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.

Amyloid-β Production Via Cleavage of Amyloid-β Protein Precursor is Modulated by Cell Density

PubMed Central

Zhang, Can; Browne, Andrew; DiVito, Jason R.; Stevenson, Jesse A.; Romano, Donna; Dong, Yuanlin; Xie, Zhongcong; Tanzi, Rudolph E.

2012-01-01

Mounting evidence suggests that Alzheimer disease (AD) is caused by the accumulation of the small peptide, Aβ, a proteolytic cleavage product of amyloid-β protein precursor (AβPP; or APP). Aβ is generated through a serial cleavage of APP by β- and γ-secretase. Aβ40 and Aβ42 are the two main components of amyloid plaques in AD brains, with Aβ42 being more prone to aggregation. APP can also be processed by α-secretase, which cleaves APP within the Aβ sequence, thereby preventing the generation of Aβ. Little is currently known regarding the effects of cell density on APP processing and Aβ generation. Here we assessed the effects of cell density on APP processing in neuronal and non-neuronal cell lines, as well as mouse primary cortical neurons. We found that decreased cell density significantly increases levels of Aβ40, Aβ42, total Aβ, and the ratio of Aβ42:Aβ40. These results also indicate that cell density is a significant modulator of APP processing. Overall, these findings carry profound implications for both previous and forthcoming studies aiming to assess the effects of various conditions and genetic/chemical factors, e.g. novel drugs on APP processing and Aβ generation in cell-based systems. Moreover, it is interesting to speculate whether cell density changes in vivo may also affect APP processing and Aβ levels in the AD brain. PMID:20847415

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

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

Membrane microdomain switching: a regulatory mechanism of amyloid precursor protein processing.

PubMed

Sakurai, Takashi; Kaneko, Kumi; Okuno, Misako; Wada, Koji; Kashiyama, Taku; Shimizu, Hideaki; Akagi, Takumi; Hashikawa, Tsutomu; Nukina, Nobuyuki

2008-10-20

Neuronal activity has an impact on beta cleavage of amyloid precursor protein (APP) by BACE1 to generate amyloid-beta peptide (Abeta). However, the molecular mechanisms underlying this effect remain to be elucidated. Cholesterol dependency of beta cleavage prompted us to analyze immunoisolated APP-containing detergent-resistant membranes from rodent brains. We found syntaxin 1 as a key molecule for activity-dependent regulation of APP processing in cholesterol-dependent microdomains. In living cells, APP associates with syntaxin 1-containing microdomains through X11-Munc18, which inhibits the APP-BACE1 interaction and beta cleavage via microdomain segregation. Phosphorylation of Munc18 by cdk5 causes a shift of APP to BACE1-containing microdomains. Neuronal hyperactivity, implicated in Abeta overproduction, promotes the switching of APP microdomain association as well as beta cleavage in a partially cdk5-dependent manner. We propose that microdomain switching is a mechanism of cholesterol- and activity-dependent regulation of APP processing in neurons.

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.

The intact Kunitz domain protects the amyloid precursor protein from being processed by matriptase-2.

PubMed

Beckmann, Anna-Madeleine; Glebov, Konstantin; Walter, Jochen; Merkel, Olaf; Mangold, Martin; Schmidt, Frederike; Becker-Pauly, Christoph; Gütschow, Michael; Stirnberg, Marit

2016-08-01

Proteolytic processing of the amyloid precursor protein (APP) leads to amyloid-β (Aβ) peptides. So far, the mechanism of APP processing is insufficiently characterized at the molecular level. Whereas the knowledge of Aβ generation by several proteases has been expanded, the contribution of the Kunitz-type protease inhibitor domain (KPI) present in two major APP isoforms to the complex proteolytic processing of APP is poorly understood. In this study, we have identified KPI-containing APP as a very potent, slow-binding inhibitor for the membrane-bound proteolytic regulator of iron homeostasis matriptase-2 by forming stable complexes with its target protease in HEK cells. Inhibition and complex formation depend on the intact KPI domain. By inhibiting matriptase-2, KPI-containing APP is protected from matriptase-2-mediated proteolysis within the Aβ region, thus preventing the generation of N-terminally truncated Aβ.

c-Abl links APP-BACE1 interaction promoting APP amyloidogenic processing in Niemann-Pick type C disease.

PubMed

Yáñez, M J; Belbin, O; Estrada, L D; Leal, N; Contreras, P S; Lleó, A; Burgos, P V; Zanlungo, S; Alvarez, A R

2016-11-01

Niemann-Pick type C (NPC) disease is characterized by lysosomal accumulation of cholesterol. Interestingly, NPC patients' brains also show increased levels of amyloid-β (Aβ) peptide, a key protein in Alzheimer's disease pathogenesis. We previously reported that the c-Abl tyrosine kinase is active in NPC neurons and in AD animal models and that Imatinib, a specific c-Abl inhibitor, decreased the amyloid burden in brains of the AD mouse model. Active c-Abl was shown to interact with the APP cytosolic domain, but the relevance of this interaction to APP processing has yet to be defined. In this work we show that c-Abl inhibition reduces APP amyloidogenic cleavage in NPC cells overexpressing APP. Indeed, we found that levels of the Aβ oligomers and the carboxy-terminal fragment βCTF were decreased when the cells were treated with Imatinib and upon shRNA-mediated c-Abl knockdown. Moreover, Imatinib decreased APP amyloidogenic processing in the brain of an NPC mouse model. In addition, we found decreased levels of βCTF in neuronal cultures from c-Abl null mice. We demonstrate that c-Abl directly interacts with APP, that c-Abl inhibition prevents this interaction, and that Tyr682 in the APP cytoplasmic tail is essential for this interaction. More importantly, we found that c-Abl inhibition by Imatinib significantly inhibits the interaction between APP and BACE1. We conclude that c-Abl activity facilitates the APP-BACE1 interaction, thereby promoting amyloidogenic processing of APP. Thus, inhibition of c-Abl could be a pharmacological target for preventing the injurious effects of increased Aβ levels in NPC disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Contribution of Kunitz protease inhibitor and transmembrane domains to amyloid precursor protein homodimerization.

PubMed

Ben Khalifa, N; Tyteca, D; Courtoy, P J; Renauld, J C; Constantinescu, S N; Octave, J N; Kienlen-Campard, P

2012-01-01

The two major isoforms of the human amyloid precursor protein (APP) are APP695 and APP751. They differ by the insertion of a Kunitz-type protease inhibitor (KPI) sequence in the extracellular domain of APP751. APP-KPI isoforms are increased in Alzheimer's disease brains, and they could be associated with disease progression. Recent studies have shown that APP processing to Aβ is regulated by homodimerization, which involves both extracellular and juxtamembrane/transmembrane (JM/TM) regions. Our aim is to understand the mechanisms controlling APP dimerization and the contribution of the ectodomain and JM/TM regions to this process. We used bimolecular fluorescence complementation approaches coupled to fluorescence-activated cell sorting analysis to measure the dimerization level of different APP isoforms and APP C-terminal fragments (C99) mutated in their JM/TM region. APP751 was found to form significantly more homodimers than APP695. Mutation of dimerization motifs in the TM domain of APP or C99 did not significantly affect fluorescence complementation. These findings indicate that the KPI domain plays a major role in APP dimerization. They set the basis for further investigation of the relation between dimerization, metabolism and function of APP. Copyright © 2012 S. Karger AG, Basel.

The kunitz protease inhibitor form of the amyloid precursor protein (KPI/APP) inhibits the proneuropeptide processing enzyme prohormone thiol protease (PTP). Colocalization of KPI/APP and PTP in secretory vesicles.

PubMed

Hook, V Y; Sei, C; Yasothornsrikul, S; Toneff, T; Kang, Y H; Efthimiopoulos, S; Robakis, N K; Van Nostrand, W

1999-01-29

Proteolytic processing of proenkephalin and proneuropeptides is required for the production of active neurotransmitters and peptide hormones. Variations in the extent of proenkephalin processing in vivo suggest involvement of endogenous protease inhibitors. This study demonstrates that "protease nexin 2 (PN2)," the secreted form of the kunitz protease inhibitor (KPI) of the amyloid precursor protein (APP), potently inhibited the proenkephalin processing enzyme known as prohormone thiol protease (PTP), with a Ki,app of 400 nM. Moreover, PTP and PN2 formed SDS-stable complexes that are typical of kunitz protease inhibitor interactions with target proteases. In vivo, KPI/APP (120 kDa), as well as a truncated form of KPI/APP that resembles PN2 in apparent molecular mass (110 kDa), were colocalized with PTP and (Met)enkephalin in secretory vesicles of adrenal medulla (chromaffin granules). KPI/APP (110-120 kDa) was also detected in pituitary secretory vesicles that contain PTP. In chromaffin cells, calcium-dependent secretion of KPI/APP with PTP and (Met)enkephalin demonstrated the colocalization of these components in functional secretory vesicles. These results suggest a role for KPI/APP inhibition of PTP in regulated secretory vesicles. In addition, these results are the first to identify an endogenous protease target of KPI/APP, which is developmentally regulated in aging and Alzheimer's disease.

Smartphone apps and the nutrition care process: Current perspectives and future considerations.

PubMed

Chen, Juliana; Gemming, Luke; Hanning, Rhona; Allman-Farinelli, Margaret

2018-04-01

To provide dietitians with practical guidance on incorporating smartphone applications (apps) in the nutrition care process (NCP) to optimize patient education and counseling. The current evidence-base for mobile health (mHealth) apps was searched using PubMed and Google Scholar. Where and how apps could be implemented by dietitians across the four steps of the NCP is discussed. With functionality to automatically convert patient dietary records into nutrient components, nutrition assessment can be streamlined using nutrition apps, allowing more time for dietitians to deliver education and nutrition counseling. Dietitians could prescribe apps to provide patients with education on nutrition skills and in counseling for better adherence to behavior change. Improved patient-provider communication is also made possible through the opportunity for real-time monitoring and evaluation of patient progress via apps. A practical framework termed the 'Mobile Nutrition Care Process Grid' provides dietitians with best-practice guidance on how to use apps. Including apps into dietetic practice could enhance the efficiency and quality of nutrition care and counseling delivered by dietitians. Apps should be considered an adjunct to enable dietetic counseling and care, rather than to replace the expertise, social support and accountability provided by dietitians. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Modifications and Trafficking of APP in the Pathogenesis of Alzheimer’s Disease

PubMed Central

Wang, Xin; Zhou, Xuan; Li, Gongying; Zhang, Yun; Wu, Yili; Song, Weihong

2017-01-01

Alzheimer’s disease (AD), the most common neurodegenerative disorder, is the leading cause of dementia. Neuritic plaque, one of the major characteristics of AD neuropathology, mainly consists of amyloid β (Aβ) protein. Aβ is derived from amyloid precursor protein (APP) by sequential cleavages of β- and γ-secretase. Although APP upregulation can promote AD pathogenesis by facilitating Aβ production, growing evidence indicates that aberrant post-translational modifications and trafficking of APP play a pivotal role in AD pathogenesis by dysregulating APP processing and Aβ generation. In this report, we reviewed the current knowledge of APP modifications and trafficking as well as their role in APP processing. More importantly, we discussed the effect of aberrant APP modifications and trafficking on Aβ generation and the underlying mechanisms, which may provide novel strategies for drug development in AD. PMID:28966576

Modifications and Trafficking of APP in the Pathogenesis of Alzheimer's Disease.

PubMed

Wang, Xin; Zhou, Xuan; Li, Gongying; Zhang, Yun; Wu, Yili; Song, Weihong

2017-01-01

Alzheimer's disease (AD), the most common neurodegenerative disorder, is the leading cause of dementia. Neuritic plaque, one of the major characteristics of AD neuropathology, mainly consists of amyloid β (Aβ) protein. Aβ is derived from amyloid precursor protein (APP) by sequential cleavages of β- and γ-secretase. Although APP upregulation can promote AD pathogenesis by facilitating Aβ production, growing evidence indicates that aberrant post-translational modifications and trafficking of APP play a pivotal role in AD pathogenesis by dysregulating APP processing and Aβ generation. In this report, we reviewed the current knowledge of APP modifications and trafficking as well as their role in APP processing. More importantly, we discussed the effect of aberrant APP modifications and trafficking on Aβ generation and the underlying mechanisms, which may provide novel strategies for drug development in AD.

Optimal processing for gel electrophoresis images: Applying Monte Carlo Tree Search in GelApp.

PubMed

Nguyen, Phi-Vu; Ghezal, Ali; Hsueh, Ya-Chih; Boudier, Thomas; Gan, Samuel Ken-En; Lee, Hwee Kuan

2016-08-01

In biomedical research, gel band size estimation in electrophoresis analysis is a routine process. To facilitate and automate this process, numerous software have been released, notably the GelApp mobile app. However, the band detection accuracy is limited due to a band detection algorithm that cannot adapt to the variations in input images. To address this, we used the Monte Carlo Tree Search with Upper Confidence Bound (MCTS-UCB) method to efficiently search for optimal image processing pipelines for the band detection task, thereby improving the segmentation algorithm. Incorporating this into GelApp, we report a significant enhancement of gel band detection accuracy by 55.9 ± 2.0% for protein polyacrylamide gels, and 35.9 ± 2.5% for DNA SYBR green agarose gels. This implementation is a proof-of-concept in demonstrating MCTS-UCB as a strategy to optimize general image segmentation. The improved version of GelApp-GelApp 2.0-is freely available on both Google Play Store (for Android platform), and Apple App Store (for iOS platform). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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

Guidelines and Recommendations for Developing Interactive eHealth Apps for Complex Messaging in Health Promotion.

PubMed

Heffernan, Kayla Joanne; Chang, Shanton; Maclean, Skye Tamara; Callegari, Emma Teresa; Garland, Suzanne Marie; Reavley, Nicola Jane; Varigos, George Andrew; Wark, John Dennis

2016-02-09

The now ubiquitous catchphrase, "There's an app for that," rings true owing to the growing number of mobile phone apps. In excess of 97,000 eHealth apps are available in major app stores. Yet the effectiveness of these apps varies greatly. While a minority of apps are developed grounded in theory and in conjunction with health care experts, the vast majority are not. This is concerning given the Hippocratic notion of "do no harm." There is currently no unified formal theory for developing interactive eHealth apps, and development is especially difficult when complex messaging is required, such as in health promotion and prevention. This paper aims to provide insight into the creation of interactive eHealth apps for complex messaging, by leveraging the Safe-D case study, which involved complex messaging required to guide safe but sufficient UV exposure for vitamin D synthesis in users. We aim to create recommendations for developing interactive eHealth apps for complex messages based on the lessons learned during Safe-D app development. For this case study we developed an Apple and Android app, both named Safe-D, to safely improve vitamin D status in young women through encouraging safe ultraviolet radiation exposure. The app was developed through participatory action research involving medical and human computer interaction researchers, subject matter expert clinicians, external developers, and target users. The recommendations for development were created from analysis of the development process. By working with clinicians and implementing disparate design examples from the literature, we developed the Safe-D app. From this development process, recommendations for developing interactive eHealth apps for complex messaging were created: (1) involve a multidisciplinary team in the development process, (2) manage complex messages to engage users, and (3) design for interactivity (tailor recommendations, remove barriers to use, design for simplicity). This research has provided principles for developing interactive eHealth apps for complex messaging as guidelines by aggregating existing design concepts and expanding these concepts and new learnings from our development process. A set of guidelines to develop interactive eHealth apps generally, and specifically those for complex messaging, was previously missing from the literature; this research has contributed these principles. Safe-D delivers complex messaging simply, to aid education, and explicitly, considering user safety.

Guidelines and Recommendations for Developing Interactive eHealth Apps for Complex Messaging in Health Promotion

PubMed Central

Heffernan, Kayla Joanne; Maclean, Skye Tamara; Callegari, Emma Teresa; Garland, Suzanne Marie; Reavley, Nicola Jane; Varigos, George Andrew; Wark, John Dennis

2016-01-01

Background The now ubiquitous catchphrase, “There’s an app for that,” rings true owing to the growing number of mobile phone apps. In excess of 97,000 eHealth apps are available in major app stores. Yet the effectiveness of these apps varies greatly. While a minority of apps are developed grounded in theory and in conjunction with health care experts, the vast majority are not. This is concerning given the Hippocratic notion of “do no harm.” There is currently no unified formal theory for developing interactive eHealth apps, and development is especially difficult when complex messaging is required, such as in health promotion and prevention. Objective This paper aims to provide insight into the creation of interactive eHealth apps for complex messaging, by leveraging the Safe-D case study, which involved complex messaging required to guide safe but sufficient UV exposure for vitamin D synthesis in users. We aim to create recommendations for developing interactive eHealth apps for complex messages based on the lessons learned during Safe-D app development. Methods For this case study we developed an Apple and Android app, both named Safe-D, to safely improve vitamin D status in young women through encouraging safe ultraviolet radiation exposure. The app was developed through participatory action research involving medical and human computer interaction researchers, subject matter expert clinicians, external developers, and target users. The recommendations for development were created from analysis of the development process. Results By working with clinicians and implementing disparate design examples from the literature, we developed the Safe-D app. From this development process, recommendations for developing interactive eHealth apps for complex messaging were created: (1) involve a multidisciplinary team in the development process, (2) manage complex messages to engage users, and (3) design for interactivity (tailor recommendations, remove barriers to use, design for simplicity). Conclusions This research has provided principles for developing interactive eHealth apps for complex messaging as guidelines by aggregating existing design concepts and expanding these concepts and new learnings from our development process. A set of guidelines to develop interactive eHealth apps generally, and specifically those for complex messaging, was previously missing from the literature; this research has contributed these principles. Safe-D delivers complex messaging simply, to aid education, and explicitly, considering user safety. PMID:26860623

Rivastigmine Lowers Aβ and Increases sAPPα Levels, Which Parallel Elevated Synaptic Markers and Metabolic Activity in Degenerating Primary Rat Neurons

PubMed Central

Bailey, Jason A.; Ray, Balmiki; Greig, Nigel H.; Lahiri, Debomoy K.

2011-01-01

Overproduction of amyloid-β (Aβ) protein in the brain has been hypothesized as the primary toxic insult that, via numerous mechanisms, produces cognitive deficits in Alzheimer's disease (AD). Cholinesterase inhibition is a primary strategy for treatment of AD, and specific compounds of this class have previously been demonstrated to influence Aβ precursor protein (APP) processing and Aβ production. However, little information is available on the effects of rivastigmine, a dual acetylcholinesterase and butyrylcholinesterase inhibitor, on APP processing. As this drug is currently used to treat AD, characterization of its various activities is important to optimize its clinical utility. We have previously shown that rivastigmine can preserve or enhance neuronal and synaptic terminal markers in degenerating primary embryonic cerebrocortical cultures. Given previous reports on the effects of APP and Aβ on synapses, regulation of APP processing represents a plausible mechanism for the synaptic effects of rivastigmine. To test this hypothesis, we treated degenerating primary cultures with rivastigmine and measured secreted APP (sAPP) and Aβ. Rivastigmine treatment increased metabolic activity in these cultured cells, and elevated APP secretion. Analysis of the two major forms of APP secreted by these cultures, attributed to neurons or glia based on molecular weight showed that rivastigmine treatment significantly increased neuronal relative to glial secreted APP. Furthermore, rivastigmine treatment increased α-secretase cleaved sAPPα and decreased Aβ secretion, suggesting a therapeutic mechanism wherein rivastigmine alters the relative activities of the secretase pathways. Assessment of sAPP levels in rodent CSF following once daily rivastigmine administration for 21 days confirmed that elevated levels of APP in cell culture translated in vivo. Taken together, rivastigmine treatment enhances neuronal sAPP and shifts APP processing toward the α-secretase pathway in degenerating neuronal cultures, which mirrors the trend of synaptic proteins, and metabolic activity. PMID:21799757

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.

A Comprehensive Onboarding and Orientation Plan for Neurocritical Care Advanced Practice Providers.

PubMed

Langley, Tamra M; Dority, Jeremy; Fraser, Justin F; Hatton, Kevin W

2018-06-01

As the role of advanced practice providers (APPs) expands to include increasingly complex patient care within the intensive care unit, the educational needs of these providers must also be expanded. An onboarding process was designed for APPs in the neurocritical care service line. Onboarding for new APPs revolved around 5 specific areas: candidate selection, proctor assignment, 3-phased orientation process, remediation, and mentorship. To ensure effective training for APPs, using the most time-conscious approach, the backbone of the process is a structured curriculum. This was developed and integrated within the standard orientation and onboarding process. The curriculum design incorporated measurable learning goals, objective assessments of phased goal achievements, and opportunities for remediation. The neurocritical care service implemented an onboarding process in 2014. Four APPs (3 nurse practitioners and 1 physician assistant) were employed by the department before the implementation of the orientation program. The length of employment ranged from 1 to 4 years. Lack of clinical knowledge and/or sufficient training was cited as reasons for departure from the position in 2 of the 4 APPs, as either self-expression or peer evaluation. Since implementation of this program, 12 APPs have completed the program, of which 10 remain within the division, creating an 83% retention rate. The onboarding process, including a 3-phased, structured orientation plan for neurocritical care, has increased APP retention since its implementation. The educational model, along with proctoring and mentorship, has improved clinical knowledge and increased nurse practitioner retention. A larger-scale study would help to support the validity of this onboarding process.

Membrane microdomain switching: a regulatory mechanism of amyloid precursor protein processing

PubMed Central

Sakurai, Takashi; Kaneko, Kumi; Okuno, Misako; Wada, Koji; Kashiyama, Taku; Shimizu, Hideaki; Akagi, Takumi; Hashikawa, Tsutomu; Nukina, Nobuyuki

2008-01-01

Neuronal activity has an impact on β cleavage of amyloid precursor protein (APP) by BACE1 to generate amyloid-β peptide (Aβ). However, the molecular mechanisms underlying this effect remain to be elucidated. Cholesterol dependency of β cleavage prompted us to analyze immunoisolated APP-containing detergent-resistant membranes from rodent brains. We found syntaxin 1 as a key molecule for activity-dependent regulation of APP processing in cholesterol-dependent microdomains. In living cells, APP associates with syntaxin 1–containing microdomains through X11–Munc18, which inhibits the APP–BACE1 interaction and β cleavage via microdomain segregation. Phosphorylation of Munc18 by cdk5 causes a shift of APP to BACE1-containing microdomains. Neuronal hyperactivity, implicated in Aβ overproduction, promotes the switching of APP microdomain association as well as β cleavage in a partially cdk5-dependent manner. We propose that microdomain switching is a mechanism of cholesterol- and activity-dependent regulation of APP processing in neurons. PMID:18936252

Development of a smartphone app for adolescents with lupus: a collaborative meeting-based methodology inclusive of a wide range of stakeholders.

PubMed

Herschman, Jessica; Kasenberg, Todd; Levy, Deborah; Ruth, Natasha; Taberner, Christy; Kaufman, Miriam; Regina, Andrea

2014-01-01

Traditional challenges of creating a medical app include hearing the voices of various stakeholders as a collective rather than in a consultative process that is sequential. This report describes the development of a mobile (smartphone) app for adolescents with lupus as well as the process that was used to overcome the challenge described above. The development of the smartphone app addressed optimal ways to incorporate information about 1) lupus, including the effects of both the disease and the medications used to treat it; 2) how life choices can affect lupus patients' condition; and 3) ways to increase self-management and communication. The collaborative concept-generating and requirements-gathering methodology was used during a two-day workshop with a range of stakeholders (ages 16 - 59 years) that focused on leveraging user-centered design methods to generate guidance to mobile app developers. The app development process conducted during the workshop included the following steps: 1) recruiting a goal-focused collaborative group, 2) defining app objectives, 3) evaluating potential needs of users, 4) brainstorming app features and use-case modeling, 5) reviewing existing app features and prototypes, 6) refining functionalities, 7) writing user narratives, 8) visualizing navigation and feature design, and 9) identifying content. The use of creative devices such as drawing interfaces fostered fun, engagement, and sustained energy, and the use of a brainstorming technique leveraged methods that ensured an inclusive process so that even participants who were shy, quiet, or easily intimidated by "professionals" felt confident to contribute. In addition to a name change for the app, project outcomes included the selection of the following app features: symptom tracking; appointment and medication reminders; a social media component; a medical summary; easy navigation; informational content; gamification; and personalization (options for customization).

APP processing and the APP-KPI domain involvement in the amyloid cascade.

PubMed

Menéndez-González, M; Pérez-Pinera, P; Martínez-Rivera, M; Calatayud, M T; Blázquez Menes, B

2005-01-01

Alternative APP mRNA splicing can generate isoforms of APP containing a Kunitz protease inhibitor (KPI) domain. KPI is one of the main serine protease inhibitors. Protein and mRNA KPI(+)APP levels are elevated in Alzheimer's disease (AD) brain and are associated with increased amyloid beta deposition. In the last years increasing evidence on multiple points in the amyloid cascade where KPI(+)APP is involved has been accumulated, admitting an outstanding position in the pathogenesis of AD to the KPI domain. This review focuses on the APP processing, the molecular activity of KPI and its physiological and pathological roles and the KPI involvement in the amyloid cascade through the nerve growth factor, the lipoprotein receptor-related protein, the tumor necrosis factor-alpha converting enzyme and the Notch1 protein.

''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…

η-Secretase processing of APP inhibits neuronal activity in the hippocampus.

PubMed

Willem, Michael; Tahirovic, Sabina; Busche, Marc Aurel; Ovsepian, Saak V; Chafai, Magda; Kootar, Scherazad; Hornburg, Daniel; Evans, Lewis D B; Moore, Steven; Daria, Anna; Hampel, Heike; Müller, Veronika; Giudici, Camilla; Nuscher, Brigitte; Wenninger-Weinzierl, Andrea; Kremmer, Elisabeth; Heneka, Michael T; Thal, Dietmar R; Giedraitis, Vilmantas; Lannfelt, Lars; Müller, Ulrike; Livesey, Frederick J; Meissner, Felix; Herms, Jochen; Konnerth, Arthur; Marie, Hélène; Haass, Christian

2015-10-15

Alzheimer disease (AD) is characterized by the accumulation of amyloid plaques, which are predominantly composed of amyloid-β peptide. Two principal physiological pathways either prevent or promote amyloid-β generation from its precursor, β-amyloid precursor protein (APP), in a competitive manner. Although APP processing has been studied in great detail, unknown proteolytic events seem to hinder stoichiometric analyses of APP metabolism in vivo. Here we describe a new physiological APP processing pathway, which generates proteolytic fragments capable of inhibiting neuronal activity within the hippocampus. We identify higher molecular mass carboxy-terminal fragments (CTFs) of APP, termed CTF-η, in addition to the long-known CTF-α and CTF-β fragments generated by the α- and β-secretases ADAM10 (a disintegrin and metalloproteinase 10) and BACE1 (β-site APP cleaving enzyme 1), respectively. CTF-η generation is mediated in part by membrane-bound matrix metalloproteinases such as MT5-MMP, referred to as η-secretase activity. η-Secretase cleavage occurs primarily at amino acids 504-505 of APP695, releasing a truncated ectodomain. After shedding of this ectodomain, CTF-η is further processed by ADAM10 and BACE1 to release long and short Aη peptides (termed Aη-α and Aη-β). CTFs produced by η-secretase are enriched in dystrophic neurites in an AD mouse model and in human AD brains. Genetic and pharmacological inhibition of BACE1 activity results in robust accumulation of CTF-η and Aη-α. In mice treated with a potent BACE1 inhibitor, hippocampal long-term potentiation was reduced. Notably, when recombinant or synthetic Aη-α was applied on hippocampal slices ex vivo, long-term potentiation was lowered. Furthermore, in vivo single-cell two-photon calcium imaging showed that hippocampal neuronal activity was attenuated by Aη-α. These findings not only demonstrate a major functionally relevant APP processing pathway, but may also indicate potential translational relevance for therapeutic strategies targeting APP processing.

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

Describing the Process of Adopting Nutrition and Fitness Apps: Behavior Stage Model Approach

PubMed Central

Sproesser, Gudrun; Schupp, Harald T; Renner, Britta

2018-01-01

Background Although mobile technologies such as smartphone apps are promising means for motivating people to adopt a healthier lifestyle (mHealth apps), previous studies have shown low adoption and continued use rates. Developing the means to address this issue requires further understanding of mHealth app nonusers and adoption processes. This study utilized a stage model approach based on the Precaution Adoption Process Model (PAPM), which proposes that people pass through qualitatively different motivational stages when adopting a behavior. Objective To establish a better understanding of between-stage transitions during app adoption, this study aimed to investigate the adoption process of nutrition and fitness app usage, and the sociodemographic and behavioral characteristics and decision-making style preferences of people at different adoption stages. Methods Participants (N=1236) were recruited onsite within the cohort study Konstanz Life Study. Use of mobile devices and nutrition and fitness apps, 5 behavior adoption stages of using nutrition and fitness apps, preference for intuition and deliberation in eating decision-making (E-PID), healthy eating style, sociodemographic variables, and body mass index (BMI) were assessed. Results Analysis of the 5 behavior adoption stages showed that stage 1 (“unengaged”) was the most prevalent motivational stage for both nutrition and fitness app use, with half of the participants stating that they had never thought about using a nutrition app (52.41%, 533/1017), whereas less than one-third stated they had never thought about using a fitness app (29.25%, 301/1029). “Unengaged” nonusers (stage 1) showed a higher preference for an intuitive decision-making style when making eating decisions, whereas those who were already “acting” (stage 4) showed a greater preference for a deliberative decision-making style (F4,1012=21.83, P<.001). Furthermore, participants differed widely in their readiness to adopt nutrition and fitness apps, ranging from having “decided to” but not yet begun to act (stage 2; nutrition: 6.88%, 70/1017; fitness: 9.23%, 95/1029) to being “disengaged” following previous adoption (stage 5; nutrition: 13.77%, 140/1017; fitness: 15.06%, 155/1029). Conclusions Using a behavior stage model approach to describe the process of adopting nutrition and fitness apps revealed motivational stage differences between nonusers (being “unengaged,” having “decided not to act,” having “decided to act,” and being “disengaged”), which might contribute to a better understanding of the process of adopting mHealth apps and thus inform the future development of digital interventions. This study highlights that new user groups might be better reached by apps designed to address a more intuitive decision-making style. PMID:29535078

Describing the Process of Adopting Nutrition and Fitness Apps: Behavior Stage Model Approach.

PubMed

König, Laura M; Sproesser, Gudrun; Schupp, Harald T; Renner, Britta

2018-03-13

Although mobile technologies such as smartphone apps are promising means for motivating people to adopt a healthier lifestyle (mHealth apps), previous studies have shown low adoption and continued use rates. Developing the means to address this issue requires further understanding of mHealth app nonusers and adoption processes. This study utilized a stage model approach based on the Precaution Adoption Process Model (PAPM), which proposes that people pass through qualitatively different motivational stages when adopting a behavior. To establish a better understanding of between-stage transitions during app adoption, this study aimed to investigate the adoption process of nutrition and fitness app usage, and the sociodemographic and behavioral characteristics and decision-making style preferences of people at different adoption stages. Participants (N=1236) were recruited onsite within the cohort study Konstanz Life Study. Use of mobile devices and nutrition and fitness apps, 5 behavior adoption stages of using nutrition and fitness apps, preference for intuition and deliberation in eating decision-making (E-PID), healthy eating style, sociodemographic variables, and body mass index (BMI) were assessed. Analysis of the 5 behavior adoption stages showed that stage 1 ("unengaged") was the most prevalent motivational stage for both nutrition and fitness app use, with half of the participants stating that they had never thought about using a nutrition app (52.41%, 533/1017), whereas less than one-third stated they had never thought about using a fitness app (29.25%, 301/1029). "Unengaged" nonusers (stage 1) showed a higher preference for an intuitive decision-making style when making eating decisions, whereas those who were already "acting" (stage 4) showed a greater preference for a deliberative decision-making style (F 4,1012 =21.83, P<.001). Furthermore, participants differed widely in their readiness to adopt nutrition and fitness apps, ranging from having "decided to" but not yet begun to act (stage 2; nutrition: 6.88%, 70/1017; fitness: 9.23%, 95/1029) to being "disengaged" following previous adoption (stage 5; nutrition: 13.77%, 140/1017; fitness: 15.06%, 155/1029). Using a behavior stage model approach to describe the process of adopting nutrition and fitness apps revealed motivational stage differences between nonusers (being "unengaged," having "decided not to act," having "decided to act," and being "disengaged"), which might contribute to a better understanding of the process of adopting mHealth apps and thus inform the future development of digital interventions. This study highlights that new user groups might be better reached by apps designed to address a more intuitive decision-making style. ©Laura M König, Gudrun Sproesser, Harald T Schupp, Britta Renner. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 13.03.2018.

Building a Mobile HIV Prevention App for Men Who Have Sex With Men: An Iterative and Community-Driven Process

PubMed Central

McDougal, Sarah J; Sullivan, Patrick S; Stekler, Joanne D; Stephenson, Rob

2015-01-01

Background Gay, bisexual, and other men who have sex with men (MSM) account for a disproportionate burden of new HIV infections in the United States. Mobile technology presents an opportunity for innovative interventions for HIV prevention. Some HIV prevention apps currently exist; however, it is challenging to encourage users to download these apps and use them regularly. An iterative research process that centers on the community’s needs and preferences may increase the uptake, adherence, and ultimate effectiveness of mobile apps for HIV prevention. Objective The aim of this paper is to provide a case study to illustrate how an iterative community approach to a mobile HIV prevention app can lead to changes in app content to appropriately address the needs and the desires of the target community. Methods In this three-phase study, we conducted focus group discussions (FGDs) with MSM and HIV testing counselors in Atlanta, Seattle, and US rural regions to learn preferences for building a mobile HIV prevention app. We used data from these groups to build a beta version of the app and theater tested it in additional FGDs. A thematic data analysis examined how this approach addressed preferences and concerns expressed by the participants. Results There was an increased willingness to use the app during theater testing than during the first phase of FGDs. Many concerns that were identified in phase one (eg, disagreements about reminders for HIV testing, concerns about app privacy) were considered in building the beta version. Participants perceived these features as strengths during theater testing. However, some disagreements were still present, especially regarding the tone and language of the app. Conclusions These findings highlight the benefits of using an interactive and community-driven process to collect data on app preferences when building a mobile HIV prevention app. Through this process, we learned how to be inclusive of the larger MSM population without marginalizing some app users. Though some issues in phase one were able to be addressed, disagreements still occurred in theater testing. If the app is going to address a large and diverse risk group, we cannot include niche functionality that may offend some of the target population. PMID:27227136

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

Kosicek, Marko, E-mail: marko.kosicek@irb.hr; Malnar, Martina, E-mail: martina.malnar@irb.hr; Goate, Alison, E-mail: goate@icarus.wustl.edu

It has been suggested that cholesterol may modulate amyloid-{beta} (A{beta}) formation, a causative factor of Alzheimer's disease (AD), by regulating distribution of the three key proteins in the pathogenesis of AD ({beta}-amyloid precursor protein (APP), {beta}-secretase (BACE1) and/or presenilin 1 (PS1)) within lipid rafts. In this work we tested whether cholesterol accumulation upon NPC1 dysfunction, which causes Niemann Pick type C disease (NPC), causes increased partitioning of APP into lipid rafts leading to increased CTF/A{beta} formation in these cholesterol-rich membrane microdomains. To test this we used CHO NPC1{sup -/-} cells (NPC cells) and parental CHOwt cells. By sucrose density gradientmore » centrifugation we observed a shift in fl-APP/CTF compartmentalization into lipid raft fractions upon cholesterol accumulation in NPC vs. wt cells. Furthermore, {gamma}-secretase inhibitor treatment significantly increased fl-APP/CTF distribution in raft fractions in NPC vs. wt cells, suggesting that upon cholesterol accumulation in NPC1-null cells increased formation of APP-CTF and its increased processing towards A{beta} occurs in lipid rafts. Our results support that cholesterol overload, such as in NPC disease, leads to increased partitioning of APP/CTF into lipid rafts resulting in increased amyloidogenic processing of APP in these cholesterol-rich membranes. This work adds to the mechanism of the cholesterol-effect on APP processing and the pathogenesis of Alzheimer's disease and supports the role of lipid rafts in these processes.« less

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.

Epic Allies: Development of a Gaming App to Improve Antiretroviral Therapy Adherence Among Young HIV-Positive Men Who Have Sex With Men.

PubMed

LeGrand, Sara; Muessig, Kathryn Elizabeth; McNulty, Tobias; Soni, Karina; Knudtson, Kelly; Lemann, Alex; Nwoko, Nkechinyere; Hightow-Weidman, Lisa B

2016-05-13

In the United States, the human immunodeficiency virus (HIV) disproportionately affects young men who have sex with men (YMSM). For HIV-positive individuals, adherence to antiretroviral therapy (ART) is critical for achieving optimal health outcomes and reducing secondary transmission of HIV. However, YMSM often struggle with ART adherence. Novel mobile phone apps that incorporate game-based mechanics and social networking elements represent a promising intervention approach for improving ART adherence among YMSM. This study used a multiphase, iterative development process to create an ART adherence app for YMSM. The three-phase development process included: (1) theory-based concept development jointly by public health researchers and the technology team, (2) assessment of the target population's ART adherence needs and app preferences and development and testing of a clickable app prototype, and (3) development and usability testing of the final app prototype. The initial theory-based app concept developed in Phase One included medication reminders, daily ART adherence tracking and visualization, ART educational modules, limited virtual interactions with other app users, and gamification elements. In Phase Two, adherence needs, including those related to information, motivation, and behavioral skills, were identified. Participants expressed preferences for an ART adherence app that was informational, interactive, social, and customizable. Based on the findings from Phase Two, additional gaming features were added in Phase Three, including an interactive battle, superhero app theme, and app storyline. Other features were modified to increase interactivity and customization options and integrate the game theme. During usability testing of the final prototype, participants were able to understand and navigate the app successfully and rated the app favorably. An iterative development process was critical for the development of an ART adherence game app that was viewed as highly acceptable, relevant, and useful by YMSM.

Epic Allies: Development of a Gaming App to Improve Antiretroviral Therapy Adherence Among Young HIV-Positive Men Who Have Sex With Men

PubMed Central

Muessig, Kathryn Elizabeth; McNulty, Tobias; Soni, Karina; Knudtson, Kelly; Lemann, Alex; Nwoko, Nkechinyere; Hightow-Weidman, Lisa B

2016-01-01

Background In the United States, the human immunodeficiency virus (HIV) disproportionately affects young men who have sex with men (YMSM). For HIV-positive individuals, adherence to antiretroviral therapy (ART) is critical for achieving optimal health outcomes and reducing secondary transmission of HIV. However, YMSM often struggle with ART adherence. Novel mobile phone apps that incorporate game-based mechanics and social networking elements represent a promising intervention approach for improving ART adherence among YMSM. Objective This study used a multiphase, iterative development process to create an ART adherence app for YMSM. Methods The three-phase development process included: (1) theory-based concept development jointly by public health researchers and the technology team, (2) assessment of the target population’s ART adherence needs and app preferences and development and testing of a clickable app prototype, and (3) development and usability testing of the final app prototype. Results The initial theory-based app concept developed in Phase One included medication reminders, daily ART adherence tracking and visualization, ART educational modules, limited virtual interactions with other app users, and gamification elements. In Phase Two, adherence needs, including those related to information, motivation, and behavioral skills, were identified. Participants expressed preferences for an ART adherence app that was informational, interactive, social, and customizable. Based on the findings from Phase Two, additional gaming features were added in Phase Three, including an interactive battle, superhero app theme, and app storyline. Other features were modified to increase interactivity and customization options and integrate the game theme. During usability testing of the final prototype, participants were able to understand and navigate the app successfully and rated the app favorably. Conclusions An iterative development process was critical for the development of an ART adherence game app that was viewed as highly acceptable, relevant, and useful by YMSM. PMID:27178752

3,4-Methylenedioxymethamphetamine (MDMA), but not morphine, alters APP processing in the rat brain.

PubMed

Kálmán, János; Bjelik, Annamária; Hugyecz, Marietta; Tímár, Júlia; Gyarmati, Zsuzsanna; Zana, Marianna; Fürst, Zsuzsanna; Janka, Zoltán; Rakonczay, Zoltán; Horváth, Zoltán; Pákáski, Magdolna

2007-04-01

The abuse of drugs such as opioids and 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') can have detrimental effects on the cognitive functions, but the exact molecular mechanism whereby these drugs promote neurodegeneration remains to be elucidated. The major purpose of the present pilot study was to determine whether the chronic in-vivo administration of morphine (10 mg/kg) or MDMA (1 mg/kg) to rats can alter the expression and processing of amyloid precursor protein (APP), the central molecule in the proposed pathomechanism of Alzheimer's disease. MDMA treatment significantly decreased the production of APP in the cytosolic fraction of the brain cortex. A concomitant 25% increase was found both in the beta-secretase (BACE) and APP mRNA levels (108%). In contrast, in the applied single dosage chronic morphine treatment did not influence either the APP and BACE protein levels or the APP mRNA production. These results indicate that the chronic use of 'ecstasy', but not morphine, may be harmful via a novel mode of action, i.e. by altering the APP expression and processing in the brain.

Content Analysis of Diet-Related Mobile Apps: A Self-Regulation Perspective.

PubMed

Zahry, Nagwan R; Cheng, Ying; Peng, Wei

2016-10-01

Diet-related mobile apps hold promise in helping individuals self-regulate their eating behaviors. Nevertheless, little is known about the extent to which diet-related mobile apps incorporate the established behavior change theories and evidence-based practices that promote dietary self-regulation. Guided by the self-regulation aspect of Bandura's social cognitive theory and the Dietary Guidelines for Americans 2010 of the U.S. Department of Agriculture, this study conducts a content analysis of diet-related mobile apps for iPhone (N = 400). In terms of the adherence to the self-regulation aspect of the social cognitive theory, results show that although 72.5% of the apps incorporate at least one theoretical construct, few apps tap all three processes of self-regulation (i.e., self-observation/monitoring, judgment process, and self-reaction). Additionally, outcome expectation is manifested in a majority of the diet-related apps. In terms of the Dietary Guidelines for Americans 2010, while the diet-related apps equally emphasize setting goals for calorie intake or nutrient consumption, more apps feature nutrient tracking than calorie tracking. Implications and limitations are discussed.

APP heterozygosity averts memory deficit in knockin mice expressing the Danish dementia BRI2 mutant.

PubMed

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

2011-05-17

An autosomal dominant mutation in the BRI2/ITM2B gene causes familial Danish dementia (FDD). Analysis of FDD(KI) mice, a mouse model of FDD genetically congruous to the human disease since they carry one mutant and one wild-type Bri2/Itm2b allele, has shown that the Danish mutation causes loss of Bri2 protein, synaptic plasticity and memory impairments. BRI2 is a physiological interactor of Aβ-precursor protein (APP), a gene associated with Alzheimer disease, which inhibits processing of APP. Here, we show that APP/Bri2 complexes are reduced in synaptic membranes of FDD(KI) mice. Consequently, APP metabolites derived from processing of APP by β-, α- and γ-secretases are increased in Danish dementia mice. APP haplodeficiency prevents memory and synaptic dysfunctions, consistent with a role for APP metabolites in the pathogenesis of memory and synaptic deficits. This genetic suppression provides compelling evidence that APP and BRI2 functionally interact, and that the neurological effects of the Danish form of BRI2 only occur when sufficient levels of APP are supplied by two alleles. This evidence establishes a pathogenic sameness between familial Danish and Alzheimer's dementias.

APP heterozygosity averts memory deficit in knockin mice expressing the Danish dementia BRI2 mutant

PubMed Central

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

2011-01-01

An autosomal dominant mutation in the BRI2/ITM2B gene causes familial Danish dementia (FDD). Analysis of FDDKI mice, a mouse model of FDD genetically congruous to the human disease since they carry one mutant and one wild-type Bri2/Itm2b allele, has shown that the Danish mutation causes loss of Bri2 protein, synaptic plasticity and memory impairments. BRI2 is a physiological interactor of Aβ-precursor protein (APP), a gene associated with Alzheimer disease, which inhibits processing of APP. Here, we show that APP/Bri2 complexes are reduced in synaptic membranes of FDDKI mice. Consequently, APP metabolites derived from processing of APP by β-, α- and γ-secretases are increased in Danish dementia mice. APP haplodeficiency prevents memory and synaptic dysfunctions, consistent with a role for APP metabolites in the pathogenesis of memory and synaptic deficits. This genetic suppression provides compelling evidence that APP and BRI2 functionally interact, and that the neurological effects of the Danish form of BRI2 only occur when sufficient levels of APP are supplied by two alleles. This evidence establishes a pathogenic sameness between familial Danish and Alzheimer's dementias. PMID:21587206

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.

[Enniatin B synthesis by a Fusarium sambucinum Fuck culture].

PubMed

Minasian, A E; Chermenskiĭ, D N; Ellanskaia, I A

1978-01-01

Three fungal strains belonging to the genus Fusarium Lk. ex. Fr. (F. sambucinum Fuck. 52377, F. avenaceum (Fr. Sacc.) 52311, F. gibbosum App. et. Wr. emend Bilai 52021) whcih form 800-1200 mg of enniatin B per litre during submerged cultivation have been selected. The morphology of F. sambucinum 52377 in the course of growth and production of enniatin B on the selected medium is described. The maximum accumulation of the product is found at the stationary growth phase. The active accumulation of fatty inclusions during this period suggests the participation of metabolism of fatty acids in the biosynthesis of enniatin B.

Car App's Persuasive Design Principles and Behavior Change

ERIC Educational Resources Information Center

Zhang, Chao; Wan, Lili; Min, Daihwan

2016-01-01

The emphasis of this study lies in behavior change after using car apps that assist users in using their vehicles and establishing a process for examining the interrelationship between car app's persuasive characteristics and behavior change. A categorizing method was developed and 697 car apps were investigated and classified into eight…

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

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.

Finding Quality Geometry Apps: Not as Simple as a[superscript 2] + b[superscript 2] = c[superscript 2

ERIC Educational Resources Information Center

Larkin, Kevin

2016-01-01

Trying to find quality apps for use in mathematics classes can be time consuming and bewildering. This article outlines a process for evaluating apps and provides teachers with access to comprehensive qualitative evaluations of 53 geometrical apps based on pedagogical, mathematical and cognitive fidelities.

The Metalloprotease Meprin β Generates Amino Terminal-truncated Amyloid β Peptide Species*

PubMed Central

Bien, Jessica; Jefferson, Tamara; Čaušević, Mirsada; Jumpertz, Thorsten; Munter, Lisa; Multhaup, Gerd; Weggen, Sascha; Becker-Pauly, Christoph; Pietrzik, Claus U.

2012-01-01

The amyloid β (Aβ) peptide, which is abundantly found in the brains of patients suffering from Alzheimer disease, is central in the pathogenesis of this disease. Therefore, to understand the processing of the amyloid precursor protein (APP) is of critical importance. Recently, we demonstrated that the metalloprotease meprin β cleaves APP and liberates soluble N-terminal APP (N-APP) fragments. In this work, we present evidence that meprin β can also process APP in a manner reminiscent of β-secretase. We identified cleavage sites of meprin β in the amyloid β sequence of the wild type and Swedish mutant of APP at positions p1 and p2, thereby generating Aβ variants starting at the first or second amino acid residue. We observed even higher kinetic values for meprin β than BACE1 for both the wild type and the Swedish mutant APP form. This enzymatic activity of meprin β on APP and Aβ generation was also observed in the absence of BACE1/2 activity using a β-secretase inhibitor and BACE knock-out cells, indicating that meprin β acts independently of β-secretase. PMID:22879596

Neuronal-Targeted TFEB Accelerates Lysosomal Degradation of APP, Reducing Aβ Generation and Amyloid Plaque Pathogenesis

PubMed Central

Xiao, Qingli; Yan, Ping; Ma, Xiucui; Liu, Haiyan; Perez, Ronaldo; Zhu, Alec; Gonzales, Ernesto; Tripoli, Danielle L.; Czerniewski, Leah; Ballabio, Andrea; Cirrito, John R.

