out of 400 apps, 156 met the inclusion criteria, of which 65 apps were randomly selected to be downloaded and assessed. Almost 30% apps (19/65) did not have privacy policy. Every app contained at least one BCT, with an average number of 7 and a maximum of 13 BCTs. All but one app had commercial affiliation, 12 consulted an expert, and none reported involving users in the app development. Only 12 of 65 apps had a peer-reviewed study connected to the app. User ratings were high, with only a quarter of the ratings falling below 4 stars. The median usability score was excellent—86.3 out of 100. Conclusions Despite the popularity of PA apps available on the commercial market, there were substantial shortcomings in the areas of data safety and likelihood of effectiveness of the apps assessed. The limited quality of the apps may represent a missed opportunity for PA promotion. PMID:29563080

Enabling Psychiatrists to be Mobile Phone App Developers: Insights Into App Development Methodologies.

PubMed

Zhang, Melvyn Wb; Tsang, Tammy; Cheow, Enquan; Ho, Cyrus Sh; Yeong, Ng Beng; Ho, Roger Cm

2014-11-11

The use of mobile phones, and specifically smartphones, in the last decade has become more and more prevalent. The latest mobile phones are equipped with comprehensive features that can be used in health care, such as providing rapid access to up-to-date evidence-based information, provision of instant communications, and improvements in organization. The estimated number of health care apps for mobile phones is increasing tremendously, but previous research has highlighted the lack of critical appraisal of new apps. This lack of appraisal of apps has largely been due to the lack of clinicians with technical knowledge of how to create an evidence-based app. We discuss two freely available methodologies for developing Web-based mobile phone apps: a website builder and an app builder. With these, users can program not just a Web-based app, but also integrate multimedia features within their app, without needing to know any programming language. We present techniques for creating a mobile Web-based app using two well-established online mobile app websites. We illustrate how to integrate text-based content within the app, as well as integration of interactive videos and rich site summary (RSS) feed information. We will also briefly discuss how to integrate a simple questionnaire survey into the mobile-based app. A questionnaire survey was administered to students to collate their perceptions towards the app. These two methodologies for developing apps have been used to convert an online electronic psychiatry textbook into two Web-based mobile phone apps for medical students rotating through psychiatry in Singapore. Since the inception of our mobile Web-based app, a total of 21,991 unique users have used the mobile app and online portal provided by WordPress, and another 717 users have accessed the app via a Web-based link. The user perspective survey results (n=185) showed that a high proportion of students valued the textbook and objective structured clinical examination videos featured in the app. A high proportion of students concurred that a self-designed mobile phone app would be helpful for psychiatry education. These methodologies can enable busy clinicians to develop simple mobile Web-based apps for academic, educational, and research purposes, without any prior knowledge of programming. This will be beneficial for both clinicians and users at large, as there will then be more evidence-based mobile phone apps, or at least apps that have been appraised by a clinician.

Enabling Psychiatrists to be Mobile Phone App Developers: Insights Into App Development Methodologies

PubMed Central

Tsang, Tammy; Cheow, Enquan; Ho, Cyrus SH; Yeong, Ng Beng; Ho, Roger CM

2014-01-01

Background The use of mobile phones, and specifically smartphones, in the last decade has become more and more prevalent. The latest mobile phones are equipped with comprehensive features that can be used in health care, such as providing rapid access to up-to-date evidence-based information, provision of instant communications, and improvements in organization. The estimated number of health care apps for mobile phones is increasing tremendously, but previous research has highlighted the lack of critical appraisal of new apps. This lack of appraisal of apps has largely been due to the lack of clinicians with technical knowledge of how to create an evidence-based app. Objective We discuss two freely available methodologies for developing Web-based mobile phone apps: a website builder and an app builder. With these, users can program not just a Web-based app, but also integrate multimedia features within their app, without needing to know any programming language. Methods We present techniques for creating a mobile Web-based app using two well-established online mobile app websites. We illustrate how to integrate text-based content within the app, as well as integration of interactive videos and rich site summary (RSS) feed information. We will also briefly discuss how to integrate a simple questionnaire survey into the mobile-based app. A questionnaire survey was administered to students to collate their perceptions towards the app. Results These two methodologies for developing apps have been used to convert an online electronic psychiatry textbook into two Web-based mobile phone apps for medical students rotating through psychiatry in Singapore. Since the inception of our mobile Web-based app, a total of 21,991 unique users have used the mobile app and online portal provided by WordPress, and another 717 users have accessed the app via a Web-based link. The user perspective survey results (n=185) showed that a high proportion of students valued the textbook and objective structured clinical examination videos featured in the app. A high proportion of students concurred that a self-designed mobile phone app would be helpful for psychiatry education. Conclusions These methodologies can enable busy clinicians to develop simple mobile Web-based apps for academic, educational, and research purposes, without any prior knowledge of programming. This will be beneficial for both clinicians and users at large, as there will then be more evidence-based mobile phone apps, or at least apps that have been appraised by a clinician. PMID:25486985

The Cytoscape app article collection

PubMed Central

Pico, Alexander R; Bader, Gary D; Demchak, Barry; Guitart Pla, Oriol; Hull, Timothy; Longabaugh, William; Lopes, Christian; Lotia, Samad; Molenaar, Piet; Montojo, Jason; Morris, John H; Ono, Keiichiro; Schwikowski, Benno; Welker, David; Ideker, Trey

2014-01-01

As a network visualization and analysis platform, Cytoscape relies on apps to provide domain-specific features and functions. There are many resources available to support Cytoscape app development and distribution, including the Cytoscape App Store and an online “cookbook” for app developers. This article collection is another resource to help researchers find out more about relevant Cytoscape apps and to provide app developers with useful implementation tips. The collection will grow over time as new Cytoscape apps are developed and published. PMID:25580224

Practical Considerations for Use of Mobile Apps at the Tactical Edge

DTIC Science & Technology

2014-06-01

and logging The commercial app stores must scale to very large numbers of users (e.g., iTunes has over 800 million accounts, most with credit cards ...over a million Android apps and a million iOS apps are available for download from the Google Play and Apple iTunes app stores, respectively. Of these...apps and a million iOS apps are available for download from the Google Play and Apple iTunes app stores, respectively. Of these, most would not be

Incorporation of Mobile Application (App) Measures Into the Diagnosis of Smartphone Addiction.

PubMed

Lin, Yu-Hsuan; Lin, Po-Hsien; Chiang, Chih-Lin; Lee, Yang-Han; Yang, Cheryl C H; Kuo, Terry B J; Lin, Sheng-Hsuan

2017-07-01

Global smartphone expansion has brought about unprecedented addictive behaviors. The current diagnosis of smartphone addiction is based solely on information from clinical interview. This study aimed to incorporate application (app)-recorded data into psychiatric criteria for the diagnosis of smartphone addiction and to examine the predictive ability of the app-recorded data for the diagnosis of smartphone addiction. Smartphone use data of 79 college students were recorded by a newly developed app for 1 month between December 1, 2013, and May 31, 2014. For each participant, psychiatrists made a diagnosis for smartphone addiction based on 2 approaches: (1) only diagnostic interview (standard diagnosis) and (2) both diagnostic interview and app-recorded data (app-incorporated diagnosis). The app-incorporated diagnosis was further used to build app-incorporated diagnostic criteria. In addition, the app-recorded data were pooled as a score to predict smartphone addiction diagnosis. When app-incorporated diagnosis was used as a gold standard for 12 candidate criteria, 7 criteria showed significant accuracy (area under receiver operating characteristic curve [AUC] > 0.7) and were constructed as app-incorporated diagnostic criteria, which demonstrated remarkable accuracy (92.4%) for app-incorporated diagnosis. In addition, both frequency and duration of daily smartphone use significantly predicted app-incorporated diagnosis (AUC = 0.70 for frequency; AUC = 0.72 for duration). The combination of duration, frequency, and frequency trend for 1 month can accurately predict smartphone addiction diagnosis (AUC = 0.79 for app-incorporated diagnosis; AUC = 0.71 for standard diagnosis). The app-incorporated diagnosis, combining both psychiatric interview and app-recorded data, demonstrated substantial accuracy for smartphone addiction diagnosis. In addition, the app-recorded data performed as an accurate screening tool for app-incorporated diagnosis. © Copyright 2017 Physicians Postgraduate Press, Inc.

A biopsy of Breast Cancer mobile applications: state of the practice review.

PubMed

Giunti, G; Giunta, D H; Guisado-Fernandez, E; Bender, J L; Fernandez-Luque, L

2018-02-01

Breast cancer is the most common cancer in women. The use of mobile software applications for health and wellbeing promotion has grown exponentially in recent years. We systematically reviewed the breast cancer apps available in today's leading smartphone application stores and characterized them based on their features, evidence base and target audiences. A cross-sectional study was performed to characterize breast cancer apps from the two major smartphone app stores (iOS and Android). Apps that matched the keywords "breast cancer" were identified and data was extracted using a structured form. Reviewers independently evaluated the eligibility and independently classified the apps. A total of 1473 apps were a match. After removing duplicates and applying the selection criteria only 599 apps remained. Inter-rater reliability was determined using Fleiss-Cohen's Kappa. The majority of apps were free 471 (78.63%). The most common type of application was Disease and Treatment information apps (29.22%), Disease Management (19.03%) and Awareness Raising apps (15.03%). Close to 1 out of 10 apps dealt with alternative or homeopathic medicine. The majority of the apps were intended for patients (75.79%). Only one quarter of all apps (24.54%) had a disclaimer about usage and less than one fifth (19.70%) mentioned references or source material. Gamification specialists determined that 19.36% contained gamification elements. This study analyzed a large number of breast cancer-focused apps available to consumers. There has been a steady increase of breast cancer apps over the years. The breast cancer app ecosystem largely consists of start-ups and entrepreneurs. Evidence base seems to be lacking in these apps and it would seem essential that expert medical personnel be involved in the creation of medical apps. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

An evaluation of diabetes targeted apps for Android smartphone in relation to behaviour change techniques.

PubMed

Hoppe, C D; Cade, J E; Carter, M

2017-06-01

Mobile applications (apps) could support diabetes management through dietary, weight and blood glucose self-monitoring, as well as by promoting behaviour change. The present study aimed to evaluate diabetes apps for content, functions and behaviour change techniques (BCTs). Diabetes self-management apps for Android smartphones were searched for on the Google Play Store. Ten apps each from the following search terms were included; 'diabetes', 'diabetes type 1', 'diabetes type 2', 'gestational diabetes'. Apps were evaluated by being scored according to their number of functions and BCTs, price, and user rating. The mean (SD) number of functions was 8.9 (5.9) out of a possible maximum of 27. Furthermore, the mean (SD) number of BCTs was 4.4 (2.6) out of a possible maximum of 26. Apps with optimum BCT had significantly more functions [13.8; 95% confidence interval (CI) = 11.9-15.9] than apps that did not (4.7; 95% CI = 3.2-6.2; P < 0.01) and significantly more BCTs (5.8; 95% CI = 4.8-7.0) than apps without (3.1; 95% CI = 2.2-4.1; P < 0.01). Additionally, apps with optimum BCT also cost more than other apps. In the adjusted models, highly rated apps had an average of 4.8 (95% CI = 0.9-8.7; P = 0.02) more functions than lower rated apps. 'Diabetes apps' include few functions or BCTs compared to the maximum score possible. Apps with optimum BCTs could indicate higher quality. App developers should consider including both specific functions and BCTs in 'diabetes apps' to make them more helpful. More research is needed to understand the components of an effective app for people with diabetes. © 2016 The British Dietetic Association Ltd.

Cannabis Mobile Apps: A Content Analysis.

PubMed

Ramo, Danielle E; Popova, Lucy; Grana, Rachel; Zhao, Shirley; Chavez, Kathryn

2015-08-12

Mobile technology is pervasive and widely used to obtain information about drugs such as cannabis, especially in a climate of rapidly changing cannabis policy; yet the content of available cannabis apps is largely unknown. Understanding the resources available to those searching for cannabis apps will clarify how this technology is being used to reflect and influence cannabis use behavior. We investigated the content of 59 cannabis-related mobile apps for Apple and Android devices as of November 26, 2014. The Apple and Google Play app stores were searched using the terms "cannabis" and "marijuana." Three trained coders classified the top 20 apps for each term and each store, using a coding guide. Apps were examined for the presence of 20 content codes derived by the researchers. Total apps available for each search term were 124 for cannabis and 218 for marijuana in the Apple App Store, and 250 each for cannabis and marijuana on Google Play. The top 20 apps in each category in each store were coded for 59 independent apps (30 Apple, 29 Google Play). The three most common content areas were cannabis strain classification (33.9%), facts about cannabis (20.3%), and games (20.3%). In the Apple App Store, most apps were free (77%), all were rated "17+" years, and the average user rating was 3.9/5 stars. The most popular apps provided cannabis strain classifications (50%), dispensary information (27%), or general facts about cannabis (27%). Only one app (3%) provided information or resources related to cannabis abuse, addiction, or treatment. On Google Play, most apps were free (93%), rated "high maturity" (79%), and the average user rating was 4.1/5. The most popular app types offered games (28%), phone utilities (eg, wallpaper, clock; 21%) and cannabis food recipes (21%); no apps addressed abuse, addiction, or treatment. Cannabis apps are generally free and highly rated. Apps were most often informational (facts, strain classification), or recreational (games), likely reflecting and influencing the growing acceptance of cannabis for medical and recreational purposes. Apps addressing addiction or cessation were underrepresented in the most popular cannabis mobile apps. Differences among apps for Apple and Android platforms likely reflect differences in the population of users, developer choice, and platform regulations.

Cannabis Mobile Apps: A Content Analysis

PubMed Central

Popova, Lucy; Grana, Rachel; Zhao, Shirley; Chavez, Kathryn

2015-01-01

Background Mobile technology is pervasive and widely used to obtain information about drugs such as cannabis, especially in a climate of rapidly changing cannabis policy; yet the content of available cannabis apps is largely unknown. Understanding the resources available to those searching for cannabis apps will clarify how this technology is being used to reflect and influence cannabis use behavior. Objective We investigated the content of 59 cannabis-related mobile apps for Apple and Android devices as of November 26, 2014. Methods The Apple and Google Play app stores were searched using the terms “cannabis” and “marijuana.” Three trained coders classified the top 20 apps for each term and each store, using a coding guide. Apps were examined for the presence of 20 content codes derived by the researchers. Results Total apps available for each search term were 124 for cannabis and 218 for marijuana in the Apple App Store, and 250 each for cannabis and marijuana on Google Play. The top 20 apps in each category in each store were coded for 59 independent apps (30 Apple, 29 Google Play). The three most common content areas were cannabis strain classification (33.9%), facts about cannabis (20.3%), and games (20.3%). In the Apple App Store, most apps were free (77%), all were rated “17+” years, and the average user rating was 3.9/5 stars. The most popular apps provided cannabis strain classifications (50%), dispensary information (27%), or general facts about cannabis (27%). Only one app (3%) provided information or resources related to cannabis abuse, addiction, or treatment. On Google Play, most apps were free (93%), rated “high maturity” (79%), and the average user rating was 4.1/5. The most popular app types offered games (28%), phone utilities (eg, wallpaper, clock; 21%) and cannabis food recipes (21%); no apps addressed abuse, addiction, or treatment. Conclusions Cannabis apps are generally free and highly rated. Apps were most often informational (facts, strain classification), or recreational (games), likely reflecting and influencing the growing acceptance of cannabis for medical and recreational purposes. Apps addressing addiction or cessation were underrepresented in the most popular cannabis mobile apps. Differences among apps for Apple and Android platforms likely reflect differences in the population of users, developer choice, and platform regulations. PMID:26268634

Smartphone use in neurosurgery? APP-solutely!

PubMed Central

Zaki, Michael; Drazin, Doniel

2014-01-01

Background: A number of smartphone medical apps have recently emerged that may be helpful for the neurosurgical patient, practitioner, and trainee. This study aims to review the current neurosurgery-focused apps available for the iPhone, iPad, and Android platforms as of December 2013. Methods: Two of the most popular smartphone app stores (Apple Store and Android Google Play Store) were surveyed for neurosurgery-focused apps in December 2013. Search results were categorized based on their description page. Data were collected on price, rating, app release date, target audience, and medical professional involvement in app design. A review of the top apps in each category was performed. Results: The search resulted in 111 unique apps, divided into these 7 categories: 16 (14%) clinical tools, 17 (15%) conference adjunct, 27 (24%) education, 18 (16%) literature, 15 (14%) marketing, 10 (9%) patient information, and 8 (7%) reference. The average cost of paid apps was $23.06 (range: $0.99-89.99). Out of the 111 apps, 71 (64%) were free, 48 (43%) had reviews, and 14 (13%) had more than 10 reviews. Seventy-three (66%) apps showed evidence of medical professional involvement. The number of apps being released every year has been increasing since 2009. Conclusions: There are a number of neurosurgery-themed apps available to all audiences. There was a lack of patient information apps for nonspinal procedures. Most apps did not have enough reviews to evaluate their quality. There was also a lack of oversight to validate the accuracy of medical information provided in these apps. PMID:25101208

A review of mobile apps for epilepsy self-management.

PubMed

Escoffery, Cam; McGee, Robin; Bidwell, Jonathan; Sims, Christopher; Thropp, Eliana Kovitch; Frazier, Cherise; Mynatt, Elizabeth D

2018-04-01

Mobile health app developers increasingly are interested in supporting the daily self-care of people with chronic conditions. The purpose of this study was to review mobile applications (apps) to promote epilepsy self-management. It investigates the following: 1) the available mobile apps for epilepsy, 2) how these apps support patient education and self-management (SM), and 3) their usefulness in supporting management of epilepsy. We conducted the review in Fall 2017 and assessed apps on the Apple App Store that related to the terms "epilepsy" and "seizure". Inclusion criteria included apps (adult and pediatric) that, as follows, were: 1) developed for patients or the community; 2) made available in English, and 3) less than $5.00. Exclusion criteria included apps that were designed for dissemination of publications, focused on healthcare providers, or were available in other languages. The search resulted in 149 apps, of which 20 met the selection criteria. A team reviewed each app in terms of three sets of criteria: 1) epilepsy-specific descriptions and SM categories employed by the apps and 2) Mobile App Rating Scale (MARS) subdomain scores for reviewing engagement, functionality, esthetics, and information; and 3) behavioral change techniques. Most apps were for adults and free. Common SM domains for the apps were treatment, seizure tracking, response, and safety. A number of epilepsy apps existed, but many offered similar functionalities and incorporated few SM domains. The findings underline the need for mobile apps to cover broader domains of SM and behavioral change techniques and to be evaluated for outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification and Evaluation of Medical Translator Mobile Applications Using an Adapted APPLICATIONS Scoring System.

PubMed

Khander, Amrin; Farag, Sara; Chen, Katherine T

2017-12-22

With an increasing number of patients requiring translator services, many providers are turning to mobile applications (apps) for assistance. However, there have been no published reviews of medical translator apps. To identify and evaluate medical translator mobile apps using an adapted APPLICATIONS scoring system. A list of apps was identified from the Apple iTunes and Google Play stores, using the search term, "medical translator." Apps not found on two different searches, not in an English-based platform, not used for translation, or not functional after purchase, were excluded. The remaining apps were evaluated using an adapted APPLICATIONS scoring system, which included both objective and subjective criteria. App comprehensiveness was a weighted score defined by the number of non-English languages included in each app relative to the proportion of non-English speakers in the United States. The Apple iTunes and Google Play stores. Medical translator apps identified using the search term "medical translator." Main Outcomes and Measures: Compilation of medical translator apps for provider usage. A total of 524 apps were initially found. After applying the exclusion criteria, 20 (8.2%) apps from the Google Play store and 26 (9.2%) apps from the Apple iTunes store remained for evaluation. The highest scoring apps, Canopy Medical Translator, Universal Doctor Speaker, and Vocre Translate, scored 13.5 out of 18.7 possible points. A large proportion of apps initially found did not function as medical translator apps. Using the APPLICATIONS scoring system, we have identified and evaluated medical translator apps for providers who care for non-English speaking patients.

Plasma signaling proteins in persons at genetic risk for Alzheimer disease: influence of APOE genotype.

PubMed

Ringman, John M; Elashoff, David; Geschwind, Daniel H; Welsh, Brian T; Gylys, Karen H; Lee, Cathy; Cummings, Jeffrey L; Cole, Greg M

2012-06-01

To study the effect of familial Alzheimer disease (FAD) mutations and APOE genotype on plasma signaling protein levels. Cross-sectional comparison of plasma levels of 77 proteins measured using multiplex immune assays. A tertiary referral dementia research center. Thirty-three persons from families harboring PSEN1 or APP mutations, aged 19 to 59 years. Protein levels were compared between FAD mutation carriers (MCs) and noncarriers (NCs) and among APOE genotype groups, using multiple linear regression models. Twenty-one participants were FAD MCs and 12 were NCs. Six had the APOE ε2/3, 6 had the ε3/4, and 21 had the ε3/3 genotype. Levels of 17 proteins differed among APOE genotype groups, and there were significant interactions between age and APOE genotype for 12 proteins. Plasma levels of apolipoprotein E and superoxide dismutase 1 were highest in the ε2 carriers, lowest in ε4 carriers, and intermediate in the ε3 carriers. Levels of multiple interleukins showed the opposite pattern and, among the ε4 carriers, demonstrated significant negative correlations with age. Although there were no significant differences between FAD MCs and NCs, there were interactions between mutation status and APOE genotype for 13 proteins. We found different patterns of inflammatory markers in young and middle-aged persons among APOE genotype groups. The APOE ε4 carriers had the lowest levels of apolipoprotein E. Young ε4 carriers have increased inflammatory markers that diminish with age. We demonstrated altered inflammatory responses in young and middle adulthood in ε4 carriers that may relate to AD risk later in life.

Diabetes Applications for Arabic Speakers: A Critical Review of Available Apps for Android and iOS Operated Smartphones.

PubMed

Alhuwail, Dari

2016-01-01

Today, 415 million adults have diabetes; more than 35 million of diabetic adults live in the Middle East and North Africa region. Smartphone penetration in the region is high and applications, or apps, for diabetics have shown promising results in recent years. This study took place between September and December 2015 and reviewed all currently available smartphone diabetes apps for Arabic speakers in both the Apple App and Google Play stores. There were only few diabetes apps for Arabic speakers; only eighteen apps were discovered and considered for this study. Most apps were informational. Only three apps offered utilities such as glucose reading conversion. The apps had issues related to information quality and adherence to latest evidence-based medical advice. There is a need for more evidence-based Arabic diabetes apps with improved functionality. Future research of Arabic diabetes apps should also focus on the involvement and engagement of the patients in the design of these apps.

The Potential of Mobile Apps for Improving Asthma Self-Management: A Review of Publicly Available and Well-Adopted Asthma Apps.

PubMed

Tinschert, Peter; Jakob, Robert; Barata, Filipe; Kramer, Jan-Niklas; Kowatsch, Tobias

2017-08-02

Effective disease self-management lowers asthma's burden of disease for both individual patients and health care systems. In principle, mobile health (mHealth) apps could enable effective asthma self-management interventions that improve a patient's quality of life while simultaneously reducing the overall treatment costs for health care systems. However, prior reviews in this field have found that mHealth apps for asthma lack clinical evaluation and are often not based on medical guidelines. Yet, beyond the missing evidence for clinical efficacy, little is known about the potential apps might have for improving asthma self-management. The aim of this study was to assess the potential of publicly available and well-adopted mHealth apps for improving asthma self-management. The Apple App store and Google Play store were systematically searched for asthma apps. In total, 523 apps were identified, of which 38 apps matched the selection criteria to be included in the review. Four requirements of app potential were investigated: app functions, potential to change behavior (by means of a behavior change technique taxonomy), potential to promote app use (by means of a gamification components taxonomy), and app quality (by means of the Mobile Application Rating Scale [MARS]). The most commonly implemented functions in the 38 reviewed asthma apps were tracking (30/38, 79%) and information (26/38, 68%) functions, followed by assessment (20/38, 53%) and notification (18/38, 47%) functions. On average, the reviewed apps applied 7.12 of 26 available behavior change techniques (standard deviation [SD]=4.46) and 4.89 of 31 available gamification components (SD=4.21). Average app quality was acceptable (mean=3.17/5, SD=0.58), whereas subjective app quality lied between poor and acceptable (mean=2.65/5, SD=0.87). Additionally, the sum scores of all review frameworks were significantly correlated (lowest correlation: r 36 =.33, P=.04 between number of functions and gamification components; highest correlation: r 36 =.80, P<.001 between number of behavior change techniques and gamification components), which suggests that an app's potential tends to be consistent across review frameworks. Several apps were identified that performed consistently well across all applied review frameworks, thus indicating the potential mHealth apps offer for improving asthma self-management. However, many apps suffer from low quality. Therefore, app reviews should be considered as a decision support tool before deciding which app to integrate into a patient's asthma self-management. Furthermore, several research-practice gaps were identified that app developers should consider addressing in future asthma apps. ©Peter Tinschert, Robert Jakob, Filipe Barata, Jan-Niklas Kramer, Tobias Kowatsch. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 02.08.2017.

Dynamic self-guiding analysis of Alzheimer's disease

PubMed Central

Kurakin, Alexei; Bredesen, Dale E.

2015-01-01

We applied a self-guiding evolutionary algorithm to initiate the synthesis of the Alzheimer's disease-related data and literature. A protein interaction network associated with amyloid-beta precursor protein (APP) and a seed model that treats Alzheimer's disease as progressive dysregulation of APP-associated signaling were used as dynamic “guides” and structural “filters” in the recursive search, analysis, and assimilation of data to drive the evolution of the seed model in size, detail, and complexity. Analysis of data and literature across sub-disciplines and system-scale discovery platforms suggests a key role of dynamic cytoskeletal connectivity in the stability, plasticity, and performance of multicellular networks and architectures. Chronic impairment and/or dysregulation of cell adhesions/synapses, cytoskeletal networks, and/or reversible epithelial-to-mesenchymal-like transitions, which enable and mediate the stable and coherent yet dynamic and reconfigurable multicellular architectures, may lead to the emergence and persistence of the disordered, wound-like pockets/microenvironments of chronically disconnected cells. Such wound-like microenvironments support and are supported by pro-inflammatory, pro-secretion, de-differentiated cellular phenotypes with altered metabolism and signaling. The co-evolution of wound-like microenvironments and their inhabitants may lead to the selection and stabilization of degenerated cellular phenotypes, via acquisition of epigenetic modifications and mutations, which eventually result in degenerative disorders such as cancer and Alzheimer's disease. PMID:26041885

Kinetic and CD/MCD spectroscopic studies of the atypical, three-His-ligated, non-heme Fe2+ center in diketone dioxygenase: the role of hydrophilic outer shell residues in catalysis.

PubMed

Straganz, Grit D; Diebold, Adrienne R; Egger, Sigrid; Nidetzky, Bernd; Solomon, Edward I

2010-02-09

Diketone cleaving enzyme (Dke1) is a dioxygenase with an atypical, three-histidine-ligated, mononuclear non-heme Fe(2+) center. To assess the role in enzyme catalysis of the hydrophilic residues in the active site pocket, residues Glu98, Arg80, Tyr70, and Thr107 were subjected to mutational analysis. Steady state and pre-steady state kinetics indicated a role for Glu98 in promoting both substrate binding and O(2) reduction. Additionally, the Glu98 substitution eliminated the pH dependence of substrate binding (k(cat)(app)/K(M)(app)-pH profile) present in wild-type Dke1 (pK(a) = 6.3 +/- 0.4 and 8.4 +/- 0.4). MCD spectroscopy revealed that the Glu98 --> Gln mutation leads to the conversion of the six-coordinate (6C) resting Fe(2+) center present in the wild-type enzyme at pH 7.0 to a mixture of five-coordinate (5C) and 6C sites. The 6C geometry was restored with a pH shift to 9.5 which also resulted in ligand field (LF) energy splittings identical to that found for wild-type (WT) Dke1 at pH 9.5. In WT Dke1, these LF transitions are shifted up in energy by approximately 300 cm(-1) at pH 9.5 relative to pH 7.0. These data, combined with CD pH titrations which reveal a pK(a) of approximately 8.2 for resting WT Dke1 and the Glu98 --> Gln variant, indicate the deprotonation of a metal-ligated water. Together, the kinetic and spectroscopic data reveal a stabilizing effect of Glu98 on the 6C geometry of the metal center, priming it for substrate ligation. Arg80 and Tyr70 are shown to promote O(2) reduction, while Thr107 stabilizes the Fe(II) cofactor.

Notch signaling proteins HES-1 and Hey-1 bind to insulin degrading enzyme (IDE) proximal promoter and repress its transcription and activity: Implications for cellular Aβ metabolism

PubMed Central

Leal, María C.; Surace, Ezequiel I.; Holgado, María P.; Ferrari, Carina C.; Tarelli, Rodolfo; Pitossi, Fernando; Wisniewski, Thomas; Castaño, Eduardo M.; Morelli, Laura

2012-01-01

Cerebral amyloid β (Aβ) accumulation is pathogenically associated with sporadic Alzheimer’s disease (SAD). BACE-1 is involved in Aβ generation while insulin-degrading enzyme (IDE) partakes in Aβ proteolytic clearance. Vulnerable regions in AD brains show increased BACE-1 protein levels and enzymatic activity while the opposite occurs with IDE. Another common feature in SAD brains is Notch1 overexpression. Here we demonstrate an increase in mRNA levels of Hey-1, a Notch target gene, and a decrease of IDE transcripts in the hippocampus of SAD brains as compared to controls. Transient transfection of Notch intracellular domain (NICD) in N2aSW cells, mouse neuroblastoma cells (N2a) stably expressing human amyloid precursor protein (APP) Swedish mutation, reduce IDE mRNA levels, promoting extracellular Aβ accumulation. Also, NICD, HES-1 and Hey-1 overexpression result in decreased IDE proximal promoter activity. This effect was mediated by 2 functional sites located at −379/−372 and −310 −303 from the first translation start site in the −575/−19 (556 bp) fragment of IDE proximal promoter. By site-directed mutagenesis of the IDE promoter region we reverted the inhibitory effect mediated by NICD transfection suggesting that these sites are indeed responsible for the Notch-mediated inhibition of the IDE gene expression. Intracranial injection of the Notch ligand JAG-1 in Tg2576 mice, expressing the Swedish mutation in human APP, induced overexpression of HES-1 and Hey-1 and reduction of IDE mRNA levels, respectively. Our results support our theory that a Notch-dependent IDE transcriptional modulation may impact on Aβ metabolism providing a functional link between Notch signaling and the amyloidogenic pathway in SAD. PMID:22036964

Support for an hypothesis linking Alzheimer`s disease and Down syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geller, L.N.; Benjamin, M.B.; Dressler, D.

1994-09-01

A connection between Alzheimer`s disease (AD) and Down syndrome (trisomy 21) is indicated by the fact that Down syndrome individuals develop AD neuropathology by the third or fourth decade of life. One explanation for the connection between AD and Down syndrome would be that the overexpression of a gene or genes on chromosome 21 results in Alzheimer`s disease, the most likely candidate being the amyloid precursor protein (APP) gene. However, mutations in the APP gene have been found to be associated with only a very small percentage of familial AD cases. An alternative cause of some Alzheimer`s disease cases maymore » be sporadic trisomy of chromosome 21, resulting from mutations or toxins that cause chromosome nondisjunction. Several predictions can be made based on this hypothesis. One prediction is that there should be more trisomy 21 in cells from AD individuals than from unaffected controls. Using quantitative fluorescence in situ hybridization to compare the number of trisomy chromosome 21 cells in cultured fibroblasts from AD and unaffected individuals, we have shown that there are a significantly larger number of trisomy 21 cells from AD individuals. Another prediction is that a defect in the mitotic spindle apparatus could be the underlying cause of the aneuploidy. Cultured lymphoblasts from AD and unaffected individuals were briefly exposed to the microtubule-disrupting agent colchicine. As assayed by the subsequent appearance of metaphase chromosomes showing centromere separation, cells from AD patients were significantly more sensitive to colchicine treatment compared to cells from unaffected individuals, supporting the prediction of an altered spindle apparatus. Finally, we would predict that both types of patients should share some physical symptoms. We have also found that AD, like Down`s patients, are hypersensitive to the effect of the cholinergic antagonist, tropicamide, on pupil dilation, which may serve as a diagnostic test for Alzheimer`s disease.« less

A genetic screen of the mutations in the Korean patients with early-onset Alzheimer’s disease

PubMed Central

An, Seong Soo; Park, Sun Ah; Bagyinszky, Eva; Bae, Sun Oh; Kim, Yoon-Jeong; Im, Ji Young; Park, Kyung Won; Park, Kee Hyung; Kim, Eun-Joo; Jeong, Jee Hyang; Kim, Jong Hun; Han, Hyun Jeong; Choi, Seong Hye; Kim, SangYun

2016-01-01

Early-onset Alzheimer’s disease (EOAD) has distinct clinical characteristics in comparison to late-onset Alzheimer’s disease (LOAD). The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS) study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer’s disease (AD) mutations in the consecutive EOAD subjects from the CREDOS study from April 2012 to February 2014. We checked the sequence of APP (exons 16–17), PSEN1 (exons 3–12), and PSEN2 (exons 3–12) genes. We identified different causative or probable pathogenic AD mutations, PSEN1 T116I, PSEN1 L226F, and PSEN2 V214L, employing 24 EOAD subjects with a family history and 80 without a family history of dementia. PSEN1 T116I case demonstrated autosomal dominant trait of inheritance, with at least 11 affected individuals over 2 generations. However, there was no family history of dementia within first-degree relation in PSEN1 L226F and PSEN2 V214L cases. Approximately, 55.7% of the EOAD subjects had APOE ε4 allele, while none of the mutation-carrying subjects had the allele. The frequency of genetic mutation in this study is lower compared to the studies from other countries. The study design that was based on nationwide cohort, which minimizes selection bias, is thought to be one of the contributors to the lower frequency of genetic mutation. However, the possibility of the greater likeliness of earlier onset of sporadic AD in Korea cannot be excluded. We suggest early AD onset and not carrying APOE ε4 allele are more reliable factors for predicting an induced genetic mutation than the presence of the family history in Korean EOAD population. PMID:28008242

Expression of APP pathway mRNAs and proteins in Alzheimer's disease.

PubMed

Matsui, Toshifumi; Ingelsson, Martin; Fukumoto, Hiroaki; Ramasamy, Karunya; Kowa, Hisatomo; Frosch, Matthew P; Irizarry, Michael C; Hyman, Bradley T

2007-08-03

In both trisomy 21 and rare cases of triplication of amyloid precursor protein (APP) Alzheimer's disease (AD) pathological changes are believed to be secondary to increased expression of APP. We hypothesized that sporadic AD may also be associated with changes in transcription of APP or its metabolic partners. To address this issue, temporal neocortex of 27 AD and 21 non-demented control brains was examined to assess mRNA levels of APP isoforms (total APP, APP containing the Kunitz protease inhibitor domain [APP-KPI] and APP770) and APP metabolic enzymatic partners (the APP cleaving enzymes beta-secretase [BACE] and presenilin-1 [PS-1], and putative clearance molecules, low-density lipoprotein receptor protein [LRP] and apolipoprotein E [apoE]). Furthermore, we evaluated how changes in APP at the mRNA level affect the amount of Tris buffer extractable APP protein and Abeta40 and 42 peptides in AD and control brains. As assessed by quantitative PCR, APP-KPI (p=0.007), APP770 (p=0.004), PS-1 (p=0.004), LRP (p=0.003), apoE (p=0.0002) and GFAP (p<0.0001) mRNA levels all increased in AD, and there was a shift from APP695 (a neuronal isoform) towards KPI containing isoforms that are present in glia as well. APP-KPI mRNA levels correlated with soluble APPalpha-KPI protein (sAPPalpha-KPI) levels measured by ELISA (tau=0.33, p=0.015 by Kendall's rank correlation); in turn, soluble APPalpha-KPI protein levels positively correlated with Tris-extractable, soluble Abeta40 (p=0.046) and 42 levels (p=0.007). The ratio of soluble APPalpha-KPI protein levels to total APP protein increased in AD, and also correlated with GFAP protein levels in AD. These results suggest that altered transcription of APP in AD is proportionately associated with Abeta peptide, may occur in the context of gliosis, and may contribute to Abeta deposition in sporadic AD.

Effective? Engaging? Secure? Applying the ORCHA-24 framework to evaluate apps for chronic insomnia disorder.

PubMed

Leigh, Simon; Ouyang, Jing; Mimnagh, Chris

2017-11-01

Mobile health offers many opportunities; however, the 'side-effects' of health apps are often unclear. With no guarantee health apps first do no harm, their role as a viable, safe and effective therapeutic option is limited. To assess the quality of apps for chronic insomnia disorder, available on the Android Google Play Store, and determine whether a novel approach to app assessment could identify high-quality and low-risk health apps in the absence of indicators such as National Health Service (NHS) approval. The Organisation for the Review of Care and Health Applications- 24 Question Assessment (ORCHA-24), 24 app assessment criteria concerning data privacy, clinical efficacy and user experience, answered on a 'yes' or 'no' and evidence-driven basis, was applied to assess 18 insomnia apps identified via the Android Google Play Store, in addition to the NHS-approved iOS app Sleepio. 63.2% of apps (12/19) provided a privacy policy, with seven (36.8%) stating no user data would be shared without explicit consent. 10.5% (2/19) stated they had been shown to be of benefit to those with insomnia, with cognitive behavioural therapy apps outperforming hypnosis and meditation apps (p=0.046). Both the number of app downloads (p=0.29) and user-review scores (p=0.23) were unrelated to ORCHA-24 scores. The NHS-approved app Sleepio, consistently outperformed non-accredited apps across all domains of the ORCHA-24. Apps for chronic insomnia disorder exhibit substantial variation in adherence to published data privacy, user experience and clinical efficacy standards, which are not clearly correlated with app downloads or user-review scores. In absence of formal app accreditation, the ORCHA-24 could feasibly be used to highlight the risk-benefit profiles of health apps prior to downloading. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Hypnosis: There’s an App for that. A systematic review of hypnosis apps

PubMed Central

Sucala, Madalina; Schnur, Julie B.; Glazier, Kimberly; Miller, Sarah J.; Green, Joseph P.; Montgomery, Guy H.

2013-01-01

The study systematically reviews the hypnosis apps available via iTunes that were compatible with iPhone or iPad. Of 1455 apps identified on iTunes, 407 met inclusion criteria and were further reviewed. Most common hypnosis app targets were: weight loss (23%), boosting self-esteem (20%), and relaxation/stress reduction (19%). 83% of apps delivered hypnosis via audio track, and 37% allowed tailoring. Less than 14% of apps reported disclaimers. None of the apps reported having been tested for efficacy, and none reported being evidence-based. Although apps have the potential to enhance hypnosis delivery, it seems as though technology has raced ahead of the supporting science. Recommendations from clinical researchers and policy makers are needed to inform responsible hypnosis app development and use. PMID:23957263

Results of the Clinician Apps Survey, How Clinicians Working With Patients With Diabetes and Obesity Use Mobile Health Apps.

PubMed

Karduck, Justine; Chapman-Novakofski, Karen

2018-01-01

To develop and administer a questionnaire to determine what factors may be associated with app use (including frequency of use, reasons to recommend to clients/patients, perceived effectiveness on health, health aspects used, features, and types of apps) by clinicians working in diabetes and weight management patient care settings. The Clinician Apps Survey was developed and contained 3 question domains (smartphone apps use, behavior theory in counseling sessions, and demographics) to explore frequency, types, preferred features, benefits/barriers of using apps, counseling techniques used, and clinician demographics. Clinicians (n = 719) were recruited to complete the online survey through 4 dietetics and diabetes professional groups. Clinician use and preferences for health-related apps for personal reasons and in patient care settings were determined, and comparisons were made between high and non-app users. Descriptive statistics were used with current practices and attitudes about apps. Chi-square test of independence compared those using apps both personally and professionally (app enthusiasts) vs those with no app use. There were more app enthusiasts (53%; n = 380) than non-app users (20%; n = 145). Whereas 68% recommended pen/paper methods for diet and physical activity monitoring, 62% recommended apps. Most agreed that apps were superior to traditional methods for patients to track dietary intake (62%) and physical activity (58%), make better food choices (34%), lose weight (45%), and track blood glucose (43%). App enthusiasts used the American Association of Diabetes Educators self-care guidelines (P = .001) and advanced counseling techniques (eg, motivational interviewing) more often than did non-app users (P < .004). Apps most frequently recommended to clients were MyFitnessPal (n = 425), CalorieKing (n = 356), and Fitbit (n = 312). Health-related smartphone apps are being widely used and recommended to patients with diabetes and obesity by clinicians for self-monitoring of dietary and physical activity behaviors. Furthermore, many clinicians believe that these types of tracking apps may improve patient outcomes compared with traditional methods of monitoring dietary and physical activity behaviors. Copyright © 2017 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

Application of low-cost methodologies for mobile phone app development.

PubMed

Zhang, Melvyn; Cheow, Enquan; Ho, Cyrus Sh; Ng, Beng Yeong; Ho, Roger; Cheok, Christopher Cheng Soon

2014-12-09

The usage of mobile phones and mobile phone apps in the recent decade has indeed become more prevalent. Previous research has highlighted a method of using just the Internet browser and a text editor to create an app, but this does not eliminate the challenges faced by clinicians. More recently, two methodologies of app development have been shared, but there has not been any disclosures pertaining to the costs involved. In addition, limitations such as the distribution and dissemination of the apps have not been addressed. The aims of this research article are to: (1) highlight a low-cost methodology that clinicians without technical knowledge could use to develop educational apps; (2) clarify the respective costs involved in the process of development; (3) illustrate how limitations pertaining to dissemination could be addressed; and (4) to report initial utilization data of the apps and to share initial users' self-rated perception of the apps. In this study, we will present two techniques of how to create a mobile app using two of the well-established online mobile app building websites. The costs of development are specified and the methodology of dissemination of the apps will be shared. The application of the low-cost methodologies in the creation of the "Mastering Psychiatry" app for undergraduates and "Déjà vu" app for postgraduates will be discussed. A questionnaire survey has been administered to undergraduate students collating their perceptions towards the app. For the Mastering Psychiatry app, a cumulative total of 722 users have used the mobile app since inception, based on our analytics. For the Déjà vu app, there has been a cumulative total of 154 downloads since inception. The utilization data demonstrated the receptiveness towards these apps, and this is reinforced by the positive perceptions undergraduate students (n=185) had towards the low-cost self-developed apps. This is one of the few studies that have demonstrated the low-cost methodologies of app development; as well as student and trainee receptivity toward self-created Web-based mobile phone apps. The results obtained have demonstrated that these Web-based low-cost apps are applicable in the real life, and suggest that the methodologies shared in this research paper might be of benefit for other specialities and disciplines.

Application of Low-Cost Methodologies for Mobile Phone App Development

PubMed Central

Ng, Beng Yeong; Ho, Roger; Cheok, Christopher Cheng Soon

2014-01-01

Background The usage of mobile phones and mobile phone apps in the recent decade has indeed become more prevalent. Previous research has highlighted a method of using just the Internet browser and a text editor to create an app, but this does not eliminate the challenges faced by clinicians. More recently, two methodologies of app development have been shared, but there has not been any disclosures pertaining to the costs involved. In addition, limitations such as the distribution and dissemination of the apps have not been addressed. Objective The aims of this research article are to: (1) highlight a low-cost methodology that clinicians without technical knowledge could use to develop educational apps; (2) clarify the respective costs involved in the process of development; (3) illustrate how limitations pertaining to dissemination could be addressed; and (4) to report initial utilization data of the apps and to share initial users’ self-rated perception of the apps. Methods In this study, we will present two techniques of how to create a mobile app using two of the well-established online mobile app building websites. The costs of development are specified and the methodology of dissemination of the apps will be shared. The application of the low-cost methodologies in the creation of the “Mastering Psychiatry” app for undergraduates and “Déjà vu” app for postgraduates will be discussed. A questionnaire survey has been administered to undergraduate students collating their perceptions towards the app. Results For the Mastering Psychiatry app, a cumulative total of 722 users have used the mobile app since inception, based on our analytics. For the Déjà vu app, there has been a cumulative total of 154 downloads since inception. The utilization data demonstrated the receptiveness towards these apps, and this is reinforced by the positive perceptions undergraduate students (n=185) had towards the low-cost self-developed apps. Conclusions This is one of the few studies that have demonstrated the low-cost methodologies of app development; as well as student and trainee receptivity toward self-created Web-based mobile phone apps. The results obtained have demonstrated that these Web-based low-cost apps are applicable in the real life, and suggest that the methodologies shared in this research paper might be of benefit for other specialities and disciplines. PMID:25491323

The Potential of Mobile Apps for Improving Asthma Self-Management: A Review of Publicly Available and Well-Adopted Asthma Apps

PubMed Central

Tinschert, Peter; Jakob, Robert; Barata, Filipe; Kramer, Jan-Niklas

2017-01-01

Background Effective disease self-management lowers asthma’s burden of disease for both individual patients and health care systems. In principle, mobile health (mHealth) apps could enable effective asthma self-management interventions that improve a patient’s quality of life while simultaneously reducing the overall treatment costs for health care systems. However, prior reviews in this field have found that mHealth apps for asthma lack clinical evaluation and are often not based on medical guidelines. Yet, beyond the missing evidence for clinical efficacy, little is known about the potential apps might have for improving asthma self-management. Objective The aim of this study was to assess the potential of publicly available and well-adopted mHealth apps for improving asthma self-management. Methods The Apple App store and Google Play store were systematically searched for asthma apps. In total, 523 apps were identified, of which 38 apps matched the selection criteria to be included in the review. Four requirements of app potential were investigated: app functions, potential to change behavior (by means of a behavior change technique taxonomy), potential to promote app use (by means of a gamification components taxonomy), and app quality (by means of the Mobile Application Rating Scale [MARS]). Results The most commonly implemented functions in the 38 reviewed asthma apps were tracking (30/38, 79%) and information (26/38, 68%) functions, followed by assessment (20/38, 53%) and notification (18/38, 47%) functions. On average, the reviewed apps applied 7.12 of 26 available behavior change techniques (standard deviation [SD]=4.46) and 4.89 of 31 available gamification components (SD=4.21). Average app quality was acceptable (mean=3.17/5, SD=0.58), whereas subjective app quality lied between poor and acceptable (mean=2.65/5, SD=0.87). Additionally, the sum scores of all review frameworks were significantly correlated (lowest correlation: r36=.33, P=.04 between number of functions and gamification components; highest correlation: r36=.80, P<.001 between number of behavior change techniques and gamification components), which suggests that an app’s potential tends to be consistent across review frameworks. Conclusions Several apps were identified that performed consistently well across all applied review frameworks, thus indicating the potential mHealth apps offer for improving asthma self-management. However, many apps suffer from low quality. Therefore, app reviews should be considered as a decision support tool before deciding which app to integrate into a patient’s asthma self-management. Furthermore, several research-practice gaps were identified that app developers should consider addressing in future asthma apps. PMID:28768606

Mobile phone applications for the care and prevention of HIV and other sexually transmitted diseases: a review.

PubMed

Muessig, Kathryn E; Pike, Emily C; Legrand, Sara; Hightow-Weidman, Lisa B

2013-01-04

Mobile phone applications (apps) provide a new platform for delivering tailored human immunodeficiency virus (HIV) and sexually transmitted disease (STD) prevention and care. To identify and evaluate currently available mobile phone apps related to the prevention and care of HIV and other STDs. We searched the Apple iTunes and Android Google Play stores for HIV/STD-related apps, excluding apps that exclusively targeted industry, providers, and researchers. Each eligible app was downloaded, tested, and assessed for user ratings and functionality as well as 6 broad content areas of HIV prevention and care: HIV/STD disease knowledge, risk reduction/safer sex, condom promotion, HIV/STD testing information, resources for HIV-positive persons, and focus on key populations. Search queries up to May 2012 identified 1937 apps. Of these, 55 unique apps met the inclusion criteria (12 for Android, 29 for iPhone, and 14 for both platforms). Among these apps, 71% provided disease information about HIV/STDs, 36% provided HIV/STD testing information or resources, 29% included information about condom use or assistance locating condoms, and 24% promoted safer sex. Only 6 apps (11%) covered all 4 of these prevention areas. Eight apps (15%) provided tools or resources specifically for HIV/STD positive persons. Ten apps included information for a range of sexual orientations, 9 apps appeared to be designed for racially/ethnically diverse audiences, and 15 apps featured interactive components. Apps were infrequently downloaded (median 100-500 downloads) and not highly rated (average customer rating 3.7 out of 5 stars). Most available HIV/STD apps have failed to attract user attention and positive reviews. Public health practitioners should work with app developers to incorporate elements of evidence-based interventions for risk reduction and improve app inclusiveness and interactivity.

LRP1 Modulates APP Intraneuronal Transport and Processing in Its Monomeric and Dimeric State

PubMed Central

Herr, Uta-Mareike; Strecker, Paul; Storck, Steffen E.; Thomas, Carolin; Rabiej, Verena; Junker, Anne; Schilling, Sandra; Schmidt, Nadine; Dowds, C. Marie; Eggert, Simone; Pietrzik, Claus U.; Kins, Stefan

2017-01-01

The low-density lipoprotein receptor-related protein 1, LRP1, interacts with APP and affects its processing. This is assumed to be mostly caused by the impact of LRP1 on APP endocytosis. More recently, also an interaction of APP and LRP1 early in the secretory pathway was reported whereat retention of LRP1 in the ER leads to decreased APP cell surface levels and in turn, to reduced Aβ secretion. Here, we extended the biochemical and immunocytochemical analyses by showing via live cell imaging analyses in primary neurons that LRP1 and APP are transported only partly in common (one third) but to a higher degree in distinct fast axonal transport vesicles. Interestingly, co-expression of LRP1 and APP caused a change of APP transport velocities, indicating that LRP1 recruits APP to a specific type of fast axonal transport vesicles. In contrast lowered levels of LRP1 facilitated APP transport. We further show that monomeric and dimeric APP exhibit similar transport characteristics and that both are affected by LRP1 in a similar way, by slowing down APP anterograde transport and increasing its endocytosis rate. In line with this, a knockout of LRP1 in CHO cells and in primary neurons caused an increase of monomeric and dimeric APP surface localization and in turn accelerated shedding by meprin β and ADAM10. Notably, a choroid plexus specific LRP1 knockout caused a much higher secretion of sAPP dimers into the cerebrospinal fluid compared to sAPP monomers. Together, our data show that LRP1 functions as a sorting receptor for APP, regulating its cell surface localization and thereby its processing by ADAM10 and meprin β, with the latter exhibiting a preference for APP in its dimeric state. PMID:28496400

Rate My Sleep: Examining the Information, Function, and Basis in Empirical Evidence Within Sleep Applications for Mobile Devices.

PubMed

Lee-Tobin, Peta A; Ogeil, Rowan P; Savic, Michael; Lubman, Dan I

2017-11-15

Sleep applications (apps) have proliferated in online spaces, but few studies have examined the validity of the information contained within the apps. This study aimed to examine the information and functions found within sleep apps, determine if the information is based on empirical evidence, and whether or not user ratings were affected by these factors. Sleep apps found in the Google Play store (n = 76) were coded using content analysis to examine the types of information, functions, and evidence base of each app. Only 32.9% of sleep apps contained empirical evidence supporting their claims, 15.8% contained clinical input, and 13.2% contained links to sleep literature. Apps also contained information on how sleep is affected by alcohol or drugs (23.7%), food (13.2%), daily activities (13.2), and stress (13.2%). A mean difference in average user rating was found between apps that contained at least one source of information compared those that did not. App user ratings were not associated with an app having multiple functions, or from an app drawing on multiple sources of evidence (except for sleep literature only). Last, there was a higher average user rating among apps that contained a sleep tip function. Sleep apps are increasingly popular, demonstrated by the large number of downloads in the Google Play store. Users favored apps that contained sleep tips; however, these tips and other information in the apps were generally not based on empirical evidence. Future research in the area of sleep apps should consider constructing sleep apps derived from empirical evidence and examining their effectiveness. © 2017 American Academy of Sleep Medicine

Mobile Apps for Teaching Intubation: Scoping Review and Critical Analysis in eLearning

PubMed Central

2017-01-01

Background Airway management is a core skill in anesthesia ensuring adequate oxygenation and delivery of inhalational agents for the patient. Objective The goals of this study were to critically evaluate the quality of airway management apps and target revised Bloom's Taxonomy cognitive levels. Methods An electronic search using the keywords “airway” and “airway management” was conducted in May 2015 across the App Store, Google Play, BlackBerry World, and Windows Store. Apps were included in the study if their content was related to airway management. App content and characteristics were extracted into a standard form and evaluated. Results A total of 65 apps met the inclusion criteria, and 73% (47/65) of apps were developed by companies or industry. Anesthesiology trainees were the target audience in only 20% (13/65) of apps. Bag mask ventilation and laryngeal mask airways were covered in only 20% (13/65) of apps. Only 2 apps were supported in the scientific literature. For Bloom’s Taxonomy, 37% (24/65) of apps targeted knowledge, 5% (3/65) comprehension, 22% (14/65) application, 28% (18/65) analysis, 9% (6/65) evaluation, and 0% synthesis. Multivariate analysis identified cost of apps, size of apps (MB), and apps targeting trainees and paramedics to be associated with higher levels of cognitive processing of revised Bloom’s Taxonomy. Conclusions Apps developed for teaching intubation target lower levels of cognitive processing and are largely not validated by research. Cost, app size, and targeted user are associated with higher cognitive levels. Trainees and all users should be aware of the paucity of the published evidence behind the efficacy of some of these apps. PMID:28874335

Mobile Apps for Teaching Intubation: Scoping Review and Critical Analysis in eLearning.

PubMed

Matava, Clyde; Leo, Anne-Marie; Alam, Fahad

2017-09-05

Airway management is a core skill in anesthesia ensuring adequate oxygenation and delivery of inhalational agents for the patient. The goals of this study were to critically evaluate the quality of airway management apps and target revised Bloom's Taxonomy cognitive levels. An electronic search using the keywords "airway" and "airway management" was conducted in May 2015 across the App Store, Google Play, BlackBerry World, and Windows Store. Apps were included in the study if their content was related to airway management. App content and characteristics were extracted into a standard form and evaluated. A total of 65 apps met the inclusion criteria, and 73% (47/65) of apps were developed by companies or industry. Anesthesiology trainees were the target audience in only 20% (13/65) of apps. Bag mask ventilation and laryngeal mask airways were covered in only 20% (13/65) of apps. Only 2 apps were supported in the scientific literature. For Bloom's Taxonomy, 37% (24/65) of apps targeted knowledge, 5% (3/65) comprehension, 22% (14/65) application, 28% (18/65) analysis, 9% (6/65) evaluation, and 0% synthesis. Multivariate analysis identified cost of apps, size of apps (MB), and apps targeting trainees and paramedics to be associated with higher levels of cognitive processing of revised Bloom's Taxonomy. Apps developed for teaching intubation target lower levels of cognitive processing and are largely not validated by research. Cost, app size, and targeted user are associated with higher cognitive levels. Trainees and all users should be aware of the paucity of the published evidence behind the efficacy of some of these apps. ©Clyde Matava, Anne-Marie Leo, Fahad Alam. Originally published in JMIR Medical Education (http://mededu.jmir.org), 05.09.2017.

A Systematic Review of Smartphone Applications for Plastic Surgery Providers: Target Audience, Uses, and Cost.

PubMed

Reusche, Ryan; Buchanan, Patrick J; Kozlow, Jeffrey H; Vercler, Christian J

2016-01-01

The growth and acceptance of smartphones among clinicians has been remarkable over the last decade. Over 87% of doctors use a smartphone or tablet capable of running third-party software known as applications (apps). In the field of plastic surgery, apps have been designed for personal practice development, education, clinical tools and guidelines, and entertainment. This study reviews the literature on apps related to plastic surgery and determines the number and types of apps available. A systematic review of the literature was performed to find articles written about plastic surgery applications. Queries were run in the Apple iPhone iOS App store and Google Play using the term "plastic surgery." Apps were reviewed for ratings, downloads, and cost. In addition, apps were categorized based on purpose. Categories include practice development, media/literature, clinical tool and guideline apps, or recreation. The literature search yielded 8 articles for review, 2 articles focused on categorizing apps and 6 articles focused on describing useful apps. Searching Apple's iTunes (iOS) store identified 273 and Google Play identified 250 apps related to plastic surgery; since 2013, a 62%, and 580% increase, respectively. The iOS store included practice development (46%), recreation (26%), media/literature (14%), and clinical tool and guideline (11%). Google Play store included recreation apps (44%), practice development (24%), clinical tools and guidelines (11%), and media and literature (9%). Apps related to the field of plastic surgery are increasing in prevalence. The content of these apps are variable, and the majority are intended for marketing and development of private practices. Apps linking to literature, texts, study materials, and clinical tools and guidelines are developed for both practicing plastic surgeons and surgical trainees. Finding "useful" apps takes time because searches are often complicated by a variety of apps.

App Usage Factor: A Simple Metric to Compare the Population Impact of Mobile Medical Apps.

PubMed

Lewis, Thomas Lorchan; Wyatt, Jeremy C

2015-08-19

One factor when assessing the quality of mobile apps is quantifying the impact of a given app on a population. There is currently no metric which can be used to compare the population impact of a mobile app across different health care disciplines. The objective of this study is to create a novel metric to characterize the impact of a mobile app on a population. We developed the simple novel metric, app usage factor (AUF), defined as the logarithm of the product of the number of active users of a mobile app with the median number of daily uses of the app. The behavior of this metric was modeled using simulated modeling in Python, a general-purpose programming language. Three simulations were conducted to explore the temporal and numerical stability of our metric and a simulated app ecosystem model using a simulated dataset of 20,000 apps. Simulations confirmed the metric was stable between predicted usage limits and remained stable at extremes of these limits. Analysis of a simulated dataset of 20,000 apps calculated an average value for the app usage factor of 4.90 (SD 0.78). A temporal simulation showed that the metric remained stable over time and suitable limits for its use were identified. A key component when assessing app risk and potential harm is understanding the potential population impact of each mobile app. Our metric has many potential uses for a wide range of stakeholders in the app ecosystem, including users, regulators, developers, and health care professionals. Furthermore, this metric forms part of the overall estimate of risk and potential for harm or benefit posed by a mobile medical app. We identify the merits and limitations of this metric, as well as potential avenues for future validation and research.

Is a Picture Worth a Thousand Words? Few Evidence-Based Features of Dietary Interventions Included in Photo Diet Tracking Mobile Apps for Weight Loss.

PubMed

Hales, Sarah; Dunn, Caroline; Wilcox, Sara; Turner-McGrievy, Gabrielle M

2016-11-01

Apps using digital photos to track dietary intake and provide feedback are common, but currently there has been no research examining what evidence-based strategies are included in these apps. A content analysis of mobile apps for photo diet tracking was conducted, including whether effective techniques for interventions promoting behavior change, including self-regulation, for healthy eating (HE) are targeted. An initial search of app stores yielded 34 apps (n = 8 Android and Apple; n = 11 Android; n = 15 Apple). One app was removed (unable to download), and other apps (n = 4) were unable to be rated (no longer available). Remaining apps (n = 29) were downloaded, reviewed, and coded by 2 independent reviewers to determine the number of known effective self-regulation and other behavior change techniques included. The raters met to compare their coding of the apps, calculate interrater agreement, resolve any discrepancies, and come to a consensus. Six apps (21%) did not utilize any of the behavior change techniques examined. Three apps (10%) provided feedback to users via crowdsourcing or collective feedback from other users and professionals, 7 apps (24%) used crowdsourcing or collective feedback, 1 app (3%) used professionals, and 18 apps (62%) did not provide any dietary feedback to users. Few photo diet-tracking apps include evidence-based strategies to improve dietary intake. Use of photos to self-monitor dietary intake and receive feedback has the potential to reduce user burden for self-monitoring, yet photo diet tracking apps need to incorporate known effective behavior strategies for HE, including self-regulation. © 2016 Diabetes Technology Society.

Expert Involvement Predicts mHealth App Downloads: Multivariate Regression Analysis of Urology Apps

PubMed Central

Osório, Luís; Cavadas, Vitor; Fraga, Avelino; Carrasquinho, Eduardo; Cardoso de Oliveira, Eduardo; Castelo-Branco, Miguel; Roobol, Monique J

2016-01-01

Background Urological mobile medical (mHealth) apps are gaining popularity with both clinicians and patients. mHealth is a rapidly evolving and heterogeneous field, with some urology apps being downloaded over 10,000 times and others not at all. The factors that contribute to medical app downloads have yet to be identified, including the hypothetical influence of expert involvement in app development. Objective The objective of our study was to identify predictors of the number of urology app downloads. Methods We reviewed urology apps available in the Google Play Store and collected publicly available data. Multivariate ordinal logistic regression evaluated the effect of publicly available app variables on the number of apps being downloaded. Results Of 129 urology apps eligible for study, only 2 (1.6%) had >10,000 downloads, with half having ≤100 downloads and 4 (3.1%) having none at all. Apps developed with expert urologist involvement (P=.003), optional in-app purchases (P=.01), higher user rating (P<.001), and more user reviews (P<.001) were more likely to be installed. App cost was inversely related to the number of downloads (P<.001). Only data from the Google Play Store and the developers’ websites, but not other platforms, were publicly available for analysis, and the level and nature of expert involvement was not documented. Conclusions The explicit participation of urologists in app development is likely to enhance its chances to have a higher number of downloads. This finding should help in the design of better apps and further promote urologist involvement in mHealth. Official certification processes are required to ensure app quality and user safety. PMID:27421338

An Evaluation of Mobile Applications for Reproductive Endocrinology and Infertility Providers.

PubMed

Shaia, Kathryn L; Farag, Sara; Chyjek, Kathy; Knopman, Jaime; Chen, Katherine T

2017-03-01

To identify and rate reproductive endocrinology and infertility (REI) mobile applications (apps) targeted toward REI providers. A list of REI apps was found in both the Apple iTunes and Google Play stores using the following seven MeSH terms: reproductive endocrinology, REI, infertility, fertility, In Vitro Fertilization, IVF, and embryology. Patient-centered apps were excluded. The remaining apps were then evaluated for accuracy using reliable references. Mobile technology. None. Accurate apps were evaluated for comprehensiveness (the extent of the ability to aid in clinical decision-making) and rated with objective and subjective components using the APPLICATIONS scoring system. Using the seven REI-related MeSH terms, 985 apps and 1,194 apps were identified in the Apple iTunes and Google Play stores, respectively. Of these unique apps, only 20 remained after excluding patient-centered apps. Upon further review for applicability to REI specifically and content accuracy, only seven apps remained. These seven apps were then rated using the APPLICATIONS scoring system. Only 0.32% of 2,179 apps reviewed for this study were useful to REI providers. There is potential for further mobile resource development in the area of REI, given the limited number and varying comprehensiveness and quality of available apps.

Growth of mobile applications in dermatology - 2017 update.

PubMed

Flaten, Hania K; St Claire, Chelsea; Schlager, Emma; Dunnick, Cory A; Dellavalle, Robert P

2018-02-15

More than 80% of households in the US have a smartphone. Growth of mobile applications (apps) has grown in parallel with access to smartphones. Mobile health apps are used in medical fields, including dermatology. These apps allow patients to access information regarding dermatology conditions as well as access physicians via teledermatology. To analyze changes in number of dermatology mobile apps since 2014 and discuss benefits and drawbacks of mobile application growth to dermatology. Apple, Android, and Windows were queried for dermatology-related apps. The apps were categorized by purpose and compared to previously published data to assess growth and change in dermatology apps. A total of 526 dermatology mobile apps were found corresponding to an 80.8% growth in dermatology apps since 2014. The market share of teledermatology increased from 11.0% in 2014 to 20.1% in 2017. Dermatology apps continue to grow at a comparable pace to general app growth. Teledermatology apps experienced significant growth from 2014 to 2017. This growth has allowed time-efficient and cost-effective access to dermatologists, especially in rural areas. The growth of dermatology apps targeting patients allows for patient autonomy but also can result in access to inaccurate information regarding dermatology conditions.

Moving Phones Tick Slower: Creating an Android App to Demonstrate Time Dilation

NASA Astrophysics Data System (ADS)

Underwood, Bret; Zhai, Yunxiao

2016-05-01

Smartphones and tablets are packed with sensors that allow us to take experimental data, essentially making them mobile physics labs. Apps exist that make it easy to capture and analyze data from these sensors, allowing users to study diverse phenomena such as free fall acceleration, the speed of sound, radioactivity, and many others. Commonly, the use of apps in the physics classroom focuses on existing apps rather than on the creation of apps themselves. This is for a good reason-writing an app usually requires advanced knowledge of programming languages and experience with app design. These skills are generally regarded as beyond the typical physics student. However, there are app development environments, such as MIT App Inventor 2 for Android, which make the process of creating an app and utilizing the sensors much more accessible to students. Putting the ability to create and configure apps within the reach of students can also help integrate computation into the curriculum. In this article, we discuss our creation of an Android app, Time Dilation Calculator, done as part of a senior undergraduate capstone project, which uses App Inventor and a mobile device's global positioning system (GPS) receiver to calculate the time dilation effect of special relativity.

Safe Sex Messages Within Dating and Entertainment Smartphone Apps: A Review.

PubMed

Huang, Evelyn Tzu-Yen; Williams, Henrietta; Hocking, Jane S; Lim, Megan Sc

2016-11-08

Smartphone apps provide a new platform for entertainment, information distribution, and health promotion activities, as well as for dating and casual sexual encounters. Previous research has shown high acceptability of sexual health interventions via smartphone apps; however, sexual health promotion apps were infrequently downloaded and underused. Integrating sexual health promotion into established apps might be a more effective method. The objective of our study was to critically review popular sex-related apps and dating apps, in order to ascertain whether they contain any sexual health content. Part 1: In January 2015, we used the term "sexual" to search for free apps in the Apple iTunes store and Android Google Play store, and categorized the sexual health content of the 137 apps identified. Part 2: We used the term "dating" to search for free geosocial-networking apps in the Apple iTunes and Android Google Play stores. The apps were downloaded to test functionality and to determine whether they included sexual health content. Part 1: Of the 137 apps identified, 15 (11.0%) had sexual health content and 15 (11.0%) contained messages about sexual assault or violence. The majority of the apps did not contain any sexual health content. Part 2: We reviewed 60 dating apps: 44 (73%) targeting heterosexual users, 9 (15%) targeting men who have sex with men (MSM), 3 (5%) targeting lesbian women, and 4 (7%) for group dating. Only 9 dating apps contained sexual health content, of which 7 targeted MSM. The majority of sex-related apps and dating apps contained no sexual health content that could educate users about and remind them of their sexual risks. Sexual health practitioners and public health departments will need to work with app developers to promote sexual health within existing popular apps. For those apps that already contain sexual health messages, further study to investigate the effectiveness of the content is needed. ©Evelyn Tzu-Yen Huang, Henrietta Williams, Jane S Hocking, Megan SC Lim. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 08.11.2016.

Medical applications for pharmacists using mobile devices.

PubMed

Aungst, Timothy Dy

2013-01-01

Mobile devices (eg, smartphones, tablet computers) have become ubiquitous and subsequently there has been a growth in mobile applications (apps). Concurrently, mobile devices have been integrated into health care practice due to the availability and quality of medical apps. These mobile medical apps offer increased access to clinical references and point-of-care tools. However, there has been little identification of mobile medical apps suitable for the practice of pharmacy. To address the shortage of recommendations of mobile medical apps for pharmacists in daily practice. Mobile medical apps were identified via the iTunes and Google Play Stores via the "Medical" app categories and key word searches (eg, drug information, medical calculators). In addition, reviews provided by professional mobile medical app review websites were used to identify apps. Mobile medical apps were included if they had been updated in the previous 3 months, were available in the US, used evidence-based information or literature support, had dedicated app support, and demonstrated stability. Exclusion criteria included apps that were not available in English, had advertisement bias, used nonreferenced sources, were available only via an institution-only subscription, and were web-based portals. Twenty-seven mobile apps were identified and reviewed that involved general pharmacy practice, including apps that involved drug references, clinical references, medical calculators, laboratory references, news and continuing medical education, and productivity. Mobile medical apps have a variety of features that are beneficial to pharmacy practice. Individual clinicians should consider several characteristics of these apps to determine which are suitable to incorporate into their daily practice.

Apps and eating disorders: A systematic clinical appraisal.

PubMed

Fairburn, Christopher G; Rothwell, Emily R

2015-11-01

Smartphone applications (apps) are proliferating and health-related apps are particularly popular. The aim of this study was to identify, characterize, and evaluate the clinical utility of apps designed either for people with eating disorders or for eating disorder professionals. A search of the major app stores identified 805 potentially relevant apps, of which 39 were primarily designed for people with eating disorders and five for professionals. The apps for people with eating disorders had four main functions. Most common was the provision of advice, the quality of which ranged from sound to potentially harmful. Five apps included self-assessment tools but only two used methods that would generally be viewed as reliable. Four apps had the self-monitoring of eating habits as a major feature. Entering information into these apps could be accomplished with varying degrees of ease, but viewing it was more difficult. One app allowed the transfer of information between patients and clinicians. The enthusiasm for apps outstrips the evidence supporting their use. Given their popularity, it is suggested that clinicians evaluate app use as part of routine assessment. The clinical utility of the existing apps is not clear. Some are capable of tracking key features over time, but none has the functions required for analytic self-monitoring as in cognitive behavioral treatments. The full potential of apps has yet to be realized. Specialized apps could be designed to augment various forms of treatment, and there is the possibility that they could deliver an entire personalized intervention. © 2015 The Authors. International Journal of Eating Disorders published by Wiley Periodicals, Inc.

Characteristics of Chinese m-Health Applications for Diabetes Self-Management.

PubMed

Nie, Lisa; Xie, Bo; Yang, Yan; Shan, Yan Min

2016-07-01

To examine the features and types of health information provided in Chinese diabetes mobile applications (apps) for patients' self-management. Through multiple rounds of screening, we identified a total of 95 relevant iOS (Apple, Cupertino, CA) and Android™ (Google, Mountain View, CA) apps and examined each app's features and health information types based on each app's description in the app stores. We used a 15-feature algorithm to evaluate the apps' abilities for supporting diabetic patients' self-management, based on U.S. national standards for diabetes self-management. We also adapted the health information wants framework to analyze the types of information that the apps provided for diabetic patients. Diabetes education was the most common feature, provided by 75% of the apps. Blood glucose checking was enabled by 65% of the apps. Diet management, insulin checking, and physical activity monitoring were enabled by 53%, 49%, and 44% of the apps, respectively. Only a small percentage of the apps enabled psychosocial support (29%) or tracking of blood pressure (14%), cholesterol (14%), or body mass index (11%). None of the apps provided all seven types of information posited by the health information wants framework. Only a small percentage of the apps provided information about psychosocial support (29%), healthcare providers (24%), or healthcare facilities (24%). Information about complementary and alternative medicine was the least likely type of information provided in the apps, with only 7% of the apps providing this type of information. Our findings have important implications for improving the quality of Chinese diabetes mobile apps to facilitate patients' self-management.

Finding a Depression App: A Review and Content Analysis of the Depression App Marketplace

PubMed Central

Shen, Nelson; Levitan, Michael-Jane; Johnson, Andrew; Bender, Jacqueline Lorene; Hamilton-Page, Michelle; Jadad, Alejandro (Alex) R

2015-01-01

Background Depression is highly prevalent and causes considerable suffering and disease burden despite the existence of wide-ranging treatment options. Mobile phone apps offer the potential to help close this treatment gap by confronting key barriers to accessing support for depression. Objectives Our goal was to identify and characterize the different types of mobile phone depression apps available in the marketplace. Methods A search for depression apps was conducted on the app stores of the five major mobile phone platforms: Android, iPhone, BlackBerry, Nokia, and Windows. Apps were included if they focused on depression and were available to people who self-identify as having depression. Data were extracted from the app descriptions found in the app stores. Results Of the 1054 apps identified by the search strategy, nearly one-quarter (23.0%, 243/1054) unique depression apps met the inclusion criteria. Over one-quarter (27.7%, 210/758) of the excluded apps failed to mention depression in the title or description. Two-thirds of the apps had as their main purpose providing therapeutic treatment (33.7%, 82/243) or psychoeducation (32.1%, 78/243). The other main purpose categories were medical assessment (16.9%, 41/243), symptom management (8.2%, 20/243), and supportive resources (1.6%, 4/243). A majority of the apps failed to sufficiently describe their organizational affiliation (65.0%, 158/243) and content source (61.7%, 150/243). There was a significant relationship (χ 2 5=50.5, P<.001) between the main purpose of the app and the reporting of content source, with most medical assessment apps reporting their content source (80.5%, 33/41). A fifth of the apps featured an e-book (20.6%, 50/243), audio therapy (16.9%, 41/243), or screening (16.9%, 41/243) function. Most apps had a dynamic user interface (72.4%, 176/243) and used text as the main type of media (51.9%, 126/243), and over a third (14.4%, 35/243) incorporated more than one form of media. Conclusion Without guidance, finding an appropriate depression app may be challenging, as the search results yielded non-depression–specific apps to depression apps at a 3:1 ratio. Inadequate reporting of organization affiliation and content source increases the difficulty of assessing the credibility and reliability of the app. While certification and vetting initiatives are underway, this study demonstrates the need for standardized reporting in app stores to help consumers select appropriate tools, particularly among those classified as medical devices. PMID:25689790

Attention and Cognitive Bias Modification Apps: Review of the Literature and of Commercially Available Apps.

PubMed

Zhang, Melvyn; Ying, JiangBo; Song, Guo; Fung, Daniel Ss; Smith, Helen

2018-05-24

Automatic processes, such as attentional biases or interpretative biases, have been purported to be responsible for several psychiatric disorders. Recent reviews have highlighted that cognitive biases may be modifiable. Advances in eHealth and mHealth have been harnessed for the delivery of cognitive bias modification. While several studies have evaluated mHealth-based bias modification intervention, no review, to our knowledge, has synthesized the evidence for it. In addition, no review has looked at commercial apps and their functionalities and methods of bias modification. A review is essential in determining whether scientifically validated apps are available commercially and the proportion of commercial apps that have been evaluated scientifically. The objective of this review was primarily to determine the proportion of attention or cognitive bias modification apps that have been evaluated scientifically and secondarily to determine whether the scientifically evaluated apps were commercially available. We also sought to identify commercially available bias modification apps and determine the functionalities of these apps, the methods used for attention or cognitive bias modification, and whether these apps had been evaluated scientifically. To identify apps in the published literature, we searched PubMed, MEDLINE, PsycINFO, and Scopus for studies published from 2000 to April 17, 2018. The search terms used were "attention bias" OR "cognitive bias" AND "smartphone" OR "smartphone application" OR "smartphone app" OR "mobile phones" OR "mobile application" OR mobile app" OR "personal digital assistant." To identify commercial apps, we conducted a manual cross-sectional search between September 15 and 25, 2017 in the Apple iTunes and Google Play app stores. The search terms used to identify the apps were "attention bias" and "cognitive bias." We also conducted a manual search on the apps with published evaluations. The effectiveness of bias modification was reported in 7 of 8 trials that we identified in the published literature. Only 1 of the 8 previously evaluated apps was commercially available. The 17 commercial apps we identified tended to use either an attention visual search or gamified task. Only 1 commercial app had been evaluated in the published literature. This is perhaps the first review to synthesize the evidence for published mHealth attention bias apps. Our review demonstrated that evidence for mHealth attention bias apps is inconclusive, and quite a few commercial apps have not been validated scientifically. ©Melvyn Zhang, JiangBo Ying, Guo Song, Daniel SS Fung, Helen Smith. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 24.05.2018.

Exploring the Far Side of Mobile Health: Information Security and Privacy of Mobile Health Apps on iOS and Android

PubMed Central

Dehling, Tobias; Gao, Fangjian; Schneider, Stephan

2015-01-01

Background Mobile health (mHealth) apps aim at providing seamless access to tailored health information technology and have the potential to alleviate global health burdens. Yet, they bear risks to information security and privacy because users need to reveal private, sensitive medical information to redeem certain benefits. Due to the plethora and diversity of available mHealth apps, implications for information security and privacy are unclear and complex. Objective The objective of this study was to establish an overview of mHealth apps offered on iOS and Android with a special focus on potential damage to users through information security and privacy infringements. Methods We assessed apps available in English and offered in the categories “Medical” and “Health & Fitness” in the iOS and Android App Stores. Based on the information retrievable from the app stores, we established an overview of available mHealth apps, tagged apps to make offered information machine-readable, and clustered the discovered apps to identify and group similar apps. Subsequently, information security and privacy implications were assessed based on health specificity of information available to apps, potential damage through information leaks, potential damage through information manipulation, potential damage through information loss, and potential value of information to third parties. Results We discovered 24,405 health-related apps (iOS; 21,953; Android; 2452). Absence or scarceness of ratings for 81.36% (17,860/21,953) of iOS and 76.14% (1867/2452) of Android apps indicates that less than a quarter of mHealth apps are in more or less widespread use. Clustering resulted in 245 distinct clusters, which were consolidated into 12 app archetypes grouping clusters with similar assessments of potential damage through information security and privacy infringements. There were 6426 apps that were excluded during clustering. The majority of apps (95.63%, 17,193/17,979; of apps) pose at least some potential damage through information security and privacy infringements. There were 11.67% (2098/17,979) of apps that scored the highest assessments of potential damages. Conclusions Various kinds of mHealth apps collect and offer critical, sensitive, private medical information, calling for a special focus on information security and privacy of mHealth apps. In order to foster user acceptance and trust, appropriate security measures and processes need to be devised and employed so that users can benefit from seamlessly accessible, tailored mHealth apps without exposing themselves to the serious repercussions of information security and privacy infringements. PMID:25599627

Exploring the Far Side of Mobile Health: Information Security and Privacy of Mobile Health Apps on iOS and Android.

PubMed

Dehling, Tobias; Gao, Fangjian; Schneider, Stephan; Sunyaev, Ali

2015-01-19

Mobile health (mHealth) apps aim at providing seamless access to tailored health information technology and have the potential to alleviate global health burdens. Yet, they bear risks to information security and privacy because users need to reveal private, sensitive medical information to redeem certain benefits. Due to the plethora and diversity of available mHealth apps, implications for information security and privacy are unclear and complex. The objective of this study was to establish an overview of mHealth apps offered on iOS and Android with a special focus on potential damage to users through information security and privacy infringements. We assessed apps available in English and offered in the categories "Medical" and "Health & Fitness" in the iOS and Android App Stores. Based on the information retrievable from the app stores, we established an overview of available mHealth apps, tagged apps to make offered information machine-readable, and clustered the discovered apps to identify and group similar apps. Subsequently, information security and privacy implications were assessed based on health specificity of information available to apps, potential damage through information leaks, potential damage through information manipulation, potential damage through information loss, and potential value of information to third parties. We discovered 24,405 health-related apps (iOS; 21,953; Android; 2452). Absence or scarceness of ratings for 81.36% (17,860/21,953) of iOS and 76.14% (1867/2452) of Android apps indicates that less than a quarter of mHealth apps are in more or less widespread use. Clustering resulted in 245 distinct clusters, which were consolidated into 12 app archetypes grouping clusters with similar assessments of potential damage through information security and privacy infringements. There were 6426 apps that were excluded during clustering. The majority of apps (95.63%, 17,193/17,979; of apps) pose at least some potential damage through information security and privacy infringements. There were 11.67% (2098/17,979) of apps that scored the highest assessments of potential damages. Various kinds of mHealth apps collect and offer critical, sensitive, private medical information, calling for a special focus on information security and privacy of mHealth apps. In order to foster user acceptance and trust, appropriate security measures and processes need to be devised and employed so that users can benefit from seamlessly accessible, tailored mHealth apps without exposing themselves to the serious repercussions of information security and privacy infringements.

Finding a depression app: a review and content analysis of the depression app marketplace.

PubMed

Shen, Nelson; Levitan, Michael-Jane; Johnson, Andrew; Bender, Jacqueline Lorene; Hamilton-Page, Michelle; Jadad, Alejandro Alex R; Wiljer, David

2015-02-16

Depression is highly prevalent and causes considerable suffering and disease burden despite the existence of wide-ranging treatment options. Mobile phone apps offer the potential to help close this treatment gap by confronting key barriers to accessing support for depression. Our goal was to identify and characterize the different types of mobile phone depression apps available in the marketplace. A search for depression apps was conducted on the app stores of the five major mobile phone platforms: Android, iPhone, BlackBerry, Nokia, and Windows. Apps were included if they focused on depression and were available to people who self-identify as having depression. Data were extracted from the app descriptions found in the app stores. Of the 1054 apps identified by the search strategy, nearly one-quarter (23.0%, 243/1054) unique depression apps met the inclusion criteria. Over one-quarter (27.7%, 210/758) of the excluded apps failed to mention depression in the title or description. Two-thirds of the apps had as their main purpose providing therapeutic treatment (33.7%, 82/243) or psychoeducation (32.1%, 78/243). The other main purpose categories were medical assessment (16.9%, 41/243), symptom management (8.2%, 20/243), and supportive resources (1.6%, 4/243). A majority of the apps failed to sufficiently describe their organizational affiliation (65.0%, 158/243) and content source (61.7%, 150/243). There was a significant relationship (χ(2) 5=50.5, P<.001) between the main purpose of the app and the reporting of content source, with most medical assessment apps reporting their content source (80.5%, 33/41). A fifth of the apps featured an e-book (20.6%, 50/243), audio therapy (16.9%, 41/243), or screening (16.9%, 41/243) function. Most apps had a dynamic user interface (72.4%, 176/243) and used text as the main type of media (51.9%, 126/243), and over a third (14.4%, 35/243) incorporated more than one form of media. Without guidance, finding an appropriate depression app may be challenging, as the search results yielded non-depression-specific apps to depression apps at a 3:1 ratio. Inadequate reporting of organization affiliation and content source increases the difficulty of assessing the credibility and reliability of the app. While certification and vetting initiatives are underway, this study demonstrates the need for standardized reporting in app stores to help consumers select appropriate tools, particularly among those classified as medical devices.

Variability of CAG tandem repeats in exon 1 of the androgen receptor gene is not related with dog intersexuality.

PubMed

Nowacka-Woszuk, J; Switonski, M

2010-02-01

Numerous mutations of the human androgen receptor (AR) gene cause an intersexual phenotype, called the androgen insensitivity syndrome. The intersexual phenotype is also quite often diagnosed in dogs. The aim of this study was to conduct a comparative analysis of the entire coding sequence (eight exons) of the AR gene in healthy and four intersex dogs, as well as in three other canids (the red fox, arctic fox and Chinese raccoon dog). The coding sequence of the studied species appeared to be conserved (similarity above 97%) and polymorphism was found in exon 1 only. Altogether, 2 SNPs were identified in healthy dogs, 14 in red foxes, 16 in arctic foxes and 6 were found in Chinese raccoon dogs, respectively. Moreover, a variable number of tandem repeats (CAG and CAA), encoding an array of glutamines, was also observed in this exon. The CAA codon numbers were invariable within species, but the CAG repeats were polymorphic. The highest number of the CAG and CAA repeats was found in dogs (from 40 to 42) and the observed variability was similar in intersex and healthy dogs. In the other canids the variability fell within the following ranges: 29-37 (red fox), 37-39 (arctic fox) and 29-32 (Chinese raccoon dog). In addition, a polymorphic microsatellite marker in intron 2 was found in the dog, red fox and Chinese raccoon dog. It was concluded that the polymorphism level of the AR gene in the dog was lower than in the other canids and none of the detected polymorphisms, including variability of the CAG tandem repeats, could be related with the intersexual phenotype of the studied dogs.

How Do Infant Feeding Apps in China Measure Up? A Content Quality Assessment.

PubMed

Zhao, Jing; Freeman, Becky; Li, Mu

2017-12-06

Globally, with the popularization of mobile phones, the number of health-related mobile phone apps has skyrocketed to 259,000 in 2016. In the digital era, people are accessing health information through their fingertips. In China, there are several apps that claim to provide infant feeding and nutrition guidance. However, the quality of information in those apps has not been extensively assessed. We aimed to assess the quality of Chinese infant feeding apps using comprehensive quality assessment criteria and to explore Chinese mothers' perceptions on apps' quality and usability. We searched for free-to-download Chinese infant feeding apps in the iTunes and Android App Stores. We conducted a comprehensive assessment of the accountability, scientific basis, accuracy of information relevant to infant feeding, advertising policy, and functionality and carried out a preliminary screening of infant formula advertisements in the apps. In addition, we also conducted exploratory qualitative research through semistructured interviews with Chinese mothers in Shanghai to elicit their views about the quality of apps. A total of 4925 apps were screened, and 26 apps that met the selection criteria were evaluated. All 26 apps were developed by commercial entities, and the majority of them were rated poorly. The highest total score was 62.2 (out of approximately 100) and the lowest was 16.7. In the four quality domains assessed, none of them fulfilled all the accountability criteria. Three out of 26 apps provided information covering the three practices from the World Health Organization's infant feeding recommendations. Only one app described its advertising policy in its terms of usage. The most common app functionality was a built-in social forum (19/26). Provision of a website link was the least common functionality (2/26). A total of 20 out of 26 apps promoted infant formula banner advertisements on their homepages. In addition, 12 apps included both e-commerce stores and featured infant formula advertisements. In total, 21 mothers were interviewed face-to-face. Mothers highly valued immediate access to parenting information and multifunctionality provided by apps. However, concerns regarding incredible information and commercial activities in apps, as well as the desire for information and support offered by health care professionals were expressed. The findings provide valuable information on Chinese infant feeding apps. The results are concerning, particularly with the relative absence of scientific basis and credibility and the large number of commercial advertisements that are displayed. Apps do seem to be able to provide an opportunity for mothers to access health information and support; it is time for tighter controls on content and advertisements. Ongoing app research and development should focus on implementation of a standard framework, which would drive the development of high-quality apps to support healthy infant feeding through cooperation among academics, health professionals, app users, app developers, and government bodies. ©Jing Zhao, Becky Freeman, Mu Li. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 06.12.2017.

Amyloid precursor protein controls cholesterol turnover needed for neuronal activity

PubMed Central

Pierrot, Nathalie; Tyteca, Donatienne; D'auria, Ludovic; Dewachter, Ilse; Gailly, Philippe; Hendrickx, Aurélie; Tasiaux, Bernadette; Haylani, Laetitia El; Muls, Nathalie; N'Kuli, Francisca; Laquerrière, Annie; Demoulin, Jean-Baptiste; Campion, Dominique; Brion, Jean-Pierre; Courtoy, Pierre J; Kienlen-Campard, Pascal; Octave, Jean-Noël

2013-01-01

Perturbation of lipid metabolism favours progression of Alzheimer disease, in which processing of Amyloid Precursor Protein (APP) has important implications. APP cleavage is tightly regulated by cholesterol and APP fragments regulate lipid homeostasis. Here, we investigated whether up or down regulation of full-length APP expression affected neuronal lipid metabolism. Expression of APP decreased HMG-CoA reductase (HMGCR)-mediated cholesterol biosynthesis and SREBP mRNA levels, while its down regulation had opposite effects. APP and SREBP1 co-immunoprecipitated and co-localized in the Golgi. This interaction prevented Site-2 protease-mediated processing of SREBP1, leading to inhibition of transcription of its target genes. A GXXXG motif in APP sequence was critical for regulation of HMGCR expression. In astrocytes, APP and SREBP1 did not interact nor did APP affect cholesterol biosynthesis. Neuronal expression of APP decreased both HMGCR and cholesterol 24-hydroxylase mRNA levels and consequently cholesterol turnover, leading to inhibition of neuronal activity, which was rescued by geranylgeraniol, generated in the mevalonate pathway, in both APP expressing and mevastatin treated neurons. We conclude that APP controls cholesterol turnover needed for neuronal activity. PMID:23554170

Do Arabic weight-loss apps adhere to evidence-informed practices?

PubMed

Alnasser, Aroub A; Amalraj, Raja E; Sathiaseelan, Arjuna; Al-Khalifa, Abdulrahman S; Marais, Debbi

2016-09-01

Mobile technology has been used successfully for promoting health and weight loss and for treating obesity. There is a high prevalence of smartphone and tablet users among the Saudi population. This study aimed to identify whether current Arabic weight-loss apps had features that adhered to evidence-informed practices. The six most relevant app stores were systematically searched using the Arabic words for weight and diet (n = 298). All apps that met the inclusion criteria (n = 65) were downloaded and examined for adherence to 13 evidence-informed practices. Latent class analysis identified two subgroups of apps: self-monitoring (15 % of apps) and advice-giving apps (85 %). The median number of evidence-informed practices was 1 (1, 2), with no apps having more than six and only nine apps including four to six. Meal planning was the most common feature (38 % of apps). These findings identify serious weaknesses in the currently available Arabic weight-loss apps. Thus, existing and future apps should include more features based on the best available evidence in the context of Arab culture.

Using Behavior Change Techniques to Guide Selections of Mobile Applications to Promote Fluid Consumption.

PubMed

Conroy, David E; Dubansky, Alexandra; Remillard, Joshua; Murray, Robert; Pellegrini, Christine A; Phillips, Siobhan M; Streeper, Necole M

2017-01-01

To determine the extent to which validated techniques for behavior change have been infused in commercially available fluid consumption applications (apps). Coders evaluated behavior change techniques represented in online descriptions for 50 fluid consumption apps and the latest version of each app. Apps incorporated a limited range of behavior change techniques (<20% of taxonomy). The number of techniques varied by operating system but not as a function of whether apps were free or paid. Limitations include the lack of experimental evidence establishing the efficacy of these apps. Patients with urolithiasis can choose from many apps to support the recommended increase in fluid intake. Apps for iOS devices incorporate more behavior change techniques compared to apps for the Android operating system. Free apps are likely to expose patients to a similar number of techniques as paid apps. Physicians and patients should screen app descriptions for features to promote self-monitoring and provide feedback on discrepancies between behavior and a fluid consumption goal. Copyright © 2016 Elsevier Inc. All rights reserved.

Behavior Change Techniques in Apps for Medication Adherence: A Content Analysis.

PubMed

Morrissey, Eimear C; Corbett, Teresa K; Walsh, Jane C; Molloy, Gerard J

2016-05-01

There are a vast number of smartphone applications (apps) aimed at promoting medication adherence on the market; however, the theory and evidence base in terms of applying established health behavior change techniques underpinning these apps remains unclear. This study aimed to code these apps using the Behavior Change Technique Taxonomy (v1) for the presence or absence of established behavior change techniques. The sample of apps was identified through systematic searches in both the Google Play Store and Apple App Store in February 2015. All apps that fell into the search categories were downloaded for analysis. The downloaded apps were screened with exclusion criteria, and suitable apps were reviewed and coded for behavior change techniques in March 2015. Two researchers performed coding independently. In total, 166 medication adherence apps were identified and coded. The number of behavior change techniques contained in an app ranged from zero to seven (mean=2.77). A total of 12 of a possible 96 behavior change techniques were found to be present across apps. The most commonly included behavior change techniques were "action planning" and "prompt/cues," which were included in 96% of apps, followed by "self-monitoring" (37%) and "feedback on behavior" (36%). The current extent to which established behavior change techniques are used in medication adherence apps is limited. The development of medication adherence apps may not have benefited from advances in the theory and practice of health behavior change. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Expert Involvement and Adherence to Medical Evidence in Medical Mobile Phone Apps: A Systematic Review.

PubMed

Subhi, Yousif; Bube, Sarah Hjartbro; Rolskov Bojsen, Signe; Skou Thomsen, Ann Sofia; Konge, Lars

2015-07-27

Both clinicians and patients use medical mobile phone apps. Anyone can publish medical apps, which leads to contents with variable quality that may have a serious impact on human lives. We herein provide an overview of the prevalence of expert involvement in app development and whether or not app contents adhere to current medical evidence. To systematically review studies evaluating expert involvement or adherence of app content to medical evidence in medical mobile phone apps. We systematically searched 3 databases (PubMed, The Cochrane Library, and EMBASE), and included studies evaluating expert involvement or adherence of app content to medical evidence in medical mobile phone apps. Two authors performed data extraction independently. Qualitative analysis of the included studies was performed. Based on inclusion criteria, 52 studies were included in this review. These studies assessed a total of 6520 apps. Studies dealt with a variety of medical specialties and topics. As much as 28 studies assessed expert involvement, which was found in 9-67% of the assessed apps. Thirty studies (including 6 studies that also assessed expert involvement) assessed adherence of app content to current medical evidence. Thirteen studies found that 10-87% of the assessed apps adhered fully to the compared evidence (published studies, recommendations, and guidelines). Seventeen studies found that none of the assessed apps (n=2237) adhered fully to the compared evidence. Most medical mobile phone apps lack expert involvement and do not adhere to relevant medical evidence.

Beyond symptom monitoring: Consumer needs for bipolar disorder self-management using smartphones.

PubMed

Nicholas, J; Boydell, K; Christensen, H

2017-07-01

To investigate the potential use of smartphone apps to support self-management in young adults with bipolar disorder. We recruited 89 young adults (18-30 years) with bipolar disorder to complete a cross-sectional online survey. The survey contained quantitative and qualitative questions regarding technology use, current use of disorder-management apps, types of apps desired for disorder management, and app features that users would consider important when selecting apps. Results were analysed using descriptive statistics and thematic analysis. Almost all participants used a smartphone daily and 40% currently used apps for disorder management. Of those not currently using apps, 79% indicated they would like to try them. On average, participants rated 61% of the self-management strategies listed as desirable for app support, with sleep-management, understanding early warning signs and triggers, and stay-well plans the most frequently endorsed. App features considered important during app selection were ease-of-use, scientific quality, flexibility/customisation, and data privacy. The results indicate that young adults with bipolar disorder are interested in a wide range of apps for self-management. Participants were interested in apps to support self-management strategies considered clinically important for disorder management. Many of these app needs are currently unmet. Results suggest diversifying and prioritising app capabilities to ensure evidence-based resources for a broader range of app functions are available to consumers. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Consumer Mobile Apps for Potential Drug-Drug Interaction Check: Systematic Review and Content Analysis Using the Mobile App Rating Scale (MARS).

PubMed

Kim, Ben Yb; Sharafoddini, Anis; Tran, Nam; Wen, Emily Y; Lee, Joon

2018-03-28

General consumers can now easily access drug information and quickly check for potential drug-drug interactions (PDDIs) through mobile health (mHealth) apps. With aging population in Canada, more people have chronic diseases and comorbidities leading to increasing numbers of medications. The use of mHealth apps for checking PDDIs can be helpful in ensuring patient safety and empowerment. The aim of this study was to review the characteristics and quality of publicly available mHealth apps that check for PDDIs. Apple App Store and Google Play were searched to identify apps with PDDI functionality. The apps' general and feature characteristics were extracted. The Mobile App Rating Scale (MARS) was used to assess the quality. A total of 23 apps were included for the review-12 from Apple App Store and 11 from Google Play. Only 5 of these were paid apps, with an average price of $7.19 CAD. The mean MARS score was 3.23 out of 5 (interquartile range 1.34). The mean MARS scores for the apps from Google Play and Apple App Store were not statistically different (P=.84). The information dimension was associated with the highest score (3.63), whereas the engagement dimension resulted in the lowest score (2.75). The total number of features per app, average rating, and price were significantly associated with the total MARS score. Some apps provided accurate and comprehensive information about potential adverse drug effects from PDDIs. Given the potentially severe consequences of incorrect drug information, there is a need for oversight to eliminate low quality and potentially harmful apps. Because managing PDDIs is complex in the absence of complete information, secondary features such as medication reminder, refill reminder, medication history tracking, and pill identification could help enhance the effectiveness of PDDI apps. ©Ben YB Kim, Anis Sharafoddini, Nam Tran, Emily Y Wen, Joon Lee. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 28.03.2018.

A standardized review of smartphone applications to promote balance for older adults.

PubMed

Reyes, Angelica; Qin, Pei; Brown, Cary A

2018-03-01

Balance is one of the risk factors for falls in older adults. The use of smartphone applications (apps) related to health (mHealth) is increasing and, while there is potential for apps to be used as a self-managed balance intervention, many healthcare providers are concerned about the content and credibility of mHealth apps overall. This study evaluates the quality of balance promoting apps and identifies strengths and areas of concern to assist healthcare providers in recommending these resources. Balance apps for the general public, offered on the iPhone Operating System (iOS) and Android platforms, were evaluated using the Mobile Application Rating Scale (MARS). Five iOS apps met the inclusion criteria. The mean scores for each of the domains in MARS were: Engagement (3.32), Information (3.7), Functionality (3.8), and Esthetics (3.8). Overall, one app (UStabilize) received a rating of 4.43 in MARS five-point scale, which was considered "good". Other apps in the review demonstrated acceptable quality. The reviewed balance apps targeted to improve or maintain physical balance were of acceptable quality. Apps address many current issues older adults have to accessing rehabilitation services and, as such, may be particularly useful for this group. Future research should focus on assessing and comparing app efficacy. Development of balance apps for the Android platform is also necessary. Implications for Rehabilitation Given the availability and accessibility of various mHealth apps and the increasing mobile device usage among older adults, mobile apps are a promising avenue for delivering rehabilitation interventions, such as balance training, to older adults. Smartphone apps exist for balance training but overall confidence in health apps within the healthcare community is low and rigorous evaluation is required. A range of apps exist that demonstrate acceptable to good quality and stakeholders should work towards having these apps listed in credible mHealth clearinghouses.

Facebook Apps for Smoking Cessation: A Review of Content and Adherence to Evidence-Based Guidelines

PubMed Central

2014-01-01

Background Facebook is the most popular social network site, with over 1 billion users globally. There are millions of apps available within Facebook, many of which address health and health behavior change. Facebook may represent a promising channel to reach smokers with cessation interventions via apps. To date, there have been no published reports about Facebook apps for smoking cessation. Objective The purpose of this study was to review the features and functionality of Facebook apps for smoking cessation and to determine the extent to which they adhere to evidence-based guidelines for tobacco dependence treatment. Methods In August 2013, we searched Facebook and three top Internet search engines using smoking cessation keywords to identify relevant Facebook apps. Resultant apps were screened for eligibility (smoking cessation-related, English language, and functioning). Eligible apps were reviewed by 2 independent coders using a standardized coding scheme. Coding included content features (interactive, informational, and social) and adherence to an established 20-item index (possible score 0-40) derived from the US Public Health Service’s Clinical Practice Guidelines for Treating Tobacco Use and Dependence. Results We screened 22 apps for eligibility; of these, 12 underwent full coding. Only 9 apps were available on Facebook. Facebook apps fell into three broad categories: public pledge to quit (n=3), quit-date–based calculator/tracker (n=4), or a multicomponent quit smoking program (n=2). All apps incorporated interactive, informational, and social features except for two quit-date–based calculator/trackers apps (lacked informational component). All apps allowed app-related posting within Facebook (ie, on self/other Facebook profile), and four had a within-app “community” feature to enable app users to communicate with each other. Adherence index summary scores among Facebook apps were low overall (mean 15.1, SD 7.8, range 7-30), with multicomponent apps scoring the highest. Conclusions There are few smoking cessation apps available within Facebook. Among those available, adherence to cessation treatment guidelines was low. Smoking cessation interventions provided via the Facebook platform are a unique and as yet untapped treatment strategy that can harness existing social support and social networks for quitting. Research is needed to examine whether apps that adhere to clinical practice guidelines for tobacco dependence treatment are more effective in promoting cessation than those that do not. PMID:25205129

Facebook apps for smoking cessation: a review of content and adherence to evidence-based guidelines.

PubMed

Jacobs, Megan A; Cobb, Caroline O; Abroms, Lorien; Graham, Amanda L

2014-09-09

Facebook is the most popular social network site, with over 1 billion users globally. There are millions of apps available within Facebook, many of which address health and health behavior change. Facebook may represent a promising channel to reach smokers with cessation interventions via apps. To date, there have been no published reports about Facebook apps for smoking cessation. The purpose of this study was to review the features and functionality of Facebook apps for smoking cessation and to determine the extent to which they adhere to evidence-based guidelines for tobacco dependence treatment. In August 2013, we searched Facebook and three top Internet search engines using smoking cessation keywords to identify relevant Facebook apps. Resultant apps were screened for eligibility (smoking cessation-related, English language, and functioning). Eligible apps were reviewed by 2 independent coders using a standardized coding scheme. Coding included content features (interactive, informational, and social) and adherence to an established 20-item index (possible score 0-40) derived from the US Public Health Service's Clinical Practice Guidelines for Treating Tobacco Use and Dependence. We screened 22 apps for eligibility; of these, 12 underwent full coding. Only 9 apps were available on Facebook. Facebook apps fell into three broad categories: public pledge to quit (n=3), quit-date-based calculator/tracker (n=4), or a multicomponent quit smoking program (n=2). All apps incorporated interactive, informational, and social features except for two quit-date-based calculator/trackers apps (lacked informational component). All apps allowed app-related posting within Facebook (ie, on self/other Facebook profile), and four had a within-app "community" feature to enable app users to communicate with each other. Adherence index summary scores among Facebook apps were low overall (mean 15.1, SD 7.8, range 7-30), with multicomponent apps scoring the highest. There are few smoking cessation apps available within Facebook. Among those available, adherence to cessation treatment guidelines was low. Smoking cessation interventions provided via the Facebook platform are a unique and as yet untapped treatment strategy that can harness existing social support and social networks for quitting. Research is needed to examine whether apps that adhere to clinical practice guidelines for tobacco dependence treatment are more effective in promoting cessation than those that do not.