2015-01-01

In AD, an imbalance between Aβ production and removal drives elevated brain Aβ levels and eventual amyloid plaque deposition. APP undergoes nonamyloidogenic processing via α-cleavage at the plasma membrane, amyloidogenic β- and γ-cleavage within endosomes to generate Aβ, or lysosomal degradation in neurons. Considering multiple reports implicating impaired lysosome function as a driver of increased amyloidogenic processing of APP, we explored the efficacy of targeting transcription factor EB (TFEB), a master regulator of lysosomal pathways, to reduce Aβ levels. CMV promoter-driven TFEB, transduced via stereotactic hippocampal injections of adeno-associated virus particles in APP/PS1 mice, localized primarily to neuronal nuclei and upregulated lysosome biogenesis. This resulted in reduction of APP protein, the α and β C-terminal APP fragments (CTFs), and in the steady-state Aβ levels in the brain interstitial fluid. In aged mice, total Aβ levels and amyloid plaque load were selectively reduced in the TFEB-transduced hippocampi. TFEB transfection in N2a cells stably expressing APP695, stimulated lysosome biogenesis, reduced steady-state levels of APP and α- and β-CTFs, and attenuated Aβ generation by accelerating flux through the endosome-lysosome pathway. Cycloheximide chase assays revealed a shortening of APP half-life with exogenous TFEB expression, which was prevented by concomitant inhibition of lysosomal acidification. These data indicate that TFEB enhances flux through lysosomal degradative pathways to induce APP degradation and reduce Aβ generation. Activation of TFEB in neurons is an effective strategy to attenuate Aβ generation and attenuate amyloid plaque deposition in AD. SIGNIFICANCE STATEMENT A key driver for AD pathogenesis is the net balance between production and clearance of Aβ, the major component of amyloid plaques. Here we demonstrate that lysosomal degradation of holo-APP influences Aβ production by limiting the availability of APP for amyloidogenic processing. Using viral gene transfer of transcription factor EB (TFEB), a master regulator of lysosome biogenesis in neurons of APP/PS1 mice, steady-state levels of APP were reduced, resulting in decreased interstitial fluid Aβ levels and attenuated amyloid deposits. These effects were caused by accelerated lysosomal degradation of endocytosed APP, reflected by reduced APP half-life and steady-state levels in TFEB-expressing cells, with resultant decrease in Aβ production and release. Additional studies are needed to explore the therapeutic potential of this approach. PMID:26338325

Implementing Project SIED: Special Education Teachers' Perceptions of a Simplified Technology Decision-Making Process for App Identification and Evaluation

ERIC Educational Resources Information Center

Schmidt, Matthew M.; Lin, Meng-Fen Grace; Paek, Seungoh; MacSuga-Gage, Ashley; Gage, Nicholas A.

2017-01-01

The worldwide explosion in popularity of mobile devices has created a dramatic increase in mobile software (apps) that are quick and easy to find and install, cheap, disposable, and usually single purpose. Hence, teachers need an equally streamlined and simplified decision-making process to help them identify educational apps--an approach that…

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.

Mitosis-specific phosphorylation of amyloid precursor protein at Threonine 668 leads to its altered processing and association with centrosomes

PubMed Central

2011-01-01

Background Atypical expression of cell cycle regulatory proteins has been implicated in Alzheimer's disease (AD), but the molecular mechanisms by which they induce neurodegeneration are not well understood. We examined transgenic mice expressing human amyloid precursor protein (APP) and presenilin 1 (PS1) for changes in cell cycle regulatory proteins to determine whether there is a correlation between cell cycle activation and pathology development in AD. Results Our studies in the AD transgenic mice show significantly higher levels of cyclin E, cyclin D1, E2F1, and P-cdc2 in the cells in the vicinity of the plaques where maximum levels of Threonine 668 (Thr668)-phosphorylated APP accumulation was observed. This suggests that the cell cycle regulatory proteins might be influencing plaque pathology by affecting APP phosphorylation. Using neuroglioma cells overexpressing APP we demonstrate that phosphorylation of APP at Thr668 is mitosis-specific. Cells undergoing mitosis show altered cellular distribution and localization of P-APP at the centrosomes. Also, Thr668 phosphorylation in mitosis correlates with increased processing of APP to generate Aβ and the C-terminal fragment of APP, which is prevented by pharmacological inhibitors of the G1/S transition. Conclusions The data presented here suggests that cell cycle-dependent phosphorylation of APP may affect its normal cellular function. For example, association of P-APP with the centrosome may affect spindle assembly and cell cycle progression, further contributing to the development of pathology in AD. The experiments with G1/S inhibitors suggest that cell cycle inhibition may impede the development of Alzheimer's pathology by suppressing modification of βAPP, and thus may represent a novel approach to AD treatment. Finally, the cell cycle regulated phosphorylation and processing of APP into Aβ and the C-terminal fragment suggest that these proteins may have a normal function during mitosis. PMID:22112898

Digital health technology and trauma: development of an app to standardize care.

PubMed

Hsu, Jeremy M

2015-04-01

Standardized practice results in less variation, therefore reducing errors and improving outcome. Optimal trauma care is achieved through standardization, as is evidenced by the widespread adoption of the Advanced Trauma Life Support approach. The challenge for an individual institution is how does one educate and promulgate these standardized processes widely and efficiently? In today's world, digital health technology must be considered in the process. The aim of this study was to describe the process of developing an app, which includes standardized trauma algorithms. The objective of the app was to allow easy, real-time access to trauma algorithms, and therefore reduce omissions/errors. A set of trauma algorithms, relevant to the local setting, was derived from the best available evidence. After obtaining grant funding, a collaborative endeavour was undertaken with an external specialist app developing company. The process required 6 months to translate the existing trauma algorithms into an app. The app contains 32 separate trauma algorithms, formatted as a single-page flow diagram. It utilizes specific smartphone features such as 'pinch to zoom', jump-words and pop-ups to allow rapid access to the desired information. Improvements in trauma care outcomes result from reducing variation. By incorporating digital health technology, a trauma app has been developed, allowing easy and intuitive access to evidenced-based algorithms. © 2015 Royal Australasian College of Surgeons.

Quantitative modelling of amyloidogenic processing and its influence by SORLA in Alzheimer's disease.

PubMed

Schmidt, Vanessa; Baum, Katharina; Lao, Angelyn; Rateitschak, Katja; Schmitz, Yvonne; Teichmann, Anke; Wiesner, Burkhard; Petersen, Claus Munck; Nykjaer, Anders; Wolf, Jana; Wolkenhauer, Olaf; Willnow, Thomas E

2012-01-04

The extent of proteolytic processing of the amyloid precursor protein (APP) into neurotoxic amyloid-β (Aβ) peptides is central to the pathology of Alzheimer's disease (AD). Accordingly, modifiers that increase Aβ production rates are risk factors in the sporadic form of AD. In a novel systems biology approach, we combined quantitative biochemical studies with mathematical modelling to establish a kinetic model of amyloidogenic processing, and to evaluate the influence by SORLA/SORL1, an inhibitor of APP processing and important genetic risk factor. Contrary to previous hypotheses, our studies demonstrate that secretases represent allosteric enzymes that require cooperativity by APP oligomerization for efficient processing. Cooperativity enables swift adaptive changes in secretase activity with even small alterations in APP concentration. We also show that SORLA prevents APP oligomerization both in cultured cells and in the brain in vivo, eliminating the preferred form of the substrate and causing secretases to switch to a less efficient non-allosteric mode of action. These data represent the first mathematical description of the contribution of genetic risk factors to AD substantiating the relevance of subtle changes in SORLA levels for amyloidogenic processing as proposed for patients carrying SORL1 risk alleles.

Quantitative modelling of amyloidogenic processing and its influence by SORLA in Alzheimer's disease

PubMed Central

Schmidt, Vanessa; Baum, Katharina; Lao, Angelyn; Rateitschak, Katja; Schmitz, Yvonne; Teichmann, Anke; Wiesner, Burkhard; Petersen, Claus Munck; Nykjaer, Anders; Wolf, Jana; Wolkenhauer, Olaf; Willnow, Thomas E

2012-01-01

The extent of proteolytic processing of the amyloid precursor protein (APP) into neurotoxic amyloid-β (Aβ) peptides is central to the pathology of Alzheimer's disease (AD). Accordingly, modifiers that increase Aβ production rates are risk factors in the sporadic form of AD. In a novel systems biology approach, we combined quantitative biochemical studies with mathematical modelling to establish a kinetic model of amyloidogenic processing, and to evaluate the influence by SORLA/SORL1, an inhibitor of APP processing and important genetic risk factor. Contrary to previous hypotheses, our studies demonstrate that secretases represent allosteric enzymes that require cooperativity by APP oligomerization for efficient processing. Cooperativity enables swift adaptive changes in secretase activity with even small alterations in APP concentration. We also show that SORLA prevents APP oligomerization both in cultured cells and in the brain in vivo, eliminating the preferred form of the substrate and causing secretases to switch to a less efficient non-allosteric mode of action. These data represent the first mathematical description of the contribution of genetic risk factors to AD substantiating the relevance of subtle changes in SORLA levels for amyloidogenic processing as proposed for patients carrying SORL1 risk alleles. PMID:21989385

How the formation of amyloid plaques and neurofibrillary tangles may be related: a mathematical modelling study

NASA Astrophysics Data System (ADS)

Kuznetsov, I. A.; Kuznetsov, A. V.

2018-02-01

We develop a mathematical model that enables us to investigate possible mechanisms by which two primary markers of Alzheimer's disease (AD), extracellular amyloid plaques and intracellular tangles, may be related. Our model investigates the possibility that the decay of anterograde axonal transport of amyloid precursor protein (APP), caused by toxic tau aggregates, leads to decreased APP transport towards the synapse and APP accumulation in the soma. The developed model thus couples three processes: (i) slow axonal transport of tau, (ii) tau misfolding and agglomeration, which we simulated by using the Finke-Watzky model and (iii) fast axonal transport of APP. Because the timescale for tau agglomeration is much larger than that for tau transport, we suggest using the quasi-steady-state approximation for formulating and solving the governing equations for these three processes. Our results suggest that misfolded tau most likely accumulates in the beginning of the axon. The analysis of APP transport suggests that APP will also likely accumulate in the beginning of the axon, causing an increased APP concentration in this region, which could be interpreted as a `traffic jam'. The APP flux towards the synapse is significantly reduced by tau misfolding, but not due to the APP traffic jam, which can be viewed as a symptom, but rather due to the reduced affinity of kinesin-1 motors to APP-transporting vesicles.

Neuronal-Targeted TFEB Accelerates Lysosomal Degradation of APP, Reducing Aβ Generation and Amyloid Plaque Pathogenesis.

PubMed

Xiao, Qingli; Yan, Ping; Ma, Xiucui; Liu, Haiyan; Perez, Ronaldo; Zhu, Alec; Gonzales, Ernesto; Tripoli, Danielle L; Czerniewski, Leah; Ballabio, Andrea; Cirrito, John R; Diwan, Abhinav; Lee, Jin-Moo

2015-09-02

In AD, an imbalance between Aβ production and removal drives elevated brain Aβ levels and eventual amyloid plaque deposition. APP undergoes nonamyloidogenic processing via α-cleavage at the plasma membrane, amyloidogenic β- and γ-cleavage within endosomes to generate Aβ, or lysosomal degradation in neurons. Considering multiple reports implicating impaired lysosome function as a driver of increased amyloidogenic processing of APP, we explored the efficacy of targeting transcription factor EB (TFEB), a master regulator of lysosomal pathways, to reduce Aβ levels. CMV promoter-driven TFEB, transduced via stereotactic hippocampal injections of adeno-associated virus particles in APP/PS1 mice, localized primarily to neuronal nuclei and upregulated lysosome biogenesis. This resulted in reduction of APP protein, the α and β C-terminal APP fragments (CTFs), and in the steady-state Aβ levels in the brain interstitial fluid. In aged mice, total Aβ levels and amyloid plaque load were selectively reduced in the TFEB-transduced hippocampi. TFEB transfection in N2a cells stably expressing APP695, stimulated lysosome biogenesis, reduced steady-state levels of APP and α- and β-CTFs, and attenuated Aβ generation by accelerating flux through the endosome-lysosome pathway. Cycloheximide chase assays revealed a shortening of APP half-life with exogenous TFEB expression, which was prevented by concomitant inhibition of lysosomal acidification. These data indicate that TFEB enhances flux through lysosomal degradative pathways to induce APP degradation and reduce Aβ generation. Activation of TFEB in neurons is an effective strategy to attenuate Aβ generation and attenuate amyloid plaque deposition in AD. A key driver for AD pathogenesis is the net balance between production and clearance of Aβ, the major component of amyloid plaques. Here we demonstrate that lysosomal degradation of holo-APP influences Aβ production by limiting the availability of APP for amyloidogenic processing. Using viral gene transfer of transcription factor EB (TFEB), a master regulator of lysosome biogenesis in neurons of APP/PS1 mice, steady-state levels of APP were reduced, resulting in decreased interstitial fluid Aβ levels and attenuated amyloid deposits. These effects were caused by accelerated lysosomal degradation of endocytosed APP, reflected by reduced APP half-life and steady-state levels in TFEB-expressing cells, with resultant decrease in Aβ production and release. Additional studies are needed to explore the therapeutic potential of this approach. Copyright © 2015 the authors 0270-6474/15/3512137-15$15.00/0.

The development of Drink Less: an alcohol reduction smartphone app for excessive drinkers.

PubMed

Garnett, Claire; Crane, David; West, Robert; Brown, Jamie; Michie, Susan

2018-05-04

Excessive alcohol consumption poses a serious problem for public health. Digital behavior change interventions have the potential to help users reduce their drinking. In accordance with Open Science principles, this paper describes the development of a smartphone app to help individuals who drink excessively to reduce their alcohol consumption. Following the UK Medical Research Council's guidance and the Multiphase Optimization Strategy, development consisted of two phases: (i) selection of intervention components and (ii) design and development work to implement the chosen components into modules to be evaluated further for inclusion in the app. Phase 1 involved a scoping literature review, expert consensus study and content analysis of existing alcohol apps. Findings were integrated within a broad model of behavior change (Capability, Opportunity, Motivation-Behavior). Phase 2 involved a highly iterative process and used the "Person-Based" approach to promote engagement. From Phase 1, five intervention components were selected: (i) Normative Feedback, (ii) Cognitive Bias Re-training, (iii) Self-monitoring and Feedback, (iv) Action Planning, and (v) Identity Change. Phase 2 indicated that each of these components presented different challenges for implementation as app modules; all required multiple iterations and design changes to arrive at versions that would be suitable for inclusion in a subsequent evaluation study. The development of the Drink Less app involved a thorough process of component identification with a scoping literature review, expert consensus, and review of other apps. Translation of the components into app modules required a highly iterative process involving user testing and design modification.

Modulation of beta-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family.

PubMed

Cam, Judy A; Bu, Guojun

2006-08-18

Amyloid-beta peptide (Abeta) accumulation in the brain is an early, toxic event in the pathogenesis of Alzheimer's disease (AD). Abeta is produced by proteolytic processing of a transmembrane protein, beta-amyloid precursor protein (APP), by beta- and gamma-secretases. Mounting evidence has demonstrated that alterations in APP cellular trafficking and localization directly impact its processing to Abeta. Recent studies have shown that members of the low-density lipoprotein receptor family, including LRP, LRP1B, SorLA/LR11, and apolipoprotein E (apoE) receptor 2, interact with APP and regulate its endocytic trafficking. Another common feature of these receptors is their ability to bind apoE, which exists in three isoforms in humans and the presence of the epsilon4 allele represents a genetic risk factor for AD. In this review, we summarize the current understanding of the function of these apoE receptors with a focus on their role in APP trafficking and processing. Knowledge of the interactions between these distinct low-density lipoprotein receptor family members and APP may ultimately influence future therapies for AD.

The Long Way From Government Open Data to Mobile Health Apps: Overcoming Institutional Barriers in the US Federal Government

PubMed Central

2014-01-01

Background Government agencies in the United States are creating mobile health (mHealth) apps as part of recent policy changes initiated by the White House’s Digital Government Strategy. Objective The objective of the study was to understand the institutional and managerial barriers for the implementation of mHealth, as well as the resulting adoption pathways of mHealth. Methods This article is based on insights derived from qualitative interview data with 35 public managers in charge of promoting the reuse of open data through Challenge.gov, the platform created to run prizes, challenges, and the vetting and implementation of the winning and vendor-created apps. Results The process of designing apps follows three different pathways: (1) entrepreneurs start to see opportunities for mobile apps, and develop either in-house or contract out to already vetted Web design vendors; (2) a top-down policy mandates agencies to adopt at least two customer-facing mobile apps; and (3) the federal government uses a policy instrument called “Prizes and Challenges”, encouraging civic hackers to design health-related mobile apps using open government data from HealthData.gov, in combination with citizen needs. All pathways of the development process incur a set of major obstacles that have to be actively managed before agencies can promote mobile apps on their websites and app stores. Conclusions Beyond the cultural paradigm shift to design interactive apps and to open health-related data to the public, the managerial challenges include accessibility, interoperability, security, privacy, and legal concerns using interactive apps tracking citizen. PMID:25537314

The Long Way From Government Open Data to Mobile Health Apps: Overcoming Institutional Barriers in the US Federal Government.

PubMed

Mergel, Ines

2014-12-23

Government agencies in the United States are creating mobile health (mHealth) apps as part of recent policy changes initiated by the White House's Digital Government Strategy. The objective of the study was to understand the institutional and managerial barriers for the implementation of mHealth, as well as the resulting adoption pathways of mHealth. This article is based on insights derived from qualitative interview data with 35 public managers in charge of promoting the reuse of open data through Challenge.gov, the platform created to run prizes, challenges, and the vetting and implementation of the winning and vendor-created apps. The process of designing apps follows three different pathways: (1) entrepreneurs start to see opportunities for mobile apps, and develop either in-house or contract out to already vetted Web design vendors; (2) a top-down policy mandates agencies to adopt at least two customer-facing mobile apps; and (3) the federal government uses a policy instrument called "Prizes and Challenges", encouraging civic hackers to design health-related mobile apps using open government data from HealthData.gov, in combination with citizen needs. All pathways of the development process incur a set of major obstacles that have to be actively managed before agencies can promote mobile apps on their websites and app stores. Beyond the cultural paradigm shift to design interactive apps and to open health-related data to the public, the managerial challenges include accessibility, interoperability, security, privacy, and legal concerns using interactive apps tracking citizen.

Privacy as Part of the App Decision-Making Process

DTIC Science & Technology

2013-02-06

concerns they may not actively consider privacy while downloading apps from smartphone application marketplaces. Currently Android users have only the... Android permissions display which appears after they have selected an app to download to help them understand how applications access their information...marketplaces. Currently, Android users have only the Android permissions display, which appears after they have selected an app to download, to help

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.

BeWell24: development and process evaluation of a smartphone "app" to improve sleep, sedentary, and active behaviors in US Veterans with increased metabolic risk.

PubMed

Buman, Matthew P; Epstein, Dana R; Gutierrez, Monica; Herb, Christine; Hollingshead, Kevin; Huberty, Jennifer L; Hekler, Eric B; Vega-López, Sonia; Ohri-Vachaspati, Punam; Hekler, Andrea C; Baldwin, Carol M

2016-09-01

Lifestyle behaviors across the 24-h spectrum (i.e., sleep, sedentary, and active behaviors) drive metabolic risk. We describe the development and process evaluation of BeWell24, a multicomponent smartphone application (or "app") that targets behavior change in these interdependent behaviors. A community-embedded iterative design framework was used to develop the app. An 8-week multiphase optimization strategy design study was used to test the initial efficacy of the sleep, sedentary, and exercise components of the app. Process evaluation outcomes included objectively measured app usage statistics (e.g., minutes of usage, self-monitoring patterns), user experience interviews, and satisfaction ratings. Participants (N = 26) logged approximately 60 % of their sleep, sedentary, and exercise behaviors, which took 3-4 min/day to complete. Usage of the sleep and sedentary components peaked at week 2 and remained high throughout the intervention. Exercise component use was low. User experiences were mixed, and overall satisfaction was modest.

The Development of the Recovery Assessments by Phone Points (RAPP): A Mobile Phone App for Postoperative Recovery Monitoring and Assessment.

PubMed

Jaensson, Maria; Dahlberg, Karuna; Eriksson, Mats; Grönlund, Åke; Nilsson, Ulrica

2015-09-11

In Sweden, day surgery is performed in almost 2 million patients per year. Patient satisfaction is closely related to potential adverse events during the recovery process. A way to empower patients and give them the opportunity to affect care delivery is to let them evaluate their recovery process. The most common evaluation method is a follow-up telephone call by a nurse one or two days after surgery. In recent years, mHealth apps have been used to evaluate the nurse-patient relationship for self-management in chronic diseases or to evaluate pain after surgery. To the best of our knowledge, no previous research has explored the recovery process after day surgery via mobile phone in a Swedish cohort. The objective of the study is to describe the process of developing a mobile phone app using a Swedish Web-based Quality of Recovery (SwQoR) questionnaire to evaluate postoperative recovery after day surgery. The development process included five steps: (1) setting up an interdisciplinary task force, (2) evaluating the potential needs of app users, (3) developing the Swedish Web version of a QoR questionnaire, (4) constructing a mobile phone app, and (5) evaluating the interface and design by staff working in a day-surgery department and patients undergoing day surgery. A task force including specialists in information and communication technology, eHealth, and nursing care worked closely together to develop a Web-based app. Modifications to the QoR questionnaire were inspired by instruments used in the field of recovery for both children and adults. The Web-based app, Recovery Assessment by Phone Points (RAPP) consists of two parts: (1) a mobile app installed on the patient's private mobile phone, and (2) an administrator interface for the researchers. The final version of the SwQoR questionnaire, which includes 31 items, was successfully installed in RAPP. The interface and the design were evaluated by asking for user opinions about the design and usefulness of the app with 10 day surgery patients. Some minor adjustments were made concerning text size and screen color. Taking advantage of joint expertise, a useable Web-based app adaptable to different technical platforms was constructed. In addition, the SwQoR was successfully transferred into digital format for use on mobile phones.

Hydrophobic and superhydrophobic surfaces fabricated using atmospheric pressure cold plasma technology: A review.

PubMed

Dimitrakellis, Panagiotis; Gogolides, Evangelos

2018-04-01

Hydrophobic surfaces are often used to reduce wetting of surfaces by water. In particular, superhydrophobic surfaces are highly desired for several applications due to their exceptional properties such as self-cleaning, anti-icing, anti-friction and others. Such surfaces can be prepared via numerous methods including plasma technology, a dry technique with low environmental impact. Atmospheric pressure plasma (APP) has recently attracted significant attention as lower-cost alternative to low-pressure plasmas, and as a candidate for continuous rather than batch processing. Although there are many reviews on water-repellent surfaces, and a few reviews on APP technology, there are hardly any review works on APP processing for hydrophobic and superhydrohobic surface fabrication, a topic of high importance in nanotechnology and interface science. Herein, we critically review the advances on hydrophobic and superhydrophobic surface fabrication using APP technology, trying also to give some perspectives in the field. After a short introduction to superhydrophobicity of nanostructured surfaces and to APPs we focus this review on three different aspects: (1) The atmospheric plasma reactor technology used for fabrication of (super)hydrophobic surfaces. (2) The APP process for hydrophobic surface preparation. The hydrophobic surface preparation processes are categorized methodologically as: a) activation, b) grafting, c) polymerization, d) roughening and hydrophobization. Each category includes subcategories related to different precursors used. (3) One of the most important sections of this review concerns superhydrophobic surfaces fabricated using APP. These are methodologically characterized as follows: a) single step processes where micro-nano textured topography and low surface energy coating are created at the same time, or b) multiple step processes, where these steps occur sequentially in or out of the plasma. We end the review with some perspectives in the field. We aspire to address scientists, who will get involved in the fields of (super)hydrophobicity and/or in atmospheric pressure plasma processing. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Differential regulation of amyloid precursor protein sorting with pathological mutations results in a distinct effect on amyloid-β production.

PubMed

Lin, Yen-Chen; Wang, Jia-Yi; Wang, Kai-Chen; Liao, Jhih-Ying; Cheng, Irene H

2014-11-01

The deposition of amyloid-β (Aβ) peptide, which is generated from amyloid precursor protein (APP), is the pathological hallmark of Alzheimer's disease (AD). Three APP familial AD mutations (D678H, D678N, and H677R) located at the sixth and seventh amino acid of Aβ have distinct effect on Aβ aggregation, but their influence on the physiological and pathological roles of APP remain unclear. We found that the D678H mutation strongly enhances amyloidogenic cleavage of APP, thus increasing the production of Aβ. This enhancement of amyloidogenic cleavage is likely because of the acceleration of APPD678H sorting into the endosomal-lysosomal pathway. In contrast, the APPD678N and APPH677R mutants do not cause the same effects. Therefore, this study indicates a regulatory role of D678H in APP sorting and processing, and provides genetic evidence for the importance of APP sorting in AD pathogenesis. The internalization of amyloid precursor protein (APP) increases its opportunity to be processed by β-secretase and to produce Amyloid-β (Aβ) that causes Alzheimer's disease (AD). We report a pathogenic APPD678H mutant that enhances APP internalization into the endosomal-lysosomal pathway and thus promotes the β-secretase cleavage and Aβ production. This study provides genetic evidence for the importance of APP sorting in AD pathogenesis. © 2014 International Society for Neurochemistry.

The use of Facebook and WhatsApp application in learning process of physics to train students’ critical thinking skills

NASA Astrophysics Data System (ADS)

Kustijono, R.; Zuhri, F.

2018-01-01

The purpose of this research is to describe the learning process by using Facebook and WhatsApp to train students’ critical thinking skills. The research steps are: 1) analysis; 2) design; 3) development; 4) implementation; 5) evaluation. The research subjects are 40 students of Physics Department of Universitas Negeri Surabaya. This research used descriptive qualitative approach. The study The validation point, practicality, effectiveness, and critical thinking skills of students assessment use Likert scale. Learning process criteria are eligible if ≥ 60% is rated good or excellent. The results are: 1) the use of Facebook and WhatsApp can be implemented in the learning process, and the existing constraints can be overcome; 2) the assessment of students’ critical thinking skills is categorized as good and excellent. These results suggest that learning by using Facebook and WhatsApp can be used to train students’ critical thinking skills.

Systematic and Iterative Development of a Smartphone App to Promote Sun-Protection Among Holidaymakers: Design of a Prototype and Results of Usability and Acceptability Testing

PubMed Central

Sniehotta, Falko F; Birch-Machin, Mark A; Olivier, Patrick; Araújo-Soares, Vera

2017-01-01

Background Sunburn and intermittent exposure to ultraviolet rays are risk factors for melanoma. Sunburn is a common experience during holidays, making tourism settings of particular interest for skin cancer prevention. Holidaymakers are a volatile populations found at different locations, which may make them difficult to reach. Given the widespread use of smartphones, evidence suggests that this might be a novel, convenient, scalable, and feasible way of reaching the target population. Objective The main objective of this study was to describe and appraise the process of systematically developing a smartphone intervention (mISkin app) to promote sun-protection during holidays. Methods The iterative development process of the mISkin app was conducted over four sequential stages: (1) identify evidence on the most effective behavior change techniques (BCTs) used (active ingredients) as well as theoretical predictors and theories, (2) evidence-based intervention design, (3) co-design with users of the mISkin app prototype, and (4) refinement of the app. Each stage provided key findings that were subsequently used to inform the design of the mISkin app. Results The sequential approach to development integrates different strands of evidence to inform the design of an evidence-based intervention. A systematic review on previously tested interventions to promote sun-protection provided cues and constraints for the design of this intervention. The development and design of the mISkin app also incorporated other sources of information, such as other literature reviews and experts’ consultations. The developed prototype of the mISkin app was evaluated by engaging potential holidaymakers in the refinement and further development of the mISkin app through usability (ease-of-use) and acceptability testing of the intervention prototype. All 17 participants were satisfied with the mISkin prototype and expressed willingness to use it. Feedback on the app was integrated in the optimization process of the mISkin app. Conclusions The mISkin app was designed to promote sun-protection among holidaymakers and was based on current evidence, experts’ knowledge and experience, and user involvement. Based on user feedback, the app has been refined and a fully functional version is ready for formal testing in a feasibility pilot study. PMID:28606892

Numb endocytic adapter proteins regulate the transport and processing of the amyloid precursor protein in an isoform-dependent manner: implications for Alzheimer disease pathogenesis.

PubMed

Kyriazis, George A; Wei, Zelan; Vandermey, Miriam; Jo, Dong-Gyu; Xin, Ouyang; Mattson, Mark P; Chan, Sic L

2008-09-12

Central to the pathogenesis of Alzheimer disease is the aberrant processing of the amyloid precursor protein (APP) to generate amyloid beta-peptide (Abeta), the principle component of amyloid plaques. The cell fate determinant Numb is a phosphotyrosine binding domain (PTB)-containing endocytic adapter protein that interacts with the carboxyl-terminal domain of APP. The physiological relevance of this interaction is unknown. Mammals produce four alternatively spliced variants of Numb that differ in the length of their PTB and proline-rich region. In the current study, we determined the influence of the four human Numb isoforms on the intracellular trafficking and processing of APP. Stable expression of Numb isoforms that differ in the PTB but not in the proline-rich region results in marked differences in the sorting of APP to the recycling and degradative pathways. Neural cells expressing Numb isoforms that lack the insert in the PTB (short PTB (SPTB)) exhibited marked accumulation of APP in Rab5A-labeled early endosomal and recycling compartments, whereas those expressing isoforms with the insertion in the PTB (long PTB (LPTB)) exhibited reduced amounts of cellular APP and its proteolytic derivatives relative to parental control cells. Neither the activities of the beta- and gamma-secretases nor the expression of APP mRNA were significantly different in the stably transfected cells, suggesting that the differential effects of the Numb proteins on APP metabolism is likely to be secondary to altered APP trafficking. In addition, the expression of SPTB-Numb increases at the expense of LPTB-Numb in neuronal cultures subjected to stress, suggesting a role for Numb in stress-induced Abeta production. Taken together, these results suggest distinct roles for the human Numb isoforms in APP metabolism and may provide a novel potential link between altered Numb isoform expression and increased Abeta generation.

Human apoB overexpression and a high-cholesterol diet differently modify the brain APP metabolism in the transgenic mouse model of atherosclerosis.

PubMed

Bjelik, Annamária; Bereczki, Erika; Gonda, Szilvia; Juhász, Anna; Rimanóczy, Agnes; Zana, Marianna; Csont, Tamás; Pákáski, Magdolna; Boda, Krisztina; Ferdinandy, Péter; Dux, László; Janka, Zoltán; Sántha, Miklós; Kálmán, János

2006-09-01

Epidemiological and biochemical data suggest a link between the cholesterol metabolism, the amyloid precursor protein (APP) processing and the increased cerebral beta-amyloid (Abeta) deposition in Alzheimer's disease (AD). The individual and combined effects of a high-cholesterol (HC) diet and the overexpression of the human apoB-100 gene were therefore examined on the cerebral expression and processing of APP in homozygous apoB-100 transgenic mice [Tg (apoB(+/+))], a validated model of atherosclerosis. When fed with 2% cholesterol for 17 weeks, only the wild-type mice exhibited significantly increased APP695 (123%) and APP770 (138%) mRNA levels in the cortex. The HC diet-induced hypercholesterolemia significantly increased the APP isoform levels in the membrane-bound fraction, not only in the wild-type animals (114%), but also in the Tg apoB(+/+) group (171%). The overexpression of human apoB-100 gene by the liver alone reduced the brain APP isoform levels in the membrane-bound fraction (78%), whereas the levels were increased by the combined effect of HC and the overexpression of the human apoB-100 gene (134%). The protein kinase C and beta-secretase protein levels were not altered by the individual or combined effects of these two factors. Our data indicate that the two atherogenic factors, the HC diet and the overexpression of the human apoB-100 gene by the liver, could exert different effects on the processing and expression of APP in the mice brain.

Regulation of Synaptic Amyloid-β Generation through BACE1 Retrograde Transport in a Mouse Model of Alzheimer's Disease

PubMed Central

Ye, Xuan; Chang, Qing; Jeong, Yu Young; Cai, Huaibin; Kusnecov, Alexander

2017-01-01

Amyloid-β (Aβ) peptides play a key role in synaptic damage and memory deficits in the early pathogenesis of Alzheimer's disease (AD). Abnormal accumulation of Aβ at nerve terminals leads to synaptic pathology and ultimately to neurodegeneration. β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is the major neuronal β-secretase for Aβ generation. However, the mechanisms regulating BACE1 distribution in axons and β cleavage of APP at synapses remain largely unknown. Here, we reveal that dynein–Snapin-mediated retrograde transport regulates BACE1 trafficking in axons and APP processing at presynaptic terminals. BACE1 is predominantly accumulated within late endosomes at the synapses of AD-related mutant human APP (hAPP) transgenic (Tg) mice and patient brains. Defective retrograde transport by genetic ablation of snapin in mice recapitulates late endocytic retention of BACE1 and increased APP processing at presynaptic sites. Conversely, overexpressing Snapin facilitates BACE1 trafficking and reduces synaptic BACE1 accumulation by enhancing the removal of BACE1 from distal AD axons and presynaptic terminals. Moreover, elevated Snapin expression via stereotactic hippocampal injections of adeno-associated virus particles in mutant hAPP Tg mouse brains decreases synaptic Aβ levels and ameliorates synapse loss, thus rescuing cognitive impairments associated with hAPP mice. Altogether, our study provides new mechanistic insights into the complex regulation of BACE1 trafficking and presynaptic localization through Snapin-mediated dynein-driven retrograde axonal transport, thereby suggesting a potential approach of modulating Aβ levels and attenuating synaptic deficits in AD. SIGNIFICANCE STATEMENT β-Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) trafficking and synaptic localization significantly influence its β secretase activity and amyloid-β (Aβ) production. In AD brains, BACE1 is accumulated within dystrophic neurites, which is thought to augment Aβ-induced synaptotoxicity by Aβ overproduction. However, it remains largely unknown whether axonal transport regulates synaptic APP processing. Here, we demonstrate that Snapin-mediated retrograde transport plays a critical role in removing BACE1 from presynaptic terminals toward the soma, thus reducing synaptic Aβ production. Adeno-associated virus–mediated Snapin overexpression in the hippocampus of mutant hAPP mice significantly decreases synaptic Aβ levels, attenuates synapse loss, and thus rescues cognitive deficits. Our study uncovers a new pathway that controls synaptic APP processing by enhancing axonal BACE1 trafficking, thereby advancing our fundamental knowledge critical for ameliorating Aβ-linked synaptic pathology. PMID:28159908

A Standards-Based Architecture Proposal for Integrating Patient mHealth Apps to Electronic Health Record Systems.

PubMed

Marceglia, S; Fontelo, P; Rossi, E; Ackerman, M J

2015-01-01

Mobile health Applications (mHealth Apps) are opening the way to patients' responsible and active involvement with their own healthcare management. However, apart from Apps allowing patient's access to their electronic health records (EHRs), mHealth Apps are currently developed as dedicated "island systems". Although much work has been done on patient's access to EHRs, transfer of information from mHealth Apps to EHR systems is still low. This study proposes a standards-based architecture that can be adopted by mHealth Apps to exchange information with EHRs to support better quality of care. Following the definition of requirements for the EHR/mHealth App information exchange recently proposed, and after reviewing current standards, we designed the architecture for EHR/mHealth App integration. Then, as a case study, we modeled a system based on the proposed architecture aimed to support home monitoring for congestive heart failure patients. We simulated such process using, on the EHR side, OpenMRS, an open source longitudinal EHR and, on the mHealth App side, the iOS platform. The integration architecture was based on the bi-directional exchange of standard documents (clinical document architecture rel2 - CDA2). In the process, the clinician "prescribes" the home monitoring procedures by creating a CDA2 prescription in the EHR that is sent, encrypted and de-identified, to the mHealth App to create the monitoring calendar. At the scheduled time, the App alerts the patient to start the monitoring. After the measurements are done, the App generates a structured CDA2-compliant monitoring report and sends it to the EHR, thus avoiding local storage. The proposed architecture, even if validated only in a simulation environment, represents a step forward in the integration of personal mHealth Apps into the larger health-IT ecosystem, allowing the bi-directional data exchange between patients and healthcare professionals, supporting the patient's engagement in self-management and self-care.

Combining apps targeting professionals and senior citizens to improve housing accessibility and influence housing provision policies.

PubMed

Helle, Tina; Iwarsson, Susanne; Lunn, Tine Bieber; Iversen, Mogens Holm; Jonsson, Oskar; Mårtensson, Knut; Svarre, Tanja; Slaug, Björn

2015-01-01

Two separate apps that address the increasingly important issue of accessible housing for senior citizens have been developed in different project settings. One of the apps was developed to facilitate the process for professional raters to assess housing accessibility in the context of individual housing adaptations. The other app was developed for senior citizens to raise their awareness of possible accessibility problems in their current dwelling and in other apartments within the available housing stock. Both apps were developed with a high degree of active user involvement in processes utilizing multiple state of the art methods. The results are two well accepted prototype apps perceived as user-friendly and appropriate for the intended user groups. By combining these two apps, our ambition is for the professional raters to benefit by gaining knowledge of their clients' perceived needs and desires, and for senior citizens to benefit by getting access to a database of professionally rated dwellings. The ultimate goal is the generation of sound knowledge reflecting the needs and desires of senior citizens and professional requirements regarding accessible housing as a means to inform and influence housing provision policies.

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

Tetrahydroxystilbene glucoside modulates amyloid precursor protein processing via activation of AKT-GSK3β pathway in cells and in APP/PS1 transgenic mice.

PubMed

Yin, Xiaomin; Chen, Chen; Xu, Ting; Li, Lin; Zhang, Lan

2018-01-01

Alternative splicing of amyloid precursor protein (APP) exon 7 generates the isoforms containing a Kunitz protease inhibitor (KPI) domain. APP-KPI levels in the brain are correlated with amyloid beta (Aβ) production. Here, we determined the effect of Tetrahydroxystilbene glucoside (TSG) on the AKT-GSK3β pathway. We found GSK3β increased APP-KPI inclusion level and interacted with the splicing factor ASF. TSG was intragastrically administered to 5-month-old APP/PS1 transgenic mice for 12 months. We found that the activated the AKT-GSK3β signaling pathway suppressed APP-KPI inclusion. Moreover, TSG treatment attenuated amyloid deposition in APP/PS1 mice. This study demonstrates the neuroprotective effect of TSG on APP expression, suggesting that TSG may be beneficial for AD prevention and treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Rapid endocytosis of the low density lipoprotein receptor-related protein modulates cell surface distribution and processing of the beta-amyloid precursor protein.

PubMed

Cam, Judy A; Zerbinatti, Celina V; Li, Yonghe; Bu, Guojun

2005-04-15

The low density lipoprotein receptor-related protein (LRP) is a approximately 600-kDa multifunctional endocytic receptor that is highly expressed in the brain. LRP and its ligands apolipoprotein E, alpha2-macroglobulin, and beta-amyloid precursor protein (APP), are genetically linked to Alzheimer disease and are found in characteristic plaque deposits in brains of patients with Alzheimer disease. To identify which extracellular domains of LRP interact with APP, we used minireceptors of each of the individual LRP ligand binding domains and assessed their ability to bind and degrade a soluble APP fragment. LRP minireceptors containing ligand binding domains II and IV, but not I or III, interacted with APP. To test whether APP trafficking is directly related to the rapid endocytosis of LRP, we generated stable Chinese hamster ovary cell lines expressing either a wild-type LRP minireceptor or its endocytosis mutants. Chinese hamster ovary cells stably expressing wild-type LRP minireceptor had less cell surface APP than pcDNA3 vector-transfected cells, whereas those stably expressing endocytosis-defective LRP minireceptors accumulated APP at the cell surface. We also found that the steady-state levels of the amyloid beta-peptides (Abeta) is dictated by the relative expression levels of APP and LRP, probably reflecting the dual roles of LRP in both Abeta production and clearance. Together, these data establish a relationship between LRP rapid endocytosis and APP trafficking and proteolytic processing to generate Abeta.

Metabolic Characterization of Intact Cells Reveals Intracellular Amyloid Beta but Not Its Precursor Protein to Reduce Mitochondrial Respiration

PubMed Central

Schaefer, Patrick M.; von Einem, Bjoern; Walther, Paul; Calzia, Enrico; von Arnim, Christine A. F.

2016-01-01

One hallmark of Alzheimer´s disease are senile plaques consisting of amyloid beta (Aβ), which derives from the processing of the amyloid precursor protein (APP). Mitochondrial dysfunction has been linked to the pathogenesis of Alzheimer´s disease and both Aβ and APP have been reported to affect mitochondrial function in isolated systems. However, in intact cells, considering a physiological localization of APP and Aβ, it is pending what triggers the mitochondrial defect. Thus, the aim of this study was to dissect the impact of APP versus Aβ in inducing mitochondrial alterations with respect to their subcellular localization. We performed an overexpression of APP or beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), increasing APP and Aβ levels or Aβ alone, respectively. Conducting a comprehensive metabolic characterization we demonstrate that only APP overexpression reduced mitochondrial respiration, despite lower extracellular Aβ levels compared to BACE overexpression. Surprisingly, this could be rescued by a gamma secretase inhibitor, oppositionally indicating an Aβ-mediated mitochondrial toxicity. Analyzing Aβ localization revealed that intracellular levels of Aβ and an increased spatial association of APP/Aβ with mitochondria are associated with reduced mitochondrial respiration. Thus, our data provide marked evidence for a prominent role of intracellular Aβ accumulation in Alzheimer´s disease associated mitochondrial dysfunction. Thereby it highlights the importance of the localization of APP processing and intracellular transport as a decisive factor for mitochondrial function, linking two prominent hallmarks of neurodegenerative diseases. PMID:28005987

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 Smartphone App for Adolescents With Sleep Disturbance: Development of the Sleep Ninja

PubMed Central

O'Dea, Bridianne; Shand, Fiona; Johnston, Lara; Frayne, Anna; Fogarty, Andrea S; Christensen, Helen

2017-01-01

Background Sleep disturbances are common in young people and have consequences for academic, social, emotional, and behavioral development. The most effective treatment is cognitive behavioral therapy for insomnia (CBT-I), with evidence suggesting that it is efficacious even when delivered digitally. Objective There are no commercially available digitally delivered CBT-I programs for use by young people. The aim of this project was to develop a smartphone app that delivers CBT-I to young people to improve sleep. Methods To inform the development of the app, young people (N=21) aged between 12 and 16 years attended one of the 3 focus groups (each with 4-10 participants). These focus groups were conducted at different stages of the development process such that the process could be iterative. Participants were asked the reasons why they might use an app to help them sleep, the kinds of features or functions that they would like to see in such an app, and any concerns they may have in using the app. Data were analyzed using a thematic analysis approach. Of the issues discussed by the participants, the researchers selected themes associated with content, functionality, and accessibility and user experience to examine, as these were most informative for the app design process. Results In terms of content, young people were interested in receiving information about recommended sleep guidelines and personalized information for their age group. They reported that keeping a sleep diary was acceptable, but they should be able to complete it flexibly, in their own time. They reported mixed views about the use of the phone’s accelerometer. Young people felt that the functionality of the app should include elements of game playing if they were to remain engaged with the app. Flexibility of use and personalized features were also desirable, and there were mixed views about the schedule of notifications and reminders. Participants reported that for the app to be accessible and usable, it should be from a trusted developer, have engaging aesthetics, have a layout that is easy to navigate, not rely on Internet coverage, and preferably be free. Participants felt that being able to conceal the purpose of the app from peers was an advantage and were willing to provide personal information to use the app if the purpose and use of that information was made clear. Overall, participants endorsed the use of the app for sleep problems among their age group and reported motivation to use it. Conclusions The Sleep Ninja is a fully-automated app that delivers CBT-I to young people, incorporating the features and information that young people reported they would expect from this app. A pilot study testing the feasibility, acceptability, and efficacy of the Sleep Ninja is now underway. PMID:28754651

Effects of acetylate hyperforin on the processing of amyloid precursor protein.

PubMed

Chen, Xiang; Feng, Wenshang; Chen, Qing; Yang, Xiangling; Yang, Depo; Wang, Dongmei; Zhong, Ling

2009-02-20

Hyperforin (HF) is a phloroglucinol compound obtained from St. John's Wort (Hypericum perforatum). Recent studies have shown that Hyperforin can be used to improve psychopathologic symptoms of Alzheimer's disease but the mechanism is not clear. This may be partly due to the difficult in studying Hyperforin, since this chemical is unstable and is sensitive to light, oxygen, and heat. In this study, we explored the effects of acetylate hyperforin (ace-HF), a stable derivative of hyperforin, on the processing of amyloid precursor protein (APP). HEK293 cells transfected with pcDNA3.1APP695sw and SH-SY5Y cells were treated with ace-HF, followed by measuring the levels of APP and sAPPα. Twelve hours of treatment led to an increase in extracellular sAPPα, but APP mRNA and protein levels were unchanged. Further studies with α-secretase and a pan PKC inhibitor, Calphostin C, indicated that ace-HF's effect on extracellular sAPPα was closely related to PKC activities and α-secretase activities. Our findings suggest that ace-HF can modulate α-secretase-mediated APP processing via a PKC signaling pathway.

Cerebrospinal fluid Aβ42 levels and APP processing pathway genes in Parkinson's disease.

PubMed

Bekris, Lynn M; Tsuang, Debby W; Peskind, Elaine R; Yu, Chang E; Montine, Thomas J; Zhang, Jing; Zabetian, Cyrus P; Leverenz, James B

2015-06-01

Of recent interest is the finding that certain cerebrospinal fluid (CSF) biomarkers traditionally linked to Alzheimer's disease (AD), specifically amyloid beta protein (Aβ), are abnormal in PD CSF. The aim of this exploratory investigation was to determine whether genetic variation within the amyloid precursor protein (APP) processing pathway genes correlates with CSF Aβ42 levels in Parkinson's disease (PD). Parkinson's disease (n = 86) and control (n = 161) DNA were genotyped for 19 regulatory region tagging single-nucleotide polymorphisms (SNPs) within nine genes (APP, ADAM10, BACE1, BACE2, PSEN1, PSEN2, PEN2, NCSTN, and APH1B) involved in the cleavage of APP. The SNP genotypes were tested for their association with CSF biomarkers and PD risk while adjusting for age, sex, and APOE ɛ4 status. Significant correlation with CSF Aβ42 levels in PD was observed for two SNPs, (APP rs466448 and APH1B rs2068143). Conversely, significant correlation with CSF Aβ42 levels in controls was observed for three SNPs (APP rs214484, rs2040273, and PSEN1 rs362344). In addition, results of this exploratory investigation suggest that an APP SNP and an APH1B SNP are marginally associated with PD CSF Aβ42 levels in APOE ɛ4 noncarriers. Further hypotheses generated include that decreased CSF Aβ42 levels are in part driven by genetic variation in APP processing genes. Additional investigation into the relationship between these findings and clinical characteristics of PD, including cognitive impairment, compared with other neurodegenerative diseases, such as AD, are warranted. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.

Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice

PubMed Central

Kraft, Andrew W.; Hu, Xiaoyan; Yoon, Hyejin; Yan, Ping; Xiao, Qingli; Wang, Yan; Gil, So Chon; Brown, Jennifer; Wilhelmsson, Ulrika; Restivo, Jessica L.; Cirrito, John R.; Holtzman, David M.; Kim, Jungsu; Pekny, Milos; Lee, Jin-Moo

2013-01-01

The accumulation of aggregated amyloid-β (Aβ) in amyloid plaques is a neuropathological hallmark of Alzheimer's disease (AD). Reactive astrocytes are intimately associated with amyloid plaques; however, their role in AD pathogenesis is unclear. We deleted the genes encoding two intermediate filament proteins required for astrocyte activation—glial fibrillary acid protein (Gfap) and vimentin (Vim)—in transgenic mice expressing mutant human amyloid precursor protein and presenilin-1 (APP/PS1). The gene deletions increased amyloid plaque load: APP/PS1 Gfap−/−Vim−/− mice had twice the plaque load of APP/PS1 Gfap+/+Vim+/+ mice at 8 and 12 mo of age. APP expression and soluble and interstitial fluid Aβ levels were unchanged, suggesting that the deletions had no effect on APP processing or Aβ generation. Astrocyte morphology was markedly altered by the deletions: wild-type astrocytes had hypertrophied processes that surrounded and infiltrated plaques, whereas Gfap−/−Vim−/− astrocytes had little process hypertrophy and lacked contact with adjacent plaques. Moreover, Gfap and Vim gene deletion resulted in a marked increase in dystrophic neurites (2- to 3-fold higher than APP/PS1 Gfap+/+Vim+/+ mice), even after normalization for amyloid load. These results suggest that astrocyte activation limits plaque growth and attenuates plaque-related dystrophic neurites. These activities may require intimate contact between astrocyte and plaque.—Kraft, A. W., Hu, X., Yoon, H., Yan, P., Xiao, Q., Wang, Y., Gil, S. C., Brown, J., Wilhelmsson, U., Restivo, J. L., Cirrito, J. R., Holtzman, D. M., Kim, J., Pekny, M., Lee, J.-M. Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice. PMID:23038755

APP Function and Lipids: A Bidirectional Link

PubMed Central

Grimm, Marcus O. W.; Mett, Janine; Grimm, Heike S.; Hartmann, Tobias

2017-01-01

Extracellular neuritic plaques, composed of aggregated amyloid-β (Aβ) peptides, are one of the major histopathological hallmarks of Alzheimer’s disease (AD), a progressive, irreversible neurodegenerative disorder and the most common cause of dementia in the elderly. One of the most prominent risk factor for sporadic AD, carrying one or two aberrant copies of the apolipoprotein E (ApoE) ε4 alleles, closely links AD to lipids. Further, several lipid classes and fatty acids have been reported to be changed in the brain of AD-affected individuals. Interestingly, the observed lipid changes in the brain seem not only to be a consequence of the disease but also modulate Aβ generation. In line with these observations, protective lipids being able to decrease Aβ generation and also potential negative lipids in respect to AD were identified. Mechanistically, Aβ peptides are generated by sequential proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. The α-secretase appears to compete with β-secretase for the initial cleavage of APP, preventing Aβ production. All APP-cleaving secretases as well as APP are transmembrane proteins, further illustrating the impact of lipids on Aβ generation. Beside the pathological impact of Aβ, accumulating evidence suggests that Aβ and the APP intracellular domain (AICD) play an important role in regulating lipid homeostasis, either by direct effects or by affecting gene expression or protein stability of enzymes involved in the de novo synthesis of different lipid classes. This review summarizes the current literature addressing the complex bidirectional link between lipids and AD and APP processing including lipid alterations found in AD post mortem brains, lipids that alter APP processing and the physiological functions of Aβ and AICD in the regulation of several lipid metabolism pathways. PMID:28344547

Co-creating and Evaluating a Web-app Mapping Real-World Health Care Services for Students: The servi-Share Protocol.

PubMed

Montagni, Ilaria; Langlois, Emmanuel; Wittwer, Jérôme; Tzourio, Christophe

2017-02-16

University students aged 18-30 years are a population group reporting low access to health care services, with high rates of avoidance and delay of medical care. This group also reports not having appropriate information about available health care services. However, university students are at risk for several health problems, and regular medical consultations are recommended in this period of life. New digital devices are popular among the young, and Web-apps can be used to facilitate easy access to information regarding health care services. A small number of electronic health (eHealth) tools have been developed with the purpose of displaying real-world health care services, and little is known about how such eHealth tools can improve access to care. This paper describes the processes of co-creating and evaluating the beta version of a Web-app aimed at mapping and describing free or low-cost real-world health care services available in the Bordeaux area of France, which is specifically targeted to university students. The co-creation process involves: (1) exploring the needs of students to know and access real-world health care services; (2) identifying the real-world health care services of interest for students; and (3) deciding on a user interface, and developing the beta version of the Web-app. Finally, the evaluation process involves: (1) testing the beta version of the Web-app with the target audience (university students aged 18-30 years); (2) collecting their feedback via a satisfaction survey; and (3) planning a long-term evaluation. The co-creation process of the beta version of the Web-app was completed in August 2016 and is described in this paper. The evaluation process started on September 7, 2016. The project was completed in December 2016 and implementation of the Web-app is ongoing. Web-apps are an innovative way to increase the health literacy of young people in terms of delivery of and access to health care. The creation of Web-apps benefits from the involvement of stakeholders (eg, students and health care providers) to correctly identify the real-world health care services to be displayed. ©Ilaria Montagni, Emmanuel Langlois, Jérôme Wittwer, Christophe Tzourio. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 16.02.2017.

Co-creating and Evaluating a Web-app Mapping Real-World Health Care Services for Students: The servi-Share Protocol

PubMed Central

Langlois, Emmanuel; Wittwer, Jérôme; Tzourio, Christophe

2017-01-01

Background University students aged 18-30 years are a population group reporting low access to health care services, with high rates of avoidance and delay of medical care. This group also reports not having appropriate information about available health care services. However, university students are at risk for several health problems, and regular medical consultations are recommended in this period of life. New digital devices are popular among the young, and Web-apps can be used to facilitate easy access to information regarding health care services. A small number of electronic health (eHealth) tools have been developed with the purpose of displaying real-world health care services, and little is known about how such eHealth tools can improve access to care. Objective This paper describes the processes of co-creating and evaluating the beta version of a Web-app aimed at mapping and describing free or low-cost real-world health care services available in the Bordeaux area of France, which is specifically targeted to university students. Methods The co-creation process involves: (1) exploring the needs of students to know and access real-world health care services; (2) identifying the real-world health care services of interest for students; and (3) deciding on a user interface, and developing the beta version of the Web-app. Finally, the evaluation process involves: (1) testing the beta version of the Web-app with the target audience (university students aged 18-30 years); (2) collecting their feedback via a satisfaction survey; and (3) planning a long-term evaluation. Results The co-creation process of the beta version of the Web-app was completed in August 2016 and is described in this paper. The evaluation process started on September 7, 2016. The project was completed in December 2016 and implementation of the Web-app is ongoing. Conclusions Web-apps are an innovative way to increase the health literacy of young people in terms of delivery of and access to health care. The creation of Web-apps benefits from the involvement of stakeholders (eg, students and health care providers) to correctly identify the real-world health care services to be displayed. PMID:28209561

A Framework for Mobile Apps in Colleges and Universities: Data Mining Perspective

ERIC Educational Resources Information Center

Singh, Archana; Ranjan, Jayanthi

2016-01-01

The Enterprise mobility communication technology provides easy and quick accessibility to data and information integrated into one single touch point device. This device incorporates or integrates all the processes into small applications or App and thus increases the workforce capability of knowledge workers. "App" which is a small set…

Evaluation Method for an App Involving Kitchen Activities.

PubMed

Burzagli, Laura; Gaggioli, Andrea

2017-01-01

An app, developed for the national Italian project "Design for all", is evaluated here. This app supports the user in most of his/her cooking activities. The evaluation process integrates different technologies, such as expert interview, cognitive walkthrough and focus group, to consider different aspects that include, but are not limited to, usability and accessibility.

APP mRNA splicing is upregulated in the brain of biglycan transgenic mice.

PubMed

Bjelik, Annamária; Pákáski, Magdolna; Bereczki, Erika; Gonda, Szilvia; Juhász, Anna; Rimanóczy, Agnes; Zana, Marianna; Janka, Zoltán; Sántha, Miklós; Kálmán, János

2007-01-01

Many of the risk factors for cerebrovascular disease and atherosclerosis also increase the risk of Alzheimer's disease, characterized by the cerebral deposition of beta-amyloid plaques resulting from the abnormal processing of the transmembrane amyloid precursor protein (APP). The initiating event of cholesterol-induced atherosclerosis is the retention and accumulation of atherogenic apolipoprotein B (apoB) together with low-density lipoproteins in the vascular intima. Biglycan, a member of the small leucine-rich protein family, was suspected of contributing to this process. The individual and combined overexpressions of biglycan and apoB-100 were therefore examined on the cortical APP mRNA levels of transgenic mice by means of semiquantitative PCR. As compared with the control littermates, transgenic biglycan mice had significantly increased cortical APP695 (122%) and APP770 (157%) mRNA levels, while the double transgenic (apoB(+/-)xbiglycan(+/-)) mice did not exhibit any changes. These results provide the first experimental evidence that the atherogenic risk factor biglycan alters APP splicing and may participate in the pathogenesis of both Alzheimer and vascular dementias.

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.

Systematic and Iterative Development of a Smartphone App to Promote Sun-Protection Among Holidaymakers: Design of a Prototype and Results of Usability and Acceptability Testing.

PubMed

Rodrigues, Angela M; Sniehotta, Falko F; Birch-Machin, Mark A; Olivier, Patrick; Araújo-Soares, Vera

2017-06-12

Sunburn and intermittent exposure to ultraviolet rays are risk factors for melanoma. Sunburn is a common experience during holidays, making tourism settings of particular interest for skin cancer prevention. Holidaymakers are a volatile populations found at different locations, which may make them difficult to reach. Given the widespread use of smartphones, evidence suggests that this might be a novel, convenient, scalable, and feasible way of reaching the target population. The main objective of this study was to describe and appraise the process of systematically developing a smartphone intervention (mISkin app) to promote sun-protection during holidays. The iterative development process of the mISkin app was conducted over four sequential stages: (1) identify evidence on the most effective behavior change techniques (BCTs) used (active ingredients) as well as theoretical predictors and theories, (2) evidence-based intervention design, (3) co-design with users of the mISkin app prototype, and (4) refinement of the app. Each stage provided key findings that were subsequently used to inform the design of the mISkin app. The sequential approach to development integrates different strands of evidence to inform the design of an evidence-based intervention. A systematic review on previously tested interventions to promote sun-protection provided cues and constraints for the design of this intervention. The development and design of the mISkin app also incorporated other sources of information, such as other literature reviews and experts' consultations. The developed prototype of the mISkin app was evaluated by engaging potential holidaymakers in the refinement and further development of the mISkin app through usability (ease-of-use) and acceptability testing of the intervention prototype. All 17 participants were satisfied with the mISkin prototype and expressed willingness to use it. Feedback on the app was integrated in the optimization process of the mISkin app. The mISkin app was designed to promote sun-protection among holidaymakers and was based on current evidence, experts' knowledge and experience, and user involvement. Based on user feedback, the app has been refined and a fully functional version is ready for formal testing in a feasibility pilot study. ©Angela M Rodrigues, Falko F Sniehotta, Mark A Birch-Machin, Patrick Olivier, Vera Araújo-Soares. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 12.06.2017.

TEAMS (Tele-Exercise and Multiple Sclerosis), a Tailored Telerehabilitation mHealth App: Participant-Centered Development and Usability Study.

PubMed

Thirumalai, Mohanraj; Rimmer, James H; Johnson, George; Wilroy, Jereme; Young, Hui-Ju; Mehta, Tapan; Lai, Byron

2018-05-24

People with multiple sclerosis face varying levels of disability and symptoms, thus requiring highly trained therapists and/or exercise trainers to design personalized exercise programs. However, for people living in geographically isolated communities, access to such trained professionals can be challenging due to a number of barriers associated with cost, access to transportation, and travel distance. Generic mobile health exercise apps often fall short of what people with multiple sclerosis need to become physically active (ie, exercise content that has been adapted to accommodate a wide range of functional limitations). This usability study describes the development process of the TEAMS (Tele-Exercise and Multiple Sclerosis) app, which is being used by people with multiple sclerosis in a large randomized controlled trial to engage in home-based telerehabilitation. Twenty-one participants with disabilities (10 people with multiple sclerosis) were involved in the double iterative design, which included the simultaneous development of the app features and exercise content (exercise videos and articles). Framed within a user-centered design approach, the development process included 2 stages: ground-level creation (focus group followed by early stage evaluations and developments), and proof of concept through 2 usability tests. Usability (effectiveness, usefulness, and satisfaction) was evaluated using a mixed-methods approach. During testing of the app's effectiveness, the second usability test resulted in an average of 1 problem per participant, a decrease of 53% compared to the initial usability test. Five themes were constructed from the qualitative data that related to app usefulness and satisfaction, namely: high perceived confidence for app usability, positive perceptions of exercise videos, viable exercise option at home, orientation and familiarity required for successful participation, and app issues. Participants acknowledged that the final app was ready to be delivered to the public after minor revisions. After including these revisions, the project team released the final app that is being used in the randomized controlled trial. A multi-level user-centered development process resulted in the development of an inclusive exercise program for people with multiple sclerosis operated through an easy-to-use app. The promotion of exercise through self-regulated mHealth programs requires a stakeholder-driven approach to app development. This ensures that app and content match the preferences and functional abilities of the end user (ie, people with varying levels of multiple sclerosis). ©Mohanraj Thirumalai, James H Rimmer, George Johnson, Jereme Wilroy, Hui-Ju Young, Tapan Mehta, Byron Lai. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 24.05.2018.

Herpes simplex virus interferes with amyloid precursor protein processing.

PubMed

Shipley, Suzanne J; Parkin, Edward T; Itzhaki, Ruth F; Dobson, Curtis B

2005-08-18

The early events underlying Alzheimer's disease (AD) remain uncertain, although environmental factors may be involved. Work in this laboratory has shown that the combination of herpes simplex virus type 1 (HSV1) in brain and carriage of the APOE-epsilon4 allele of the APOE gene strongly increases the risk of developing AD. The development of AD is thought to involve abnormal aggregation or deposition of a 39-43 amino acid protein--beta amyloid (Abeta)--within the brain. This is cleaved from the much larger transmembranal protein 'amyloid precursor protein' (APP). Any agent able to interfere directly with Abeta or APP metabolism may therefore have the capacity to contribute towards AD. One recent report showed that certain HSV1 glycoprotein peptides may aggregate like Abeta; a second study described a role for APP in transport of virus in squid axons. However to date the effects of acute herpesvirus infection on metabolism of APP in human neuronal-type cells have not been investigated. In order to find if HSV1 directly affects APP and its degradation, we have examined this protein from human neuroblastoma cells (normal and transfected with APP 695) infected with the virus, using Western blotting. We have found that acute HSV1 (and also HSV2) infection rapidly reduces full length APP levels--as might be expected--yet surprisingly markedly increases levels of a novel C-terminal fragment of APP of about 55 kDa. This band was not increased in cells treated with the protein synthesis inhibitor cycloheximide Herpes virus infection leads to rapid loss of full length APP from cells, yet also causes increased levels of a novel 55 kDa C-terminal APP fragment. These data suggest that infection can directly alter the processing of a transmembranal protein intimately linked to the aetiology of AD.

Amyloid Precursor Protein Processing and Alzheimer’s Disease

PubMed Central

O’Brien, Richard J.; Wong, Philip C.

2011-01-01

Alzheimer’s disease (AD), the leading cause of dementia worldwide, is characterized by the accumulation of the β-amyloid peptide (Aβ) within the brain along with hyperphosphorylated and cleaved forms of the microtubule-associated protein tau. Genetic, biochemical, and behavioral research suggest that physiologic generation of the neurotoxic Aβ peptide from sequential amyloid precursor protein (APP) proteolysis is the crucial step in the development of AD. APP is a single-pass transmembrane protein expressed at high levels in the brain and metabolized in a rapid and highly complex fashion by a series of sequential proteases, including the intramembranous γ-secretase complex, which also process other key regulatory molecules. Why Aβ accumulates in the brains of elderly individuals is unclear but could relate to changes in APP metabolism or Aβ elimination. Lessons learned from biochemical and genetic studies of APP processing will be crucial to the development of therapeutic targets to treat AD. PMID:21456963

An app for patient education and self-audit within an enhanced recovery program for bowel surgery: a pilot study assessing validity and usability.

PubMed

Pecorelli, Nicolò; Fiore, Julio F; Kaneva, Pepa; Somasundram, Abarna; Charlebois, Patrick; Liberman, A Sender; Stein, Barry L; Carli, Franco; Feldman, Liane S

2018-05-01

While patient engagement and clinical audit are key components of successful enhanced recovery programs (ERPs), they require substantial resource allocation. The objective of this study was to assess the validity and usability of a novel mobile device application for education and self-reporting of adherence for patients undergoing bowel surgery within an established ERP. Prospectively recruited patients undergoing bowel surgery within an ERP used a novel app specifically designed to provide daily recovery milestones and record adherence to 15 different ERP processes and six patient-reported outcomes (PROs). Validity was measured by the agreement index (Cohen's kappa coefficient for categorical, and interclass correlation coefficient (ICC) for continuous variables) between patient-reported data through the app and data recorded by a clinical auditor. Acceptability and usability of the app were measured by the System Usability Scale (SUS). Forty-five patients participated in the study (mean age 61, 64% male). Overall, patients completed 159 of 179 (89%) of the available questionnaires through the app. Median time to complete a questionnaire was 2 min 49 s (i.q.r. 2'32″-4'36″). Substantial (kappa > 0.6) or almost perfect agreement (kappa > 0.8) and strong correlation (ICC > 0.7) between data collected through the app and by the clinical auditor was found for 14 ERP processes and four PROs. Patient-reported usability was high; mean SUS score was 87 (95% CI 83-91). Only 6 (13%) patients needed technical support to use the app. Forty (89%) patients found the app was helpful to achieve their daily goals, and 34 (76%) thought it increased their motivation to recover after surgery. This novel application provides a tool to record patient adherence to care processes and PROs, with high agreement with traditional clinical audit, high usability, and patient satisfaction. Future studies should investigate the use of mobile device apps as strategies to increase adherence to perioperative interventions.

The Cognitive Processing of an Educational App with Electroencephalogram and "Eye Tracking"

ERIC Educational Resources Information Center

Cuesta-Cambra, Ubaldo; Niño-González, José Ignacio; Rodríguez-Terceño, José

2017-01-01

The use of apps in education is becoming more frequent. However, the mechanisms of attention and processing of their contents and their consequences in learning have not been sufficiently studied. The objective of this work is to analyze how information is processed and learned and how visual attention takes place. It also investigates the…

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.

Nicergoline stimulates protein kinase C mediated alpha-secretase processing of the amyloid precursor protein in cultured human neuroblastoma SH-SY5Y cells.

PubMed

Cedazo-Minguez, A; Bonecchi, L; Winblad, B; Post, C; Wong, E H; Cowburn, R F; Benatti, L

1999-10-01

We investigated the ability of the antidementia agents, nicergoline, aniracetam and hydergine to stimulate PKC mediated alpha-secretase amyloid precursor protein (APP) processing in cultured human neuroblastoma SH-SY5Y cells. Western immunoblotting of cell conditioned media using the Mabs 22C11 and 6E10 revealed the presence of 2 bands with molecular mass of 90 and 120 kDa, corresponding to possible alternatively glycosylated forms of secreted APP (APPs). Short-term (30 min and 2 h) treatment of cells with nicergoline gave an increased intensity of both bands, compared to non-treated cells. Maximal nicergoline effects, of the order of 150-200% over basal APPs release, were seen at concentrations between 1 and 10 microM. Under the same condition, 1 microM PdBu, used as a positive control, gave 500-1000% increases of basal APPs release. In contrast, aniracetam and hydergine, did not show any effect on APPs secretion. 2 h treatment with nicergoline had no effect on cellular full-length APP levels, as determined by immunoblotting of cell extracts with 22C11 and CT15 antibodies. Immunoblotting with PKC isoform specific antibodies of soluble and membrane fractions prepared from 2 h treated cells, showed that nicergoline (50 microM) and PdBu (1 microM) both induced translocation of PKC alpha, gamma and epsilon, but not PKC beta. The involvement of PKC in mediating nicergoline stimulated APPs release was also studied using specific inhibitors. 1 microM calphostin C, a broad range PKC inhibitor, significantly reduced both PdBu (1 microM) and nicergoline (10 microM) induced APPs release. In contrast, Go6976 (1 microM), a selective PKC alpha and beta1 inhibitor, as well as the cAMP-dependent protein kinase inhibitor, H89 (1 microM) were without effect. These results indicate that nicergoline can modulate alpha-secretase APP processing by a PKC dependent mechanism that is likely to involve the gamma and epsilon isoforms of this enzyme.

A Standards-Based Architecture Proposal for Integrating Patient mHealth Apps to Electronic Health Record Systems

PubMed Central

Fontelo, P.; Rossi, E.; Ackerman, MJ

2015-01-01

Summary Background Mobile health Applications (mHealth Apps) are opening the way to patients’ responsible and active involvement with their own healthcare management. However, apart from Apps allowing patient’s access to their electronic health records (EHRs), mHealth Apps are currently developed as dedicated “island systems”. Objective Although much work has been done on patient’s access to EHRs, transfer of information from mHealth Apps to EHR systems is still low. This study proposes a standards-based architecture that can be adopted by mHealth Apps to exchange information with EHRs to support better quality of care. Methods Following the definition of requirements for the EHR/mHealth App information exchange recently proposed, and after reviewing current standards, we designed the architecture for EHR/mHealth App integration. Then, as a case study, we modeled a system based on the proposed architecture aimed to support home monitoring for congestive heart failure patients. We simulated such process using, on the EHR side, OpenMRS, an open source longitudinal EHR and, on the mHealth App side, the iOS platform. Results The integration architecture was based on the bi-directional exchange of standard documents (clinical document architecture rel2 – CDA2). In the process, the clinician “prescribes” the home monitoring procedures by creating a CDA2 prescription in the EHR that is sent, encrypted and de-identified, to the mHealth App to create the monitoring calendar. At the scheduled time, the App alerts the patient to start the monitoring. After the measurements are done, the App generates a structured CDA2-compliant monitoring report and sends it to the EHR, thus avoiding local storage. Conclusions The proposed architecture, even if validated only in a simulation environment, represents a step forward in the integration of personal mHealth Apps into the larger health-IT ecosystem, allowing the bi-directional data exchange between patients and healthcare professionals, supporting the patient’s engagement in self-management and self-care. PMID:26448794

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

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

Mobile Apps to Support and Assess Foreign Language Learning

ERIC Educational Resources Information Center

Berns, Anke; Palomo-Duarte, Manuel; Dodero, Juan Manuel; Ruiz-Ladrón, Juan Miguel; Márquez, Andrea Calderón

2015-01-01

In the last two decades there have been many attempts to integrate all kinds of mobile devices and apps to support formal as well as informal learning processes. However, most of the available apps still support mainly individual learning, using mobile devices to deliver content rather than providing learners with the opportunity to interact with…

Co-Designing Mobile Apps to Assist in Clinical Nursing Education: A Study Protocol.

PubMed

O'Connor, Siobhan; Andrews, Tom

2016-01-01

Mobile applications (apps) to train health professionals is gaining momentum as the benefits of mobile learning (mLearning) are becoming apparent in complex clinical environments. However, most educational apps are generic, off-the-shelf pieces of software that do not take into consideration the unique needs of nursing students. The proposed study will apply a user-centred design process to create a tailored mobile app for nursing students to learn and apply clinical skills in practice. The app will be piloted and evaluated to understand how nursing students use mobile technology in clinical settings to support their learning and educational needs.

Suppression of angiogenesis by atmospheric pressure plasma in human aortic endothelial cells

NASA Astrophysics Data System (ADS)

Gweon, Bomi; Kim, Hyeonyu; Kim, Kijung; Kim, Mina; Shim, Eunyoung; Kim, Sunja; Choe, Wonho; Shin, Jennifer H.

2014-03-01

Atmospheric pressure plasma (APP) has been recognized as a promising tool for cancer therapy based on its ability to remove cancer cells by causing apoptosis and necrosis. However, the effect of APP on the neighboring tissues of tumors remains unknown. Moreover, the role of APP on the vessels near tumors could be very important, because once a tumor becomes vascularized, the potential for metastasis can increase dramatically. We show in the present study that APP can induce cell cycle arrest in endothelial cells and further suppress the angiogenesis process. These results strongly support the use of APP in cancer treatment.

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.

Novel Roles of Amyloid-Beta Protein Precursor Metabolites in Fragile X Syndrome and Autism

PubMed Central

Westmark, Cara J.; Sokol, Deborah K.; Maloney, Bryan; Lahiri, Debomoy K.

2017-01-01

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and is associated with up to 5% of autism cases. Several promising drugs are in preclinical testing for FXS; however, bench-to-bedside plans for the clinic are severely limited due to lack of validated biomarkers and outcome measures. Published work from our laboratories has demonstrated altered levels of amyloid-beta (Aβ) protein precursor (APP) and its metabolites in FXS and idiopathic autism. Westmark and colleagues have focused on β-secretase (amyloidogenic) processing and the accumulation of Aβ peptides in adult FXS models while Lahiri and Sokol have studied α-secretase (nonamyloidogenic or anabolic) processing and altered levels of sAPPα and Aβ in pediatric autism and FXS. Thus, our groups have hypothesized a pivotal role for these Alzheimer’s disease (AD)-related proteins in the neurodevelopmental disorders of FXS and autism. In this review, we discuss the contribution of APP metabolites to FXS and autism pathogenesis as well as the potential use of these metabolites as blood-based biomarkers and therapeutic targets. Our future focus is to identify key underlying mechanisms through which APP metabolites contribute to FXS and autism condition-to-disease pathology. Positive outcomes will support utilizing APP metabolites as blood-based biomarkers in clinical trials as well as testing drugs that modulate APP processing as potential disease therapeutics. Our studies to understand the role of APP metabolites in developmental conditions such as FXS and autism are a quantum leap for the neuroscience field, which has traditionally restricted any role of APP to AD and aging. PMID:27573877

Patient characteristics and process factors associated with antipsychotic polypharmacy in a nationwide sample of psychiatric inpatients in Italy.

PubMed

Santone, Giovanni; Bellantuono, Cesario; Rucci, Paola; Picardi, Angelo; Preti, Antonio; de Girolamo, Giovanni

2011-05-01

The present study investigated: (i) the rate of prescription of antipsychotic (AP) polypharmacy (APP) in a large, representative sample of psychiatric inpatients; and (ii) the relationship between APP prescription and the characteristics of patients and facilities. The sample included 1022 psychiatric patients scheduled to be discharged from acute inpatient facilities with drug therapies including AP. Demographic and clinical data were obtained from the treating physician or retrieved from patients' records through a standardized Patient Form. Patients were administered the 24-item Brief Psychiatric Rating Scale. Three indicators were used to describe the process of care in the facilities: a Restrictiveness score, a Standardization score, and a Treatment score. A multilevel mixed-effect logistic regression was used to predict APP using patient and facility as the variables. APP was prescribed to 333 (32.5%) patients, the most common patterns being a first-generation and a second-generation AP (n = 178, 17.6%) or of two first-generation APs (n = 80, 7.8%). Patients with a diagnosis of schizophrenia and poorer insight into illness at admission were significantly more likely to receive APP. The availability of more complex therapeutic interventions in the facility was also associated with APP. In our nationwide sample of psychiatric inpatients, APP was frequently prescribed to treat the more severe patients. However, it was also associated with process of care characteristics such as delivery of more complex therapeutic interventions, and was therefore not used only to control patient behavior. Copyright © 2010 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

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.

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.

A Smartphone App for Adolescents With Sleep Disturbance: Development of the Sleep Ninja.

PubMed

Werner-Seidler, Aliza; O'Dea, Bridianne; Shand, Fiona; Johnston, Lara; Frayne, Anna; Fogarty, Andrea S; Christensen, Helen

2017-07-28

Sleep disturbances are common in young people and have consequences for academic, social, emotional, and behavioral development. The most effective treatment is cognitive behavioral therapy for insomnia (CBT-I), with evidence suggesting that it is efficacious even when delivered digitally. There are no commercially available digitally delivered CBT-I programs for use by young people. The aim of this project was to develop a smartphone app that delivers CBT-I to young people to improve sleep. To inform the development of the app, young people (N=21) aged between 12 and 16 years attended one of the 3 focus groups (each with 4-10 participants). These focus groups were conducted at different stages of the development process such that the process could be iterative. Participants were asked the reasons why they might use an app to help them sleep, the kinds of features or functions that they would like to see in such an app, and any concerns they may have in using the app. Data were analyzed using a thematic analysis approach. Of the issues discussed by the participants, the researchers selected themes associated with content, functionality, and accessibility and user experience to examine, as these were most informative for the app design process. In terms of content, young people were interested in receiving information about recommended sleep guidelines and personalized information for their age group. They reported that keeping a sleep diary was acceptable, but they should be able to complete it flexibly, in their own time. They reported mixed views about the use of the phone's accelerometer. Young people felt that the functionality of the app should include elements of game playing if they were to remain engaged with the app. Flexibility of use and personalized features were also desirable, and there were mixed views about the schedule of notifications and reminders. Participants reported that for the app to be accessible and usable, it should be from a trusted developer, have engaging aesthetics, have a layout that is easy to navigate, not rely on Internet coverage, and preferably be free. Participants felt that being able to conceal the purpose of the app from peers was an advantage and were willing to provide personal information to use the app if the purpose and use of that information was made clear. Overall, participants endorsed the use of the app for sleep problems among their age group and reported motivation to use it. The Sleep Ninja is a fully-automated app that delivers CBT-I to young people, incorporating the features and information that young people reported they would expect from this app. A pilot study testing the feasibility, acceptability, and efficacy of the Sleep Ninja is now underway. ©Aliza Werner-Seidler, Bridianne O'Dea, Fiona Shand, Lara Johnston, Anna Frayne, Andrea S Fogarty, Helen Christensen. Originally published in JMIR Mental Health (http://mental.jmir.org), 28.07.2017.

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

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.

The Role of Gay Identity Confusion and Outness in Sex-Seeking on Mobile Dating Apps Among Men Who Have Sex With Men: A Conditional Process Analysis.

PubMed

Chan, Lik Sam

2017-01-01

Mobile dating apps are now a popular platform for men who have sex with men (MSM) to connect with others. Based on the uses and gratifications (U&G) theory, this study explores the relationship between sex-seeking and the number of casual sex partners met through MSM-based mobile dating apps (Grindr, Jack'd, and SCRUFF). The conditional process analysis (N = 401) shows that this relationship was significant and was mediated by the intensity of app use. That is, sex-seeking indirectly affected the number of casual sex partners through the intensity of app use. Furthermore, gay identity confusion and outness to the world moderated this indirect effect: it was stronger when the user was either more confused about his sexuality or was less out to the world. This research introduces an alternative way to incorporate psychographics variables into the U&G framework.

The use of atmospheric pressure plasma as a curing process for canned ground ham.

PubMed

Lee, Juri; Jo, Kyung; Lim, Yubong; Jeon, Hee Joon; Choe, Jun Ho; Jo, Cheorun; Jung, Samooel

2018-02-01

This study investigated the potential use of atmospheric pressure plasma (APP) treatment as a curing process for canned ground ham. APP treatment for 60min while mixing increased the nitrite content in the meat batters from 0.64 to 60.50mgkg -1 while the pH and the total content of aerobic bacteria in the meat batters were unchanged. The canned ground hams cured by the APP treatment for 30min displayed no difference in their physicochemical qualities, such as nitrosyl hemochrome, color, residual nitrite, texture, lipid oxidation, and protein oxidation, compared with those of canned ground hams cured with sodium nitrite or celery powder at 42mgkg -1 of nitrite. The canned ground hams cured by the APP treatment received a higher score in taste and overall acceptability than those cured with sodium nitrite. Canned ground ham can be cured by the APP treatment without nitrite additives. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of acetylate hyperforin on the processing of amyloid precursor protein

PubMed Central

Chen, Xiang; Feng, Wenshang; Chen, Qing; Yang, Xiangling; Yang, Depo; Wang, Dongmei; Zhong, Ling

2009-01-01

Hyperforin (HF) is a phloroglucinol compound obtained from St. John's Wort (Hypericum perforatum). Recent studies have shown that Hyperforin can be used to improve psychopathologic symptoms of Alzheimer's disease but the mechanism is not clear. This may be partly due to the difficult in studying Hyperforin, since this chemical is unstable and is sensitive to light, oxygen, and heat. In this study, we explored the effects of acetylate hyperforin (ace-HF), a stable derivative of hyperforin, on the processing of amyloid precursor protein (APP). HEK293 cells transfected with pcDNA3.1APP695sw and SH-SY5Y cells were treated with ace-HF, followed by measuring the levels of APP and sAPPα. Twelve hours of treatment led to an increase in extracellular sAPPα, but APP mRNA and protein levels were unchanged. Further studies with α-secretase and a pan PKC inhibitor, Calphostin C, indicated that ace-HF's effect on extracellular sAPPα was closely related to PKC activities and α-secretase activities. Our findings suggest that ace-HF can modulate α-secretase-mediated APP processing via a PKC signaling pathway. PMID:21383880

TEAMS (Tele-Exercise and Multiple Sclerosis), a Tailored Telerehabilitation mHealth App: Participant-Centered Development and Usability Study

PubMed Central

Rimmer, James H; Johnson, George; Wilroy, Jereme; Young, Hui-Ju; Mehta, Tapan; Lai, Byron

2018-01-01

Background People with multiple sclerosis face varying levels of disability and symptoms, thus requiring highly trained therapists and/or exercise trainers to design personalized exercise programs. However, for people living in geographically isolated communities, access to such trained professionals can be challenging due to a number of barriers associated with cost, access to transportation, and travel distance. Generic mobile health exercise apps often fall short of what people with multiple sclerosis need to become physically active (ie, exercise content that has been adapted to accommodate a wide range of functional limitations). Objective This usability study describes the development process of the TEAMS (Tele-Exercise and Multiple Sclerosis) app, which is being used by people with multiple sclerosis in a large randomized controlled trial to engage in home-based telerehabilitation. Methods Twenty-one participants with disabilities (10 people with multiple sclerosis) were involved in the double iterative design, which included the simultaneous development of the app features and exercise content (exercise videos and articles). Framed within a user-centered design approach, the development process included 2 stages: ground-level creation (focus group followed by early stage evaluations and developments), and proof of concept through 2 usability tests. Usability (effectiveness, usefulness, and satisfaction) was evaluated using a mixed-methods approach. Results During testing of the app’s effectiveness, the second usability test resulted in an average of 1 problem per participant, a decrease of 53% compared to the initial usability test. Five themes were constructed from the qualitative data that related to app usefulness and satisfaction, namely: high perceived confidence for app usability, positive perceptions of exercise videos, viable exercise option at home, orientation and familiarity required for successful participation, and app issues. Participants acknowledged that the final app was ready to be delivered to the public after minor revisions. After including these revisions, the project team released the final app that is being used in the randomized controlled trial. Conclusions A multi-level user-centered development process resulted in the development of an inclusive exercise program for people with multiple sclerosis operated through an easy-to-use app. The promotion of exercise through self-regulated mHealth programs requires a stakeholder-driven approach to app development. This ensures that app and content match the preferences and functional abilities of the end user (ie, people with varying levels of multiple sclerosis). PMID:29798832

The Na+/H+ exchanger NHE6 modulates endosomal pH to control processing of amyloid precursor protein in a cell culture model of Alzheimer disease.

PubMed

Prasad, Hari; Rao, Rajini

2015-02-27

Early intervention may be key to safe and effective therapies in patients with Alzheimer disease. Endosomal dysfunction is an early step in neurodegeneration. Endosomes are a major site of production of Aβ peptide from the processing of amyloid precursor protein (APP) by clipping enzymes (β- and γ-secretases). The β-secretase enzyme BACE1 requires acidic lumen pH for optimum function, and acid pH promotes Aβ aggregation. The Na(+)/H(+) exchanger NHE6 provides a leak pathway for protons, limiting luminal acidification by proton pumps. Like APP, NHE6 expression was induced upon differentiation of SH-SY5Y neuroblastoma cells and localized to an endosomal compartment. Therefore, we investigated whether NHE6 expression altered APP localization and processing in a stably transfected cell culture model of human APP expression. We show that co-expression with NHE6 or treatment with the Na(+)/H(+) ionophore monensin shifted APP away from the trans-Golgi network into early and recycling endosomes in HEK293 cells. NHE6 alkalinized the endosomal lumen, similar to monensin, and significantly attenuated APP processing and Aβ secretion. In contrast, Aβ production was elevated upon NHE6 knockdown. We show that NHE6 transcript and protein levels are lowered in Alzheimer brains relative to control. These findings, taken together with emerging genetic evidence linking endosomal Na(+)/H(+) exchangers with Alzheimer disease, suggest that proton leak pathways may regulate Aβ generation and contribute to disease etiology. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The Na+/H+ Exchanger NHE6 Modulates Endosomal pH to Control Processing of Amyloid Precursor Protein in a Cell Culture Model of Alzheimer Disease*

PubMed Central

Prasad, Hari; Rao, Rajini

2015-01-01

Early intervention may be key to safe and effective therapies in patients with Alzheimer disease. Endosomal dysfunction is an early step in neurodegeneration. Endosomes are a major site of production of Aβ peptide from the processing of amyloid precursor protein (APP) by clipping enzymes (β- and γ-secretases). The β-secretase enzyme BACE1 requires acidic lumen pH for optimum function, and acid pH promotes Aβ aggregation. The Na+/H+ exchanger NHE6 provides a leak pathway for protons, limiting luminal acidification by proton pumps. Like APP, NHE6 expression was induced upon differentiation of SH-SY5Y neuroblastoma cells and localized to an endosomal compartment. Therefore, we investigated whether NHE6 expression altered APP localization and processing in a stably transfected cell culture model of human APP expression. We show that co-expression with NHE6 or treatment with the Na+/H+ ionophore monensin shifted APP away from the trans-Golgi network into early and recycling endosomes in HEK293 cells. NHE6 alkalinized the endosomal lumen, similar to monensin, and significantly attenuated APP processing and Aβ secretion. In contrast, Aβ production was elevated upon NHE6 knockdown. We show that NHE6 transcript and protein levels are lowered in Alzheimer brains relative to control. These findings, taken together with emerging genetic evidence linking endosomal Na+/H+ exchangers with Alzheimer disease, suggest that proton leak pathways may regulate Aβ generation and contribute to disease etiology. PMID:25561733

The low density lipoprotein receptor-related protein 1B retains beta-amyloid precursor protein at the cell surface and reduces amyloid-beta peptide production.

PubMed

Cam, Judy A; Zerbinatti, Celina V; Knisely, Jane M; Hecimovic, Silva; Li, Yonghe; Bu, Guojun

2004-07-09

The low density lipoprotein (LDL) receptor-related protein 1B (LRP1B) is a newly identified member of the LDL receptor family that shares high homology with the LDL receptor-related protein (LRP). LRP1B was originally described as a putative tumor suppressor in lung cancer cells; however, its expression profile in several regions of adult human brain suggests it may have additional functions in the central nervous system. Since LRP1B has overlapping ligand binding properties with LRP, we investigated whether LRP1B, like LRP, could interact with the beta-amyloid precursor protein (APP) and modulate its processing to amyloid-beta peptides (Abetas). Using an LRP1B minireceptor (mLRP1B4) generated to study the trafficking of LRP1B, we found that mLRP1B4 and APP form an immunoprecipitable complex. Furthermore mLRP1B4 bound and facilitated the degradation of a soluble isoform of APP containing a Kunitz proteinase inhibitor domain but not soluble APP lacking a Kunitz proteinase inhibitor domain. A functional consequence of mLRP1B4 expression was a significant accumulation of APP at the cell surface, which is likely related to the slow endocytosis rate of LRP1B. More importantly, mLRP1B4-expressing cells that accumulated cell surface APP produced less Abeta and secreted more soluble APP. These findings reveal that LRP1B is a novel binding partner of APP that functions to decrease APP processing to Abeta. Consequently LRP1B expression could function to protect against the pathogenesis of Alzheimer's disease.

Citrulline diet supplementation improves specific age-related raft changes in wild-type rodent hippocampus.

PubMed

Marquet-de Rougé, Perrine; Clamagirand, Christine; Facchinetti, Patricia; Rose, Christiane; Sargueil, Françoise; Guihenneuc-Jouyaux, Chantal; Cynober, Luc; Moinard, Christophe; Allinquant, Bernadette

2013-10-01

The levels of molecules crucial for signal transduction processing change in the brain with aging. Lipid rafts are membrane microdomains involved in cell signaling. We describe here substantial biophysical and biochemical changes occurring within the rafts in hippocampus neurons from aging wild-type rats and mice. Using continuous sucrose density gradients, we observed light-, medium-, and heavy raft subpopulations in young adult rodent hippocampus neurons containing very low levels of amyloid precursor protein (APP) and almost no caveolin-1 (CAV-1). By contrast, old rodents had a homogeneous age-specific high-density caveolar raft subpopulation containing significantly more cholesterol (CHOL), CAV-1, and APP. C99-APP-Cter fragment detection demonstrates that the first step of amyloidogenic APP processing takes place in this caveolar structure during physiological aging of the rat brain. In this age-specific caveolar raft subpopulation, levels of the C99-APP-Cter fragment are exponentially correlated with those of APP, suggesting that high APP concentrations may be associated with a risk of large increases in beta-amyloid peptide levels. Citrulline (an intermediate amino acid of the urea cycle) supplementation in the diet of aged rats for 3 months reduced these age-related hippocampus raft changes, resulting in raft patterns tightly close to those in young animals: CHOL, CAV-1, and APP concentrations were significantly lower and the C99-APP-Cter fragment was less abundant in the heavy raft subpopulation than in controls. Thus, we report substantial changes in raft structures during the aging of rodent hippocampus and describe new and promising areas of investigation concerning the possible protective effect of citrulline on brain function during aging.

There’s an App for That: A Guide for Healthcare Practitioners and Researchers on Smartphone Technology

PubMed Central

Trevena, Lyndal

2015-01-01

Smartphone technology is nascent compared to other technologies; however, it has shown an unprecedented uptake amongst lay consumers and professionals. This article presents the history, components, and key features of smartphones, as well as their related concepts and how they work, and it also delineates the process of smartphone applications (apps) development and publishing in the app stores. It also describes and discusses smartphone technology utilisation for health consumers, healthcare professionals, and health researchers, as well as the regulations of health-related apps. PMID:26392848

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.

Development of an Ecological Momentary Assessment Mobile App for a Low-Literacy, Mexican American Population to Collect Disordered Eating Behaviors

PubMed Central

Stein, Karen F; Chaudry, Beenish; Trabold, Nicole

2016-01-01

Background Ecological momentary assessment (EMA) is a popular method for understanding population health in which participants report their experiences while in naturally occurring contexts in order to increase the reliability and ecological validity of the collected data (as compared to retrospective recall). EMA studies, however, have relied primarily on text-based questionnaires, effectively eliminating low-literacy populations from the samples. Objective To provide a case study of design of an EMA mobile app for a low-literacy population. In particular, we present the design process and final design of an EMA mobile app for low literate, Mexican American women to record unhealthy eating and weight control behaviors (UEWCBs). Methods An iterative, user-centered design process was employed to develop the mobile app. An existing EMA protocol to measure UEWCBs in college-enrolled Mexican American women was used as the starting point for the application. The app utilizes an icon interface, with optional audio prompts, that is culturally sensitive and usable by a low-literacy population. A total of 41 women participated over the course of 4 phases of the design process, which included 2 interview and task-based phases (n=8, n=11), focus groups (n=15), and a 5-day, in situ deployment (n=7). Results Participants’ mental models of UEWCBs differed substantially from prevailing definitions found in the literature, prompting a major reorganization of the app interface. Differences in health literacy and numeracy were better identified with the Newest Vital Sign tool, as compared with the Short Assessment of Health Literacy tool. Participants had difficulty imagining scenarios in the interviews to practice recording a specific UEWCB; instead, usability was best tested in situ. Participants were able to use the EMA mobile app over the course of 5 days to record UEWCBs. Conclusions Results suggest that the iterative, user-centered design process was essential for designing the app to be made usable by the target population. Simply taking the protocol designed for a higher-literacy population and replacing words with icons and/or audio would have been unsuccessful with this population. PMID:27418020

Oiling the gate: a mobile application to improve the admissions process from the emergency department to an academic community hospital inpatient medicine service.

PubMed

Fung, Russell; Hyde, Jensen Hart; Davis, Mike

2018-01-01

The process of admitting patients from the emergency department (ED) to an academic internal medicine (AIM) service in a community teaching hospital is one fraught with variability and disorder. This results in an inconsistent volume of patients admitted to academic versus private hospitalist services and results in frustration of both ED and AIM clinicians. We postulated that implementation of a mobile application (app) would improve provider satisfaction and increase admissions to the academic service. The app was designed and implemented to be easily accessible to ED physicians, regularly updated by academic residents on call, and a real-time source of the number of open AIM admission spots. We found a significant improvement in ED and AIM provider satisfaction with the admission process. There was also a significant increase in admissions to the AIM service after implementation of the app. We submit that the implementation of a mobile app is a viable, cost-efficient, and effective method to streamline the admission process from the ED to AIM services at community-based hospitals.

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

Redundancy and divergence in the amyloid precursor protein family.

PubMed

Shariati, S Ali M; De Strooper, Bart

2013-06-27

Gene duplication provides genetic material required for functional diversification. An interesting example is the amyloid precursor protein (APP) protein family. The APP gene family has experienced both expansion and contraction during evolution. The three mammalian members have been studied quite extensively in combined knock out models. The underlying assumption is that APP, amyloid precursor like protein 1 and 2 (APLP1, APLP2) are functionally redundant. This assumption is primarily supported by the similarities in biochemical processing of APP and APLPs and on the fact that the different APP genes appear to genetically interact at the level of the phenotype in combined knockout mice. However, unique features in each member of the APP family possibly contribute to specification of their function. In the current review, we discuss the evolution and the biology of the APP protein family with special attention to the distinct properties of each homologue. We propose that the functions of APP, APLP1 and APLP2 have diverged after duplication to contribute distinctly to different neuronal events. Our analysis reveals that APLP2 is significantly diverged from APP and APLP1. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Hypoxic stress, brain vascular system, and β-amyloid: a primary cell culture study.

PubMed

Muche, Abebe; Bürger, Susanne; Arendt, Thomas; Schliebs, Reinhard

2015-01-01

This study stresses the hypothesis whether hypoxic events contribute to formation and deposition of β-amyloid (Aβ) in cerebral blood vessels by affecting the processing of endothelial amyloid precursor protein (APP). Therefore, cerebral endothelial cells (ECs) derived from transgenic Tg2576 mouse brain, were subjected to short periods of hypoxic stress, followed by assessment of formation and secretion of APP cleavage products sAPPα, sAPPβ, and Aβ as well as the expression of endothelial APP. Hypoxic stress of EC leads to enhanced secretion of sAPPβ into the culture medium as compared to normoxic controls, which is accompanied by increased APP expression, induction of vascular endothelial growth factor (VEGF) synthesis, nitric oxide production, and differential changes in endothelial p42/44 (ERK1/2) expression. The hypoxia-mediated up-regulation of p42/44 at a particular time of incubation was accompanied by a corresponding down-regulation of the phosphorylated form of p42/44. To reveal any role of hypoxia-induced VEGF in endothelial APP processing, ECs were exposed by VEGF. VEGF hardly affected the amount of sAPPβ and Aβ(1-40) secreted into the culture medium, whereas the suppression of the VEGF receptor action by SU-5416 resulted in decreased release of sAPPβ and Aβ(1-40) in comparison to control incubations, suggesting a role of VEGF in controlling the activity of γ-secretase, presumably via the VEGF receptor-associated tyrosine kinase. The data suggest that hypoxic stress represents a mayor risk factor in causing Aβ deposition in the brain vascular system by favoring the amyloidogenic route of endothelial APP processing. The hypoxic-stress-induced changes in β-secretase activity are presumably mediated by altering the phosphorylation status of p42/44, whereas the stress-induced up-regulation of VEGF appears to play a counteracting role by maintaining the balance of physiological APP processing.