Commercially Available Smartphone Apps to Support Postoperative Pain Self-Management: Scoping Review

PubMed Central

Shah, Ushma; Birnie, Kathryn A; Davies-Chalmers, Cleo; Rivera, Jordan; Stinson, Jennifer; Campbell, Fiona

2017-01-01

Background Recently, the use of smartphones to deliver health-related content has experienced rapid growth, with more than 165,000 mobile health (mHealth) apps currently available in the digital marketplace. With 3 out of 4 Canadians currently owning a smartphone, mHealth apps offer opportunities to deliver accessible health-related knowledge and support. Many individuals experience pain after surgery, which can negatively impact their health-related quality of life, including sleep, emotional, and social functioning. Smartphone apps that provide remote real-time monitoring and symptom management have the potential to improve self-management skills in patients experiencing postoperative pain. Increased confidence and practice of self-management skills could contribute to decreased postoperative pain and reduce risk of developing persistent pain. Published reviews of general pain self-management apps demonstrate a lack of evidence-based content, theoretical grounding, and health care professional involvement. However, no review to date has focused on the app marketplace specific for individuals with postoperative pain. Objective The aim of this study was to characterize and critically appraise the content and functionality of commercially available postoperative pain self-management apps. Methods An electronic search and extraction was conducted between December 2016 and March 2017 of the official Canadian app stores for the three major smartphone operating systems (iPhone operating system [iOS], Android, and Windows). Stores were searched separately using predetermined search terms. Two authors screened apps based on information provided in the public app description. Metadata from all included apps were abstracted into a standard spreadsheet. Two authors verified the data with reference to the apps and downloaded apps themselves. The content and functionality of each app as it pertained to postoperative pain self-management was rated. Results A total of 10 apps met the inclusion criteria. All included apps were designed exclusively for the Android platform. Education was the most common self-management feature offered (8/10, 80%), with none of the apps offering features related to goal setting or social support. Overall, no single app was comprehensive in terms of pain self-management content. Five (50%) apps reported the involvement of a health care provider in their development. However, not a single app involved end users in their development, and none of the apps underwent scientific evaluation. Additionally, none of the apps were designed for use in pediatric patients. Conclusions Currently available postoperative pain apps for patients lack evidence-based content, goal setting, and social support functions. There is a need to develop and test comprehensive theory-based apps to support patients with pain self-management care following surgery. PMID:29061558

Commercially Available Smartphone Apps to Support Postoperative Pain Self-Management: Scoping Review.

PubMed

Lalloo, Chitra; Shah, Ushma; Birnie, Kathryn A; Davies-Chalmers, Cleo; Rivera, Jordan; Stinson, Jennifer; Campbell, Fiona

2017-10-23

Recently, the use of smartphones to deliver health-related content has experienced rapid growth, with more than 165,000 mobile health (mHealth) apps currently available in the digital marketplace. With 3 out of 4 Canadians currently owning a smartphone, mHealth apps offer opportunities to deliver accessible health-related knowledge and support. Many individuals experience pain after surgery, which can negatively impact their health-related quality of life, including sleep, emotional, and social functioning. Smartphone apps that provide remote real-time monitoring and symptom management have the potential to improve self-management skills in patients experiencing postoperative pain. Increased confidence and practice of self-management skills could contribute to decreased postoperative pain and reduce risk of developing persistent pain. Published reviews of general pain self-management apps demonstrate a lack of evidence-based content, theoretical grounding, and health care professional involvement. However, no review to date has focused on the app marketplace specific for individuals with postoperative pain. The aim of this study was to characterize and critically appraise the content and functionality of commercially available postoperative pain self-management apps. An electronic search and extraction was conducted between December 2016 and March 2017 of the official Canadian app stores for the three major smartphone operating systems (iPhone operating system [iOS], Android, and Windows). Stores were searched separately using predetermined search terms. Two authors screened apps based on information provided in the public app description. Metadata from all included apps were abstracted into a standard spreadsheet. Two authors verified the data with reference to the apps and downloaded apps themselves. The content and functionality of each app as it pertained to postoperative pain self-management was rated. A total of 10 apps met the inclusion criteria. All included apps were designed exclusively for the Android platform. Education was the most common self-management feature offered (8/10, 80%), with none of the apps offering features related to goal setting or social support. Overall, no single app was comprehensive in terms of pain self-management content. Five (50%) apps reported the involvement of a health care provider in their development. However, not a single app involved end users in their development, and none of the apps underwent scientific evaluation. Additionally, none of the apps were designed for use in pediatric patients. Currently available postoperative pain apps for patients lack evidence-based content, goal setting, and social support functions. There is a need to develop and test comprehensive theory-based apps to support patients with pain self-management care following surgery. ©Chitra Lalloo, Ushma Shah, Kathryn A Birnie, Cleo Davies-Chalmers, Jordan Rivera, Jennifer Stinson, Fiona Campbell. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 23.10.2017.

Keep Using My Health Apps: Discover Users' Perception of Health and Fitness Apps with the UTAUT2 Model.

PubMed

Yuan, Shupei; Ma, Wenjuan; Kanthawala, Shaheen; Peng, Wei

2015-09-01

Health and fitness applications (apps) are one of the major app categories in the current mobile app market. Few studies have examined this area from the users' perspective. This study adopted the Extended Unified Theory of Acceptance and Use of Technology (UTAUT2) Model to examine the predictors of the users' intention to adopt health and fitness apps. A survey (n=317) was conducted with college-aged smartphone users at a Midwestern university in the United States. Performance expectancy, hedonic motivations, price value, and habit were significant predictors of users' intention of continued usage of health and fitness apps. However, effort expectancy, social influence, and facilitating conditions were not found to predict users' intention of continued usage of health and fitness apps. This study extends the UTATU2 Model to the mobile apps domain and provides health professions, app designers, and marketers with the insights of user experience in terms of continuously using health and fitness apps.

Choosing between responsive-design websites versus mobile apps for your mobile behavioral intervention: presenting four case studies.

PubMed

Turner-McGrievy, Gabrielle M; Hales, Sarah B; Schoffman, Danielle E; Valafar, Homay; Brazendale, Keith; Weaver, R Glenn; Beets, Michael W; Wirth, Michael D; Shivappa, Nitin; Mandes, Trisha; Hébert, James R; Wilcox, Sara; Hester, Andrew; McGrievy, Matthew J

2017-06-01

Both mobile apps and responsive-design websites (web apps) can be used to deliver mobile health (mHealth) interventions, but it can be difficult to discern which to use in research. The goal of this paper is to present four case studies from behavioral interventions that developed either a mobile app or a web app for research and present an information table to help researchers determine which mobile option would work best for them. Four behavioral intervention case studies (two developed a mobile app, and two developed a web app) presented include time, cost, and expertise. Considerations for adopting a mobile app or a web app-such as time, cost, access to programmers, data collection, security needs, and intervention components- are presented. Future studies will likely integrate both mobile app and web app modalities. The considerations presented here can help guide researchers on which platforms to choose prior to starting an mHealth intervention.

Current Status of Cardiovascular Disease-Related Smartphone Apps Downloadable in China.

PubMed

Xiao, Qian; Lu, Sai; Wang, Yanling; Sun, Liu; Wu, Ying

2017-03-01

Smartphone apps present a great opportunity for the management of cardiovascular disease (CVD) as the adoption of apps becomes increasingly popular in China. Yet, little is known about the status of CVD-related Smartphone apps in the country. The aim of this study was to examine the current status of CVD-related smartphone apps available for download in China. Using CVD-related keywords written either in Chinese or English, the top 6 most popular smartphone app online stores in China were searched in September 2015. The information accountability of the selected apps was assessed with the Silberg scale. The key topic areas identified from the European Guidelines on cardiovascular disease prevention served to determine information coverage of the top 5 downloaded apps. The average Silberg score of 151 apps was 2.87 (out of 9) with most apps not revealing authors' qualifications and information references. There was also a lack of sponsorship disclosure and information update. Moreover, none of the top 5 downloaded apps covered all key areas of CVD management as recommended by the European Guidelines on cardiovascular disease prevention. There was little evidence of health professionals' involvement in the formation of the CVD-related apps. This study identified areas for improvement concerning information accountability and the scope of coverage of CVD-related apps downloadable in China. The findings may guide the future advancement of CVD-related apps and benefit CVD management in China.

Risk of appendiceal endometriosis among women with deep-infiltrating endometriosis.

PubMed

Moulder, Janelle K; Siedhoff, Matthew T; Melvin, Kathryn L; Jarvis, Elizabeth G; Hobbs, Kumari A; Garrett, Joanne

2017-11-01

To determine whether deep-infiltrating endometriosis (DE) carries an increased risk of appendiceal endometriosis (AppE) as compared with superficial endometriosis or no endometriosis. In a retrospective study, data were obtained by chart review of an internal database for women who underwent coincidental appendectomy during benign gynecologic surgery between July 2009 and February 2014 at a tertiary referral center in the USA. Univariate, bivariate, and regression analyses were performed. The primary exposure was surgically documented endometriosis (DE, superficial, or no endometriosis). The primary outcome was AppE. Endometriosis was diagnosed for 151 (38.2%) of 395 women; 82 (54.3%) had DE. The prevalence of AppE was 13.2% (52/395) overall; 8 (11.6%) of 69 women with superficial endometriosis and 32 (39.0%) of 82 with DE were affected. Frequency of AppE was increased among women with DE, abnormal appendix appearance, and surgical indication (all P<0.001). Women with DE had a 5.9-fold (95% confidence interval [CI] 2.9-11.9) higher risk of AppE compared with women without endometriosis, controlling for appendiceal appearance and surgical indication, and a 2.7-fold (95% CI 1.2-6.2) higher risk of AppE compared with those with superficial endometriosis. Women with DE have increased risk of AppE. Coincidental appendectomy should form part of complete endometriosis excision for these patients. © 2017 International Federation of Gynecology and Obstetrics.

How Do Infant Feeding Apps in China Measure Up? A Content Quality Assessment

PubMed Central

Freeman, Becky; Li, Mu

2017-01-01

Background Globally, with the popularization of mobile phones, the number of health-related mobile phone apps has skyrocketed to 259,000 in 2016. In the digital era, people are accessing health information through their fingertips. In China, there are several apps that claim to provide infant feeding and nutrition guidance. However, the quality of information in those apps has not been extensively assessed. Objective We aimed to assess the quality of Chinese infant feeding apps using comprehensive quality assessment criteria and to explore Chinese mothers’ perceptions on apps’ quality and usability. Methods We searched for free-to-download Chinese infant feeding apps in the iTunes and Android App Stores. We conducted a comprehensive assessment of the accountability, scientific basis, accuracy of information relevant to infant feeding, advertising policy, and functionality and carried out a preliminary screening of infant formula advertisements in the apps. In addition, we also conducted exploratory qualitative research through semistructured interviews with Chinese mothers in Shanghai to elicit their views about the quality of apps. Results A total of 4925 apps were screened, and 26 apps that met the selection criteria were evaluated. All 26 apps were developed by commercial entities, and the majority of them were rated poorly. The highest total score was 62.2 (out of approximately 100) and the lowest was 16.7. In the four quality domains assessed, none of them fulfilled all the accountability criteria. Three out of 26 apps provided information covering the three practices from the World Health Organization’s infant feeding recommendations. Only one app described its advertising policy in its terms of usage. The most common app functionality was a built-in social forum (19/26). Provision of a website link was the least common functionality (2/26). A total of 20 out of 26 apps promoted infant formula banner advertisements on their homepages. In addition, 12 apps included both e-commerce stores and featured infant formula advertisements. In total, 21 mothers were interviewed face-to-face. Mothers highly valued immediate access to parenting information and multifunctionality provided by apps. However, concerns regarding incredible information and commercial activities in apps, as well as the desire for information and support offered by health care professionals were expressed. Conclusions The findings provide valuable information on Chinese infant feeding apps. The results are concerning, particularly with the relative absence of scientific basis and credibility and the large number of commercial advertisements that are displayed. Apps do seem to be able to provide an opportunity for mothers to access health information and support; it is time for tighter controls on content and advertisements. Ongoing app research and development should focus on implementation of a standard framework, which would drive the development of high-quality apps to support healthy infant feeding through cooperation among academics, health professionals, app users, app developers, and government bodies. PMID:29212627

The fitness of apps: a theory-based examination of mobile fitness app usage over 5 months.

PubMed

Herrmann, Lynn Katherine; Kim, Jinsook

2017-01-01

There are thousands of fitness-related smartphone applications ("apps") available for free and purchase, but there is uncertainty if these apps help individuals achieve and maintain personal fitness. Technology usage attrition is also a concern among research studies on health technologies. Usage of three fitness apps was examined over 5 months to assess adherence and effectiveness. Initially, 64 participants downloaded three free apps available on Android and iOS and 47 remained in the study until posttest. With a one group pre-posttest design and checkpoints at months 1, 3, and 5, exercise and exercise with fitness apps were examined in the framework of the Theory of Planned Behavior (TPB) using a validated survey. Apps were selected based on their function from the Functional Triad. Perceived fitness was also measured. T -tests, sign tests, Fisher's exact tests, and linear and logistic regression were used to compare pre to posttests and users to non-users of the apps. Forty-seven participants completed both pre and posttests. Individual item scores indicated no significant change pre to posttest except for decreases observed in usefulness of using apps for exercise (attitude) (-0.78, P<0.01), peer influence on exercise (subjective norm) (-0.51, P<0.05), peer influence on exercise with apps (subjective norm) (-1.02, P<0.01), perceived difficulties in exercising with apps (perceived behavioral control) (-1.29, P<0.001), and the expected frequency of exercise with apps over the next 2 weeks (behavioral intention) (P<0.0001 in a sign test). Subscale total scores indicated significant decreases in subjective norm regarding exercise (-0.72, P<0.05), subjective norm regarding exercise with apps (-1.72, P<0.01), and perceived behavioral control over exercising with apps (-2.56, P<0.01) between pre and posttest. When comparing app users (n=32) to non-users (n=15), there was only a significant difference in subscale total scores at posttest for attitude toward exercising using apps, which was significantly more favorable among users than non-users (32.3 vs . 27.6, P<0.05). Fitness perception did not change over 5 months regarding cardiovascular fitness, strength, endurance, flexibility, or body composition. Technology usage attrition was desirable at 31.9%. App usage and effectiveness appears to have a connection to usefulness (attitude) and to perceived difficulties of exercising using apps (perceived behavioral control). Exercise and exercise using apps are not influenced by peer influence (subjective norm). Intention to exercise using these particular apps decreased (behavioral intention). Those who utilized the apps were more likely to have a positive attitude about the apps. Usefulness and perceived difficulties in particular should be considered with future app development. App usefulness and ease of use may be facilitated by using health behavior theories to guide development.

Effects of Three Motivationally Targeted Mobile Device Applications on Initial Physical Activity and Sedentary Behavior Change in Midlife and Older Adults: A Randomized Trial.

PubMed

King, Abby C; Hekler, Eric B; Grieco, Lauren A; Winter, Sandra J; Sheats, Jylana L; Buman, Matthew P; Banerjee, Banny; Robinson, Thomas N; Cirimele, Jesse

2016-01-01

While there has been an explosion of mobile device applications (apps) promoting healthful behaviors, including physical activity and sedentary patterns, surprisingly few have been based explicitly on strategies drawn from behavioral theory and evidence. This study provided an initial 8-week evaluation of three different customized physical activity-sedentary behavior apps drawn from conceptually distinct motivational frames in comparison with a commercially available control app. Ninety-five underactive adults ages 45 years and older with no prior smartphone experience were randomized to use an analytically framed app, a socially framed app, an affectively framed app, or a diet-tracker control app. Daily physical activity and sedentary behavior were measured using the smartphone's built-in accelerometer and daily self-report measures. Mixed-effects models indicated that, over the 8-week period, the social app users showed significantly greater overall increases in weekly accelerometry-derived moderate to vigorous physical activity relative to the other three arms (P values for between-arm differences = .04-.005; Social vs. Control app: d = 1.05, CI = 0.44,1.67; Social vs. Affect app: d = 0.89, CI = 0.27,1.51; Social vs. Analytic app: d = 0.89, CI = 0.27,1.51), while more variable responses were observed among users of the other two motivationally framed apps. Social app users also had significantly lower overall amounts of accelerometry-derived sedentary behavior relative to the other three arms (P values for between-arm differences = .02-.001; Social vs. Control app: d = 1.10,CI = 0.48,1.72; Social vs. Affect app: d = 0.94, CI = 0.32,1.56; Social vs. Analytic app: d = 1.24, CI = 0.59,1.89). Additionally, Social and Affect app users reported lower overall sitting time compared to the other two arms (P values for between-arm differences < .001; Social vs. Control app: d = 1.59,CI = 0.92, 2.25; Social vs. Analytic app: d = 1.89,CI = 1.17, 2.61; Affect vs. Control app: d = 1.19,CI = 0.56, 1.81; Affect vs. Analytic app: d = 1.41,CI = 0.74, 2.07). The results provide initial support for the use of a smartphone-delivered social frame in the early induction of both physical activity and sedentary behavior changes. The information obtained also sets the stage for further investigation of subgroups that might particularly benefit from different motivationally framed apps in these two key health promotion areas. ClinicalTrials.gov NCT01516411.

Apps to improve diet, physical activity and sedentary behaviour in children and adolescents: a review of quality, features and behaviour change techniques.

PubMed

Schoeppe, Stephanie; Alley, Stephanie; Rebar, Amanda L; Hayman, Melanie; Bray, Nicola A; Van Lippevelde, Wendy; Gnam, Jens-Peter; Bachert, Philip; Direito, Artur; Vandelanotte, Corneel

2017-06-24

The number of commercial apps to improve health behaviours in children is growing rapidly. While this provides opportunities for promoting health, the content and quality of apps targeting children and adolescents is largely unexplored. This review systematically evaluated the content and quality of apps to improve diet, physical activity and sedentary behaviour in children and adolescents, and examined relationships of app quality ratings with number of app features and behaviour change techniques (BCTs) used. Systematic literature searches were conducted in iTunes and Google Play stores between May-November 2016. Apps were included if they targeted children or adolescents, focused on improving diet, physical activity and/or sedentary behaviour, had a user rating of at least 4+ based on at least 20 ratings, and were available in English. App inclusion, downloading and user-testing for quality assessment and content analysis were conducted independently by two reviewers. Spearman correlations were used to examine relationships between app quality, and number of technical app features and BCTs included. Twenty-five apps were included targeting diet (n = 12), physical activity (n = 18) and sedentary behaviour (n = 7). On a 5-point Mobile App Rating Scale (MARS), overall app quality was moderate (total MARS score: 3.6). Functionality was the highest scoring domain (mean: 4.1, SD: 0.6), followed by aesthetics (mean: 3.8, SD: 0.8), and lower scoring for engagement (mean: 3.6, SD: 0.7) and information quality (mean: 2.8, SD: 0.8). On average, 6 BCTs were identified per app (range: 1-14); the most frequently used BCTs were providing 'instructions' (n = 19), 'general encouragement' (n = 18), 'contingent rewards' (n = 17), and 'feedback on performance' (n = 13). App quality ratings correlated positively with numbers of technical app features (rho = 0.42, p < 0.05) and BCTs included (rho = 0.54, p < 0.01). Popular commercial apps to improve diet, physical activity and sedentary behaviour in children and adolescents had moderate quality overall, scored higher in terms of functionality. Most apps incorporated some BCTs and higher quality apps included more app features and BCTs. Future app development should identify factors that promote users' app engagement, be tailored to specific population groups, and be informed by health behaviour theories.

Popular Mobile Phone Apps for Diet and Weight Loss: A Content Analysis.

PubMed

Zaidan, Sarah; Roehrer, Erin

2016-07-11

A review of the literature has revealed that the rates of overweight and obesity have been increasing in Australia over the last two decades and that wellness mobile phone apps play a significant role in monitoring and managing individuals' weight. Although mobile phone app markets (iTunes and Google Play) list thousands of mobile phone health apps, it is not always clear whether those apps are supported by credible sources. Likewise, despite the prevailing use of mobile phone apps to aid with weight management, the usability features of these apps are not well characterized. The research explored how usability taxonomy could inform the popularity of downloaded, socially focused wellness mobile phone apps, in particular weight loss and diet apps. The aim of the study was to investigate the Australian mobile phone app stores (iTunes and Google Play) in order to examine the usability features of the most popular (ie, most downloaded) wellness apps. The design of this study comprises 3 main stages: stage 1, identifying apps; stage 2, development of weight loss and diet evaluation framework; and stage 3, application of the evaluation framework. Each stage includes specific data collection, analysis tools, and techniques. The study has resulted in the development of a justified evaluation framework for weight loss and diet mobile phone apps. Applying the evaluation framework to the identified apps has shown that the most downloaded iTunes and Google Play apps are not necessarily the most usable or effective. In addition, the research found that search algorithms for iTunes and Google Play are biased toward apps' titles and keywords that do not accurately define the real functionality of the app. Moreover, the study has also analyzed the apps' user reviews, which served as justification for the developed evaluation framework. The analysis has shown that ease of use, reminder, bar code scanning, motivation, usable for all, and synchronization are significant attributes that should be included in weight loss and diet mobile phone apps and ultimately in potential weight loss and diet evaluation frameworks.

Health App Use Among US Mobile Phone Owners: A National Survey.

PubMed

Krebs, Paul; Duncan, Dustin T

2015-11-04

Mobile phone health apps may now seem to be ubiquitous, yet much remains unknown with regard to their usage. Information is limited with regard to important metrics, including the percentage of the population that uses health apps, reasons for adoption/nonadoption, and reasons for noncontinuance of use. The purpose of this study was to examine health app use among mobile phone owners in the United States. We conducted a cross-sectional survey of 1604 mobile phone users throughout the United States. The 36-item survey assessed sociodemographic characteristics, history of and reasons for health app use/nonuse, perceived effectiveness of health apps, reasons for stopping use, and general health status. A little over half (934/1604, 58.23%) of mobile phone users had downloaded a health-related mobile app. Fitness and nutrition were the most common categories of health apps used, with most respondents using them at least daily. Common reasons for not having downloaded apps were lack of interest, cost, and concern about apps collecting their data. Individuals more likely to use health apps tended to be younger, have higher incomes, be more educated, be Latino/Hispanic, and have a body mass index (BMI) in the obese range (all P<.05). Cost was a significant concern among respondents, with a large proportion indicating that they would not pay anything for a health app. Interestingly, among those who had downloaded health apps, trust in their accuracy and data safety was quite high, and most felt that the apps had improved their health. About half of the respondents (427/934, 45.7%) had stopped using some health apps, primarily due to high data entry burden, loss of interest, and hidden costs. These findings suggest that while many individuals use health apps, a substantial proportion of the population does not, and that even among those who use health apps, many stop using them. These data suggest that app developers need to better address consumer concerns, such as cost and high data entry burden, and that clinical trials are necessary to test the efficacy of health apps to broaden their appeal and adoption.

Health App Use Among US Mobile Phone Owners: A National Survey

PubMed Central

Duncan, Dustin T

2015-01-01

Background Mobile phone health apps may now seem to be ubiquitous, yet much remains unknown with regard to their usage. Information is limited with regard to important metrics, including the percentage of the population that uses health apps, reasons for adoption/nonadoption, and reasons for noncontinuance of use. Objective The purpose of this study was to examine health app use among mobile phone owners in the United States. Methods We conducted a cross-sectional survey of 1604 mobile phone users throughout the United States. The 36-item survey assessed sociodemographic characteristics, history of and reasons for health app use/nonuse, perceived effectiveness of health apps, reasons for stopping use, and general health status. Results A little over half (934/1604, 58.23%) of mobile phone users had downloaded a health-related mobile app. Fitness and nutrition were the most common categories of health apps used, with most respondents using them at least daily. Common reasons for not having downloaded apps were lack of interest, cost, and concern about apps collecting their data. Individuals more likely to use health apps tended to be younger, have higher incomes, be more educated, be Latino/Hispanic, and have a body mass index (BMI) in the obese range (all P<.05). Cost was a significant concern among respondents, with a large proportion indicating that they would not pay anything for a health app. Interestingly, among those who had downloaded health apps, trust in their accuracy and data safety was quite high, and most felt that the apps had improved their health. About half of the respondents (427/934, 45.7%) had stopped using some health apps, primarily due to high data entry burden, loss of interest, and hidden costs. Conclusions These findings suggest that while many individuals use health apps, a substantial proportion of the population does not, and that even among those who use health apps, many stop using them. These data suggest that app developers need to better address consumer concerns, such as cost and high data entry burden, and that clinical trials are necessary to test the efficacy of health apps to broaden their appeal and adoption. PMID:26537656

There's an app for that: content analysis of paid health and fitness apps.

PubMed

West, Joshua H; Hall, P Cougar; Hanson, Carl L; Barnes, Michael D; Giraud-Carrier, Christophe; Barrett, James

2012-05-14

The introduction of Apple's iPhone provided a platform for developers to design third-party apps, which greatly expanded the functionality and utility of mobile devices for public health. This study provides an overview of the developers' written descriptions of health and fitness apps and appraises each app's potential for influencing behavior change. Data for this study came from a content analysis of health and fitness app descriptions available on iTunes during February 2011. The Health Education Curriculum Analysis Tool (HECAT) and the Precede-Proceed Model (PPM) were used as frameworks to guide the coding of 3336 paid apps. Compared to apps with a cost less than US $0.99, apps exceeding US $0.99 were more likely to be scored as intending to promote health or prevent disease (92.55%, 1925/3336 vs 83.59%, 1411/3336; P<.001), to be credible or trustworthy (91.11%, 1895/3336 vs 86.14%, 1454/3349; P<.001), and more likely to be used personally or recommended to a health care client (72.93%, 1517/2644 vs 66.77%, 1127/2644; P<.001). Apps related to healthy eating, physical activity, and personal health and wellness were more common than apps for substance abuse, mental and emotional health, violence prevention and safety, and sexual and reproductive health. Reinforcing apps were less common than predisposing and enabling apps. Only 1.86% (62/3336) of apps included all 3 factors (ie, predisposing, enabling, and reinforcing). Development efforts could target public health behaviors for which few apps currently exist. Furthermore, practitioners should be cautious when promoting the use of apps as it appears most provide health-related information (predisposing) or make attempts at enabling behavior, with almost none including all theoretical factors recommended for behavior change.

Apps in therapy: occupational therapists' use and opinions.

PubMed

Seifert, Anna M; Stotz, Nicole; Metz, Alexia E

2017-11-01

To gather information on occupational therapy practitioners' use and opinions of apps, an online survey was distributed to occupational therapy practitioners licensed in the state of Ohio. The survey sought information regarding clinical populations and skill areas for which apps are used, potential barriers to use of apps and preferred apps/app features. OTs working in medical and education-based settings and with clients of all ages responded to the survey. Over half (53%) reported not using apps in therapy, with "not having access to the technology at work" being the leading reason endorsed. Of practitioners who did report using apps, the majority used them with ≤25% of their case load and primarily used tablets to do so. Clinicians indicated that they use apps for a wide variety of reasons, including to promote skill building and to support the therapeutic process. Preferred features included the ability to grade difficulty up/down, multiple uses and accurate feedback. Recommendations from peers were the most commonly reported way respondents found new apps. The results suggest that occupational therapy practitioners employ clinical reasoning when implementing apps in therapy. Possible ways to improve access to apps for therapists who would like to implement them are discussed. Implications for Rehabilitation Many occupational therapy practitioners are using apps with at least a portion of their caseloads. Therapists select apps based on peer recommendations, most commonly selecting those which promote skill building and support the therapeutic process. More therapists might make use of apps if potential barriers were reduced or eliminated, including availability of technology in the clinical practice setting, therapist training and education, therapist input into app development and an enhanced evidence base.

Apps and eating disorders: A systematic clinical appraisal

PubMed Central

Rothwell, Emily R.

2015-01-01

ABSTRACT Objective Smartphone applications (apps) are proliferating and health‐related apps are particularly popular. The aim of this study was to identify, characterize, and evaluate the clinical utility of apps designed either for people with eating disorders or for eating disorder professionals. Method A search of the major app stores identified 805 potentially relevant apps, of which 39 were primarily designed for people with eating disorders and five for professionals. Results The apps for people with eating disorders had four main functions. Most common was the provision of advice, the quality of which ranged from sound to potentially harmful. Five apps included self‐assessment tools but only two used methods that would generally be viewed as reliable. Four apps had the self‐monitoring of eating habits as a major feature. Entering information into these apps could be accomplished with varying degrees of ease, but viewing it was more difficult. One app allowed the transfer of information between patients and clinicians. Discussion The enthusiasm for apps outstrips the evidence supporting their use. Given their popularity, it is suggested that clinicians evaluate app use as part of routine assessment. The clinical utility of the existing apps is not clear. Some are capable of tracking key features over time, but none has the functions required for analytic self‐monitoring as in cognitive behavioral treatments. The full potential of apps has yet to be realized. Specialized apps could be designed to augment various forms of treatment, and there is the possibility that they could deliver an entire personalized intervention. © 2015 The Authors. International Journal of Eating Disorders published by Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:1038–1046) PMID:25728705

There is an app for that! The current state of mobile applications (apps) for DSM-5 obsessive-compulsive disorder, posttraumatic stress disorder, anxiety and mood disorders.

PubMed

Van Ameringen, Michael; Turna, Jasmine; Khalesi, Zahra; Pullia, Katrina; Patterson, Beth

2017-06-01

Mental health apps are viewed as a promising modality to extend the reach of mental health care beyond the clinic. They do so by providing a means of assessment, tracking, and treatment through a smartphone. Given that nearly 2/3 of the American population owns a smartphone, mental health apps offer the possibility of overcoming treatment barriers such as geographic location or financial barriers. Unfortunately, the excitement surrounding mental health apps may be premature as the current supporting literature regarding their efficacy is limited. The app marketplace is littered with apps claiming to treat or assess symptoms, but even those created by reputable organizations or those incorporating components of evidence-based treatments have not yet been validated in terms of their efficacy. This review aims to provide a comprehensive review of the current state of the mental health app literature by examining published reports of apps designed for DSM-5 anxiety and mood disorders, OCD, and PTSD. The breadth of apps reviewed includes those oriented around assessment, symptom tracking, and treatment as well as "multipurpose" apps, which incorporate several of these components. This review will also present some of the most popular mental health apps which may have clinical utility and could be prescribed to clients. While we discuss many potential benefits of mental health apps, we focus on a number of issues that the current state of the app literature presents. Overall there is a significant disconnect between app developers, the scientific community and health care, leaving the utility of existing apps questionable. © 2017 Wiley Periodicals, Inc.

Unaddressed privacy risks in accredited health and wellness apps: a cross-sectional systematic assessment.

PubMed

Huckvale, Kit; Prieto, José Tomás; Tilney, Myra; Benghozi, Pierre-Jean; Car, Josip

2015-09-07

Poor information privacy practices have been identified in health apps. Medical app accreditation programs offer a mechanism for assuring the quality of apps; however, little is known about their ability to control information privacy risks. We aimed to assess the extent to which already-certified apps complied with data protection principles mandated by the largest national accreditation program. Cross-sectional, systematic, 6-month assessment of 79 apps certified as clinically safe and trustworthy by the UK NHS Health Apps Library. Protocol-based testing was used to characterize personal information collection, local-device storage and information transmission. Observed information handling practices were compared against privacy policy commitments. The study revealed that 89% (n = 70/79) of apps transmitted information to online services. No app encrypted personal information stored locally. Furthermore, 66% (23/35) of apps sending identifying information over the Internet did not use encryption and 20% (7/35) did not have a privacy policy. Overall, 67% (53/79) of apps had some form of privacy policy. No app collected or transmitted information that a policy explicitly stated it would not; however, 78% (38/49) of information-transmitting apps with a policy did not describe the nature of personal information included in transmissions. Four apps sent both identifying and health information without encryption. Although the study was not designed to examine data handling after transmission to online services, security problems appeared to place users at risk of data theft in two cases. Systematic gaps in compliance with data protection principles in accredited health apps question whether certification programs relying substantially on developer disclosures can provide a trusted resource for patients and clinicians. Accreditation programs should, as a minimum, provide consistent and reliable warnings about possible threats and, ideally, require publishers to rectify vulnerabilities before apps are released.

Amyloid precursor protein regulates migration and metalloproteinase gene expression in prostate cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyazaki, Toshiaki; Ikeda, Kazuhiro; Horie-Inoue, Kuniko

Highlights: • APP knockdown reduced proliferation and migration of prostate cancer cells. • APP knockdown reduced expression of metalloproteinase and EMT-related genes. • APP overexpression promoted LNCaP cell migration. • APP overexpression increased expression of metalloproteinase and EMT-related genes. - Abstract: Amyloid precursor protein (APP) is a type I transmembrane protein, and one of its processed forms, β-amyloid, is considered to play a central role in the development of Alzheimer’s disease. We previously showed that APP is a primary androgen-responsive gene in prostate cancer and that its increased expression is correlated with poor prognosis for patients with prostate cancer. APPmore » has also been implicated in several human malignancies. Nevertheless, the mechanism underlying the pro-proliferative effects of APP on cancers is still not well-understood. In the present study, we explored a pathophysiological role for APP in prostate cancer cells using siRNA targeting APP (siAPP). The proliferation and migration of LNCaP and DU145 prostate cancer cells were significantly suppressed by siAPP. Differentially expressed genes in siAPP-treated cells compared to control siRNA-treated cells were identified by microarray analysis. Notably, several metalloproteinase genes, such as ADAM10 and ADAM17, and epithelial–mesenchymal transition (EMT)-related genes, such as VIM, and SNAI2, were downregulated in siAPP-treated cells as compared to control cells. The expression of these genes was upregulated in LNCaP cells stably expressing APP when compared with control cells. APP-overexpressing LNCaP cells exhibited enhanced migration in comparison to control cells. These results suggest that APP may contribute to the proliferation and migration of prostate cancer cells by modulating the expression of metalloproteinase and EMT-related genes.« less

A Review of Apps for Calming, Relaxation, and Mindfulness Interventions for Pediatric Palliative Care Patients.

PubMed

Weekly, Taelyr; Walker, Nicole; Beck, Jill; Akers, Sean; Weaver, Meaghann

2018-01-26

Patients and families increasingly use mobile apps as a relaxation and distraction intervention for children with complex, chronic medical conditions in the waiting room setting or during inpatient hospitalizations; and yet, there is limited data on app quality assessment or review of these apps for level of engagement, functionality, aesthetics, or applicability for palliative pediatric patients. The pediatric palliative care study team searched smartphone application platforms for apps relevant to calming, relaxation, and mindfulness for pediatric and adolescent patients. Apps were reviewed using a systematic data extraction tool. Validated Mobile Application Rating Scale (MARS) scores were determined by two blinded reviewers. Apps were then characterized by infant, child, adolescent, and adult caregiver group categories. Reviewer discussion resulted in consensus. Sixteen of the 22 apps identified were included in the final analysis. The apps operated on either iOS or Android platforms. All were available in English with four available in Spanish. Apps featured a relaxation approach (12/16), soothing images (8/16), and breathing techniques (8/16). Mood and sleep patterns were the main symptoms targeted by apps. Provision of mobile apps resource summary has the potential to foster pediatric palliative care providers' knowledge of app functionality and applicability as part of ongoing patient care.

Apps for immunization: Leveraging mobile devices to place the individual at the center of care.

PubMed

Wilson, Kumanan; Atkinson, Katherine M; Westeinde, Jacqueline

2015-01-01

Mobile technology and applications (apps) have disrupted several industries including healthcare. The advantage of apps, being personally focused and permitting bidirectional communication, make them well suited to address many immunization challenges. As of April 25, 2015 searching the Android app store with the words 'immunize app' and 'immunization app' in Canada yielded 225 apps. On the Apple App Store a similar search produced 98 results. These include apps that provide immunization related information, permit vaccine tracking both for individuals and for animals, assist with the creation of customized schedules and identification of vaccine clinics and serve as sources of education. The diverse functionality of mobile apps creates the potential for transformation of immunization practice both at a personal level and a system level. For individuals, mobile apps offer the opportunity for better record keeping, assistance with the logistics of vaccination, and novel ways of communicating with and receiving information from public health officials. For the system, mobile apps offer the potential to improve the quality of information residing in immunization information systems and program evaluation, facilitate harmonization of immunization information between individuals, health care providers and public health as well as reduce vaccine hesitancy. As mobile technology continues to rapidly evolve there will emerge new ways in which apps can enhance immunization practice.

Relationship between Student Pharmacist Decision Making Preferences and Experiential Learning.

PubMed

Williams, Charlene R; McLaughlin, Jacqueline E; Cox, Wendy C; Shepherd, Greene

2016-09-25

Objective. To determine if student pharmacists' preferences towards experiential and rational thinking are associated with performance on advanced pharmacy practice experiences (APPEs) and whether thinking style preference changes following APPEs. Methods. The Rational Experiential Inventory (REI), a validated survey of thinking style, was administered to student pharmacists before starting APPEs and re-administered after completing APPEs. APPE grades were compared to initial REI scores. Results. Rational Experiential Inventory scores remained consistent before and after APPEs. Overall, APPE grades were independent of REI scores. In a regression model, the REI experiential score was a significant negative predictor of hospital APPE grades. Conclusion. These findings suggest that overall APPE performance is independent of decision-making preference, and decision-making style does not change following immersion into APPEs. Instead of targeting teaching strategies towards a specific decision-making style, preceptors may use pedagogical approaches that promote sound clinical decision-making skills through critical thinking and reflection.

Relationship between Student Pharmacist Decision Making Preferences and Experiential Learning

PubMed Central

McLaughlin, Jacqueline E.; Cox, Wendy C.; Shepherd, Greene

2016-01-01

Objective. To determine if student pharmacists’ preferences towards experiential and rational thinking are associated with performance on advanced pharmacy practice experiences (APPEs) and whether thinking style preference changes following APPEs. Methods. The Rational Experiential Inventory (REI), a validated survey of thinking style, was administered to student pharmacists before starting APPEs and re-administered after completing APPEs. APPE grades were compared to initial REI scores. Results. Rational Experiential Inventory scores remained consistent before and after APPEs. Overall, APPE grades were independent of REI scores. In a regression model, the REI experiential score was a significant negative predictor of hospital APPE grades. Conclusion. These findings suggest that overall APPE performance is independent of decision-making preference, and decision-making style does not change following immersion into APPEs. Instead of targeting teaching strategies towards a specific decision-making style, preceptors may use pedagogical approaches that promote sound clinical decision-making skills through critical thinking and reflection. PMID:27756927

Psych-related iPhone apps.

PubMed

Harrison, Anthony Mark; Goozee, Rhianna

2014-02-01

iPhone apps are a widely utilised technology that have recently been identified as a useful medium for health research, clinical interventions and education. While some researchers have discussed advances in app technology, others promote specific apps that are not free to access. To our knowledge, no study has conducted a review of current, free iPhone apps related to psychology, psychiatry and mental health. Therefore, we conducted a pilot, web-based review exploring free iPhone apps using a replicable search strategy within the iTunes Store search function. A selection of apps were selected and subjectively assessed in terms of their usability, utility, graphics, and associated costs for the consumer. We concluded that the apps reviewed, though novel, are limited in their scope and utility. We also note a significant gap in more scientific, evidence-based app technology, and pose some pertinent ethical questions when developing future psych-related apps.

Geosocial Networking App Use Among Men Who Have Sex With Men in Serious Romantic Relationships.

PubMed

Macapagal, Kathryn; Coventry, Ryan; Puckett, Jae A; Phillips, Gregory; Mustanski, Brian

2016-08-01

Geosocial networking (GSN) mobile phone applications ("apps") are used frequently among men who have sex with men (MSM) to socialize and meet sexual partners. Though GSN apps are used by some MSM in partnered relationships, little is known about how the use of GSN apps among MSM in serious romantic relationships can influence couples' sexual and relationship health. MSM in serious relationships (N = 323; M age = 40 years) were recruited through a popular GSN app for MSM. Participants completed open-ended items regarding the costs and benefits of app use to their relationships, discussions of app use with their partners, and preferences for relationship education related to app use. Reported benefits of app use included improving sex and communication with one's primary partner and fulfilling unmet sexual needs. Although approximately half had not discussed app use with their partners, citing app use as a "non-issue," many cited various drawbacks to app use, including jealousy and being a distraction from the relationship. Few described sexual health concerns as a drawback to meeting partners through apps. Regarding relationship education preferences, most wanted help with general communication skills and how to express one's sexual needs to a partner. Although GSN app use can enhance relationships and sex among partnered MSM, unclear communication about app use may contribute to negative relationship outcomes and could prevent partners from having sexual needs met. Relationship and sexual health education programs for male couples should consider addressing social media and technology use in their curricula.

Preference and Frequency of Mobile Phone App Use for Drug Information Among Student Pharmacists

PubMed Central

Park, Sharon K.; Purnell, Miriam C.; Freeman, Maisha Kelly; Reese, Racquel V.; Varga, Stefan

2017-01-01

Background: Health care professionals commonly use mobile devices to retrieve drug information (DI) in clinical practice. The preference and frequency of such use by student pharmacists are not well understood. Objective: To investigate the preference and frequency of mobile phone application (app) use for retrieving DI among student pharmacists. Methods: DI specialists from 3 pharmacy schools generated a 13-question survey relating to students’ preference and frequency of DI app use via their mobile phone. The survey was tested and electronically disseminated to all current P1 through P4 students from all 3 schools. Data were collected for student demographics, availability of mobile phone and DI apps, frequency of using DI apps, and whether DI apps were purchased. Data were analyzed descriptively and statistically. Results: About 74% (n = 221) of students reported using their mobile phone apps for retrieving DI. About 95% of the students used 1 to 3 apps for DI purposes and more than 85% used them a few times a week or more. About 17.6% of the students reported purchasing apps for the purpose of finding DI and that purchased apps are more accurate (27.6%), more comprehensive (36.2%), and more current (26.2%), compared with free apps. Conclusions: Student pharmacists used 1 to 3 mobile apps, at least a few times a week for DI. Some students purchased apps for DI use in addition to free subscriptions from their school. Students perceived purchased DI apps being more accurate, more comprehensive, and more up to date than the free apps.

Mobile Health Applications for Pediatric Care: Review and Comparison.

PubMed

Morse, Samantha Sangie; Murugiah, Muthu Kumar; Soh, Yee Chang; Wong, Tin Wui; Ming, Long Chiau

2018-05-01

Despite the surge in mobile health (mHealth) applications (apps) about pediatric care in commercial app stores, to our knowledge, reviews of the quality of such apps are lacking. Consequently, it is a great challenge for health care professionals (HCPs) to identify appropriate and reliable mHealth apps for delivering health care services. Thus, we performed a structured review of the extant literature about mHealth apps in pediatric care and quality assessment of selected apps found in commercial app stores. A review and comparison of mHealth apps in pediatric care found in Google's Play Store (Android system) and Apple's App Store (iOS system) were performed. For the structured review of the available literature, Google Scholar, PubMed, IEEE Xplore Digital Library, and Science Direct online databases were used for the literature search. The assessment criteria used for comparison included requirement for Internet connection, size of application, information on disease, diagnostic tools, medical calculator, information on disease treatments, dosage recommendations, and drug interaction checker. Fifty mHealth apps for general pediatric care and 8 mHealth apps for specific pediatric diseases were discussed in the literature. Of the 90 mHealth apps we reviewed, 27 that fulfilled the study criteria were selected for quality assessment. Medscape, Skyscape, and iGuideline scored the highest (score=7), while PediaBP scored the lowest (score=3). Medscape, Skyscape, and iGuideline are the most comprehensive mHealth apps for HCPs as quick references for pediatric care. More studies about mHealth apps in pediatric care are warranted to ensure the quality and reliability of mHealth apps.

Amyloid precursor protein interaction network in human testis: sentinel proteins for male reproduction.

PubMed

Silva, Joana Vieira; Yoon, Sooyeon; Domingues, Sara; Guimarães, Sofia; Goltsev, Alexander V; da Cruz E Silva, Edgar Figueiredo; Mendes, José Fernando F; da Cruz E Silva, Odete Abreu Beirão; Fardilha, Margarida

2015-01-16

Amyloid precursor protein (APP) is widely recognized for playing a central role in Alzheimer's disease pathogenesis. Although APP is expressed in several tissues outside the human central nervous system, the functions of APP and its family members in other tissues are still poorly understood. APP is involved in several biological functions which might be potentially important for male fertility, such as cell adhesion, cell motility, signaling, and apoptosis. Furthermore, APP superfamily members are known to be associated with fertility. Knowledge on the protein networks of APP in human testis and spermatozoa will shed light on the function of APP in the male reproductive system. We performed a Yeast Two-Hybrid screen and a database search to study the interaction network of APP in human testis and sperm. To gain insights into the role of APP superfamily members in fertility, the study was extended to APP-like protein 2 (APLP2). We analyzed several topological properties of the APP interaction network and the biological and physiological properties of the proteins in the APP interaction network were also specified by gene ontologyand pathways analyses. We classified significant features related to the human male reproduction for the APP interacting proteins and identified modules of proteins with similar functional roles which may show cooperative behavior for male fertility. The present work provides the first report on the APP interactome in human testis. Our approach allowed the identification of novel interactions and recognition of key APP interacting proteins for male reproduction, particularly in sperm-oocyte interaction.

Mobile Health Applications for Diabetes and Endocrinology: Promise and Peril?

PubMed Central

Eng, Donna S; Lee, Joyce M.

2013-01-01

We are in the midst of what some have called a “mobile health revolution”. Medical applications ("apps") for mobile phones are proliferating in the marketplace and clinicians are likely encountering patients with questions about the medical value of these apps. We conducted a review of medical apps focused on endocrine disease. We found a higher percentage of relevant apps in our searches of the iPhone app store compared with the Android marketplace. For our diabetes search in the iPhone store, the majority of apps (33%) focused on health tracking (blood sugars, insulin doses, carbohydrates), requiring manual entry of health data. Only two apps directly inputted blood sugars from glucometers attached to the mobile phone. The remainder of diabetes apps were teaching/training apps (22%), food reference databases (8%), social blogs/forums (5%), and physician directed apps (8%). We found a number of insulin dose calculator apps which technically meet criteria for being a medically regulated mobile application, but did not find evidence for FDA-approval despite their availability to consumers. Far fewer apps were focused on other endocrine disease and included medical reference for the field of endocrinology, access to endocrine journals, height predictors, medication trackers, and fertility apps. Although mobile health apps have great potential for improving chronic disease care, they face a number of challenges including lack of evidence of clinical effectiveness, lack of integration with the health care delivery system, the need for formal evaluation and review and organized searching for health apps, and potential threats to safety and privacy. PMID:23627878

Molecular epidemiological study of Arctic rabies virus isolates from Greenland and comparison with isolates from throughout the Arctic and Baltic regions.

PubMed

Mansfield, K L; Racloz, V; McElhinney, L M; Marston, D A; Johnson, N; Rønsholt, L; Christensen, L S; Neuvonen, E; Botvinkin, A D; Rupprecht, C E; Fooks, A R

2006-03-01

We report a molecular epidemiological study of rabies in Arctic countries by comparing a panel of novel Greenland isolates to a larger cohort of viral sequences from both Arctic and Baltic regions. Rabies virus isolates originating from wildlife (Arctic/red foxes, raccoon-dogs and reindeer), from domestic animals (dogs/cats) and from two human cases were investigated. The resulting 400 bp N-gene sequences were compared with isolates representing neighbouring Arctic or Baltic countries from North America, the former Soviet Union and Europe. Phylogenetic analysis demonstrated similarities between sequences from the Arctic and Arctic-like viruses, which were distinct from rabies isolates originating in the Baltic region of Europe, the Steppes in Russia and from North America. The Arctic-like group consist of isolates from India, Pakistan, southeast Siberia and Japan. The Arctic group was differentiated into two lineages, Arctic 1 and Arctic 2, with good bootstrap support. Arctic 1 is mainly comprised of Canadian isolates with a single fox isolate from Maine in the USA. Arctic 2 was further divided into sub-lineages: 2a/2b. Arctic 2a comprises isolates from the Arctic regions of Yakutia in northeast Siberia and Alaska. Arctic 2b isolates represent a biotype, which is dispersed throughout the Arctic region. The broad distribution of rabies in the Arctic regions including Greenland, Canada and Alaska provides evidence for the movement of rabies across borders.

The Most Popular Smartphone Apps for Weight Loss: A Quality Assessment

PubMed Central

Cade, Janet E

2015-01-01

Background Advancements in mobile phone technology have led to the development of smartphones with the capability to run apps. The availability of a plethora of health- and fitness-related smartphone apps has the potential, both on a clinical and public health level, to facilitate healthy behavior change and weight management. However, current top-rated apps in this area have not been extensively evaluated in terms of scientific quality and behavioral theory evidence base. Objective The purpose of this study was to evaluate the quality of the most popular dietary weight-loss smartphone apps on the commercial market using comprehensive quality assessment criteria, and to quantify the behavior change techniques (BCTs) incorporated. Methods The top 200-rated Health & Fitness category apps from the free and paid sections of Google Play and iTunes App Store in Australia (n=800) were screened in August 2014. To be included in further analysis, an app had to focus on weight management, include a facility to record diet intake (self-monitoring), and be in English. One researcher downloaded and used the eligible apps thoroughly for 5 days and assessed the apps against quality assessment criteria which included the following domains: accountability, scientific coverage and content accuracy of information relevant to weight management, technology-enhanced features, usability, and incorporation of BCTs. For inter-rater reliability purposes, a second assessor provided ratings on 30% of the apps. The accuracy of app energy intake calculations was further investigated by comparison with results from a 3-day weighed food record (WFR). Results Across the eligible apps reviewed (n=28), only 1 app (4%) received full marks for accountability. Overall, apps included an average of 5.1 (SD 2.3) out of 14 technology-enhanced features, and received a mean score of 13.5 (SD 3.7) out of 20 for usability. The majority of apps provided estimated energy requirements (24/28, 86%) and used a food database to calculate energy intake (21/28, 75%). When compared against the WFR, the mean absolute energy difference of apps which featured energy intake calculations (23/28, 82%) was 127 kJ (95% CI -45 to 299). An average of 6.3 (SD 3.7) of 26 BCTs were included. Conclusions Overall, the most popular commercial apps for weight management are suboptimal in quality, given the inadequate scientific coverage and accuracy of weight-related information, and the relative absence of BCTs across the apps reviewed. With the limited regulatory oversight around the quality of these types of apps, this evaluation provides clinicians and consumers an informed view of the highest-quality apps in the current popular app pool appropriate for recommendation and uptake. Further research is necessary to assess the effectiveness of apps for weight management. PMID:26678569

Mobile Apps for Eye Care in Canada: An Analysis of the iTunes Store.

PubMed

Rodin, Alexander; Shachak, Aviv; Miller, Aaron; Akopyan, Vladimir; Semenova, Nataliya

2017-06-14

Mobile phone screens can facilitate stimulation to various components of the visual system and many mobile apps are accepted as a means of providing clinical assessments for the oculo-visual system. Although many of these apps are intended for use in clinical settings, there is a growing number of apps in eye care developed for self-tests and eye exercises for lay people. These and other features, however, have not yet been well described. Our objective was to identify, describe, and categorize mobile apps related to eye care that are available to users in the Canadian iTunes market. We conducted an extensive search of the Apple iTunes Store for apps related to eye care. We used the terms "eye," "eye care," "vision," and "eye test" and included apps that are targeted at both lay people and medical professionals. We excluded apps whose primary function is not related to eye care. Eligible apps were categorized by primary purpose, based on how they were described by their developers in the iTunes Store. Our search yielded 10,657 apps, of which 427 met our inclusion criteria. After removing duplicates, 355 unique apps were subject to further review. We assigned the eligible apps to three distinct categories: 39/355 apps (11.0%) were intended for use by medical professionals, 236 apps (66.5%, 236/355) were intended for use by lay people, and 80 apps (22.5%, 80/355) were intended for marketing eye care and eye-care products. We identified 9 subcategories of apps based on the descriptions of their primary functions. Apps for medical professionals fell into three subcategories: clinical calculators (n=6), clinical diagnostic tools (n=18), and education and networking apps for professionals (n=15). Apps for lay people fell into four subcategories: self-testing (n=153), eye exercises (n=30), patient tools and low vision aids (n=35), and apps for patient education (n=18). Mixed-use apps (n=80) were placed into two subcategories: marketing of individual practitioners or eye-care products (n=72) and marketing of multiple eye-care products or professional services. The most extensive subcategory pertaining to eye care consisted of apps for use by lay people, especially for conducting self-tests (n=236). This study revealed a previously uncharacterized category of apps intended for use by doctors and patients, of which the primary goal is marketing of eye-care services and products (n=80). ©Alexander Rodin, Aviv Shachak, Aaron Miller, Vladimir Akopyan, Nataliya Semenova. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 14.06.2017.

Tracing the Potential Flow of Consumer Data: A Network Analysis of Prominent Health and Fitness Apps

PubMed Central

Held, Fabian P; Bero, Lisa A

2017-01-01

Background A great deal of consumer data, collected actively through consumer reporting or passively through sensors, is shared among apps. Developers increasingly allow their programs to communicate with other apps, sensors, and Web-based services, which are promoted as features to potential users. However, health apps also routinely pose risks related to information leaks, information manipulation, and loss of information. There has been less investigation into the kinds of user data that developers are likely to collect, and who might have access to it. Objective We sought to describe how consumer data generated from mobile health apps might be distributed and reused. We also aimed to outline risks to individual privacy and security presented by this potential for aggregating and combining user data across apps. Methods We purposively sampled prominent health and fitness apps available in the United States, Canada, and Australia Google Play and iTunes app stores in November 2015. Two independent coders extracted data from app promotional materials on app and developer characteristics, and the developer-reported collection and sharing of user data. We conducted a descriptive analysis of app, developer, and user data collection characteristics. Using structural equivalence analysis, we conducted a network analysis of sampled apps’ self-reported sharing of user-generated data. Results We included 297 unique apps published by 231 individual developers, which requested 58 different permissions (mean 7.95, SD 6.57). We grouped apps into 222 app families on the basis of shared ownership. Analysis of self-reported data sharing revealed a network of 359 app family nodes, with one connected central component of 210 app families (58.5%). Most (143/222, 64.4%) of the sampled app families did not report sharing any data and were therefore isolated from each other and from the core network. Fifteen app families assumed more central network positions as gatekeepers on the shortest paths that data would have to travel between other app families. Conclusions This cross-sectional analysis highlights the possibilities for user data collection and potential paths that data is able to travel among a sample of prominent health and fitness apps. While individual apps may not collect personally identifiable information, app families and the partners with which they share data may be able to aggregate consumer data, thus achieving a much more comprehensive picture of the individual consumer. The organizations behind the centrally connected app families represent diverse industries, including apparel manufacturers and social media platforms that are not traditionally involved in health or fitness. This analysis highlights the potential for anticipated and voluntary but also possibly unanticipated and involuntary sharing of user data, validating privacy and security concerns in mobile health. PMID:28659254

A Framework to Assist Health Professionals in Recommending High-Quality Apps for Supporting Chronic Disease Self-Management: Illustrative Assessment of Type 2 Diabetes Apps.

PubMed

Hale, Kelli; Capra, Sandra; Bauer, Judith

2015-09-14

This paper presents an approach to assist health professionals in recommending high quality apps for supporting chronic disease self-management. Most app reviews focus on popularity, aesthetics, functionality, usability, and information quality. There is no doubt these factors are important in selecting trustworthy apps which are appealing to users, but behavioral theory may be also be useful in matching the apps to user needs. The framework developed aims to be methodologically sound, capable of selecting popular apps which include content covered by evidence-based programs, consistent with behavioral theory, as well as a patient-centered approach for matching apps to patients' individual needs. A single disease-type 2 diabetes-was selected to illustrate how the framework can be applied as this was deemed to represent the types of strategies used in many chronic diseases. A systematic approach based on behavioral theory and recommendations from best practice guidelines was developed for matching apps to patients' needs. In March 2014, a series of search strategies was used to identify top-rated iPhone and Android health apps, representing 29 topics from five categories of type 2 diabetes self-management strategies. The topics were chosen from published international guidelines for the management of diabetes. The senior author (KH) assessed the most popular apps found that addressed these topics using the Behavioral Theory Content Survey (BTS), which is based on traditional behavioral theory. A tool to assist decision making when using apps was developed and trialed with health professionals for ease of use and understanding. A total of 14 apps were assessed representing all five topic categories of self-management. Total theoretical scores (BTS scores) were less than 50 on a 100-point scale for all apps. Each app scored less than 50% of the total possible BTS score for all four behavioral theories and for most of the 20 behavioral strategies; however, apps scored higher than 50% of the total possible BTS score for specific strategies related to their primary focus. Our findings suggest that the apps studied would be more effective when used in conjunction with therapy than as stand-alone apps. Apps were categorized according to topic and core intervention strategies. A framework for matching apps to identified patient needs was developed based on app categorization and principles of patient-centered care. The approach was well accepted and understood by a convenience sample of health practitioners. The framework presented can be used by health practitioners to better match apps with client needs. Some apps incorporate highly interactive strategies of behavioral theory, and when used as an adjunct may increase patient participation and the effectiveness of therapy.

Direct to Consumer Mobile Teledermatology Apps: An Exploratory Study.

PubMed

Kochmann, Matthias; Locatis, Craig

2016-08-01

Since 2012, "Direct to Consumer" mobile teledermatology apps have become more available, relinquishing many data collection tasks normally done by healthcare professionals directly to patients. To determine user friendliness, diagnostic quality, and service of commercially available mobile teledermatology apps. All mobile teledermatology apps available at the Apple App Store were reviewed. The two most popular mobile teledermatology apps were identified and tested together with three apps having similar functionality using a single case of a patient who was also examined by a dermatologist in-person. Apps varied in diagnostic scope, data gathering methods, services, rendered results, and in geographic coverage and cost. None of the apps take a history as thoroughly as recommended by textbooks. Key medical questions like current medications and allergies are not asked often. Most apps rendered concordant results, except for the one having the least thorough history taking. Mobile teledermatology application interfaces, services, and cost vary, with some risking medical errors and possible distribution of continuity of care. The American Telemedicine Association's guidelines for teledermatology need to address the use of direct to consumer apps. To protect consumers, app regulation, certification, or guidelines suggesting appropriate development and use might be considered.

Student pharmacists' preparedness to evaluate primary literature pre- and post-Advanced Pharmacy Practice Experiences.

PubMed

Momary, Kathryn M; Lundquist, Lisa M

2017-05-01

The primary objective of this study was to assess the effect of formal primary literature evaluation (PLE) during advanced pharmacy practice experiences (APPEs) on student pharmacists' preparedness and knowledge related to literature evaluation. A perception of preparedness survey and knowledge assessment was given to student pharmacists pre- and post-APPEs. Student pharmacists were also asked to characterize their opportunities for formal PLE during APPEs. Literature evaluation experiences, knowledge base and preparedness data were compared between student pharmacists who completed two or more PLE on APPE and those who did not. A total of 211 student pharmacists completed 529 formal PLE during their APPE experiences. Quiz grades and average perception of preparedness increased significantly from pre- to post-APPE regardless of whether student pharmacists had the opportunity for formal PLE on APPE. Student pharmacists who completed two or more PLE on APPE stated they felt more confident in evaluating primary literature after APPE, had greater post-APPE preparedness scores and a trend towards higher post-APPE quiz scores. APPEs provide an important opportunity for student pharmacists to improve their PLE knowledge. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluating diabetes mobile applications for health literate designs and functionality, 2014.

PubMed

Caburnay, Charlene A; Graff, Kaitlin; Harris, Jenine K; McQueen, Amy; Smith, Madeleine; Fairchild, Maggie; Kreuter, Matthew W

2015-05-07

The expansion of mobile health technologies, particularly for diabetes-related applications (apps), grew exponentially in the past decade. This study sought to examine the extent to which current mobile apps for diabetes have health literate features recommended by participants in an Institute of Medicine Roundtable and compare the health literate features by app cost (free or not). We used diabetes-related keywords to identify diabetes-related apps for iOS devices. A random sample of 110 apps (24% of total number of apps identified) was selected for coding. The coding scheme was adapted from the discussion paper produced by participants in the Institute of Medicine Roundtable. Most diabetes apps in this sample addressed diabetes management and therapeutics, and paid apps were more likely than free apps to use plain language strategies, to label links clearly, and to have at least 1 feature (a "back" button) that helps with the organization. Paid apps were more likely than free apps to use strategies that should be more useful and engaging for people with low health literacy. Future work can investigate ways to make free diabetes mobile apps more user-friendly and accessible.

Apps for asthma self-management: a systematic assessment of content and tools

PubMed Central

2012-01-01

Background Apps have been enthusiastically adopted by the general public. They are increasingly recognized by policy-makers as a potential medium for supporting self-management of long-term conditions. We assessed the degree to which current smartphone and tablet apps for people with asthma offer content and tools of appropriate quality to support asthma self-management. Methods We adapted systematic review methodology to the assessment of apps. We identified English-language asthma apps for all ages through a systematic search of official app stores. We systematically assessed app content using criteria derived from international guidelines and systematic review of strategies for asthma self-management. We covered three domains: comprehensiveness of asthma information, consistency of advice with evidence and compliance with health information best practice principles. Results We identified 103 apps for asthma in English, of which 56 were sources of information about the condition and 47 provided tools for the management of asthma. No apps offered both types of functionality. Only three information apps approached our definition of comprehensiveness of information about asthma. No apps provided advice on lay management of acute asthma that included details of appropriate reliever medication use. In 32 of 72 instances, apps made unequivocal recommendations about strategies for asthma control or prophylaxis that were unsupported by current evidence. Although 90% of apps stated a clear purpose, compliance with other best practice principles for health information was variable. Contact details were located for 55%, funding source for 18% and confidentiality policy for 17%. Conclusions No apps for people with asthma combined reliable, comprehensive information about the condition with supportive tools for self-management. Healthcare professionals considering recommending apps to patients as part of asthma self-management should exercise caution, recognizing that some apps like calculators may be unsafe; that no current app will meet the need of every patient; and that ways of working must be adapted if apps are to be introduced, supported and sustained in routine care. Policy-makers need to consider the potential role for assurance mechanisms in relation to apps. There remains much to be done if apps are to find broad use in clinical practice; clinicians cannot recommend tools that are inaccurate, unsafe or lack an evidence base. PMID:23171675

Apps seeking theories: results of a study on the use of health behavior change theories in cancer survivorship mobile apps.

PubMed

Vollmer Dahlke, Deborah; Fair, Kayla; Hong, Y Alicia; Beaudoin, Christopher E; Pulczinski, Jairus; Ory, Marcia G

2015-03-27

Thousands of mobile health apps are now available for use on mobile phones for a variety of uses and conditions, including cancer survivorship. Many of these apps appear to deliver health behavior interventions but may fail to consider design considerations based in human computer interface and health behavior change theories. This study is designed to assess the presence of and manner in which health behavior change and health communication theories are applied in mobile phone cancer survivorship apps. The research team selected a set of criteria-based health apps for mobile phones and assessed each app using qualitative coding methods to assess the application of health behavior change and communication theories. Each app was assessed using a coding derived from the taxonomy of 26 health behavior change techniques by Abraham and Michie with a few important changes based on the characteristics of mHealth apps that are specific to information processing and human computer interaction such as control theory and feedback systems. A total of 68 mobile phone apps and games built on the iOS and Android platforms were coded, with 65 being unique. Using a Cohen's kappa analysis statistic, the inter-rater reliability for the iOS apps was 86.1 (P<.001) and for the Android apps, 77.4 (P<.001). For the most part, the scores for inclusion of theory-based health behavior change characteristics in the iOS platform cancer survivorship apps were consistently higher than those of the Android platform apps. For personalization and tailoring, 67% of the iOS apps (24/36) had these elements as compared to 38% of the Android apps (12/32). In the area of prompting for intention formation, 67% of the iOS apps (34/36) indicated these elements as compared to 16% (5/32) of the Android apps. Mobile apps are rapidly emerging as a way to deliver health behavior change interventions that can be tailored or personalized for individuals. As these apps and games continue to evolve and include interactive and adaptive sensors and other forms of dynamic feedback, their content and interventional elements need to be grounded in human computer interface design and health behavior and communication theory and practice.

Apps Seeking Theories: Results of a Study on the Use of Health Behavior Change Theories in Cancer Survivorship Mobile Apps

PubMed Central

Fair, Kayla; Hong, Y Alicia; Beaudoin, Christopher E; Pulczinski, Jairus; Ory, Marcia G

2015-01-01

Background Thousands of mobile health apps are now available for use on mobile phones for a variety of uses and conditions, including cancer survivorship. Many of these apps appear to deliver health behavior interventions but may fail to consider design considerations based in human computer interface and health behavior change theories. Objective This study is designed to assess the presence of and manner in which health behavior change and health communication theories are applied in mobile phone cancer survivorship apps. Methods The research team selected a set of criteria-based health apps for mobile phones and assessed each app using qualitative coding methods to assess the application of health behavior change and communication theories. Each app was assessed using a coding derived from the taxonomy of 26 health behavior change techniques by Abraham and Michie with a few important changes based on the characteristics of mHealth apps that are specific to information processing and human computer interaction such as control theory and feedback systems. Results A total of 68 mobile phone apps and games built on the iOS and Android platforms were coded, with 65 being unique. Using a Cohen’s kappa analysis statistic, the inter-rater reliability for the iOS apps was 86.1 (P<.001) and for the Android apps, 77.4 (P<.001). For the most part, the scores for inclusion of theory-based health behavior change characteristics in the iOS platform cancer survivorship apps were consistently higher than those of the Android platform apps. For personalization and tailoring, 67% of the iOS apps (24/36) had these elements as compared to 38% of the Android apps (12/32). In the area of prompting for intention formation, 67% of the iOS apps (34/36) indicated these elements as compared to 16% (5/32) of the Android apps. Conclusions Mobile apps are rapidly emerging as a way to deliver health behavior change interventions that can be tailored or personalized for individuals. As these apps and games continue to evolve and include interactive and adaptive sensors and other forms of dynamic feedback, their content and interventional elements need to be grounded in human computer interface design and health behavior and communication theory and practice. PMID:25830810

MEDication reminder APPs to improve medication adherence in Coronary Heart Disease (MedApp-CHD) Study: a randomised controlled trial protocol

PubMed Central

Chow, Clara K; Thiagalingam, Aravinda; Rogers, Kris; Chalmers, John; Redfern, Julie

2017-01-01

Introduction The growing number of smartphone health applications available in the app stores makes these apps a promising tool to help reduce the global problem of non-adherence to long-term medications. However, to date, there is limited evidence that available medication reminder apps are effective. This study aims to determine the impact of medication reminder apps on adherence to cardiovascular medication when compared with usual care for people with coronary heart disease (CHD) and to determine whether an advanced app compared with a basic app is associated with higher adherence. Methods and analysis Randomised controlled trial with follow-up at 3 months to evaluate the feasibility and effectiveness of medication reminder apps on medication adherence compared with usual care. An estimated sample size of 156 patients with CHD will be randomised to one of three groups (usual care group, basic medication reminder app group and advanced medication reminder app group). The usual care group will receive standard care for CHD with no access to a medication reminder app. The basic medication reminder app group will have access to a medication reminder app with a basic feature of providing simple daily reminders with no interactivity. The advanced medication reminder app group will have access to a medication reminder app with additional interactive and customisable features. The primary outcome is medication adherence measured by the eight-item Morisky Medication Adherence Scale at 3 months. Secondary outcomes include clinical measurements of blood pressure and cholesterol levels, and medication knowledge. A process evaluation will also be performed to assess the feasibility of the intervention by evaluating the acceptability, utility and engagement with the apps. Ethics and dissemination Ethical approval has been obtained from the Western Sydney Local Health Network Human Research Ethics Committee (AU/RED/HREC/1/WMEAD/3). Study findings will be disseminated via usual scientific forums. Trial registration number ACTRN12616000661471; Pre-results PMID:28993388

Mobile Phone Applications for the Care and Prevention of HIV and Other Sexually Transmitted Diseases: A Review

PubMed Central

Pike, Emily C; LeGrand, Sara; Hightow-Weidman, Lisa B

2013-01-01

Background Mobile phone applications (apps) provide a new platform for delivering tailored human immunodeficiency virus (HIV) and sexually transmitted disease (STD) prevention and care. Objective To identify and evaluate currently available mobile phone apps related to the prevention and care of HIV and other STDs. Methods We searched the Apple iTunes and Android Google Play stores for HIV/STD-related apps, excluding apps that exclusively targeted industry, providers, and researchers. Each eligible app was downloaded, tested, and assessed for user ratings and functionality as well as 6 broad content areas of HIV prevention and care: HIV/STD disease knowledge, risk reduction/safer sex, condom promotion, HIV/STD testing information, resources for HIV-positive persons, and focus on key populations. Results Search queries up to May 2012 identified 1937 apps. Of these, 55 unique apps met the inclusion criteria (12 for Android, 29 for iPhone, and 14 for both platforms). Among these apps, 71% provided disease information about HIV/STDs, 36% provided HIV/STD testing information or resources, 29% included information about condom use or assistance locating condoms, and 24% promoted safer sex. Only 6 apps (11%) covered all 4 of these prevention areas. Eight apps (15%) provided tools or resources specifically for HIV/STD positive persons. Ten apps included information for a range of sexual orientations, 9 apps appeared to be designed for racially/ethnically diverse audiences, and 15 apps featured interactive components. Apps were infrequently downloaded (median 100-500 downloads) and not highly rated (average customer rating 3.7 out of 5 stars). Conclusions Most available HIV/STD apps have failed to attract user attention and positive reviews. Public health practitioners should work with app developers to incorporate elements of evidence-based interventions for risk reduction and improve app inclusiveness and interactivity. PMID:23291245

App Usage Factor: A Simple Metric to Compare the Population Impact of Mobile Medical Apps

PubMed Central

Wyatt, Jeremy C

2015-01-01

Background One factor when assessing the quality of mobile apps is quantifying the impact of a given app on a population. There is currently no metric which can be used to compare the population impact of a mobile app across different health care disciplines. Objective The objective of this study is to create a novel metric to characterize the impact of a mobile app on a population. Methods We developed the simple novel metric, app usage factor (AUF), defined as the logarithm of the product of the number of active users of a mobile app with the median number of daily uses of the app. The behavior of this metric was modeled using simulated modeling in Python, a general-purpose programming language. Three simulations were conducted to explore the temporal and numerical stability of our metric and a simulated app ecosystem model using a simulated dataset of 20,000 apps. Results Simulations confirmed the metric was stable between predicted usage limits and remained stable at extremes of these limits. Analysis of a simulated dataset of 20,000 apps calculated an average value for the app usage factor of 4.90 (SD 0.78). A temporal simulation showed that the metric remained stable over time and suitable limits for its use were identified. Conclusions A key component when assessing app risk and potential harm is understanding the potential population impact of each mobile app. Our metric has many potential uses for a wide range of stakeholders in the app ecosystem, including users, regulators, developers, and health care professionals. Furthermore, this metric forms part of the overall estimate of risk and potential for harm or benefit posed by a mobile medical app. We identify the merits and limitations of this metric, as well as potential avenues for future validation and research. PMID:26290093

Consumer Mobile Apps for Potential Drug-Drug Interaction Check: Systematic Review and Content Analysis Using the Mobile App Rating Scale (MARS)

PubMed Central

Kim, Ben YB; Sharafoddini, Anis; Tran, Nam; Wen, Emily Y

2018-01-01

Background General consumers can now easily access drug information and quickly check for potential drug-drug interactions (PDDIs) through mobile health (mHealth) apps. With aging population in Canada, more people have chronic diseases and comorbidities leading to increasing numbers of medications. The use of mHealth apps for checking PDDIs can be helpful in ensuring patient safety and empowerment. Objective The aim of this study was to review the characteristics and quality of publicly available mHealth apps that check for PDDIs. Methods Apple App Store and Google Play were searched to identify apps with PDDI functionality. The apps’ general and feature characteristics were extracted. The Mobile App Rating Scale (MARS) was used to assess the quality. Results A total of 23 apps were included for the review—12 from Apple App Store and 11 from Google Play. Only 5 of these were paid apps, with an average price of $7.19 CAD. The mean MARS score was 3.23 out of 5 (interquartile range 1.34). The mean MARS scores for the apps from Google Play and Apple App Store were not statistically different (P=.84). The information dimension was associated with the highest score (3.63), whereas the engagement dimension resulted in the lowest score (2.75). The total number of features per app, average rating, and price were significantly associated with the total MARS score. Conclusions Some apps provided accurate and comprehensive information about potential adverse drug effects from PDDIs. Given the potentially severe consequences of incorrect drug information, there is a need for oversight to eliminate low quality and potentially harmful apps. Because managing PDDIs is complex in the absence of complete information, secondary features such as medication reminder, refill reminder, medication history tracking, and pill identification could help enhance the effectiveness of PDDI apps. PMID:29592848

Characterizing Geosocial-Networking App Use Among Young Black Men Who Have Sex With Men: A Multi-City Cross-Sectional Survey in the Southern United States.

PubMed

Duncan, Dustin T; Park, Su Hyun; Hambrick, H Rhodes; Dangerfield Ii, Derek T; Goedel, William C; Brewer, Russell; Mgbako, Ofole; Lindsey, Joseph; Regan, Seann D; Hickson, DeMarc A

2018-06-14

Understanding where and how young black men who have sex with men (YBMSM) in the southern United States meet their sexual partners is germane to understanding the underlying factors contributing to the ongoing HIV transmission in this community. Men who have sex with men (MSM) commonly use geosocial networking apps to meet sexual partners. However, there is a lack of literature exploring geosocial networking app use in this particular population. Our aim was to examine the characteristics, preferences, and behaviors of a geographically diverse sample of geosocial networking app-using YBMSM in the southern United States. Data were collected from a sample of 75 YBMSM across three cities (Gulfport, Mississippi; Jackson, Mississippi; and New Orleans, Louisiana). Multiple aspects of geosocial networking app use were assessed, including overall app use, age of participant at first app use, specific apps used, reasons for app use, photos presented on apps, logon times and duration, number of messages sent and received, and characteristics of and behaviors with partners met on apps. Survey measures of app-met partner and sexual behavior characteristics assessed at midpoint (Day 7) and completion visits (Day 14) were compared using McNemar's test or Wilcoxon signed-rank test. In addition, we assessed activity spaces derived from GPS devices that participants wore for 2 weeks. Of the 70 participants who responded to the overall app-use item, almost three-quarters (53/70, 76%) had ever used geosocial networking apps. Jack'd was the most commonly used geosocial networking app (37/53, 70%), followed by Adam4Adam (22/53, 42%), and Grindr (19/53, 36%). The mean and median number of apps used were 4.3 (SD 2.7) and 4.0 (range 0-13), respectively. Most app-using participants displayed their face on the profile picture (35/52, 67%), whereas fewer displayed their bare legs (2/52, 4%) or bare buttocks (or ass; 2/52, 4%). The mean age at the initiation of app use was 20.1 years (SD 2.78) ranging from 13-26 years. Two-thirds (35/53, 66%) of the sample reported using the apps to "kill time" when bored. A minority (9/53, 17%) reported using the apps to meet people to have sex/hook up with. The vast majority of participants reported meeting black partners for sex. Over two-thirds (36/53, 68%) reported that the HIV status of their app-met partners was negative, and 26% (14/53) reported that they did not know their partner's HIV status. There was a significant difference in GPS activity spaces between app using YBMSM compared to nonapp using YBMSM (2719.54 km 2 vs 1855.68 km 2 , P=.011). Use of geosocial networking apps to meet sexual partners among our sample of YBMSM in the southern United States was common, with a diverse range of app use behaviors being reported. Further research should characterize the association between geosocial networking app use and engagement in sexual behaviors that increase risk for HIV acquisition and transmission. In addition, geosocial networking apps present a promising platform for HIV prevention interventions targeting YBMSM who use these apps. ©Dustin T Duncan, Su Hyun Park, H. Rhodes Hambrick, Derek T Dangerfield II, William C Goedel, Russell Brewer, Ofole Mgbako, Joseph Lindsey, Seann D Regan, DeMarc A Hickson. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 14.06.2018.

Quality and Usability of Arthritic Pain Self-Management Apps for Older Adults: A Systematic Review.

PubMed

Bhattarai, Priyanka; Newton-John, T R O; Phillips, Jane L

2018-03-01

To appraise the quality and usability of currently available pain applications that could be used by community-dwelling older adults to self-manage their arthritic pain. A systematic review. Searches were conducted in App Store and Google Play to identify pain self-management apps relevant to arthritic pain management. English language pain management apps providing pain assessment and documentation function and pain management education were considered for inclusion. A quality evaluation audit tool based on the Stanford Arthritis Self-Management Program was developed a priori to evaluate app content quality. The usability of included apps was assessed using an established usability evaluation tool. Out of the 373 apps that were identified, four met the inclusion criteria. The included apps all included a pain assessment and documentation function and instructions on medication use, communication with health professionals, cognitive behavioral therapy-based pain management, and physical exercise. Management of mood, depression, anxiety, and sleep were featured in most apps (N = 3). Three-quarters (N = 3) of the apps fell below the acceptable moderate usability score (≥3), while one app obtained a moderate score (3.2). Few of the currently available pain apps offer a comprehensive pain self-management approach incorporating evidence-based strategies in accordance with the Stanford Arthritis Self-Management Program. The moderate-level usability across the included apps indicates a need to consider the usability needs of the older population in future pain self-management app development endeavors.

Platelet amyloid precursor protein isoform expression in Alzheimer's disease: evidence for peripheral marker.

PubMed

Vignini, A; Sartini, D; Morganti, S; Nanetti, L; Luzzi, S; Provinciali, L; Mazzanti, L; Emanuelli, M

2011-01-01

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by a progressive cognitive and memory decline. Among peripheral markers of AD, great interest has been focused on the amyloid precursor protein (APP). In this regard, platelets represent an important peripheral source of APP since it has been demonstrated that the three major isoforms, that are constituted of 770, 751 and 695 aa residues, are inserted in the membrane of resting platelets. APP 751 and APP 770 contain a Kunitz-type serine protease inhibitor domain (APP KPI) and APP 695 lacks this domain. To address this issue, we first examined the platelet APP isoform mRNAs prospectively as biomarker for the diagnosis of AD by means of real-time quantitative PCR, and then evaluated the correlation between APP mRNA expression levels and cognitive impairment of enrolled subjects. Differential gene expression measurements in the AD patient group (n=18) revealed a significant up-regulation of APP TOT (1.52-fold), APP KPI (1.32-fold), APP 770 (1.33-fold) and APP 751 (1.26-fold) compared to controls (n=22). Moreover, a statistically significant positive correlation was found between APP mRNA levels (TOT, KPI, 770 and 751) and cognitive impairment. Since AD definitive diagnosis still relies on pathological evaluation at autopsy, the present results are consistent with the hypothesis that platelet APP could be considered a potential reliable peripheral marker for studying AD and could contribute to define a signature for the presence of AD pathology.

A quality review of smartphone applications for the management of pain.

PubMed

Portelli, Pamela; Eldred, Clare

2016-08-01

Smartphone applications (apps) are recent innovations that have not been studied extensively. The lack of regulatory body assessing the content of existing apps means that their quality is often unknown. This review aims to assess the quality of smartphone apps that claim to provide information and treatment for pain conditions. It assesses the degree to which apps adhere to evidence-based practices in psychological research for pain management and which stand the best chance of being effective for consumers. Another aim is to identify potential apps health-care professionals may wish to recommend to clients. Pain management apps on the official iPhone and Android stores were searched in January 2014. Those containing a psychological component in the app description were downloaded and rated for quality using a checklist devised by two researchers. The checklist was based on cognitive behavioural therapy (CBT) guidelines since the latter is the most effective intervention for computerized programs. A total of 195 apps met inclusion criteria. Although CBT is a promising alternative to traditional psychological interventions, only six apps endorsed theoretical reference to CBT principles. Existing apps are often constructed by lay people or software developers, with little input from health-care professionals. Pain apps sometimes promise a solution to pain without a consideration of app content. The development of evidence-based apps and rigorous evaluation of any long-term outcomes are important in enhancing understanding of the potential of these apps.

A quality review of smartphone applications for the management of pain

PubMed Central

Portelli, Pamela; Eldred, Clare

2016-01-01

Smartphone applications (apps) are recent innovations that have not been studied extensively. The lack of regulatory body assessing the content of existing apps means that their quality is often unknown. This review aims to assess the quality of smartphone apps that claim to provide information and treatment for pain conditions. It assesses the degree to which apps adhere to evidence-based practices in psychological research for pain management and which stand the best chance of being effective for consumers. Another aim is to identify potential apps health-care professionals may wish to recommend to clients. Pain management apps on the official iPhone and Android stores were searched in January 2014. Those containing a psychological component in the app description were downloaded and rated for quality using a checklist devised by two researchers. The checklist was based on cognitive behavioural therapy (CBT) guidelines since the latter is the most effective intervention for computerized programs. A total of 195 apps met inclusion criteria. Although CBT is a promising alternative to traditional psychological interventions, only six apps endorsed theoretical reference to CBT principles. Existing apps are often constructed by lay people or software developers, with little input from health-care professionals. Pain apps sometimes promise a solution to pain without a consideration of app content. The development of evidence-based apps and rigorous evaluation of any long-term outcomes are important in enhancing understanding of the potential of these apps. PMID:27583140

The fitness of apps: a theory-based examination of mobile fitness app usage over 5 months

PubMed Central

Kim, Jinsook

2017-01-01

Background There are thousands of fitness-related smartphone applications (“apps”) available for free and purchase, but there is uncertainty if these apps help individuals achieve and maintain personal fitness. Technology usage attrition is also a concern among research studies on health technologies. Methods Usage of three fitness apps was examined over 5 months to assess adherence and effectiveness. Initially, 64 participants downloaded three free apps available on Android and iOS and 47 remained in the study until posttest. With a one group pre-posttest design and checkpoints at months 1, 3, and 5, exercise and exercise with fitness apps were examined in the framework of the Theory of Planned Behavior (TPB) using a validated survey. Apps were selected based on their function from the Functional Triad. Perceived fitness was also measured. T-tests, sign tests, Fisher’s exact tests, and linear and logistic regression were used to compare pre to posttests and users to non-users of the apps. Results Forty-seven participants completed both pre and posttests. Individual item scores indicated no significant change pre to posttest except for decreases observed in usefulness of using apps for exercise (attitude) (−0.78, P<0.01), peer influence on exercise (subjective norm) (−0.51, P<0.05), peer influence on exercise with apps (subjective norm) (−1.02, P<0.01), perceived difficulties in exercising with apps (perceived behavioral control) (−1.29, P<0.001), and the expected frequency of exercise with apps over the next 2 weeks (behavioral intention) (P<0.0001 in a sign test). Subscale total scores indicated significant decreases in subjective norm regarding exercise (−0.72, P<0.05), subjective norm regarding exercise with apps (−1.72, P<0.01), and perceived behavioral control over exercising with apps (−2.56, P<0.01) between pre and posttest. When comparing app users (n=32) to non-users (n=15), there was only a significant difference in subscale total scores at posttest for attitude toward exercising using apps, which was significantly more favorable among users than non-users (32.3 vs. 27.6, P<0.05). Fitness perception did not change over 5 months regarding cardiovascular fitness, strength, endurance, flexibility, or body composition. Technology usage attrition was desirable at 31.9%. Conclusions App usage and effectiveness appears to have a connection to usefulness (attitude) and to perceived difficulties of exercising using apps (perceived behavioral control). Exercise and exercise using apps are not influenced by peer influence (subjective norm). Intention to exercise using these particular apps decreased (behavioral intention). Those who utilized the apps were more likely to have a positive attitude about the apps. Usefulness and perceived difficulties in particular should be considered with future app development. App usefulness and ease of use may be facilitated by using health behavior theories to guide development. PMID:28293619

Tracing the Potential Flow of Consumer Data: A Network Analysis of Prominent Health and Fitness Apps.

PubMed

Grundy, Quinn; Held, Fabian P; Bero, Lisa A

2017-06-28

A great deal of consumer data, collected actively through consumer reporting or passively through sensors, is shared among apps. Developers increasingly allow their programs to communicate with other apps, sensors, and Web-based services, which are promoted as features to potential users. However, health apps also routinely pose risks related to information leaks, information manipulation, and loss of information. There has been less investigation into the kinds of user data that developers are likely to collect, and who might have access to it. We sought to describe how consumer data generated from mobile health apps might be distributed and reused. We also aimed to outline risks to individual privacy and security presented by this potential for aggregating and combining user data across apps. We purposively sampled prominent health and fitness apps available in the United States, Canada, and Australia Google Play and iTunes app stores in November 2015. Two independent coders extracted data from app promotional materials on app and developer characteristics, and the developer-reported collection and sharing of user data. We conducted a descriptive analysis of app, developer, and user data collection characteristics. Using structural equivalence analysis, we conducted a network analysis of sampled apps' self-reported sharing of user-generated data. We included 297 unique apps published by 231 individual developers, which requested 58 different permissions (mean 7.95, SD 6.57). We grouped apps into 222 app families on the basis of shared ownership. Analysis of self-reported data sharing revealed a network of 359 app family nodes, with one connected central component of 210 app families (58.5%). Most (143/222, 64.4%) of the sampled app families did not report sharing any data and were therefore isolated from each other and from the core network. Fifteen app families assumed more central network positions as gatekeepers on the shortest paths that data would have to travel between other app families. This cross-sectional analysis highlights the possibilities for user data collection and potential paths that data is able to travel among a sample of prominent health and fitness apps. While individual apps may not collect personally identifiable information, app families and the partners with which they share data may be able to aggregate consumer data, thus achieving a much more comprehensive picture of the individual consumer. The organizations behind the centrally connected app families represent diverse industries, including apparel manufacturers and social media platforms that are not traditionally involved in health or fitness. This analysis highlights the potential for anticipated and voluntary but also possibly unanticipated and involuntary sharing of user data, validating privacy and security concerns in mobile health. ©Quinn Grundy, Fabian P Held, Lisa A Bero. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 28.06.2017.

Attention and Cognitive Bias Modification Apps: Review of the Literature and of Commercially Available Apps

PubMed Central

Ying, JiangBo; Song, Guo; Fung, Daniel SS; Smith, Helen

2018-01-01

Background Automatic processes, such as attentional biases or interpretative biases, have been purported to be responsible for several psychiatric disorders. Recent reviews have highlighted that cognitive biases may be modifiable. Advances in eHealth and mHealth have been harnessed for the delivery of cognitive bias modification. While several studies have evaluated mHealth-based bias modification intervention, no review, to our knowledge, has synthesized the evidence for it. In addition, no review has looked at commercial apps and their functionalities and methods of bias modification. A review is essential in determining whether scientifically validated apps are available commercially and the proportion of commercial apps that have been evaluated scientifically. Objective The objective of this review was primarily to determine the proportion of attention or cognitive bias modification apps that have been evaluated scientifically and secondarily to determine whether the scientifically evaluated apps were commercially available. We also sought to identify commercially available bias modification apps and determine the functionalities of these apps, the methods used for attention or cognitive bias modification, and whether these apps had been evaluated scientifically. Methods To identify apps in the published literature, we searched PubMed, MEDLINE, PsycINFO, and Scopus for studies published from 2000 to April 17, 2018. The search terms used were “attention bias” OR “cognitive bias” AND “smartphone” OR “smartphone application” OR “smartphone app” OR “mobile phones” OR “mobile application” OR mobile app” OR “personal digital assistant.” To identify commercial apps, we conducted a manual cross-sectional search between September 15 and 25, 2017 in the Apple iTunes and Google Play app stores. The search terms used to identify the apps were “attention bias” and “cognitive bias.” We also conducted a manual search on the apps with published evaluations. Results The effectiveness of bias modification was reported in 7 of 8 trials that we identified in the published literature. Only 1 of the 8 previously evaluated apps was commercially available. The 17 commercial apps we identified tended to use either an attention visual search or gamified task. Only 1 commercial app had been evaluated in the published literature. Conclusions This is perhaps the first review to synthesize the evidence for published mHealth attention bias apps. Our review demonstrated that evidence for mHealth attention bias apps is inconclusive, and quite a few commercial apps have not been validated scientifically. PMID:29793899

Global Outreach of a Locally-Developed Mobile Phone App for Undergraduate Psychiatry Education

PubMed Central

Cheok, Christopher CS; Ho, Roger CM

2015-01-01

Background Over the past decade, there have been massive developments in both Web-based and mobile phone technologies. Mobile phones are well accepted by students, trainees, and doctors. A review of the current literature has identified the following specialties that have used mobile phones in education: pediatrics, ophthalmology, nephrology, plastic surgery, orthopedics, pharmacology, and urology. However, to date, there are no published papers examining the application of the latest mobile phone technologies for psychiatry education internationally. Objectives The main objectives of this study are (1) to determine the feasibility and receptiveness of a locally-developed psychiatry mobile phone app and user perspectives (both quantitative and qualitative) towards it, and (2) to determine the receptiveness of a locally-developed app for psychiatry education internationally. Methods A Web-based app that contained textbook contents, videos, and quizzes was developed using HTML5 technologies in 2012. Native apps were subsequently developed in 2013. Information about the apps was disseminated locally to Singaporean medical students, but the respective native apps were made available on the app stores. A user perspective survey was conducted locally to determine student’s perception of the app. Results From the inception of the app until the time of preparation of this manuscript, there have been a cumulative total of 28,500 unique visits of the responsive HTML5 Web-based mobile phone app. There have been a cumulative total of 2200 downloads of the Mastering Psychiatry app from the Apple app store and 7000 downloads of the same app from the Android app store. The initial user perspective survey conducted locally highlighted that approximately a total of 95.2% (177/186) of students felt that having a psychiatry mobile phone app was deemed to be useful. Further chi-squared analysis demonstrated that there was a significant difference between males and females in their perception of having textbook contents in the mobile phone app (χ2 4=12.9, P=.0012). Conclusions To the best of our knowledge, this is the first study to demonstrate the feasibility and global acceptance of a local, self-designed educational app for psychiatry education. Whilst the current research has managed to demonstrate the feasibility and acceptance of such an app, future studies would be warranted to look, in-depth, into whether there are cultural differences in terms of perceptions towards having such an app in psychiatry and what contents different cultures and cohorts of students might want within an app. PMID:27731838

Global Outreach of a Locally-Developed Mobile Phone App for Undergraduate Psychiatry Education.

PubMed

Zhang, Melvyn Wb; Cheok, Christopher Cs; Ho, Roger Cm

2015-06-08

Over the past decade, there have been massive developments in both Web-based and mobile phone technologies. Mobile phones are well accepted by students, trainees, and doctors. A review of the current literature has identified the following specialties that have used mobile phones in education: pediatrics, ophthalmology, nephrology, plastic surgery, orthopedics, pharmacology, and urology. However, to date, there are no published papers examining the application of the latest mobile phone technologies for psychiatry education internationally. The main objectives of this study are (1) to determine the feasibility and receptiveness of a locally-developed psychiatry mobile phone app and user perspectives (both quantitative and qualitative) towards it, and (2) to determine the receptiveness of a locally-developed app for psychiatry education internationally. A Web-based app that contained textbook contents, videos, and quizzes was developed using HTML5 technologies in 2012. Native apps were subsequently developed in 2013. Information about the apps was disseminated locally to Singaporean medical students, but the respective native apps were made available on the app stores. A user perspective survey was conducted locally to determine student's perception of the app. From the inception of the app until the time of preparation of this manuscript, there have been a cumulative total of 28,500 unique visits of the responsive HTML5 Web-based mobile phone app. There have been a cumulative total of 2200 downloads of the Mastering Psychiatry app from the Apple app store and 7000 downloads of the same app from the Android app store. The initial user perspective survey conducted locally highlighted that approximately a total of 95.2% (177/186) of students felt that having a psychiatry mobile phone app was deemed to be useful. Further chi-squared analysis demonstrated that there was a significant difference between males and females in their perception of having textbook contents in the mobile phone app (χ 2 4 =12.9, P=.0012). To the best of our knowledge, this is the first study to demonstrate the feasibility and global acceptance of a local, self-designed educational app for psychiatry education. Whilst the current research has managed to demonstrate the feasibility and acceptance of such an app, future studies would be warranted to look, in-depth, into whether there are cultural differences in terms of perceptions towards having such an app in psychiatry and what contents different cultures and cohorts of students might want within an app.

The Use of Apps for Health in Persons with Multiple Sclerosis, Parkinson's Disease and Stroke - Barriers and Facilitators.

PubMed

Winberg, C; Kylberg, M; Pettersson, C; Harnett, T; Hedvall, P-O; Mattsson, T; Månsson Lexell, E

2017-01-01

The importance of mobile health has increased during recent years but few studies have described the use of apps among persons with neurological disabilities. The aim of this paper was to describe how persons ageing with a neurological disability experience barriers and facilitators in relation to using apps in everyday life. A qualitative approach was used. 16 persons with neurological disorders participated in two group discussions. Data were analyzed by content analysis. The analysis formed four categories; Impairments make apps harder to use, Use of apps is increased by learnability and sharing, Valuating the information in an app, and Apps act supportive and motivating. The participants used apps in the same way as persons without disabilities. Impairments and trustworthiness were perceived as barriers, which need to be acknowledged when developing apps for this population. Use of apps was facilitated by the possibility to share data and to connect with others. Apps may have the potential to improve self-management for persons ageing with disabilities but further research is needed.

The polarity protein Par3 regulates APP trafficking and processing through the endocytic adaptor protein Numb.

PubMed

Sun, Miao; Asghar, Suwaiba Z; Zhang, Huaye

2016-09-01

The processing of amyloid precursor protein (APP) into β-amyloid peptide (Aβ) is a key step in the pathogenesis of Alzheimer's disease (AD), and trafficking dysregulations of APP and its secretases contribute significantly to altered APP processing. Here we show that the cell polarity protein Par3 plays an important role in APP processing and trafficking. We found that the expression of full length Par3 is significantly decreased in AD patients. Overexpression of Par3 promotes non-amyloidogenic APP processing, while depletion of Par3 induces intracellular accumulation of Aβ. We further show that Par3 functions by regulating APP trafficking. Loss of Par3 decreases surface expression of APP by targeting APP to the late endosome/lysosome pathway. Finally, we show that the effects of Par3 are mediated through the endocytic adaptor protein Numb, and Par3 functions by interfering with the interaction between Numb and APP. Together, our studies show a novel role for Par3 in regulating APP processing and trafficking. Copyright © 2016 Elsevier Inc. All rights reserved.

''Are Chemistry Educational Apps Useful?''--A Quantitative Study with Three In-House Apps

ERIC Educational Resources Information Center

Ping, Grace Lee Yuan; Lok, Chang; Yeat, Tan Wei; Cherynn, Tan Jie Ying; Tan, Emelyn Sue Qing

2018-01-01

Three internally developed mobile apps, "3D Sym Op", "SM2 Chem" and "ARMolVis," available for free on both the Apple App Store and Google Play Store were evaluated in seven studies. Each study was a systematic process of Pre-Test, In-lecture App Demo, App Assisted Interactive Tutorials (AAITs) and/or Independent App…

Surfaces modulate beta-amyloid peptide aggregation associated with Alzheimer's disease

NASA Astrophysics Data System (ADS)

Yates, Elizabeth Anne

A hallmark of Alzheimer's disease, a late onset neurodegenerative disease, is the presence of neuritic amyloid plaques deposited within the brain composed of beta-amyloid (Abeta) peptide aggregates. Abeta can aggregate into a variety of polymorphic aggregate structures under different chemical environments, specifically affected by the presence of differing surfaces. There are several point mutations clustered around the central hydrophobic core of Abeta (E22G Arctic mutation, E22K Italian mutation, D23N Iowa mutation, and A21G Flemish mutation). These mutations are associated with hereditary diseases ranging from almost pure cerebral amyloid angiopathy to typical Alzheimer's disease pathology with both plaques and tangles. To determine how these different point mutations, which modify both peptide charge and hydrophobic character, altered Abeta aggregation and morphology under free solution conditions, at an anionic surface/liquid interface and in the presence of supported lipid bilayers, atomic force microscopy was used. Additionally, the non-native conformation of Abeta leads to the formation of nanoscale, toxic aggregates which have been shown to strongly interact with supported lipid bilayers, which may represent a key step in potential toxic mechanisms. Understanding how specific regions of Abeta regulate its aggregation in the absence and presence of surfaces can provide insight into the fundamental interaction of Abeta with cellular surfaces. Specific fragments of Abeta (Abeta1-11, Abeta 1-28, Abeta10-26, Abeta12-24, Abeta 16-22, Abeta22-35, and Abeta1-40), represent a variety of chemically unique regions along Abeta, i.e., the extracellular domain, the central hydrophobic core, and transmembrane domain. Using various scanning probe microscopic techniques, the interaction of these Abeta sequences with lipid membranes was shown to alter aggregate morphology and induce mechanical changes of lipid bilayers compared to aggregates formed under free solution conditions. Lastly, in order to determine how chemical environment can lead to distinct polymorph fibril formation influencing disease pathology, various peptide preparation and fibril growth conditions of Abeta were studied in free solution and with a model lipid membrane.

Public health guidelines for physical activity: is there an app for that? A review of android and apple app stores.

PubMed

Knight, Emily; Stuckey, Melanie I; Prapavessis, Harry; Petrella, Robert J

2015-05-21

Physical activity participation is an important behavior for modifying lifestyle-related disease risk. Mobile health apps for chronic disease management and prevention are being developed at a rapid rate. However, it is unclear whether these apps are evidence-based. Current public health recommendations for physical activity participation for adults highlight the importance of engaging in 150 minutes weekly of purposeful exercise, and muscle strengthening activities on at least 2 days of the week. The aims of the present review were to (1) identify available evidence-based physical activity apps, and (2) identify technological features that could be leveraged to improve health outcomes. iTunes and Google Play mobile app stores were searched using keyword and category searching during a single day (February 18, 2014) for physical activity apps available in English. The description pages of eligible apps were reviewed by 4 independent reviewers for evidence-based content, technological, and descriptive features. An a priori subset of apps was downloaded for further review (n=6 affiliated with a non-commercial agency; n=10 top rated; n=10 random selection), and developers were contacted for information regarding evidence-informed content. The initial search yielded 2400 apps, of which 379 apps (n=206 iTunes; n=173 Google Play) were eligible. Primary results demonstrated no apps (n=0) adhering to evidence-based guidelines for aerobic physical activity, and 7 out of 379 implementing evidence-based guidelines for resistance training physical activity. Technological features of apps included social networking (n=207), pairing with a peripheral health device (n=61), and measuring additional health parameters (n=139). Secondary results revealed 1 app that referenced physical activity guidelines (150 minutes/weekly of exercise), and demonstrated that apps were based on various physical activity reports (n=4) or personal expertise (n=2). The present study demonstrated a shortage of evidence-based physical activity apps. This gap underscores the need for development of evidence-informed mobile apps. Results highlight the opportunity to develop evidence-informed mobile apps that can be used clinically to enhance health outcomes.

Just a fad? Gamification in health and fitness apps.

PubMed

Lister, Cameron; West, Joshua H; Cannon, Ben; Sax, Tyler; Brodegard, David

2014-08-04

Gamification has been a predominant focus of the health app industry in recent years. However, to our knowledge, there has yet to be a review of gamification elements in relation to health behavior constructs, or insight into the true proliferation of gamification in health apps. The objective of this study was to identify the extent to which gamification is used in health apps, and analyze gamification of health and fitness apps as a potential component of influence on a consumer's health behavior. An analysis of health and fitness apps related to physical activity and diet was conducted among apps in the Apple App Store in the winter of 2014. This analysis reviewed a sample of 132 apps for the 10 effective game elements, the 6 core components of health gamification, and 13 core health behavior constructs. A regression analysis was conducted in order to measure the correlation between health behavior constructs, gamification components, and effective game elements. This review of the most popular apps showed widespread use of gamification principles, but low adherence to any professional guidelines or industry standard. Regression analysis showed that game elements were associated with gamification (P<.001). Behavioral theory was associated with gamification (P<.05), but not game elements, and upon further analysis gamification was only associated with composite motivational behavior scores (P<.001), and not capacity or opportunity/trigger. This research, to our knowledge, represents the first comprehensive review of gamification use in health and fitness apps, and the potential to impact health behavior. The results show that use of gamification in health and fitness apps has become immensely popular, as evidenced by the number of apps found in the Apple App Store containing at least some components of gamification. This shows a lack of integrating important elements of behavioral theory from the app industry, which can potentially impact the efficacy of gamification apps to change behavior. Apps represent a very promising, burgeoning market and landscape in which to disseminate health behavior change interventions. Initial results show an abundant use of gamification in health and fitness apps, which necessitates the in-depth study and evaluation of the potential of gamification to change health behaviors.