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

Simplified Novel Application (SNApp) framework: a guide to developing and implementing second-generation mobile applications for behavioral health research.

PubMed

Fillo, Jennifer; Staplefoote-Boynton, B Lynette; Martinez, Angel; Sontag-Padilla, Lisa; Shadel, William G; Martino, Steven C; Setodji, Claude M; Meeker, Daniella; Scharf, Deborah

2016-12-01

Advances in mobile technology and mobile applications (apps) have opened up an exciting new frontier for behavioral health researchers, with a "second generation" of apps allowing for the simultaneous collection of multiple streams of data in real time. With this comes a host of technical decisions and ethical considerations unique to this evolving approach to research. Drawing on our experience developing a second-generation app for the simultaneous collection of text message, voice, and self-report data, we provide a framework for researchers interested in developing and using second-generation mobile apps to study health behaviors. Our Simplified Novel Application (SNApp) framework breaks the app development process into four phases: (1) information and resource gathering, (2) software and hardware decisions, (3) software development and testing, and (4) study start-up and implementation. At each phase, we address common challenges and ethical issues and make suggestions for effective and efficient app development. Our goal is to help researchers effectively balance priorities related to the function of the app with the realities of app development, human subjects issues, and project resource constraints.

Amyloid precursor protein expression is enhanced in human platelets from subjects with Alzheimer's disease and frontotemporal lobar degeneration: a real-time PCR study.

PubMed

Vignini, Arianna; Morganti, Stefano; Salvolini, Eleonora; Sartini, Davide; Luzzi, Simona; Fiorini, Rosamaria; Provinciali, Leandro; Di Primio, Roberto; Mazzanti, Laura; Emanuelli, Monica

2013-12-01

Frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD) represent the most frequent causes of early-onset and late-onset degenerative dementia, respectively. A correct diagnosis entails the choice of appropriate therapies. In this view the present study aimed to identify biomarkers that could improve the differential diagnosis. We recently found an overexpression of platelet amyloid precursor protein (APP) in AD; furthermore, recent studies have suggested the presence of changes in APP processing in FTLD. In this context, we analyzed the mRNA expression level of Total APP (TOT) and APP containing a Kunitz-type serine protease inhibitor domain (KPI) in platelets obtained from AD patients, subjects with FTLD, and healthy subjects. In addition, we evaluated the correlation between platelet APP mRNA expression levels and cognitive impairment.Differential gene expression measurements revealed a significant up-regulation of APP TOT and APP KPI in both AD and FTLD patients compared to the controls (being AD/Controls: 1.67 for APP TOT and 1.47 for APP KPI; FTLD/Controls: 1.62 for APP TOT and 1.51 for APP KPI; p < 0.05), although it is interesting to note that in FTLD patients this expression did not correlate with the severity of cognitive impairment.This could be related to a reduced beta-amyloid (Aβ) formation, caused by an alteration of secretase enzymatic activity, even though a post-transcriptional regulation of APP mRNAs in FTLD cannot be excluded.

Amyloid precursor protein expression is enhanced in human platelets from subjects with Alzheimer's disease and Frontotemporal lobar degeneration: A Real-time PCR study.

PubMed

Vignini, Arianna; Morganti, Stefano; Salvolini, Eleonora; Sartini, Davide; Luzzi, Simona; Fiorini, Rosamaria; Provinciali, Leandro; Di Primio, Roberto; Mazzanti, Laura; Emanuelli, Monica

2013-10-26

Frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD) represent the most frequent causes of early-onset and late-onset degenerative dementia, respectively. A correct diagnosis entails the choice of appropriate therapies. In this view the present study aimed to identify biomarkers that could improve the differential diagnosis. We recently found an overexpression of platelet amyloid precursor protein (APP) in AD; furthermore, recent studies have suggested the presence of changes in APP processing in FTLD. In this context, we analyzed the mRNA expression level of Total APP (TOT) and APP containing a Kunitz-type serine protease inhibitor domain (KPI) in platelets obtained from AD patients, subjects with FTLD, and healthy subjects. In addition, we evaluated the correlation between platelet APP mRNA expression levels and cognitive impairment. Differential gene expression measurements revealed a significant up-regulation of APP TOT and APP KPI in both AD and FTLD patients compared to the controls (being AD/Controls: 1.67 for APP TOT and 1.47 for APP KPI; FTLD/Controls: 1.62 for APP TOT and 1.51 for APP KPI; p<0.05) , although it is interesting to note that in FTLD patients this expression did not correlate with the severity of cognitive impairment. This could be related to a reduced beta-amyloid (Aβ) formation, caused by an alteration of secretase enzymatic activity, even though a post-transcriptional regulation of APP mRNAs in FTLD cannot be excluded. © 2013.

32 CFR 513.4 - Conditions creditors must meet before getting help in debt processing.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., Oklahoma, and Wyoming. (4) DOD Standards of Fairness (app B) define fair and just dealings with soldiers... Relief Act of 1940, as amended (50 U.S.C. app, section 501 et seq., (1970)) if applicable. (See DA Pam 27... Standards of Fairness (app B) showing compliance with one of the following: (A) The Truth-in-Lending Act. (B...

Teaching in a World with Photomath

ERIC Educational Resources Information Center

Webel, Corey; Otten, Samuel

2015-01-01

In October 2014, an interesting new app became freely available in the Apple Store®. It is called PhotoMath®: (1) Hold a phone or tablet up to a mathematics problem in a textbook; (2) The app shows the answer to the problem; and (3) Select Steps to see the step-by-step process for getting from the problem to the solution. The app works for simple…

Development of a Culturally Appropriate Bilingual Electronic App About Hepatitis B for Indigenous Australians: Towards Shared Understandings.

PubMed

Davies, Jane; Bukulatjpi, Sarah; Sharma, Suresh; Caldwell, Luci; Johnston, Vanessa; Davis, Joshua Saul

2015-06-10

Hepatitis B is endemic in Indigenous communities in Northern Australia; however, there is a lack of culturally appropriate educational tools. Health care workers and educators in this setting have voiced a desire for visual, interactive tools in local languages. Mobile phones are increasingly used and available in remote Indigenous communities. In this context, we identified the need for a tablet-based health education app about hepatitis B, developed in partnership with an Australian remote Indigenous community. To develop a culturally appropriate bilingual app about hepatitis B for Indigenous Australians in Arnhem Land using a participatory action research (PAR) framework. This project was a partnership between the Menzies School of Health Research, Miwatj Aboriginal Health Corporation, Royal Darwin Hospital Liver Clinic, and Dreamedia Darwin. We have previously published a qualitative study that identified major knowledge gaps about hepatitis B in this community, and suggested that a tablet-based app would be an appropriate and popular tool to improve this knowledge. The process of developing the app was based on PAR principles, particularly ongoing consultation, evaluation, and discussion with the community throughout each iterative cycle. Stages included development of the storyboard, the translation process (forward translation and backtranslation), prelaunch community review, launch and initial community evaluation, and finally, wider launch and evaluation at a viral hepatitis conference. We produced an app called "Hep B Story" for use with iPad, iPhone, Android tablets, and mobile phones or personal computers. The app is culturally appropriate, audiovisual, interactive, and users can choose either English or Yolŋu Matha (the most common language in East Arnhem Land) as their preferred language. The initial evaluation demonstrated a statistically significant improvement in Hep B-related knowledge for 2 of 3 questions (P=.01 and .02, respectively) and overwhelmingly positive opinion regarding acceptability and ease of use (median rating of 5, on a 5-point Likert-type scale when users were asked if they would recommend the app to others). We describe the process of development of a bilingual hepatitis B-specific app for Indigenous Australians, using a PAR framework. The approach was found to be successful with positive evaluations.

Herpes simplex virus interferes with amyloid precursor protein processing

PubMed Central

Shipley, Suzanne J; Parkin, Edward T; Itzhaki, Ruth F; Dobson, Curtis B

2005-01-01

Background The early events underlying Alzheimer's disease (AD) remain uncertain, although environmental factors may be involved. Work in this laboratory has shown that the combination of herpes simplex virus type 1 (HSV1) in brain and carriage of the APOE-ε4 allele of the APOE gene strongly increases the risk of developing AD. The development of AD is thought to involve abnormal aggregation or deposition of a 39–43 amino acid protein – β amyloid (Aβ) – within the brain. This is cleaved from the much larger transmembranal protein 'amyloid precursor protein' (APP). Any agent able to interfere directly with Aβ or APP metabolism may therefore have the capacity to contribute towards AD. One recent report showed that certain HSV1 glycoprotein peptides may aggregate like Aβ; a second study described a role for APP in transport of virus in squid axons. However to date the effects of acute herpesvirus infection on metabolism of APP in human neuronal-type cells have not been investigated. In order to find if HSV1 directly affects APP and its degradation, we have examined this protein from human neuroblastoma cells (normal and transfected with APP 695) infected with the virus, using Western blotting. Results We have found that acute HSV1 (and also HSV2) infection rapidly reduces full length APP levels – as might be expected – yet surprisingly markedly increases levels of a novel C-terminal fragment of APP of about 55 kDa. This band was not increased in cells treated with the protein synthesis inhibitor cycloheximide Conclusion Herpes virus infection leads to rapid loss of full length APP from cells, yet also causes increased levels of a novel 55 kDa C-terminal APP fragment. These data suggest that infection can directly alter the processing of a transmembranal protein intimately linked to the aetiology of AD. PMID:16109164

Spatial Segregation of γ-Secretase and Substrates in Distinct Membrane Domains*

PubMed Central

Vetrivel, Kulandaivelu S.; Cheng, Haipeng; Kim, Seong-Hun; Chen, Ying; Barnes, Natalie Y.; Parent, Ange‘le T.; Sisodia, Sangram S.; Thinakaran, Gopal

2005-01-01

γ-Secretase facilitates the regulated intramembrane proteolysis of select type I membrane proteins that play diverse physiological roles in multiple cell types and tissue. In this study, we used biochemical approaches to examine the distribution of amyloid precursor protein (APP) and several additional γ-secretase substrates in membrane microdomains. We report that APP C-terminal fragments (CTFs) and γ-secretase reside in Lubrol WX detergent-insoluble membranes (DIM) of cultured cells and adult mouse brain. APP CTFs that accumulate in cells lacking γ-secretase activity preferentially associate with DIM. Cholesterol depletion and magnetic im-munoisolation studies indicate recruitment of APP CTFs into cholesterol- and sphingolipid-rich lipid rafts, and co-residence of APP CTFs, PS1, and syntaxin 6 in DIM patches derived from the trans-Golgi network. Photoaffinity cross-linking studies provided evidence for the preponderance of active γ-secretase in lipid rafts of cultured cells and adult brain. Remarkably, unlike the case of APP, CTFs derived from Notch1, Jagged2, deleted in colorectal cancer (DCC), and N-cadherin remain largely detergent-soluble, indicative of their spatial segregation in non-raft domains. In embryonic brain, the majority of PS1 and nicastrin is present in Lubrol WX-soluble membranes, wherein the CTFs derived from APP, Notch1, DCC, and N-cadherin also reside. We suggest that γ-secretase residence in non-raft membranes facilitates proteolysis of diverse substrates during embryonic development but that the translocation of γ-secretase to lipid rafts in adults ensures processing of certain substrates, including APP CTFs, while limiting processing of other potential substrates. PMID:15886206

Spatial segregation of gamma-secretase and substrates in distinct membrane domains.

PubMed

Vetrivel, Kulandaivelu S; Cheng, Haipeng; Kim, Seong-Hun; Chen, Ying; Barnes, Natalie Y; Parent, Angèle T; Sisodia, Sangram S; Thinakaran, Gopal

2005-07-08

Gamma-secretase facilitates the regulated intramembrane proteolysis of select type I membrane proteins that play diverse physiological roles in multiple cell types and tissue. In this study, we used biochemical approaches to examine the distribution of amyloid precursor protein (APP) and several additional gamma-secretase substrates in membrane microdomains. We report that APP C-terminal fragments (CTFs) and gamma-secretase reside in Lubrol WX detergent-insoluble membranes (DIM) of cultured cells and adult mouse brain. APP CTFs that accumulate in cells lacking gamma-secretase activity preferentially associate with DIM. Cholesterol depletion and magnetic immunoisolation studies indicate recruitment of APP CTFs into cholesterol- and sphingolipid-rich lipid rafts, and co-residence of APP CTFs, PS1, and syntaxin 6 in DIM patches derived from the trans-Golgi network. Photoaffinity cross-linking studies provided evidence for the preponderance of active gamma-secretase in lipid rafts of cultured cells and adult brain. Remarkably, unlike the case of APP, CTFs derived from Notch1, Jagged2, deleted in colorectal cancer (DCC), and N-cadherin remain largely detergent-soluble, indicative of their spatial segregation in non-raft domains. In embryonic brain, the majority of PS1 and nicastrin is present in Lubrol WX-soluble membranes, wherein the CTFs derived from APP, Notch1, DCC, and N-cadherin also reside. We suggest that gamma-secretase residence in non-raft membranes facilitates proteolysis of diverse substrates during embryonic development but that the translocation of gamma-secretase to lipid rafts in adults ensures processing of certain substrates, including APP CTFs, while limiting processing of other potential substrates.

Mobile Visualization and Analysis Tools for Spatial Time-Series Data

NASA Astrophysics Data System (ADS)

Eberle, J.; Hüttich, C.; Schmullius, C.

2013-12-01

The Siberian Earth System Science Cluster (SIB-ESS-C) provides access and analysis services for spatial time-series data build on products from the Moderate Resolution Imaging Spectroradiometer (MODIS) and climate data from meteorological stations. Until now a webportal for data access, visualization and analysis with standard-compliant web services was developed for SIB-ESS-C. As a further enhancement a mobile app was developed to provide an easy access to these time-series data for field campaigns. The app sends the current position from the GPS receiver and a specific dataset (like land surface temperature or vegetation indices) - selected by the user - to our SIB-ESS-C web service and gets the requested time-series data for the identified pixel back in real-time. The data is then being plotted directly in the app. Furthermore the user has possibilities to analyze the time-series data for breaking points and other phenological values. These processings are executed on demand of the user on our SIB-ESS-C web server and results are transfered to the app. Any processing can also be done at the SIB-ESS-C webportal. The aim of this work is to make spatial time-series data and analysis functions available for end users without the need of data processing. In this presentation the author gives an overview on this new mobile app, the functionalities, the technical infrastructure as well as technological issues (how the app was developed, our made experiences).

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.

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

Targeting Parents for Childhood Weight Management: Development of a Theory-Driven and User-Centered Healthy Eating App.

PubMed

Curtis, Kristina Elizabeth; Lahiri, Sudakshina; Brown, Katherine Elizabeth

2015-06-18

The proliferation of health promotion apps along with mobile phones' array of features supporting health behavior change offers a new and innovative approach to childhood weight management. However, despite the critical role parents play in children's weight related behaviors, few industry-led apps aimed at childhood weight management target parents. Furthermore, industry-led apps have been shown to lack a basis in behavior change theory and evidence. Equally important remains the issue of how to maximize users' engagement with mobile health (mHealth) interventions where there is growing consensus that inputs from the commercial app industry and the target population should be an integral part of the development process. The aim of this study is to systematically design and develop a theory and evidence-driven, user-centered healthy eating app targeting parents for childhood weight management, and clearly document this for the research and app development community. The Behavior Change Wheel (BCW) framework, a theoretically-based approach for intervention development, along with a user-centered design (UCD) philosophy and collaboration with the commercial app industry, guided the development process. Current evidence, along with a series of 9 focus groups (total of 46 participants) comprised of family weight management case workers, parents with overweight and healthy weight children aged 5-11 years, and consultation with experts, provided data to inform the app development. Thematic analysis of focus groups helped to extract information related to relevant theoretical, user-centered, and technological components to underpin the design and development of the app. Inputs from parents and experts working in the area of childhood weight management helped to identify the main target behavior: to help parents provide appropriate food portion sizes for their children. To achieve this target behavior, the behavioral diagnosis revealed the need for eliciting change in parents' capability, motivation, and opportunity in 10-associated Theoretical Domains Framework (TDF) domains. Of the 9 possible intervention functions, 6 were selected to bring about this change which guided the selection of 21 behavior change techniques. Parents' preferences for healthy eating app features revolved around four main themes (app features, time saving and convenience, aesthetics, and gamification) whereupon a criterion was applied to guide the selection on which preferences should be integrated into the design of the app. Collaboration with the app company helped to build on users' preferences for elements of gamification such as points, quizzes, and levels to optimize user engagement. Feedback from parents on interactive mock-ups helped to inform the final development of the prototype app. Here, we fully explicate a systematic approach applied in the development of a family-oriented, healthy eating health promotion app grounded in theory and evidence, and balanced with users' preferences to help maximize its engagement with the target population.

Protein biosynthesis in mitochondria.

PubMed

Kuzmenko, A V; Levitskii, S A; Vinogradova, E N; Atkinson, G C; Hauryliuk, V; Zenkin, N; Kamenski, P A

2013-08-01

Translation, that is biosynthesis of polypeptides in accordance with information encoded in the genome, is one of the most important processes in the living cell, and it has been in the spotlight of international research for many years. The mechanisms of protein biosynthesis in bacteria and in the eukaryotic cytoplasm are now understood in great detail. However, significantly less is known about translation in eukaryotic mitochondria, which is characterized by a number of unusual features. In this review, we summarize current knowledge about mitochondrial translation in different organisms while paying special attention to the aspects of this process that differ from cytoplasmic protein biosynthesis.

The Impact of WhatsApp Use on Success in Education Process

ERIC Educational Resources Information Center

Cetinkaya, Levent

2017-01-01

The purpose of this study is to explore the effects of WhatsApp use for education and determine the opinions of students towards the process. The study was designed in mixed research model which combines both qualitative and quantitative data. In the quantitative aspect of the study, quasi-experimental design, with a pretest-posttest control…

Embedding technology into inter-professional best practices in home safety evaluation.

PubMed

Burns, Suzanne Perea; Pickens, Noralyn Davel

2017-08-01

To explore inter-professional home evaluators' perspectives and needs for building useful and acceptable decision-support tools for the field of home modifications. Twenty semi-structured interviews were conducted with a range of home modification professionals from different regions of the United States. The interview transcripts were analyzed with a qualitative, descriptive, perspective approach. Technology supports current best practice and has potential to inform decision making through features that could enhance home evaluation processes, quality, efficiency and inter-professional communication. Technological advances with app design have created numerous opportunities for the field of home modifications. Integrating technology and inter-professional best practices will improve home safety evaluation and intervention development to meet client-centred and societal needs. Implications for rehabilitation Understanding home evaluators technology needs for home safety evaluations contributes to the development of app-based assessments. Integrating inter-professional perspectives of best practice and technological needs in an app for home assessments improves processes. Novice and expert home evaluators would benefit from decision support systems embedded in app-based assessments. Adoption of app-based assessment would improve efficiency while remaining client-centred.

App Factory: A flexible approach to rehabilitation engineering in an era of rapid technology advancement.

PubMed

Jones, Michael; Mueller, James; Morris, John

2017-01-01

This article describes a flexible and effective approach to research and development in an era of rapid technological advancement. The approach relies on secondary dispersal of grant funds to commercial developers through a competitive selection process. This "App Factory" model balances the practical reliance on multi-year funding needed to sustain a rehabilitation engineering research center (RERC), with the need for agility and adaptability of development efforts undertaken in a rapidly changing technology environment. This approach also allows us to take advantage of technical expertise needed to accomplish a particular development task, and provides incentives to deliver successful products in a cost-effective manner. In this article, we describe the App Factory structure, process, and results achieved to date; and we discuss the lessons learned and the potential relevance of this approach for other grant-funded research and development efforts. Data presented on the direct costs and number of downloads of the 16 app development projects funded in the App Factory's first 3 years show that it can be an effective means for supporting focused, short-term assistive technology development projects.

The Analysis Of Smartphone Apps In Geomatics Education

NASA Astrophysics Data System (ADS)

Teo, T.-A.; Wu, H.-M.; Shih, T.-Y.; Tsai, F.

2014-04-01

Geomatics is a discipline of collecting, processing and analysing geospatial data. Data collection is a core process of geomatics which usually adopt precise equipment to measure geospatial data. With the development of technology, a smartphone in this present era is not simply for communication; several low cost measurement devices such as Global Positioning System (GPS), gyro and camera are assembled in a smartphone. Although the devices assembled in a smartphone could not meet the needs of accuracy requirement for many geomatics applications, millions of mobile applications (Apps) can be downloaded and installed from Google Play and Apple Store freely, and a variety of sensors can be chosen for user. Considering that the popularity and convenience of a smartphone, and assuming that the accuracy of those collected data is acceptable for learning purposes, it is expected that a smartphone can be employed in geomatics for hand-on education. For example, Vespucci OSM Editor is an App to edit the OpenStreetMap on Android. The user may have the hand-on experience on GPS positioning, web services and mapping via Vespucci OSM Editor. The aim of this paper is to collect and analyze different Apps for geomatics education. The Apps are classified into four categories, namely, surveying, remote sensing, GPS and Geographic Information System (GIS). In this paper, more than 20 free Apps are collected and analysed for different hand-on studies in geomatics education. Finally, all the related Apps are listed on a website for updating.

Identifying Medication Management Smartphone App Features Suitable for Young Adults With Developmental Disabilities: Delphi Consensus Study

PubMed Central

Salgado, Teresa M; Fedrigon, Alexa; Riccio Omichinski, Donna; Meade, Michelle A

2018-01-01

Background Smartphone apps can be a tool to facilitate independent medication management among persons with developmental disabilities. At present, multiple medication management apps exist in the market, but only 1 has been specifically designed for persons with developmental disabilities. Before initiating further app development targeting this population, input from stakeholders including persons with developmental disabilities, caregivers, and professionals regarding the most preferred features should be obtained. Objective The aim of this study was to identify medication management app features that are suitable to promote independence in the medication management process by young adults with developmental disabilities using a Delphi consensus method. Methods A compilation of medication management app features was performed by searching the iTunes App Store, United States, in February 2016, using the following terms: adherence, medication, medication management, medication list, and medication reminder. After identifying features within the retrieved apps, a final list of 42 features grouped into 4 modules (medication list, medication reminder, medication administration record, and additional features) was included in a questionnaire for expert consensus rating. A total of 52 experts in developmental disabilities, including persons with developmental disabilities, caregivers, and professionals, were invited to participate in a 3-round Delphi technique. The purpose was to obtain consensus on features that are preferred and suitable to promote independence in the medication management process among persons with developmental disabilities. Consensus for the first, second, and third rounds was defined as ≥90%, ≥80%, and ≥75% agreement, respectively. Results A total of 75 responses were received over the 3 Delphi rounds—30 in the first round, 24 in the second round, and 21 in the third round. At the end of the third round, cumulative consensus was achieved for 60% (12/20) items in the medication list module, 100% (3/3) in the medication reminder module, 67% (2/3) in the medication administration record module, and 63% (10/16) in the additional features module. In addition to the medication list, medication reminder, and medication administration record features, experts selected the following top 3 most important additional features: automatic refills through pharmacies; ability to share medication information from the app with providers; and ability to share medication information from the app with family, friends, and caregivers. The top 3 least important features included a link to an official drug information source, privacy settings and password protection, and prescription refill reminders. Conclusions Although several mobile apps for medication management exist, few are specifically designed to support persons with developmental disabilities in the complex medication management process. Of the 42 different features assessed, 64% (27/42) achieved consensus for inclusion in a future medication management app. This study provides information on the features of a medication management app that are most important to persons with developmental disabilities, caregivers, and professionals. PMID:29792292

Amyloid precursor protein modulates ERK-1 and -2 signaling.

PubMed

Venezia, Valentina; Nizzari, Mario; Repetto, Emanuela; Violani, Elisabetta; Corsaro, Alessandro; Thellung, Stefano; Villa, Valentina; Carlo, Pia; Schettini, Gennaro; Florio, Tullio; Russo, Claudio

2006-12-01

The amyloid precursor protein (APP) is a transmembrane protein with a short cytoplasmic tail whose physiological function is unclear, although it is well documented that the proteolytic processing of APP could influence the development of Alzheimer's disease (AD) through the formation of membrane-bound C-terminal fragments (CTFs) and of beta-amyloid peptides (Abeta). We have recently shown that tyrosine-phosphorylated APP and CTFs may interact with Grb2 and ShcA adaptor proteins and that this coupling occurs at a higher extent in AD subjects only. To study the interaction between APP or CTFs and ShcA/Grb2 and to investigate their molecular target we have used as experimental model two different cell lines: H4 human neuroglioma cells and APP/APLP null mouse embryonic fibroblast cells (MEFs). Here we show that in H4 cells APP interacts with Grb2; conversely in APP/APLP-null MEF cells this interaction is possible only after the reintroduction of human APP by transfection. We have also shown that in MEF cells the transfection of a plasmid encoding for human APP wild-type enhances the phosphorylation of ERK-1 and -2 as revealed by Western blotting and immunofluorescence experiments. Finally, also in H4 cells the overexpression of APP upregulates the levels of phospho-ERK-1 and -2. In summary our data suggest that APP may influence phospho-ERK-1 and -2 signaling through its binding with Grb2 and ShcA adaptors. The meaning of this event is not clear, but APP interaction with these adaptors could be relevant to regulate mitogenic pathway.

"WhatsApp"ening in orthopedic care: a concise report from a 300-bedded tertiary care teaching center.

PubMed

Khanna, Vishesh; Sambandam, Senthil N; Gul, Arif; Mounasamy, Varatharaj

2015-07-01

Smartphones have emerged as essential tools providing assistance in patient care, monitoring, rehabilitation, communication, diagnosis, teaching, research and reference. Among innumerable communication apps, WhatsApp has been widely popular and cost effective. The aim of our study was to report the impact of introduction of a smartphone app "WhatsApp" as an intradepartmental communication tool on (1) awareness of patient-related information, (2) efficiency of the handover process and (3) duration of traditional morning handovers among orthopedic residents in a 300-bedded tertiary care teaching center. Written handovers and paging used for communication at our center led to occasional inefficiencies among residents. Widespread use, low cost, availability and double password protection (phone lock and WhatsApp lock) made WhatsApp's group conversation feature an ideal tool for intradepartmental patient-related communication. Twenty-five consecutive admissions before and after WhatsApp (BW, AW) were included in the study. Eight orthopedic residents attempted fifty randomly arranged questions based on the twenty-five patients in each study period. A null hypothesis that introduction of WhatsApp group would neither increase the awareness of patient-related information nor improve the efficiency of the handovers among residents was assumed. A significant improvement observed in scores obtained by residents in the AW group led to rejection of the null hypothesis. The residents also reported swifter and efficient handovers after the introduction of WhatsApp. Our results indicate that the introduction of a smartphone app "WhatsApp" as an intradepartmental communication tool can bring about an improvement in patient-related awareness, communication and handovers among orthopedic residents.

Developing a Mobile App for Prevention and Treatment of Pressure Injuries.

PubMed

Salomé, Geraldo Magela; Ferreira, Lydia Masako

2018-02-01

This descriptive study describes the planning and development of a mobile application (app) for prevention and treatment of pressure injuries for use by providers in a university research center. The app delineates risk factors for pressure injury development, provides an evaluation of the wound, recommends wound cleansing procedures, performs pressure injury staging, and recommends treatment interventions. A mobile app was developed using a contextualized instructional design, which involves a constructivist proposal and planning, developing, and applying specific didactic situations, thus incorporating mechanisms that favor contextualization. A literature search was conducted to identify relevant studies for the construction of the mobile app. The development process involved the selection of app tools, definition of the navigation structure, and planning of the environment configuration. The environment for downloading the app software on the Internet and installing it on the mobile device was created. The literature search yielded 18 articles, 2 books, and 1 master's degree thesis. A mobile app was created with an easy-to-use graphic interface. The app stores the patient's demographic characteristics and provides an evaluation of his/her wound, a list of risk factors for pressure injury development, wound cleansing procedures, and treatment interventions. The developed app may be useful in clinical practice, helping to prevent pressure injuries and promote select nursing interventions for the treatment of patients with pressure injury.

Putting education in "educational" apps: lessons from the science of learning.

PubMed

Hirsh-Pasek, Kathy; Zosh, Jennifer M; Golinkoff, Roberta Michnick; Gray, James H; Robb, Michael B; Kaufman, Jordy

2015-05-01

Children are in the midst of a vast, unplanned experiment, surrounded by digital technologies that were not available but 5 years ago. At the apex of this boom is the introduction of applications ("apps") for tablets and smartphones. However, there is simply not the time, money, or resources available to evaluate each app as it enters the market. Thus, "educational" apps-the number of which, as of January 2015, stood at 80,000 in Apple's App Store (Apple, 2015)-are largely unregulated and untested. This article offers a way to define the potential educational impact of current and future apps. We build upon decades of work on the Science of Learning, which has examined how children learn best. From this work, we abstract a set of principles for two ultimate goals. First, we aim to guide researchers, educators, and designers in evidence-based app development. Second, by creating an evidence-based guide, we hope to set a new standard for evaluating and selecting the most effective existing children's apps. In short, we will show how the design and use of educational apps aligns with known processes of children's learning and development and offer a framework that can be used by parents and designers alike. Apps designed to promote active, engaged, meaningful, and socially interactive learning-four "pillars" of learning-within the context of a supported learning goal are considered educational. © The Author(s) 2015.

Modern use of smartphone applications in the perioperative management in microsurgical breast reconstruction.

PubMed

Patel, Nakul Gamanlal; Rozen, Warren Matthew; Marsh, Daniel; Chow, Whitney T H; Vickers, Tobias; Khan, Lubna; Miller, George S; Hunter-Smith, David J; Ramakrishnan, Venkat V

2016-04-01

Advances in mobile telecommunication, improved mobile internet and affordability have led to a significant increase in smartphone use within medicine. The capability of instant messaging, photography, videography, word processing, drawing and internet access allow significant potential in this small portable device. Smartphone use within medicine has grown tremendously worldwide given its affordability, improved internet and capabilities. We have searched for apps specifically helpful in the perioperative care of microsurgical breast reconstructive patients. The useful apps have been subdivided: (I) communication apps-multimedia messaging, WhatsApp, PicSafeMedi: allow efficient communication via text, picture and video messages leading to earlier assessment and definitive management of free flaps; (II) storage apps-Notability, Elogbook: electronic storage of patient notes and logbooks of case which can be shared with others if required; (III) educational apps-FlapApp, Touch Surgery, PubMed on tap: step by step guides to surgical procedures to aid learning and medical journal database; (IV) flap monitoring app-SilpaRamanitor: free flap monitoring app based on photographic analysis for earlier detection of compromised flaps. There has been remarkable growth in smartphones use among surgeons. Apps are being developed for every conceivable use. The future will be in wearable smart devices that allow continuous monitoring with the potential to instigate change should deviations from the norm occur. The smart watch is the start of this digital revolution.

The use of smartphone health apps and other mobile health (mHealth) technologies in dietetic practice: a three country study.

PubMed

Chen, J; Lieffers, J; Bauman, A; Hanning, R; Allman-Farinelli, M

2017-08-01

Smartphone health applications (apps) and other mobile health (mHealth) technologies may assist dietitians in improving the efficiency of patient care. The present study investigated the use of health apps and text messaging in dietetic practice and formulated intervention recommendations for supporting app uptake by dietitians based on the behavioural 'COM-B' system, where interactions between capability, opportunity and motivation influence behaviour. A 52-item online survey tool, taking 20 min to complete, was developed and piloted, with questions exploring the use of health apps and text messaging in dietetic practice, types of apps dietitians recommended and that patients used, and barriers and enablers to app use in dietetic practice. The Australian, New Zealand and British dietetic associations distributed the survey to their members. A 5% response rate was achieved internationally, with 570 completed responses included for further analysis. Health apps, namely nutrition apps, were used by 62% of dietitians in their practice, primarily as an information resource (74%) and for patient self-monitoring (60%). The top two nutrition apps recommended were MyFitnessPal ® (62%) and the Monash University Low FODMAP Diet ® (44%). Text messaging was used by 51% of respondents, mainly for appointment-related purposes (84%). Although the reported use of smartphone health apps in dietetic practice is high, health apps and other mHealth technologies are not currently being used for behaviour change, nor are they an integral part of the nutrition care process. Dietetic associations should provide training, education and advocacy to enable the profession to more effectively engage with and implement apps into their practice. © 2017 The British Dietetic Association Ltd.

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.

Proteasome stress leads to APP axonal transport defects by promoting its amyloidogenic processing in lysosomes.

PubMed

Otero, María Gabriela; Fernandez Bessone, Ivan; Hallberg, Alan Earle; Cromberg, Lucas Eneas; De Rossi, María Cecilia; Saez, Trinidad M; Levi, Valeria; Almenar-Queralt, Angels; Falzone, Tomás Luis

2018-06-11

Alzheimer disease (AD) pathology includes the accumulation of poly-ubiquitylated (also known as poly-ubiquitinated) proteins and failures in proteasome-dependent degradation. Whereas the distribution of proteasomes and its role in synaptic function have been studied, whether proteasome activity regulates the axonal transport and metabolism of the amyloid precursor protein (APP), remains elusive. By using live imaging in primary hippocampal neurons, we showed that proteasome inhibition rapidly and severely impairs the axonal transport of APP. Fluorescence cross-correlation analyses and membrane internalization blockage experiments showed that plasma membrane APP does not contribute to transport defects. Moreover, by western blotting and double-color APP imaging, we demonstrated that proteasome inhibition precludes APP axonal transport by enhancing its endo-lysosomal delivery, where β-cleavage is induced. Taken together, we found that proteasomes control the distal transport of APP and can re-distribute Golgi-derived vesicles to the endo-lysosomal pathway. This crosstalk between proteasomes and lysosomes regulates the intracellular APP dynamics, and defects in proteasome activity can be considered a contributing factor that leads to abnormal APP metabolism in AD.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

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

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

A user-centered model for designing consumer mobile health (mHealth) applications (apps).

PubMed

Schnall, Rebecca; Rojas, Marlene; Bakken, Suzanne; Brown, William; Carballo-Dieguez, Alex; Carry, Monique; Gelaude, Deborah; Mosley, Jocelyn Patterson; Travers, Jasmine

2016-04-01

Mobile technologies are a useful platform for the delivery of health behavior interventions. Yet little work has been done to create a rigorous and standardized process for the design of mobile health (mHealth) apps. This project sought to explore the use of the Information Systems Research (ISR) framework as guide for the design of mHealth apps. Our work was guided by the ISR framework which is comprised of 3 cycles: Relevance, Rigor and Design. In the Relevance cycle, we conducted 5 focus groups with 33 targeted end-users. In the Rigor cycle, we performed a review to identify technology-based interventions for meeting the health prevention needs of our target population. In the Design Cycle, we employed usability evaluation methods to iteratively develop and refine mock-ups for a mHealth app. Through an iterative process, we identified barriers and facilitators to the use of mHealth technology for HIV prevention for high-risk MSM, developed 'use cases' and identified relevant functional content and features for inclusion in a design document to guide future app development. Findings from our work support the use of the ISR framework as a guide for designing future mHealth apps. Results from this work provide detailed descriptions of the user-centered design and system development and have heuristic value for those venturing into the area of technology-based intervention work. Findings from this study support the use of the ISR framework as a guide for future mHealth app development. Use of the ISR framework is a potentially useful approach for the design of a mobile app that incorporates end-users' design preferences. Copyright © 2016 Elsevier Inc. All rights reserved.

Design and evaluation of a mobile application to assist the self-monitoring of the chronic kidney disease in developing countries.

PubMed

Sobrinho, Alvaro; da Silva, Leandro Dias; Perkusich, Angelo; Pinheiro, Maria Eliete; Cunha, Paulo

2018-01-12

The chronic kidney disease (CKD) is a worldwide critical problem, especially in developing countries. CKD patients usually begin their treatment in advanced stages, which requires dialysis and kidney transplantation, and consequently, affects mortality rates. This issue is faced by a mobile health (mHealth) application (app) that aims to assist the early diagnosis and self-monitoring of the disease progression. A user-centered design (UCD) approach involving health professionals (nurse and nephrologists) and target users guided the development process of the app between 2012 and 2016. In-depth interviews and prototyping were conducted along with healthcare professionals throughout the requirements elicitation process. Elicited requirements were translated into a native mHealth app targeting the Android platform. Afterward, the Cohen's Kappa coefficient statistics was applied to evaluate the agreement between the app and three nephrologists who analyzed test results collected from 60 medical records. Finally, eight users tested the app and were interviewed about usability and user perceptions. A mHealth app was designed to assist the CKD early diagnosis and self-monitoring considering quality attributes such as safety, effectiveness, and usability. A global Kappa value of 0.7119 showed a substantial degree of agreement between the app and three nephrologists. Results of face-to-face interviews with target users indicated a good user satisfaction. However, the task of CKD self-monitoring proved difficult because most of the users did not fully understand the meaning of specific biomarkers (e.g., creatinine). The UCD approach provided mechanisms to develop the app based on the real needs of users. Even with no perfect Kappa degree of agreement, results are satisfactory because it aims to refer patients to nephrologists in early stages, where they may confirm the CKD diagnosis.

Substance P activates ADAM9 mRNA expression and induces α-secretase-mediated amyloid precursor protein cleavage.

PubMed

Marolda, R; Ciotti, M T; Matrone, C; Possenti, R; Calissano, P; Cavallaro, S; Severini, C

2012-04-01

Altered levels of Substance P (SP), a neuropeptide endowed with neuroprotective and anti-apoptotic properties, were found in brain areas and spinal fluid of Alzheimer's disease (AD) patients. One of the hallmarks of AD is the abnormal extracellular deposition of neurotoxic beta amyloid (Aβ) peptides, derived from the proteolytic processing of amyloid precursor protein (APP). In the present study, we confirmed, the neurotrophic action of SP in cultured rat cerebellar granule cells (CGCs) and investigated its effects on APP metabolism. Incubation with low (5 mM) potassium induced apoptotic cell death of CGCs and amyloidogenic processing of APP, whereas treatment with SP (200 nM) reverted these effects via NK1 receptors. The non-amyloidogenic effect of SP consisted of reduction of Aβ(1-42), increase of sAPPα and enhanced α-secretase activity, without a significant change in steady-state levels of cellular APP. The intracellular mechanisms whereby SP alters APP metabolism were further investigated by measuring mRNA and/or steady-state protein levels of key enzymes involved with α-, β- and γ-secretase activity. Among them, Adam9, both at the mRNA and protein level, was the only enzyme to be significantly down-regulated following the induction of apoptosis (K5) and up-regulated after SP treatment. In addition to its neuroprotective properties, this study shows that SP is able to stimulate non-amyloidogenic APP processing, thereby reducing the possibility of generation of toxic Aβ peptides in brain. Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

What makes a good clinical app? Introducing the RCP Health Informatics Unit checklist.

PubMed

Wyatt, Jeremy C; Thimbleby, Harold; Rastall, Paul; Hoogewerf, Jan; Wooldridge, Darren; Williams, John

2015-12-01

Doctors increasingly rely on medical apps running on smart phones or tablet computers to support their work. However, these apps vary hugely in the quality of their data input screens, internal data processing, the methods used to handle sensitive patient data and how they communicate their output to the user. Inspired by Donabedian's approach to assessing quality and the principles of good user interface design, the Royal College of Physicians' Health Informatics Unit has developed and piloted an 18-item checklist to help clinicians assess the structure, functions and impact of medical apps. Use of this checklist should help clinicians to feel more confident about using medical apps themselves, about recommending them to their staff or prescribing them for patients. © Royal College of Physicians 2015. All rights reserved.

Development of smartphone applications for nutrition and physical activity behavior change.

PubMed

Hebden, Lana; Cook, Amelia; van der Ploeg, Hidde P; Allman-Farinelli, Margaret

2012-08-22

Young adults (aged 18 to 35) are a population group at high risk for weight gain, yet we know little about how to intervene in this group. Easy access to treatment and support with self-monitoring of their behaviors may be important. Smartphones are gaining in popularity with this population group and software applications ("apps") used on these mobile devices are a novel technology that can be used to deliver brief health behavior change interventions directly to individuals en masse, with potentially favorable cost-utility. However, existing apps for modifying nutrition or physical activity behaviors may not always reflect best practice guidelines for weight management. This paper describes the process of developing four apps aimed at modifying key lifestyle behaviors associated with weight gain during young adulthood, including physical activity, and consumption of take-out foods (fast food), fruit and vegetables, and sugar-sweetened drinks. The development process involved: (1) deciding on the behavior change strategies, relevant guidelines, graphic design, and potential data collection; (2) selecting the platform (Web-based versus native); (3) creating the design, which required decisions about the user interface, architecture of the relational database, and programming code; and (4) testing the prototype versions with the target audience (young adults aged 18 to 35). The four apps took 18 months to develop, involving the fields of marketing, nutrition and dietetics, physical activity, and information technology. Ten subjects provided qualitative feedback about using the apps. The slow running speed of the apps (due to a reliance on an active Internet connection) was the primary issue identified by this group, as well as the requirement to log in to the apps. Smartphone apps may be an innovative medium for delivering individual health behavior change intervention en masse, but researchers must give consideration to the target population, available technologies, existing commercial apps, and the possibility that their use will be irregular and short-lived.

Development and Testing of a Mobile Phone App for Self-Monitoring of Calcium Intake in Young Women.

PubMed

Tay, Ilona; Garland, Suzanne; Gorelik, Alexandra; Wark, John Dennis

2017-03-07

Interventions to prevent osteoporosis by increasing dairy intake or physical activity in young women have been limited to increasing osteoporosis knowledge and awareness. However, findings have shown that this does not always lead to a change in behaviors. Self-monitoring using mobile devices in behavioral interventions has yielded significant and positive outcomes. Yet, to our knowledge, mobile self-monitoring has not been used as an intervention strategy to increase calcium intake, particularly in young women, for better bone health outcomes. As development and testing of mobile app-based interventions requires a sequence of steps, our study focused on testing the acceptability and usability of Calci-app, a dietary app to self-monitor calcium consumption, before it is used in a behavioral change intervention in young women aged 18-25 years. Calci-app development followed 4 steps: (1) conceptualization, (2) development and pretesting, (3) pilot testing, and (4) mixed methods evaluation. We present the development process of Calci-app and evaluation of the acceptability and usability of the app in young women. Overall, 78% (31/40) of study participants completed the 5-day food record with high compliance levels (defined as more than 3 days of full or partial completion). There was a significant reduction in the proportion of participants completing all meal entries over the 5 days (P=.01). Participants generally found Calci-app easy and convenient to use, but it was time-consuming and they expressed a lack of motivation to use the app. We present a detailed description of the development process of Calci-app and an evaluation of its usability and acceptability to self-monitor dietary calcium intake. The findings from this preliminary study demonstrated acceptable use of Calci-app to self-monitor calcium consumption. However, for regular and long-term use the self-monitoring function in Calci-app could be expanded to allow participants to view their total daily calcium intake compared with the recommended daily intake. Additionally, to facilitate sustainable lifestyle behavior modifications, a combination of various behavior change techniques should be considered, such as education, goal setting, and advice to participants based on their stage of change. The feedback on barriers and facilitators from testing Calci-app will be used to design a bone health mHealth intervention to modify risky lifestyle behaviors in young women for better bone health outcomes. ©Ilona Tay, Suzanne Garland, Alexandra Gorelik, John Dennis Wark. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 07.03.2017.

Targeting Parents for Childhood Weight Management: Development of a Theory-Driven and User-Centered Healthy Eating App

PubMed Central

Lahiri, Sudakshina; Brown, Katherine Elizabeth

2015-01-01

Background The proliferation of health promotion apps along with mobile phones' array of features supporting health behavior change offers a new and innovative approach to childhood weight management. However, despite the critical role parents play in children’s weight related behaviors, few industry-led apps aimed at childhood weight management target parents. Furthermore, industry-led apps have been shown to lack a basis in behavior change theory and evidence. Equally important remains the issue of how to maximize users’ engagement with mobile health (mHealth) interventions where there is growing consensus that inputs from the commercial app industry and the target population should be an integral part of the development process. Objective The aim of this study is to systematically design and develop a theory and evidence-driven, user-centered healthy eating app targeting parents for childhood weight management, and clearly document this for the research and app development community. Methods The Behavior Change Wheel (BCW) framework, a theoretically-based approach for intervention development, along with a user-centered design (UCD) philosophy and collaboration with the commercial app industry, guided the development process. Current evidence, along with a series of 9 focus groups (total of 46 participants) comprised of family weight management case workers, parents with overweight and healthy weight children aged 5-11 years, and consultation with experts, provided data to inform the app development. Thematic analysis of focus groups helped to extract information related to relevant theoretical, user-centered, and technological components to underpin the design and development of the app. Results Inputs from parents and experts working in the area of childhood weight management helped to identify the main target behavior: to help parents provide appropriate food portion sizes for their children. To achieve this target behavior, the behavioral diagnosis revealed the need for eliciting change in parents’ capability, motivation, and opportunity in 10-associated Theoretical Domains Framework (TDF) domains. Of the 9 possible intervention functions, 6 were selected to bring about this change which guided the selection of 21 behavior change techniques. Parents’ preferences for healthy eating app features revolved around four main themes (app features, time saving and convenience, aesthetics, and gamification) whereupon a criterion was applied to guide the selection on which preferences should be integrated into the design of the app. Collaboration with the app company helped to build on users’ preferences for elements of gamification such as points, quizzes, and levels to optimize user engagement. Feedback from parents on interactive mock-ups helped to inform the final development of the prototype app. Conclusions Here, we fully explicate a systematic approach applied in the development of a family-oriented, healthy eating health promotion app grounded in theory and evidence, and balanced with users’ preferences to help maximize its engagement with the target population. PMID:26088692

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.

Comparative metabolomics in vanilla pod and vanilla bean revealing the biosynthesis of vanillin during the curing process of vanilla.

PubMed

Gu, Fenglin; Chen, Yonggan; Hong, Yinghua; Fang, Yiming; Tan, Lehe

2017-12-01

High-performance liquid chromatography-mass spectrometry (LC-MS) was used for comprehensive metabolomic fingerprinting of vanilla fruits prepared from the curing process. In this study, the metabolic changes of vanilla pods and vanilla beans were characterized using MS-based metabolomics to elucidate the biosynthesis of vanillin. The vanilla pods were significantly different from vanilla beans. Seven pathways of vanillin biosynthesis were constructed, namely, glucovanillin, glucose, cresol, capsaicin, vanillyl alcohol, tyrosine, and phenylalanine pathways. Investigations demonstrated that glucose, cresol, capsaicin, and vanillyl alcohol pathway were detected in a wide range of distribution in microbial metabolism. Thus, microorganisms might have participated in vanillin biosynthesis during vanilla curing. Furthermore, the ion strength of glucovanillin was stable, which indicated that glucovanillin only participated in the vanillin biosynthesis during the curing of vanilla.

Development of a Culturally Appropriate Bilingual Electronic App About Hepatitis B for Indigenous Australians: Towards Shared Understandings

PubMed Central

Bukulatjpi, Sarah; Sharma, Suresh; Caldwell, Luci; Johnston, Vanessa; Davis, Joshua Saul

2015-01-01

Background Hepatitis B is endemic in Indigenous communities in Northern Australia; however, there is a lack of culturally appropriate educational tools. Health care workers and educators in this setting have voiced a desire for visual, interactive tools in local languages. Mobile phones are increasingly used and available in remote Indigenous communities. In this context, we identified the need for a tablet-based health education app about hepatitis B, developed in partnership with an Australian remote Indigenous community. Objective To develop a culturally appropriate bilingual app about hepatitis B for Indigenous Australians in Arnhem Land using a participatory action research (PAR) framework. Methods This project was a partnership between the Menzies School of Health Research, Miwatj Aboriginal Health Corporation, Royal Darwin Hospital Liver Clinic, and Dreamedia Darwin. We have previously published a qualitative study that identified major knowledge gaps about hepatitis B in this community, and suggested that a tablet-based app would be an appropriate and popular tool to improve this knowledge. The process of developing the app was based on PAR principles, particularly ongoing consultation, evaluation, and discussion with the community throughout each iterative cycle. Stages included development of the storyboard, the translation process (forward translation and backtranslation), prelaunch community review, launch and initial community evaluation, and finally, wider launch and evaluation at a viral hepatitis conference. Results We produced an app called “Hep B Story” for use with iPad, iPhone, Android tablets, and mobile phones or personal computers. The app is culturally appropriate, audiovisual, interactive, and users can choose either English or Yolŋu Matha (the most common language in East Arnhem Land) as their preferred language. The initial evaluation demonstrated a statistically significant improvement in Hep B-related knowledge for 2 of 3 questions (P=.01 and .02, respectively) and overwhelmingly positive opinion regarding acceptability and ease of use (median rating of 5, on a 5-point Likert-type scale when users were asked if they would recommend the app to others). Conclusions We describe the process of development of a bilingual hepatitis B-specific app for Indigenous Australians, using a PAR framework. The approach was found to be successful with positive evaluations. PMID:26063474

Decreasing the expression of PICALM reduces endocytosis and the activity of β-secretase: implications for Alzheimer's disease.

PubMed

Thomas, Rhian S; Henson, Alex; Gerrish, Amy; Jones, Lesley; Williams, Julie; Kidd, Emma J

2016-07-18

Polymorphisms in the gene for phosphatidylinositol binding clathrin assembly protein (PICALM), an endocytic-related protein, are associated with a small, increased risk of developing Alzheimer's disease (AD), strongly suggesting that changes in endocytosis are involved in the aetiology of the disease. We have investigated the involvement of PICALM in the processing of amyloid precursor protein (APP) to understand how PICALM could be linked to the development of AD. We used siRNA to deplete levels of PICALM, its isoforms and clathrin heavy chain in the human brain-derived H4 neuroglioma cell line that expresses endogenous levels of APP. We then used Western blotting, ELISA and immunohistochemistry to detect intra- and extracellular protein levels of endocytic-related proteins, APP and APP metabolites including β-amyloid (Aβ). Levels of functional endocytosis were quantified using ALEXA 488-conjugated transferrin and flow cytometry as a marker of clathrin-mediated endocytosis (CME). Following depletion of all the isoforms of PICALM by siRNA in H4 cells, levels of intracellular APP, intracellular β-C-terminal fragment (β-CTF) and secreted sAPPβ (APP fragments produced by β-secretase cleavage) were significantly reduced but Aβ40 was not affected. Functional endocytosis was significantly reduced after both PICALM and clathrin depletion, highlighting the importance of PICALM in this process. However, depletion of clathrin did not affect APP but did reduce β-CTF levels. PICALM depletion altered the intracellular distribution of clathrin while clathrin reduction affected the subcellular pattern of PICALM labelling. Both PICALM and clathrin depletion reduced the expression of BACE1 mRNA and PICALM siRNA reduced protein levels. Individual depletion of PICALM isoforms 1 and 2 did not affect APP levels while clathrin depletion had a differential effect on the isoforms, increasing isoform 1 while decreasing isoform 2 expression. The depletion of PICALM in brain-derived cells has significant effects on the processing of APP, probably by reducing CME. In particular, it affects the production of β-CTF which is increasingly considered to be an important mediator in AD independent of Aβ. Thus a decrease in PICALM expression in the brain could be beneficial to slow or prevent the development of AD.

Increased Alzheimer's disease-like pathology in the APP/ PS1ΔE9 mouse model lacking Nrf2 through modulation of autophagy.

PubMed

Joshi, Gururaj; Gan, Kok Ann; Johnson, Delinda A; Johnson, Jeffrey A

2015-02-01

The presence of senile plaques is one of the major pathologic hallmarks of the brain with Alzheimer's disease (AD). The plaques predominantly contain insoluble amyloid β-peptide, a cleavage product of the larger amyloid precursor protein (APP). Two enzymes, named β and γ secretase, generate the neurotoxic amyloid-β peptide from APP. Mature APP is also turned over endogenously by autophagy, more specifically by the endosomal-lysosomal pathway. A defective lysosomal system is known to be pathogenic in AD. Modulation of NF-E2 related factor 2 (Nrf2) has been shown in several neurodegenerative disorders, and Nrf2 has become a potential therapeutic target for various neurodegenerative disorders, including AD, Parkinson's disease, and amyotrophic lateral sclerosis. In the current study, we explored the effect of genetic ablation of Nrf2 on APP/Aβ processing and/or aggregation as well as changes in autophagic dysfunction in APP/PS1 mice. There was a significant increase in inflammatory response in APP/PS1 mice lacking Nrf2. This was accompanied by increased intracellular levels of APP, Aβ (1-42), and Aβ (1-40), without a change total full-length APP. There was a shift of APP and Aβ into the insoluble fraction, as well as increased poly-ubiquitin conjugated proteins in mice lacking Nrf2. APP/PS1-mediated autophagic dysfunction is also enhanced in Nrf2-deficient mice. Finally, neurons in the APP/PS1/Nrf2-/- mice had increased accumulation of multivesicular bodies, endosomes, and lysosomes. These outcomes provide a better understanding of the role of Nrf2 in modulating autophagy in an AD mouse model and may help design better Nrf2 targeted therapeutics that could be efficacious in the treatment of AD. Published by Elsevier Inc.

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

The Amyloid Precursor Protein (APP) Triplicated Gene Impairs Neuronal Precursor Differentiation and Neurite Development through Two Different Domains in the Ts65Dn Mouse Model for Down Syndrome*

PubMed Central

Trazzi, Stefania; Fuchs, Claudia; Valli, Emanuele; Perini, Giovanni; Bartesaghi, Renata; Ciani, Elisabetta

2013-01-01

Intellectual disability in Down syndrome (DS) appears to be related to severe proliferation impairment during brain development. Recent evidence shows that it is not only cellular proliferation that is heavily compromised in DS, but also cell fate specification and dendritic maturation. The amyloid precursor protein (APP), a gene that is triplicated in DS, plays a key role in normal brain development by influencing neural precursor cell proliferation, cell fate specification, and neuronal maturation. APP influences these processes via two separate domains, the APP intracellular domain (AICD) and the soluble secreted APP. We recently found that the proliferation impairment of neuronal precursors (NPCs) from the Ts65Dn mouse model for DS was caused by derangement of the Shh pathway due to overexpression of patched1(Ptch1), its inhibitory regulator. Ptch1 overexpression was related to increased levels within the APP/AICD system. The overall goal of this study was to determine whether APP contributes to neurogenesis impairment in DS by influencing in addition to proliferation, cell fate specification, and neurite development. We found that normalization of APP expression restored the reduced neuronogenesis, the increased astrogliogenesis, and the reduced neurite length of trisomic NPCs, indicating that APP overexpression underpins all aspects of neurogenesis impairment. Moreover, we found that two different domains of APP impair neuronal differentiation and maturation in trisomic NPCs. The APP/AICD system regulates neuronogenesis and neurite length through the Shh pathway, whereas the APP/secreted AP system promotes astrogliogenesis through an IL-6-associated signaling cascade. These results provide novel insight into the mechanisms underlying brain development alterations in DS. PMID:23740250

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

Alpha-Linolenic Acid from Perilla frutescens var. japonica Oil Protects Aβ-Induced Cognitive Impairment through Regulation of APP Processing and Aβ Degradation.

PubMed

Lee, Ah Young; Lee, Myoung Hee; Lee, Sanghyun; Cho, Eun Ju

2017-12-13

Alzheimer's disease (AD) is characterized by progressive cognitive and memory impairment. The major pathological hallmark of AD is the accumulation of amyloid beta (Aβ), which is produced from the amyloid precursor protein (APP) through cleavage of β- and γ-secretase. Recently, dietary plant oil containing ω-3 polyunsaturated fatty acid has become an attractive alternative source to fish oil containing eicosapentaenoic acid or docosahexaenoic acid (DHA). We investigated whether ALA isolated from perilla oil has direct effects on improvement of cognitive ability and molecular mechanisms in APP processing in comparison with DHA. In the present study, ICR mice were treated orally with ALA or DHA (100 mg/kg/day) for 14 days after i.c.v. injection of Aβ 25-35 . Administration of ALA resulted in a prevention of learning and memory deficit in Aβ 25-35 -injected mice compared with the control group, as observed in T-maze, novel object recognition, and Morris water maze tests. ALA supplementation also markedly ameliorated the Aβ 25-35 -induced oxidative stress by inhibition of lipid peroxidation and nitric oxide overproduction in the mouse brain, liver, and kidney, almost down to the levels in DHA-administered group. These effects of ALA on protective mechanisms were related to the regulation of APP processing via promoting nonamyloidogenic pathway such as up-regulation of soluble APP alpha, C-terminal fragment alpha/beta ratio, and A disintegrin and metalloprotease10 protein expressions. Furthermore, ALA inhibited the amyloidogenic pathway through the down-regulation of β-site APP-cleaving enzyme and presenilin2. ALA also enhanced Aβ degradation enzyme, insulin-degrading enzyme. In conclusion, the present study indicated a beneficial effect of ALA in improving the cognitive ability against Aβ 25-35 , and these effects were comparable to those exerted by DHA. Its neuroprotective effects are mediated, in part, by regulation of APP processing and Aβ degradation, and thus, ALA might be a potential candidate for prevention or treatment of neurodegenerative diseases such as AD.

Acute phase proteins in healthy goats: establishment of reference intervals.

PubMed

Heller, Meera C; Johns, Jennifer L

2015-03-01

Acute inflammatory processes can trigger increased production of acute phase proteins (APPs) that can be useful biomarkers of inflammation. APPs are diverse and include proteins involved in coagulation, opsonization, iron regulation, and limitation of tissue injury. Haptoglobin, serum amyloid A, and alpha-1 acid glycoprotein have been proposed as useful APPs in goats. APPs can differ markedly by species, therefore species-specific reference intervals and studies are necessary. The objective of this study was to determine species-specific reference intervals for 4 APPs in goats. Haptoglobin, serum amyloid A, lipopolysaccharide binding protein, and alpha-1 acid glycoprotein were measured in in 54 clinically normal adult goats. APPs were measured using goat-specific commercial enzyme-linked immunosorbent assay kits. Results were analyzed by 1-way analysis of variance to compare sexes and breeding status. Reference Value Advisor was used to calculate reference limits according to the IFCC-CLSI guidelines. Only 1 APP was found to vary in healthy animals; serum haptoglobin was increased in lactating animals and decreased in pregnant does in their second trimester when compared with open, nonlactating does. No sex-based differences were seen for any of the APPs measured. We report normal reference intervals for 4 serum APPs that may be useful as disease markers. Haptoglobin should be interpreted with caution in animals with unknown pregnancy status. Further studies are needed to determine whether these APPs are useful biomarkers in goat disease states. © 2015 The Author(s).

Development and Testing of a Smartphone Application Prototype for Oral Health Promotion.

PubMed

Nolen, Sara L; Giblin-Scanlon, Lori J; Boyd, Linda D; Rainchuso, Lori

2018-04-01

Purpose: The purpose of this study was to develop and test a smartphone application (app) prototype, ToothSense, as an oral health promotion tool for the prevention of Early Childhood Caries (ECC) based on the Theory of Planned Behavior (TPB). Methods: A quantitative and qualitative design process based on the TPB was used for the app development in the first phase of the study. A behavioral intervention technologic model was used to document the app features design, accounting for Doshi's intervention strategies for the TPB. Beta-testing of the app was hosted via an online software program. Testers were presented with a series of tasks and prompts followed by a 5-point Likert-scale questionnaire that quantitatively measured perceptions of the app's interactive design based on Jakob Nielsen's principles and behavioral strategies. A Net Promotor Score was calculated to determine the tester's likelihood to recommend the app prototype. Audio and video aspects of the app were qualitatively measured using a template approach. Results: Beta testers agreed the app met the majority of the five usability statements. The Net Promotor Score indicated a likelihood to recommend the app prototype. Thematic analyses revealed the following themes: interface design, navigation, terminology, information, and oral health promotion. Conclusion: Beta testing results from this study provided health promotion project design information for the prevention of ECC using the TPB and highlighted the importance and usability of smartphone app for oral health promotion. Copyright © 2018 The American Dental Hygienists’ Association.

Can existing mobile apps support healthier food purchasing behaviour? Content analysis of nutrition content, behaviour change theory and user quality integration.

PubMed

Flaherty, Sarah-Jane; McCarthy, Mary; Collins, Alan; McAuliffe, Fionnuala

2018-02-01

To assess the quality of nutrition content and the integration of user quality components and behaviour change theory relevant to food purchasing behaviour in a sample of existing mobile apps. Descriptive comparative analysis of eleven mobile apps comprising an assessment of their alignment with existing evidence on nutrition, behaviour change and user quality, and their potential ability to support healthier food purchasing behaviour. Mobile apps freely available for public use in GoogePlay were assessed and scored according to agreed criteria to assess nutrition content quality and integration of behaviour change theory and user quality components. A sample of eleven mobile apps that met predefined inclusion criteria to ensure relevance and good quality. The quality of the nutrition content varied. Improvements to the accuracy and appropriateness of nutrition content are needed to ensure mobile apps support a healthy behaviour change process and are accessible to a wider population. There appears to be a narrow focus towards behaviour change with an overemphasis on behavioural outcomes and a small number of behaviour change techniques, which may limit effectiveness. A significant effort from the user was required to use the mobile apps appropriately which may negatively influence user acceptability and subsequent utilisation. Existing mobile apps may offer a potentially effective approach to supporting healthier food purchasing behaviour but improvements in mobile app design are required to maximise their potential effectiveness. Engagement of mobile app users and nutrition professionals is recommended to support effective design.

COPS5 (Jab1) protein increases β site processing of amyloid precursor protein and amyloid β peptide generation by stabilizing RanBP9 protein levels.

PubMed

Wang, Hongjie; Dey, Debleena; Carrera, Ivan; Minond, Dmitriy; Bianchi, Elisabetta; Xu, Shaohua; Lakshmana, Madepalli K

2013-09-13

Increased processing of amyloid precursor protein (APP) and accumulation of neurotoxic amyloid β peptide (Aβ) in the brain is central to the pathogenesis of Alzheimer's disease (AD). Therefore, the identification of molecules that regulate Aβ generation is crucial for future therapeutic approaches for AD. We demonstrated previously that RanBP9 regulates Aβ generation in a number of cell lines and primary neuronal cultures by forming tripartite protein complexes with APP, low-density lipoprotein-related protein, and BACE1, consequently leading to increased amyloid plaque burden in the brain. RanBP9 is a scaffold protein that exists and functions in multiprotein complexes. To identify other proteins that may bind RanBP9 and regulate Aβ levels, we used a two-hybrid analysis against a human brain cDNA library and identified COPS5 as a novel RanBP9-interacting protein. This interaction was confirmed by coimmunoprecipitation experiments in both neuronal and non-neuronal cells and mouse brain. Colocalization of COPS5 and RanBP9 in the same subcellular compartments further supported the interaction of both proteins. Furthermore, like RanBP9, COPS5 robustly increased Aβ generation, followed by increased soluble APP-β (sAPP-β) and decreased soluble-APP-α (sAPP-α) levels. Most importantly, down-regulation of COPS5 by siRNAs reduced Aβ generation, implying that endogenous COPS5 regulates Aβ generation. Finally, COPS5 levels were increased significantly in AD brains and APΔE9 transgenic mice, and overexpression of COPS5 strongly increased RanBP9 protein levels by increasing its half-life. Taken together, these results suggest that COPS5 increases Aβ generation by increasing RanBP9 levels. Thus, COPS5 is a novel RanBP9-binding protein that increases APP processing and Aβ generation by stabilizing RanBP9 protein levels.

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

Arf6 controls beta-amyloid production by regulating macropinocytosis of the Amyloid Precursor Protein to lysosomes.

PubMed

Tang, Weihao; Tam, Joshua H K; Seah, Claudia; Chiu, Justin; Tyrer, Andrea; Cregan, Sean P; Meakin, Susan O; Pasternak, Stephen H

2015-07-14

Alzheimer's disease (AD) is characterized by the deposition of Beta-Amyloid (Aβ) peptides in the brain. Aβ peptides are generated by cleavage of the Amyloid Precursor Protein (APP) by the β - and γ - secretase enzymes. Although this process is tightly linked to the internalization of cell surface APP, the compartments responsible are not well defined. We have found that APP can be rapidly internalized from the cell surface to lysosomes, bypassing early and late endosomes. Here we show by confocal microscopy and electron microscopy that this pathway is mediated by macropinocytosis. APP internalization is enhanced by antibody binding/crosslinking of APP suggesting that APP may function as a receptor. Furthermore, a dominant negative mutant of Arf6 blocks direct transport of APP to lysosomes, but does not affect classical endocytosis to endosomes. Arf6 expression increases through the hippocampus with the development of Alzheimer's disease, being expressed mostly in the CA1 and CA2 regions in normal individuals but spreading through the CA3 and CA4 regions in individuals with pathologically diagnosed AD. Disruption of lysosomal transport of APP reduces both Aβ40 and Aβ42 production by more than 30 %. Our findings suggest that the lysosome is an important site for Aβ production and that altering APP trafficking represents a viable strategy to reduce Aβ production.

Women's experiences with using a smartphone app (the Pregnant+ app) to manage gestational diabetes mellitus in a randomised controlled trial.

PubMed

Skar, Jeanette B; Garnweidner-Holme, Lisa M; Lukasse, Mirjam; Terragni, Laura

2018-03-01

The purpose of this study was to explore the experiences of women with gestational diabetes mellitus (GDM) with controlling their blood glucose values and receiving health and nutrition information using a smartphone app (the Pregnant+ app). The study utilised the interpretative phenomenological analysis method. Semi-structured interviews were conducted with 17 participants among those participating to the randomised controlled trial. The women experienced sorrow and disappointment when they were diagnosed with GDM, but they all went through a process of learning to self-manage their condition that was strongly motivated by theirdesire to care for their unborn babies. The women found that the app increased their confidence in their self management of GDM and their motivation for behavioural change. For some women, the app contributed to feelings offrustration or obsession. In addition, some technological problems and a lack of support from health-care professionals limited several women from using the app. The findings suggest that asmartphone app may have potential for supporting women with GDM, particularly in their blood glucose management. However, it also highlights some of the potential challenges of using mHealth technologies. The findings indicate that a closer collaboration between health-care professionals and patients is of great importance in the implementation of apps for women with GDM. Copyright © 2018 Elsevier Ltd. All rights reserved.

Transforming paper-based assessment forms to a digital format: Exemplified by the Housing Enabler prototype app.

PubMed

Svarre, Tanja; Lunn, Tine Bieber Kirkegaard; Helle, Tina

2017-11-01

The aim of this paper is to provide the reader with an overall impression of the stepwise user-centred design approach including the specific methods used and lessons learned when transforming paper-based assessment forms into a prototype app, taking the Housing Enabler as an example. Four design iterations were performed, building on a domain study, workshops, expert evaluation and controlled and realistic usability tests. The user-centred design process involved purposefully selected participants with different Housing Enabler knowledge and housing adaptation experience. The design iterations resulted in the development of a Housing Enabler prototype app. The prototype app has several features and options that are new compared with the original paper-based Housing Enabler assessment form. These new features include a user friendly overview of the assessment form; easy navigation by swiping back and forth between items; onsite data analysis; and ranking of the accessibility score, photo documentation and a data export facility. Based on the presented stepwise approach, a high-fidelity Housing Enabler prototype app was successfully developed. The development process has emphasized the importance of combining design participants' knowledge and experiences, and has shown that methods should seem relevant to participants to increase their engagement.

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

Direct Reading of Bona Fide Barcode Assays for Diagnostics with Smartphone Apps.

PubMed

Wong, Jessica X H; Li, Xiaochun; Liu, Frank S F; Yu, Hua-Zhong

2015-06-30

The desire to develop new point-of-care (POC) diagnostic tools has led to the adaptation of smartphones to tackle limitations in state-of-the-art instrumentation and centralized laboratory facilities. Today's smartphones possess the computer-like ability to image and process data using mobile apps; barcode scanners are one such type of apps. We demonstrate herein that a diagnostic assay can be performed by patterning immunoassay strips in a bona fide barcode format such that after target binding and signal enhancement, the linear barcode can be read directly with a standard smartphone app. Quantitative analysis can then be performed based on the grayscale intensities with a customized mobile app. This novel diagnostic concept has been validated for a real-world application, i.e., the detection of human chorionic gonadotropin, a pregnancy hormone. With the possibility of multiplex detection, the barcode assay protocol promises to boost POC diagnosis research by the direct adaptation of mobile devices and apps.

Direct Reading of Bona Fide Barcode Assays for Diagnostics with Smartphone Apps

PubMed Central

Wong, Jessica X. H.; Li, Xiaochun; Liu, Frank S. F.; Yu, Hua-Zhong

2015-01-01

The desire to develop new point-of-care (POC) diagnostic tools has led to the adaptation of smartphones to tackle limitations in state-of-the-art instrumentation and centralized laboratory facilities. Today’s smartphones possess the computer-like ability to image and process data using mobile apps; barcode scanners are one such type of apps. We demonstrate herein that a diagnostic assay can be performed by patterning immunoassay strips in a bona fide barcode format such that after target binding and signal enhancement, the linear barcode can be read directly with a standard smartphone app. Quantitative analysis can then be performed based on the grayscale intensities with a customized mobile app. This novel diagnostic concept has been validated for a real-world application, i.e., the detection of human chorionic gonadotropin, a pregnancy hormone. With the possibility of multiplex detection, the barcode assay protocol promises to boost POC diagnosis research by the direct adaptation of mobile devices and apps. PMID:26122608

Developing Smartphone Apps for Education, Outreach, Science, and Engineering

NASA Astrophysics Data System (ADS)

Weatherwax, A. T.; Fitzsimmons, Z.; Czajkowski, J.; Breimer, E.; Hellman, S. B.; Hunter, S.; Dematteo, J.; Savery, T.; Melsert, K.; Sneeringer, J.

2010-12-01

The increased popularity of mobile phone apps provide scientists with a new avenue for sharing and distributing data and knowledge with colleagues, while also providing meaningful education and outreach products for consumption by the general public. Our initial development of iPhone and Android apps centered on the distribution of exciting auroral images taken at the South Pole for education and outreach purposes. These portable platforms, with limited resources when compared to computers, presented a unique set of design and implementation challenges that we will discuss in this presentation. For example, the design must account for limited memory; screen size; processing power; battery life; and potentially high data transport costs. Some of these unique requirements created an environment that enabled undergraduate and high-school students to participate in the creation of these apps. Additionally, during development it became apparent that these apps could also serve as data analysis and engineering tools. Our presentation will further discuss our plans to use apps not only for Education and Public Outreach, but for teaching, science and engineering.

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.

Direct Reading of Bona Fide Barcode Assays for Diagnostics with Smartphone Apps

NASA Astrophysics Data System (ADS)

Wong, Jessica X. H.; Li, Xiaochun; Liu, Frank S. F.; Yu, Hua-Zhong

2015-06-01

The desire to develop new point-of-care (POC) diagnostic tools has led to the adaptation of smartphones to tackle limitations in state-of-the-art instrumentation and centralized laboratory facilities. Today’s smartphones possess the computer-like ability to image and process data using mobile apps; barcode scanners are one such type of apps. We demonstrate herein that a diagnostic assay can be performed by patterning immunoassay strips in a bona fide barcode format such that after target binding and signal enhancement, the linear barcode can be read directly with a standard smartphone app. Quantitative analysis can then be performed based on the grayscale intensities with a customized mobile app. This novel diagnostic concept has been validated for a real-world application, i.e., the detection of human chorionic gonadotropin, a pregnancy hormone. With the possibility of multiplex detection, the barcode assay protocol promises to boost POC diagnosis research by the direct adaptation of mobile devices and apps.

Blood Culture Testing via a Mobile App That Uses a Mobile Phone Camera: A Feasibility Study

PubMed Central

Chong, Yong Pil; Jang, Seongsoo; Kim, Mi Na; Kim, Jeong Hoon; Kim, Woo Sung

2016-01-01

Background To evaluate patients with fever of unknown origin or those with suspected bacteremia, the precision of blood culture tests is critical. An inappropriate step in the test process or error in a parameter could lead to a false-positive result, which could then affect the direction of treatment in critical conditions. Mobile health apps can be used to resolve problems with blood culture tests, and such apps can hence ensure that point-of-care guidelines are followed and processes are monitored for blood culture tests. Objective In this pilot project, we aimed to investigate the feasibility of using a mobile blood culture app to manage blood culture test quality. We implemented the app at a university hospital in South Korea to assess the potential for its utilization in a clinical environment by reviewing the usage data among a small group of users and by assessing their feedback and the data related to blood culture sampling. Methods We used an iOS-based blood culture app that uses an embedded camera to scan the patient identification and sample number bar codes. A total of 4 medical interns working at 2 medical intensive care units (MICUs) participated in this project, which spanned 3 weeks. App usage and blood culture sampling parameters (including sampler, sampling site, sampling time, and sample volume) were analyzed. The compliance of sampling parameter entry was also measured. In addition, the participants’ opinions regarding patient safety, timeliness, efficiency, and usability were recorded. Results In total, 356/644 (55.3%) of all blood culture samples obtained at the MICUs were examined using the app, including 254/356 (71.3%) with blood collection volumes of 5-7 mL and 256/356 (71.9%) with blood collection from the peripheral veins. The sampling volume differed among the participants. Sampling parameters were completely entered in 354/356 cases (99.4%). All the participants agreed that the app ensured good patient safety, disagreed on its timeliness, and did not believe that it was efficient. Although the bar code scanning speed was acceptable, the Wi-Fi environment required improvement. Moreover, the participants requested feedback regarding their sampling quality. Conclusions Although this app could be used in the clinical setting, improvements in the app functions, environment network, and internal policy of blood culture testing are needed to ensure hospital-wide use. PMID:27784649

Blood Culture Testing via a Mobile App That Uses a Mobile Phone Camera: A Feasibility Study.

PubMed

Lee, Guna; Lee, Yura; Chong, Yong Pil; Jang, Seongsoo; Kim, Mi Na; Kim, Jeong Hoon; Kim, Woo Sung; Lee, Jae-Ho

2016-10-26

To evaluate patients with fever of unknown origin or those with suspected bacteremia, the precision of blood culture tests is critical. An inappropriate step in the test process or error in a parameter could lead to a false-positive result, which could then affect the direction of treatment in critical conditions. Mobile health apps can be used to resolve problems with blood culture tests, and such apps can hence ensure that point-of-care guidelines are followed and processes are monitored for blood culture tests. In this pilot project, we aimed to investigate the feasibility of using a mobile blood culture app to manage blood culture test quality. We implemented the app at a university hospital in South Korea to assess the potential for its utilization in a clinical environment by reviewing the usage data among a small group of users and by assessing their feedback and the data related to blood culture sampling. We used an iOS-based blood culture app that uses an embedded camera to scan the patient identification and sample number bar codes. A total of 4 medical interns working at 2 medical intensive care units (MICUs) participated in this project, which spanned 3 weeks. App usage and blood culture sampling parameters (including sampler, sampling site, sampling time, and sample volume) were analyzed. The compliance of sampling parameter entry was also measured. In addition, the participants' opinions regarding patient safety, timeliness, efficiency, and usability were recorded. In total, 356/644 (55.3%) of all blood culture samples obtained at the MICUs were examined using the app, including 254/356 (71.3%) with blood collection volumes of 5-7 mL and 256/356 (71.9%) with blood collection from the peripheral veins. The sampling volume differed among the participants. Sampling parameters were completely entered in 354/356 cases (99.4%). All the participants agreed that the app ensured good patient safety, disagreed on its timeliness, and did not believe that it was efficient. Although the bar code scanning speed was acceptable, the Wi-Fi environment required improvement. Moreover, the participants requested feedback regarding their sampling quality. Although this app could be used in the clinical setting, improvements in the app functions, environment network, and internal policy of blood culture testing are needed to ensure hospital-wide use.

Consent Processes for Mobile App Mediated Research: Systematic Review.

PubMed

Moore, Sarah; Tassé, Anne-Marie; Thorogood, Adrian; Winship, Ingrid; Zawati, Ma'n; Doerr, Megan

2017-08-30

Since the launch of ResearchKit on the iOS platform in March 2015 and ResearchStack on the Android platform in June 2016, many academic and commercial institutions around the world have adapted these frameworks to develop mobile app-based research studies. These studies cover a wide variety of subject areas including melanoma, cardiomyopathy, and autism. Additionally, these app-based studies target a variety of participant populations, including children and pregnant women. The aim of this review was to document the variety of self-administered remote informed consent processes used in app-based research studies available between May and September 2016. Remote consent is defined as any consenting process with zero in-person steps, when a participant is able to join a study without ever seeing a member of the research team. This type of review has not been previously conducted. The research community would benefit from a rigorous interrogation of the types of consent taken as part of the seismic shift to entirely mobile meditated research studies. This review examines both the process of information giving and specific content shared, with special attention to data privacy, aggregation, and sharing. Consistency across some elements of the app-based consent processes was found; for example, informing participants about how data will be curated from the phone. Variations in other elements were identified; for example, where specific information is shared and the level of detail disclosed. Additionally, several novel elements present in eConsent not typically seen in traditional consent for research were highlighted. This review advocates the importance of participant informedness in a novel and largely unregulated research setting. ©Sarah Moore, Anne-Marie Tassé, Adrian Thorogood, Ingrid Winship, Ma'n Zawati, Megan Doerr. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 30.08.2017.

The Large Hydrophilic Loop of Presenilin 1 Is Important for Regulating γ-Secretase Complex Assembly and Dictating the Amyloid β Peptide (Aβ) Profile without Affecting Notch Processing*

PubMed Central

Wanngren, Johanna; Frånberg, Jenny; Svensson, Annelie I.; Laudon, Hanna; Olsson, Fredrik; Winblad, Bengt; Liu, Frank; Näslund, Jan; Lundkvist, Johan; Karlström, Helena

2010-01-01

γ-Secretase is an enzyme complex that mediates both Notch signaling and β-amyloid precursor protein (APP) processing, resulting in the generation of Notch intracellular domain, APP intracellular domain, and the amyloid β peptide (Aβ), the latter playing a central role in Alzheimer disease (AD). By a hitherto undefined mechanism, the activity of γ-secretase gives rise to Aβ peptides of different lengths, where Aβ42 is considered to play a particular role in AD. In this study we have examined the role of the large hydrophilic loop (amino acids 320–374, encoded by exon 10) of presenilin 1 (PS1), the catalytic subunit of γ-secretase, for γ-secretase complex formation and activity on Notch and APP processing. Deletion of exon 10 resulted in impaired PS1 endoproteolysis, γ-secretase complex formation, and had a differential effect on Aβ-peptide production. Although the production of Aβ38, Aβ39, and Aβ40 was severely impaired, the effect on Aβ42 was affected to a lesser extent, implying that the production of the AD-related Aβ42 peptide is separate from the production of the Aβ38, Aβ39, and Aβ40 peptides. Interestingly, formation of the intracellular domains of both APP and Notch was intact, implying a differential cleavage activity between the ϵ/S3 and γ sites. The most C-terminal amino acids of the hydrophilic loop were important for regulating APP processing. In summary, the large hydrophilic loop of PS1 appears to differentially regulate the relative production of different Aβ peptides without affecting Notch processing, two parameters of significance when considering γ-secretase as a target for pharmaceutical intervention in AD. PMID:20106965

Consent Processes for Mobile App Mediated Research: Systematic Review

PubMed Central

Tassé, Anne-Marie; Thorogood, Adrian; Winship, Ingrid; Zawati, Ma'n; Doerr, Megan

2017-01-01

Background Since the launch of ResearchKit on the iOS platform in March 2015 and ResearchStack on the Android platform in June 2016, many academic and commercial institutions around the world have adapted these frameworks to develop mobile app-based research studies. These studies cover a wide variety of subject areas including melanoma, cardiomyopathy, and autism. Additionally, these app-based studies target a variety of participant populations, including children and pregnant women. Objective The aim of this review was to document the variety of self-administered remote informed consent processes used in app-based research studies available between May and September 2016. Remote consent is defined as any consenting process with zero in-person steps, when a participant is able to join a study without ever seeing a member of the research team. This type of review has not been previously conducted. The research community would benefit from a rigorous interrogation of the types of consent taken as part of the seismic shift to entirely mobile meditated research studies. Methods This review examines both the process of information giving and specific content shared, with special attention to data privacy, aggregation, and sharing. Results Consistency across some elements of the app-based consent processes was found; for example, informing participants about how data will be curated from the phone. Variations in other elements were identified; for example, where specific information is shared and the level of detail disclosed. Additionally, several novel elements present in eConsent not typically seen in traditional consent for research were highlighted. Conclusions This review advocates the importance of participant informedness in a novel and largely unregulated research setting. PMID:28855147

My Interventional Drug-Eluting Stent Educational App (MyIDEA): Patient-Centered Design Methodology

PubMed Central

Shroff, Adhir; Groo, Vicki; Dickens, Carolyn; Field, Jerry; Baumann, Matthew; Welland, Betty; Gutowski, Gerry; Flores Jr, Jose D; Zhao, Zhongsheng; Bahroos, Neil; Hynes, Denise M; Wilkie, Diana J

2015-01-01

Background Patient adherence to medication regimens is critical in most chronic disease treatment plans. This study uses a patient-centered tablet app, “My Interventional Drug-Eluting Stent Educational App (MyIDEA).” This is an educational program designed to improve patient medication adherence. Objective Our goal is to describe the design, methodology, limitations, and results of the MyIDEA tablet app. We created a mobile technology-based patient education app to improve dual antiplatelet therapy adherence in patients who underwent a percutaneous coronary intervention and received a drug-eluting stent. Methods Patient advisers were involved in the development process of MyIDEA from the initial wireframe to the final launch of the product. The program was restructured and redesigned based on the patient advisers’ suggestions as well as those from multidisciplinary team members. To accommodate those with low health literacy, we modified the language and employed attractive color schemes to improve ease of use. We assumed that the target patient population may have little to no experience with electronic tablets, and therefore, we designed the interface to be as intuitive as possible. Results The MyIDEA app has been successfully deployed to a low-health-literate elderly patient population in the hospital setting. A total of 6 patients have interacted with MyIDEA for an average of 17.6 minutes/session. Conclusions Including patient advisers in the early phases of a mobile patient education development process is critical. A number of changes in text order, language, and color schemes occurred to improve ease of use. The MyIDEA program has been successfully deployed to a low-health-literate elderly patient population. Leveraging patient advisers throughout the development process helps to ensure implementation success. PMID:26139587

Development and Testing of a Mobile Phone App for Self-Monitoring of Calcium Intake in Young Women

PubMed Central

Tay, Ilona

2017-01-01

Background Interventions to prevent osteoporosis by increasing dairy intake or physical activity in young women have been limited to increasing osteoporosis knowledge and awareness. However, findings have shown that this does not always lead to a change in behaviors. Self-monitoring using mobile devices in behavioral interventions has yielded significant and positive outcomes. Yet, to our knowledge, mobile self-monitoring has not been used as an intervention strategy to increase calcium intake, particularly in young women, for better bone health outcomes. Objective As development and testing of mobile app–based interventions requires a sequence of steps, our study focused on testing the acceptability and usability of Calci-app, a dietary app to self-monitor calcium consumption, before it is used in a behavioral change intervention in young women aged 18-25 years. Methods Calci-app development followed 4 steps: (1) conceptualization, (2) development and pretesting, (3) pilot testing, and (4) mixed methods evaluation. Results We present the development process of Calci-app and evaluation of the acceptability and usability of the app in young women. Overall, 78% (31/40) of study participants completed the 5-day food record with high compliance levels (defined as more than 3 days of full or partial completion). There was a significant reduction in the proportion of participants completing all meal entries over the 5 days (P=.01). Participants generally found Calci-app easy and convenient to use, but it was time-consuming and they expressed a lack of motivation to use the app. Conclusions We present a detailed description of the development process of Calci-app and an evaluation of its usability and acceptability to self-monitor dietary calcium intake. The findings from this preliminary study demonstrated acceptable use of Calci-app to self-monitor calcium consumption. However, for regular and long-term use the self-monitoring function in Calci-app could be expanded to allow participants to view their total daily calcium intake compared with the recommended daily intake. Additionally, to facilitate sustainable lifestyle behavior modifications, a combination of various behavior change techniques should be considered, such as education, goal setting, and advice to participants based on their stage of change. The feedback on barriers and facilitators from testing Calci-app will be used to design a bone health mHealth intervention to modify risky lifestyle behaviors in young women for better bone health outcomes. PMID:28270379

A Self-Regulation Theory–Based Asthma Management Mobile App for Adolescents: A Usability Assessment

PubMed Central

2017-01-01

Background Self-regulation theory suggests people learn to influence their own behavior through self-monitoring, goal-setting, feedback, self-reward, and self-instruction, all of which smartphones are now capable of facilitating. Several mobile apps exist to manage asthma; however, little evidence exists about whether these apps employ user-centered design processes that adhere to government usability guidelines for mobile apps. Objective Building upon a previous study that documented adolescent preferences for an asthma self-management app, we employed a user-centered approach to assess the usability of a high-fidelity wireframe for an asthma self-management app intended for use by adolescents with persistent asthma. Methods Individual interviews were conducted with adolescents (ages 11-18 years) with persistent asthma who owned a smartphone (N=8). Adolescents were asked to evaluate a PDF app wireframe consisting of 76 screen shots displaying app features, including log in and home screen, profile setup, settings and info, self-management features, and graphical displays for charting asthma control and medication. Preferences, comments, and suggestions for each set of screen shots were assessed using the audio-recorded interviews. Two coders reached consensus on adolescent evaluations of the following aspects of app features: (1) usability, (2) behavioral intentions to use, (3) confusing aspects, and (4) suggestions for improvement. Results The app wireframe was generally well received, and several suggestions for improvement were recorded. Suggestions included increased customization of charts and notifications, reminders, and alerts. Participants preferred longitudinal data about asthma control and medication use to be displayed using line graphs. All participants reported that they would find an asthma management app like the one depicted in the wireframe useful for managing their asthma. Conclusions Early stage usability tests guided by government usability guidelines (usability.gov) revealed areas for improvement for an asthma self-management app for adolescents. Addressing these areas will be critical to developing an engaging and effective asthma self-management app that is capable of improving adolescent asthma outcomes. PMID:28148471

LRP in amyloid-beta production and metabolism.

PubMed

Bu, Guojun; Cam, Judy; Zerbinatti, Celina

2006-11-01

Amyloid-beta peptide (Abeta) production and accumulation in the brain is a central event in the pathogenesis of Alzheimer's disease (AD). Recent studies have shown that apolipoprotein E (apoE) receptors, members of the low-density lipoprotein receptor (LDLR) family, modulate Abeta production as well as Abeta cellular uptake. Abeta is derived from proteolytic processing of the amyloid precursor protein (APP), which interacts with several members of the LDLR family. Studies from our laboratory have focused on two members of the LDLR family, the LDLR-related protein (LRP) and LRP1B. Our in vitro studies have shown that while LRP's rapid endocytosis facilitates APP endocytic trafficking and processing to Abeta, LRP1B's slow endocytosis inhibits these processes. In addition to modulating APP endocytic trafficking, LRP's rapid endocytosis also facilitates Abeta cellular uptake by binding to Abeta either directly or via LRP ligands such as apoE. Our in vivo studies using transgenic mice have shown that overexpression of LRP in central nervous system (CNS) neurons increases soluble brain Abeta and this increase correlates with deficits in memory. Together our studies demonstrate that members of the LDLR family modulate APP processing and Abeta metabolism by several independent mechanisms. Understanding the pathways that modulate brain Abeta metabolism may enable the rational design of molecular medicine to treat AD.

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.

Spatially-Selective Membrane Permeabilization Induced by Cell-Solution Electrode Atmospheric Pressure Plasma Irradiation

NASA Astrophysics Data System (ADS)

Sasaki, Shota; Hokari, Yutaro; Kanzaki, Makoto; Kaneko, Toshiro

2015-09-01

Gene transfection, which is the process of deliberately introducing nucleic acids into cells, is expected to play an important role in medical treatment because the process is necessary for gene therapy and creation of induced pluripotent stem (iPS) cells. However, the conventional transfection methods have some problems, so we focus attention on promising transfection methods by atmospheric pressure plasma (APP). We have previously reported that the cell membrane permeability, which is closely related with gene transfection, is improved using a cell-solution electrode for generating He-APP. He-APP is irradiated to the solution containing the adherent cells and delivery materials such as fluorescent dyes (YOYO-1) and plasmid DNA (GFP). In case of YOYO-1 delivery, more than 80% of cells can be transferred only in the plasma-irradiated area and the spatially-selective membrane permeabilization is realized by the plasma irradiation. In addition, it is confirmed that plasmid DNA is transfected and the GFP genes are expressed using same APP irradiation system with no obvious cellular damage.

Mindfulness-Based Symptom and Stress Management Apps for Adults With Chronic Lung Disease: Systematic Search in App Stores

PubMed Central

2018-01-01

Background Up to 70% of lung cancer survivors are affected by chronic obstructive pulmonary disease (COPD), a common, debilitating, comorbid disease. Lung cancer and COPD are both characterized by symptoms such as breathlessness, fatigue, and psychological distress. These distressing chronic symptoms are exacerbated by stress and detract from an individual’s quality of life. Objective The aim of this study was to identify and evaluate evidence-based, commercially available apps for promoting mindfulness-based strategies among adults with a COPD or lung cancer history (ie, chronic lung disease). Methods For this review, an interdisciplinary research team used 19 keyword combinations in the search engines of Google and iOS app stores in May 2017. Evaluations were conducted on the apps’ (1) content, (2) usability heuristics, (3) grade-level readability, and (4) cultural sensitivity. Results The search resulted in 768 apps (508 in iOS and 260 in Google stores). A total of 9 apps met the inclusion criteria and received further evaluation. Only 1 app had below an eighth-grade reading level; the ninth one did not have enough text to calculate a readability score. None of the 9 apps met the cultural sensitivity evaluation criteria. Conclusions This systematic review identified critical design flaws that may affect the ease of using the apps in this study. Few mobile apps promote mindfulness-based strategies among adults with chronic lung disease (ie, COPD or lung cancer or both), but those that exist, overall, do not meet the latest scientific evidence. Recommendations include more stringent regulation of health-related apps, use of evidence-based frameworks and participatory design processes, following evidence-based usability practices, use of culturally sensitive language and images, and ensuring that content is written in plain language. PMID:29764800

Impact of an iDevice application on student learning in an occupational therapy kinesiology course.

PubMed

Hughes, Jason K; Kearney, Pamalyn

2017-01-01

As technology continues to evolve, and information is increasingly accessed through smartphones and tablets, it is essential for university faculty to reassess teaching methodologies. This study explored how use of an iDevice application (app) by participants enrolled in an entry-level occupational therapy kinesiology course affected student learning in the course. This iDevice app was developed through a collaboration between the lead author and the Department of Technology Enhanced Learning and Innovation at Augusta University. The iDevice app was released to the public via the Apple ® App Store at the midpoint of the kinesiology course. All students were invited to use the app. Focus groups were conducted with 19 students recruited from the first year cohort of occupational therapy graduate students. These focus groups were conducted at the end of the semester once grades had been submitted. Thematic analysis of focus group transcripts revealed three themes reflecting how participants perceived app use impacting their learning. Participants report the app facilitated learning through provision of visual content, serving as a reliable source of information, and generally supporting the learning process. The Kinesiology Pro Consult App provided on demand learning, allowing students to be more autonomous with their learning and take advantage of opportunities to learn anywhere and anytime. Finally, participants reported the app allowed them to be more efficient in their learning, possibly allowing more time for other courses. Mobile device apps that support student learning in specific content areas may provide positive benefits to student learning both in the specific course related to the app but also in other courses as a result of increased efficiency in learning.

Impact of an iDevice application on student learning in an occupational therapy kinesiology course

PubMed Central

Kearney, Pamalyn

2017-01-01

Background As technology continues to evolve, and information is increasingly accessed through smartphones and tablets, it is essential for university faculty to reassess teaching methodologies. This study explored how use of an iDevice application (app) by participants enrolled in an entry-level occupational therapy kinesiology course affected student learning in the course. This iDevice app was developed through a collaboration between the lead author and the Department of Technology Enhanced Learning and Innovation at Augusta University. Methods The iDevice app was released to the public via the Apple® App Store at the midpoint of the kinesiology course. All students were invited to use the app. Focus groups were conducted with 19 students recruited from the first year cohort of occupational therapy graduate students. These focus groups were conducted at the end of the semester once grades had been submitted. Results Thematic analysis of focus group transcripts revealed three themes reflecting how participants perceived app use impacting their learning. Participants report the app facilitated learning through provision of visual content, serving as a reliable source of information, and generally supporting the learning process. The Kinesiology Pro Consult App provided on demand learning, allowing students to be more autonomous with their learning and take advantage of opportunities to learn anywhere and anytime. Finally, participants reported the app allowed them to be more efficient in their learning, possibly allowing more time for other courses. Conclusions Mobile device apps that support student learning in specific content areas may provide positive benefits to student learning both in the specific course related to the app but also in other courses as a result of increased efficiency in learning. PMID:29184895

Quality of Mobile Phone and Tablet Mobile Apps for Speech Sound Disorders: Protocol for an Evidence-Based Appraisal.

PubMed

Furlong, Lisa M; Morris, Meg E; Erickson, Shane; Serry, Tanya A

2016-11-29

Although mobile apps are readily available for speech sound disorders (SSD), their validity has not been systematically evaluated. This evidence-based appraisal will critically review and synthesize current evidence on available therapy apps for use by children with SSD. The main aims are to (1) identify the types of apps currently available for Android and iOS mobile phones and tablets, and (2) to critique their design features and content using a structured quality appraisal tool. This protocol paper presents and justifies the methods used for a systematic review of mobile apps that provide intervention for use by children with SSD. The primary outcomes of interest are (1) engagement, (2) functionality, (3) aesthetics, (4) information quality, (5) subjective quality, and (6) perceived impact. Quality will be assessed by 2 certified practicing speech-language pathologists using a structured quality appraisal tool. Two app stores will be searched from the 2 largest operating platforms, Android and iOS. Systematic methods of knowledge synthesis shall include searching the app stores using a defined procedure, data extraction, and quality analysis. This search strategy shall enable us to determine how many SSD apps are available for Android and for iOS compatible mobile phones and tablets. It shall also identify the regions of the world responsible for the apps' development, the content and the quality of offerings. Recommendations will be made for speech-language pathologists seeking to use mobile apps in their clinical practice. This protocol provides a structured process for locating apps and appraising the quality, as the basis for evaluating their use in speech pathology for children in English-speaking nations. ©Lisa M Furlong, Meg E Morris, Shane Erickson, Tanya A Serry. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 29.11.2016.

Understanding the Relationships between mHealth Apps' Characteristics, Trialability, and mHealth Literacy.

PubMed

Lin, Trisha T C; Bautista, John Robert

2017-04-01

The widespread adoption of mobile phones has increased the potential of mHealth to improve health communication and health outcomes because these devices could serve as a ubiquitous and affordable means to disseminate health information to large populations. Given that mHealth apps offer free or limited trials as part of promotional strategies, potential users' trialability is a critical step of the preadoption process. Drawing from Rogers' diffusion of innovation theory, this study examines the relationships of adopters' perceived characteristics of mHealth apps (i.e., relative advantage, complexity, compatibility, and observability) with their trialability. It further investigates how the perceived control of mobile devices and trialability of mHealth apps influence two dimensions of mHealth literacy, namely seeking and appraisal of health information. This web survey recruited 295 young mHealth app users from a Singaporean university. Results of partial least squares regression show that the observability of mHealth apps is the only factor positively related to mHealth trialability. Perceived control of mobile devices and trialability of mHealth apps are positively associated with seeking and appraisal of health information. Practical and theoretical implications to mHealth are discussed.