Health App Use Among Individuals With Symptoms of Depression and Anxiety: A Survey Study With Thematic Coding

PubMed Central

Rubanovich, Caryn Kseniya; Mohr, David C

2017-01-01

Background Researchers have largely turned to commercial app stores, randomized trials, and systematic reviews to make sense of the mHealth landscape. Few studies have approached understanding by collecting information from target end users. The end user perspective is critical as end user interest in and use of mHealth technologies will ultimately drive the efficacy of these tools. Objective The purpose of this study was to obtain information from end users of mHealth technologies to better understand the physical and mental health apps people use and for what purposes. Methods People with depressive or anxious symptoms (N=176) seeking entry into a trial of mental health and well-being apps for Android devices completed online questionnaires assessing depression and anxiety (Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7), past and current mental health treatment-seeking behavior, overall mobile device use, and use of mobile health apps. Participants reported the physical health and mental health apps on their devices and their reasons for using them. Data were extracted from the participant self-reports and apps and app purposes were coded in order to categorize them. Results Participants were largely white, middle-aged females from the Midwest region of the United States recruited via a health care organization and Web-based advertising (135 female, 41 male, mean age 38.64 years, age range 19-75 years.) Over three-quarters (137/176, 77.8%) of participants indicated having a health app on their device. The top 3 kinds of apps were exercise, fitness, and pedometers or heart rate monitoring apps (93/176, 52.8%); diet, food, or calorie counting apps (65/177, 36.9%); and mental health/wellness apps (46/177, 26.1%). The mean number of mobile physical and mental health apps on a participant’s phone was 2.15 (SD 3.195). Of 176 participants, 107 (60.8%) specifically reported the top 5 health apps that they used and their purposes. Across the 107 participants, a total of 285 apps were reported, with 139 being unique apps. The majority of these apps were free (129/139, 92.8%). Almost two-thirds of participants (67/107, 62.6%) reported using health apps at least on a daily basis. Conclusions Among those seeking support for their well-being via physical and mental health apps, people are using a variety of health apps. These people use health apps on a daily basis, especially free apps. The most common reason for using a health app is to track some health-related data; for mental health apps specifically, training or habit building was the most popular reason. Understanding the end user perspective is important because it allows us to build on the foundation of previously established mHealth research and may help guide future work in mHealth. Trial Registration Clinicaltrials.gov NCT02176226; https://clinicaltrials.gov/ct2/show/NCT02176226 (Archived by WebCite at http://www.webcitation.org/6rGc1MGyM) PMID:28645891

Health App Use Among Individuals With Symptoms of Depression and Anxiety: A Survey Study With Thematic Coding.

PubMed

Rubanovich, Caryn Kseniya; Mohr, David C; Schueller, Stephen M

2017-06-23

Researchers have largely turned to commercial app stores, randomized trials, and systematic reviews to make sense of the mHealth landscape. Few studies have approached understanding by collecting information from target end users. The end user perspective is critical as end user interest in and use of mHealth technologies will ultimately drive the efficacy of these tools. The purpose of this study was to obtain information from end users of mHealth technologies to better understand the physical and mental health apps people use and for what purposes. People with depressive or anxious symptoms (N=176) seeking entry into a trial of mental health and well-being apps for Android devices completed online questionnaires assessing depression and anxiety (Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7), past and current mental health treatment-seeking behavior, overall mobile device use, and use of mobile health apps. Participants reported the physical health and mental health apps on their devices and their reasons for using them. Data were extracted from the participant self-reports and apps and app purposes were coded in order to categorize them. Participants were largely white, middle-aged females from the Midwest region of the United States recruited via a health care organization and Web-based advertising (135 female, 41 male, mean age 38.64 years, age range 19-75 years.) Over three-quarters (137/176, 77.8%) of participants indicated having a health app on their device. The top 3 kinds of apps were exercise, fitness, and pedometers or heart rate monitoring apps (93/176, 52.8%); diet, food, or calorie counting apps (65/177, 36.9%); and mental health/wellness apps (46/177, 26.1%). The mean number of mobile physical and mental health apps on a participant's phone was 2.15 (SD 3.195). Of 176 participants, 107 (60.8%) specifically reported the top 5 health apps that they used and their purposes. Across the 107 participants, a total of 285 apps were reported, with 139 being unique apps. The majority of these apps were free (129/139, 92.8%). Almost two-thirds of participants (67/107, 62.6%) reported using health apps at least on a daily basis. Among those seeking support for their well-being via physical and mental health apps, people are using a variety of health apps. These people use health apps on a daily basis, especially free apps. The most common reason for using a health app is to track some health-related data; for mental health apps specifically, training or habit building was the most popular reason. Understanding the end user perspective is important because it allows us to build on the foundation of previously established mHealth research and may help guide future work in mHealth. Clinicaltrials.gov NCT02176226; https://clinicaltrials.gov/ct2/show/NCT02176226 (Archived by WebCite at http://www.webcitation.org/6rGc1MGyM). ©Caryn Kseniya Rubanovich, David C Mohr, Stephen M Schueller. Originally published in JMIR Mental Health (http://mental.jmir.org), 23.06.2017.

Analysis of the amyloid precursor protein role in neuritogenesis reveals a biphasic SH-SY5Y neuronal cell differentiation model.

PubMed

da Rocha, Joana Fernandes; da Cruz e Silva, Odete A B; Vieira, Sandra Isabel

2015-07-01

The existence of an intrinsic programme controlling neuritogenesis and activated during early neuronal differentiation and regeneration stages is well established. However, the identity and role of each molecular player and event, as well as how such a programme is modified by environmental signals, remain a focus of research. The amyloid precursor protein (APP) is a neuromodulator of the developing and mature nervous system, although in a highly complex manner which is far from clear. To study APP-induced neuritogenesis, the retinoic acid (RA)-induced SH-SY5Y cell differentiation model was first minutely characterized in terms of RA dose, morphological outputs and relevant biochemical markers. The findings reported here unveiled two differentiation phases for the 10 μM RA dose: 1-4 (4 days excluded) and 4-8 days, clearly defined by fold increases in the ratio between APP and acetylated Tubulin. Moreover, we describe, for the first time, a unique peak of secreted APP (sAPP)/APP ratio in the first phase. Subsequent APP and sAPP modulations confirmed that a high sAPP/APP ratio potentiates the elongation of smaller processes at the earlier neuritogenic phase. This sAPP/APP ratio drops in the second phase, as holoAPP levels increase to assist the maintenance of the longer neurites, potentially via their stabilization. © 2015 International Society for Neurochemistry.

Perceptions of Smartphone User-Centered Mobile Health Tracking Apps Across Various Chronic Illness Populations: An Integrative Review.

PubMed

Birkhoff, Susan D; Smeltzer, Suzanne C

2017-07-01

This integrative review presents a synthesis of the current qualitative research addressing the motivating factors, usability, and experiences of mobile health tracking applications (apps) across various chronic disease populations. Integrative review of the literature. Databases used to conduct this integrative review included: PubMed Plus, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Google Scholar, Science Direct, and EBSCO megafile. The following search terms were used in all five databases: smartphone apps, apps, mHealth, eHealth, mobile health apps, health tracking apps, user-centered apps, wireless technology, engagement, qualitative, and usability. The initial literature review yielded 689 results. Once inclusion and exclusion criteria were employed, 11 studies met the criteria set forth for this review. The reviewed studies provided insight into users' perceptions, experiences, and motivations to incorporate smartphone mobile health apps into their daily lives when living with chronic illnesses. This review indicates the growing interest in user-centered mobile health tracking apps, but with little understanding of motivating factors that foster sustained app use. Mobile health tracking apps targeted to users with chronic conditions need to have a high level of usability in order to motivate users to sustain engagement with their mobile health tracking app. User-centered mobile health tracking app technology is being used with increasing frequency to potentially provide individualized support to chronic illness populations. © 2017 Sigma Theta Tau International.

Learn CPR You Can Do It!

MedlinePlus

... free mobile training apps for the iPhone and Android Phones. Get the iPhone App Here - Get the Android App Here STANDARD CPR FOR ADULTS - CPR in ... Take the videos wherever you go free. FREE ANDROID APP - Free training app for Android equipped phones. ...

Is There a Good App for That? Evaluating m-Health Apps for Strategies That Promote Pediatric Medication Adherence.

PubMed

Nguyen, Eve; Bugno, Lindsey; Kandah, Cassandra; Plevinsky, Jill; Poulopoulos, Natasha; Wojtowicz, Andrea; Schneider, Kristin L; Greenley, Rachel Neff

2016-11-01

Mobile health medication reminder apps may be a useful supplement to traditional adherence-promotion interventions for pediatric chronic illness populations because they can give real-time reminders and provide education and promote behavior modification (components known to enhance adherence in traditional interventions) in an engaging and developmentally acceptable way. Moreover, apps have the potential to be used by youth and parents, an important consideration given that shared involvement in condition management is associated with better adherence. This study evaluated the content and usability of existing medication reminder apps operating on the Apple platform. Two researchers coded 101 apps on 15 desirable reminder, educational, and behavioral modification features. Usability testing was conducted with the subset of apps (n = 8) that had the greatest number of content features using a validated measure. Apps contained an average of 4.21 of 15 content features, with medication reminder features being more common than either educational or behavioral modification features. Apps most commonly included a medication name storage feature (95%), a time-based reminder feature (87%), and a medication dosage storage feature (68%). Of the eight apps that had the highest number of content features, Mango Health, myRX Planner, and MediSafe evidenced the highest usability ratings. No apps identified were specifically designed for pediatric use. Most apps lacked content known to be useful in traditional pediatric adherence-promotion interventions. Greater attention to educational and behavioral modification features may enhance the usefulness of medication reminder apps for pediatric groups. Collaborations between behavioral medicine providers and app developers may improve the quality of medication reminder apps for use in pediatric populations.

Review and Evaluation of Mindfulness-Based iPhone Apps

PubMed Central

Kavanagh, David J; Hides, Leanne; Stoyanov, Stoyan R

2015-01-01

Background There is growing evidence for the positive impact of mindfulness on wellbeing. Mindfulness-based mobile apps may have potential as an alternative delivery medium for training. While there are hundreds of such apps, there is little information on their quality. Objective This study aimed to conduct a systematic review of mindfulness-based iPhone mobile apps and to evaluate their quality using a recently-developed expert rating scale, the Mobile Application Rating Scale (MARS). It also aimed to describe features of selected high-quality mindfulness apps. Methods A search for “mindfulness” was conducted in iTunes and Google Apps Marketplace. Apps that provided mindfulness training and education were included. Those containing only reminders, timers or guided meditation tracks were excluded. An expert rater reviewed and rated app quality using the MARS engagement, functionality, visual aesthetics, information quality and subjective quality subscales. A second rater provided MARS ratings on 30% of the apps for inter-rater reliability purposes. Results The “mindfulness” search identified 700 apps. However, 94 were duplicates, 6 were not accessible and 40 were not in English. Of the remaining 560, 23 apps met inclusion criteria and were reviewed. The median MARS score was 3.2 (out of 5.0), which exceeded the minimum acceptable score (3.0). The Headspace app had the highest average score (4.0), followed by Smiling Mind (3.7), iMindfulness (3.5) and Mindfulness Daily (3.5). There was a high level of inter-rater reliability between the two MARS raters. Conclusions Though many apps claim to be mindfulness-related, most were guided meditation apps, timers, or reminders. Very few had high ratings on the MARS subscales of visual aesthetics, engagement, functionality or information quality. Little evidence is available on the efficacy of the apps in developing mindfulness. PMID:26290327

The use of mobile apps to improve nutrition outcomes: A systematic literature review.

PubMed

DiFilippo, Kristen N; Huang, Wen-Hao; Andrade, Juan E; Chapman-Novakofski, Karen M

2015-07-01

We conducted a systematic review to determine if the use of nutrition apps resulted in improved outcomes, including knowledge and behavior, among healthy adults. Using app(s), cellular phone, iPads, mobile phone, mobile telephone, smart phone, mobile and mHealth as search terms with diet, food and nutrition as qualifiers we searched PubMed, CINAHL (January 2008-October 2013) and Web of Science (January 2008-January 2014). Inclusion criteria were peer-reviewed randomized controlled trials, non-controlled trials, and cohort studies published in English that used apps to increase nutrition knowledge or improve behavior related to nutrition. Studies that were descriptive, did not include apps, focused on app development, app satisfaction app feasibility, text messaging, or digital photography were excluded. We evaluated article quality using the Academy of Nutrition and Dietetics Evidence Analysis Manual. Data was extracted for knowledge, behavior and weight change. Our initial search identified 12,010 titles from PubMed, 260 from CINAHL and 4762 from Web of Science; of these, only four articles met all search criteria. Positive quality ratings were given to three articles; only one reported knowledge outcomes (non-significant). All four articles evaluated weight loss and suggested an advantage to using nutrition apps. Behavioral changes in reviewed studies included increased adherence to diet monitoring (p < 0.001) and decreased effort to continue diet without app (p = 0.024). Few studies, however, have explored the use of nutrition apps as supportive educational interventions. Most apps focus on weight loss with inconsistent outcomes. We conclude that using apps for education needs additional research which includes behavior theory within the app and improved study design. © The Author(s) 2015.

Characteristics of Men Who Have Sex With Men Who Use Smartphone Geosocial Networking Applications and Implications for HIV Interventions: A Systematic Review and Meta-Analysis.

PubMed

Zou, Huachun; Fan, Song

2017-05-01

Men who have sex with men (MSM) are increasingly using geosocial networking (GSN) mobile applications (apps) designed for MSM to socialize and seek sex partners. We systematically reviewed studies on the characteristics of app-using MSM and the potential feasibility of app-based HIV interventions. Existing studies provided limited parameters to compare characteristics and sexual behaviors between app-using and non-app-using MSM. Available data showed that: compared to non-app-using MSM, app-using MSM tended to be younger, identified as White (in the US and Australia), have higher educational level, report higher incomes, and had a higher rate of engagement in risky sexual behaviors and STIs. Compared to non-app-using MSM, app-using MSM were more likely to have tested for HIV in lifetime (Pooled odds ratio = 2.1, 95 % confidence interval: 1.7-2.6) and have similar HIV prevalence. Up to 676 MSM were recruited in 1 day via apps. In the current literature, there was a lack of (1) comparable parameters to measure sexual risk; (2) large longitudinal studies to clarify behavioral changes and HIV/STI incidence over time, comparing app-using and non-app-using MSM; (3) studies to examine the feasibility and efficacy of using apps to promote HIV testing among MSM; and (4) studies on similar topics from countries other than the US, Australia, and China. MSM GSN apps should be utilized in future HIV prevention and control endeavors. Researchers and health providers should collaborate with GSN app developers on these endeavors.

The promise and peril of mobile health applications for diabetes and endocrinology.

PubMed

Eng, Donna S; Lee, Joyce M

2013-06-01

We are in the midst of what some have called a "mobile health revolution". Medical applications ("apps") for mobile phones are proliferating in the marketplace and clinicians are likely encountering patients with questions about the medical value of these apps. We conducted a review of medical apps focused on endocrine disease. We found a higher percentage of relevant apps in our searches of the iPhone app store compared with the Android marketplace. For our diabetes search in the iPhone store, the majority of apps (33%) focused on health tracking (blood sugars, insulin doses, carbohydrates), requiring manual entry of health data. Only two apps directly inputted blood sugars from glucometers attached to the mobile phone. The remainder of diabetes apps were teaching/training apps (22%), food reference databases (8%), social blogs/forums (5%), and physician directed apps (8%). We found a number of insulin dose calculator apps which technically meet criteria for being a medically regulated mobile application, but did not find evidence for FDA-approval despite their availability to consumers. Far fewer apps were focused on other endocrine disease and included medical reference for the field of endocrinology, access to endocrine journals, height predictors, medication trackers, and fertility apps. Although mobile health apps have great potential for improving chronic disease care, they face a number of challenges including lack of evidence of clinical effectiveness, lack of integration with the health care delivery system, the need for formal evaluation and review and organized searching for health apps, and potential threats to safety and privacy. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Review and Evaluation of Mindfulness-Based iPhone Apps.

PubMed

Mani, Madhavan; Kavanagh, David J; Hides, Leanne; Stoyanov, Stoyan R

2015-08-19

There is growing evidence for the positive impact of mindfulness on wellbeing. Mindfulness-based mobile apps may have potential as an alternative delivery medium for training. While there are hundreds of such apps, there is little information on their quality. This study aimed to conduct a systematic review of mindfulness-based iPhone mobile apps and to evaluate their quality using a recently-developed expert rating scale, the Mobile Application Rating Scale (MARS). It also aimed to describe features of selected high-quality mindfulness apps. A search for "mindfulness" was conducted in iTunes and Google Apps Marketplace. Apps that provided mindfulness training and education were included. Those containing only reminders, timers or guided meditation tracks were excluded. An expert rater reviewed and rated app quality using the MARS engagement, functionality, visual aesthetics, information quality and subjective quality subscales. A second rater provided MARS ratings on 30% of the apps for inter-rater reliability purposes. The "mindfulness" search identified 700 apps. However, 94 were duplicates, 6 were not accessible and 40 were not in English. Of the remaining 560, 23 apps met inclusion criteria and were reviewed. The median MARS score was 3.2 (out of 5.0), which exceeded the minimum acceptable score (3.0). The Headspace app had the highest average score (4.0), followed by Smiling Mind (3.7), iMindfulness (3.5) and Mindfulness Daily (3.5). There was a high level of inter-rater reliability between the two MARS raters. Though many apps claim to be mindfulness-related, most were guided meditation apps, timers, or reminders. Very few had high ratings on the MARS subscales of visual aesthetics, engagement, functionality or information quality. Little evidence is available on the efficacy of the apps in developing mindfulness.

Validated Smartphone-Based Apps for Ear and Hearing Assessments: A Review

PubMed Central

Pallawela, Danuk

2016-01-01

Background An estimated 360 million people have a disabling hearing impairment globally, the vast majority of whom live in low- and middle-income countries (LMICs). Early identification through screening is important to negate the negative effects of untreated hearing impairment. Substantial barriers exist in screening for hearing impairment in LMICs, such as the requirement for skilled hearing health care professionals and prohibitively expensive specialist equipment to measure hearing. These challenges may be overcome through utilization of increasingly available smartphone app technologies for ear and hearing assessments that are easy to use by unskilled professionals. Objective Our objective was to identify and compare available apps for ear and hearing assessments and consider the incorporation of such apps into hearing screening programs Methods In July 2015, the commercial app stores Google Play and Apple App Store were searched to identify apps for ear and hearing assessments. Thereafter, six databases (EMBASE, MEDLINE, Global Health, Web of Science, CINAHL, and mHealth Evidence) were searched to assess which of the apps identified in the commercial review had been validated against gold standard measures. A comparison was made between validated apps. Results App store search queries returned 30 apps that could be used for ear and hearing assessments, the majority of which are for performing audiometry. The literature search identified 11 eligible validity studies that examined 6 different apps. uHear, an app for self-administered audiometry, was validated in the highest number of peer reviewed studies against gold standard pure tone audiometry (n=5). However, the accuracy of uHear varied across these studies. Conclusions Very few of the available apps have been validated in peer-reviewed studies. Of the apps that have been validated, further independent research is required to fully understand their accuracy at detecting ear and hearing conditions. PMID:28582261

Proceedings of the Conference Arctic '85; Civil Engineering in the Artic offshore

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bennett, F.L.; Machemehl, J.L.

1985-01-01

Topics of the 1985 Conference included: Arctic construction, Arctic foundation, Arctic structures, and ocean effects. Arctic terminals and coastal offshore bases, protecting the Arctic environment, and probabilistic methods in Arctic offshore engineering were also discussed. Ice mechanics, marine pipelines in the Arctic, and the role of universities in training civil engineers for Arctic offshore development were highlighted. Sessions on remote sensing, surveying, and mapping were included, and offshore installations in the Bering Sea were discussed. Another topic of discussion was research in Civil Engineering for development of the Arctic offshore. The overall thrust of the conference was the application ofmore » Arctic offshore engineering principles and research in the field of oil and gas exploration and exploitation activity.« less

The Use of Communication Apps by Medical Staff in the Australian Health Care System: Survey Study on Prevalence and Use

PubMed Central

Wickramasinghe, Nilmini; Claydon-Platt, Damian; Balakrishnan, Vikram; Smart, Philip

2018-01-01

Background The use of communication apps on mobile phones offers an efficient, unobtrusive, and portable mode of communication for medical staff. The potential enhancements in patient care and education appear significant, with clinical details able to be shared quickly within multidisciplinary teams, supporting rapid integration of disparate information, and more efficient patient care. However, sharing patient data in this way also raises legal and ethical issues. No data is currently available demonstrating how widespread the use of these apps are, doctor’s attitudes towards them, or what guides clinician choice of app. Objective The objective of this study was to quantify and qualify the use of communication apps among medical staff in clinical situations, their role in patient care, and knowledge and attitudes towards safety, key benefits, potential disadvantages, and policy implications. Methods Medical staff in hospitals across Victoria (Australia) were invited to participate in an anonymous 33-question survey. The survey collected data on respondent’s demographics, their use of communication apps in clinical settings, attitudes towards communication apps, perceptions of data “safety,” and why one communication app was chosen over others. Results Communication apps in Victorian hospitals are in widespread use from students to consultants, with WhatsApp being the primary app used. The median number of messages shared per day was 12, encompassing a range of patient information. All respondents viewed these apps positively in quickly communicating patient information in a clinical setting; however, all had concerns about the privacy implications arising from sharing patient information in this way. In total, 67% (60/90) considered patient data “moderately safe” on these apps, and 50% (46/90) were concerned the use of these apps was inconsistent with current legislation and policy. Apps were more likely to be used if they were fast, easy to use, had an easy login process, and were already in widespread use. Conclusions Communication app use by medical personnel in Victorian hospitals is pervasive. These apps contribute to enhanced communication between medical staff, but their use raises compliance issues, most notably with Australian privacy legislation. Development of privacy-compliant apps such as MedX needs to prioritize a user-friendly interface and market the product as a privacy-compliant comparator to apps previously adapted to health care settings. PMID:29426813

Supply and Demand in mHealth Apps for Persons With Multiple Sclerosis: Systematic Search in App Stores and Scoping Literature Review.

PubMed

Giunti, Guido; Guisado Fernández, Estefanía; Dorronzoro Zubiete, Enrique; Rivera Romero, Octavio

2018-05-23

Multiple sclerosis (MS) is a non-curable chronic inflammatory disease of the central nervous system that affects more than 2 million people worldwide. MS-related symptoms impact negatively on the quality of life of persons with MS, who need to be active in the management of their health. mHealth apps could support these patient groups by offering useful tools, providing reliable information, and monitoring symptoms. A previous study from this group identified needs, barriers, and facilitators for the use of mHealth solutions among persons with MS. It is unknown how commercially available health apps meet these needs. The main objective of this review was to assess how the features present in MS apps meet the reported needs of persons with MS. We followed a combination of scoping review methodology and systematic assessment of features and content of mHealth apps. A search strategy was defined for the two most popular app stores (Google Play and Apple App Store) to identify relevant apps. Reviewers independently conducted a screening process to filter apps according to the selection criteria. Interrater reliability was assessed through the Fleiss-Cohen coefficient (k=.885). Data from the included MS apps were extracted and explored according to classification criteria. An initial total of 581 potentially relevant apps was found. After removing duplicates and applying inclusion and exclusion criteria, 30 unique apps were included in the study. A similar number of apps was found in both stores. The majority of the apps dealt with disease management and disease and treatment information. Most apps were developed by small and medium-sized enterprises, followed by pharmaceutical companies. Patient education and personal data management were among the most frequently included features in these apps. Energy management and remote monitoring were often not present in MS apps. Very few contained gamification elements. Currently available MS apps fail to meet the needs and demands of persons with MS. There is a need for health professionals, researchers, and industry partners to collaborate in the design of mHealth solutions for persons with MS to increase adoption and engagement. ©Guido Giunti, Estefanía Guisado Fernández, Enrique Dorronzoro Zubiete, Octavio Rivera Romero. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 23.05.2018.

Characterization of Apps and Other e-Tools for Medication Use: Insights Into Possible Benefits and Risks.

PubMed

van Kerkhof, Linda Wilhelmina Maria; van der Laar, Catharina Walthera Egbertha; de Jong, Charlie; Weda, Marjolein; Hegger, Ingrid

2016-04-06

In the past years, an enormous increase in the number of available health-related applications (apps) has occurred, from approximately 5800 in 2011 to over 23,000 in 2013, in the iTunes store. However, little is still known regarding the use, possible effectiveness, and risks of these applications. In this study, we focused on apps and other e-tools related to medicine use. A large subset of the general population uses medicines and might benefit from tools that aid in the use of medicine. The aim of the present study was to gain more insight into the characteristics, possible risks, and possible benefits of health apps and e-tools related to medication use. We first made an inventory of apps and other e-tools for medication use (n=116). Tools were coded by two independent researchers, based on the information available in the app stores and websites. Subsequently, for one type of often downloaded apps (aimed at people with diabetes), we investigated users' experiences using an online questionnaire. Results of the inventory show that many apps for medication use are available and that they mainly offer simple functionalities. In line with this, the most experienced benefit by users of apps for regulating blood glucose levels in the online questionnaire was "information quick and conveniently available". Other often experienced benefits were improving health and self-reliance. Results of the inventory show that a minority of the apps for medication use has potentially high risks and for many of the apps it is unclear whether and how personal data are stored. In contrast, online questionnaire among users of apps for blood glucose regulation indicates that they hardly ever experience problems or doubts considering reliability and/or privacy. Although, respondents do mention to experience disadvantages of use due to incomplete apps and apps with poor ease of use. Respondents not using app(s) indicate that they might use them in the future if reliability of the apps and instructions on how to use them are more clear. This study shows that for apps and e-tools related to medicine use a small subset of tools might involve relatively high risks. For the large group of nonmedical devices apps, risks are lower, but risks lie in the enormous availability and low levels of regulation. In addition, both users and nonusers indicated that overall quality of apps (ease of use, completeness, good functionalities) is an issue. Considering that important benefits (eg, improving health and self-reliance) are experienced by many of the respondents using apps for regulating blood glucose levels, improving reliability and quality of apps is likely to have many profits. In addition, creating better awareness regarding the existence and how to use apps will likely improve proper use by more people, enhancing the profits of these tools.

Characterization of Apps and Other e-Tools for Medication Use: Insights Into Possible Benefits and Risks

PubMed Central

van der Laar, Catharina Walthera Egbertha; de Jong, Charlie; Weda, Marjolein; Hegger, Ingrid

2016-01-01

Background In the past years, an enormous increase in the number of available health-related applications (apps) has occurred, from approximately 5800 in 2011 to over 23,000 in 2013, in the iTunes store. However, little is still known regarding the use, possible effectiveness, and risks of these applications. In this study, we focused on apps and other e-tools related to medicine use. A large subset of the general population uses medicines and might benefit from tools that aid in the use of medicine. Objective The aim of the present study was to gain more insight into the characteristics, possible risks, and possible benefits of health apps and e-tools related to medication use. Methods We first made an inventory of apps and other e-tools for medication use (n=116). Tools were coded by two independent researchers, based on the information available in the app stores and websites. Subsequently, for one type of often downloaded apps (aimed at people with diabetes), we investigated users’ experiences using an online questionnaire. Results Results of the inventory show that many apps for medication use are available and that they mainly offer simple functionalities. In line with this, the most experienced benefit by users of apps for regulating blood glucose levels in the online questionnaire was “information quick and conveniently available”. Other often experienced benefits were improving health and self-reliance. Results of the inventory show that a minority of the apps for medication use has potentially high risks and for many of the apps it is unclear whether and how personal data are stored. In contrast, online questionnaire among users of apps for blood glucose regulation indicates that they hardly ever experience problems or doubts considering reliability and/or privacy. Although, respondents do mention to experience disadvantages of use due to incomplete apps and apps with poor ease of use. Respondents not using app(s) indicate that they might use them in the future if reliability of the apps and instructions on how to use them are more clear. Conclusions This study shows that for apps and e-tools related to medicine use a small subset of tools might involve relatively high risks. For the large group of nonmedical devices apps, risks are lower, but risks lie in the enormous availability and low levels of regulation. In addition, both users and nonusers indicated that overall quality of apps (ease of use, completeness, good functionalities) is an issue. Considering that important benefits (eg, improving health and self-reliance) are experienced by many of the respondents using apps for regulating blood glucose levels, improving reliability and quality of apps is likely to have many profits. In addition, creating better awareness regarding the existence and how to use apps will likely improve proper use by more people, enhancing the profits of these tools. PMID:27052946

Mobile applications for diabetics: a systematic review and expert-based usability evaluation considering the special requirements of diabetes patients age 50 years or older.

PubMed

Arnhold, Madlen; Quade, Mandy; Kirch, Wilhelm

2014-04-09

A multitude of mhealth (mobile health) apps have been developed in recent years to support effective self-management of patients with diabetes mellitus type 1 or 2. We carried out a systematic review of all currently available diabetes apps for the operating systems iOS and Android. We considered the number of newly released diabetes apps, range of functions, target user groups, languages, acquisition costs, user ratings, available interfaces, and the connection between acquisition costs and user ratings. Additionally, we examined whether the available applications serve the special needs of diabetes patients aged 50 or older by performing an expert-based usability evaluation. We identified relevant keywords, comparative categories, and their specifications. Subsequently, we performed the app review based on the information given in the Google Play Store, the Apple App Store, and the apps themselves. In addition, we carried out an expert-based usability evaluation based on a representative 10% sample of diabetes apps. In total, we analyzed 656 apps finding that 355 (54.1%) offered just one function and 348 (53.0%) provided a documentation function. The dominating app language was English (85.4%, 560/656), patients represented the main user group (96.0%, 630/656), and the analysis of the costs revealed a trend toward free apps (53.7%, 352/656). The median price of paid apps was €1.90. The average user rating was 3.6 stars (maximum 5). Our analyses indicated no clear differences in the user rating between free and paid apps. Only 30 (4.6%) of the 656 available diabetes apps offered an interface to a measurement device. We evaluated 66 apps within the usability evaluation. On average, apps were rated best regarding the criterion "comprehensibility" (4.0 out of 5.0), while showing a lack of "fault tolerance" (2.8 out of 5.0). Of the 66 apps, 48 (72.7%) offered the ability to read the screen content aloud. The number of functions was significantly negative correlated with usability. The presence of documentation and analysis functions reduced the usability score significantly by 0.36 and 0.21 points. A vast number of diabetes apps already exist, but the majority offer similar functionalities and combine only one to two functions in one app. Patients and physicians alike should be involved in the app development process to a greater extent. We expect that the data transmission of health parameters to physicians will gain more importance in future applications. The usability of diabetes apps for patients aged 50 or older was moderate to good. But this result applied mainly to apps offering a small range of functions. Multifunctional apps performed considerably worse in terms of usability. Moreover, the presence of a documentation or analysis function resulted in significantly lower usability scores. The operability of accessibility features for diabetes apps was quite limited, except for the feature "screen reader".

Content, Usability, and Utilization of Plain Language in Breast Cancer Mobile Phone Apps: A Systematic Analysis

PubMed Central

Shah, Sayyed Fawad Ali; West, Andrew J; Bentley, Joshua M; Caburnay, Charlene A; Kreuter, Matthew W; Kinney, Anita Y

2017-01-01

Background Breast cancer is one of the leading contributors to preventable illness and death among women. Although mobile phone apps provide unprecedented opportunity to engage women along the cancer continuum, little is known about the availability, content, and usability of breast cancer mobile phone apps. Objective This study analyzed the content and adherence to literate design standards of all breast cancer-related apps available on the App Store and Google Play, as well as the relationship between their content, user ratings, and price. Methods Following identification and downloading of all available breast cancer mobile phone apps in October 2015, 101 apps were confirmed as focusing on breast cancer. Based on prior research, we adapted and applied a content analysis scheme that was specific to breast cancer apps, including their main purpose, relevance to the cancer care continuum, and adherence to usability standards outlined by the Institute of Medicine (IOM). Results The most common aim of apps was educational (73/101, 72.3%), followed by behavior change (24/101, 23.9%), fundraising (20/101, 19.8%), and advocacy (14/101, 13.9%). On the cancer continuum, primary prevention (strategies to prevent cancer cells from occurring) was mentioned in almost one-third of the apps (30/101, 29.7%). Less than half of the apps (46/101, 45.5%) presented information about mammography and/or breast clinical exam, and 53 apps (52.5%) discussed breast self-exam (which is no longer recommended). Symptoms of cancer prediagnosis, such as a lump, were discussed in almost half of the apps (48/101, 47.5%) and a similar number of apps included information about genetic risk for breast cancer (47/101, 46.5%). Information about breast cancer diagnosis was included in 42 apps (41.58%) and 43 (42.6%) apps discussed treatment options. Survivorship issues were addressed in 17 (16.8%) apps. Only one (1.0%) app discussed hospice. Adherence to usability recommendations was low. The median composite score was 3 (mean 2.60, SD 1.20) of the six recommended usability items. With eight plain language items, the median of the composite health literacy score was 5 (mean 5.06, SD 2.00). Most apps did not use easy-to-understand words (44/101, 43.6%) and few (24/101, 23.8%) defined key terms. Conclusions Current breast cancer apps provide important information about breast cancer, but the most common topic covered is breast self-examination, a non-evidence-based screening strategy. Apps that focus on evidence-based strategies on the cancer continuum are needed, with a notable pressing need for apps that would address survivorship and end of life. Finally, developers of breast cancer apps should adhere to IOM standards to meet the needs of diverse populations and reduce current disparities. PMID:28288954

The Kunitz-protease inhibitor domain in amyloid precursor protein reduces cellular mitochondrial enzymes expression and function.

PubMed

Chua, Li-Min; Lim, Mei-Li; Wong, Boon-Seng

2013-08-09

Mitochondrial dysfunction is a prominent feature of Alzheimer's disease (AD) and this can be contributed by aberrant metabolic enzyme function. But, the mechanism causing this enzymatic impairment is unclear. Amyloid precursor protein (APP) is known to be alternatively spliced to produce three major isoforms in the brain (APP695, APP751, APP770). Both APP770 and APP751 contain the Kunitz Protease Inhibitory (KPI) domain, but the former also contain an extra OX-2 domain. APP695 on the other hand, lacks both domains. In AD, up-regulation of the KPI-containing APP isoforms has been reported. But the functional contribution of this elevation is unclear. In the present study, we have expressed and compared the effect of the non-KPI containing APP695 and the KPI-containing APP751 on mitochondrial function. We found that the KPI-containing APP751 significantly decreased the expression of three major mitochondrial metabolic enzymes; citrate synthase, succinate dehydrogenase and cytochrome c oxidase (COX IV). This reduction lowers the NAD(+)/NADH ratio, COX IV activity and mitochondrial membrane potential. Overall, this study demonstrated that up-regulation of the KPI-containing APP isoforms is likely to contribute to the impairment of metabolic enzymes and mitochondrial function in AD. Copyright © 2013 Elsevier Inc. All rights reserved.

A content analysis of precede-proceed constructs in stress management mobile apps

PubMed Central

Wilkinson, Jessica; West, Joshua H.; Bernhardt, Jay M.

2016-01-01

Background The emergence of Apple’s iPhone provides a platform for freelance developers to design third party apps, which greatly expands the functionality and utility of mobile devices for stress management. This study provides a basic overview of the stress management apps under the health and fitness category of the Apple App store and appraises each app’s potential for influencing behavior change. Methods Data for this study came from a content analysis of health and fitness app descriptions available in the App Store on iTunes. Trained research assistants used the Precede-Proceed Model (PPM) as a framework to guide the coding of paid stress management apps and to evaluate each app’s potential for effecting health behavior change. Results Most apps were rated as being plausible (96.9%) and intending to address stress management (98.5%), but only 63.3% were rated as recommendable to others for their use. Reinforcing apps were less common than predisposing and enabling apps. Less than one percent (0.39%) of apps included all three factors (predisposing, enabling and reinforcing). Conclusions Practitioners should be cautious when promoting the use of stress management apps, as most provide only health-related information (predisposing) or suggestions for enabling behavior, but almost none include all three theoretical factors recommended for behavior change. PMID:28293583

Many Mobile Health Apps Target High-Need, High-Cost Populations, But Gaps Remain.

PubMed

Singh, Karandeep; Drouin, Kaitlin; Newmark, Lisa P; Lee, JaeHo; Faxvaag, Arild; Rozenblum, Ronen; Pabo, Erika A; Landman, Adam; Klinger, Elissa; Bates, David W

2016-12-01

With rising smartphone ownership, mobile health applications (mHealth apps) have the potential to support high-need, high-cost populations in managing their health. While the number of available mHealth apps has grown substantially, no clear strategy has emerged on how providers should evaluate and recommend such apps to patients. Key stakeholders, including medical professional societies, insurers, and policy makers, have largely avoided formally recommending apps, which forces patients to obtain recommendations from other sources. To help stakeholders overcome barriers to reviewing and recommending apps, we evaluated 137 patient-facing mHealth apps-those intended for use by patients to manage their health-that were highly rated by consumers and recommended by experts and that targeted high-need, high-cost populations. We found that there is a wide variety of apps in the marketplace but that few apps address the needs of the patients who could benefit the most. We also found that consumers' ratings were poor indications of apps' clinical utility or usability and that most apps did not respond appropriately when a user entered potentially dangerous health information. Going forward, data privacy and security will continue to be major concerns in the dissemination of mHealth apps. Project HOPE—The People-to-People Health Foundation, Inc.

Geosocial Networking App Use Among Men Who Have Sex With Men in Serious Romantic Relationships

PubMed Central

Coventry, Ryan; Puckett, Jae A.; Phillips, Gregory; Mustanski, Brian

2016-01-01

Geosocial networking (GSN) mobile phone applications (“apps”) are used frequently among men who have sex with men (MSM) to socialize and meet sexual partners. Though GSN apps are used by some MSM in partnered relationships, little is known about how the use of GSN apps among MSM in serious romantic relationships can influence couples' sexual and relationship health. MSM in serious relationships (N = 323; M age = 40 years) were recruited through a popular GSN app for MSM. Participants completed open-ended items regarding the costs and benefits of app use to their relationships, discussions of app use with their partners, and preferences for relationship education related to app use. Reported benefits of app use included improving sex and communication with one's primary partner and fulfilling unmet sexual needs. Although approximately half had not discussed app use with their partners, citing app use as a “non-issue,” many cited various drawbacks to app use, including jealousy and being a distraction from the relationship. Few described sexual health concerns as a drawback to meeting partners through apps. Regarding relationship education preferences, most wanted help with general communication skills and how to express one's sexual needs to a partner. Although GSN app use can enhance relationships and sex among partnered MSM, unclear communication about app use may contribute to negative relationship outcomes and could prevent partners from having sexual needs met. Relationship and sexual health education programs for male couples should consider addressing social media and technology use in their curricula. PMID:26969319

Smartphone medication adherence apps: Potential benefits to patients and providers

PubMed Central

Dayer, Lindsey; Heldenbrand, Seth; Anderson, Paul; Gubbins, Paul O.; Martin, Bradley C.

2014-01-01

Objectives To provide an overview of medication adherence, discuss the potential for smartphone medication adherence applications (adherence apps) to improve medication nonadherence, evaluate features of adherence apps across operating systems (OSs), and identify future opportunities and barriers facing adherence apps. Practice description Medication nonadherence is a common, complex, and costly problem that contributes to poor treatment outcomes and consumes health care resources. Nonadherence is difficult to measure precisely, and interventions to mitigate it have been largely unsuccessful. Practice innovation Using smartphone adherence apps represents a novel approach to improving adherence. This readily available technology offers many features that can be designed to help patients and health care providers improve medication-taking behavior. Main outcome measures Currently available apps were identified from the three main smartphone OSs (Apple, Android, and Blackberry). In addition, desirable features for adherence apps were identified and ranked by perceived importance to user desirability using a three-point rating system: 1, modest; 2, moderate; or 3, high. The 10 highest-rated apps were installed and subjected to user testing to assess app attributes using a standard medication regimen. Results 160 adherence apps were identified and ranked. These apps were most prevalent for the Android OS. Adherence apps with advanced functionality were more prevalent on the Apple iPhone OS. Among all apps, MyMedSchedule, MyMeds, and RxmindMe rated the highest because of their basic medication reminder features coupled with their enhanced levels of functionality. Conclusion Despite being untested, medication apps represent a possible strategy that pharmacists can recommend to nonadherent patients and incorporate into their practice. PMID:23571625

Assessing the global reach and value of a provider-facing healthcare app using large-scale analytics.

PubMed

O'Reilly-Shah, Vikas; Easton, George; Gillespie, Scott

2017-01-01

The rapid global adoption of mobile health (mHealth) smartphone apps by healthcare providers presents challenges and opportunities in medicine. Challenges include ensuring the delivery of high-quality, up-to-date and optimised information. Opportunities include the ability to study global practice patterns, access to medical and surgical care and continuing medical education needs. We studied users of a free anaesthesia calculator app used worldwide. We combined traditional app analytics with in-app surveys to collect user demographics and feedback. 31 173 subjects participated. Users were from 206 countries and represented a spectrum of healthcare provider roles. Low-income country users had greater rates of app use (p<0.001) and ascribed greater importance of the app to their practice (p<0.001). Physicians from low-income countries were more likely to adopt the app (p<0.001). The app was used primarily for paediatric patients. The app was used around the clock, peaking during times typical for first start cases. This mHealth app is a valuable decision support tool for global healthcare providers, particularly those in more resource-limited settings and with less training. App adoption and use may provide a mechanism for measuring longitudinal changes in access to surgical care and engaging providers in resource-limited settings. In-app surveys and app analytics provide a window into healthcare provider behaviour at a breadth and level of detail previously impossible to achieve. Given the potentially immense value of crowdsourced information, healthcare providers should be encouraged to participate in these types of studies.

Locking it down: The privacy and security of mobile medication apps.

PubMed

Grindrod, Kelly; Boersema, Jonathan; Waked, Khrystine; Smith, Vivian; Yang, Jilan; Gebotys, Catherine

2017-01-01

To explore the privacy and security of free medication applications (apps) available to Canadian consumers. The authors searched the Canadian iTunes store for iOS apps and the Canadian Google Play store for Android apps related to medication use and management. Using an Apple iPad Air 2 and a Google Nexus 7 tablet, 2 reviewers generated a list of apps that met the following inclusion criteria: free, available in English, intended for consumer use and related to medication management. Using a standard data collection form, 2 reviewers independently coded each app for the presence/absence of passwords, the storage of personal health information, a privacy statement, encryption, remote wipe and third-party sharing. A Cohen's Kappa statistic was used to measure interrater agreement. Of the 184 apps evaluated, 70.1% had no password protection or sign-in system. Personal information, including name, date of birth and gender, was requested by 41.8% (77/184) of apps. Contact information, such as address, phone number and email, was requested by 25% (46/184) of apps. Finally, personal health information, other than medication name, was requested by 89.1% (164/184) of apps. Only 34.2% (63/184) of apps had a privacy policy in place. Most free medication apps offer very limited authentication and privacy protocols. As a result, the onus currently falls on patients to input information in these apps selectively and to be aware of the potential privacy issues. Until more secure systems are built, health care practitioners cannot fully support patients wanting to use such apps.

App Use in Psychiatric Education: A Medical Student Survey.

PubMed

Lau, Cecilia; Kolli, Venkata

2017-02-01

The objective of the study is to understand and appraise app use by medical students during their clerkships. Following Creighton University IRB approval, a voluntary and anonymous paper-based, 15-question survey was distributed to third-year medical students. Data were analyzed using Microsoft Excel. Of 112 medical students available, 76.7% (86) participated in the survey. All participants owned a smartphone or tablet with 84.9% using Apple iOS, followed by 12.8% using Android platform. Students reported using the fewest number of apps during surgery, psychiatry, and obstetrics and gynecology clerkships. The largest number of apps were used during the internal medicine rotation (70.3%). The three most popular apps were Epocrates, UpToDate, and UWorld. The most common uses for these apps were as references during the clerkship, followed by improving knowledge, and test taking. Perceived major benefits included accessibility (96% of student respondents) and interactivity (39.5%). Common apps used during the psychiatry clerkship included UpToDate (71%), Epocrates (51%), and Medscape (43%). Despite less frequent app use during their psychiatry clerkship, 90% felt there was a utility for educational apps in psychiatric education. Consistent with the previous literature on medical students preferring educational apps, students suggest developers focus on question bank-type apps, followed by clinical support-focused and self-directed case-based learning apps for psychiatry clerkship learning. Educators should factor these modes of educational delivery into future educational app development. This survey shows a high degree of smartphone and tablet use among medical students, and they attest to mobile phone app utility in psychiatric education.

Anxiety: There is an app for that. A systematic review of anxiety apps.

PubMed

Sucala, Madalina; Cuijpers, Pim; Muench, Frederick; Cardoș, Roxana; Soflau, Radu; Dobrean, Anca; Achimas-Cadariu, Patriciu; David, Daniel

2017-06-01

Smartphones and mobile devices have become ubiquitous, and with the rapid advance of technology, the number of health applications (apps) that are available for consumers on these devices is constantly growing. In particular, there has been a recent proliferation of anxiety apps. However, there has been no review of the quality or content of these anxiety apps and little is known about their purpose, the features they contain, and their empirical support. The goal of this systematic review was to assess the commercially available anxiety apps. A list of anxiety apps was collected in January 2017, using the Power Search function of iTunes and Google Play. Of 5,078 identified apps, 52 met our inclusion criteria (i.e., being defined as an anxiety/worry relief app, and offering psychological techniques aimed primarily at reducing anxiety) and were further reviewed. The majority (67.3%) of the currently available anxiety apps were found to lack the involvement of health care professionals in their development, and very few (3.8%) of them have been rigorously tested. At the moment, although anxiety apps have the potential to enhance access to mental health care, there is a marked discrepancy between the wealth of commercially available apps, and the paucity of data regarding their efficacy and effectiveness. Although the great promise of apps is their ability to increasing access to evidence-based mental health, the field is not quite there yet and the full potential of apps for treating anxiety has yet to be exploited. © 2017 Wiley Periodicals, Inc.

Cloning and Expression of Phytase appA Gene from Shigella sp. CD2 in Pichia pastoris and Comparison of Properties with Recombinant Enzyme Expressed in E. coli

PubMed Central

Pal Roy, Moushree; Mazumdar, Deepika; Dutta, Subhabrata; Saha, Shyama Prasad; Ghosh, Shilpi

2016-01-01

The phytase gene appAS was isolated from Shigella sp. CD2 genomic library. The 3.8 kb DNA fragment contained 1299 bp open reading frame encoding 432 amino acid protein (AppAS) with 22 amino acid signal peptide at N-terminal and three sites of N-glycosylation. AppAS contained the active site RHGXRXP and HDTN sequence motifs, which are conserved among histidine acid phosphatases. It showed maximum identity with phytase AppA of Escherichia coli and Citrobacter braakii. The appAS was expressed in Pichia pastoris and E. coli to produce recombinant phytase rAppAP and rAppAE, respectively. Purified glycosylated rAppAP and nonglycosylated rAppAE had specific activity of 967 and 2982 U mg-1, respectively. Both had pH optima of 5.5 and temperature optima of 60°C. Compared with rAppAE, rAppAP was 13 and 17% less active at pH 3.5 and 7.5 and 11 and 18% less active at temperature 37 and 50°C, respectively; however, it was more active at higher incubation temperatures. Thermotolerance of rAppAP was 33% greater at 60°C and 24% greater at 70°C, when compared with rAppAE. Both the recombinant enzymes showed high specificity to phytate and resistance to trypsin. To our knowledge, this is the first report on cloning and expression of phytase from Shigella sp. PMID:26808559

Cloning and Expression of Phytase appA Gene from Shigella sp. CD2 in Pichia pastoris and Comparison of Properties with Recombinant Enzyme Expressed in E. coli.

PubMed

Pal Roy, Moushree; Mazumdar, Deepika; Dutta, Subhabrata; Saha, Shyama Prasad; Ghosh, Shilpi

2016-01-01

The phytase gene appAS was isolated from Shigella sp. CD2 genomic library. The 3.8 kb DNA fragment contained 1299 bp open reading frame encoding 432 amino acid protein (AppAS) with 22 amino acid signal peptide at N-terminal and three sites of N-glycosylation. AppAS contained the active site RHGXRXP and HDTN sequence motifs, which are conserved among histidine acid phosphatases. It showed maximum identity with phytase AppA of Escherichia coli and Citrobacter braakii. The appAS was expressed in Pichia pastoris and E. coli to produce recombinant phytase rAppAP and rAppAE, respectively. Purified glycosylated rAppAP and nonglycosylated rAppAE had specific activity of 967 and 2982 U mg(-1), respectively. Both had pH optima of 5.5 and temperature optima of 60°C. Compared with rAppAE, rAppAP was 13 and 17% less active at pH 3.5 and 7.5 and 11 and 18% less active at temperature 37 and 50°C, respectively; however, it was more active at higher incubation temperatures. Thermotolerance of rAppAP was 33% greater at 60°C and 24% greater at 70°C, when compared with rAppAE. Both the recombinant enzymes showed high specificity to phytate and resistance to trypsin. To our knowledge, this is the first report on cloning and expression of phytase from Shigella sp.

Clinical relevance of smartphone apps for diabetes management: A global overview.

PubMed

Huang, Zhilian; Soljak, Michael; Boehm, Bernhard Otto; Car, Josip

2018-05-01

We assessed the number, proportion, and clinical relevance of diabetes self-management apps in major languages spoken by 10 countries with the highest number of people with diabetes. China, India, USA, Brazil, Russian Federation, Mexico, Indonesia, Egypt, Japan, and Pakistan were identified as the 10 countries with the largest number of people with diabetes based on the latest NCD-RisC survey. Android and iOS apps in the 10 national languages were extracted with a search strategy. App titles and descriptions were systematically screened by trained reviewers, including apps specific for diabetes self-management and excluding apps for health care providers, general well-being, health and product promotion, and traditional cure. Eighteen apps in the above languages were then downloaded based on availability and popularity and assessed for clinical relevance to diabetes self-management with reference to current clinical guidelines. The diabetes-related search terms identified 3374 Android and 4477 iOS apps, where 1019 Android and 1303 iOS apps were screened as being relevant for diabetes self-management. Chinese and English language apps constitute above 80% of the diabetes apps, have more downloads, and more comprehensive clinically relevant functions compared with other languages. None of the apps assessed met all criteria for information provision and app functionalities nor provided information cited from accredited sources. Our study showed that apps could play an important role in complementing multifaceted diabetes care, but should preferably be regulated, context specific, and more tailored to users' needs with clear guidance for patients and clinicians about the choices. Copyright © 2018 John Wiley & Sons, Ltd.

Assessing the global reach and value of a provider-facing healthcare app using large-scale analytics

PubMed Central

Easton, George; Gillespie, Scott

2017-01-01

Background The rapid global adoption of mobile health (mHealth) smartphone apps by healthcare providers presents challenges and opportunities in medicine. Challenges include ensuring the delivery of high-quality, up-to-date and optimised information. Opportunities include the ability to study global practice patterns, access to medical and surgical care and continuing medical education needs. Methods We studied users of a free anaesthesia calculator app used worldwide. We combined traditional app analytics with in-app surveys to collect user demographics and feedback. Results 31 173 subjects participated. Users were from 206 countries and represented a spectrum of healthcare provider roles. Low-income country users had greater rates of app use (p<0.001) and ascribed greater importance of the app to their practice (p<0.001). Physicians from low-income countries were more likely to adopt the app (p<0.001). The app was used primarily for paediatric patients. The app was used around the clock, peaking during times typical for first start cases. Conclusions This mHealth app is a valuable decision support tool for global healthcare providers, particularly those in more resource-limited settings and with less training. App adoption and use may provide a mechanism for measuring longitudinal changes in access to surgical care and engaging providers in resource-limited settings. In-app surveys and app analytics provide a window into healthcare provider behaviour at a breadth and level of detail previously impossible to achieve. Given the potentially immense value of crowdsourced information, healthcare providers should be encouraged to participate in these types of studies. PMID:29082007

Interrater Reliability of mHealth App Rating Measures: Analysis of Top Depression and Smoking Cessation Apps.