Barriers to Expanding Advanced Pharmacy Practice Experience Site Availability in an Experiential Education Consortium

PubMed Central

Byrd, Debbie C.; Duke, Lori J.; Fetterman, James W.; Unterwagner, Whitney L.; Staton, April G.; Miller, Mindi S.; Sheffield, Melody C.; Kennedy, William K.; McDuffie, Charles H.; Stevenson, T. Lynn; Thompson, Paula A.; McCullough, Elizabeth S.

2009-01-01

Objectives To compare 2006-2007 and projected 2010-2011 advanced pharmacy practice experience (APPE) availability and needs for 4 colleges and schools of pharmacy in Georgia and Alabama and to examine barriers and offer potential solutions to increase APPE site and preceptor availability. Methods Data on APPE needs and availability were gathered prospectively and evaluated relative to current and projected enrollment and planned programmatic changes. Results Combined 2006-2007 non-community APPE needs and availabilities were 3,590 and 4,427, respectively, with a surplus availability of 837. Combined projected 2010-2011 non-community APPEs were estimated at 4,309. Assuming 2006-2007 non-community availability remained unchanged, the surplus availability declined to 118. Conclusions The need for quality experiential education represents a significant barrier and rate-limiting step to the matriculation of the increased numbers of pharmacists. Barriers to expanding APPE availability include: introductory pharmacy practice experience (IPPE) and APPE expansion, growth of new and existing pharmacy programs, financial instability of acute care facilities, and lack of preceptor development resources. Regional experiential education consortiums can provide a constructive approach to improve access to quality sites and preceptors through standardizing processes and leveraging resources. PMID:19777097

Opposite Dysregulation of Fragile-X Mental Retardation Protein and Heteronuclear Ribonucleoprotein C Protein Associates with Enhanced APP Translation in Alzheimer Disease.

PubMed

Borreca, Antonella; Gironi, Katia; Amadoro, Giusy; Ammassari-Teule, Martine

2016-07-01

Amyloid precursor protein (APP) is overexpressed in familiar and sporadic Alzheimer Disease (AD) patients suggesting that, in addition to abnormalities in APP cleavage, enhanced levels of APP full length might contribute to the pathology. Based on data showing that the two RNA binding proteins (RBPs), Fragile-X Mental Retardation Protein (FMRP) and heteronuclear Ribonucleoprotein C (hnRNP C), exert an opposite control on APP translation, we have analyzed whether expression and translation of these two RBPs vary in relation to changes in APP protein and mRNA levels in the AD brain at 1, 3, and 6 months of age. Here, we show that, as expected, human APP is overexpressed in hippocampal total extract from Tg2576 mice at all age points. APP overexpression, however, is not stable over time but reaches its maximal level in 1-month-old mutants in association with the stronger (i) reduction of FMRP and (ii) augmentation of hnRNP C. APP levels then decrease progressively as a function of age in close relationship with the gradual normalization of FMRP and hnRNP C levels. Consistent with the mouse data, expression of FMRP and hnRNP C are, respectively, decreased and increased in hippocampal synaptosomes from sporadic AD patients. Our findings identify two RBP targets that might be manipulated for reducing abnormally elevated levels of APP in the AD brain, with the hypothesis that acting upstream of amyloidogenic processing might contribute to attenuate the amyloid burden.

Exploring the Usability of Mobile Apps Supporting Radiologists' Training in Diagnostic Decision Making.

PubMed

Kim, Min Soon; Aro, Michael R; Lage, Kraig J; Ingalls, Kevin L; Sindhwani, Vivek; Markey, Mia K

2016-03-01

The objective of this study was to conduct a usability evaluation of mobile apps for supporting education and training in radiologic diagnostic decision-making processes. Of 381 mobile apps available at two major stores (Google Play and iTunes), eight iOS apps were selected for laboratory-based usability tests. Six staff radiologists completed eight app-specific task sets, using a think-aloud strategy. The triangular methods approach included quantitative performance measures, System Usability Scale (SUS), and qualitative thematic analysis using heuristic usability principles of usability issues. Overall, radiologists achieved higher than 70% success, with favorable SUS scores, in completing the tasks for seven of the eight apps. However, task success rate and SUS score had a weak relation (r = 0.23), indicating that the perceived usability may not reflect the holistic usability of the app. Task analysis and self-report revealed 108 usability issues, which were condensed to 55 unique issues and categorized by nine usability themes and mapped to ten usability heuristics. Nonintuitive functionality (eg, nonintuitive or misleading labels) was the most frequent theme observed, leading to inefficient navigation. These usability findings were consistent with the 13 improvements the radiologists suggested. This study demonstrates the feasibility of usability evaluation of radiology mobile apps and suggests potential improvements in the development of radiology mobile apps. This study also suggests that proficiency with mobile devices may not be equivalent to being an expert user, proficient in using the apps. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

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".

Intracellular trafficking of the β-secretase and processing of amyloid precursor protein.

PubMed

Zhi, Pei; Chia, Pei Zhi Cheryl; Chia, Cheryl; Gleeson, Paul A

2011-09-01

The main component of the amyloid plaques found in the brains of those with Alzheimer's disease (AD) is a polymerized form of the β-amyloid peptide (Aβ) and is considered to play a central role in the pathogenesis of this neurodegenerative disorder. Aβ is derived from the proteolytic processing of the amyloid precursor protein (APP). Beta site APP-cleaving enzyme, BACE1 (also known as β-secretase) is a membrane-bound aspartyl protease responsible for the initial step in the generation of Aβ peptide and is thus a prime target for therapeutic intervention. Substantive evidence now indicates that the processing of APP by BACE1 is regulated by the intracellular sorting of the enzyme and, moreover, perturbations in these intracellular trafficking pathways have been linked to late-onset AD. In this review, we highlight the recent advances in the understanding of the regulation of the intracellular sorting of BACE1 and APP and illustrate why the trafficking of these cargos represent a key issue for understanding the membrane-mediated events associated with the generation of the neurotoxic Aβ products in AD. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.

Specific Inhibition of β-Secretase Processing of the Alzheimer Disease Amyloid Precursor Protein.

PubMed

Ben Halima, Saoussen; Mishra, Sabyashachi; Raja, K Muruga Poopathi; Willem, Michael; Baici, Antonio; Simons, Kai; Brüstle, Oliver; Koch, Philipp; Haass, Christian; Caflisch, Amedeo; Rajendran, Lawrence

2016-03-08

Development of disease-modifying therapeutics is urgently needed for treating Alzheimer disease (AD). AD is characterized by toxic β-amyloid (Aβ) peptides produced by β- and γ-secretase-mediated cleavage of the amyloid precursor protein (APP). β-secretase inhibitors reduce Aβ levels, but mechanism-based side effects arise because they also inhibit β-cleavage of non-amyloid substrates like Neuregulin. We report that β-secretase has a higher affinity for Neuregulin than it does for APP. Kinetic studies demonstrate that the affinities and catalytic efficiencies of β-secretase are higher toward non-amyloid substrates than toward APP. We show that non-amyloid substrates are processed by β-secretase in an endocytosis-independent manner. Exploiting this compartmentalization of substrates, we specifically target the endosomal β-secretase by an endosomally targeted β-secretase inhibitor, which blocked cleavage of APP but not non-amyloid substrates in many cell systems, including induced pluripotent stem cell (iPSC)-derived neurons. β-secretase inhibitors can be designed to specifically inhibit the Alzheimer process, enhancing their potential as AD therapeutics without undesired side effects. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Cross-linking of cell surface amyloid precursor protein leads to increased β-amyloid peptide production in hippocampal neurons: implications for Alzheimer's disease.

PubMed

Lefort, Roger; Pozueta, Julio; Shelanski, Michael

2012-08-01

The accumulation of the β-amyloid peptide (Aβ) in Alzheimer's disease (AD) is thought to play a causative role in triggering synaptic dysfunction in neurons, leading to their eventual demise through apoptosis. Aβ is produced and secreted upon sequential cleavage of the amyloid precursor protein (APP) by β-secretases and γ-secretases. However, while Aβ levels have been shown to be increased in the brains of AD patients, little is known about how the cleavage of APP and the subsequent generation of Aβ is influenced, or whether the cleavage process changes over time. It has been proposed that Aβ can bind APP and promote amyloidogenic processing of APP, further enhancing Aβ production. Proof of this idea has remained elusive because a clear mechanism has not been identified, and the promiscuous nature of Aβ binding complicates the task of demonstrating the idea. To work around these problems, we used an antibody-mediated approach to bind and cross-link cell-surface APP in cultured rat primary hippocampal neurons. Here we show that cross-linking of APP is sufficient to raise the levels of Aβ in viable neurons with a concomitant increase in the levels of the β-secretase BACE1. This appears to occur as a result of a sorting defect that stems from the caspase-3-mediated inactivation of a key sorting adaptor protein, namely GGA3, which prevents the lysosomal degradation of BACE1. Together, our data suggest the occurrence of a positive pathogenic feedback loop involving Aβ and APP in affected neurons possibly allowing Aβ to spread to nearby healthy neurons.

Interferon-γ and Tumor Necrosis Factor-α Regulate Amyloid-β Plaque Deposition and β-Secretase Expression in Swedish Mutant APP Transgenic Mice

PubMed Central

Yamamoto, Masaru; Kiyota, Tomomi; Horiba, Masahide; Buescher, James L.; Walsh, Shannon M.; Gendelman, Howard E.; Ikezu, Tsuneya

2007-01-01

Reactive astrocytes and microglia in Alzheimer’s disease surround amyloid plaques and secrete proinflammatory cytokines that affect neuronal function. Relationship between cytokine signaling and amyloid-β peptide (Aβ) accumulation is poorly understood. Thus, we generated a novel Swedish β-amyloid precursor protein mutant (APP) transgenic mouse in which the interferon (IFN)-γ receptor type I was knocked out (APP/GRKO). IFN-γ signaling loss in the APP/GRKO mice reduced gliosis and amyloid plaques at 14 months of age. Aggregated Aβ induced IFN-γ production from co-culture of astrocytes and microglia, and IFN-γ elicited tumor necrosis factor (TNF)-α secretion in wild type (WT) but not GRKO microglia co-cultured with astrocytes. Both IFN-γ and TNF-α enhanced Aβ production from APP-expressing astrocytes and cortical neurons. TNF-α directly stimulated β-site APP-cleaving enzyme (BACE1) expression and enhanced β-processing of APP in astrocytes. The numbers of reactive astrocytes expressing BACE1 were increased in APP compared with APP/GRKO mice in both cortex and hippocampus. IFN-γ and TNF-α activation of WT microglia suppressed Aβ degradation, whereas GRKO microglia had no changes. These results support the idea that glial IFN-γ and TNF-α enhance Aβ deposition through BACE1 expression and suppression of Aβ clearance. Taken together, these observations suggest that proinflammatory cytokines are directly linked to Alzheimer’s disease pathogenesis. PMID:17255335

Development of Smartphone Applications for Nutrition and Physical Activity Behavior Change

PubMed Central

Cook, Amelia; van der Ploeg, Hidde P; Allman-Farinelli, Margaret

2012-01-01

Background Young adults (aged 18 to 35) are a population group at high risk for weight gain, yet we know little about how to intervene in this group. Easy access to treatment and support with self-monitoring of their behaviors may be important. Smartphones are gaining in popularity with this population group and software applications (“apps”) used on these mobile devices are a novel technology that can be used to deliver brief health behavior change interventions directly to individuals en masse, with potentially favorable cost-utility. However, existing apps for modifying nutrition or physical activity behaviors may not always reflect best practice guidelines for weight management. Objective This paper describes the process of developing four apps aimed at modifying key lifestyle behaviors associated with weight gain during young adulthood, including physical activity, and consumption of take-out foods (fast food), fruit and vegetables, and sugar-sweetened drinks. Methods The development process involved: (1) deciding on the behavior change strategies, relevant guidelines, graphic design, and potential data collection; (2) selecting the platform (Web-based versus native); (3) creating the design, which required decisions about the user interface, architecture of the relational database, and programming code; and (4) testing the prototype versions with the target audience (young adults aged 18 to 35). Results The four apps took 18 months to develop, involving the fields of marketing, nutrition and dietetics, physical activity, and information technology. Ten subjects provided qualitative feedback about using the apps. The slow running speed of the apps (due to a reliance on an active Internet connection) was the primary issue identified by this group, as well as the requirement to log in to the apps. Conclusions Smartphone apps may be an innovative medium for delivering individual health behavior change intervention en masse, but researchers must give consideration to the target population, available technologies, existing commercial apps, and the possibility that their use will be irregular and short-lived. PMID:23611892

Smoking cessation apps for smartphones: content analysis with the self-determination theory.

PubMed

Choi, Jounghwa; Noh, Ghee-Young; Park, Dong-Jin

2014-02-12

Smartphones are increasingly receiving attention from public health scholars and practitioners as a means to assist individuals' health management. A number of smartphone apps for smoking cessation are also available; however, little effort has been made to evaluate the content and functions of these apps employing a theoretical framework. The present study aims to analyze and evaluate the contents of smoking cessation apps available in South Korea employing the self-determination theory (SDT) as a theoretical framework for analysis. This study analyzes the extent to which smoking cessation apps have features that satisfy the basic needs identified in the SDT, which stimulate autonomous motivation. The type of motivational goal content manifested in the apps and how the goal content was framed are also explored. By assessing the features of smoking cessation apps based on the SDT, this study aims to offer direction for improvement for these apps. Out of 309 apps identified from the iTunes store and Google Play (excluding 27 duplications), 175 apps were randomly drawn and analyzed. The coding scheme was drafted by the authors based on the SDT and gain/loss framing theory and was further finely tuned through the process of coder training and by establishing intercoder reliability. Once the intercoder reliability was established, the coders divided up the rest of the sample and coded them independently. The analysis revealed that most apps (94.3%, 165/175) had at least one feature that tapped at least 1 of the 3 basic needs. Only 18 of 175 apps (10.3%) addressed all 3 basic needs. For goal content, money (53.7%, 94/175) showed the highest frequency, followed by health (32.0%, 56/175), time (7.4%, 13/175), and appearance (1.1%, 2/175), suggesting that extrinsic goals are more dominantly presented in smoking cessation apps. For the framing of goal content, gain framing appeared more frequently (41.7%, 73/175). The results suggest that these smoking cessation apps may not sufficiently stimulate autonomous motivation; a small number of apps addressed all 3 basic needs suggested by the SDT (ie, autonomy, competence, and relatedness). The apps also tended to present extrinsic goal content (primarily in terms of money) over intrinsic ones (ie, health) by primarily adopting gain framing. Implications of these findings for public health practitioners and consumers are discussed.

Smoking Cessation Apps for Smartphones: Content Analysis With the Self-Determination Theory

PubMed Central

Noh, Ghee-Young; Park, Dong-Jin

2014-01-01

Background Smartphones are increasingly receiving attention from public health scholars and practitioners as a means to assist individuals’ health management. A number of smartphone apps for smoking cessation are also available; however, little effort has been made to evaluate the content and functions of these apps employing a theoretical framework. Objective The present study aims to analyze and evaluate the contents of smoking cessation apps available in South Korea employing the self-determination theory (SDT) as a theoretical framework for analysis. This study analyzes the extent to which smoking cessation apps have features that satisfy the basic needs identified in the SDT, which stimulate autonomous motivation. The type of motivational goal content manifested in the apps and how the goal content was framed are also explored. By assessing the features of smoking cessation apps based on the SDT, this study aims to offer direction for improvement for these apps. Methods Out of 309 apps identified from the iTunes store and Google Play (excluding 27 duplications), 175 apps were randomly drawn and analyzed. The coding scheme was drafted by the authors based on the SDT and gain/loss framing theory and was further finely tuned through the process of coder training and by establishing intercoder reliability. Once the intercoder reliability was established, the coders divided up the rest of the sample and coded them independently. Results The analysis revealed that most apps (94.3%, 165/175) had at least one feature that tapped at least 1 of the 3 basic needs. Only 18 of 175 apps (10.3%) addressed all 3 basic needs. For goal content, money (53.7%, 94/175) showed the highest frequency, followed by health (32.0%, 56/175), time (7.4%, 13/175), and appearance (1.1%, 2/175), suggesting that extrinsic goals are more dominantly presented in smoking cessation apps. For the framing of goal content, gain framing appeared more frequently (41.7%, 73/175). Conclusions The results suggest that these smoking cessation apps may not sufficiently stimulate autonomous motivation; a small number of apps addressed all 3 basic needs suggested by the SDT (ie, autonomy, competence, and relatedness). The apps also tended to present extrinsic goal content (primarily in terms of money) over intrinsic ones (ie, health) by primarily adopting gain framing. Implications of these findings for public health practitioners and consumers are discussed. PMID:24521881

Protection of Radial Glial-Like Cells in the Hippocampus of APP/PS1 Mice: a Novel Mechanism of Memantine in the Treatment of Alzheimer's Disease.

PubMed

Sun, Dayu; Chen, Junhua; Bao, Xiaohang; Cai, Yulong; Zhao, Jinghui; Huang, Jing; Huang, Wei; Fan, Xiaotang; Xu, Haiwei

2015-08-01

The failure of adult neurogenesis in the hippocampal dentate gyrus (DG) is closely correlated with memory decline in Alzheimer's disease (AD). Radial glial-like cells (RGLs) localized to the adult DG generate intermediate progenitor cells and immature neurons and thus contribute to adult hippocampus neurogenesis. Memantine (MEM) has been indicated to dramatically increase hippocampal neurogenesis by promoting the proliferation of RGLs. In this study, we examined the effect of MEM on the capacity for hippocampal cell proliferation and the amount of RGLs in APPswe/PS1∆E9 transgenic (APP/PS1) mice between 9 and 13 months of age. MEM could enhance hippocampal neurogenesis and increase the number of RGLs in the DG subgranular zone (DG-SGZ) of APP/PS1 mice of both ages. Moreover, MEM decreased amyloidogenesis in 13-month-old APP/PS1 mice and protected cultured radial glia cells (RGCs, L2.3 cells) from apoptosis induced by the β amyloid peptide (Aβ). Additionally, MEM inhibited microglial activation in a vertical process in DG-SGZ of APP/PS1 mice and decreased interacting with RGL processes. Reelin is involved in the proliferation of RGLs in the hippocampus, which was typically upregulated in the hippocampus of APP/PS1 mice by MEM and thought to be an active signaling pathway associated with the MEM-induced increase in RGLs. Our data suggest a previously uncharacterized role for MEM in treating AD.

A Smartphone App to Promote an Active Lifestyle in Lower-Educated Working Young Adults: Development, Usability, Acceptability, and Feasibility Study

PubMed Central

De Bourdeaudhuij, Ilse; Clarys, Peter; De Cocker, Katrien; Vandelanotte, Corneel; Deforche, Benedicte

2018-01-01

Background Physical activity (PA) levels are problematic in lower-educated working young adults (18-26 years). To promote PA, smartphone apps have great potential, but there is no evidence for their effectiveness in this population. To increase the likelihood that a newly developed app will be effective, formative research and user testing are required. Objective The aim of this study was to describe the development, usability, acceptability, and feasibility of a new theory- and evidence-based smartphone app to promote an active lifestyle in lower-educated working young adults. Methods The new app was developed by applying 4 steps. First, determinants important to promote an active lifestyle in this population were selected. Second, evidence-based behavior change techniques were selected to convert the determinants into practical applications. Third, a new smartphone app was developed. Fourth, volunteers (n=11, both lower and higher educated) tested the app on usability, and lower-educated working young adults (n=16) tested its acceptability and feasibility via (think aloud) interviews, a questionnaire, and Google Analytics. The app was accordingly adapted for the final version. Results A new Android app, Active Coach, was developed that focused on knowledge, attitude, social support, and self-efficacy (based on outcomes from step 1), and that applied self-regulation techniques (based on outcomes from step 2). The app consists of a 9-week program with personal goals, practical tips, and scientific facts to encourage an active lifestyle. To ensure all-day and automatic self-monitoring of the activity behavior, the Active Coach app works in combination with a wearable activity tracker, the Fitbit Charge. Issues detected by the usability test (eg, text errors, wrong messages) were all fixed. The acceptability and feasibility test showed that participants found the app clear, understandable, and motivating, although some aspects needed to be more personal. Conclusions By applying a stepwise, user-centered approach that regularly consulted the target group, the new app is adapted to their specific needs and preferences. The Active Coach app was overall positively evaluated by the lower-educated working young adults at the end of the development process. PMID:29463491

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.

Amyloid Precursor Protein (APP) Mediated Regulation of Ganglioside Homeostasis Linking Alzheimer's Disease Pathology with Ganglioside Metabolism

PubMed Central

Grimm, Marcus O. W.; Zinser, Eva G.; Grösgen, Sven; Hundsdörfer, Benjamin; Rothhaar, Tatjana L.; Burg, Verena K.; Kaestner, Lars; Bayer, Thomas A.; Lipp, Peter; Müller, Ulrike; Grimm, Heike S.; Hartmann, Tobias

2012-01-01

Gangliosides are important players for controlling neuronal function and are directly involved in AD pathology. They are among the most potent stimulators of Aβ production, are enriched in amyloid plaques and bind amyloid beta (Aβ). However, the molecular mechanisms linking gangliosides with AD are unknown. Here we identified the previously unknown function of the amyloid precursor protein (APP), specifically its cleavage products Aβ and the APP intracellular domain (AICD), of regulating GD3-synthase (GD3S). Since GD3S is the key enzyme converting a- to b-series gangliosides, it therefore plays a major role in controlling the levels of major brain gangliosides. This regulation occurs by two separate and additive mechanisms. The first mechanism directly targets the enzymatic activity of GD3S: Upon binding of Aβ to the ganglioside GM3, the immediate substrate of the GD3S, enzymatic turnover of GM3 by GD3S was strongly reduced. The second mechanism targets GD3S expression. APP cleavage results, in addition to Aβ release, in the release of AICD, a known candidate for gene transcriptional regulation. AICD strongly down regulated GD3S transcription and knock-in of an AICD deletion mutant of APP in vivo, or knock-down of Fe65 in neuroblastoma cells, was sufficient to abrogate normal GD3S functionality. Equally, knock-out of the presenilin genes, presenilin 1 and presenilin 2, essential for Aβ and AICD production, or of APP itself, increased GD3S activity and expression and consequently resulted in a major shift of a- to b-series gangliosides. In addition to GD3S regulation by APP processing, gangliosides in turn altered APP cleavage. GM3 decreased, whereas the ganglioside GD3, the GD3S product, increased Aβ production, resulting in a regulatory feedback cycle, directly linking ganglioside metabolism with APP processing and Aβ generation. A central aspect of this homeostatic control is the reduction of GD3S activity via an Aβ-GM3 complex and AICD-mediated repression of GD3S transcription. PMID:22470521

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

Mindfulness-Based Symptom and Stress Management Apps for Adults With Chronic Lung Disease: Systematic Search in App Stores.

PubMed

Owens, Otis L; Beer, Jenay M; Reyes, Ligia I; Gallerani, David G; Myhren-Bennett, Amanda R; McDonnell, Karen K

2018-05-15

Up to 70% of lung cancer survivors are affected by chronic obstructive pulmonary disease (COPD), a common, debilitating, comorbid disease. Lung cancer and COPD are both characterized by symptoms such as breathlessness, fatigue, and psychological distress. These distressing chronic symptoms are exacerbated by stress and detract from an individual's quality of life. The aim of this study was to identify and evaluate evidence-based, commercially available apps for promoting mindfulness-based strategies among adults with a COPD or lung cancer history (ie, chronic lung disease). For this review, an interdisciplinary research team used 19 keyword combinations in the search engines of Google and iOS app stores in May 2017. Evaluations were conducted on the apps' (1) content, (2) usability heuristics, (3) grade-level readability, and (4) cultural sensitivity. The search resulted in 768 apps (508 in iOS and 260 in Google stores). A total of 9 apps met the inclusion criteria and received further evaluation. Only 1 app had below an eighth-grade reading level; the ninth one did not have enough text to calculate a readability score. None of the 9 apps met the cultural sensitivity evaluation criteria. This systematic review identified critical design flaws that may affect the ease of using the apps in this study. Few mobile apps promote mindfulness-based strategies among adults with chronic lung disease (ie, COPD or lung cancer or both), but those that exist, overall, do not meet the latest scientific evidence. Recommendations include more stringent regulation of health-related apps, use of evidence-based frameworks and participatory design processes, following evidence-based usability practices, use of culturally sensitive language and images, and ensuring that content is written in plain language. ©Otis L Owens, Jenay M Beer, Ligia I Reyes, David G Gallerani, Amanda R Myhren-Bennett, Karen K McDonnell. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 15.05.2018.

Usability Testing of the BRANCH Smartphone App Designed to Reduce Harmful Drinking in Young Adults.

PubMed

Milward, Joanna; Deluca, Paolo; Drummond, Colin; Watson, Rod; Dunne, Jacklyn; Kimergård, Andreas

2017-08-08

Electronic screening and brief intervention (eSBI) apps demonstrate potential to reduce harmful drinking. However, low user engagement rates with eSBI reduce overall effectiveness of interventions. As "Digital Natives," young adults have high expectations of app quality. Ensuring that the design, content, and functionality of an eSBI app are acceptable to young adults is an integral stage to the development process. The objective of this study was to identify usability barriers and enablers for an app, BRANCH, targeting harmful drinking in young adults. The BRANCH app contains a drinking diary, alcohol reduction goal setting functions, normative drinking feedback, and information on risks and advice for cutting down. The app includes a social feature personalized to motivate cutting down and to promote engagement with a point-based system for usage. Three focus groups were conducted with 20 users who had tested the app for 1 week. A detailed thematic analysis was undertaken. The first theme, "Functionality" referred to how users wanted an easy-to-use interface, with minimum required user-input. Poor functionality was considered a major usability barrier. The second theme, "Design" described how an aesthetic with minimum text, clearly distinguishable tabs and buttons and appealing infographics was integral to the level of usability. The final theme, "Content" described how participants wanted all aspects of the app to be automatically personalized to them, as well as providing them with opportunities to personalize the app themselves, with increased options for social connectivity. There are high demands for apps such as BRANCH that target skilled technology users including young adults. Key areas to optimize eSBI app development that emerged from testing BRANCH with representative users include high-quality functionality, appealing aesthetics, and improved personalization. ©Joanna Milward, Paolo Deluca, Colin Drummond, Rod Watson, Jacklyn Dunne, Andreas Kimergård. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 08.08.2017.

Usability Testing of the BRANCH Smartphone App Designed to Reduce Harmful Drinking in Young Adults

PubMed Central

Deluca, Paolo; Drummond, Colin; Watson, Rod; Dunne, Jacklyn; Kimergård, Andreas

2017-01-01

Background Electronic screening and brief intervention (eSBI) apps demonstrate potential to reduce harmful drinking. However, low user engagement rates with eSBI reduce overall effectiveness of interventions. As “Digital Natives,” young adults have high expectations of app quality. Ensuring that the design, content, and functionality of an eSBI app are acceptable to young adults is an integral stage to the development process. Objective The objective of this study was to identify usability barriers and enablers for an app, BRANCH, targeting harmful drinking in young adults. Methods The BRANCH app contains a drinking diary, alcohol reduction goal setting functions, normative drinking feedback, and information on risks and advice for cutting down. The app includes a social feature personalized to motivate cutting down and to promote engagement with a point-based system for usage. Three focus groups were conducted with 20 users who had tested the app for 1 week. A detailed thematic analysis was undertaken. Results The first theme, “Functionality” referred to how users wanted an easy-to-use interface, with minimum required user-input. Poor functionality was considered a major usability barrier. The second theme, “Design” described how an aesthetic with minimum text, clearly distinguishable tabs and buttons and appealing infographics was integral to the level of usability. The final theme, “Content” described how participants wanted all aspects of the app to be automatically personalized to them, as well as providing them with opportunities to personalize the app themselves, with increased options for social connectivity. Conclusions There are high demands for apps such as BRANCH that target skilled technology users including young adults. Key areas to optimize eSBI app development that emerged from testing BRANCH with representative users include high-quality functionality, appealing aesthetics, and improved personalization. PMID:28790022

Tetrahydrohyperforin Inhibits the Proteolytic Processing of Amyloid Precursor Protein and Enhances Its Degradation by Atg5-Dependent Autophagy

PubMed Central

Muñoz, Vanessa C.; Yefi, Claudia P.; Bustamante, Hianara A.; Barraza, Rafael R.; Tapia-Rojas, Cheril; Otth, Carola; Barrera, María José; González, Carlos; Mardones, Gonzalo A.; Inestrosa, Nibaldo C.; Burgos, Patricia V.

2015-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) peptide. We have previously shown that the compound tetrahydrohyperforin (IDN5706) prevents accumulation of Aβ species in an in vivo model of AD, however the mechanism that explains this reduction is not well understood. We show herein that IDN5706 decreases the levels of ER degradation enhancer, mannosidase alpha-like 1 (EDEM1), a key chaperone related to endoplasmic-reticulum-associated degradation (ERAD). Moreover, we observed that low levels of EDEM1 correlated with a strong activation of autophagy, suggesting a crosstalk between these two pathways. We observed that IDN5706 perturbs the glycosylation and proteolytic processing of the amyloid precursor protein (APP), resulting in the accumulation of immature APP (iAPP) in the endoplasmic reticulum. To investigate the contribution of autophagy, we tested the effect of IDN5706 in Atg5-depleted cells. We found that depletion of Atg5 enhanced the accumulation of iAPP in response to IDN5706 by slowing down its degradation. Our findings reveal that IDN5706 promotes degradation of iAPP via the activation of Atg5-dependent autophagy, shedding light on the mechanism that may contribute to the reduction of Aβ production in vivo. PMID:26308941

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

Tetrahydrohyperforin Inhibits the Proteolytic Processing of Amyloid Precursor Protein and Enhances Its Degradation by Atg5-Dependent Autophagy.

PubMed

Cavieres, Viviana A; González, Alexis; Muñoz, Vanessa C; Yefi, Claudia P; Bustamante, Hianara A; Barraza, Rafael R; Tapia-Rojas, Cheril; Otth, Carola; Barrera, María José; González, Carlos; Mardones, Gonzalo A; Inestrosa, Nibaldo C; Burgos, Patricia V

2015-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) peptide. We have previously shown that the compound tetrahydrohyperforin (IDN5706) prevents accumulation of Aβ species in an in vivo model of AD, however the mechanism that explains this reduction is not well understood. We show herein that IDN5706 decreases the levels of ER degradation enhancer, mannosidase alpha-like 1 (EDEM1), a key chaperone related to endoplasmic-reticulum-associated degradation (ERAD). Moreover, we observed that low levels of EDEM1 correlated with a strong activation of autophagy, suggesting a crosstalk between these two pathways. We observed that IDN5706 perturbs the glycosylation and proteolytic processing of the amyloid precursor protein (APP), resulting in the accumulation of immature APP (iAPP) in the endoplasmic reticulum. To investigate the contribution of autophagy, we tested the effect of IDN5706 in Atg5-depleted cells. We found that depletion of Atg5 enhanced the accumulation of iAPP in response to IDN5706 by slowing down its degradation. Our findings reveal that IDN5706 promotes degradation of iAPP via the activation of Atg5-dependent autophagy, shedding light on the mechanism that may contribute to the reduction of Aβ production in vivo.

Nuclear 82-kDa choline acetyltransferase decreases amyloidogenic APP metabolism in neurons from APP/PS1 transgenic mice.

PubMed

Albers, Shawn; Inthathirath, Fatima; Gill, Sandeep K; Winick-Ng, Warren; Jaworski, Ewa; Wong, Daisy Y L; Gros, Robert; Rylett, R Jane

2014-09-01

Alzheimer disease (AD) is associated with increased amyloidogenic processing of amyloid precursor protein (APP) to β-amyloid peptides (Aβ), cholinergic neuron loss with decreased choline acetyltransferase (ChAT) activity, and cognitive dysfunction. Both 69-kDa ChAT and 82-kDa ChAT are expressed in cholinergic neurons in human brain and spinal cord with 82-kDa ChAT localized predominantly to neuronal nuclei, suggesting potential alternative functional roles for the enzyme. By gene microarray analysis, we found that 82-kDa ChAT-expressing IMR32 neural cells have altered expression of genes involved in diverse cellular functions. Importantly, genes for several proteins that regulate APP processing along amyloidogenic and non-amyloidogenic pathways are differentially expressed in 82-kDa ChAT-containing cells. The predicted net effect based on observed changes in expression patterns of these genes would be decreased amyloidogenic APP processing with decreased Aβ production. This functional outcome was verified experimentally as a significant decrease in BACE1 protein levels and activity and a concomitant reduction in the release of endogenous Aβ1-42 from neurons cultured from brains of AD-model APP/PS1 transgenic mice. The expression of 82-kDa ChAT in neurons increased levels of GGA3, which is involved in trafficking BACE1 to lysosomes for degradation. shRNA-induced decreases in GGA3 protein levels attenuated the 82-kDa ChAT-mediated decreases in BACE1 protein and activity and Aβ1-42 release. Evidence that 82-kDa ChAT can enhance GGA3 gene expression is shown by enhanced GGA3 gene promoter activity in SN56 neural cells expressing this ChAT protein. These studies indicate a novel relationship between cholinergic neurons and APP processing, with 82-kDa ChAT acting as a negative regulator of Aβ production. This decreased formation of Aβ could result in protection for cholinergic neurons, as well as protection of other cells in the vicinity that are sensitive to increased levels of Aβ. Decreasing levels of 82-kDa ChAT due to increasing age or neurodegeneration could alter the balance towards increasing Aβ production, with this potentiating the decline in function of cholinergic neurons. Copyright © 2014 Elsevier Inc. All rights reserved.

Quality of Mobile Phone and Tablet Mobile Apps for Speech Sound Disorders: Protocol for an Evidence-Based Appraisal

PubMed Central

Morris, Meg E; Erickson, Shane; Serry, Tanya A

2016-01-01

Background Although mobile apps are readily available for speech sound disorders (SSD), their validity has not been systematically evaluated. This evidence-based appraisal will critically review and synthesize current evidence on available therapy apps for use by children with SSD. Objective The main aims are to (1) identify the types of apps currently available for Android and iOS mobile phones and tablets, and (2) to critique their design features and content using a structured quality appraisal tool. Methods This protocol paper presents and justifies the methods used for a systematic review of mobile apps that provide intervention for use by children with SSD. The primary outcomes of interest are (1) engagement, (2) functionality, (3) aesthetics, (4) information quality, (5) subjective quality, and (6) perceived impact. Quality will be assessed by 2 certified practicing speech-language pathologists using a structured quality appraisal tool. Two app stores will be searched from the 2 largest operating platforms, Android and iOS. Systematic methods of knowledge synthesis shall include searching the app stores using a defined procedure, data extraction, and quality analysis. Results This search strategy shall enable us to determine how many SSD apps are available for Android and for iOS compatible mobile phones and tablets. It shall also identify the regions of the world responsible for the apps’ development, the content and the quality of offerings. Recommendations will be made for speech-language pathologists seeking to use mobile apps in their clinical practice. Conclusions This protocol provides a structured process for locating apps and appraising the quality, as the basis for evaluating their use in speech pathology for children in English-speaking nations. PMID:27899341

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

Development and Application of a Stepwise Assessment Process for Rational Redesign of Sequential Skills-Based Courses.

PubMed

Gallimore, Casey E; Porter, Andrea L; Barnett, Susanne G

2016-10-25

Objective. To develop and apply a stepwise process to assess achievement of course learning objectives related to advanced pharmacy practice experiences (APPEs) preparedness and inform redesign of sequential skills-based courses. Design. Four steps comprised the assessment and redesign process: (1) identify skills critical for APPE preparedness; (2) utilize focus groups and course evaluations to determine student competence in skill performance; (3) apply course mapping to identify course deficits contributing to suboptimal skill performance; and (4) initiate course redesign to target exposed deficits. Assessment. Focus group participants perceived students were least prepared for skills within the Accreditation Council for Pharmacy Education's pre-APPE core domains of Identification and Assessment of Drug-related Problems and General Communication Abilities. Course mapping identified gaps in instruction, performance, and assessment of skills within aforementioned domains. Conclusions. A stepwise process that identified strengths and weaknesses of a course, was used to facilitate structured course redesign. Strengths of the process included input and corroboration from both preceptors and students. Limitations included feedback from a small number of pharmacy preceptors and increased workload on course coordinators.

Microbial biosynthesis and secretion of l-malic acid and its applications.

PubMed

Chi, Zhe; Wang, Zhi-Peng; Wang, Guang-Yuan; Khan, Ibrar; Chi, Zhen-Ming

2016-01-01

l-Malic acid has many uses in food, beverage, pharmaceutical, chemical and medical industries. It can be produced by one-step fermentation, enzymatic transformation of fumaric acid to l-malate and acid hydrolysis of polymalic acid. However, the process for one-step fermentation is preferred as it has many advantages over any other process. The pathways of l-malic acid biosynthesis in microorganisms are partially clear and three metabolic pathways including non-oxidative pathway, oxidative pathway and glyoxylate cycle for the production of l-malic acid from glucose have been identified. Usually, high levels of l-malate are produced under the nitrogen starvation conditions, l-malate, as a calcium salt, is secreted from microbial cells and CaCO3 can play an important role in calcium malate biosynthesis and regulation. However, it is still unclear how it is secreted into the medium. To enhance l-malate biosynthesis and secretion by microbial cells, it is very important to study the mechanisms of l-malic acid biosynthesis and secretion at enzymatic and molecular levels.

Herpes Simplex Virus Dances with Amyloid Precursor Protein while Exiting the Cell

PubMed Central

Cheng, Shi-Bin; Ferland, Paulette; Webster, Paul; Bearer, Elaine L.

2011-01-01

Herpes simplex type 1 (HSV1) replicates in epithelial cells and secondarily enters local sensory neuronal processes, traveling retrograde to the neuronal nucleus to enter latency. Upon reawakening newly synthesized viral particles travel anterograde back to the epithelial cells of the lip, causing the recurrent cold sore. HSV1 co-purifies with amyloid precursor protein (APP), a cellular transmembrane glycoprotein and receptor for anterograde transport machinery that when proteolyzed produces A-beta, the major component of senile plaques. Here we focus on transport inside epithelial cells of newly synthesized virus during its transit to the cell surface. We hypothesize that HSV1 recruits cellular APP during transport. We explore this with quantitative immuno-fluorescence, immuno-gold electron-microscopy and live cell confocal imaging. After synchronous infection most nascent VP26-GFP-labeled viral particles in the cytoplasm co-localize with APP (72.8+/−6.7%) and travel together with APP inside living cells (81.1+/−28.9%). This interaction has functional consequences: HSV1 infection decreases the average velocity of APP particles (from 1.1+/−0.2 to 0.3+/−0.1 µm/s) and results in APP mal-distribution in infected cells, while interplay with APP-particles increases the frequency (from 10% to 81% motile) and velocity (from 0.3+/−0.1 to 0.4+/−0.1 µm/s) of VP26-GFP transport. In cells infected with HSV1 lacking the viral Fc receptor, gE, an envelope glycoprotein also involved in viral axonal transport, APP-capsid interactions are preserved while the distribution and dynamics of dual-label particles differ from wild-type by both immuno-fluorescence and live imaging. Knock-down of APP with siRNA eliminates APP staining, confirming specificity. Our results indicate that most intracellular HSV1 particles undergo frequent dynamic interplay with APP in a manner that facilitates viral transport and interferes with normal APP transport and distribution. Such dynamic interactions between APP and HSV1 suggest a mechanistic basis for the observed clinical relationship between HSV1 seropositivity and risk of Alzheimer's disease. PMID:21483850

A Self-Regulation Theory-Based Asthma Management Mobile App for Adolescents: A Usability Assessment.

PubMed

Sage, Adam; Roberts, Courtney; Geryk, Lorie; Sleath, Betsy; Tate, Deborah; Carpenter, Delesha

2017-02-01

Self-regulation theory suggests people learn to influence their own behavior through self-monitoring, goal-setting, feedback, self-reward, and self-instruction, all of which smartphones are now capable of facilitating. Several mobile apps exist to manage asthma; however, little evidence exists about whether these apps employ user-centered design processes that adhere to government usability guidelines for mobile apps. Building upon a previous study that documented adolescent preferences for an asthma self-management app, we employed a user-centered approach to assess the usability of a high-fidelity wireframe for an asthma self-management app intended for use by adolescents with persistent asthma. Individual interviews were conducted with adolescents (ages 11-18 years) with persistent asthma who owned a smartphone (N=8). Adolescents were asked to evaluate a PDF app wireframe consisting of 76 screen shots displaying app features, including log in and home screen, profile setup, settings and info, self-management features, and graphical displays for charting asthma control and medication. Preferences, comments, and suggestions for each set of screen shots were assessed using the audio-recorded interviews. Two coders reached consensus on adolescent evaluations of the following aspects of app features: (1) usability, (2) behavioral intentions to use, (3) confusing aspects, and (4) suggestions for improvement. The app wireframe was generally well received, and several suggestions for improvement were recorded. Suggestions included increased customization of charts and notifications, reminders, and alerts. Participants preferred longitudinal data about asthma control and medication use to be displayed using line graphs. All participants reported that they would find an asthma management app like the one depicted in the wireframe useful for managing their asthma. Early stage usability tests guided by government usability guidelines (usability.gov) revealed areas for improvement for an asthma self-management app for adolescents. Addressing these areas will be critical to developing an engaging and effective asthma self-management app that is capable of improving adolescent asthma outcomes. ©Adam Sage, Courtney Roberts, Lorie Geryk, Betsy Sleath, Deborah Tate, Delesha Carpenter. Originally published in JMIR Human Factors (http://humanfactors.jmir.org), 01.02.2017.

Ear2 deletion causes early memory and learning deficits in APP/PS1 mice.

PubMed

Kummer, Markus P; Hammerschmidt, Thea; Martinez, Ana; Terwel, Dick; Eichele, Gregor; Witten, Anika; Figura, Stefanie; Stoll, Monika; Schwartz, Stephanie; Pape, Hans-Christian; Schultze, Joachim L; Weinshenker, David; Heneka, Michael T; Urban, Inga

2014-06-25

To assess the consequences of locus ceruleus (LC) degeneration and subsequent noradrenaline (NA) deficiency in early Alzheimer's disease (AD), mice overexpressing mutant amyloid precursor protein and presenilin-1 (APP/PS1) were crossed with Ear2(-/-) mice that have a severe loss of LC neurons projecting to the hippocampus and neocortex. Testing spatial memory and hippocampal long-term potentiation revealed an impairment in APP/PS1 Ear2(-/-) mice, whereas APP/PS1 or Ear2(-/-) mice showed only minor changes. These deficits were associated with distinct synaptic changes including reduced expression of the NMDA 2A subunit and increased levels of NMDA receptor 2B in APP/PS1 Ear2(-/-) mice. Acute pharmacological replacement of NA by L-threo-DOPS partially restored phosphorylation of β-CaMKII and spatial memory performance in APP/PS1 Ear2(-/-) mice. These changes were not accompanied by altered APP processing or amyloid β peptide (Aβ) deposition. Thus, early LC degeneration and subsequent NA reduction may contribute to cognitive deficits via CaMKII and NMDA receptor dysfunction independent of Aβ and suggests that NA supplementation could be beneficial in treating AD. Copyright © 2014 the authors 0270-6474/14/348845-10$15.00/0.

[Possibilities of mobile applications for managing obesity according to professionals].

PubMed

Aguilar-Martínez, Alicia; Tort, Elena; Medina, F Xavier; Saigí-Rubió, Francesc

2015-01-01

Given the increasing use and importance of mobile telephone applications (apps) in the health setting, this study aimed to ascertain the views of health professionals involved in the treatment of obesity about their current needs and gaps in their requirements, their willingness to use mobile apps, and the features these devices should have for the treatment of obesity. A qualitative study was conducted through semi-structured interviews with experts treating obesity. The experts believed that apps could be useful to interact or deal with patients. However, their willingness to use apps contrasts with the current limited use of these devices. Practitioners felt that apps could partly compensate for the lack of daily contact between patients and professionals and could increase interaction with patients, achieving more favourable weight control results, especially with regard to improved adherence and motivation. In terms of the functionality and requirements of such apps, the main elements to be included were records of weight, physical activity and food consumption. Adding apps to the existing treatment of overweight and obesity still requires further definition of its functions. Additionally, further investigation is needed into both the role and involvement of professionals in the design process and during treatment. Copyright © 2015 SESPAS. Published by Elsevier Espana. All rights reserved.

A phonology-free mobile communication app.

PubMed

Kondapalli, Ananya; Zhang, Lee R; Patel, Shreya; Han, Xiao; Kim, Hee Jin; Li, Xintong; Altschuler, Eric L

2016-11-01

Aphasia - loss of comprehension or expression of language - is a devastating functional sequela of stroke. There are as yet no effective methods for rehabilitation of aphasia. An assistive device that allows aphasia patients to communicate and interact at speeds approaching real time is urgently needed. Behavioral and linguistic studies of aphasia patients show that they retain normal thinking processes and most aspects of language. They lack only phonology: the ability to translate (input) and/or output sounds (or written words) such as "ta-ble" into the image of a four-legged object with a top at which one works or eats. We have made a phonology-free communication mobile app that may be useful for patients with aphasia and other communication disorders. Particular innovations of our app include calling Google Images as a "subroutine" to allow a near-infinite number of choices (e.g. food or clothing items) for patients without having to make countless images, and by the use of animation for words, phrases or concepts that cannot be represented by a single image. We have tested our app successfully in one patient. The app may be of great benefit to patients with aphasia and other communication disorders. Implications for Rehabilitation We have made a phonology-free mobile communication app. This app may facilitate communication for patients with aphasia and other communication disorders.

More Stamina, a Gamified mHealth Solution for Persons with Multiple Sclerosis: Research Through Design.

PubMed

Giunti, Guido; Mylonopoulou, Vasiliki; Rivera Romero, Octavio

2018-03-02

Multiple sclerosis (MS) is one of the world's most common neurologic disorders. Fatigue is one of most common symptoms that persons with MS experience, having significant impact on their quality of life and limiting their activity levels. Self-management strategies are used to support them in the care of their health. Mobile health (mHealth) solutions are a way to offer persons with chronic conditions tools to successfully manage their symptoms and problems. Gamification is a current trend among mHealth apps used to create engaging user experiences and is suggested to be effective for behavioral change. To be effective, mHealth solutions need to be designed to specifically meet the intended audience needs. User-centered design (UCD) is a design philosophy that proposes placing end users' needs and characteristics in the center of design and development, involving users early in the different phases of the software life cycle. There is a current gap in mHealth apps for persons with MS, which presents an interesting area to explore. The purpose of this study was to describe the design and evaluation process of a gamified mHealth solution for behavioral change in persons with MS using UCD. Building on previous work of our team where we identified needs, barriers, and facilitators for mHealth apps for persons with MS, we followed UCD to design and evaluate a mobile app prototype aimed to help persons with MS self-manage their fatigue. Design decisions were evidence-driven and guided by behavioral change models (BCM). Usability was assessed through inspection methods using Nielsen's heuristic evaluation. The mHealth solution More Stamina was designed. It is a task organization tool designed to help persons with MS manage their energy to minimize the impact of fatigue in their day-to-day life. The tool acts as a to-do list where users can input tasks in a simple manner and assign Stamina Credits, a representation of perceived effort, to the task to help energy management and energy profiling. The app also features personalization and positive feedback. The design process gave way to relevant lessons to the design of a gamified behavioral change mHealth app such as the importance of metaphors in concept design, negotiate requirements with the BCM constructs, and tailoring of gamified experiences among others. Several usability problems were discovered during heuristic evaluation and guided the iterative design of our solution. In this paper, we designed an app targeted for helping persons with MS in their fatigue management needs. We illustrate how UCD can help in designing mHealth apps and the benefits and challenges that designers might face when using this approach. This paper provides insight into the design process of gamified behavioral change mHealth apps and the negotiation process implied in it. ©Guido Giunti, Vasiliki Mylonopoulou, Octavio Rivera Romero. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 02.03.2018.

More Stamina, a Gamified mHealth Solution for Persons with Multiple Sclerosis: Research Through Design

PubMed Central

Mylonopoulou, Vasiliki; Rivera Romero, Octavio

2018-01-01

Background Multiple sclerosis (MS) is one of the world’s most common neurologic disorders. Fatigue is one of most common symptoms that persons with MS experience, having significant impact on their quality of life and limiting their activity levels. Self-management strategies are used to support them in the care of their health. Mobile health (mHealth) solutions are a way to offer persons with chronic conditions tools to successfully manage their symptoms and problems. Gamification is a current trend among mHealth apps used to create engaging user experiences and is suggested to be effective for behavioral change. To be effective, mHealth solutions need to be designed to specifically meet the intended audience needs. User-centered design (UCD) is a design philosophy that proposes placing end users’ needs and characteristics in the center of design and development, involving users early in the different phases of the software life cycle. There is a current gap in mHealth apps for persons with MS, which presents an interesting area to explore. Objective The purpose of this study was to describe the design and evaluation process of a gamified mHealth solution for behavioral change in persons with MS using UCD. Methods Building on previous work of our team where we identified needs, barriers, and facilitators for mHealth apps for persons with MS, we followed UCD to design and evaluate a mobile app prototype aimed to help persons with MS self-manage their fatigue. Design decisions were evidence-driven and guided by behavioral change models (BCM). Usability was assessed through inspection methods using Nielsen’s heuristic evaluation. Results The mHealth solution More Stamina was designed. It is a task organization tool designed to help persons with MS manage their energy to minimize the impact of fatigue in their day-to-day life. The tool acts as a to-do list where users can input tasks in a simple manner and assign Stamina Credits, a representation of perceived effort, to the task to help energy management and energy profiling. The app also features personalization and positive feedback. The design process gave way to relevant lessons to the design of a gamified behavioral change mHealth app such as the importance of metaphors in concept design, negotiate requirements with the BCM constructs, and tailoring of gamified experiences among others. Several usability problems were discovered during heuristic evaluation and guided the iterative design of our solution. Conclusions In this paper, we designed an app targeted for helping persons with MS in their fatigue management needs. We illustrate how UCD can help in designing mHealth apps and the benefits and challenges that designers might face when using this approach. This paper provides insight into the design process of gamified behavioral change mHealth apps and the negotiation process implied in it. PMID:29500159

An App for the Cathedral in Freiberg--An Interdisciplinary Project Seminar

ERIC Educational Resources Information Center

Kröber, Cindy; Münster, Sander

2014-01-01

This project seminar aims at creating and evaluating a manual for interdisciplinary projects as part of a learning process. Working together, pedagogies and students from different disciplines assess tools and recommendations for successful collaborations while developing an app for the cathedral in Freiberg. As part of the project the students…

Mobile Apps for Weight Management: A Scoping Review.

PubMed

Rivera, Jordan; McPherson, Amy; Hamilton, Jill; Birken, Catherine; Coons, Michael; Iyer, Sindoora; Agarwal, Arnav; Lalloo, Chitra; Stinson, Jennifer

2016-07-26

Obesity remains a major public health concern. Mobile apps for weight loss/management are found to be effective for improving health outcomes in adults and adolescents, and are pursued as a cost-effective and scalable intervention for combating overweight and obesity. In recent years, the commercial market for 'weight loss apps' has expanded at rapid pace, yet little is known regarding the evidence-based quality of these tools for weight control. To characterize the inclusion of evidence-based strategies, health care expert involvement, and scientific evaluation of commercial mobile apps for weight loss/management. An electronic search was conducted between July 2014 and July 2015 of the official app stores for four major mobile operating systems. Three raters independently identified apps with a stated goal of weight loss/management, as well as weight loss/management apps targeted to pediatric users. All discrepancies regarding selection were resolved through discussion with a fourth rater. Metadata from all included apps were abstracted into a standard assessment criteria form and the evidence-based strategies, health care expert involvement, and scientific evaluation of included apps was assessed. Evidence-based strategies included: self-monitoring, goal-setting, physical activity support, healthy eating support, weight and/or health assessment, personalized feedback, motivational strategies, and social support. A total of 393 apps were included in this review. Self-monitoring was most common (139/393, 35.3%), followed by physical activity support (108/393, 27.5%), weight assessment (100/393, 25.4%), healthy eating support (91/393, 23.2%), goal-setting (84/393, 21.4%), motivational strategies (28/393, 7.1%), social support (21/393, 5.3%), and personalized feedback (7/393, 1.8%). Of apps, 0.8% (3/393) underwent scientific evaluation and 0.3% (1/393) reported health care expert involvement. No apps were comprehensive in the assessment criteria, with the majority of apps meeting less than two criteria. Commercial mobile apps for weight loss/management lack important evidence-based features, do not involve health care experts in their development process, and have not undergone rigorous scientific testing. This calls into question the validity of apps' claims regarding their effectiveness and safety, at a time when the availability and growth in adoption of these tools is rapidly increasing. Collaborative efforts between developers, researchers, clinicians, and patients are needed to develop and test high-quality, evidence-based mobile apps for weight loss/management before they are widely disseminated in commercial markets.

APP with Kunitz type protease inhibitor domain (KPI) correlates with neuritic plaque density but not with cortical synaptophysin immunoreactivity in Alzheimer's disease and non-demented aged subjects: a multifactorial analysis.

PubMed

Zhan, S S; Sandbrink, R; Beyreuther, K; Schmitt, H P

1995-01-01

The formation of beta A4 amyloid protein in neuritic plaques in Alzheimer's disease (AD) and advanced age is a complex process that involves a number of both cellular and molecular mechanisms, the interrelations of which are not yet completely understood. We have examined quantitatively, in AD and aged controls an extended spectrum of amyloid plaque-related cellular and molecular factors and the cortical synaptophysin immunoreactivity (synaptic density) in order to check for interrelations between them by multifactorial analysis. In 3 cases of senile dementia of the Alzheimer type (SDAT) aged 72, 80 and 82 years, and 9 controls aged 43-88 (mean age 65) years, the cortical synaptophysin immunoreactivity was assessed, together with the numbers of neurons, astrocytes and microglial cells, senile plaques, of tangle-bearing neurons, and the amount of beta A4 amyloid precursor protein (APP) with and without the Kunitz type serine protease inhibitor (KPI) domain. The main results were: APP including the KPI domain (KPI-APP) correlated with the number of neuritic plaques, regardless of whether they occurred in SDAT or non-demented controls. There was no significant difference in the amount of KPI-APP between SDAT and controls. Conversely, APP695 (without KPI) was significantly reduced in SDAT. KPI-APP did not correlate with the synaptophysin immunoreactivity (RGVA), while APP695 showed a significant correlation with the latter in all evaluations. It also correlated with the neuron counts, which was not true for KPI-APP. These results support previous findings indicating that KPI-APP is an important local factor for amyloid deposition in the neuritic plaques, both in AD and in non-demented aged people. On the contrary, KPI-APP does not seem to be significantly involved in the mechanisms of synaptic change outside of the plaques.

Development and testing of a mobile application to support diabetes self-management for people with newly diagnosed type 2 diabetes: a design thinking case study.

PubMed

Petersen, Mira; Hempler, Nana F

2017-06-26

Numerous mobile applications have been developed to support diabetes-self-management. However, the majority of these applications lack a theoretical foundation and the involvement of people with diabetes during development. The aim of this study was to develop and test a mobile application (app) supporting diabetes self-management among people with newly diagnosed type 2 diabetes using design thinking. The app was developed and tested in 2015 using a design-based research approach involving target users (individuals newly diagnosed with type 2 diabetes), research scientists, healthcare professionals, designers, and app developers. The research approach comprised three major phases: inspiration, ideation, and implementation. The first phase included observations of diabetes education and 12 in-depth interviews with users regarding challenges and needs related to living with diabetes. The ideation phrase consisted of four interactive workshops with users focusing on app needs, in which ideas were developed and prioritized. Finally, 14 users tested the app over 4 weeks; they were interviewed about usability and perceptions about the app as a support tool. A multifunctional app was useful for people with newly diagnosed type 2 diabetes. The final app comprised five major functions: overview of diabetes activities after diagnosis, recording of health data, reflection games and goal setting, knowledge games and recording of psychological data such as sleep, fatigue, and well-being. Users found the app to be a valuable tool for support, particularly for raising their awareness about their psychological health and for informing and guiding them through the healthcare system after diagnosis. The design thinking processes used in the development and implementation of the mobile health app were crucial to creating value for users. More attention should be paid to the training of professionals who introduce health apps. Danish Data Protection Agency: 2012-58-0004. Registered 6 February 2016.

Functionalization of nanomaterials by non-thermal large area atmospheric pressure plasmas: application to flexible dye-sensitized solar cells.

PubMed

Jung, Heesoo; Park, Jaeyoung; Yoo, Eun Sang; Han, Gill-Sang; Jung, Hyun Suk; Ko, Min Jae; Park, Sanghoo; Choe, Wonho

2013-09-07

A key challenge to the industrial application of nanotechnology is the development of fabrication processes for functional devices based on nanomaterials which can be scaled up for mass production. In this report, we disclose the results of non-thermal radio-frequency (rf) atmospheric pressure plasma (APP) based deposition of TiO2 nanoparticles on a flexible substrate for the fabrication of dye-sensitized solar cells (DSSCs). Operating at 190 °C without a vacuum enclosure, the APP method can avoid thermal damage and vacuum compatibility restrictions and utilize roll-to-roll processing over a large area. The various analyses of the TiO2 films demonstrate that superior film properties can be obtained by the non-thermal APP method when compared with the thermal sintering process operating at 450 °C. The crystallinity of the anatase TiO2 nanoparticles is significantly improved without thermal agglomeration, while the surface defects such as Ti(3+) ions are eliminated, thus providing efficient charge collecting properties for solar cells. Finally, we successfully fabricated a flexible DSSC with an energy conversion efficiency of 4.2% using a transparent plastic substrate. This work demonstrates the potential of non-thermal APP technology in the area of device-level, nano-enabled material manufacturing.

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

Long-Term Mangiferin Extract Treatment Improves Central Pathology and Cognitive Deficits in APP/PS1 Mice.

PubMed

Infante-Garcia, Carmen; Ramos-Rodriguez, Juan Jose; Delgado-Olmos, Irene; Gamero-Carrasco, Carlos; Fernandez-Ponce, Maria Teresa; Casas, Lourdes; Mantell, Casimiro; Garcia-Alloza, Monica

2017-08-01

Alzheimer's disease (AD) is the most common cause of dementia; however, available treatments have had limited success. Therefore AD patients are in tremendous need of new pharmacological approaches that may delay or slow the progression of the disease. In addition to the classical neuropathological features, immunological and inflammatory processes are also involved in AD pathogenesis. Naturally occurring compounds, such as Mangifera indica Linn (MGF) extracts have previously been shown to significantly reduce peripheral inflammatory processes. In order to explore the role of MGF in AD central pathology, we have orally treated APP/PS1 mice for 22 weeks. While MGF did not affect amyloid pathology, tau hyperphosphorylation was significantly reduced in the cortex and hippocampus. Also, inflammatory processes, measured by microglia and astrocyte burdens, were diminished in MGF-treated mice. Moreover, neuronal morphological alterations, such as abnormal neurite curvature and dystrophies, highly increased in APP/PS1 mice, were significantly ameliorated by long-term MGF treatment. Reduction of all these pathological features were accompanied by compelling improvements of episodic and spatial memory in APP/PS1 mice treated with MGF. Altogether our data suggest that MGF may provide a useful tool to target different aspects of AD pathology and could lead to more effective future therapeutic or preventive strategies.

The pattern of trabecular bone microarchitecture in the distal femur of typically developing children and its effect on processing of magnetic resonance images.

PubMed

Modlesky, Christopher M; Whitney, Daniel G; Carter, Patrick T; Allerton, Brianne M; Kirby, Joshua T; Miller, Freeman

2014-03-01

Magnetic resonance imaging (MRI) is used to assess trabecular bone microarchitecture in humans; however, image processing can be labor intensive and time consuming. One aim of this study was to determine the pattern of trabecular bone microarchitecture in the distal femur of typically developing children. A second aim was to determine the proportion and location of magnetic resonance images that need to be processed to yield representative estimates of trabecular bone microarchitecture. Twenty-six high resolution magnetic resonance images were collected immediately above the growth plate in the distal femur of 6-12year-old typically developing children (n=40). Measures of trabecular bone microarchitecture [i.e., apparent trabecular bone volume to total volume (appBV/TV), trabecular number (appTb.N), trabecular thickness (appTb.Th) and trabecular separation (appTb.Sp)] in the lateral aspect of the distal femur were determined using the twenty most central images (20IM). The average values for appBV/TV, appTb.N, appTb.Th and appTb.Sp from 20IM were compared to the average values from 10 images (10IM), 5 images (5IM) and 3 images (3IM) equally dispersed throughout the total image set and one image (1IM) from the center of the total image set using linear regression analysis. The resulting mathematical models were cross-validated using the leave-one-out technique. Distance from the growth plate was strongly and inversely related to appBV/TV (r(2)=0.68, p<0.001) and appTb.N (r(2)=0.92, p<0.001) and was strongly and positively related to appTb.Sp (r(2)=0.86, p<0.001). The relationship between distance from the growth plate and appTb.Th was not linear (r(2)=0.06, p=0.28), but instead it was quadratic and statistically significant (r(2)=0.54, p<0.001). Trabecular bone microarchitecture estimates from 10IM, 5IM, 3IM and 1IM were not different from estimates from 20IM (p>0.05). However, there was a progressive decrease in the strength of the relationships as a smaller proportion of images were used to predict estimates from 20IM (r(2)=0.98 to 0.99 using 10IM, 0.94 to 0.96 using 5IM, 0.87 to 0.90 using 3IM and 0.66 to 0.72 using 1IM; all p<0.001). Using the resulting mathematical models and the leave-one-out cross-validation analysis, measures of trabecular bone microarchitecture estimated from the 10IM and 5IM partial image sets agreed extremely well with estimates from 20IM. The findings indicate that partial magnetic resonance image sets can be used to provide reasonable estimates of trabecular bone microarchitecture status in the distal femur of typically developing children. However, because the relative amount of trabecular bone in the distal femur decreases with distance from the growth plate due to a decrease in trabecular number, careful positioning of the region of interest and sampling from throughout the region of interest is necessary. Copyright © 2013 Elsevier Inc. All rights reserved.

Smartphone Applications for Educating and Helping Non-motivating Patients Adhere to Medication That Treats Mental Health Conditions: Aims and Functioning.

PubMed

Kassianos, Angelos P; Georgiou, Giorgos; Papaconstantinou, Electra P; Detzortzi, Angeliki; Horne, Rob

2017-01-01

Background: Patients prescribed with medication that treats mental health conditions benefit the most compared to those prescribed with other types of medication. However, they are also the most difficult to adhere. The development of mobile health (mHealth) applications ("apps") to help patients monitor their adherence is fast growing but with limited evidence on their efficacy. There is no evidence on the content of these apps for patients taking psychotropic medication. The aim of this study is to identify and evaluate the aims and functioning of available apps that are aiming to help and educate patients to adhere to medication that treats mental health conditions. Method: Three platform descriptions (Apple, Google, and Microsoft) were searched between October 2015 and February 2016. Included apps need to focus on adherence to medication that treats mental health conditions and use at least a reinforcement strategy. Descriptive information was extracted and apps evaluated on a number of assessment criteria using content analysis. Results: Sixteen apps were identified. All apps included self-monitoring properties like reminders and psycho-educational properties like mood logs. It was unclear how the latter were used or how adherence was measured. Major barriers to medication adherence like patients' illness and medication beliefs and attitudes were not considered nor where information to patients about mediation side effects. Very few apps were tailored and none was developed based on established theories explaining the processes for successful medication adherence like cognitions and beliefs. Reported information on app development and validation was poor. Discussion: A variety of apps with different properties that tackle both intentional and unintentional non-adherence from a different perspective are identified. An evidence-based approach and co-creation with patients is needed. This will ensure that the apps increase the possibility to impact on non-adherence. Theories like social cognition models can be useful in ensuring that patients' education, motivation, skills, beliefs, and type of adherence are taken into consideration when developing the apps. Findings from this study can help clinicians and patients make informed choices and pursue policy-makers to integrate evidence when developing future apps. Quality-assurance tools are needed to ensure the apps are systematically evaluated.

A Smartphone App to Promote an Active Lifestyle in Lower-Educated Working Young Adults: Development, Usability, Acceptability, and Feasibility Study.

PubMed

Simons, Dorien; De Bourdeaudhuij, Ilse; Clarys, Peter; De Cocker, Katrien; Vandelanotte, Corneel; Deforche, Benedicte

2018-02-20

Physical activity (PA) levels are problematic in lower-educated working young adults (18-26 years). To promote PA, smartphone apps have great potential, but there is no evidence for their effectiveness in this population. To increase the likelihood that a newly developed app will be effective, formative research and user testing are required. The aim of this study was to describe the development, usability, acceptability, and feasibility of a new theory- and evidence-based smartphone app to promote an active lifestyle in lower-educated working young adults. The new app was developed by applying 4 steps. First, determinants important to promote an active lifestyle in this population were selected. Second, evidence-based behavior change techniques were selected to convert the determinants into practical applications. Third, a new smartphone app was developed. Fourth, volunteers (n=11, both lower and higher educated) tested the app on usability, and lower-educated working young adults (n=16) tested its acceptability and feasibility via (think aloud) interviews, a questionnaire, and Google Analytics. The app was accordingly adapted for the final version. A new Android app, Active Coach, was developed that focused on knowledge, attitude, social support, and self-efficacy (based on outcomes from step 1), and that applied self-regulation techniques (based on outcomes from step 2). The app consists of a 9-week program with personal goals, practical tips, and scientific facts to encourage an active lifestyle. To ensure all-day and automatic self-monitoring of the activity behavior, the Active Coach app works in combination with a wearable activity tracker, the Fitbit Charge. Issues detected by the usability test (eg, text errors, wrong messages) were all fixed. The acceptability and feasibility test showed that participants found the app clear, understandable, and motivating, although some aspects needed to be more personal. By applying a stepwise, user-centered approach that regularly consulted the target group, the new app is adapted to their specific needs and preferences. The Active Coach app was overall positively evaluated by the lower-educated working young adults at the end of the development process. ©Dorien Simons, Ilse De Bourdeaudhuij, Peter Clarys, Katrien De Cocker, Corneel Vandelanotte, Benedicte Deforche. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 20.02.2018.

Genetically Augmenting Aβ42 Levels in Skeletal Muscle Exacerbates Inclusion Body Myositis-Like Pathology and Motor Deficits in Transgenic Mice

PubMed Central

Kitazawa, Masashi; Green, Kim N.; Caccamo, Antonella; LaFerla, Frank M.

2006-01-01

The pathogenic basis of inclusion body myositis (IBM), the leading muscle degenerative disease afflicting the elderly, is unknown, although the histopathological features are remarkably similar to those observed in Alzheimer’s disease. One leading hypothesis is that the buildup of amyloid-β (Aβ) peptide within selective skeletal muscle fibers contributes to the degenerative phenotype. Aβ is a small peptide derived via endoproteolysis of the amyloid precursor protein (APP). To determine the pathogenic effect of augmenting Aβ42 levels in skeletal muscle, we used a genetic approach to replace the endogenous wild-type presenilin-1 (PS1) allele with the PS1M146V allele in MCK-APP mice. Although APP transgene expression was unaltered, Aβ levels, particularly Aβ42, were elevated in skeletal muscle of the double transgenic (MCK-APP/PS1) mice compared to the parental MCK-APP line. Elevated phospho-tau accumulation was found in the MCK-APP/PS1 mice, and the greater activation of GSK-3β and cdk5 were observed. Other IBM-like pathological features, such as inclusion bodies and inflammatory infiltrates, were more severe and prominent in the MCK-APP/PS1 mice. Motor coordination and balance were more adversely affected and manifested at an earlier age in the MCK-APP/PS1 mice. The data presented here provide experimental evidence that Aβ42 plays a proximal and critical role in the muscle degenerative process. PMID:16723713

Cocreated Smartphone App to Improve the Quality of Life of Adolescents and Young Adults with Cancer (Kræftværket): Protocol for a Quantitative and Qualitative Evaluation

PubMed Central

Elsbernd, Abbey; Hjerming, Maiken; Visler, Camilla; Hjalgrim, Lisa Lyngsie; Niemann, Carsten Utoft; Boisen, Kirsten

2018-01-01

Background Adolescents and young adults with cancer face significant challenges during the course of their medical treatment and recovery from illness. Many adolescents and young adults struggle with long-term complications in the physical, psychosocial, economic, and academic domains. Mobile health (mHealth) interventions provide an innovative platform for delivering supportive care, particularly through the utilization of apps on smartphones and tablets. To create a successful mHealth intervention for adolescents and young adults, youth input and feedback is essential. The process of cocreation, in which the target app user has a direct role in dictating design and function, was utilized to create the prototype smartphone app for adolescents and young adults with cancer, “Kræftværket.” Objective The objective of this paper is to describe the protocol for the evaluation of the Kræftværket app, a prototype app designed via cocreation, to support and improve health-related quality of life for adolescents and young adults with cancer. Methods The Kræftværket app has three primary features, (1) a symptom and activity diary, (2) a supportive communication network between app users, and (3) a “one-stop shop” information bank with practical information as well as links to patient organizations and other resources. The app will be evaluated in two phases, a pilot test and an implementation test. In the pilot test, the app will be launched to a test group of 20 adolescents and young adults aged 15 to 29 years, selected for equal representation amongst age group and treatment status. Patients will be allowed to utilize the app over the course of six weeks and will complete a baseline and follow-up European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) health-related quality of life inventory. In addition, participant focus group interviews will be conducted according to a semistructured interview guide. Resulting data will be analyzed using thematic analysis. Results and appropriate analysis from both the qualitative and quantitative branches of the pilot test will be discussed amongst the research group, and appropriate changes based on user feedback will be made to the app before the final project phase. In the implementation test, the app will be provided and utilized by a sample of 50 adolescents and young adults aged 15-29 years selected for equal representation amongst gender, age group, diagnosis, and treatment status over the course of 3 months. Participants will be asked to complete a baseline and follow-up EORTC QLQ-C30 HRQoL inventory. Results Pilot testing is expected to take place in February 2018, and implementation testing is expected to begin May 2018. Conclusions It is the hope that Kræftværket app will serve as a beneficial and easily utilized product. The process of evaluating the app and its effect on quality of life will address the absence of evidence-based mHealth interventions, and attempt to validate new approaches to benefitting adolescents and young adult oncology patients in the digital world. Registered Report Identifier RR1-10.2196/10098 PMID:29748162

Cocreated Smartphone App to Improve the Quality of Life of Adolescents and Young Adults with Cancer (Kræftværket): Protocol for a Quantitative and Qualitative Evaluation.

PubMed

Elsbernd, Abbey; Hjerming, Maiken; Visler, Camilla; Hjalgrim, Lisa Lyngsie; Niemann, Carsten Utoft; Boisen, Kirsten; Pappot, Helle

2018-05-10

Adolescents and young adults with cancer face significant challenges during the course of their medical treatment and recovery from illness. Many adolescents and young adults struggle with long-term complications in the physical, psychosocial, economic, and academic domains. Mobile health (mHealth) interventions provide an innovative platform for delivering supportive care, particularly through the utilization of apps on smartphones and tablets. To create a successful mHealth intervention for adolescents and young adults, youth input and feedback is essential. The process of cocreation, in which the target app user has a direct role in dictating design and function, was utilized to create the prototype smartphone app for adolescents and young adults with cancer, "Kræftværket." The objective of this paper is to describe the protocol for the evaluation of the Kræftværket app, a prototype app designed via cocreation, to support and improve health-related quality of life for adolescents and young adults with cancer. The Kræftværket app has three primary features, (1) a symptom and activity diary, (2) a supportive communication network between app users, and (3) a "one-stop shop" information bank with practical information as well as links to patient organizations and other resources. The app will be evaluated in two phases, a pilot test and an implementation test. In the pilot test, the app will be launched to a test group of 20 adolescents and young adults aged 15 to 29 years, selected for equal representation amongst age group and treatment status. Patients will be allowed to utilize the app over the course of six weeks and will complete a baseline and follow-up European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) health-related quality of life inventory. In addition, participant focus group interviews will be conducted according to a semistructured interview guide. Resulting data will be analyzed using thematic analysis. Results and appropriate analysis from both the qualitative and quantitative branches of the pilot test will be discussed amongst the research group, and appropriate changes based on user feedback will be made to the app before the final project phase. In the implementation test, the app will be provided and utilized by a sample of 50 adolescents and young adults aged 15-29 years selected for equal representation amongst gender, age group, diagnosis, and treatment status over the course of 3 months. Participants will be asked to complete a baseline and follow-up EORTC QLQ-C30 HRQoL inventory. Pilot testing is expected to take place in February 2018, and implementation testing is expected to begin May 2018. It is the hope that Kræftværket app will serve as a beneficial and easily utilized product. The process of evaluating the app and its effect on quality of life will address the absence of evidence-based mHealth interventions, and attempt to validate new approaches to benefitting adolescents and young adult oncology patients in the digital world. RR1-10.2196/10098. ©Abbey Elsbernd, Maiken Hjerming, Camilla Visler, Lisa Lyngsie Hjalgrim, Carsten Utoft Niemann, Kirsten Boisen, Helle Pappot. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 10.05.2018.

Effect of Time-Dependent Sorption on the Dissipation of Water-Extractable Pesticides in Soils.

PubMed

Motoki, Yutaka; Iwafune, Takashi; Seike, Nobuyasu; Inao, Keiya; Otani, Takashi

2016-06-08

The dissipation behavior of water-extractable pesticides in soils is important when assessing the phytoavailability of pesticides in soils. This process is less understood than pesticide extraction with organic solvents. To elucidate the dissipation behavior of water-extractable pesticides in soils, we conducted an incubation study using 27 pesticides and five Japanese soils. The rate of decrease of the level of pesticides in water extracts was faster in soils than that of total extracts (water extracts and acetone extracts). This suggests that time-dependent sorption contributed to the difference in the dissipation between the pesticides in water and total extracts from soils. Increased apparent sorption coefficients (Kd,app) with time were positively and significantly correlated with Kd,app values of a 0 day incubation [Kd,app(t0)]. This empirical relationship suggests that Kd,app(t0) values can predict the time-dependent increase in Kd,app and the dissipation of water-extractable pesticides in soils.

Intracellular APP Domain Regulates Serine-Palmitoyl-CoA Transferase Expression and Is Affected in Alzheimer's Disease

PubMed Central

Grimm, Marcus O. W.; Grösgen, Sven; Rothhaar, Tatjana L.; Burg, Verena K.; Hundsdörfer, Benjamin; Haupenthal, Viola J.; Friess, Petra; Müller, Ulrike; Fassbender, Klaus; Riemenschneider, Matthias; Grimm, Heike S.; Hartmann, Tobias

2011-01-01

Lipids play an important role as risk or protective factors in Alzheimer's disease (AD), a disease biochemically characterized by the accumulation of amyloid beta peptides (Aβ), released by proteolytic processing of the amyloid precursor protein (APP). Changes in sphingolipid metabolism have been associated to the development of AD. The key enzyme in sphingolipid de novo synthesis is serine-palmitoyl-CoA transferase (SPT). In the present study we identified a new physiological function of APP in sphingolipid synthesis. The APP intracellular domain (AICD) was found to decrease the expression of the SPT subunit SPTLC2, the catalytic subunit of the SPT heterodimer, resulting in that decreased SPT activity. AICD function was dependent on Fe65 and SPTLC2 levels are increased in APP knock-in mice missing a functional AICD domain. SPTLC2 levels are also increased in familial and sporadic AD postmortem brains, suggesting that SPT is involved in AD pathology. PMID:21660213

Chinese Cardiovascular Disease Mobile Apps’ Information Types, Information Quality, and Interactive Functions for Self-Management: Systematic Review

PubMed Central

Xie, Bo; Su, Zhaohui; Zhang, Wenhui

2017-01-01

Background 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. Objective 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. Methods 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. Results 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. Conclusions 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. PMID:29242176

The Possible Mechanism of Advanced Glycation End Products (AGEs) for Alzheimer’s Disease

PubMed Central

Ko, Shun-Yao; Ko, Hshin-An; Chu, Kuo-Hsiung; Shieh, Tzong-Ming; Chi, Tzong-Cherng; Chen, Hong-I; Chang, Weng-Cheng; Chang, Shu-Shing

2015-01-01

Amyloid precursor protein (APP) has been modified by β and γ-secretase that cause amyloid deposits (plaques) in neuronal cells. Glyceraldhyde-derived AGEs has been identified as a major source of neurotoxicity in Alzheimer’s disease (AD). In a previous study, we demonstrated that glyceraldehyde-derived AGEs increase APP and Aβ via ROS. Furthermore, the combination of AGEs and Aβ has been shown to enhance neurotoxicity. In mice, APP expression is increased by tail vein injection of AGEs. This evidence suggests a correlation between AGEs and the development of AD. However, the role played by AGEs in the pathogenesis of AD remains unclear. In this report, we demonstrate that AGEs up-regulate APP processing protein (BACE and PS1) and Sirt1 expression via ROS, but do not affect the expression of downstream antioxidant genes HO-1 and NQO-1. Moreover, we found that AGEs increase GRP78 expression and enhance the cell death-related pathway p53, bcl-2/bax ratio, caspase 3. These results indicate that AGEs impair the neuroprotective effects of Sirt1 and lead to neuronal cell death via ER stress. Our findings suggest that AGEs increase ROS production, which stimulates downstream pathways related to APP processing, Aβ production, Sirt1, and GRP78, resulting in the up-regulation of cell death related pathway. This in-turn enhances neuronal cell death, which leads to the development of AD. PMID:26587989

The Possible Mechanism of Advanced Glycation End Products (AGEs) for Alzheimer's Disease.

PubMed

Ko, Shun-Yao; Ko, Hshin-An; Chu, Kuo-Hsiung; Shieh, Tzong-Ming; Chi, Tzong-Cherng; Chen, Hong-I; Chang, Weng-Cheng; Chang, Shu-Shing

2015-01-01

Amyloid precursor protein (APP) has been modified by β and γ-secretase that cause amyloid deposits (plaques) in neuronal cells. Glyceraldhyde-derived AGEs has been identified as a major source of neurotoxicity in Alzheimer's disease (AD). In a previous study, we demonstrated that glyceraldehyde-derived AGEs increase APP and Aβ via ROS. Furthermore, the combination of AGEs and Aβ has been shown to enhance neurotoxicity. In mice, APP expression is increased by tail vein injection of AGEs. This evidence suggests a correlation between AGEs and the development of AD. However, the role played by AGEs in the pathogenesis of AD remains unclear. In this report, we demonstrate that AGEs up-regulate APP processing protein (BACE and PS1) and Sirt1 expression via ROS, but do not affect the expression of downstream antioxidant genes HO-1 and NQO-1. Moreover, we found that AGEs increase GRP78 expression and enhance the cell death-related pathway p53, bcl-2/bax ratio, caspase 3. These results indicate that AGEs impair the neuroprotective effects of Sirt1 and lead to neuronal cell death via ER stress. Our findings suggest that AGEs increase ROS production, which stimulates downstream pathways related to APP processing, Aβ production, Sirt1, and GRP78, resulting in the up-regulation of cell death related pathway. This in-turn enhances neuronal cell death, which leads to the development of AD.

Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease

PubMed Central

Grimm, Marcus O. W.; Haupenthal, Viola J.; Rothhaar, Tatjana L.; Zimmer, Valerie C.; Grösgen, Sven; Hundsdörfer, Benjamin; Lehmann, Johannes; Grimm, Heike S.; Hartmann, Tobias

2013-01-01

Alzheimer’s disease (AD) is characterized by extracellular accumulation of amyloid-β peptide (Aβ), generated by proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. Aβ generation is inhibited when the initial ectodomain shedding is caused by α-secretase, cleaving APP within the Aβ domain. Therefore, an increase in α-secretase activity is an attractive therapeutic target for AD treatment. APP and the APP-cleaving secretases are all transmembrane proteins, thus local membrane lipid composition is proposed to influence APP processing. Although several studies have focused on γ-secretase, the effect of the membrane lipid microenvironment on α-secretase is poorly understood. In the present study, we systematically investigated the effect of fatty acid (FA) acyl chain length (10:0, 12:0, 14:0, 16:0, 18:0, 20:0, 22:0, 24:0), membrane polar lipid headgroup (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine), saturation grade and the FA double-bond position on α-secretase activity. We found that α-secretase activity is significantly elevated in the presence of FAs with short chain length and in the presence of polyunsaturated FAs, whereas variations in the phospholipid headgroups, as well as the double-bond position, have little or no effect on α-secretase activity. Overall, our study shows that local lipid membrane composition can influence α-secretase activity and might have beneficial effects for AD. PMID:23485990

Enhance wound healing monitoring through a thermal imaging based smartphone app

NASA Astrophysics Data System (ADS)

Yi, Steven; Lu, Minta; Yee, Adam; Harmon, John; Meng, Frank; Hinduja, Saurabh

2018-03-01

In this paper, we present a thermal imaging based app to augment traditional appearance based wound growth monitoring. Accurate diagnose and track of wound healing enables physicians to effectively assess, document, and individualize the treatment plan given to each wound patient. Currently, wounds are primarily examined by physicians through visual appearance and wound area. However, visual information alone cannot present a complete picture on a wound's condition. In this paper, we use a smartphone attached thermal imager and evaluate its effectiveness on augmenting visual appearance based wound diagnosis. Instead of only monitoring wound temperature changes on a wound, our app presents physicians a comprehensive measurements including relative temperature, wound healing thermal index, and wound blood flow. Through the rat wound experiments and by monitoring the integrated thermal measurements over 3 weeks of time frame, our app is able to show the underlying healing process through the blood flow. The implied significance of our app design and experiment includes: (a) It is possible to use a low cost smartphone attached thermal imager for added value on wound assessment, tracking, and treatment; and (b) Thermal mobile app can be used for remote wound healing assessment for mobile health based solution.

Organizing a Community Advanced Pharmacy Practice Experience

PubMed Central

Koenigsfeld, Carrie Foust; Tice, Angela L

2006-01-01

Setting up a community advanced pharmacy practice experience can be an overwhelming task for many pharmacy preceptors. This article provides guidance to pharmacist preceptors in developing a complete and effective community advanced pharmacy practice experience (APPE). When preparing for the APPE, initial discussions with the college or school of pharmacy are key. Benefits, training, and requirements should be addressed. Site preparation, including staff education, will assist in the development process. The preceptor should plan orientation day activities and determine appropriate evaluation and feedback methods. With thorough preparation, the APPE will be rewarding for both the student and the pharmacy site. PMID:17136163

Organizing a community advanced pharmacy practice experience.

PubMed

Koenigsfeld, Carrie Foust; Tice, Angela L

2006-02-15

Setting up a community advanced pharmacy practice experience can be an overwhelming task for many pharmacy preceptors. This article provides guidance to pharmacist preceptors in developing a complete and effective community advanced pharmacy practice experience (APPE). When preparing for the APPE, initial discussions with the college or school of pharmacy are key. Benefits, training, and requirements should be addressed. Site preparation, including staff education, will assist in the development process. The preceptor should plan orientation day activities and determine appropriate evaluation and feedback methods. With thorough preparation, the APPE will be rewarding for both the student and the pharmacy site.

Suppression of amyloid beta A11 antibody immunoreactivity by vitamin C: possible role of heparan sulfate oligosaccharides derived from glypican-1 by ascorbate-induced, nitric oxide (NO)-catalyzed degradation.

PubMed

Cheng, Fang; Cappai, Roberto; Ciccotosto, Giuseppe D; Svensson, Gabriel; Multhaup, Gerd; Fransson, Lars-Åke; Mani, Katrin

2011-08-05

Amyloid β (Aβ) is generated from the copper- and heparan sulfate (HS)-binding amyloid precursor protein (APP) by proteolytic processing. APP supports S-nitrosylation of the HS proteoglycan glypican-1 (Gpc-1). In the presence of ascorbate, there is NO-catalyzed release of anhydromannose (anMan)-containing oligosaccharides from Gpc-1-nitrosothiol. We investigated whether these oligosaccharides interact with Aβ during APP processing and plaque formation. anMan immunoreactivity was detected in amyloid plaques of Alzheimer (AD) and APP transgenic (Tg2576) mouse brains by immunofluorescence microscopy. APP/APP degradation products detected by antibodies to the C terminus of APP, but not Aβ oligomers detected by the anti-Aβ A11 antibody, colocalized with anMan immunoreactivity in Tg2576 fibroblasts. A 50-55-kDa anionic, sodium dodecyl sulfate-stable, anMan- and Aβ-immunoreactive species was obtained from Tg2576 fibroblasts using immunoprecipitation with anti-APP (C terminus). anMan-containing HS oligo- and disaccharide preparations modulated or suppressed A11 immunoreactivity and oligomerization of Aβ42 peptide in an in vitro assay. A11 immunoreactivity increased in Tg2576 fibroblasts when Gpc-1 autoprocessing was inhibited by 3-β[2(diethylamino)ethoxy]androst-5-en-17-one (U18666A) and decreased when Gpc-1 autoprocessing was stimulated by ascorbate. Neither overexpression of Gpc-1 in Tg2576 fibroblasts nor addition of copper ion and NO donor to hippocampal slices from 3xTg-AD mice affected A11 immunoreactivity levels. However, A11 immunoreactivity was greatly suppressed by the subsequent addition of ascorbate. We speculate that temporary interaction between the Aβ domain and small, anMan-containing oligosaccharides may preclude formation of toxic Aβ oligomers. A portion of the oligosaccharides are co-secreted with the Aβ peptides and deposited in plaques. These results support the notion that an inadequate supply of vitamin C could contribute to late onset AD in humans.

Antifouling paint particles: Sources, occurrence, composition and dynamics.

PubMed

Soroldoni, Sanye; Castro, Ítalo Braga; Abreu, Fiamma; Duarte, Fabio Andrei; Choueri, Rodrigo Brasil; Möller, Osmar Olinto; Fillmann, Gilberto; Pinho, Grasiela Lopes Leães

2018-06-15

Sources, occurrence, composition and dynamics of antifouling paint particles (APPs) were assessed in Patos Lagoon estuary (PLE), Southern Brazil. Ten areas including boatyards, a marina and artisanal fishing harbors were identified in the estuarine system as potential sources of APPs. The APPs generated in these areas were highly heterogeneous considering the size, shape and composition. Based on an estimate of antifouling paint usage and amount of boats in each studied area, artisanal fishing harbors could be the main source of particles to PLE. However, relatively high amounts of APPs, which ranged from 130 to 40,300 μg g -1 , were detected in sediments collected in front of boatyards and a marina. The uneven distribution of APPs levels among the sediment samples were probably due to the presence of diffuse sources (fishing harbors) associated to "hotspots" (boatyards and marina) along the study area. Additionally, data of settling experiment indicate that size, shape and density of APPs, combined to local hydrodynamics, appears to contribute to the mobility of these residues within the estuary. In the main channel of PLE, smaller particles tend to be transported to adjacent coastal zone while particles tend to be deposited in the sediment surface of sheltered areas. Since different trace metals, and booster biocides were detected in APPs that were not correctly disposed, these particles can be considered as an important source of contamination to aquatic environments. The present data suggest that APPs represent an environmental problem for aquatic systems in Brazil, since the country lacks legislation in addition to inefficient control mechanisms. An improvement in boat maintenance processes are urgently needed to avoid this continuous release of APPs into the aquatic systems. Copyright © 2018 Elsevier Ltd. All rights reserved.

Using WhatsApp to Create a Space of Language and Content for Students of International Relations

ERIC Educational Resources Information Center

Keogh, Conor

2017-01-01

For language learners of this generation, the smart phone represents a key cultural artefact that complements the learning process. Instant messaging applications such as WhatsApp are widely used in personal, professional and, increasingly, academic circles to maintain constant contact among friends, colleagues, or classmates. This study seeks to…

Development and use of the Cytoscape app GFD-Net for measuring semantic dissimilarity of gene networks

PubMed Central

Diaz-Montana, Juan J.; Diaz-Diaz, Norberto

2014-01-01

Gene networks are one of the main computational models used to study the interaction between different elements during biological processes being widely used to represent gene–gene, or protein–protein interaction complexes. We present GFD-Net, a Cytoscape app for visualizing and analyzing the functional dissimilarity of gene networks. PMID:25400907

Development of a Mobile Clinical Prediction Tool to Estimate Future Depression Severity and Guide Treatment in Primary Care: User-Centered Design

PubMed Central

2018-01-01

Background Around the world, depression is both under- and overtreated. The diamond clinical prediction tool was developed to assist with appropriate treatment allocation by estimating the 3-month prognosis among people with current depressive symptoms. Delivering clinical prediction tools in a way that will enhance their uptake in routine clinical practice remains challenging; however, mobile apps show promise in this respect. To increase the likelihood that an app-delivered clinical prediction tool can be successfully incorporated into clinical practice, it is important to involve end users in the app design process. Objective The aim of the study was to maximize patient engagement in an app designed to improve treatment allocation for depression. Methods An iterative, user-centered design process was employed. Qualitative data were collected via 2 focus groups with a community sample (n=17) and 7 semistructured interviews with people with depressive symptoms. The results of the focus groups and interviews were used by the computer engineering team to modify subsequent protoypes of the app. Results Iterative development resulted in 3 prototypes and a final app. The areas requiring the most substantial changes following end-user input were related to the iconography used and the way that feedback was provided. In particular, communicating risk of future depressive symptoms proved difficult; these messages were consistently misinterpreted and negatively viewed and were ultimately removed. All participants felt positively about seeing their results summarized after completion of the clinical prediction tool, but there was a need for a personalized treatment recommendation made in conjunction with a consultation with a health professional. Conclusions User-centered design led to valuable improvements in the content and design of an app designed to improve allocation of and engagement in depression treatment. Iterative design allowed us to develop a tool that allows users to feel hope, engage in self-reflection, and motivate them to treatment. The tool is currently being evaluated in a randomized controlled trial. PMID:29685864

Mobile Application to Promote Adherence to Oral Chemotherapy and Symptom Management: A Protocol for Design and Development

PubMed Central

MacDonald, James John; Amoyal Pensak, Nicole; Jacobs, Jamie Michele; Flanagan, Clare; Jethwani, Kamal

2017-01-01

Background Oral chemotherapy is increasingly used in place of traditional intravenous chemotherapy to treat patients with cancer. While oral chemotherapy includes benefits such as ease of administration, convenience, and minimization of invasive infusions, patients receive less oversight, support, and symptom monitoring from clinicians. Additionally, adherence is a well-documented challenge for patients with cancer prescribed oral chemotherapy regimens. With the ever-growing presence of smartphones and potential for efficacious behavioral intervention technology, we created a mobile health intervention for medication and symptom management. Objective The objective of this study was to develop and evaluate the usability and acceptability of a smartphone app to support adherence to oral chemotherapy and symptom management in patients with cancer. Methods We used a 5-step development model to create a comprehensive mobile app with theoretically informed content. The research and technical development team worked together to develop and iteratively test the app. In addition to the research team, key stakeholders including patients and family members, oncology clinicians, health care representatives, and practice administrators contributed to the content refinement of the intervention. Patient and family members also participated in alpha and beta testing of the final prototype to assess usability and acceptability before we began the randomized controlled trial. Results We incorporated app components based on the stakeholder feedback we received in focus groups and alpha and beta testing. App components included medication reminders, self-reporting of medication adherence and symptoms, an education library including nutritional information, Fitbit integration, social networking resources, and individually tailored symptom management feedback. We are conducting a randomized controlled trial to determine the effectiveness of the app in improving adherence to oral chemotherapy, quality of life, and burden of symptoms and side effects. At every stage in this trial, we are engaging stakeholders to solicit feedback on our progress and next steps. Conclusions To our knowledge, we are the first to describe the development of an app designed for people taking oral chemotherapy. The app addresses many concerns with oral chemotherapy, such as medication adherence and symptom management. Soliciting feedback from stakeholders with broad perspectives and expertise ensured that the app was acceptable and potentially beneficial for patients, caregivers, and clinicians. In our development process, we instantiated 7 of the 8 best practices proposed in a recent review of mobile health app development. Our process demonstrated the importance of effective communication between research groups and technical teams, as well as meticulous planning of technical specifications before development begins. Future efforts should consider incorporating other proven strategies in software, such as gamification, to bolster the impact of mobile health apps. Forthcoming results from our randomized controlled trial will provide key data on the effectiveness of this app in improving medication adherence and symptom management. Trial Registration ClinicalTrials.gov NCT02157519; https://clinicaltrials.gov/ct2/show/NCT02157519 (Archived by WebCite at http://www.webcitation.org/6prj3xfKA) PMID:28428158

A Smartphone App for Increasing Live Organ Donation.

PubMed

Kumar, K; King, E A; Muzaale, A D; Konel, J M; Bramstedt, K A; Massie, A B; Segev, D L; Cameron, A M

2016-12-01

The incidence of live donor transplantation has declined over the past decade, and waitlisted candidates report substantial barriers to identifying a live donor. Since asking someone to donate feels awkward and unfamiliar, candidates are hesitant to ask directly and may be more comfortable with a passive approach. In collaboration with Facebook leadership (Facebook Inc., Menlo Park, CA), we developed a mobile application-an app-that enables waitlisted candidates to create a Facebook post about their experience with organ failure and their need for a live donor. We conducted a single-center prospective cohort study of 54 adult kidney-only and liver-only waitlisted candidates using the Facebook app. Cox proportional hazards models were used to describe donor referral on behalf of candidates using the app compared with matched controls. The majority of candidates who used the app reported it to be "good" or "excellent" with regard to the installation process (82.9%), readability (88.6%), simplicity (70.6%), clarity (87.5%) and the information provided (85.3%). Compared with controls, candidates using the Facebook app were 2.43 6.61 17.98 times more likely to have a donor come forward on their behalf (p < 0.001). The Facebook app is an easy-to-use instrument that enables waitlisted candidates to passively communicate with their social network about their need for a live donor. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

Smartphone Applications for Educating and Helping Non-motivating Patients Adhere to Medication That Treats Mental Health Conditions: Aims and Functioning

PubMed Central

Kassianos, Angelos P.; Georgiou, Giorgos; Papaconstantinou, Electra P.; Detzortzi, Angeliki; Horne, Rob

2017-01-01

Background: Patients prescribed with medication that treats mental health conditions benefit the most compared to those prescribed with other types of medication. However, they are also the most difficult to adhere. The development of mobile health (mHealth) applications (“apps”) to help patients monitor their adherence is fast growing but with limited evidence on their efficacy. There is no evidence on the content of these apps for patients taking psychotropic medication. The aim of this study is to identify and evaluate the aims and functioning of available apps that are aiming to help and educate patients to adhere to medication that treats mental health conditions. Method: Three platform descriptions (Apple, Google, and Microsoft) were searched between October 2015 and February 2016. Included apps need to focus on adherence to medication that treats mental health conditions and use at least a reinforcement strategy. Descriptive information was extracted and apps evaluated on a number of assessment criteria using content analysis. Results: Sixteen apps were identified. All apps included self-monitoring properties like reminders and psycho-educational properties like mood logs. It was unclear how the latter were used or how adherence was measured. Major barriers to medication adherence like patients' illness and medication beliefs and attitudes were not considered nor where information to patients about mediation side effects. Very few apps were tailored and none was developed based on established theories explaining the processes for successful medication adherence like cognitions and beliefs. Reported information on app development and validation was poor. Discussion: A variety of apps with different properties that tackle both intentional and unintentional non-adherence from a different perspective are identified. An evidence-based approach and co-creation with patients is needed. This will ensure that the apps increase the possibility to impact on non-adherence. Theories like social cognition models can be useful in ensuring that patients' education, motivation, skills, beliefs, and type of adherence are taken into consideration when developing the apps. Findings from this study can help clinicians and patients make informed choices and pursue policy-makers to integrate evidence when developing future apps. Quality-assurance tools are needed to ensure the apps are systematically evaluated. PMID:29075216

Management of the General Process of Parenteral Nutrition Using mHealth Technologies: Evaluation and Validation Study

PubMed Central

2018-01-01

Background Any system applied to the control of parenteral nutrition (PN) ought to prove that the process meets the established requirements and include a repository of records to allow evaluation of the information about PN processes at any time. Objective The goal of the research was to evaluate the mobile health (mHealth) app and validate its effectiveness in monitoring the management of the PN process. Methods We studied the evaluation and validation of the general process of PN using an mHealth app. The units of analysis were the PN bags prepared and administered at the Son Espases University Hospital, Palma, Spain, from June 1 to September 6, 2016. For the evaluation of the app, we used the Poststudy System Usability Questionnaire and subsequent analysis with the Cronbach alpha coefficient. Validation was performed by checking the compliance of control for all operations on each of the stages (validation and transcription of the prescription, preparation, conservation, and administration) and by monitoring the operative control points and critical control points. Results The results obtained from 387 bags were analyzed, with 30 interruptions of administration. The fulfillment of stages was 100%, including noncritical nonconformities in the storage control. The average deviation in the weight of the bags was less than 5%, and the infusion time did not present deviations greater than 1 hour. Conclusions The developed app successfully passed the evaluation and validation tests and was implemented to perform the monitoring procedures for the overall PN process. A new mobile solution to manage the quality and traceability of sensitive medicines such as blood-derivative drugs and hazardous drugs derived from this project is currently being deployed. PMID:29615389

Huperzine A alleviates synaptic deficits and modulates amyloidogenic and nonamyloidogenic pathways in APPswe/PS1dE9 transgenic mice.