PubMed

Powell, Adam C; Torous, John; Chan, Steven; Raynor, Geoffrey Stephen; Shwarts, Erik; Shanahan, Meghan; Landman, Adam B

2016-02-10

There are over 165,000 mHealth apps currently available to patients, but few have undergone an external quality review. Furthermore, no standardized review method exists, and little has been done to examine the consistency of the evaluation systems themselves. We sought to determine which measures for evaluating the quality of mHealth apps have the greatest interrater reliability. We identified 22 measures for evaluating the quality of apps from the literature. A panel of 6 reviewers reviewed the top 10 depression apps and 10 smoking cessation apps from the Apple iTunes App Store on these measures. Krippendorff's alpha was calculated for each of the measures and reported by app category and in aggregate. The measure for interactiveness and feedback was found to have the greatest overall interrater reliability (alpha=.69). Presence of password protection (alpha=.65), whether the app was uploaded by a health care agency (alpha=.63), the number of consumer ratings (alpha=.59), and several other measures had moderate interrater reliability (alphas>.5). There was the least agreement over whether apps had errors or performance issues (alpha=.15), stated advertising policies (alpha=.16), and were easy to use (alpha=.18). There were substantial differences in the interrater reliabilities of a number of measures when they were applied to depression versus smoking apps. We found wide variation in the interrater reliability of measures used to evaluate apps, and some measures are more robust across categories of apps than others. The measures with the highest degree of interrater reliability tended to be those that involved the least rater discretion. Clinical quality measures such as effectiveness, ease of use, and performance had relatively poor interrater reliability. Subsequent research is needed to determine consistent means for evaluating the performance of apps. Patients and clinicians should consider conducting their own assessments of apps, in conjunction with evaluating information from reviews.

Interrater Reliability of mHealth App Rating Measures: Analysis of Top Depression and Smoking Cessation Apps

PubMed Central

Chan, Steven; Raynor, Geoffrey Stephen; Shwarts, Erik; Shanahan, Meghan; Landman, Adam B

2016-01-01

Background There are over 165,000 mHealth apps currently available to patients, but few have undergone an external quality review. Furthermore, no standardized review method exists, and little has been done to examine the consistency of the evaluation systems themselves. Objective We sought to determine which measures for evaluating the quality of mHealth apps have the greatest interrater reliability. Methods We identified 22 measures for evaluating the quality of apps from the literature. A panel of 6 reviewers reviewed the top 10 depression apps and 10 smoking cessation apps from the Apple iTunes App Store on these measures. Krippendorff’s alpha was calculated for each of the measures and reported by app category and in aggregate. Results The measure for interactiveness and feedback was found to have the greatest overall interrater reliability (alpha=.69). Presence of password protection (alpha=.65), whether the app was uploaded by a health care agency (alpha=.63), the number of consumer ratings (alpha=.59), and several other measures had moderate interrater reliability (alphas>.5). There was the least agreement over whether apps had errors or performance issues (alpha=.15), stated advertising policies (alpha=.16), and were easy to use (alpha=.18). There were substantial differences in the interrater reliabilities of a number of measures when they were applied to depression versus smoking apps. Conclusions We found wide variation in the interrater reliability of measures used to evaluate apps, and some measures are more robust across categories of apps than others. The measures with the highest degree of interrater reliability tended to be those that involved the least rater discretion. Clinical quality measures such as effectiveness, ease of use, and performance had relatively poor interrater reliability. Subsequent research is needed to determine consistent means for evaluating the performance of apps. Patients and clinicians should consider conducting their own assessments of apps, in conjunction with evaluating information from reviews. PMID:26863986

The Diabetes App Challenge: User-Led Development and Piloting of Internet Applications Enabling Young People With Diabetes to Set the Focus for Their Diabetes Consultations

PubMed Central

Ashurst, Emily J; Abraham, Charles; Jenner, Martin; Boddy, Kate; Besser, Rachel EJ; Hammersley, Suzanne

2014-01-01

Background Traditionally, some teenagers and young adults with diabetes have not engaged well at diabetes appointments, giving rise to concerns about long-term health risks. We considered that apps might help this group of patients to improve preparation for, and therefore engagement at their appointments. Although there are already many apps for young people with type 1 diabetes (YPD), we thought that by supporting YPD themselves to develop apps, the resulting products would have greater “authenticity” and relevance. Objective To test the feasibility of an online competition to (1) recruit and support YPD to develop apps (mobile or Internet based) to help prepare for clinic appointments, and (2) for these apps to be tested and rated by YPD. Methods The “Diabetes App Challenge” was a United Kingdom (UK) national competition, run between June and October 2012 for teams including at least one YPD (aged 16-25) to pilot the design and development of apps for use by other YPD prior to clinic appointments. The competition was advertised by social media, email, AdWords and postings on the Diabetes UK website. Registrants for the competition were supported via email and discussion forum. After app development, other YPD were invited (November 2012-February 2013) to trial the apps, choose and use one prior to a clinic appointment, and review their experiences. Results Of 56 people (including 28 YPD) who expressed interest in the competition, 6 teams (14 people) developed and submitted an app. Two apps aimed to facilitate agenda setting in clinic consultations, 2 enabled data logging and 2 helped insulin dose calculation. Of 135 YPD who registered to trial the apps, 83 (61.5%) took part (mean age 18.98, 37/83 male). Agenda setting apps were considered most useful for preparing for and setting the focus of clinic appointments (P=.02). Just over half (46/83, 55%) said they would use their chosen app again and 4/5 (67/83, 81%) would recommend it to a friend. Conclusions This competition to engage YPD in developing and reviewing apps proved successful. App designers and testers saw a need for a range of functions. However, this may, in part, reflect a lack of detailed knowledge of all existing apps and be limited by the technical skills of YPD. App competitions appear worth applying to other patient groups, but future competitions should include a review stage and perhaps focus on ideas for app design for subsequent professional implementation. PMID:25654312

The diabetes app challenge: user-led development and piloting of internet applications enabling young people with diabetes to set the focus for their diabetes consultations.

PubMed

Ashurst, Emily J; Jones, Ray B; Abraham, Charles; Jenner, Martin; Boddy, Kate; Besser, Rachel Ej; Hammersley, Suzanne; Pinkney, Jonathan

2014-11-07

Traditionally, some teenagers and young adults with diabetes have not engaged well at diabetes appointments, giving rise to concerns about long-term health risks. We considered that apps might help this group of patients to improve preparation for, and therefore engagement at their appointments. Although there are already many apps for young people with type 1 diabetes (YPD), we thought that by supporting YPD themselves to develop apps, the resulting products would have greater "authenticity" and relevance. To test the feasibility of an online competition to (1) recruit and support YPD to develop apps (mobile or Internet based) to help prepare for clinic appointments, and (2) for these apps to be tested and rated by YPD. The "Diabetes App Challenge" was a United Kingdom (UK) national competition, run between June and October 2012 for teams including at least one YPD (aged 16-25) to pilot the design and development of apps for use by other YPD prior to clinic appointments. The competition was advertised by social media, email, AdWords and postings on the Diabetes UK website. Registrants for the competition were supported via email and discussion forum. After app development, other YPD were invited (November 2012-February 2013) to trial the apps, choose and use one prior to a clinic appointment, and review their experiences. Of 56 people (including 28 YPD) who expressed interest in the competition, 6 teams (14 people) developed and submitted an app. Two apps aimed to facilitate agenda setting in clinic consultations, 2 enabled data logging and 2 helped insulin dose calculation. Of 135 YPD who registered to trial the apps, 83 (61.5%) took part (mean age 18.98, 37/83 male). Agenda setting apps were considered most useful for preparing for and setting the focus of clinic appointments (P=.02). Just over half (46/83, 55%) said they would use their chosen app again and 4/5 (67/83, 81%) would recommend it to a friend. This competition to engage YPD in developing and reviewing apps proved successful. App designers and testers saw a need for a range of functions. However, this may, in part, reflect a lack of detailed knowledge of all existing apps and be limited by the technical skills of YPD. App competitions appear worth applying to other patient groups, but future competitions should include a review stage and perhaps focus on ideas for app design for subsequent professional implementation.

The AppScale Cloud Platform

PubMed Central

Krintz, Chandra

2013-01-01

AppScale is an open source distributed software system that implements a cloud platform as a service (PaaS). AppScale makes cloud applications easy to deploy and scale over disparate cloud fabrics, implementing a set of APIs and architecture that also makes apps portable across the services they employ. AppScale is API-compatible with Google App Engine (GAE) and thus executes GAE applications on-premise or over other cloud infrastructures, without modification. PMID:23828721

Methods for Evaluating the Content, Usability, and Efficacy of Commercial Mobile Health Apps

PubMed Central

Silfee, Valerie J; Waring, Molly E; Boudreaux, Edwin D; Sadasivam, Rajani S; Mullen, Sean P; Carey, Jennifer L; Hayes, Rashelle B; Ding, Eric Y; Bennett, Gary G; Pagoto, Sherry L

2017-01-01

Commercial mobile apps for health behavior change are flourishing in the marketplace, but little evidence exists to support their use. This paper summarizes methods for evaluating the content, usability, and efficacy of commercially available health apps. Content analyses can be used to compare app features with clinical guidelines, evidence-based protocols, and behavior change techniques. Usability testing can establish how well an app functions and serves its intended purpose for a target population. Observational studies can explore the association between use and clinical and behavioral outcomes. Finally, efficacy testing can establish whether a commercial app impacts an outcome of interest via a variety of study designs, including randomized trials, multiphase optimization studies, and N-of-1 studies. Evidence in all these forms would increase adoption of commercial apps in clinical practice, inform the development of the next generation of apps, and ultimately increase the impact of commercial apps. PMID:29254914

Amyloid precursor protein at node of Ranvier modulates nodal formation

PubMed Central

Xu, De-En; Zhang, Wen-Min; Yang, Zara Zhuyun; Zhu, Hong-Mei; Yan, Ke; Li, Shao; Bagnard, Dominique; Dawe, Gavin S; Ma, Quan-Hong; Xiao, Zhi-Cheng

2014-01-01

Amyloid precursor protein (APP), commonly associated with Alzheimer disease, is upregulated and distributes evenly along the injured axons, and therefore, also known as a marker of demyelinating axonal injury and axonal degeneration. However, the physiological distribution and function of APP along myelinated axons was unknown. We report that APP aggregates at nodes of Ranvier (NOR) in the myelinated central nervous system (CNS) axons but not in the peripheral nervous system (PNS). At CNS NORs, APP expression co-localizes with tenascin-R and is flanked by juxtaparanodal potassium channel expression demonstrating that APP localized to NOR. In APP-knockout (KO) mice, nodal length is significantly increased, while sodium channels are still clustered at NORs. Moreover, APP KO and APP-overexpressing transgenic (APP TG) mice exhibited a decreased and an increased thickness of myelin in spinal cords, respectively, although the changes are limited in comparison to their littermate WT mice. The thickness of myelin in APP KO sciatic nerve also increased in comparison to that in WT mice. Our observations indicate that APP acts as a novel component at CNS NORs, modulating nodal formation and has minor effects in promoting myelination. PMID:25482638

Sex Ed to Go: A Content Analysis of Comprehensive Sexual Education Apps.

PubMed

Kalke, Kerstin M; Ginossar, Tamar; Shah, Sayyed Fawad Ali; West, Andrew J

2017-12-01

Mobile applications ("apps") designed for sexual health education have the potential to reach teens and young adults that are hard to reach through traditional platforms; however, little is known about availability of these apps and their adherence to existing guidelines. Following a search on the two major app stores, data from 2,693 apps were analyzed. Only 697 (25%) addressed sexual health, and only 15 (1%) of apps met inclusion criteria for comprehensive programs and their content was further analyzed. The content of most of these apps narrowly focused on sexually transmitted infections and pregnancy prevention and lacked information on puberty, sexual identity, and personal safety. Theoretically grounded strategies including self-efficacy and modeling behavior to strengthen behavior change efforts were largely absent. Last, we identified significant shortcomings in the literate design of these apps, including limited use of interactive features, such as videos, quizzes, or games. These findings indicate that the potential of apps as sexual health promotion tools has not yet been fully realized. We outline recommendations for developing theory- and evidence-based sexual education apps and provide suggestions for health educators on how to select relevant apps when working for youth.

Phosphorylation of FE65 Ser610 by serum- and glucocorticoid-induced kinase 1 modulates Alzheimer's disease amyloid precursor protein processing

PubMed Central

Chow, Wan Ning Vanessa; Ngo, Jacky Chi Ki; Li, Wen; Chen, Yu Wai; Tam, Ka Ming Vincent; Chan, Ho Yin Edwin; Miller, Christopher C.J.; Lau, Kwok-Fai

2015-01-01

Alzheimer's disease (AD) is a fatal neurodegenerative disease affecting 36 million people worldwide. Genetic and biochemical research indicate that the excessive generation of amyloid-β peptide (Aβ) from amyloid precursor protein (APP), is a major part of AD pathogenesis. FE65 is a brain-enriched adaptor protein that binds to APP. However, the role of FE65 in APP processing and the mechanisms that regulate binding of FE65 to APP are not fully understood. In the present study, we show that serum- and glucocorticoid-induced kinase 1 (SGK1) phosphorylates FE65 on Ser610 and that this phosphorylation attenuates FE65 binding to APP. We also show that FE65 promotes amyloidogenic processing of APP and that FE65 Ser610 phosphorylation inhibits this effect. Furthermore, we found that the effect of FE65 Ser610 phosphorylation on APP processing is linked to a role of FE65 in metabolic turnover of APP via the proteasome. Thus FE65 influences APP degradation via the proteasome and phosphorylation of FE65 Ser610 by SGK1 regulates binding of FE65 to APP, APP turnover and processing. PMID:26188042

An Android Communication App Forensic Taxonomy.

PubMed

Azfar, Abdullah; Choo, Kim-Kwang Raymond; Liu, Lin

2016-09-01

Due to the popularity of Android devices and applications (apps), Android forensics is one of the most studied topics within mobile forensics. Communication apps, such as instant messaging and Voice over IP (VoIP), are one popular app category used by mobile device users, including criminals. Therefore, a taxonomy outlining artifacts of forensic interest involving the use of Android communication apps will facilitate the timely collection and analysis of evidentiary materials from such apps. In this paper, 30 popular Android communication apps were examined, where a logical extraction of the Android phone images was collected using XRY, a widely used mobile forensic tool. Various information of forensic interest, such as contact lists and chronology of messages, was recovered. Based on the findings, a two-dimensional taxonomy of the forensic artifacts of the communication apps is proposed, with the app categories in one dimension and the classes of artifacts in the other dimension. Finally, the artifacts identified in the study of the 30 communication apps are summarized using the taxonomy. It is expected that the proposed taxonomy and the forensic findings in this paper will assist forensic investigations involving Android communication apps. © 2016 American Academy of Forensic Sciences.

Implementation of behavior change techniques in mobile applications for physical activity.

PubMed

Yang, Chih-Hsiang; Maher, Jaclyn P; Conroy, David E

2015-04-01

Mobile applications (apps) for physical activity are popular and hold promise for promoting behavior change and reducing non-communicable disease risk. App marketing materials describe a limited number of behavior change techniques (BCTs), but apps may include unmarketed BCTs, which are important as well. To characterize the extent to which BCTs have been implemented in apps from a systematic user inspection of apps. Top-ranked physical activity apps (N=100) were identified in November 2013 and analyzed in 2014. BCTs were coded using a contemporary taxonomy following a user inspection of apps. Users identified an average of 6.6 BCTs per app and most BCTs in the taxonomy were not represented in any apps. The most common BCTs involved providing social support, information about others' approval, instructions on how to perform a behavior, demonstrations of the behavior, and feedback on the behavior. A latent class analysis of BCT configurations revealed that apps focused on providing support and feedback as well as support and education. Contemporary physical activity apps have implemented a limited number of BCTs and have favored BCTs with a modest evidence base over others with more established evidence of efficacy (e.g., social media integration for providing social support versus active self-monitoring by users). Social support is a ubiquitous feature of contemporary physical activity apps and differences between apps lie primarily in whether the limited BCTs provide education or feedback about physical activity. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Mobile applications for obesity and weight management: current market characteristics.

PubMed

Nikolaou, C K; Lean, M E J

2017-01-01

Mobile-Health (mHealth) is the fastest-developing eHealth sector, with over 100 000 health applications (apps) currently available. Overweight/obesity is a problem of wide public concern that is potentially treatable/preventable through mHealth. This study describes the current weight-management app-market. Five app stores (Apple, Google, Amazon, Windows and Blackberry) in UK, US, Russia, Japan and Germany, Italy, France, China, Australia and Canada were searched for keywords: 'weight', 'calorie', 'weight-loss', 'slimming', 'diet', 'dietitian' and 'overweight' in January/February 2016 using App-Annie software. The 10 most downloaded apps in the lifetime of an app were recorded. Developers' lists and the app descriptions were searched to identify any professional input with keywords 'professional', 'dietitian' and 'nutritionist'. A total of 28 905 relevant apps were identified as follows: Apple iTunes=8559 (4634, 54% paid), Google Play=1762 (597, 33.9% paid), Amazon App=13569 (4821, 35.5% paid), Windows=2419 (819, 17% paid) and Blackberry=2596 (940, 36% paid). The 28 905 identified apps focused mainly on physical activity (34%), diet (31%), and recording/monitoring of exercise, calorie intake and body weight (23%). Only 17 apps (0.05%) were developed with identifiable professional input. Apps on weight management are widely available and very popular but currently lack professional content expertise. Encouraging app development based on evidence-based online approaches would assure content quality, allowing healthcare professionals to recommend their use.

Memory deficiency, cerebral amyloid angiopathy, and amyloid-β plaques in APP+PS1 double transgenic rat model of Alzheimer's disease.

PubMed

Klakotskaia, Diana; Agca, Cansu; Richardson, Rachel A; Stopa, Edward G; Schachtman, Todd R; Agca, Yuksel

2018-01-01

Transgenic rat models of Alzheimer's disease were used to examine differences in memory and brain histology. Double transgenic female rats (APP+PS1) over-expressing human amyloid precursor protein (APP) and presenilin 1 (PS1) and single transgenic rats (APP21) over-expressing human APP were compared with wild type Fischer rats (WT). The Barnes maze assessed learning and memory and showed that both APP21 and APP+PS1 rats made significantly more errors than the WT rats during the acquisition phase, signifying slower learning. Additionally, the APP+PS1 rats made significantly more errors following a retention interval, indicating impaired memory compared to both the APP21 and WT rats. Immunohistochemistry using an antibody against amyloid-β (Aβ) showed extensive and mostly diffuse Aβ plaques in the hippocampus and dense plaques that contained tau in the cortex of the brains of the APP+PS1 rats. Furthermore, the APP+PS1 rats also showed vascular changes, including cerebral amyloid angiopathy with extensive Aβ deposits in cortical and leptomeningeal blood vessel walls and venous collagenosis. In addition to the Aβ accumulation observed in arterial, venous, and capillary walls, APP+PS1 rats also displayed enlarged blood vessels and perivascular space. Overall, the brain histopathology and behavioral assessment showed that the APP+PS1 rats demonstrated behavioral characteristics and vascular changes similar to those commonly observed in patients with Alzheimer's disease.

Social anxiety apps: a systematic review and assessment of app descriptors across mobile store platforms.

PubMed

Alyami, Mohsen; Giri, Bachan; Alyami, Hussain; Sundram, Frederick

2017-08-01

The aim of this systematic review is twofold: (1) to characterise the purpose and description of available social anxiety apps and (2) to review the evidence on the effectiveness of social anxiety apps. A search was conducted on three major mobile platforms: Apple iTunes, Google Play and Windows Store. Apps were included if they addressed social anxiety and used an English language interface. A systematic review of the literature from MEDLINE, EMBASE, PsycINFO, Cochrane, Scopus and Web of Science to identify evidence-based evaluations of social anxiety apps was also undertaken. Of the 1154 apps identified, 38 apps met the inclusion criteria: iTunes (n=18), Google Play (n=16) and Windows Store (n=4). Over 60% of apps were exclusively focused on social anxiety, while the remainder targeted social anxiety and related conditions. Most developers did not provide information on their organisational affiliations or their content source. Most apps used multimedia while 17 apps used text only. Finally, although the systematic review of the literature identified 94 articles, none of which met inclusion criteria. Social anxiety apps have the potential to overcome barriers to accessing treatment; however, none of the apps identified have had studies on their effectiveness published. As the evidence base is lacking, it is therefore not currently possible to recommend their use. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Evaluation of Smartphone Applications for Cardiopulmonary Resuscitation Training in South Korea

PubMed Central

Cho, Yongtak; Song, Yeongtak; Lim, Tae Ho; Kang, Hyunggoo

2016-01-01

Objective. There are many smartphone-based applications (apps) for cardiopulmonary resuscitation (CPR) training. We investigated the conformity and the learnability/usability of these apps for CPR training and real-life supports. Methods. We conducted a mixed-method, sequential explanatory study to assess CPR training apps downloaded on two apps stores in South Korea. Apps were collected with inclusion criteria as follows, Korean-language instruction, training features, and emergency supports for real-life incidents, and analyzed with two tests; 15 medical experts evaluated the apps' contents according to current Basic Life Support guidelines in conformity test, and 15 nonmedical individuals examined the apps using System Usability Scale (SUS) in the learnability/usability test. Results. Out of 79 selected apps, five apps were included and analyzed. For conformity (ICC, 0.95, p < 0.001), means of all apps were greater than 12 of 20 points, indicating that they were well designed according to current guidelines. Three of the five apps yielded acceptable level (greater than 68 of 100 points) for learnability/usability. Conclusion. All the included apps followed current BLS guidelines and a majority offered acceptable learnability/usability for layperson. Current and developmental smartphone-based CPR training apps should include accurate CPR information and be easy to use for laypersons that are potential rescuers in real-life incidents. For Clinical Trials. This is a clinical trial, registered at the Clinical Research Information Service (CRIS, cris.nih.go.kr), number KCT0001840. PMID:27668257

Assessing the Medication Adherence App Marketplace From the Health Professional and Consumer Vantage Points

PubMed Central

2017-01-01

Background Nonadherence produces considerable health consequences and economic burden to patients and payers. One approach to improve medication nonadherence that has gained interest in recent years is the use of smartphone adherence apps. The development of smartphone adherence apps has increased rapidly since 2012; however, literature evaluating the clinical app and effectiveness of smartphone adherence apps to improve medication adherence is generally lacking. Objective The aims of this study were to (1) provide an updated evaluation and comparison of medication adherence apps in the marketplace by assessing the features, functionality, and health literacy (HL) of the highest-ranking adherence apps and (2) indirectly measure the validity of our rating methodology by determining the relationship between our app evaluations and Web-based consumer ratings. Methods Two independent reviewers assessed the features and functionality using a 4-domain rating tool of all adherence apps identified based on developer claims. The same reviewers downloaded and tested the 100 highest-ranking apps including an additional domain for assessment of HL. Pearson product correlations were estimated between the consumer ratings and our domain and total scores. Results A total of 824 adherence apps were identified; of these, 645 unique apps were evaluated after applying exclusion criteria. The median initial score based on descriptions was 14 (max of 68; range 0-60). As a result, 100 of the highest-scoring unique apps underwent user testing. The median overall user-tested score was 31.5 (max of 73; range 0-60). The majority of the user tested the adherence apps that underwent user testing reported a consumer rating score in their respective online marketplace. The mean consumer rating was 3.93 (SD 0.84). The total user-tested score was positively correlated with consumer ratings (r=.1969, P=.04). Conclusions More adherence apps are available in the Web-based marketplace, and the quality of these apps varies considerably. Consumer ratings are positively but weakly correlated with user-testing scores suggesting that our rating tool has some validity but that consumers and clinicians may assess adherence app quality differently. PMID:28428169

MEDication reminder APPs to improve medication adherence in Coronary Heart Disease (MedApp-CHD) Study: a randomised controlled trial protocol.

PubMed

Santo, Karla; Chow, Clara K; Thiagalingam, Aravinda; Rogers, Kris; Chalmers, John; Redfern, Julie

2017-10-08

The growing number of smartphone health applications available in the app stores makes these apps a promising tool to help reduce the global problem of non-adherence to long-term medications. However, to date, there is limited evidence that available medication reminder apps are effective. This study aims to determine the impact of medication reminder apps on adherence to cardiovascular medication when compared with usual care for people with coronary heart disease (CHD) and to determine whether an advanced app compared with a basic app is associated with higher adherence. Randomised controlled trial with follow-up at 3 months to evaluate the feasibility and effectiveness of medication reminder apps on medication adherence compared with usual care. An estimated sample size of 156 patients with CHD will be randomised to one of three groups (usual care group, basic medication reminder app group and advanced medication reminder app group). The usual care group will receive standard care for CHD with no access to a medication reminder app. The basic medication reminder app group will have access to a medication reminder app with a basic feature of providing simple daily reminders with no interactivity. The advanced medication reminder app group will have access to a medication reminder app with additional interactive and customisable features. The primary outcome is medication adherence measured by the eight-item Morisky Medication Adherence Scale at 3 months. Secondary outcomes include clinical measurements of blood pressure and cholesterol levels, and medication knowledge. A process evaluation will also be performed to assess the feasibility of the intervention by evaluating the acceptability, utility and engagement with the apps. Ethical approval has been obtained from the Western Sydney Local Health Network Human Research Ethics Committee (AU/RED/HREC/1/WMEAD/3). Study findings will be disseminated via usual scientific forums. ACTRN12616000661471; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Popular Mobile Phone Apps for Diet and Weight Loss: A Content Analysis

PubMed Central

Roehrer, Erin

2016-01-01

Background A review of the literature has revealed that the rates of overweight and obesity have been increasing in Australia over the last two decades and that wellness mobile phone apps play a significant role in monitoring and managing individuals’ weight. Although mobile phone app markets (iTunes and Google Play) list thousands of mobile phone health apps, it is not always clear whether those apps are supported by credible sources. Likewise, despite the prevailing use of mobile phone apps to aid with weight management, the usability features of these apps are not well characterized. Objective The research explored how usability taxonomy could inform the popularity of downloaded, socially focused wellness mobile phone apps, in particular weight loss and diet apps. The aim of the study was to investigate the Australian mobile phone app stores (iTunes and Google Play) in order to examine the usability features of the most popular (ie, most downloaded) wellness apps. Methods The design of this study comprises 3 main stages: stage 1, identifying apps; stage 2, development of weight loss and diet evaluation framework; and stage 3, application of the evaluation framework. Each stage includes specific data collection, analysis tools, and techniques. Results The study has resulted in the development of a justified evaluation framework for weight loss and diet mobile phone apps. Applying the evaluation framework to the identified apps has shown that the most downloaded iTunes and Google Play apps are not necessarily the most usable or effective. In addition, the research found that search algorithms for iTunes and Google Play are biased toward apps’ titles and keywords that do not accurately define the real functionality of the app. Moreover, the study has also analyzed the apps’ user reviews, which served as justification for the developed evaluation framework. Conclusions The analysis has shown that ease of use, reminder, bar code scanning, motivation, usable for all, and synchronization are significant attributes that should be included in weight loss and diet mobile phone apps and ultimately in potential weight loss and diet evaluation frameworks. PMID:27400806

Using Mobile Apps to Promote a Healthy Lifestyle Among Adolescents and Students: A Review of the Theoretical Basis and Lessons Learned.

PubMed

Dute, Denise Jantine; Bemelmans, Wanda Jose Erika; Breda, João

2016-05-05

European adolescents and students tend to have low levels of physical activity and eat unhealthy foods, and the prevalence of overweight and obesity has increased, which poses a public health challenge. Mobile apps play an important role in their daily lives, suggesting their potential to be used in health-promoting strategies. This review aimed to explore how mobile apps can contribute to the promotion of healthy nutrition, physical activity, and prevention of overweight in adolescents and students. For the apps identified, the review describes the content, the theoretical mechanisms applied, and lessons learned. The databases Scopus, MEDLINE, Embase, and PsycINFO were searched for English-language publications from January 2009 to November 2013. Studies were included if (1) the primary component of the intervention involves an app; (2) the intervention targets healthy nutrition, or physical activity, or overweight prevention; and (3) the target group included adolescents or students (aged 12-25 years). A total of 15 studies were included, which describe 12 unique apps. Ten of these apps functioned as monitoring tools for assessing dietary intake or physical activity levels. The other apps used a Web-based platform to challenge users to exercise and to allow users to list and photograph their problem foods. For 5 apps, the behavioral theory underpinning their development was clearly specified. Frequently applied behavior change techniques are prompting self-monitoring of behavior and providing feedback on performance. Apps can function self-contained, but most of them are used as part of therapy or to strengthen school programs. From the age of 10 years users may be capable of using apps. Only 4 apps were developed specifically for adolescents. All apps were tested on a small scale and for a short period. Despite large potential and abundant usage by young people, limited research is available on apps and health promotion for adolescents. Apps seem to be a promising health promotion strategy as a monitoring tool. Apps can enable users to set targets, enhance self-monitoring, and increase awareness. Three apps incorporated social features, making them "social media," but hardly any evidence appeared available about their potential.

Smartphone Applications to Support Tuberculosis Prevention and Treatment: Review and Evaluation.

PubMed

Iribarren, Sarah J; Schnall, Rebecca; Stone, Patricia W; Carballo-Diéguez, Alex

2016-05-13

Tuberculosis (TB) remains a major global health problem and is the leading killer due to a single infectious disease. Mobile health (mHealth)-based tools such as smartphone apps have been suggested as tools to support TB control efforts (eg, identification, contact tracing, case management including patient support). The purpose of this review was to identify and assess the functionalities of mobile apps focused on prevention and treatment of TB. We searched 3 online mobile app stores. Apps were included if they were focused on TB and were in English, Spanish, or Portuguese. For each included app, 11 functionalities were assessed (eg, inform, instruct, record), and searches were conducted to identify peer-review publications of rigorous testing of the available apps. A total of 1332 potentially relevant apps were identified, with 24 meeting our inclusion criteria. All of the apps were free to download, but 7 required login and password and were developed for specific clinics, regional sites, or research studies. Targeted users were mainly clinicians (n=17); few (n=4) apps were patient focused. Most apps (n=17) had 4 or fewer functions out of 11 (range 1-6). The most common functionalities were inform and record (n=15). Although a number of apps were identified with various functionalities to support TB efforts, some had issues such as incorrect spelling and grammar, inconsistent responses to data entry, problems with crashing, or links to features that had no data. Of more concern, some apps provided potentially harmful information to patients, such as links to natural remedies for TB and natural healers. One-third of the apps (8/24) had not been updated for more than a year and may no longer be supported. Peer-reviewed publications were identified for only two of the included apps. In the gray literature (not found in the app stores), three TB-related apps were identified as in progress, being launched, or tested. Apps identified for TB prevention and treatment had minimal functionality, primarily targeted frontline health care workers, and focused on TB information (eg, general information, guidelines, and news) or data collection (eg, replace paper-based notification or tracking). Few apps were developed for use by patients and none were developed to support TB patient involvement and management in their care (eg, follow-up alerts/reminders, side effects monitoring) or improve interaction with their health care providers, limiting the potential of these apps to facilitate patient-centered care. Our evaluation shows that more refined work is needed to be done in the area of apps to support patients with active TB. Involving TB patients in treatment in the design of these apps is recommended.

Plasma Signaling Proteins in Persons at Genetic Risk for Alzheimer Disease

PubMed Central

Ringman, John M.; Elashoff, David; Geschwind, Daniel H.; Welsh, Brian T.; Gylys, Karen H.; Lee, Cathy; Cummings, Jeffrey L.; Cole, Greg M.

2013-01-01

Objective To study the effect of familial Alzheimer disease (FAD) mutations and APOE genotype on plasma signaling protein levels. Design Cross-sectional comparison of plasma levels of 77 proteins measured using multiplex immune assays. Setting A tertiary referral dementia research center. Participants Thirty-three persons from families harboring PSEN1 or APP mutations, aged 19 to 59 years. Main Outcome Measures Protein levels were compared between FAD mutation carriers (MCs) and non-carriers (NCs) and among APOE genotype groups, using multiple linear regression models. Results Twenty-one participants were FAD MCs and 12 were NCs. Six had the APOE ε2/3, 6 had the ε3/4, and 21 had the ε3/3 genotype. Levels of 17 proteins differed among APOE genotype groups, and there were significant interactions between age and APOE genotype for 12 proteins. Plasma levels of apolipoprotein E and superoxide dismutase 1 were highest in the ε2 carriers, lowest in ε4 carriers, and intermediate in the ε3 carriers. Levels of multiple interleukins showed the opposite pattern and, among the ε4 carriers, demonstrated significant negative correlations with age. Although there were no significant differences between FAD MCs and NCs, there were interactions between mutation status and APOE genotype for 13 proteins. Conclusions We found different patterns of inflammatory markers in young and middle-aged persons among APOE genotype groups. The APOE ε4 carriers had the lowest levels of apolipoprotein E. Young ε4 carriers have increased inflammatory markers that diminish with age. We demonstrated altered inflammatory responses in young and middle adulthood in ε4 carriers that may relate to AD risk later in life. PMID:22689192

Mobile Phone Apps for the Prevention of Unintended Pregnancy: A Systematic Review and Content Analysis

PubMed Central

Lebrun, Victoria; Muessig, Kathryn E

2016-01-01

Background Over 50% of pregnancies in the United States are unintended, meaning that the pregnancy is mistimed, unplanned, or unwanted. Unintended pregnancy increases health risks for mother and child, leads to high economic costs for society, and increases social disparities. Mobile phone ownership is rapidly increasing, providing opportunities to reach at-risk populations with reproductive health information and tailored unintended pregnancy prevention interventions through mobile phone apps. However, apps that offer support for unintended pregnancy prevention remain unevaluated. Objective To identify, describe, and evaluate mobile phone apps that purport to help users prevent unintended pregnancy. Methods We conducted an extensive search of the Apple iTunes and Android Google Play stores for apps that explicitly included or advertised pregnancy prevention or decision-making support in the context of fertility information/tracking, birth control reminders, contraceptive information, pregnancy decision-making, abortion information or counseling, sexual communication/negotiation, and pregnancy tests. We excluded apps that targeted medical professionals or that cost more than US $1.99. Eligible apps were downloaded and categorized by primary purpose. Data extraction was performed on a minimum of 143 attributes in 3 domains: (1) pregnancy prevention best practices, (2) contraceptive methods and clinical services, and (3) user interface. Apps were assigned points for their inclusion of features overall and for pregnancy prevention best practices and contraceptive information. Results Our search identified 6805 app descriptions in iTunes and Google Play. Of these, 218 unique apps met inclusion criteria and were included in the review. Apps were grouped into 9 categories: fertility trackers (n=72), centers and resources (n=38), birth control reminders (n=35), general sexual and reproductive health (SRH) information (n=17), SRH information targeted specifically to young adults (YA) (n=16), contraceptive information (n=15), service or condom locators (n=12), pregnancy tests (n=10), and games (n=3). Twelve apps scored at least 50 points (out of 94) for overall number of features and at least 15 points (out of 21) for contraceptive information and pregnancy prevention best practices. Overall, 41% of apps did not mention any modern contraceptive methods and 23% mentioned only 1 method. Of apps that did mention a modern contraceptive method, fewer than 50% of these apps provided information on how to use it. YA SRH apps had the highest percentage of pregnancy prevention best practices in each app. Demographic and interface evaluation found that most apps (72%) did not target any race and only 10% explicitly targeted youth. Communication interface features were present in fewer than 50% of apps. Conclusions This review identified several useful, evidence-based apps that support the prevention of unintended pregnancy. However, most apps miss opportunities to provide users with valuable information, interactive decision aids, and evidence-based interventions for unintended pregnancy prevention. Further, some apps in this space may increase the likelihood of unintended pregnancy due to the low effectiveness of the contraceptive methods promoted. PMID:26787311

Mobile Phone Apps for the Prevention of Unintended Pregnancy: A Systematic Review and Content Analysis.

PubMed

Mangone, Emily Rose; Lebrun, Victoria; Muessig, Kathryn E

2016-01-19

Over 50% of pregnancies in the United States are unintended, meaning that the pregnancy is mistimed, unplanned, or unwanted. Unintended pregnancy increases health risks for mother and child, leads to high economic costs for society, and increases social disparities. Mobile phone ownership is rapidly increasing, providing opportunities to reach at-risk populations with reproductive health information and tailored unintended pregnancy prevention interventions through mobile phone apps. However, apps that offer support for unintended pregnancy prevention remain unevaluated. To identify, describe, and evaluate mobile phone apps that purport to help users prevent unintended pregnancy. We conducted an extensive search of the Apple iTunes and Android Google Play stores for apps that explicitly included or advertised pregnancy prevention or decision-making support in the context of fertility information/tracking, birth control reminders, contraceptive information, pregnancy decision-making, abortion information or counseling, sexual communication/negotiation, and pregnancy tests. We excluded apps that targeted medical professionals or that cost more than US $1.99. Eligible apps were downloaded and categorized by primary purpose. Data extraction was performed on a minimum of 143 attributes in 3 domains: (1) pregnancy prevention best practices, (2) contraceptive methods and clinical services, and (3) user interface. Apps were assigned points for their inclusion of features overall and for pregnancy prevention best practices and contraceptive information. Our search identified 6805 app descriptions in iTunes and Google Play. Of these, 218 unique apps met inclusion criteria and were included in the review. Apps were grouped into 9 categories: fertility trackers (n=72), centers and resources (n=38), birth control reminders (n=35), general sexual and reproductive health (SRH) information (n=17), SRH information targeted specifically to young adults (YA) (n=16), contraceptive information (n=15), service or condom locators (n=12), pregnancy tests (n=10), and games (n=3). Twelve apps scored at least 50 points (out of 94) for overall number of features and at least 15 points (out of 21) for contraceptive information and pregnancy prevention best practices. Overall, 41% of apps did not mention any modern contraceptive methods and 23% mentioned only 1 method. Of apps that did mention a modern contraceptive method, fewer than 50% of these apps provided information on how to use it. YA SRH apps had the highest percentage of pregnancy prevention best practices in each app. Demographic and interface evaluation found that most apps (72%) did not target any race and only 10% explicitly targeted youth. Communication interface features were present in fewer than 50% of apps. This review identified several useful, evidence-based apps that support the prevention of unintended pregnancy. However, most apps miss opportunities to provide users with valuable information, interactive decision aids, and evidence-based interventions for unintended pregnancy prevention. Further, some apps in this space may increase the likelihood of unintended pregnancy due to the low effectiveness of the contraceptive methods promoted.

A Classification Scheme for Analyzing Mobile Apps Used to Prevent and Manage Disease in Late Life

PubMed Central

Wang, Aiguo; Lu, Xin; Chen, Hongtu; Li, Changqun; Levkoff, Sue

2014-01-01

Background There are several mobile apps that offer tools for disease prevention and management among older adults, and promote health behaviors that could potentially reduce or delay the onset of disease. A classification scheme that categorizes apps could be useful to both older adult app users and app developers. Objective The objective of our study was to build and evaluate the effectiveness of a classification scheme that classifies mobile apps available for older adults in the “Health & Fitness” category of the iTunes App Store. Methods We constructed a classification scheme for mobile apps according to three dimensions: (1) the Precede-Proceed Model (PPM), which classifies mobile apps in terms of predisposing, enabling, and reinforcing factors for behavior change; (2) health care process, specifically prevention versus management of disease; and (3) health conditions, including physical health and mental health. Content analysis was conducted by the research team on health and fitness apps designed specifically for older adults, as well as those applicable to older adults, released during the months of June and August 2011 and August 2012. Face validity was assessed by a different group of individuals, who were not related to the study. A reliability analysis was conducted to confirm the accuracy of the coding scheme of the sample apps in this study. Results After applying sample inclusion and exclusion criteria, a total of 119 apps were included in the study sample, of which 26/119 (21.8%) were released in June 2011, 45/119 (37.8%) in August 2011, and 48/119 (40.3%) in August 2012. Face validity was determined by interviewing 11 people, who agreed that this scheme accurately reflected the nature of this application. The entire study sample was successfully coded, demonstrating satisfactory inter-rater reliability by two independent coders (95.8% initial concordance and 100% concordance after consensus was reached). The apps included in the study sample were more likely to be used for the management of disease than prevention of disease (109/119, 91.6% vs 15/119, 12.6%). More apps contributed to physical health rather than mental health (81/119, 68.1% vs 47/119, 39.5%). Enabling apps (114/119, 95.8%) were more common than reinforcing (20/119, 16.8%) or predisposing apps (10/119, 8.4%). Conclusions The findings, including face validity and inter-rater reliability, support the integrity of the proposed classification scheme for categorizing mobile apps for older adults in the “Health and Fitness” category available in the iTunes App Store. Using the proposed classification system, older adult app users would be better positioned to identify apps appropriate for their needs, and app developers would be able to obtain the distributions of available mobile apps for health-related concerns of older adults more easily. PMID:25098687

Long QT interval in Turner syndrome--a high prevalence of LQTS gene mutations.

PubMed

Trolle, Christian; Mortensen, Kristian H; Pedersen, Lisbeth N; Berglund, Agnethe; Jensen, Henrik K; Andersen, Niels H; Gravholt, Claus H

2013-01-01

QT-interval prolongation of unknown aetiology is common in Turner syndrome. This study set out to explore the presence of known long QT mutations in Turner syndrome and to examine the corrected QT-interval (QTc) over time and relate the findings to the Turner syndrome phenotype. Adult women with Turner syndrome (n = 88) were examined thrice and 68 age-matched healthy controls were examined once. QTc was measured by one blinded reader (intra-reader variability: 0.7%), and adjusted for influence of heart rate by Bazett's (bQTc) and Hodges's formula (hQTc). The prevalence of mutations in genes related to Long QT syndrome was determined in women with Turner syndrome and a QTc >432.0 milliseconds (ms). Echocardiographic assessment of aortic valve morphology, 24-hour blood pressures and blood samples were done. The mean hQTc in women with Turner syndrome (414.0 ± 25.5 ms) compared to controls (390.4 ± 17.8 ms) was prolonged (p<0.001) and did not change over time (416.9 ± 22.6 vs. 415.6 ± 25.5 ms; p =0.4). 45,X karyotype was associated with increased hQTc prolongation compared to other Turner syndrome karyotypes (418.2 ± 24.8 vs. 407.6 ± 25.5 ms; p = 0.055). In women with Turner syndrome and a bQTc >432 ms, 7 had mutations in major Long QT syndrome genes (SCN5A and KCNH2) and one in a minor Long QT syndrome gene (KCNE2). There is a high prevalence of mutations in the major LQTS genes in women with TS and prolonged QTc. It remains to be settled, whether these findings are related to the unexplained excess mortality in Turner women. NCT00624949. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol/sid/S0001FLI/selectaction/View/ts/3/uid/U000099E.

Attention Deficit Hyperactivity Disorder: Is There an App for That? Suitability Assessment of Apps for Children and Young People With ADHD

PubMed Central

Parker, Jack; Robertson, Naomi; Harpin, Valerie

2017-01-01

Background Attention-deficit/hyperactivity disorder (ADHD) is a complex highly comorbid disorder, which can have a huge impact on those with ADHD, their family, and the community around them. ADHD is currently managed using pharmacological and nonpharmacological interventions. However, with advances in technology and an increase in the use of mobile apps, managing ADHD can be augmented using apps specifically designed for this population. However, little is known regarding the suitability and usability of currently available apps. Objective The aim of this study was to explore the suitability of the top 10 listed apps for children and young people with ADHD and clinicians who work with them. It is hypothesized that mobile apps designed for this population could be more suitably designed for this population. Methods The top 10 listed apps that are specifically targeted toward children and young people with ADHD in the United Kingdom were identified via the Google Play (n=5) and iTunes store (n=5). Interviews were then undertaken with 5 clinicians who specialize in treating this population and 5 children and young people with ADHD themselves, to explore their opinions of the 10 apps identified and what they believe the key components are for apps to be suitable for this population. Results Five themes emerged from clinician and young people interviews: the accessibility of the technology, the importance of relating to apps, addressing ADHD symptoms and related difficulties, age appropriateness, and app interaction. Three additional themes emerged from the clinician interviews alone: monitoring symptoms, side effects and app effect on relationships, and the impact of common comorbid conditions. The characteristics of the apps did not appear to match well with the views of our sample. Conclusions These findings suggest that the apps may not be suitable in meeting the complex needs associated with this condition. Further research is required to explore the value of apps for children and young people with ADHD and their families and, in particular, any positive role for apps in the management of ADHD in this age group. A systematic review on how technology can be used to engage this population and how it can be used to help them would be a useful way forward. This could be the platform to begin exploring the use of apps further. PMID:28978497

Infant Feeding Websites and Apps: A Systematic Assessment of Quality and Content

PubMed Central

Campbell, Karen J; Russell, Catherine G; Elliott, Rosalind; Laws, Rachel; Denney-Wilson, Elizabeth

2015-01-01

Background Internet websites and smartphone apps have become a popular resource to guide parents in their children’s feeding and nutrition. Given the diverse range of websites and apps on infant feeding, the quality of information in these resources should be assessed to identify whether consumers have access to credible and reliable information. Objective This systematic analysis provides perspectives on the information available about infant feeding on websites and smartphone apps. Methods A systematic analysis was conducted to assess the quality, comprehensibility, suitability, and readability of websites and apps on infant feeding using a developed tool. Google and Bing were used to search for websites from Australia, while the App Store for iOS and Google Play for Android were used to search for apps. Specified key words including baby feeding, breast feeding, formula feeding and introducing solids were used to assess websites and apps addressing feeding advice. Criteria for assessing the accuracy of the content were developed using the Australian Infant Feeding Guidelines. Results A total of 600 websites and 2884 apps were screened, and 44 websites and 46 apps met the selection criteria and were analyzed. Most of the websites (26/44) and apps (43/46) were noncommercial, some websites (10/44) and 1 app were commercial and there were 8 government websites; 2 apps had university endorsement. The majority of the websites and apps were rated poor quality. There were two websites that had 100% coverage of information compared to those rated as fair or poor that had low coverage. Two-thirds of the websites (65%) and almost half of the apps (47%) had a readability level above the 8th grade level. Conclusions The findings of this unique analysis highlight the potential for website and app developers to merge user requirements with evidence-based content to ensure that information on infant feeding is of high quality. There are currently no apps available to consumers that address a variety of infant feeding topics. To keep up with the rapid turnover of the evolving technology, health professionals need to consider developing an app that will provide consumers with a credible and reliable source of information about infant feeding, using quality assessment tools and evidence-based content. PMID:26420339

Designing Health Apps to Support Dietetic Professional Practice and Their Patients: Qualitative Results From an International Survey

PubMed Central

Lieffers, Jessica; Bauman, Adrian; Hanning, Rhona; Allman-Farinelli, Margaret

2017-01-01

Background Dietitians are engaging with mobile health (mHealth) technologies, particularly with diet and nutrition apps in their patient care. Despite the plethora of apps available, the majority are not designed with a dietitian’s input. Objective The aim of this study was to identify the user preferences of dietitians in relation to tools, resources, and design features for smartphone health apps that would support their dietetic professional practice and their patients. Methods As part of a larger international Web-based survey of health-app use among dietitians, three open-ended responses were included for specific exploration of app design features and additional resources or tools that could guide the development of apps for use in dietetic practice and patient care. Inductive thematic analysis of responses was conducted using the qualitative data analysis program, NVivo version 11 (QSR International Pty Ltd), to understand the design preferences and features valued by dietitians. Results The responses from 381 dietitian respondents were analyzed. Five key themes were identified. Dietitians wanted access to credible apps, suggesting that dietetic associations should have greater involvement in reviewing and endorsing evidence-based apps for use in dietary counseling. Improvements to the usability of apps, relating to their ease of use and design, were also raised, as self-monitoring of dietary behaviors using existing nutrition apps was deemed to be burdensome. Furthermore, apps providing dietitian-oriented support were favored, for example, those with the ability to streamline the dietary assessment process, so that dietitians could spend more time on dietary counseling and negotiating patient goals for dietary and lifestyle behavior change. Provision of patient-oriented support, such as functionality to tailor apps to patient-specific needs, was also considered important. Finally, respondents valued apps that could integrate into their work systems to enhance the quality of the dietitian-patient relationship. Conclusions App developers should draw upon the features and characteristics valued by dietitians to guide their development of apps that support dietetic practice and enhance patient care. Moreover, to achieve better dietitian and patient-centered app design, it is imperative that app developers take a collaborative approach with dietitians, their professional associations, and their patients. PMID:28363882

Smartphone Apps for Measuring Human Health and Climate Change Co-Benefits: A Comparison and Quality Rating of Available Apps

PubMed Central

Sullivan, Rachel K; Marsh, Samantha; Halvarsson, Jakob; Holdsworth, Michelle; Waterlander, Wilma; Poelman, Maartje P; Salmond, Jennifer Ann; Christian, Hayley; Koh, Lenny SC; Cade, Janet E; Spence, John C; Woodward, Alistair

2016-01-01

Background Climate change and the burden of noncommunicable diseases are major global challenges. Opportunities exist to investigate health and climate change co-benefits through a shift from motorized to active transport (walking and cycling) and a shift in dietary patterns away from a globalized diet to reduced consumption of meat and energy dense foods. Given the ubiquitous use and proliferation of smartphone apps, an opportunity exists to use this technology to capture individual travel and dietary behavior and the associated impact on the environment and health. Objective The objective of the study is to identify, describe the features, and rate the quality of existing smartphone apps which capture personal travel and dietary behavior and simultaneously estimate the carbon cost and potential health consequences of these actions. Methods The Google Play and Apple App Stores were searched between October 19 and November 6, 2015, and a secondary Google search using the apps filter was conducted between August 8 and September 18, 2016. Eligible apps were required to estimate the carbon cost of personal behaviors with the potential to include features to maximize health outcomes. The quality of included apps was assessed by 2 researchers using the Mobile Application Rating Scale (MARS). Results Out of 7213 results, 40 apps were identified and rated. Multiple travel-related apps were identified, however no apps solely focused on the carbon impact or health consequences of dietary behavior. None of the rated apps provided sufficient information on the health consequences of travel and dietary behavior. Some apps included features to maximize participant engagement and encourage behavior change towards reduced greenhouse gas emissions. Most apps were rated as acceptable quality as determined by the MARS; 1 was of poor quality and 10 apps were of good quality. Interrater reliability of the 2 evaluators was excellent (ICC=0.94, 95% CI 0.87-0.97). Conclusions Existing apps capturing travel and dietary behavior and the associated health and environmental impact are of mixed quality. Most apps do not include all desirable features or provide sufficient health information. Further research is needed to determine the potential of smartphone apps to evoke behavior change resulting in climate change and health co-benefits. PMID:27993762

A Systematic Assessment of Smartphone Tools for Suicide Prevention

PubMed Central

Larsen, Mark Erik; Nicholas, Jennifer; Christensen, Helen

2016-01-01

Background Suicide is a leading cause of death globally, and there has been a rapid growth in the use of new technologies such as mobile health applications (apps) to help identify and support those at risk. However, it is not known whether these apps are evidence-based, or indeed contain potentially harmful content. This review examines the concordance of features in publicly available apps with current scientific evidence of effective suicide prevention strategies. Methods Apps referring to suicide or deliberate self-harm (DSH) were identified on the Android and iOS app stores. Systematic review methodology was employed to screen and review app content. App features were labelled using a coding scheme that reflected the broad range of evidence-based medical and population-based suicide prevention interventions. Best-practice for suicide prevention was based upon a World Health Organization report and supplemented by other reviews of the literature. Results One hundred and twenty-three apps referring to suicide were identified and downloaded for full review, 49 of which were found to contain at least one interactive suicide prevention feature. Most apps focused on obtaining support from friends and family (n = 27) and safety planning (n = 14). Of the different suicide prevention strategies contained within the apps, the strongest evidence in the literature was found for facilitating access to crisis support (n = 13). All reviewed apps contained at least one strategy that was broadly consistent with the evidence base or best-practice guidelines. Apps tended to focus on a single suicide prevention strategy (mean = 1.1), although safety plan apps provided the opportunity to provide a greater number of techniques (mean = 3.9). Potentially harmful content, such as listing lethal access to means or encouraging risky behaviour in a crisis, was also identified. Discussion Many suicide prevention apps are available, some of which provide elements of best practice, but none that provide comprehensive evidence-based support. Apps with potentially harmful content were also identified. Despite the number of apps available, and their varied purposes, there is a clear need to develop useful, pragmatic, and multifaceted mobile resources for this population. Clinicians should be wary in recommending apps, especially as potentially harmful content can be presented as helpful. Currently safety plan apps are the most comprehensive and evidence-informed, for example, “Safety Net” and “MoodTools—Depression Aid”. PMID:27073900

A Systematic Assessment of Smartphone Tools for Suicide Prevention.

PubMed

Larsen, Mark Erik; Nicholas, Jennifer; Christensen, Helen

2016-01-01

Suicide is a leading cause of death globally, and there has been a rapid growth in the use of new technologies such as mobile health applications (apps) to help identify and support those at risk. However, it is not known whether these apps are evidence-based, or indeed contain potentially harmful content. This review examines the concordance of features in publicly available apps with current scientific evidence of effective suicide prevention strategies. Apps referring to suicide or deliberate self-harm (DSH) were identified on the Android and iOS app stores. Systematic review methodology was employed to screen and review app content. App features were labelled using a coding scheme that reflected the broad range of evidence-based medical and population-based suicide prevention interventions. Best-practice for suicide prevention was based upon a World Health Organization report and supplemented by other reviews of the literature. One hundred and twenty-three apps referring to suicide were identified and downloaded for full review, 49 of which were found to contain at least one interactive suicide prevention feature. Most apps focused on obtaining support from friends and family (n = 27) and safety planning (n = 14). Of the different suicide prevention strategies contained within the apps, the strongest evidence in the literature was found for facilitating access to crisis support (n = 13). All reviewed apps contained at least one strategy that was broadly consistent with the evidence base or best-practice guidelines. Apps tended to focus on a single suicide prevention strategy (mean = 1.1), although safety plan apps provided the opportunity to provide a greater number of techniques (mean = 3.9). Potentially harmful content, such as listing lethal access to means or encouraging risky behaviour in a crisis, was also identified. Many suicide prevention apps are available, some of which provide elements of best practice, but none that provide comprehensive evidence-based support. Apps with potentially harmful content were also identified. Despite the number of apps available, and their varied purposes, there is a clear need to develop useful, pragmatic, and multifaceted mobile resources for this population. Clinicians should be wary in recommending apps, especially as potentially harmful content can be presented as helpful. Currently safety plan apps are the most comprehensive and evidence-informed, for example, "Safety Net" and "Mood-Tools--Depression Aid".

Just a Fad? Gamification in Health and Fitness Apps

PubMed Central

2014-01-01

Background Gamification has been a predominant focus of the health app industry in recent years. However, to our knowledge, there has yet to be a review of gamification elements in relation to health behavior constructs, or insight into the true proliferation of gamification in health apps. Objective The objective of this study was to identify the extent to which gamification is used in health apps, and analyze gamification of health and fitness apps as a potential component of influence on a consumer’s health behavior. Methods An analysis of health and fitness apps related to physical activity and diet was conducted among apps in the Apple App Store in the winter of 2014. This analysis reviewed a sample of 132 apps for the 10 effective game elements, the 6 core components of health gamification, and 13 core health behavior constructs. A regression analysis was conducted in order to measure the correlation between health behavior constructs, gamification components, and effective game elements. Results This review of the most popular apps showed widespread use of gamification principles, but low adherence to any professional guidelines or industry standard. Regression analysis showed that game elements were associated with gamification (P<.001). Behavioral theory was associated with gamification (P<.05), but not game elements, and upon further analysis gamification was only associated with composite motivational behavior scores (P<.001), and not capacity or opportunity/trigger. Conclusions This research, to our knowledge, represents the first comprehensive review of gamification use in health and fitness apps, and the potential to impact health behavior. The results show that use of gamification in health and fitness apps has become immensely popular, as evidenced by the number of apps found in the Apple App Store containing at least some components of gamification. This shows a lack of integrating important elements of behavioral theory from the app industry, which can potentially impact the efficacy of gamification apps to change behavior. Apps represent a very promising, burgeoning market and landscape in which to disseminate health behavior change interventions. Initial results show an abundant use of gamification in health and fitness apps, which necessitates the in-depth study and evaluation of the potential of gamification to change health behaviors. PMID:25654660

How Do Apps Work? An Analysis of Physical Activity App Users' Perceptions of Behavior Change Mechanisms.

PubMed

Hoj, Taylor H; Covey, Emarie L; Jones, Allyn C; Haines, Amanda C; Hall, P Cougar; Crookston, Benjamin T; West, Joshua H

2017-08-03

Physical activity apps are commonly used to increase levels of activity and health status. To date, the focus of research has been to determine the potential of apps to influence behavior, to ascertain the efficacy of a limited number of apps to change behavior, and to identify the characteristics of apps that users prefer. The purpose of this study was to identify the mechanisms by which the use of physical activity apps may influence the users' physical activity behavior. This study used a cross-sectional survey of users of health-related physical activity apps during the past 6 months. An electronic survey was created in Qualtrics' Web-based survey software and deployed on Amazon Mechanical Turk. Individuals who had used at least one physical activity app in the past 6 months were eligible to respond. The final sample comprised 207 adults living in the United States. 86.0% (178/207) of respondents were between the ages of 26 and 54 years, with 51.2% (106/207) of respondents being female. Behavior change theory informed the creation of 20 survey items relating to the mechanisms of behavior change. Respondents also reported about engagement with the apps, app likeability, and physical activity behavior. Respondents reported that using a physical activity app in the past 6 months resulted in a change in their attitudes, beliefs, perceptions, and motivation. Engagement with the app (P<.001), frequency of app use (P=.03), and app price (P=.01) were related to the reported impact of the behavior change theory or mechanisms of change. The mechanisms of change were associated with self-reported physical activity behaviors (P<.001). The findings from this study provide an overview of the mechanisms by which apps may impact behavior. App developers may wish to incorporate these mechanisms in an effort to increase impact. Practitioners should consider the extent to which behavior change theory is integrated into a particular app when they consider making recommendations to others wishing to increase levels of physical activity. ©Taylor H Hoj, Emarie L Covey, Allyn C Jones, Amanda C Haines, P Cougar Hall, Benjamin T Crookston, Joshua H West. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 03.08.2017.

Lack of tau proteins rescues neuronal cell death and decreases amyloidogenic processing of APP in APP/PS1 mice.

PubMed

Leroy, Karelle; Ando, Kunie; Laporte, Vincent; Dedecker, Robert; Suain, Valérie; Authelet, Michèle; Héraud, Céline; Pierrot, Nathalie; Yilmaz, Zehra; Octave, Jean-Noël; Brion, Jean-Pierre

2012-12-01

Lack of tau expression has been reported to protect against excitotoxicity and to prevent memory deficits in mice expressing mutant amyloid precursor protein (APP) identified in familial Alzheimer disease. In APP mice, mutant presenilin 1 (PS1) enhances generation of Aβ42 and inhibits cell survival pathways. It is unknown whether the deficient phenotype induced by concomitant expression of mutant PS1 is rescued by absence of tau. In this study, we have analyzed the effect of tau deletion in mice expressing mutant APP and PS1. Although APP/PS1/tau(+/+) mice had a reduced survival, developed spatial memory deficits at 6 months and motor impairments at 12 months, these deficits were rescued in APP/PS1/tau(-/-) mice. Neuronal loss and synaptic loss in APP/PS1/tau(+/+) mice were rescued in the APP/PS1/tau(-/-) mice. The amyloid plaque burden was decreased by roughly 50% in the cortex and the spinal cord of the APP/PS1/tau(-/-) mice. The levels of soluble and insoluble Aβ40 and Aβ42, and the Aβ42/Aβ40 ratio were reduced in APP/PS1/tau(-/-) mice. Levels of phosphorylated APP, of β-C-terminal fragments (CTFs), and of β-secretase 1 (BACE1) were also reduced, suggesting that β-secretase cleavage of APP was reduced in APP/PS1/tau(-/-) mice. Our results indicate that tau deletion had a protective effect against amyloid induced toxicity even in the presence of mutant PS1 and reduced the production of Aβ. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Activation of Ras-ERK Signaling and GSK-3 by Amyloid Precursor Protein and Amyloid Beta Facilitates Neurodegeneration in Alzheimer's Disease.

PubMed

Kirouac, Lisa; Rajic, Alexander J; Cribbs, David H; Padmanabhan, Jaya

2017-01-01

It is widely accepted that amyloid β (Aβ) generated from amyloid precursor protein (APP) oligomerizes and fibrillizes to form neuritic plaques in Alzheimer's disease (AD), yet little is known about the contribution of APP to intracellular signaling events preceding AD pathogenesis. The data presented here demonstrate that APP expression and neuronal exposure to oligomeric Aβ42 enhance Ras/ERK signaling cascade and glycogen synthase kinase 3 (GSK-3) activation. We find that RNA interference (RNAi)-directed knockdown of APP in B103 rat neuroblastoma cells expressing APP inhibits Ras-ERK signaling and GSK-3 activation, indicating that APP acts upstream of these signal transduction events. Both ERK and GSK-3 are known to induce hyperphosphorylation of tau and APP at Thr668, and our findings suggest that aberrant signaling by APP facilitates these events. Supporting this notion, analysis of human AD brain samples showed increased expression of Ras, activation of GSK-3, and phosphorylation of APP and tau, which correlated with Aβ levels in the AD brains. Furthermore, treatment of primary rat neurons with Aβ recapitulated these events and showed enhanced Ras-ERK signaling, GSK-3 activation, upregulation of cyclin D1, and phosphorylation of APP and tau. The finding that Aβ induces Thr668 phosphorylation on APP, which enhances APP proteolysis and Aβ generation, denotes a vicious feedforward mechanism by which APP and Aβ promote tau hyperphosphorylation and neurodegeneration in AD. Based on these results, we hypothesize that aberrant proliferative signaling by APP plays a fundamental role in AD neurodegeneration and that inhibition of this would impede cell cycle deregulation and neurodegeneration observed in AD.

The Use of Mobile Phone and Medical Apps among General Practitioners in Hangzhou City, Eastern China.

PubMed

Liu, Ying; Ren, Wen; Qiu, Yan; Liu, Juanjuan; Yin, Pei; Ren, Jingjing

2016-05-24

Mobile phones and mobile phone apps have expanded new forms of health professionals' work. There are many studies on the use of mobile phone apps for different specialists. However, there are no studies on the current use of mobile phone apps among general practitioners (GPs). The objective of the study was to investigate the extent to which GPs own smartphones with apps and use them to aid their clinical activities. A questionnaire survey of GPs was undertaken in Hangzhou, Eastern China. Data probing GPs' current use of medical apps in their clinical activities and factors influencing app use were collected and analyzed 125 GPs participated in the survey. 90.4% of GPs owned a mobile phone, with 48.7% owning an iPhone and 47.8% owning an Android phone. Most mobile phone owners had 1-3 medical-related apps, with very few owning more than 4. There was no difference in number of apps between iPhone and Android owners (χ(2)=1.388, P=0.846). 36% of GPs reported using medical-related apps on a daily basis. The majority of doctors reported using apps to aid clinical activities less than 30 minutes per day. A high level of mobile phone ownership and usage among GPs was found in this study, but few people chose medical-related apps to support their clinical practice.

Free blood donation mobile applications.

PubMed

Ouhbi, Sofia; Fernández-Alemán, José Luis; Toval, Ambrosio; Idri, Ali; Pozo, José Rivera

2015-05-01

Blood donation (BD) is a noble act and mobile applications (apps) can help increase awareness about it. This paper analyzes and assesses the characteristics of free apps for BD as regards features and functionality. A search in Google Play, Apple Apps store, Blackberry App World and Windows Mobile App store was carried out to select 169 free BD apps from the 188 apps identified. The results presented in this paper show that the majority of the apps selected have been developed for the Android operating system. Moreover, most of the apps selected are available to help users search for donors. Few of the apps could not be installed and/or accessed. Of those that could be installed: half of them do not require any kind of authentication; a few of them are available in more than one language; half of them have a geographical restriction; around 60 % of them do not notify the user of BD events and requests; one, which is available for Android and iOS, can connect with a laboratory; around 45 % of them allow users to share information via social networks, and the majority of them do not provide BD recommendations. These results are used as a basis to provide app developers with certain recommendations. There is a need for better BD apps with more features in order to increase the number of volunteer donors.

Development of a Mobile App for Family Planning Providers.

PubMed

Halsall, Viannella; Rogers, Jennifer; Witt, Jacki; Song, Sejun; Nguyen, Hoang Duc Huy; Kelly, Patricia

To provide an overview of lessons learned during the development process of an app for iOS and Android based on national recommendations for providing quality family planning services. After a review of existing apps was conducted to determine whether an app of clinical recommendations for family planning existed, a team of clinicians, training specialists, and app developers created a resource app by first drafting a comprehensive content map. A prototype of the app was then pilot tested using smart tablets by a volunteer convenience sample of women's healthcare professionals. Outcomes measured included usability, acceptability, download analytics, and satisfaction by clinicians as reported through an investigator-developed tool. Sixty-nine professionals tested a prototype of the app, and completed a user satisfaction tool. Overall, user feedback was positive, and a zoom function was added to the final version as a result of the pilot test. Within 3 months of being publicly available, the app was downloaded 677 times, with 97% of downloads occurring on smart phones, 76% downloads occurring on iOS devices, and 24% on Android devices. This trend persisted throughout the following 3 months. Clinicians with an interest in developing an app should consider a team approach to development, pilot test the app prior to wider distribution, and develop a web-based version of the app to be used by clinicians who are unable to access smart devices in their practice setting.

Content, Usability, and Utilization of Plain Language in Breast Cancer Mobile Phone Apps: A Systematic Analysis.

PubMed

Ginossar, Tamar; Shah, Sayyed Fawad Ali; West, Andrew J; Bentley, Joshua M; Caburnay, Charlene A; Kreuter, Matthew W; Kinney, Anita Y

2017-03-13

Breast cancer is one of the leading contributors to preventable illness and death among women. Although mobile phone apps provide unprecedented opportunity to engage women along the cancer continuum, little is known about the availability, content, and usability of breast cancer mobile phone apps. This study analyzed the content and adherence to literate design standards of all breast cancer-related apps available on the App Store and Google Play, as well as the relationship between their content, user ratings, and price. Following identification and downloading of all available breast cancer mobile phone apps in October 2015, 101 apps were confirmed as focusing on breast cancer. Based on prior research, we adapted and applied a content analysis scheme that was specific to breast cancer apps, including their main purpose, relevance to the cancer care continuum, and adherence to usability standards outlined by the Institute of Medicine (IOM). The most common aim of apps was educational (73/101, 72.3%), followed by behavior change (24/101, 23.9%), fundraising (20/101, 19.8%), and advocacy (14/101, 13.9%). On the cancer continuum, primary prevention (strategies to prevent cancer cells from occurring) was mentioned in almost one-third of the apps (30/101, 29.7%). Less than half of the apps (46/101, 45.5%) presented information about mammography and/or breast clinical exam, and 53 apps (52.5%) discussed breast self-exam (which is no longer recommended). Symptoms of cancer prediagnosis, such as a lump, were discussed in almost half of the apps (48/101, 47.5%) and a similar number of apps included information about genetic risk for breast cancer (47/101, 46.5%). Information about breast cancer diagnosis was included in 42 apps (41.58%) and 43 (42.6%) apps discussed treatment options. Survivorship issues were addressed in 17 (16.8%) apps. Only one (1.0%) app discussed hospice. Adherence to usability recommendations was low. The median composite score was 3 (mean 2.60, SD 1.20) of the six recommended usability items. With eight plain language items, the median of the composite health literacy score was 5 (mean 5.06, SD 2.00). Most apps did not use easy-to-understand words (44/101, 43.6%) and few (24/101, 23.8%) defined key terms. Current breast cancer apps provide important information about breast cancer, but the most common topic covered is breast self-examination, a non-evidence-based screening strategy. Apps that focus on evidence-based strategies on the cancer continuum are needed, with a notable pressing need for apps that would address survivorship and end of life. Finally, developers of breast cancer apps should adhere to IOM standards to meet the needs of diverse populations and reduce current disparities. ©Tamar Ginossar, Sayyed Fawad Ali Shah, Andrew J West, Joshua M Bentley, Charlene A Caburnay, Matthew W Kreuter, Anita Y Kinney. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 13.03.2017.

Mobile Applications for Diabetics: A Systematic Review and Expert-Based Usability Evaluation Considering the Special Requirements of Diabetes Patients Age 50 Years or Older

PubMed Central

Quade, Mandy; Kirch, Wilhelm

2014-01-01

Background A multitude of mhealth (mobile health) apps have been developed in recent years to support effective self-management of patients with diabetes mellitus type 1 or 2. Objective We carried out a systematic review of all currently available diabetes apps for the operating systems iOS and Android. We considered the number of newly released diabetes apps, range of functions, target user groups, languages, acquisition costs, user ratings, available interfaces, and the connection between acquisition costs and user ratings. Additionally, we examined whether the available applications serve the special needs of diabetes patients aged 50 or older by performing an expert-based usability evaluation. Methods We identified relevant keywords, comparative categories, and their specifications. Subsequently, we performed the app review based on the information given in the Google Play Store, the Apple App Store, and the apps themselves. In addition, we carried out an expert-based usability evaluation based on a representative 10% sample of diabetes apps. Results In total, we analyzed 656 apps finding that 355 (54.1%) offered just one function and 348 (53.0%) provided a documentation function. The dominating app language was English (85.4%, 560/656), patients represented the main user group (96.0%, 630/656), and the analysis of the costs revealed a trend toward free apps (53.7%, 352/656). The median price of paid apps was €1.90. The average user rating was 3.6 stars (maximum 5). Our analyses indicated no clear differences in the user rating between free and paid apps. Only 30 (4.6%) of the 656 available diabetes apps offered an interface to a measurement device. We evaluated 66 apps within the usability evaluation. On average, apps were rated best regarding the criterion “comprehensibility” (4.0 out of 5.0), while showing a lack of “fault tolerance” (2.8 out of 5.0). Of the 66 apps, 48 (72.7%) offered the ability to read the screen content aloud. The number of functions was significantly negative correlated with usability. The presence of documentation and analysis functions reduced the usability score significantly by 0.36 and 0.21 points. Conclusions A vast number of diabetes apps already exist, but the majority offer similar functionalities and combine only one to two functions in one app. Patients and physicians alike should be involved in the app development process to a greater extent. We expect that the data transmission of health parameters to physicians will gain more importance in future applications. The usability of diabetes apps for patients aged 50 or older was moderate to good. But this result applied mainly to apps offering a small range of functions. Multifunctional apps performed considerably worse in terms of usability. Moreover, the presence of a documentation or analysis function resulted in significantly lower usability scores. The operability of accessibility features for diabetes apps was quite limited, except for the feature “screen reader”. PMID:24718852

A Guide to Help Consumers Choose Apps and Avoid App Overload

ERIC Educational Resources Information Center

Schuster, Ellen; Zimmerman, Lynda

2014-01-01

Mobile technology has transformed the way consumers access and use information. The exponential growth of mobile apps makes finding suitable, easy-to-use nutrition and health-related apps challenging. A guide for consumers helps them ask important questions before downloading apps. The guide can be adapted for other Extension disciplines.

From Common to Rare Variants: The Genetic Component of Alzheimer Disease.

PubMed

Nicolas, Gaël; Charbonnier, Camille; Campion, Dominique

2016-01-01

Alzheimer disease (AD) is a remarkable example of genetic heterogeneity. Extremely rare variants in the APP, PSEN1, or PSEN2 genes, or duplications of the APP gene cause autosomal dominant forms, generally with complete penetrance by the age of 65 years. Nonautosomal dominant forms are considered as a complex disorder with a high genetic component, whatever the age of onset. Although genetically heterogeneous, AD is defined by the same neuropathological criteria in all configurations. According to the amyloid cascade hypothesis, the Aβ peptide, which aggregates in AD brains, is a key player. APP, PSEN1, or PSEN2 gene mutations increase the production of more aggregation-prone forms of the Aβ peptide, triggering the pathological process. Several risk factors identified in association studies hit genes involved in Aβ production/secretion, aggregation, clearance, or toxicity. Among them, the APOE ε4 allele is a rare example of a common allele with a large effect size, the ORs ranging from 4 to 11-14 for heterozygous and homozygous carriers, respectively. In addition, genome-wide association studies have identified more than two dozen loci with a weak but significant association, the OR of the at-risk allele ranging from 1.08 to 1.30. Recently, the use of massive parallel sequencing has enabled the analysis of rare variants in a genome-wide manner. Two rare variants have been nominally associated with AD risk or protection (TREM2 p.R47H, MAF approximately 0.002, OR approximately 4 and APP p.A673T, MAF approximately 0.0005, OR approximately 0.2). Association analyses at the gene level identified rare loss-of-function and missense, predicted damaging, variants (MAF <0.01) in the SORL1 and ABCA7 genes associated with a moderate relative risk (OR approximately 5 and approximately 2.8, respectively). Although the latter analyses revealed association signals with moderately rare variants by collapsing them, the power to detect genes hit by extremely rare variants is still limited. An alternative approach is to consider the de novo paradigm, stating that de novo variants may contribute to AD genetics in sporadic patients. Here, we critically review AD genetics reports with a special focus on rare variants. © 2016 S. Karger AG, Basel.

Uncovering the popularity mechanisms for Facebook applications

NASA Astrophysics Data System (ADS)

Li, Sheng-Nan; Guo, Qiang; Yang, Kai; Liu, Jian-Guo; Zhang, Yi-Cheng

2018-03-01

Understanding the popularity dynamics of online application(App) is significant for the online social systems. In this paper, by dividing the Facebook Apps into different groups in terms of their popularities, we empirically investigate the popularity dynamics for different kinds of Facebook Apps. Then, taking into account the influence of cumulative and recent popularities on the user choice, we present a model to regenerate the growth of popularity for different App groups. The experimental results of 917 Facebook Apps show that as the popularities of Facebook Apps increase, the recent popularity plays more important role. Specifically, the recent popularity plays more important role in regenerating the popularity dynamics for more popular Apps, and the cumulative popularity plays more important role for unpopular Apps. We also conduct temporal analysis on the growth characteristic of individual App by comparing the increment at each time with the average of historical records. The results show that the growth of more popular App tends to fluctuate more greatly. Our work may shed some lights for deeply understanding the popularity mechanism for online applications.

Research on the development and preliminary application of Beijing agricultural sci-tech service hotline WebApp in agricultural consulting services

NASA Astrophysics Data System (ADS)

Yu, Weishui; Luo, Changshou; Zheng, Yaming; Wei, Qingfeng; Cao, Chengzhong

2017-09-01

To deal with the “last kilometer” problem during the agricultural science and technology information service, we analyzed the feasibility, necessity and advantages of WebApp applied to agricultural information service and discussed the modes of WebApp used in agricultural information service based on the requirements analysis and the function of WebApp. To overcome the existing App’s defects of difficult installation and weak compatibility between the mobile operating systems, the Beijing Agricultural Sci-tech Service Hotline WebApp was developed based on the HTML and JAVA technology. The WebApp has greater compatibility and simpler operation than the Native App, what’s more, it can be linked to the WeChat public platform making it spread easily and run directly without setup process. The WebApp was used to provide agricultural expert consulting services and agriculture information push, obtained a good preliminary application achievement. Finally, we concluded the creative application of WebApp in agricultural consulting services and prospected the development of WebApp in agricultural information service.

A Social Network Analysis of the Financial Links Backing Health and Fitness Apps.

PubMed

Grundy, Quinn; Held, Fabian; Bero, Lisa

2017-11-01

To identify the major stakeholders in mobile health app development and to describe their financial relationships using social network analysis. We conducted a structured content analysis of a purposive sample of prominent health and fitness apps available in November 2015 in the United States, Canada, and Australia. We conducted a social network analysis of apps' developers, investors, other funding sources, and content advisors to describe the financial relationships underpinning health app development. Prominent health and fitness apps are largely developed by private companies based in North America, with an average of 4.7 (SD = 5.5) financial relations, including founders, external investors, acquiring companies, and commercial partnerships. Network analysis revealed a core of 41 sampled apps connected to 415 other entities by 466 financial relations. This core largely comprised apps published by major technology, pharmaceutical, and fashion corporations. About one third of apps named advisors, many of whom had commercial affiliations. Public health needs to extend its scrutiny and advocacy beyond the health messages contained within apps to understanding commercial influences on health and, when necessary, challenging them.

Activity-induced convergence of APP and BACE-1 in acidic microdomains via an endocytosis-dependent pathway

PubMed Central

Das, Utpal; Scott, David; Ganguly, Archan; Koo, Edward H.; Tang, Yong; Roy, Subhojit

2013-01-01

The convergence of APP (substrate) and BACE-1 (enzyme) is a rate-limiting, obligatory event triggering the amyloidogenic pathway – a key step in Alzheimer’s disease (AD) pathology. However, as both APP/BACE-1 are highly expressed in brain, mechanisms precluding their unabated convergence are unclear. Exploring dynamic localization of APP/BACE-1 in cultured hippocampal neurons, we found that after synthesis via the secretory-pathway, dendritic APP/BACE-1-containing vesicles are largely segregated in physiologic states. While BACE-1 is largely sorted into acidic recycling endosomes, APP is conveyed in Golgi-derived vesicles. However upon activity-induction – a known trigger of the amyloidogenic pathway – APP is routed into BACE-1-positive recycling endosomes via a clathrin-dependent mechanism. A partitioning/convergence of APP/BACE-1 vesicles is also apparent in control/AD brains respectively. Considering BACE-1 is optimally active in an acidic environment, our experiments suggest that neurons have evolved trafficking strategies that normally limit APP/BACE-1 proximity; and also uncover a pathway routing APP into BACE-1-containing organelles – triggering amyloidogenesis. PMID:23931995

mHealth App for Cannabis Users: Satisfaction and Perceived Usefulness.

PubMed

Monney, Grégoire; Penzenstadler, Louise; Dupraz, Olivia; Etter, Jean-François; Khazaal, Yasser

2015-01-01

The aim of this study was to describe the characteristics of cannabis users and their levels of satisfaction with Stop-cannabis, an app intended for cannabis users who want to stop or reduce their cannabis use or prevent relapse. A cross-sectional online survey was administered to users of Stop-cannabis, a French-language app for iOS and Android devices. All app users were invited to participate in the survey via a message sent to the app. For hundred and eighty-two users answered the survey. The app was used daily by 348 of the participants (around 70%). More than 80% of participants (397) considered the app to have helped them "a little" or "a lot" to stop or reduce cannabis consumption. Most of the users' suggestions were related to the number or the quality of the messages sent by, or displayed in, the app. This pilot study supports the feasibility of such an app and its perceived usefulness. A self-selection bias, however, limits the conclusions of the study. The efficacy of the app should be evaluated in a randomized controlled trial.

Mobile Apps for Self-Injury: A Content Analysis.

PubMed

Vieira, Aaron M; Lewis, Stephen P

2018-05-01

A growing body of research points to the salience of the Internet and mobile material among individuals who self-injure. However, to date, no research has investigated the mobile apps related to nonsuicidal self-injury (NSSI). Such information would clarify which apps may be useful for those who self-injure while highlighting whether app-related content warrants improvement. The current study examined the content and usability of NSSI apps available on the two largest app-related platforms (Google Play and iTunes). Using content analysis, apps were examined regarding their content (e.g., presence of NSSI myths and types of coping strategies) as well as usability (e.g., app performance). Results indicate that NSSI apps have varied content, with few developed by, or affiliated with, a trusted source (e.g., university). NSSI apps tend to not propagate NSSI myths that vary with respect to the quality of coping strategies offered. They also tend to be rated favorably in terms of their usability. Overall, the present findings add to the NSSI literature and highlight several implications and avenues for future work, which are discussed.

The Use of Communication Apps by Medical Staff in the Australian Health Care System: Survey Study on Prevalence and Use.

PubMed

Nikolic, Amanda; Wickramasinghe, Nilmini; Claydon-Platt, Damian; Balakrishnan, Vikram; Smart, Philip

2018-02-09

The use of communication apps on mobile phones offers an efficient, unobtrusive, and portable mode of communication for medical staff. The potential enhancements in patient care and education appear significant, with clinical details able to be shared quickly within multidisciplinary teams, supporting rapid integration of disparate information, and more efficient patient care. However, sharing patient data in this way also raises legal and ethical issues. No data is currently available demonstrating how widespread the use of these apps are, doctor's attitudes towards them, or what guides clinician choice of app. The objective of this study was to quantify and qualify the use of communication apps among medical staff in clinical situations, their role in patient care, and knowledge and attitudes towards safety, key benefits, potential disadvantages, and policy implications. Medical staff in hospitals across Victoria (Australia) were invited to participate in an anonymous 33-question survey. The survey collected data on respondent's demographics, their use of communication apps in clinical settings, attitudes towards communication apps, perceptions of data "safety," and why one communication app was chosen over others. Communication apps in Victorian hospitals are in widespread use from students to consultants, with WhatsApp being the primary app used. The median number of messages shared per day was 12, encompassing a range of patient information. All respondents viewed these apps positively in quickly communicating patient information in a clinical setting; however, all had concerns about the privacy implications arising from sharing patient information in this way. In total, 67% (60/90) considered patient data "moderately safe" on these apps, and 50% (46/90) were concerned the use of these apps was inconsistent with current legislation and policy. Apps were more likely to be used if they were fast, easy to use, had an easy login process, and were already in widespread use. Communication app use by medical personnel in Victorian hospitals is pervasive. These apps contribute to enhanced communication between medical staff, but their use raises compliance issues, most notably with Australian privacy legislation. Development of privacy-compliant apps such as MedX needs to prioritize a user-friendly interface and market the product as a privacy-compliant comparator to apps previously adapted to health care settings. ©Amanda Nikolic, Nilmini Wickramasinghe, Damian Claydon-Platt, Vikram Balakrishnan, Philip Smart. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 09.02.2018.

mHealth and Mobile Medical Apps: A Framework to Assess Risk and Promote Safer Use

PubMed Central

2014-01-01

The use of mobile medical apps by clinicians and others has grown considerably since the introduction of mobile phones. Medical apps offer clinicians the ability to access medical knowledge and patient data at the point of care, but several studies have highlighted apps that could compromise patient safety and are potentially dangerous. This article identifies a range of different kinds of risks that medical apps can contribute to and important contextual variables that can modify these risks. We have also developed a simple generic risk framework that app users, developers, and other stakeholders can use to assess the likely risks posed by a specific app in a specific context. This should help app commissioners, developers, and users to manage risks and improve patient safety. PMID:25223398

mHealth and mobile medical Apps: a framework to assess risk and promote safer use.

PubMed

Lewis, Thomas Lorchan; Wyatt, Jeremy C

2014-09-15

The use of mobile medical apps by clinicians and others has grown considerably since the introduction of mobile phones. Medical apps offer clinicians the ability to access medical knowledge and patient data at the point of care, but several studies have highlighted apps that could compromise patient safety and are potentially dangerous. This article identifies a range of different kinds of risks that medical apps can contribute to and important contextual variables that can modify these risks. We have also developed a simple generic risk framework that app users, developers, and other stakeholders can use to assess the likely risks posed by a specific app in a specific context. This should help app commissioners, developers, and users to manage risks and improve patient safety.

Relevance of Trust Marks and CE Labels in German-Language Store Descriptions of Health Apps: Analysis

PubMed Central

Hillebrand, Uta; von Jan, Ute

2018-01-01

Background In addition to mandatory CE marking (“CE” representing Conformité Européenne, with the CE marking being a symbol of free marketability in the European Economic Area) for medical devices, there are various seals, initiatives, action groups, etc, in the health app context. However, whether manufacturers use them to distinguish their apps and attach relevance to them is unclear. Objective The objective was to take a snapshot of quality seals, regulatory marks, and other orientation aids available on the German app market and to determine whether manufacturers deem such labels relevant enough to apply them to their apps, namely as reflected by mentions in app description texts in a typical app store (ie, Apple’s App Store). Methods A full survey of the metadata of 103,046 apps from Apple’s German App Store in the Medicine and Health & Fitness categories was carried out. For apps with German-language store descriptions (N=8767), these were automatically searched for the occurrence of relevant keywords and validated manually (N=41). In addition, the websites of various app seal providers were checked for assigned seals. Results Few manufacturers referenced seals in the descriptions (5/41), although this would have been expected more often based on the seals we were able to identify from the seal providers’ Web pages, and there were 34 of 41 that mentioned CE status in the descriptions. Two apps referenced an app directory curated by experts; however, this is not an alternative to CE marks and seals of approval. Conclusions Currently, quality seals seem to be irrelevant for manufacturers. In line with regulatory requirements, mentions of medical device status are more frequent; however, neither characteristic is effective for identifying high-quality apps. To improve this situation, a possibly legally obligatory, standardized reporting system should be implemented. PMID:29695374

Awareness and Use of mHealth Apps: A Study from England

PubMed Central

Kayyali, Reem; Peletidi, Aliki; Ismail, Muhammad; Hashim, Zahra; Bandeira, Pedro; Bonnah, Jennifer

2017-01-01

Purpose: Mobile health (mHealth) solutions have become an inevitable element of the healthcare landscape. The recommendation and use of mHealth is important, but it is often underutilised. This study was conducted in England. It aimed to determine the use and recommendation of mHealth apps by pharmacists, the public’s perceptions of mHealth apps in general, and the awareness and use of health apps by diabetic patients in particular. Methods: The study used a mixed research approach, utilising a sequence of survey-based questionnaires with pharmacists and the general public, followed by semi-structured interviews with diabetic patients. Results: Pharmacists’ questionnaires revealed that 56% of the respondents were aware of health apps, 60% of which recommended them to patients. Over 76% of the individuals owned a smartphone. The types of applications that saw the most use from the general public were health and lifestyle apps (24%), social apps (19%), followed by news (18%). Although eight out of nine diabetic patients owned a smartphone, only three used diabetes apps. Diabetic patients also suggested an interest in using diabetes apps to aid in optimising care via the utilisation of visual aids, reminders, recording patient data, social coaching, and remote collaboration with healthcare professionals (HCPs), but time was seen as the biggest obstacle to using a diabetes mHealth application. Conclusion: Despite the growing number of mHealth apps, the level of awareness and usability of such apps by patients and pharmacists was still relatively low. Nevertheless, the majority who used health apps found them to be beneficial, and the public agreed that it helped them to live a healthier lifestyle. Therefore, health apps have great potential in health promotion. Pharmacists are ideally placed to promote them and make patients more aware of them. To increase the use of these apps, it is necessary to first increase awareness and knowledge of these apps, both to the public and to healthcare professionals. PMID:28970445

Interest in a Mobile App for Two-Way Risk Communication: A Survey Study Among European Healthcare Professionals and Patients.

PubMed

de Vries, Sieta T; Denig, Petra; Lasheras Ruiz, Carmen; Houÿez, François; Wong, Lisa; Sutcliffe, Alastair; Mol, Peter G M

2018-07-01

Previously, an app has been developed for healthcare professionals (HCPs) and patients to report adverse drug reactions (ADRs) to national medicines agencies and to receive drug safety information. This study aimed to assess (1) European HCPs' and patients' interest in an app for this two-way risk communication; (2) their preferences and perceptions towards specific app characteristics; and (3) which HCPs and patients are particularly interested in the app. In addition, these aspects were studied specifically for the countries where such an app was already available, i.e. Croatia, The Netherlands, and The UK. European HCPs and patients were asked to complete a web-based survey developed in the context of the Web-Recognizing Adverse Drug Reactions (Web-RADR) project. Data on app interest and preferences and perceptions towards app characteristics were analysed descriptively. Logistic regression analyses were conducted to assess the association of HCP characteristics and patient characteristics on the level of interest in the app (i.e. very interested vs. not/somewhat interested). In total, 399 HCPs and 656 patients completed the survey. About half of the patients (48%; ranging from 38% from The Netherlands to 54% from The UK), and 61% of the HCPs (ranging from 42% from The Netherlands to 54% from The UK) were very interested in the app. A faster means of reporting ADRs and easier access to the reporting form were the main perceived benefits. HCPs and patients who already use a health app were particularly interested in the app (HCPs: odds ratio [OR] 3.52; 95% confidence interval [CI] 1.96-6.30, patients: OR 1.64; 95% CI 1.19-2.27). An app is positively perceived by HCPs and patients for reporting ADRs quickly and for receiving drug safety information from national medicines agencies. In particular, HCPs and patients who already use other health apps were interested in the app.

There’s an App for That: Content Analysis of Paid Health and Fitness Apps

PubMed Central

Hall, P. Cougar; Hanson, Carl L; Barnes, Michael D; Giraud-Carrier, Christophe; Barrett, James

2012-01-01

Background The introduction of Apple’s iPhone provided a platform for developers to design third-party apps, which greatly expanded the functionality and utility of mobile devices for public health. Objective This study provides an overview of the developers’ written descriptions of health and fitness apps and appraises each app’s potential for influencing behavior change. Methods Data for this study came from a content analysis of health and fitness app descriptions available on iTunes during February 2011. The Health Education Curriculum Analysis Tool (HECAT) and the Precede-Proceed Model (PPM) were used as frameworks to guide the coding of 3336 paid apps. Results Compared to apps with a cost less than US $0.99, apps exceeding US $0.99 were more likely to be scored as intending to promote health or prevent disease (92.55%, 1925/3336 vs 83.59%, 1411/3336; P<.001), to be credible or trustworthy (91.11%, 1895/3336 vs 86.14%, 1454/3349; P<.001), and more likely to be used personally or recommended to a health care client (72.93%, 1517/2644 vs 66.77%, 1127/2644; P<.001). Apps related to healthy eating, physical activity, and personal health and wellness were more common than apps for substance abuse, mental and emotional health, violence prevention and safety, and sexual and reproductive health. Reinforcing apps were less common than predisposing and enabling apps. Only 1.86% (62/3336) of apps included all 3 factors (ie, predisposing, enabling, and reinforcing). Conclusions Development efforts could target public health behaviors for which few apps currently exist. Furthermore, practitioners should be cautious when promoting the use of apps as it appears most provide health-related information (predisposing) or make attempts at enabling behavior, with almost none including all theoretical factors recommended for behavior change. PMID:22584372

Who are mobile app users from healthy lifestyle websites? Analysis of patterns of app use and user characteristics.

PubMed

Elavsky, Steriani; Smahel, David; Machackova, Hana

2017-12-01

The use of online communities and websites for health information has proliferated along with the use of mobile apps for managing health behaviors such as diet and exercise. The scarce evidence available to date suggests that users of these websites and apps differ in significant ways from non-users but most data come from US- and UK-based populations. In this study, we recruited users of nutrition, weight management, and fitness-oriented websites in the Czech Republic to better understand who uses mobile apps and who does not, including user sociodemographic and psychological profiles. Respondents aged 13-39 provided information on app use through an online survey (n = 669; M age = 24.06, SD = 5.23; 84% female). Among users interested in health topics, respondents using apps for managing nutrition, weight, and fitness (n = 403, 60%) were more often female, reported more frequent smartphone use, and more expert phone skills. In logistic regression models, controlling for sociodemographics, web, and phone activity, mHealth app use was predicted by levels of excessive exercise (OR 1.346, 95% CI 1.061-1.707, p < .01). Among app users, we found differences in types of apps used by gender, age, and weight status. Controlling for sociodemographics and web and phone use, drive for thinness predicted the frequency of use of apps for healthy eating (β = 0.14, p < .05), keeping a diet (β = 0.27, p < .001), and losing weight (β = 0.33, p < .001), whereas excessive exercise predicted the use of apps for keeping a diet (β = 0.18, p < .01), losing weight (β = 0.12, p < .05), and managing sport/exercise (β = 0.28, p < .001). Sensation seeking was negatively associated with the frequency of use of apps for maintaining weight (β = - 0.13, p < .05). These data unveil the user characteristics of mHealth app users from nutrition, weight management, and fitness websites, helping inform subsequent design of mHealth apps and mobile intervention strategies.

APP Processing Induced by Herpes Simplex Virus Type 1 (HSV-1) Yields Several APP Fragments in Human and Rat Neuronal Cells

PubMed Central

Civitelli, Livia; Argnani, Rafaela; Piacentini, Roberto; Ripoli, Cristian; Manservigi, Roberto; Grassi, Claudio; Garaci, Enrico; Palamara, Anna Teresa

2010-01-01

Lifelong latent infections of the trigeminal ganglion by the neurotropic herpes simplex virus type 1 (HSV-1) are characterized by periodic reactivation. During these episodes, newly produced virions may also reach the central nervous system (CNS), causing productive but generally asymptomatic infections. Epidemiological and experimental findings suggest that HSV-1 might contribute to the pathogenesis of Alzheimer's disease (AD). This multifactorial neurodegenerative disorder is related to an overproduction of amyloid beta (Aβ) and other neurotoxic peptides, which occurs during amyloidogenic endoproteolytic processing of the transmembrane amyloid precursor protein (APP). The aim of our study was to identify the effects of productive HSV-1 infection on APP processing in neuronal cells. We found that infection of SH-SY5Y human neuroblastoma cells and rat cortical neurons is followed by multiple cleavages of APP, which result in the intra- and/or extra-cellular accumulation of various neurotoxic species. These include: i) APP fragments (APP-Fs) of 35 and 45 kDa (APP-F35 and APP-F45) that comprise portions of Aβ; ii) N-terminal APP-Fs that are secreted; iii) intracellular C-terminal APP-Fs; and iv) Aβ1-40 and Aβ1-42. Western blot analysis of infected-cell lysates treated with formic acid suggests that APP-F35 may be an Aβ oligomer. The multiple cleavages of APP that occur in infected cells are produced in part by known components of the amyloidogenic APP processing pathway, i.e., host-cell β-secretase, γ-secretase, and caspase-3-like enzymes. These findings demonstrate that HSV-1 infection of neuronal cells can generate multiple APP fragments with well-documented neurotoxic potentials. It is tempting to speculate that intra- and extracellular accumulation of these species in the CNS resulting from repeated HSV-1 reactivation could, in the presence of other risk factors, play a co-factorial role in the development of AD. PMID:21085580

Relevance of Trust Marks and CE Labels in German-Language Store Descriptions of Health Apps: Analysis.

PubMed

Albrecht, Urs-Vito; Hillebrand, Uta; von Jan, Ute

2018-04-25

In addition to mandatory CE marking ("CE" representing Conformité Européenne, with the CE marking being a symbol of free marketability in the European Economic Area) for medical devices, there are various seals, initiatives, action groups, etc, in the health app context. However, whether manufacturers use them to distinguish their apps and attach relevance to them is unclear. The objective was to take a snapshot of quality seals, regulatory marks, and other orientation aids available on the German app market and to determine whether manufacturers deem such labels relevant enough to apply them to their apps, namely as reflected by mentions in app description texts in a typical app store (ie, Apple's App Store). A full survey of the metadata of 103,046 apps from Apple's German App Store in the Medicine and Health & Fitness categories was carried out. For apps with German-language store descriptions (N=8767), these were automatically searched for the occurrence of relevant keywords and validated manually (N=41). In addition, the websites of various app seal providers were checked for assigned seals. Few manufacturers referenced seals in the descriptions (5/41), although this would have been expected more often based on the seals we were able to identify from the seal providers' Web pages, and there were 34 of 41 that mentioned CE status in the descriptions. Two apps referenced an app directory curated by experts; however, this is not an alternative to CE marks and seals of approval. Currently, quality seals seem to be irrelevant for manufacturers. In line with regulatory requirements, mentions of medical device status are more frequent; however, neither characteristic is effective for identifying high-quality apps. To improve this situation, a possibly legally obligatory, standardized reporting system should be implemented. ©Urs-Vito Albrecht, Uta Hillebrand, Ute von Jan. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 25.04.2018.

Hospital-Owned Apps in Taiwan: Nationwide Survey

PubMed Central

Liu, Hao-Yen; Sun, Ying-Chou; Fen, Jun-Jeng; Chen, Tzeng-Ji; Chou, Li-Fang; Hwang, Shinn-Jang

2018-01-01

Background Over the last decade, the use of mobile phone apps in the health care industry has grown rapidly. Owing to the high penetration rate of Internet use in Taiwan, hospitals are eager to provide their own apps to improve the accessibility of medical care for patients. Objective The aims of this study were to provide an overview of the currently available hospital-owned apps in Taiwan and to conduct a cross-hospital comparison of app features. Methods In May 2017, the availability of apps from all 414 hospitals in Taiwan was surveyed from the hospital home pages and the Google Play app store. The features of the downloaded apps were then examined in detail and, for each app, the release date of the last update, download frequency, and rating score were obtained from Google Play. Results Among all the 414 hospitals in Taiwan, 150 (36.2%) owned Android apps that had been made available for public use, including 95% (18/19) of the academic medical centers, 77% (63/82) of the regional hospitals, and 22.0% (69/313) of the local community hospitals. Among the 13 different functionalities made available by the various hospital-owned apps, the most common were the doctor search (100%, 150/150), real-time queue monitoring (100%, 150/150), and online appointment scheduling (94.7%, 142/150) functionalities. The majority of apps (57.3%, 86/150) had a rating greater than 4 out of 5, 49.3% (74/150) had been updated at some point in 2017, and 36.0% (54/150) had been downloaded 10,000 to 50,000 times. Conclusions More than one-third of the hospitals owned apps intended to increase patient access to health care. The most common app features might reflect the health care situation in Taiwan, where the overcrowded outpatient departments of hospitals operate in an open-access mode without any strict referral system. Further research should focus on the effectiveness and safety of these apps. PMID:29339347

Challenges During Implementation of a Patient-Facing Mobile App for Surgical Rehabilitation: Feasibility Study

PubMed Central

Piper, Kalman; Bokor, Desmond; Martin, Paige; Lau, Victor SL; Coiera, Enrico

2017-01-01

Background Translating research into practice, especially the implementation of digital health technologies in routine care, is increasingly important. Yet, there are few studies examining the challenges of implementing patient-facing digital technologies in health care settings. Objective The aim of this study was to report challenges experienced when implementing mobile apps for patients to support their postsurgical rehabilitation in an orthopedic setting. Methods A mobile app was tailored to the needs of patients undergoing rotator cuff repair. A 30-min usability session and a 12-week feasibility study were conducted with patients to evaluate the app in routine care. Implementation records (observation reports, issues log, and email correspondence) explored factors that hindered or facilitated patient acceptance. Interviews with clinicians explored factors that influenced app integration in routine care. Results Participant completion was low (47%, 9/19). Factors that affected patient acceptance included digital literacy, health status, information technology (IT) infrastructure at home, privacy concerns, time limitations, the role of a caregiver, inconsistencies in instruction received from clinicians and the app, and app advice not reflective of patient progress over time. Factors that negatively influenced app integration in routine care included competing demands among clinicians, IT infrastructure in health care settings, identifying the right time to introduce the app to patients, user interface complexity for older patients, lack of coordination among multidisciplinary clinicians, and technical issues with app installation. Conclusions Three insights were identified for mobile app implementation in routine care: (1) apps for patients need to reflect their journey over time and in particular, postoperative apps ought to be introduced as part of preoperative care with opportunities for patients to learn and adopt the app during their postoperative journey; (2) strategies to address digital literacy issues among patients and clinicians are essential; and (3) impact of the app on patient outcomes and clinician workflow needs to be communicated, monitored, and reviewed. Lastly, digital health interventions should supplement but not replace patient interaction with clinicians. PMID:29217504

Building Mobile Apps for Underrepresented Mental Health care Consumers: A Grounded Theory Approach.

PubMed

Leung, Ricky; Hastings, Julia F; Keefe, Robert H; Brownstein-Evans, Carol; Chan, Keith T; Mullick, Rosemary

2016-01-01

Cell phone mobile application ("app") use has risen dramatically within the past several years. Many individuals access apps to address mental health issues. Unlike individuals from privileged backgrounds, individuals from oppressed backgrounds may rely on apps rather than costly mental health treatment. To date, very little research has been published evaluating mental health apps' effectiveness. This paper focuses on three methods through which grounded theory can facilitate app development and evaluation for people underrepresented in mental health care. Recommendations are made to advance mobile app technology that will help clinicians provide effective treatment, and consumers to realize positive treatment outcomes.

Chinese Cardiovascular Disease Mobile Apps' Information Types, Information Quality, and Interactive Functions for Self-Management: Systematic Review.

PubMed

Xie, Bo; Su, Zhaohui; Zhang, Wenhui; Cai, Run

2017-12-14

China has a large population with cardiovascular disease (CVD) that requires extensive self-management. Mobile health (mHealth) apps may be a useful tool for CVD self-management. Little is currently known about the types and quality of health information provided in Chinese CVD mobile apps and whether app functions are conducive to promoting CVD self-management. We undertook a systematic review to evaluate the types and quality of health information provided in Chinese CVD mobile apps and interactive app functions for promoting CVD self-management. Mobile apps targeting end users in China with CVD conditions were selected in February 2017 through a multi-stage process. Three frameworks were used to evaluate the selected apps: (1) types of health information offered were assessed using our Health Information Wants framework, which encompasses 7 types of information; (2) quality of information provided in the apps was assessed using the 11 guidelines recommended by the National Library of Medicine of the National Institutes of Health; and (3) types of interactive app functions for CVD self-management were assessed using a 15-item framework adapted from the literature, including our own prior work. Of 578 apps identified, 82 were eligible for final review. Among these, information about self-care (67/82, 82%) and information specifically regarding CVD (63/82, 77%) were the most common types of information provided, while information about health care providers (22/82, 27%) and laboratory tests (5/82, 6%) were least common. The most common indicators of information quality were the revealing of apps' providers (82/82, 100%) and purpose (82/82, 100%), while the least common quality indicators were the revealing of how apps' information was selected (1/82, 1%) and app sponsorship (0/82, 0%). The most common interactive functions for CVD self-management were those that enabled user interaction with the app provider (57/82, 70%) and with health care providers (36/82, 44%), while the least common interactive functions were those that enabled lifestyle management (13/82, 16%) and psychological health management (6/82, 7%). None of the apps covered all 7 types of health information, all 11 indicators of information quality, or all 15 interactive functions for CVD self-management. Chinese CVD apps are insufficient in providing comprehensive health information, high-quality information, and interactive functions to facilitate CVD self-management. End users should exercise caution when using existing apps. Health care professionals and app developers should collaborate to better understand end users' preferences and follow evidence-based guidelines to develop mHealth apps conducive to CVD self-management. ©Bo Xie, Zhaohui Su, Wenhui Zhang, Run Cai. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 14.12.2017.

Locking it down

PubMed Central

Grindrod, Kelly; Boersema, Jonathan; Waked, Khrystine; Smith, Vivian; Yang, Jilan; Gebotys, Catherine

2016-01-01

Objective: To explore the privacy and security of free medication applications (apps) available to Canadian consumers. Methods: The authors searched the Canadian iTunes store for iOS apps and the Canadian Google Play store for Android apps related to medication use and management. Using an Apple iPad Air 2 and a Google Nexus 7 tablet, 2 reviewers generated a list of apps that met the following inclusion criteria: free, available in English, intended for consumer use and related to medication management. Using a standard data collection form, 2 reviewers independently coded each app for the presence/absence of passwords, the storage of personal health information, a privacy statement, encryption, remote wipe and third-party sharing. A Cohen’s Kappa statistic was used to measure interrater agreement. Results: Of the 184 apps evaluated, 70.1% had no password protection or sign-in system. Personal information, including name, date of birth and gender, was requested by 41.8% (77/184) of apps. Contact information, such as address, phone number and email, was requested by 25% (46/184) of apps. Finally, personal health information, other than medication name, was requested by 89.1% (164/184) of apps. Only 34.2% (63/184) of apps had a privacy policy in place. Conclusion: Most free medication apps offer very limited authentication and privacy protocols. As a result, the onus currently falls on patients to input information in these apps selectively and to be aware of the potential privacy issues. Until more secure systems are built, health care practitioners cannot fully support patients wanting to use such apps. PMID:28286594

An Australian survey of women's use of pregnancy and parenting apps.

PubMed

Lupton, Deborah; Pedersen, Sarah

2016-08-01

There are now many pregnancy and parenting apps available on the market for both pregnancy and parenting. To investigate how Australian women use pregnancy and parenting apps, their attitudes about the information provided and data privacy and security related to such use, and what features they look for in these apps. An online survey was completed by 410 women who were pregnant or had given birth to at least one child in the past three years, were aged between 18 and 45 and were competent in English. The use of pregnancy and parenting apps was common among the respondents. Almost three quarters of respondents had used at least one pregnancy app; half reported using at least one parenting app. Respondents found the apps useful or helpful, particularly for providing information, monitoring foetal or child development and changes in their own bodies and providing reassurance. Yet many users were not actively assessing the validity of the content of these apps or considering issues concerning the security and privacy of the personal information about themselves and their children that these apps collect. Apps are becoming important as a source of information and self-monitoring and for providing reassurance for Australian pregnant women and mothers with young children. Midwives and other healthcare professionals providing care and support for pregnant women and women in the early years of motherhood need to take women's app use into account and recognise both the potential and limitations of these apps. Copyright © 2016 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Free mobile apps on depression for Indian users: A brief overview and critique.

PubMed

Kumar, Satish; Mehrotra, Seema

2017-08-01

The present study aimed at identifying the nature of mobile apps available to Indian android phone users who might search for free apps to help them deal with depression. The specific objectives were to examine the available interactive self-care apps in terms of guidance provided to users to make decisions regarding use of app, inclusion of elements that encourage professional help-seeking, guidance regarding managing psychological crisis and the range of therapeutic strategies incorporated. Using the search term 'depression', 278 apps were identified in the first step and these spanned a wide range of categories. Information on coping with depression and stand alone screening tools formed the two largest types of free apps. Features of interactive self-care apps (N = 33) were reviewed further and this exercise showed that less than 10% of the apps incorporated explicit delineation of their scope or initial screening for suitability. Guidance regarding managing suicidal crisis were incorporated in only about 12% of the interactive apps. Slightly more than one third of these apps included content aimed at encouraging professional help seeking when needed or an explicit mention of their theoretical or empirical basis. Monitoring moods, thoughts and behaviors were the commonest therapeutic strategies incorporated in these apps, in addition, to a wide range of other strategies such as behavioral activation, identifying and correcting cognitive errors, mindfulness exercises, cultivation of gratitude, and medication management. The challenges for a potential user of these apps are discussed and ways to address the same are highlighted. Copyright © 2017 Elsevier B.V. All rights reserved.

iPhone applications for eye care professionals: a review of current capabilities and concerns.

PubMed

Cheng, Nicholas M; Chakrabarti, Rahul; Kam, Jonathan K

2014-04-01

To quantitatively review and categorize the eye care-related iPhone(®) (Apple(®), Cupertino, CA) applications ("apps") currently available, evaluate qualified professional involvement in app development, and suggest future needs in this emerging area of mobile health. The Apple iTunes(®) store was searched for iPhone eye care-themed apps using the general terms "ophthalmology," "ophthalmologist," "optometry," "optometrist," "eye care," and "ocular," in addition to terms based on the Centers for Disease Control and Prevention's common eye conditions. Data collected from each app included publication date, target audience, category of app, estimated number of downloads, average user rating, and documented involvement of qualified professionals. In total, 182 apps were identified. The majority of apps lacked community user ratings and had 3,000 or fewer downloads (84% and 69%, respectively). Consistent with other medical specialties, only 37% of apps had documented qualified professional involvement in their development. When stratified by intended audience, 52% and 44% of apps designed for ophthalmologists and optometrists, respectively, had professional input, compared with 31% for non-eye care clinicians and 21% for the general public. Smartphone apps are likely to become of increasingly greater relevance to the modern eye care professional with tremendous versatility in daily practice. However, despite the rapid emergence of eye care apps, a low level of qualified professional involvement in app development and a lack of peer review after publishing remain. There is a clear need for evidence-based principles and standards of app development to be adopted in this emerging area.

Lysosome and calcium dysregulation in Alzheimer's disease: partners in crime.

PubMed

McBrayer, MaryKate; Nixon, Ralph A

2013-12-01

Early-onset FAD (familial Alzheimer's disease) is caused by mutations of PS1 (presenilin 1), PS2 (presenilin 2) and APP (amyloid precursor protein). Beyond the effects of PS1 mutations on proteolytic functions of the γ-secretase complex, mutant or deficient PS1 disrupts lysosomal function and Ca2+ homoeostasis, both of which are considered strong pathogenic factors in FAD. Loss of PS1 function compromises assembly and proton-pumping activity of the vacuolar-ATPase on lysosomes, leading to defective lysosomal acidification and marked impairment of autophagy. Additional dysregulation of cellular Ca2+ by mutant PS1 in FAD has been ascribed to altered ion channels in the endoplasmic reticulum; however, rich stores of Ca2+ in lysosomes are also abnormally released in PS1-deficient cells secondary to the lysosomal acidification defect. The resultant rise in cytosolic Ca2+ activates Ca2+-dependent enzymes, contributing substantially to calpain overactivation that is a final common pathway leading to neurofibrillary degeneration in all forms of AD (Alzheimer's disease). In the present review, we discuss the close inter-relationships among deficits of lysosomal function, autophagy and Ca2+ homoeostasis as a pathogenic process in PS1-related FAD and their relevance to sporadic AD.

The Totality App — General Lessons and Future Eclipses

NASA Astrophysics Data System (ADS)

Bennett, Jeffrey

2018-06-01

With the excitement around the 2017 eclipse, I worked with an app development company to create the Totality app, which featured eclipse predictions from the code of Xavier Jubier. We have since updated the app for future eclipses, including a Spanish version given the upcoming eclipses in Chile/Argentina. I will briefly discuss the current app, the process through which we developed it, and relevant lessons learned along the way that may be useful to others interested in developing apps for astronomy education.

Reconstruction of Arctic surface temperature in past 100 years using DINEOF

NASA Astrophysics Data System (ADS)

Zhang, Qiyi; Huang, Jianbin; Luo, Yong

2015-04-01

Global annual mean surface temperature has not risen apparently since 1998, which is described as global warming hiatus in recent years. However, measuring of temperature variability in Arctic is difficult because of large gaps in coverage of Arctic region in most observed gridded datasets. Since Arctic has experienced a rapid temperature change in recent years that called polar amplification, and temperature risen in Arctic is faster than global mean, the unobserved temperature in central Arctic will result in cold bias in both global and Arctic temperature measurement compared with model simulations and reanalysis datasets. Moreover, some datasets that have complete coverage in Arctic but short temporal scale cannot show Arctic temperature variability for long time. Data Interpolating Empirical Orthogonal Function (DINEOF) were applied to fill the coverage gap of NASA's Goddard Institute for Space Studies Surface Temperature Analysis (GISTEMP 250km smooth) product in Arctic with IABP dataset which covers entire Arctic region between 1979 and 1998, and to reconstruct Arctic temperature in 1900-2012. This method provided temperature reconstruction in central Arctic and precise estimation of both global and Arctic temperature variability with a long temporal scale. Results have been verified by extra independent station records in Arctic by statistical analysis, such as variance and standard deviation. The result of reconstruction shows significant warming trend in Arctic in recent 30 years, as the temperature trend in Arctic since 1997 is 0.76°C per decade, compared with 0.48°C and 0.67°C per decade from 250km smooth and 1200km smooth of GISTEMP. And global temperature trend is two times greater after using DINEOF. The discrepancies above stress the importance of fully consideration of temperature variance in Arctic because gaps of coverage in Arctic cause apparent cold bias in temperature estimation. The result of global surface temperature also proves that global warming in recent years is not as slow as thought.

Smartphone, Smart Surgeon, what about a 'Smart Logbook'?

PubMed

Adam, A; Spencer, K; Moon, S; Jacub, I

2016-06-01

Mobile phone applications (Apps) have become a vital assistant to medical personnel in today's technologically advanced era. The utility of Apps with case logbook capabilities has not yet been explored. To assess and evaluate all currently available surgical and procedural case logbook Apps. A comprehensive search was conducted in April 2015 on the Android Play Store, iTunes (Apple App Store, iOS), and BlackBerry World for surgical and/or procedural logbooks. The search terms'surgical logbook', 'logbook', 'procedure logbook' and 'surgical log' were used. Apps which could not be utilized as a surgical/procedural logbook were excluded. Each App was individually assessed and rated using preset criteria, by the unit consultant, registrars, and medical officer. In total, 2 740 Apps were assessed. After applying our exclusion criteria, only 16 Apps were relevant, and 11 suitable for critical review. Data sizes ranged from 510Kb to 12.2Mb. Costing of the Apps ranged from ZAR 0.00 to ZAR 105.32. The overall study scores revealed the following top five rated Apps: Surgical Logbook by Surgilog ; Surgeon Logbook Pro ; Surgery Notebook , Surgical Logbook , and Universal Logbook . The current mobile Apps available are efficient in replacing traditional case logbooks. The use of the 'Smart Logbook' may become common practice in the life of the modern-day surgeon.

Use of mobile device applications in Canadian dietetic practice.

PubMed

Lieffers, Jessica R L; Vance, Vivienne A; Hanning, Rhona M

2014-01-01

A cross-sectional web-based survey of dietitians was used to explore topics related to mobile devices and their applications (apps) in Canadian dietetic practice. A survey was drafted, posted on SurveyMonkey, and pretested with dietitians and dietetic interns. Dietitians of Canada (DC), a supporter of this work, promoted the survey to members through its monthly electronic newsletters from January 2012 to April 2012. Of 139 dietitians who answered some survey questions, 118 finished the survey; this represents a response rate of approximately 3%. Overall, 57.3% of respondents reported app use in practice, and 54.2% had a client ask about or use a nutrition/food app. About 40.5% of respondents had recommended nutrition/food apps to clients. Respondents were enthusiastic about apps, but many described challenges with use. From the survey data, three themes emerged that can affect dietitians' use of apps and whether they recommend apps to clients: mobile device and app factors (access to information/tools, content quality, usability, accessibility/compatibility, and cost), personal factors (knowledge, interest, suitability, and willingness/ability to pay), and workplace factors. Apps are now infiltrating dietetic practice. Several factors can affect dietitians' use of apps and whether they recommend them to clients. These findings will help guide future development and use of apps in practice.

Identification of a novel amyloid precursor protein processing pathway that generates secreted N-terminal fragments.

PubMed

Vella, Laura J; Cappai, Roberto

2012-07-01

Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system. The proteolytic processing of the amyloid precursor protein (APP) into the β-amyloid (Aβ) peptide is a central event in AD. While the pathway that generates Aβ is well described, many questions remain concerning general APP metabolism and its metabolites. It is becoming clear that the amino-terminal region of APP can be processed to release small N-terminal fragments (NTFs). The purpose of this study was to investigate the occurrence and generation of APP NTFs in vivo and in cell culture (SH-SY5Y) in order to delineate the cellular pathways implicated in their generation. We were able to detect 17- to 28-kDa APP NTFs in human and mouse brain tissue that are distinct from N-APP fragments previously reported. We show that the 17- to 28-kDa APP NTFs were highly expressed in mice from the age of 2 wk to adulthood. SH-SY5Y studies indicate the generation of APP NTFs involves a novel APP processing pathway, regulated by protein kinase C, but independent of α-secretase or β-secretase 1 (BACE) activity. These results identify a novel, developmentally regulated APP processing pathway that may play an important role in the physiological function of APP.

Mobile phone applications in Parkinson's disease: A systematic review.

PubMed

Linares-Del Rey, M; Vela-Desojo, L; Cano-de la Cuerda, R

2017-05-23

Parkinson's disease (PD) is the second most common neurodegenerative disease. However, diagnosing, assessing, and treating these patients is a complex process requiring continuous monitoring. In this context, smartphones may be useful in the management of patients with PD. The purpose of this study is to perform a systematic review of the literature addressing the use of mobile phone applications (apps) in PD. We conducted a literature search of articles published in English or Spanish between 2011 and 2016 analysing or validating apps specifically designed for or useful in PD. In addition, we searched for apps potentially useful for PD patients in the leading app stores. The literature and app searches yielded a total of 125 apps, 56 of which were classified as potentially useful in PD and 69 as specifically designed for PD (23 information apps, 29 assessment apps, 13 treatment apps, and 4 assessment and treatment apps). Numerous mobile apps are potentially useful in or specifically designed for PD management. However, scientific evidence of their usefulness is scarce and of poor quality. Further studies are needed to validate these tools and regulate their use. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Consumer Mobile Health Apps: Current State, Barriers, and Future Directions.

PubMed

Kao, Cheng-Kai; Liebovitz, David M

2017-05-01

This paper discusses the current state, barriers, and future directions of consumer-facing applications (apps). There are currently more than 165,000 mobile health apps publicly available in major app stores, the vast majority of which are designed for patients. The top 2 categories are wellness management and disease management apps, whereas other categories include self-diagnosis, medication reminder, and electronic patient portal apps. Apps specific to physical medicine and rehabilitation also are reviewed. These apps have the potential to provide low-cost, around-the-clock access to high-quality, evidence-based health information to end users on a global scale. However, they have not yet lived up to their potential due to multiple barriers, including lack of regulatory oversight, limited evidence-based literature, and concerns of privacy and security. The future directions may consist of improving data integration into the health care system, an interoperable app platform allowing access to electronic health record data, cloud-based personal health record across health care networks, and increasing app prescription by health care providers. For consumer mobile health apps to fully contribute value to health care delivery and chronic disease management, all stakeholders within the ecosystem must collaborate to overcome the significant barriers. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Popularity Modeling for Mobile Apps: A Sequential Approach.

PubMed

Zhu, Hengshu; Liu, Chuanren; Ge, Yong; Xiong, Hui; Chen, Enhong

2015-07-01

The popularity information in App stores, such as chart rankings, user ratings, and user reviews, provides an unprecedented opportunity to understand user experiences with mobile Apps, learn the process of adoption of mobile Apps, and thus enables better mobile App services. While the importance of popularity information is well recognized in the literature, the use of the popularity information for mobile App services is still fragmented and under-explored. To this end, in this paper, we propose a sequential approach based on hidden Markov model (HMM) for modeling the popularity information of mobile Apps toward mobile App services. Specifically, we first propose a popularity based HMM (PHMM) to model the sequences of the heterogeneous popularity observations of mobile Apps. Then, we introduce a bipartite based method to precluster the popularity observations. This can help to learn the parameters and initial values of the PHMM efficiently. Furthermore, we demonstrate that the PHMM is a general model and can be applicable for various mobile App services, such as trend based App recommendation, rating and review spam detection, and ranking fraud detection. Finally, we validate our approach on two real-world data sets collected from the Apple Appstore. Experimental results clearly validate both the effectiveness and efficiency of the proposed popularity modeling approach.

Review and Analysis of Existing Mobile Phone Apps to Support Heart Failure Symptom Monitoring and Self-Care Management Using the Mobile Application Rating Scale (MARS).

PubMed

Masterson Creber, Ruth M; Maurer, Mathew S; Reading, Meghan; Hiraldo, Grenny; Hickey, Kathleen T; Iribarren, Sarah

2016-06-14

Heart failure is the most common cause of hospital readmissions among Medicare beneficiaries and these hospitalizations are often driven by exacerbations in common heart failure symptoms. Patient collaboration with health care providers and decision making is a core component of increasing symptom monitoring and decreasing hospital use. Mobile phone apps offer a potentially cost-effective solution for symptom monitoring and self-care management at the point of need. The purpose of this review of commercially available apps was to identify and assess the functionalities of patient-facing mobile health apps targeted toward supporting heart failure symptom monitoring and self-care management. We searched 3 Web-based mobile app stores using multiple terms and combinations (eg, "heart failure," "cardiology," "heart failure and self-management"). Apps meeting inclusion criteria were evaluated using the Mobile Application Rating Scale (MARS), IMS Institute for Healthcare Informatics functionality scores, and Heart Failure Society of America (HFSA) guidelines for nonpharmacologic management. Apps were downloaded and assessed independently by 2-4 reviewers, interclass correlations between reviewers were calculated, and consensus was met by discussion. Of 3636 potentially relevant apps searched, 34 met inclusion criteria. Most apps were excluded because they were unrelated to heart failure, not in English or Spanish, or were games. Interrater reliability between reviewers was high. AskMD app had the highest average MARS total (4.9/5). More than half of the apps (23/34, 68%) had acceptable MARS scores (>3.0). Heart Failure Health Storylines (4.6) and AskMD (4.5) had the highest scores for behavior change. Factoring MARS, functionality, and HFSA guideline scores, the highest performing apps included Heart Failure Health Storylines, Symple, ContinuousCare Health App, WebMD, and AskMD. Peer-reviewed publications were identified for only 3 of the 34 apps. This review suggests that few apps meet prespecified criteria for quality, content, or functionality, highlighting the need for further refinement and mapping to evidence-based guidelines and room for overall quality improvement in heart failure symptom monitoring and self-care related apps.

Preferences for a Mobile HIV Prevention App for Men Who Have Sex With Men.

PubMed

Goldenberg, Tamar; McDougal, Sarah J; Sullivan, Patrick S; Stekler, Joanne D; Stephenson, Rob

2014-10-29

The Centers for Disease Control and Prevention recommends that sexually active men who have sex with men (MSM) in the United States test for human immunodeficiency virus (HIV) at least three times per year, but actual testing frequency is much less frequent. Though mHealth is a popular vehicle for delivering HIV interventions, there are currently no mobile phone apps that target MSM with the specific aim of building an HIV testing plan, and none that focuses on developing a comprehensive prevention plan and link MSM to additional HIV prevention and treatment resources. Previous research has suggested a need for more iterative feedback from the target population to ensure use of these interventions. The purpose of this study is to understand MSM's preferences for functionality, format, and design of a mobile phone-based HIV prevention app and to examine MSM's willingness to use an app for HIV prevention. We conducted focus group discussions with 38 gay and bisexual men, with two in-person groups in Atlanta, two in Seattle, and one online focus group discussion with gay and bisexual men in rural US regions. These discussions addressed MSM's general preferences for apps, HIV testing barriers and facilitators for MSM, and ways that an HIV prevention app could address these barriers and facilitators to increase the frequency of HIV testing and prevention among MSM. During focus group discussions, participants were shown screenshots and provided feedback on potential app functions. Participants provided preferences on functionality of the app, including the type and delivery of educational content, the value of interactive engagement, and the importance of social networking as an app component. Participants also discussed preferences on how the language should be framed for the delivery of information, identifying that an app needs to be simultaneously fun and professional. Privacy and altruistic motivation were considered to be important factors in men's willingness to use a mobile HIV prevention app. Finally, men described the potential impact that a mobile HIV prevention app could have, identifying individual, interpersonal, and community-based benefits. In summary, participants described a comprehensive app that should incorporate innovative ideas to educate and engage men so that they would be motivated to use the app. In order for an app to be useful, it needs to feel safe and trustworthy, which is essential when considering the app's language and privacy. Participants provided a range of preferences for using an HIV prevention app, including what they felt MSM need with regards to HIV prevention and what they want in order to engage with an app. Making an HIV prevention app enjoyable and usable for MSM is a difficult challenge. However, the usability of the app is vital because no matter how great the intervention, if MSM do not use the app, then it will not be useful.

Mobile Exercise Apps and Increased Leisure Time Exercise Activity: A Moderated Mediation Analysis of the Role of Self-Efficacy and Barriers

PubMed Central

Rosen, Zohn; Spierer, David; Weinberger-Litman, Sarah; Goldschein, Akiva; Robinson, Jonathan

2015-01-01

Background There are currently over 1000 exercise apps for mobile devices on the market. These apps employ a range of features, from tracking exercise activity to providing motivational messages. However, virtually nothing is known about whether exercise apps improve exercise levels and health outcomes and, if so, the mechanisms of these effects. Objective Our aim was to examine whether the use of exercise apps is associated with increased levels of exercise and improved health outcomes. We also develop a framework within which to understand how exercise apps may affect health and test multiple models of possible mechanisms of action and boundary conditions of these relationships. Within this framework, app use may increase physical activity by influencing variables such as self-efficacy and may help to overcome exercise barriers, leading to improved health outcomes such as lower body mass index (BMI). Methods In this study, 726 participants with one of three backgrounds were surveyed about their use of exercise apps and health: (1) those who never used exercise apps, (2) those who used exercise apps but discontinued use, and (3) those who are currently using exercise apps. Participants were asked about their long-term levels of exercise and about their levels of exercise during the previous week with the International Physical Activity Questionnaire (IPAQ). Results Nearly three-quarters of current app users reported being more active compared to under half of non-users and past users. The IPAQ showed that current users had higher total leisure time metabolic equivalent of task (MET) expenditures (1169 METs), including walking and vigorous exercise, compared to those who stopped using their apps (612 METs) or who never used apps (577 METs). Importantly, physical activity levels in domains other than leisure time activity were similar across the groups. The results also showed that current users had lower BMI (25.16) than past users (26.8) and non-users (26.9) and that this association was mediated by exercise levels and self-efficacy. That relationship was also moderated by perceived barriers to exercise. Multiple serial mediation models were tested, which revealed that the association between app use and BMI is mediated by increased self-efficacy and increased exercise. Conclusions Exercise app users are more likely to exercise during their leisure time, compared to those who do not use exercise apps, essentially fulfilling the role that many of these apps were designed to accomplish. Data also suggest that one way that exercise apps may increase exercise levels and health outcomes such as BMI is by making it easier for users to overcome barriers to exercise, leading to increased self-efficacy. We discuss ways of improving the effectiveness of apps by incorporating theory-driven approaches. We conclude that exercise apps can be viewed as intervention delivery systems consisting of features that help users overcome specific barriers. PMID:26276227

Mobile Exercise Apps and Increased Leisure Time Exercise Activity: A Moderated Mediation Analysis of the Role of Self-Efficacy and Barriers.

PubMed

Litman, Leib; Rosen, Zohn; Spierer, David; Weinberger-Litman, Sarah; Goldschein, Akiva; Robinson, Jonathan

2015-08-14

There are currently over 1000 exercise apps for mobile devices on the market. These apps employ a range of features, from tracking exercise activity to providing motivational messages. However, virtually nothing is known about whether exercise apps improve exercise levels and health outcomes and, if so, the mechanisms of these effects. Our aim was to examine whether the use of exercise apps is associated with increased levels of exercise and improved health outcomes. We also develop a framework within which to understand how exercise apps may affect health and test multiple models of possible mechanisms of action and boundary conditions of these relationships. Within this framework, app use may increase physical activity by influencing variables such as self-efficacy and may help to overcome exercise barriers, leading to improved health outcomes such as lower body mass index (BMI). In this study, 726 participants with one of three backgrounds were surveyed about their use of exercise apps and health: (1) those who never used exercise apps, (2) those who used exercise apps but discontinued use, and (3) those who are currently using exercise apps. Participants were asked about their long-term levels of exercise and about their levels of exercise during the previous week with the International Physical Activity Questionnaire (IPAQ). Nearly three-quarters of current app users reported being more active compared to under half of non-users and past users. The IPAQ showed that current users had higher total leisure time metabolic equivalent of task (MET) expenditures (1169 METs), including walking and vigorous exercise, compared to those who stopped using their apps (612 METs) or who never used apps (577 METs). Importantly, physical activity levels in domains other than leisure time activity were similar across the groups. The results also showed that current users had lower BMI (25.16) than past users (26.8) and non-users (26.9) and that this association was mediated by exercise levels and self-efficacy. That relationship was also moderated by perceived barriers to exercise. Multiple serial mediation models were tested, which revealed that the association between app use and BMI is mediated by increased self-efficacy and increased exercise. Exercise app users are more likely to exercise during their leisure time, compared to those who do not use exercise apps, essentially fulfilling the role that many of these apps were designed to accomplish. Data also suggest that one way that exercise apps may increase exercise levels and health outcomes such as BMI is by making it easier for users to overcome barriers to exercise, leading to increased self-efficacy. We discuss ways of improving the effectiveness of apps by incorporating theory-driven approaches. We conclude that exercise apps can be viewed as intervention delivery systems consisting of features that help users overcome specific barriers.

78 FR 12033 - Programs and Research Projects Affecting the Arctic

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-21

... ARCTIC RESEARCH COMMISSION Programs and Research Projects Affecting the Arctic Notice is hereby given that the U.S. Arctic Research Commission will hold its 100th meeting in Anchorage and Bethel... presentations concerning Arctic research activities The focus of the meeting will be Arctic research activities...

Apps Developed by Academics

ERIC Educational Resources Information Center

Shing, Sophia; Yuan, Benjamin

2016-01-01

In the days of the digital Wild West, developers from all backgrounds have joined in the gold rush trying to profit from the almost unbridled spending of well-to-do parents on educational products. In 2016, the Apple App Store had over 80,000 educational apps. The proliferation of educational apps has happened at a furious pace and more apps are…

Selecting "App"ealing and "App"ropriate Book Apps for Beginning Readers

ERIC Educational Resources Information Center

Cahill, Maria; McGill-Franzen, Anne

2013-01-01

Beginning with a brief rationale for selecting quality digital picture book apps for beginning readers, the authors describe the elements of digital picture books and provide a brief review of the instructional benefits of digital picture book use for beginning readers. They then present a detailed taxonomy for selecting quality picture book apps.…

Evaluating Instructional Apps Using the App Checklist for Educators (ACE)

ERIC Educational Resources Information Center

Lubniewski, Kathryn L.; McArthur, Carol L.; Harriott, Wendy

2018-01-01

The use of iPads and apps has become common in K-12 inclusive classrooms. Special education teachers frequently use this tool to support instruction. Data from electronic surveys were used to determine criteria that teachers identified as important for choosing apps for classroom use. Using this information, the authors developed an App Checklist…

Creating Innovative Student Projects with App Smashing

ERIC Educational Resources Information Center

Young, Donna

2014-01-01

The potential for using various apps to improve student learning is tremendous. Yet, despite the iPad's possibilities, apps are often limited in their functionality. No one has created that magical, one-size-fits-all app that accomplishes all of the tasks that you had in mind. Luckily, there is an answer to this common problem: app smashing.…

Cell inactivation, repair and mutation induction in bacteria after heavy ion exposure: results from experiments at accelerators and in space.

PubMed

Horneck, G; Schafer, M; Baltschukat, K; Weisbrod, U; Micke, U; Facius, R; Bucker, H

1989-01-01

To understand the mechanisms of accelerated heavy ions on biological matter, the responses of spores of B. subtilis to this structured high LET radiation was investigated applying two different approaches. 1) By the use of the Biostack concept, the inactivation probability as a function of radial distance to single particles' trajectory (i.e. impact parameter) was determined in space experiments as well as at accelerators using low fluences of heavy ions. It was found that spores can survive even a central hit and that the effective range of inactivation extends far beyond impact parameters where inactivation by delta-ray dose would be effective. Concerning the space experiment, the inactivation cross section exceeds those from comparable accelerator experiments by roughly a factor of 20. 2) From fluence effect curves, cross sections for inactivation and mutation induction, and the efficiency of repair processes were determined. They are influenced by the ions characteristics in a complex manner. According to dependence on LET, at least 3 LET ranges can be differentiated: A low LET range (app. < 200 keV/micrometers), where cross sections for inactivation and mutation induction follow a common curve for different ions and where repair processes are effective; an intermediate LET range of the so-called saturation cross section with negligible mutagenic and repair efficiency; and a high LET range (>1000 keV/micrometers) where the biological endpoints are majorly dependent on atomic mass and energy of the ion under consideration.

Smartphone apps for the self-management of low back pain: A systematic review.

PubMed

Machado, Gustavo C; Pinheiro, Marina B; Lee, Hopin; Ahmed, Osman H; Hendrick, Paul; Williams, Chris; Kamper, Steven J

2016-12-01

Guidelines for low back pain (LBP) often recommend the use of self-management such as unsupervised exercise, booklets, and online education. Another potentially useful way for patients to self-manage LBP is by using smartphone applications (apps). However, to date, there has been no rigorous evaluation of LBP apps and no guidance for consumers on how to select high-quality, evidence-based apps. This chapter reviews smartphone apps for the self-management of LBP and evaluates their content quality and whether they recommend evidence-based interventions. This chapter shows that generally app developers are selecting interventions that are endorsed by guidelines, although their quality is low. There are many apps available for the self-management of LBP, but their effectiveness in improving patient outcomes has not been rigorously assessed. App developers need to work closely with healthcare professionals, researchers, and patients to ensure app content is accurate, evidence based, and engaging. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of a Mobile Phone App for Providing Adolescents With Sexual and Reproductive Health Information, New York City, 2013-2016.

PubMed

Steinberg, Allyna; Griffin-Tomas, Marybec; Abu-Odeh, Desiree; Whitten, Alzen

The New York City (NYC) Department of Health and Mental Hygiene released the Teens in NYC mobile phone application (app) in 2013 as part of a program to promote sexual and reproductive health among adolescents aged 12-19 in NYC. The app featured a locator that allowed users to search for health service providers by sexual health services, contraceptive methods, and geographic locations. We analyzed data on searches from the Where to Go section of the app to understand the patterns of use of the app's search functionality. From January 7, 2013, through March 20, 2016, the app was downloaded more than 20 000 times, and more than 25 000 unique searches were conducted within the app. Results suggest that the app helped adolescents discover and access a wide range of sexual health services, including less commonly used contraceptives. Those designing similar apps should consider incorporating search functionality by sexual health service (including abortion), contraceptive method, and user location.

Android and iPhone Apps for Viewing Browse Plots from the Magnetospheric Imaging Instrument (MIMI) on Cassin

NASA Astrophysics Data System (ADS)

Vandegriff, J. D.; Kusterer, M. B.; Byun, S.; Steele, R. J.; Mitchell, D. G.

2017-12-01

We present a new mobile app for Android and an existing app for iPhone, both capable of viewing the numerous browse plots available for data collected by the MIMI suite on NASA's Cassini spacecraft. Both apps allow convenient mobile access to pre-made plots of data from various instruments on the suite, including daily, and monthly plots of particle intensities (line plots and spectrograms) from LEMMS, CHEMS and INCA. Also, the apps can show short movies made from sequences of INCA neutral atom images. Browsing the plots or movies is as simple as swiping to the left or right, and the app hides all access details needed to finding the images. Note that the app requires a data connection, since it locates and downloads the plot files live from various instrument team servers. We will demonstrate the current versions of both apps, which are available in Apple's App Store and the Google Play Store.

mHealth and Application Technology Supporting Clinical Trials: Today’s Limitations and Future Perspective of smartRCTs

PubMed Central

Vogel, Marco M. E.; Combs, Stephanie E.; Kessel, Kerstin A.

2017-01-01

Nowadays, applications (apps) for smartphones and tablets have become indispensable especially for young generations. The estimated number of mobile devices will exceed 2.16 billion in 2016. Over 2.2 million apps are available in the Google Play store®, and about 1.8 million apps are available in the Apple App Store®. Google and Apple distribute nearly 70,000 apps each in the category Health and Fitness, and about 33,000 and 46,000 each in medical apps. It seems like the willingness to use mHealth apps is high and the intention to share data for health research is existing. This leads to one conclusion: the time for app-accompanied clinical trials (smartRCTs) has come. In this perspective article, we would like to point out the stones put in the way while trying to implement apps in clinical research. Further, we try to offer a glimpse of what the future of smartRCT research may hold. PMID:28348978

Mobile Videoconferencing Apps for Telemedicine

PubMed Central

Liu, Wei-Li; Locatis, Craig; Ackerman, Michael

2016-01-01

Abstract Introduction: The quality and performance of several videoconferencing applications (apps) tested on iOS (Apple, Cupertino, CA) and Android™ (Google, Mountain View, CA) mobile platforms using Wi-Fi (802.11), third-generation (3G), and fourth-generation (4G) cellular networks are described. Materials and Methods: The tests were done to determine how well apps perform compared with videoconferencing software installed on computers or with more traditional videoconferencing using dedicated hardware. The rationale for app assessment and the testing methodology are described. Results: Findings are discussed in relation to operating system platform (iOS or Android) for which the apps were designed and the type of network (Wi-Fi, 3G, or 4G) used. The platform, network, and apps interact, and it is impossible to discuss videoconferencing experienced on mobile devices in relation to one of these factors without referencing the others. Conclusions: Apps for mobile devices can vary significantly from other videoconferencing software or hardware. App performance increased over the testing period due to improvements in network infrastructure and how apps manage bandwidth. PMID:26204322

Mobile Videoconferencing Apps for Telemedicine.

PubMed

Zhang, Kai; Liu, Wei-Li; Locatis, Craig; Ackerman, Michael

2016-01-01

The quality and performance of several videoconferencing applications (apps) tested on iOS (Apple, Cupertino, CA) and Android (Google, Mountain View, CA) mobile platforms using Wi-Fi (802.11), third-generation (3G), and fourth-generation (4G) cellular networks are described. The tests were done to determine how well apps perform compared with videoconferencing software installed on computers or with more traditional videoconferencing using dedicated hardware. The rationale for app assessment and the testing methodology are described. Findings are discussed in relation to operating system platform (iOS or Android) for which the apps were designed and the type of network (Wi-Fi, 3G, or 4G) used. The platform, network, and apps interact, and it is impossible to discuss videoconferencing experienced on mobile devices in relation to one of these factors without referencing the others. Apps for mobile devices can vary significantly from other videoconferencing software or hardware. App performance increased over the testing period due to improvements in network infrastructure and how apps manage bandwidth.

Acceptance of Using an Ecosystem of Mobile Apps for Use in Diabetes Clinic for Self-Management of Gestational Diabetes Mellitus.

PubMed

Pais, Sarita; Parry, Dave; Petrova, Krassie; Rowan, Janet

2017-01-01

Mobile applications (apps) for self-management of diseases such as diabetes and for general well-being, including keeping track of food, diet, and exercise, are widely available. However, consumers face a flood of new mobile apps in the app stores and have no guidance from clinicians about choosing the appropriate app. As much as clinicians would like to support a patient-centered approach and promote health and wellness mobile apps, they may be unable to provide advice due to the lack of comprehensive and reliable app reviews. This research reviewed a selection of health and wellness mobile apps suitable for the self-management of gestational diabetes mellitus (GDM). A prototype of an ecosystem that integrated the data generated by the apps was built and its usefulness and ease of use were evaluated. The results show that the ecosystem can provide support for GDM self-management by sharing health and wellness data across the diabetes clinic.

Smartphones in ecology and evolution: a guide for the app-rehensive.

PubMed

Teacher, Amber G F; Griffiths, David J; Hodgson, David J; Inger, Richard

2013-12-01

Smartphones and their apps (application software) are now used by millions of people worldwide and represent a powerful combination of sensors, information transfer, and computing power that deserves better exploitation by ecological and evolutionary researchers. We outline the development process for research apps, provide contrasting case studies for two new research apps, and scan the research horizon to suggest how apps can contribute to the rapid collection, interpretation, and dissemination of data in ecology and evolutionary biology. We emphasize that the usefulness of an app relies heavily on the development process, recommend that app developers are engaged with the process at the earliest possible stage, and commend efforts to create open-source software scaffolds on which customized apps can be built by nonexperts. We conclude that smartphones and their apps could replace many traditional handheld sensors, calculators, and data storage devices in ecological and evolutionary research. We identify their potential use in the high-throughput collection, analysis, and storage of complex ecological information.

The Arctic Research Consortium of the United States (ARCUS): Connecting Arctic Research

NASA Astrophysics Data System (ADS)

Rich, R. H.; Wiggins, H. V.; Creek, K. R.; Sheffield Guy, L.

2015-12-01

This presentation will highlight the recent activities of the Arctic Research Consortium of the United States (ARCUS) to connect Arctic research. ARCUS is a nonprofit membership organization of universities and institutions that have a substantial commitment to research in the Arctic. ARCUS was formed in 1988 to serve as a forum for planning, facilitating, coordinating, and implementing interdisciplinary studies of the Arctic; to act as a synthesizer and disseminator of scientific information on arctic research; and to educate scientists and the general public about the needs and opportunities for research in the Arctic. ARCUS, in collaboration with the broader science community, relevant agencies and organizations, and other stakeholders, coordinates science planning and educational activities across disciplinary and organizational boundaries. Examples of ARCUS projects include: Arctic Sea Ice Outlook - an international effort that provides monthly summer reports synthesizing community estimates of the expected sea ice minimum. Sea Ice for Walrus Outlook - a resource for Alaska Native subsistence hunters, coastal communities, and others that provides weekly reports with information on sea ice conditions relevant to walrus in Alaska waters. PolarTREC (Teachers and Researchers Exploring and Collaborating) - a program whereby K-12 educators and researchers work together in hands-on field experiences in the Arctic and Antarctic to advance polar science education. ArcticInfo mailing list, Witness the Arctic newsletter, and the Arctic Calendar - communication tools for the arctic science community to keep apprised of relevant news, meetings, and announcements. Coordination for the Study of Environmental Arctic Change (SEARCH) program, which aims to provide scientific understanding of arctic environmental change to help society understand and respond to a rapidly changing Arctic. More information about these and other ARCUS activities can be found at the ARCUS website at: http://www.arcus.org.

Scenarios Creation and Use in the Arctic Council's Arctic Marine Shipping Assessment

NASA Astrophysics Data System (ADS)

Brigham, L. W.

2016-12-01

The Arctic Council's Arctic Marine Shipping Assessment (AMSA), conducted 2004-2009, used a scenarios-based approach to reveal the complexity of future Arctic marine navigation and to develop a set of plausible futures. The initial task was to use experts and stakeholders in brainstorming sessions to identify the key drivers and uncertainties for Arctic marine navigation. AMSA scenario participants identified 120 driving forces or factors that may influence future levels of marine activity. This effort illustrated the broad, global connections that can impact future use of the Arctic Ocean. Two primary factors were selected to anchor, as axes of uncertainty, the scenarios matrix: resources and trade (the level of demand for Arctic natural resources and trade); and, governance (the degree of relative stability of rules and standards for marine use both within the Arctic and internationally). Four scenarios were created by crossing the two primary drivers: a Polar Lows scenario (low demand and unstable governance); an Arctic Race scenario (high demand and unstable governance); a Polar Preserve scenario (low demand and stable governance); and, an Arctic Saga scenario (high demand and stable governance). The AMSA scenarios effort proved to be an effective and powerful way to communicate to the Arctic Council diplomats, Arctic indigenous peoples, maritime stakeholders and many other actors in the global community the complexities influencing the future of Arctic shipping and marine operations. The scenarios approach facilitated unconstrained thinking and identified the many plausible linkages of the Arctic to the global economic system. The AMSA scenarios work was influential in the Arctic ministers' approval of the framework set of AMSA recommendations that are being implemented today to enhance Arctic marine safety and environmental protection.

User Experience of Cognitive Behavioral Therapy Apps for Depression: An Analysis of App Functionality and User Reviews.

PubMed

Stawarz, Katarzyna; Preist, Chris; Tallon, Debbie; Wiles, Nicola; Coyle, David

2018-06-06

Hundreds of mental health apps are available to the general public. With increasing pressures on health care systems, they offer a potential way for people to support their mental health and well-being. However, although many are highly rated by users, few are evidence-based. Equally, our understanding of what makes apps engaging and valuable to users is limited. The aim of this paper was to analyze functionality and user opinions of mobile apps purporting to support cognitive behavioral therapy for depression and to explore key factors that have an impact on user experience and support engagement. We systematically identified apps described as being based on cognitive behavioral therapy for depression. We then conducted 2 studies. In the first, we analyzed the therapeutic functionality of apps. This corroborated existing work on apps' fidelity to cognitive behavioral therapy theory, but we also extended prior work by examining features designed to support user engagement. Engagement features found in cognitive behavioral therapy apps for depression were compared with those found in a larger group of apps that support mental well-being in a more general sense. Our second study involved a more detailed examination of user experience, through a thematic analysis of publicly available user reviews of cognitive behavioral therapy apps for depression. We identified 31 apps that purport to be based on cognitive behavioral therapy for depression. Functionality analysis (study 1) showed that they offered an eclectic mix of features, including many not based on cognitive behavioral therapy practice. Cognitive behavioral therapy apps used less varied engagement features compared with 253 other mental well-being apps. The analysis of 1287 user reviews of cognitive behavioral therapy apps for depression (study 2) showed that apps are used in a wide range of contexts, both replacing and augmenting therapy, and allowing users to play an active role in supporting their mental health and well-being. Users, including health professionals, valued and used apps that incorporated both core cognitive behavioral therapy and non-cognitive behavioral therapy elements, but concerns were also expressed regarding the unsupervised use of apps. Positivity was seen as important to engagement, for example, in the context of automatic thoughts, users expressed a preference to capture not just negative but also positive ones. Privacy, security, and trust were crucial to the user experience. Cognitive behavioral therapy apps for depression need to improve with respect to incorporating evidence-based cognitive behavioral therapy elements. Equally, a positive user experience is dependent on other design factors, including consideration of varying contexts of use. App designers should be able to clearly identify the therapeutic basis of their apps, but they should also draw on evidence-based strategies to support a positive and engaging user experience. The most effective apps are likely to strike a balance between evidence-based cognitive behavioral therapy strategies and evidence-based design strategies, including the possibility of eclectic therapeutic techniques. ©Katarzyna Stawarz, Chris Preist, Debbie Tallon, Nicola Wiles, David Coyle. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 06.06.2018.

The International Polar year 2007-2008; the Arctic human health legacy.

PubMed

Parkinson, Alan J

2007-01-01

Life expectancy in Arctic populations has greatly improved over the last 50 years. Much of this improvement can be attributed health research that has resulted in a reduction in morbidity and mortality from infectious diseases, such as tuberculosis, and the vaccine-preventable diseases of childhood. However, despite these improvements in health indicators of Arctic residents, life expectancy and infant mortality remain higher in indigenous Arctic residents in the US Arctic, northern Canada, and Greenland when compared to Arctic residents of Nordic countries. The International Polar Year (IPY) represents a unique opportunity to focus world attention on Arctic human health and to further stimulate Circumpolar cooperation on emerging Arctic human health concerns. The Arctic Human Health Initiative (AHHI) is an Arctic Council IPY initiative that aims to build and expand on existing Arctic Council and International Union for Circumpolar Health (IUCH) human health research activities. The human health legacy of the IPY will be increased visibility of the human health concerns of Arctic communities, revitalization of cooperative Arctic human health research focused on those concerns, the development of health policies based on research findings, and the subsequent implementation of appropriate interventions, prevention and control measures at the community level.

Plausibility of Menstrual Cycle Apps Claiming to Support Conception.

PubMed

Freis, Alexander; Freundl-Schütt, Tanja; Wallwiener, Lisa-Maria; Baur, Sigfried; Strowitzki, Thomas; Freundl, Günter; Frank-Herrmann, Petra

2018-01-01

The interval of peak fertility during the menstrual cycle is of limited duration, and the day of ovulation varies, even in women with fairly regular cycles. Therefore, menstrual cycle apps identifying the "fertile window" for women trying to conceive must be quite precise. A deviation of a few days may lead the couple to focus on less- or non-fertile days for sexual intercourse and thus may be worse than random intercourse. The aim of the present investigation was to develop a scoring system for rating available apps for determining the fertile window and secondarily pilot test 12 apps currently available in both German and English (consisting of 6 calendar-based apps: Clue Menstruations- und Zykluskalender, Flo Menstruationskalender, Maya-Mein Periodentracker, Menstruationskalender Pro, Period Tracker Deluxe, and WomanLog-Pro-Kalender; 2 calculothermal apps: Ovy and Natural Cycles; and 4 symptothermal apps: myNFP, Lady Cycle, Lily, and OvuView). The calendar-based apps were investigated by entering several series of cycles with varying lengths, whereas the symptom-based apps were examined by entering data of cycles with known temperature rise, cervical mucus pattern, and clinical ovulation. The main criteria for evaluating the cycle apps were as follows: (1) What methods/parameters were used to determine the fertile window? (2) What study results exist concerning that underlying method/parameters? (3) What study results exist concerning the app itself? (4) Was there a qualified counseling service? The calendar-based apps predicted the fertile days based on data of previous cycles. They obtained zero points in our scoring system, as they did not comply with any of the evaluated criteria. Calculothermal apps had similar deficits for predicting the most fertile days and produced suboptimal results (Ovy 3/30 points and Natural Cycles 2/30 points). The symptothermal apps determined the fertile days based on parameters of the current cycle: Lady Cycle scored 20/30 points, myNFP 20/30 points, Lily 19/30 points, and OvuView 11/30 points. We concluded that the available cycle apps vary according to their underlying scientific quality and clear rating criteria have been suggested. Three of the tested apps were judged to be eligible for further study. The scientific evaluation of cycle apps depends on good prospective studies undertaken by independent investigators who are free of commercial bias.

A review and content analysis of engagement, functionality, aesthetics, information quality, and change techniques in the most popular commercial apps for weight management.

PubMed

Bardus, Marco; van Beurden, Samantha B; Smith, Jane R; Abraham, Charles

2016-03-10

There are thousands of apps promoting dietary improvement, increased physical activity (PA) and weight management. Despite a growing number of reviews in this area, popular apps have not been comprehensively analysed in terms of features related to engagement, functionality, aesthetics, information quality, and content, including the types of change techniques employed. The databases containing information about all Health and Fitness apps on GP and iTunes (7,954 and 25,491 apps) were downloaded in April 2015. Database filters were applied to select the most popular apps available in both stores. Two researchers screened the descriptions selecting only weight management apps. Features, app quality and content were independently assessed using the Mobile App Rating Scale (MARS) and previously-defined categories of techniques relevant to behaviour change. Inter-coder reliabilities were calculated, and correlations between features explored. Of the 23 popular apps included in the review 16 were free (70%), 15 (65%) addressed weight control, diet and PA combined; 19 (83%) allowed behavioural tracking. On 5-point MARS scales, apps were of average quality (Md = 3.2, IQR = 1.4); "functionality" (Md = 4.0, IQR = 1.1) was the highest and "information quality" (Md = 2.0, IQR = 1.1) was the lowest domain. On average, 10 techniques were identified per app (range: 1-17) and of the 34 categories applied, goal setting and self-monitoring techniques were most frequently identified. App quality was positively correlated with number of techniques included (rho = .58, p < .01) and number of "technical" features (rho = .48, p < .05), which was also associated with the number of techniques included (rho = .61, p < .01). Apps that provided tracking used significantly more techniques than those that did not. Apps with automated tracking scored significantly higher in engagement, aesthetics, and overall MARS scores. Those that used change techniques previously associated with effectiveness (i.e., goal setting, self-monitoring and feedback) also had better "information quality". Popular apps assessed have overall moderate quality and include behavioural tracking features and a range of change techniques associated with behaviour change. These apps may influence behaviour, although more attention to information quality and evidence-based content are warranted to improve their quality.

Assessing the Medication Adherence App Marketplace From the Health Professional and Consumer Vantage Points.

PubMed

Dayer, Lindsey E; Shilling, Rebecca; Van Valkenburg, Madalyn; Martin, Bradley C; Gubbins, Paul O; Hadden, Kristie; Heldenbrand, Seth

2017-04-19

Nonadherence produces considerable health consequences and economic burden to patients and payers. One approach to improve medication nonadherence that has gained interest in recent years is the use of smartphone adherence apps. The development of smartphone adherence apps has increased rapidly since 2012; however, literature evaluating the clinical app and effectiveness of smartphone adherence apps to improve medication adherence is generally lacking. The aims of this study were to (1) provide an updated evaluation and comparison of medication adherence apps in the marketplace by assessing the features, functionality, and health literacy (HL) of the highest-ranking adherence apps and (2) indirectly measure the validity of our rating methodology by determining the relationship between our app evaluations and Web-based consumer ratings. Two independent reviewers assessed the features and functionality using a 4-domain rating tool of all adherence apps identified based on developer claims. The same reviewers downloaded and tested the 100 highest-ranking apps including an additional domain for assessment of HL. Pearson product correlations were estimated between the consumer ratings and our domain and total scores. A total of 824 adherence apps were identified; of these, 645 unique apps were evaluated after applying exclusion criteria. The median initial score based on descriptions was 14 (max of 68; range 0-60). As a result, 100 of the highest-scoring unique apps underwent user testing. The median overall user-tested score was 31.5 (max of 73; range 0-60). The majority of the user tested the adherence apps that underwent user testing reported a consumer rating score in their respective online marketplace. The mean consumer rating was 3.93 (SD 0.84). The total user-tested score was positively correlated with consumer ratings (r=.1969, P=.04). More adherence apps are available in the Web-based marketplace, and the quality of these apps varies considerably. Consumer ratings are positively but weakly correlated with user-testing scores suggesting that our rating tool has some validity but that consumers and clinicians may assess adherence app quality differently. ©Lindsey E Dayer, Rebecca Shilling, Madalyn Van Valkenburg, Bradley C Martin, Paul O Gubbins, Kristie Hadden, Seth Heldenbrand. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 19.04.2017.