PubMed

Wang, Ying; Tang, Xi Can; Zhang, Hai Yan

2012-02-01

Huperzine A (HupA) is a potent acetylcholinesterase inhibitor (AChEI) used in the treatment of Alzheimer's disease (AD). Recently, HupA was shown to be active in modulating the nonamyloidogenic metabolism of β-amyloid precursor protein (APP) in APP-transfected human embryonic kidney cell line (HEK293swe). However, in vivo research concerning the mechanism of HupA in APP transgenic mice has not yet been fully elucidated. The present study indicates that the loss of dendritic spine density and synaptotagmin levels in the brain of APPswe/presenilin-1 (PS1) transgenic mice was significantly ameliorated by chronic HupA treatment and provides evidence that this neuroprotection was associated with reduced amyloid plaque burden and oligomeric β-amyloid (Aβ) levels in the cortex and hippocampus of APPswe/PS1dE9 transgenic mice. Our findings further demonstrate that the amelioration effect of HupA on Aβ deposits may be mediated, at least in part, by regulation of the compromised expression of a disintegrin and metalloprotease 10 (ADAM10) and excessive membrane trafficking of β-site APP cleavage enzyme 1 (BACE1) in these transgenic mice. In addition, extracellular signal-regulated kinases 1/2 (Erk1/2) phosphorylation may also be partially involved in the effect of HupA on APP processing. In conclusion, our work for the first time demonstrates the neuroprotective effect of HupA on synaptic deficits in APPswe/PS1dE9 transgenic mice and further clarifies the potential pharmacological targets for this protective effect, in which modulation of nonamyloidogenic and amyloidogenic APP processing pathways may be both involved. These findings may provide adequate evidence for the clinical and experimental benefits gained from HupA treatment. Copyright © 2011 Wiley Periodicals, Inc.

iOS and OS X Apps for Exploring Earthquake Activity

NASA Astrophysics Data System (ADS)

Ammon, C. J.

2015-12-01

The U.S. Geological Survey and many other agencies rapidly provide information following earthquakes. This timely information garners great public interest and provides a rich opportunity to engage students in discussion and analysis of earthquakes and tectonics. In this presentation I will describe a suite of iOS and Mac OS X apps that I use for teaching and that Penn State employs in outreach efforts in a small museum run by the College of Earth and Mineral Sciences. The iOS apps include a simple, global overview of earthquake activity, epicentral, designed for a quick review or event lookup. A more full-featured iPad app, epicentral-plus, includes a simple global overview along with views that allow a more detailed exploration of geographic regions of interest. In addition, epicentral-plus allows the user to monitor ground motions using seismic channel lists compatible with the IRIS web services. Some limited seismogram processing features are included to allow focus on appropriate signal bandwidths. A companion web site, which includes background material on earthquakes, and a blog that includes sample images and channel lists appropriate for monitoring earthquakes in regions of recent earthquake activity can be accessed through the a third panel in the app. I use epicentral-plus at the beginning of each earthquake seismology class to review recent earthquake activity and to stimulate students to formulate and to ask questions that lead to discussions of earthquake and tectonic processes. Less interactive OS X versions of the apps are used to display a global map of earthquake activity and seismograms in near real time in a small museum on the ground floor of the building hosting Penn State's Geoscience Department.

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

[The inhibitor of free radical processes decrease of protein biosynthesis in gun short wound tissues and weaken development of the general adaptation syndrome].

PubMed

Todorov, I N; Bogdanov, G N; Mitrokhin, Iu I; Varfolomeev, V N; Sidorenko, L I; Mishchenko, D V

2006-01-01

The dynamics of total protein biosynthesis and procollagen biosynthesis in skeletal muscle of injury tissues with the antioxidant BHT (dibunol) treatment and with common healing were studied. The obtained date indicate that the AO treatment reduce the rate of biosynthesis both the total proteins and procollagen at the 3th day of healing. Dibunol also considerably reduce the protein biosynthesis in adrenals and brake of corticosteroids biogenesis as measured by ESR-signals intensity of reduced adrenodoxine. AO treatment also reduce the protein biosynthesis in thymus, spleen and bone marrow. The lowering of functional activity of endocrine and immune systems indicate that the AO significantly inhibit the systemic reactions of organism induced by acute wound affect. It was suggested that as "primary mediator" of stress-reaction may be considered lipoperoxide radicals and decay products of lipohydroperoide.

Biosynthesis and function of chondroitin sulfate.

PubMed

Mikami, Tadahisa; Kitagawa, Hiroshi

2013-10-01

Chondroitin sulfate proteoglycans (CSPGs) are principal pericellular and extracellular components that form regulatory milieu involving numerous biological and pathophysiological phenomena. Diverse functions of CSPGs can be mainly attributed to structural variability of their polysaccharide moieties, chondroitin sulfate glycosaminoglycans (CS-GAG). Comprehensive understanding of the regulatory mechanisms for CS biosynthesis and its catabolic processes is required in order to understand those functions. Here, we focus on recent advances in the study of enzymatic regulatory pathways for CS biosynthesis including successive modification/degradation, distinct CS functions, and disease phenotypes that have been revealed by perturbation of the respective enzymes in vitro and in vivo. Fine-tuned machineries for CS production/degradation are crucial for the functional expression of CS chains in developmental and pathophysiological processes. Control of enzymes responsible for CS biosynthesis/catabolism is a potential target for therapeutic intervention for the CS-associated disorders. Copyright © 2013 Elsevier B.V. All rights reserved.

γ-Secretase Modulators and APH1 Isoforms Modulate γ-Secretase Cleavage but Not Position of ε-Cleavage of the Amyloid Precursor Protein (APP).

PubMed

Lessard, Christian B; Cottrell, Barbara A; Maruyama, Hiroko; Suresh, Suraj; Golde, Todd E; Koo, Edward H

2015-01-01

The relative increase in Aβ42 peptides from familial Alzheimer disease (FAD) linked APP and PSEN mutations can be related to changes in both ε-cleavage site utilization and subsequent step-wise cleavage. Cleavage at the ε-site releases the amyloid precursor protein (APP) intracellular domain (AICD), and perturbations in the position of ε-cleavage are closely associated with changes in the profile of amyloid β-protein (Aβ) species that are produced and secreted. The mechanisms by which γ-secretase modulators (GSMs) or FAD mutations affect the various γ-secretase cleavages to alter the generation of Aβ peptides have not been fully elucidated. Recent studies suggested that GSMs do not modulate ε-cleavage of APP, but the data were derived principally from recombinant truncated epitope tagged APP substrate. Here, using full length APP from transfected cells, we investigated whether GSMs modify the ε-cleavage of APP under more native conditions. Our results confirmed the previous findings that ε-cleavage is insensitive to GSMs. In addition, fenofibrate, an inverse GSM (iGSM), did not alter the position or kinetics of ε-cleavage position in vitro. APH1A and APH1B, a subunit of the γ-secretase complex, also modulated Aβ42/Aβ40 ratio without any alterations in ε-cleavage, a result in contrast to what has been observed with PS1 and APP FAD mutations. Consequently, GSMs and APH1 appear to modulate γ-secretase activity and Aβ42 generation by altering processivity but not ε-cleavage site utilization.

Nutrient Losses from Non-Point Sources or from Unidentified Point Sources? Application Examples of the Smartphone Based Nitrate App.

NASA Astrophysics Data System (ADS)

Rozemeijer, J.; Ekkelenkamp, R.; van der Zaan, B.

2017-12-01

In 2016 Deltares launched the free to use Nitrate App which accurately reads and interprets nitrate test strips. The app directly displays the measured concentration and gives the option to share the result. Shared results are visualised in map functionality within the app and online. Since its introduction we've been seeing an increasing number of nitrate app applications. In this presentation we show some unanticipated types of application. The Nitrate App was originally intended to enable farmers to measure nitrate concentrations on their own farms. This may encourage farmers to talk to specialists about the right nutrient best management practices (BMP's) for their farm. Several groups of farmers have recently started to apply the Nitrate App and to discuss their results with each other and with the authorities. Nitrate concentration routings in catchments have proven to be another useful application. Within a day a person can generate a catchment scale nitrate concentration map identifying nitrate loss hotspots. In several routings in agricultural catchments clear point sources were found, for example at small scale manure processing plants. These routings proved that the Nitrate App can help water managers to target conservation practices more accurately to areas with the highest nitrate concentrations and loads. Other current applications are the screening of domestic water wells in California, the collection of extra measurements (also pH and NH4) in the National Monitoring Network for the Evaluation of the Manure Policy in the Netherlands, and several educational initiatives in cooperation with schools and universities.

Photo dynamics of BLUF domain mutant H44R of AppA from Rhodobacter sphaeroides

NASA Astrophysics Data System (ADS)

Zirak, P.; Penzkofer, A.; Hegemann, P.; Mathes, T.

2007-05-01

The photo-cycle dynamics of the H44R mutant of the BLUF domain of the transcriptional anti-repressor protein AppA (AppA-H44R) from the non-sulfur anoxyphototropic purple bacterium Rhodobacter sphaeroides is studied in order to gain information on the involvement of His44 in the photo-cyclic mechanism of the AppA BLUF domain and to add information to the involved processes. The amino acid residue histidine at position 44 is replaced by arginine. A 12 nm red-shifted signalling state is formed upon blue-light excitation, while in wild-type AppA (AppA-wt) the red-shift is 16 nm. The recovery to the receptor dark state is approximately a factor of 2.5 faster ( τrec ≈ 6.5 min) than the recovery of the wild-type counterpart. Extended light exposure of the mutant causes photo-degradation of flavin (mainly free flavin conversion to lumichrome and re-equilibration between free and non-covalently bound flavin) and protein aggregation (showing up as light scattering). No photo-degradation was observed for AppA-wt. The quantum efficiency of signalling-state formation determined by intensity dependent absorption measurements is found to be ϕs ≈ 0.3 (for AppA-wt: ϕs ≈ 0.24). A two-component single-exponential fluorescence relaxation was observed, which is interpreted as fast fluorescence quenching to an equilibrium value by photo-induced electron transfer followed by slower fluorescence decay due to charge recombination. Based on the experimental findings, an extended photo-cycle model for BLUF domains is proposed.

Development of 'Twazon': An Arabic App for Weight Loss.

PubMed

Alnasser, Aroub; Sathiaseelan, Arjuna; Al-Khalifa, Abdulrahman; Marais, Debbi

2016-05-16

Weight gain and its related illnesses have become a major public health issue across the world, with Saudi Arabia and other Gulf countries seeing dramatic increases in obesity and overweight, and yet there is very little information on how to intervene with this demographic due to cultural and linguistic barriers. As the use of smartphones and apps has also increased in the region, information communication technologies could be a cost-effective means of facilitating the delivery of behavior-modification interventions directly to the target population. Although there are existing apps that offer lifestyle-modification tools, they do not give consideration to the evidence-based practices for weight management. This offers an opportunity to create an Arabic language weight loss app that offers localized content and adheres to evidence-informed practices that are needed for effective weight loss. This paper describes the process of developing an Arabic weight loss app designed to facilitate the modification of key nutritional and physical activity behaviors among Saudi adults, while taking into consideration cultural norms. The development of the Twazon app involved: (1) reviewing all available Arabic weight loss apps and compared with evidence-based practices for weight loss, (2) conducting a qualitative study with overweight and obese Saudi women to ascertain their preferences, (3) selecting which behavioral change strategies and guidelines to be used in the app, (4) creating the Saudi Food Database, (5) deciding on graphic design for both iPhone operating system and Android platforms, including user interface, relational database, and programming code, and (6) testing the beta version of the app with health professionals and potential users. The Twazon app took 23 months to develop and included the compilation of an original Saudi Food database. Eight subjects gave feedback regarding the content validity and usability of the app and its features during a pilot study. The predominant issue among the group was the lack of information explaining how to use the app. This has since been resolved through the implementation of a tutorial. No other changes were required to be made. Information communication technologies, such as smartphone apps, may be an effective tool for facilitating the modification of unhealthy lifestyle habits in Saudi; however, consideration must be given to the target population, cultural norms, and changing trends in the global market. The effectiveness of the app will be better determined during a 6-month intervention with 200 overweight and obese Saudi women.

AppEEARS: A Simple Tool that Eases Complex Data Integration and Visualization Challenges for Users

NASA Astrophysics Data System (ADS)

Maiersperger, T.

2017-12-01

The Application for Extracting and Exploring Analysis-Ready Samples (AppEEARS) offers a simple and efficient way to perform discovery, processing, visualization, and acquisition across large quantities and varieties of Earth science data. AppEEARS brings significant value to a very broad array of user communities by 1) significantly reducing data volumes, at-archive, based on user-defined space-time-variable subsets, 2) promoting interoperability across a wide variety of datasets via format and coordinate reference system harmonization, 3) increasing the velocity of both data analysis and insight by providing analysis-ready data packages and by allowing interactive visual exploration of those packages, and 4) ensuring veracity by making data quality measures more apparent and usable and by providing standards-based metadata and processing provenance. Development and operation of AppEEARS is led by the National Aeronautics and Space Administration (NASA) Land Processes Distributed Active Archive Center (LP DAAC). The LP DAAC also partners with several other archives to extend the capability across a larger federation of geospatial data providers. Over one hundred datasets are currently available, covering a diversity of variables including land cover, population, elevation, vegetation indices, and land surface temperature. Many hundreds of users have already used this new web-based capability to make the complex tasks of data integration and visualization much simpler and more efficient.

Development of an IOS App Using Situated Learning, Communities of Practice, and Augmented Reality for Autism Spectrum Disorder

ERIC Educational Resources Information Center

Clarkson, Jessica

2014-01-01

This paper presents the development process and framework used to construct a transportation app that uses situated learning, augmented reality, and communities of practice. Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can cause social impairments as well as the limit the potential for the individual to achieve independence…

Exploring Learning Performance toward Cognitive Approaches of a Virtual Companion System in LINE App for m-Learning

ERIC Educational Resources Information Center

Hsieh, Sheng-Wen; Wu, Min-Ping

2013-01-01

This paper used a Virtual Companion System (VCS) to examine how specific design variables within virtual learning companion affect the learning process of learners as defined by the cognitive continuum of field-dependent, field-independent and field-mixed learners in LINE app for m-learning. The data were collected from 198 participants in a…

Online thesis guidance management information system

NASA Astrophysics Data System (ADS)

Nasution, T. H.; Pratama, F.; Tanjung, K.; Siregar, I.; Amalia, A.

2018-03-01

The development of internet technology in education is still not maximized, especially in the process of thesis guidance between students and lecturers. Difficulties met the lecturers to help students during thesis guidance is the limited communication time and the compatibility of schedule between students and lecturer. To solve this problem, we designed an online thesis guidance management information system that helps students and lecturers to do thesis tutoring process anytime, anywhere. The system consists of a web-based admin app for usage management and an android-based app for students and lecturers.

Smartphone Analytics: Mobilizing the Lab into the Cloud for Omic-Scale Analyses.

PubMed

Montenegro-Burke, J Rafael; Phommavongsay, Thiery; Aisporna, Aries E; Huan, Tao; Rinehart, Duane; Forsberg, Erica; Poole, Farris L; Thorgersen, Michael P; Adams, Michael W W; Krantz, Gregory; Fields, Matthew W; Northen, Trent R; Robbins, Paul D; Niedernhofer, Laura J; Lairson, Luke; Benton, H Paul; Siuzdak, Gary

2016-10-04

Active data screening is an integral part of many scientific activities, and mobile technologies have greatly facilitated this process by minimizing the reliance on large hardware instrumentation. In order to meet with the increasingly growing field of metabolomics and heavy workload of data processing, we designed the first remote metabolomic data screening platform for mobile devices. Two mobile applications (apps), XCMS Mobile and METLIN Mobile, facilitate access to XCMS and METLIN, which are the most important components in the computer-based XCMS Online platforms. These mobile apps allow for the visualization and analysis of metabolic data throughout the entire analytical process. Specifically, XCMS Mobile and METLIN Mobile provide the capabilities for remote monitoring of data processing, real time notifications for the data processing, visualization and interactive analysis of processed data (e.g., cloud plots, principle component analysis, box-plots, extracted ion chromatograms, and hierarchical cluster analysis), and database searching for metabolite identification. These apps, available on Apple iOS and Google Android operating systems, allow for the migration of metabolomic research onto mobile devices for better accessibility beyond direct instrument operation. The utility of XCMS Mobile and METLIN Mobile functionalities was developed and is demonstrated here through the metabolomic LC-MS analyses of stem cells, colon cancer, aging, and bacterial metabolism.

Smartphone Analytics: Mobilizing the Lab into the Cloud for Omic-Scale Analyses

PubMed Central

2016-01-01

Active data screening is an integral part of many scientific activities, and mobile technologies have greatly facilitated this process by minimizing the reliance on large hardware instrumentation. In order to meet with the increasingly growing field of metabolomics and heavy workload of data processing, we designed the first remote metabolomic data screening platform for mobile devices. Two mobile applications (apps), XCMS Mobile and METLIN Mobile, facilitate access to XCMS and METLIN, which are the most important components in the computer-based XCMS Online platforms. These mobile apps allow for the visualization and analysis of metabolic data throughout the entire analytical process. Specifically, XCMS Mobile and METLIN Mobile provide the capabilities for remote monitoring of data processing, real time notifications for the data processing, visualization and interactive analysis of processed data (e.g., cloud plots, principle component analysis, box-plots, extracted ion chromatograms, and hierarchical cluster analysis), and database searching for metabolite identification. These apps, available on Apple iOS and Google Android operating systems, allow for the migration of metabolomic research onto mobile devices for better accessibility beyond direct instrument operation. The utility of XCMS Mobile and METLIN Mobile functionalities was developed and is demonstrated here through the metabolomic LC-MS analyses of stem cells, colon cancer, aging, and bacterial metabolism. PMID:27560777

Smartphone Analytics: Mobilizing the Lab into the Cloud for Omic-Scale Analyses

DOE PAGES

Montenegro-Burke, J. Rafael; Phommavongsay, Thiery; Aisporna, Aries E.; ...

2016-08-25

Active data screening is an integral part of many scientific activities, and mobile technologies have greatly facilitated this process by minimizing the reliance on large hardware instrumentation. In order to meet with the increasingly growing field of metabolomics and heavy workload of data processing, we designed the first remote metabolomic data screening platform for mobile devices. Two mobile applications (apps), XCMS Mobile and METLIN Mobile, facilitate access to XCMS and METLIN, which are the most important components in the computer-based XCMS Online platforms. These mobile apps allow for the visualization and analysis of metabolic data throughout the entire analytical process.more » Specifically, XCMS Mobile and METLIN Mobile provide the capabilities for remote monitoring of data processing, real time notifications for the data processing, visualization and interactive analysis of processed data (e.g., cloud plots, principle component analysis, box-plots, extracted ion chromatograms, and hierarchical cluster analysis), and database searching for metabolite identification. These apps, available on Apple iOS and Google Android operating systems, allow for the migration of metabolomic research onto mobile devices for better accessibility beyond direct instrument operation. The utility of XCMS Mobile and METLIN Mobile functionalities was developed and is demonstrated here through the metabolomic LC-MS analyses of stem cells, colon cancer, aging, and bacterial metabolism.« less

Smartphone Analytics: Mobilizing the Lab into the Cloud for Omic-Scale Analyses

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

Montenegro-Burke, J. Rafael; Phommavongsay, Thiery; Aisporna, Aries E.

Active data screening is an integral part of many scientific activities, and mobile technologies have greatly facilitated this process by minimizing the reliance on large hardware instrumentation. In order to meet with the increasingly growing field of metabolomics and heavy workload of data processing, we designed the first remote metabolomic data screening platform for mobile devices. Two mobile applications (apps), XCMS Mobile and METLIN Mobile, facilitate access to XCMS and METLIN, which are the most important components in the computer-based XCMS Online platforms. These mobile apps allow for the visualization and analysis of metabolic data throughout the entire analytical process.more » Specifically, XCMS Mobile and METLIN Mobile provide the capabilities for remote monitoring of data processing, real time notifications for the data processing, visualization and interactive analysis of processed data (e.g., cloud plots, principle component analysis, box-plots, extracted ion chromatograms, and hierarchical cluster analysis), and database searching for metabolite identification. These apps, available on Apple iOS and Google Android operating systems, allow for the migration of metabolomic research onto mobile devices for better accessibility beyond direct instrument operation. The utility of XCMS Mobile and METLIN Mobile functionalities was developed and is demonstrated here through the metabolomic LC-MS analyses of stem cells, colon cancer, aging, and bacterial metabolism.« less

A study on interaction App platform between expert knowledge and community applied on disaster education

NASA Astrophysics Data System (ADS)

Ruljigaljig, T.; Huang, M. L.

2015-12-01

This study development interface for Mobile Application (App) use cloud technology, Web 2.0 and online community of technology to build the Environmental-Geological Disaster Network(EDN). The interaction App platform between expert knowledge and community is developed as a teaching tool, which bases on the open data released by Central Geological Survey. The APP can through Augmented Reality technology to potential hazards position through the camera lens, the real show in real-world environment. The interaction with experts in the community to improve the general public awareness of disaster. Training people to record the occurrence of geological disasters precursor, thereby awakened their to natural disaster consciousness and attention.General users obtain real-time information during travel, mountaineering and teaching process. Using App platform to upload and represent the environmental geological disaster data collected by themselves. It is expected that by public joint the open platform can accumulate environmental geological disaster data effectively, quickly, extensively and correctly. The most important thing of this study is rooting the concept of disaster prevention, reduction, and avoidance through public participation.

MyShake - A smartphone app to detect earthquake

NASA Astrophysics Data System (ADS)

Kong, Q.; Allen, R. M.; Schreier, L.; Kwon, Y. W.

2015-12-01

We designed an android app that harnesses the accelerometers in personal smartphones to record earthquake-shaking data for research, hazard information and warnings. The app has the function to distinguish earthquake shakings from daily human activities based on the different patterns behind the movements. It also can be triggered by the traditional earthquake early warning (EEW) system to record for a certain amount of time to collect earthquake data. When the app is triggered by the earthquake-like movements, it sends the trigger information back to our server which contains time and location of the trigger, at the same time, it stores the waveform data on local phone first, and upload to our server later. Trigger information from multiple phones will be processed in real time on the server to find the coherent signal to confirm the earthquakes. Therefore, the app provides the basis to form a smartphone seismic network that can detect earthquake and even provide warnings. A planned public roll-out of MyShake could collect millions of seismic recordings for large earthquakes in many regions around the world.

The Space Apps Challenge: Using Open Innovation Competitions to Engage The Public in the Scientific Process

NASA Astrophysics Data System (ADS)

Gupta, S. S.

2016-12-01

NASA's Space Apps Challenge encourages innovation, creativity and collaborative problem solving by gathering coders, builders, artists, designers, and storytellers in a 48-hour hackathon. Open Innovation competitions such as the Space Apps Challenge bring the scientific world to members of the public, regardless of age, experience, credentials, or expertise. In the past five years, this model of public engagement has been widely employed by government, nonprofit and academic institutions, allowing the building of partnerships between the scientific community and the individuals and communities they serve. Furthermore, advances in technology and challenge models have lowered the barriers and costs to scientific collaboration with and for the public. NASA's Space Apps Challenge, structured as a competition seeking solutions from the public to posed problems, brings together teams and forges collaborations between individuals and groups who would otherwise have never worked together for a short but high intensity problem solving session, Space Apps has has created a pathway to public engagement and innovation that is often faster, cheaper, and more impactful than traditional approaches.

BIDS apps: Improving ease of use, accessibility, and reproducibility of neuroimaging data analysis methods

PubMed Central

Auer, Tibor; Churchill, Nathan W.; Flandin, Guillaume; Guntupalli, J. Swaroop; Raffelt, David; Quirion, Pierre-Olivier; Smith, Robert E.; Strother, Stephen C.; Varoquaux, Gaël

2017-01-01

The rate of progress in human neurosciences is limited by the inability to easily apply a wide range of analysis methods to the plethora of different datasets acquired in labs around the world. In this work, we introduce a framework for creating, testing, versioning and archiving portable applications for analyzing neuroimaging data organized and described in compliance with the Brain Imaging Data Structure (BIDS). The portability of these applications (BIDS Apps) is achieved by using container technologies that encapsulate all binary and other dependencies in one convenient package. BIDS Apps run on all three major operating systems with no need for complex setup and configuration and thanks to the comprehensiveness of the BIDS standard they require little manual user input. Previous containerized data processing solutions were limited to single user environments and not compatible with most multi-tenant High Performance Computing systems. BIDS Apps overcome this limitation by taking advantage of the Singularity container technology. As a proof of concept, this work is accompanied by 22 ready to use BIDS Apps, packaging a diverse set of commonly used neuroimaging algorithms. PMID:28278228

Secreted Amyloid β-Proteins in a Cell Culture Model Include N-Terminally Extended Peptides That Impair Synaptic Plasticity

PubMed Central

2014-01-01

Evidence for a central role of amyloid β-protein (Aβ) in the genesis of Alzheimer’s disease (AD) has led to advanced human trials of Aβ-lowering agents. The “amyloid hypothesis” of AD postulates deleterious effects of small, soluble forms of Aβ on synaptic form and function. Because selectively targeting synaptotoxic forms of soluble Aβ could be therapeutically advantageous, it is important to understand the full range of soluble Aβ derivatives. We previously described a Chinese hamster ovary (CHO) cell line (7PA2 cells) that stably expresses mutant human amyloid precursor protein (APP). Here, we extend this work by purifying an sodium dodecyl sulfate (SDS)-stable, ∼8 kDa Aβ species from the 7PA2 medium. Mass spectrometry confirmed its identity as a noncovalently bonded Aβ40 homodimer that impaired hippocampal long-term potentiation (LTP) in vivo. We further report the detection of Aβ-containing fragments of APP in the 7PA2 medium that extend N-terminal from Asp1 of Aβ. These N-terminally extended Aβ-containing monomeric fragments are distinct from soluble Aβ oligomers formed from Aβ1-40/42 monomers and are bioactive synaptotoxins secreted by 7PA2 cells. Importantly, decreasing β-secretase processing of APP elevated these alternative synaptotoxic APP fragments. We conclude that certain synaptotoxic Aβ-containing species can arise from APP processing events N-terminal to the classical β-secretase cleavage site. PMID:24840308

Smartphone Applications with Sensors Used in a Tertiary Hospital—Current Status and Future Challenges

PubMed Central

Park, Yu Rang; Lee, Yura; Lee, Guna; Lee, Jae Ho; Shin, Soo-Yong

2015-01-01

Smartphones have been widely used recently to monitor heart rate and activity, since they have the necessary processing power, non-invasive and cost-effective sensors, and wireless communication capabilities. Consequently, healthcare applications (apps) using smartphone-based sensors have been highlighted for non-invasive physiological monitoring. In addition, several healthcare apps have received FDA clearance. However, in spite of their potential, healthcare apps with smartphone-based sensors are mostly used outside of hospitals and have not been widely adopted for patient care in hospitals until recently. In this paper, we describe the experience of using smartphone apps with sensors in a large medical center in Korea. Among >20 apps developed in our medical center, four were extensively analyzed (“My Cancer Diary”, “Point-of-Care HIV Check”, “Blood Culture” and “mAMIS”), since they use smartphone-based sensors such as the camera and barcode reader to enter data into the electronic health record system. By analyzing the usage patterns of these apps for data entry with sensors, the current limitations of smartphone-based sensors in a clinical setting, hurdles against adoption in the medical center, benefits of smartphone-based sensors and potential future research directions could be evaluated. PMID:25923933

Formative research to develop a lifestyle application (app) for African American breast cancer survivors

PubMed Central

Smith, Selina A.; Whitehead, Mary S.; Sheats, Joyce Q.; Fontenot, Brittney; Alema-Mensah, Ernest; Ansa, Benjamin

2016-01-01

Background There is a proliferation of lifestyle-oriented mobile technologies; however, few have targeted users. Through intervention mapping, investigators and community partners completed Steps 1–3 (needs assessment, formulation of change objectives, and selection of theory-based methods) of a process to develop a mobile cancer prevention application (app) for cancer prevention. The aim of this qualitative study was to complete Step 4 (intervention development) by eliciting input from African American (AA) breast cancer survivors (BCSs) to guide app development. Methods Four focus group discussions (n=60) and three individual semi-structured interviews (n=36) were conducted with AA BCSs (40–72 years of age) to assess barriers and strategies for lifestyle change. All focus groups and interviews were recorded and transcribed verbatim. Data were analyzed with NVivo qualitative data analysis software version 10, allowing categories, themes, and patterns to emerge. Results Three categories and related themes emerged from the analysis: 1) perceptions about modifiable risk factors; 2) strategies related to adherence to cancer prevention guidelines; and 3) app components to address barriers to adherence. Participant perceptions, strategies, and recommended components guided development of the app. Conclusions For development of a mobile cancer prevention app, these findings will assist investigators in targeting features that are usable, acceptable, and accessible for AA BCSs. PMID:27583307

Engineering microorganisms for improving polyhydroxyalkanoate biosynthesis.

PubMed

Chen, Guo-Qiang; Jiang, Xiao-Ran

2017-11-20

Biosynthesis of polyhydroxyalkanoates (PHA) has been studied since the 1920s. The biosynthesis pathways have been well understood and various attempts have been made to improve the PHA biosynthesis efficiency. Recent progresses have been focused on systematic improvements on PHA biosynthesis including changing growth pattern for rapid proliferation, engineering to enlarge cell sizes for more PHA accumulation space, reprogramming the PHA synthesis pathways using optimized RBS and promoter, redirecting metabolic flux to PHA synthesis using CRISPR/Cas9 tools, and very importantly, the employment of non-traditional host such as halophiles for reduced complexity on PHA production. All of the efforts should lead to ultrahigh PHA accumulation, controllable PHA compositions and molecular weights, open and continuous PHA production with gravity separation processes, resulting in competitive PHA production cost. Copyright © 2017 Elsevier Ltd. All rights reserved.

Essential Roles of Local Auxin Biosynthesis in Plant Development and in Adaptation to Environmental Changes.

PubMed

Zhao, Yunde

2018-04-29

It has been a dominant dogma in plant biology that the self-organizing polar auxin transport system is necessary and sufficient to generate auxin maxima and minima that are essential for almost all aspects of plant growth and development. However, in the past few years, it has become clear that local auxin biosynthesis is required for a suite of developmental processes, including embryogenesis, endosperm development, root development, and floral initiation and patterning. Moreover, it was discovered that local auxin biosynthesis maintains optimal plant growth in response to environmental signals, including light, temperature, pathogens, and toxic metals. In this article, I discuss the recent progress in auxin biosynthesis research and the paradigm shift in recognizing the important roles of local auxin biosynthesis in plant biology.

Implementation of a Substance Use Recovery Support Mobile Phone App in Community Settings: Qualitative Study of Clinician and Staff Perspectives of Facilitators and Barriers.

PubMed

Lord, Sarah; Moore, Sarah K; Ramsey, Alex; Dinauer, Susan; Johnson, Kimberly

2016-06-28

Research supports the effectiveness of technology-based treatment approaches for substance use disorders. These approaches have the potential to broaden the reach of evidence-based care. Yet, there is limited understanding of factors associated with implementation of technology-based care approaches in different service settings. In this study, we explored provider and staff perceptions of facilitators and barriers to implementation of a mobile phone substance use recovery support app with clients in 4 service settings. Interviews were conducted with leadership and provider stakeholders (N=12) from 4 agencies in the first year of an implementation trial of the mobile phone app. We used the Consolidated Framework for Implementation Research as the conceptual foundation for identifying facilitators and barriers to implementation. Implementation process facilitators included careful planning of all aspects of implementation before launch, engaging a dedicated team to implement and foster motivation, working collaboratively with the app development team to address technical barriers and adapt the app to meet client and agency needs, and consistently reviewing app usage data to inform progress. Implementation support strategies included training all staff to promote organization awareness about the recovery support app and emphasize its priority as a clinical care tool, encouraging clients to try the technology before committing to use, scaling rollout to clients, setting clear expectations with clients about use of the app, and using peer coaches and consistent client-centered messaging to promote engagement. Perceived compatibility of the mobile phone app with agency and client needs and readiness to implement emerged as salient agency-level implementation facilitators. Facilitating characteristics of the recovery support app itself included evidence of its impact for recovery support, perceived relative advantage of the app over usual care, the ability to adapt the app to improve client use, and its ease of use. The mobile phone itself was a strong motivation for clients to opt in to use the app in settings that provided phones. App access was limited in settings that did not provide phones owing to lack of mobile phone ownership or incompatibility of the app with clients' mobile phones. Individual differences in technology literacy and provider beliefs about substance use care either facilitated or challenged implementation. Awareness of patient needs and resources facilitated implementation, whereas external policies and regulations regarding technology use introduced barriers to implementation. The conceptually grounded facilitators and barriers identified in this study can guide systematic targeting of strategies to improve implementation of mobile phone interventions in community treatment settings. Results also inform the design of technology-based therapeutic tools. This study highlights directions for research with regard to implementation of technology-based behavioral health care approaches.

Implementation of a Substance Use Recovery Support Mobile Phone App in Community Settings: Qualitative Study of Clinician and Staff Perspectives of Facilitators and Barriers

PubMed Central

Moore, Sarah K; Ramsey, Alex; Dinauer, Susan; Johnson, Kimberly

2016-01-01

Background Research supports the effectiveness of technology-based treatment approaches for substance use disorders. These approaches have the potential to broaden the reach of evidence-based care. Yet, there is limited understanding of factors associated with implementation of technology-based care approaches in different service settings. Objectives In this study, we explored provider and staff perceptions of facilitators and barriers to implementation of a mobile phone substance use recovery support app with clients in 4 service settings. Methods Interviews were conducted with leadership and provider stakeholders (N=12) from 4 agencies in the first year of an implementation trial of the mobile phone app. We used the Consolidated Framework for Implementation Research as the conceptual foundation for identifying facilitators and barriers to implementation. Results Implementation process facilitators included careful planning of all aspects of implementation before launch, engaging a dedicated team to implement and foster motivation, working collaboratively with the app development team to address technical barriers and adapt the app to meet client and agency needs, and consistently reviewing app usage data to inform progress. Implementation support strategies included training all staff to promote organization awareness about the recovery support app and emphasize its priority as a clinical care tool, encouraging clients to try the technology before committing to use, scaling rollout to clients, setting clear expectations with clients about use of the app, and using peer coaches and consistent client-centered messaging to promote engagement. Perceived compatibility of the mobile phone app with agency and client needs and readiness to implement emerged as salient agency-level implementation facilitators. Facilitating characteristics of the recovery support app itself included evidence of its impact for recovery support, perceived relative advantage of the app over usual care, the ability to adapt the app to improve client use, and its ease of use. The mobile phone itself was a strong motivation for clients to opt in to use the app in settings that provided phones. App access was limited in settings that did not provide phones owing to lack of mobile phone ownership or incompatibility of the app with clients’ mobile phones. Individual differences in technology literacy and provider beliefs about substance use care either facilitated or challenged implementation. Awareness of patient needs and resources facilitated implementation, whereas external policies and regulations regarding technology use introduced barriers to implementation. Conclusions The conceptually grounded facilitators and barriers identified in this study can guide systematic targeting of strategies to improve implementation of mobile phone interventions in community treatment settings. Results also inform the design of technology-based therapeutic tools. This study highlights directions for research with regard to implementation of technology-based behavioral health care approaches. PMID:27352884

Popular Nutrition-Related Mobile Apps: A Feature Assessment.

PubMed

Franco, Rodrigo Zenun; Fallaize, Rosalind; Lovegrove, Julie A; Hwang, Faustina

2016-08-01

A key challenge in human nutrition is the assessment of usual food intake. This is of particular interest given recent proposals of eHealth personalized interventions. The adoption of mobile phones has created an opportunity for assessing and improving nutrient intake as they can be used for digitalizing dietary assessments and providing feedback. In the last few years, hundreds of nutrition-related mobile apps have been launched and installed by millions of users. This study aims to analyze the main features of the most popular nutrition apps and to compare their strategies and technologies for dietary assessment and user feedback. Apps were selected from the two largest online stores of the most popular mobile operating systems-the Google Play Store for Android and the iTunes App Store for iOS-based on popularity as measured by the number of installs and reviews. The keywords used in the search were as follows: calorie(s), diet, diet tracker, dietician, dietitian, eating, fit, fitness, food, food diary, food tracker, health, lose weight, nutrition, nutritionist, weight, weight loss, weight management, weight watcher, and ww calculator. The inclusion criteria were as follows: English language, minimum number of installs (1 million for Google Play Store) or reviews (7500 for iTunes App Store), relation to nutrition (ie, diet monitoring or recommendation), and independence from any device (eg, wearable) or subscription. A total of 13 apps were classified as popular for inclusion in the analysis. Nine apps offered prospective recording of food intake using a food diary feature. Food selection was available via text search or barcode scanner technologies. Portion size selection was only textual (ie, without images or icons). All nine of these apps were also capable of collecting physical activity (PA) information using self-report, the global positioning system (GPS), or wearable integrations. Their outputs focused predominantly on energy balance between dietary intake and PA. None of these nine apps offered features directly related to diet plans and motivational coaching. In contrast, the remaining four of the 13 apps focused on these opportunities, but without food diaries. One app-FatSecret-also had an innovative feature for connecting users with health professionals, and another-S Health-provided a nutrient balance score. The high number of installs indicates that there is a clear interest and opportunity for diet monitoring and recommendation using mobile apps. All the apps collecting dietary intake used the same nutrition assessment method (ie, food diary record) and technologies for data input (ie, text search and barcode scanner). Emerging technologies, such as image recognition, natural language processing, and artificial intelligence, were not identified. None of the apps had a decision engine capable of providing personalized diet advice.

[Reimbursement of health apps by the German statutory health insurance].

PubMed

Gregor-Haack, Johanna

2018-03-01

A reimbursement category for "apps" does not exist in German statutory health insurance. Nevertheless different ways for reimbursement of digital health care products or processes exist. This article provides an overview and a description of the most relevant finance and reimbursement categories for apps in German statutory health insurance. The legal qualifications and preconditions of reimbursement in the context of single contracts with one health insurance fund will be discussed as well as collective contracts with national statutory health insurance funds. The benefit of a general outline appeals especially in respect to the numerous new players and products in the health care market. The article will highlight that health apps can challenge existing legal market access and reimbursement criteria and paths. At the same time, these criteria and paths exist. In terms of a learning system, they need to be met and followed.

WhatsApp Messenger as an Adjunctive Tool for Telemedicine: An Overview

PubMed Central

2017-01-01

Background The advent of telemedicine has allowed physicians to deliver medical treatment to patients from a distance. Mobile apps such as WhatsApp Messenger, an instant messaging service, came as a novel concept in all fields of social life, including medicine. The use of instant messaging services has been shown to improve communication within medical teams by providing means for quick teleconsultation, information sharing, and starting treatment as soon as possible. Objective The aim of this study was to perform a comprehensive systematic review of present literature on the use of the WhatsApp Messenger app as an adjunctive health care tool for medical doctors. Methods Searches were performed in PubMed, EMBASE, and the Cochrane Library using the term “whatsapp*” in articles published before January 2016. A bibliography of all relevant original articles that used the WhatsApp Messenger app was created. The level of evidence of each study was determined according to the Oxford Levels of Evidence ranking system produced by the Oxford Centre for Evidence-Based Medicine. The impact and the indications of WhatsApp Messenger are discussed in order to understand the extent to which this app currently functions as an adjunctive tool for telemedicine. Results The database search identified a total of 30 studies in which the term “whatsapp*” was used. Each article’s list of references was evaluated item-by-item. After literature reviews, letters to the editor, and low-quality studies were excluded, a total of 10 studies were found to be eligible for inclusion. Of these studies, 9 had been published in the English language and 1 had been published in Spanish. Five were published by medical doctors. Conclusions The pooled data presents compelling evidence that the WhatsApp Messenger app is a promising system, whether used as a communication tool between health care professionals, as a means of communication between health care professionals and the general public, or as a learning tool for providing health care information to professionals or to the general population. However, high-quality and properly evaluated research is needed, as are improvements in descriptions of the methodology and the study processes. These improvements will allow WhatsApp Messenger to be categorically defined as an effective telemedicine tool in many different fields of health care. PMID:28733273

Chemical-genetic profile analysis of five inhibitory compounds in yeast.

PubMed

Alamgir, Md; Erukova, Veronika; Jessulat, Matthew; Azizi, Ali; Golshani, Ashkan

2010-08-06

Chemical-genetic profiling of inhibitory compounds can lead to identification of their modes of action. These profiles can help elucidate the complex interactions between small bioactive compounds and the cell machinery, and explain putative gene function(s). Colony size reduction was used to investigate the chemical-genetic profile of cycloheximide, 3-amino-1,2,4-triazole, paromomycin, streptomycin and neomycin in the yeast Saccharomyces cerevisiae. These compounds target the process of protein biosynthesis. More than 70,000 strains were analyzed from the array of gene deletion mutant yeast strains. As expected, the overall profiles of the tested compounds were similar, with deletions for genes involved in protein biosynthesis being the major category followed by metabolism. This implies that novel genes involved in protein biosynthesis could be identified from these profiles. Further investigations were carried out to assess the activity of three profiled genes in the process of protein biosynthesis using relative fitness of double mutants and other genetic assays. Chemical-genetic profiles provide insight into the molecular mechanism(s) of the examined compounds by elucidating their potential primary and secondary cellular target sites. Our follow-up investigations into the activity of three profiled genes in the process of protein biosynthesis provided further evidence concerning the usefulness of chemical-genetic analyses for annotating gene functions. We termed these genes TAE2, TAE3 and TAE4 for translation associated elements 2-4.

A Reverse-Genetics Mutational Analysis of the Barley HvDWARF Gene Results in Identification of a Series of Alleles and Mutants with Short Stature of Various Degree and Disturbance in BR Biosynthesis Allowing a New Insight into the Process.

PubMed

Gruszka, Damian; Gorniak, Malgorzata; Glodowska, Ewelina; Wierus, Ewa; Oklestkova, Jana; Janeczko, Anna; Maluszynski, Miroslaw; Szarejko, Iwona

2016-04-22

Brassinosteroids (BRs) are plant steroid hormones, regulating a broad range of physiological processes. The largest amount of data related with BR biosynthesis has been gathered in Arabidopsis thaliana, however understanding of this process is far less elucidated in monocot crops. Up to now, only four barley genes implicated in BR biosynthesis have been identified. Two of them, HvDWARF and HvBRD, encode BR-6-oxidases catalyzing biosynthesis of castasterone, but their relation is not yet understood. In the present study, the identification of the HvDWARF genomic sequence, its mutational and functional analysis and characterization of new mutants are reported. Various types of mutations located in different positions within functional domains were identified and characterized. Analysis of their impact on phenotype of the mutants was performed. The identified homozygous mutants show reduced height of various degree and disrupted skotomorphogenesis. Mutational analysis of the HvDWARF gene with the "reverse genetics" approach allowed for its detailed functional analysis at the level of protein functional domains. The HvDWARF gene function and mutants' phenotypes were also validated by measurement of endogenous BR concentration. These results allowed a new insight into the BR biosynthesis in barley.

Lessons from the pilot of a mobile application to map assistive technology suppliers in Africa.

PubMed

Visagie, Surona J; Matter, Rebecca; Kayange, George M; Chiwaula, Mussa; Harniss, Mark; Mji, Gubela; Scheffler, Elsje

2018-01-01

A pilot project to develop and implement a mobile smartphone application (App) that tracks and maps assistive technology (AT) availability in southern Africa was launched in Botswana in 2016. The App was developed and tested through an iterative process. The concept of the App (AT-Info-Map) was well received by most stakeholders within the pilot country, and broader networks. Several technical and logistical obstacles were encountered. These included high data costs; difficulty in accessing AT information from the public healthcare sector, the largest supplier of AT; and the high human resource demand of collecting and keeping up-to-date device-level information within a complex and fragmented supply sector that spans private, public and civil society entities. The challenges were dealt with by keeping the data burden low and eliminating product-level tracking. The App design was expanded to include disability services, contextually specific AT categories and make navigation more intuitive. Long-term sustainability strategies like generating funding through advertisements on the App or supplier usage fees must be explored. Outreach and sensitisation programmes about both the App and AT in general must be intensified. The project team must continually strengthen partnerships with private and public stakeholders to ensure ongoing project engagement. The lessons learnt might be of value to others who wish to embark on initiatives in AT and/or implement Apps in health or disability in southern Africa and in low-resourced settings around the world.

GPR3 Stimulates Aβ Production via Interactions with APP and β-Arrestin2

PubMed Central

Nelson, Christopher D.; Sheng, Morgan

2013-01-01

The orphan G protein-coupled receptor (GPCR) GPR3 enhances the processing of Amyloid Precursor Protein (APP) to the neurotoxic beta-amyloid (Aβ) peptide via incompletely understood mechanisms. Through overexpression and shRNA knockdown experiments in HEK293 cells, we show that β-arrestin2 (βarr2), a GPCR-interacting scaffold protein reported to bind γ-secretase, is an essential factor for GPR3-stimulated Aβ production. For a panel of GPR3 receptor mutants, the degree of stimulation of Aβ production correlates with receptor-β-arrestin binding and receptor trafficking to endocytic vesicles. However, GPR3’s recruitment of βarr2 cannot be the sole explanation, because interaction with βarr2 is common to most GPCRs, whereas GPR3 is relatively unique among GPCRs in enhancing Aβ production. In addition to β-arrestin, APP is present in a complex with GPR3 and stimulation of Aβ production by GPR3 mutants correlates with their level of APP binding. Importantly, among a broader selection of GPCRs, only GPR3 and prostaglandin E receptor 2 subtype EP2 (PTGER2; another GPCR that increases Aβ production) interact with APP, and PTGER2 does so in an agonist-stimulated manner. These data indicate that a subset of GPCRs, including GPR3 and PTGER2, can associate with APP when internalized via βarr2, and thereby promote the cleavage of APP to generate Aβ. PMID:24069330

Autism, Alzheimer disease, and fragile X: APP, FMRP, and mGluR5 are molecular links.

PubMed

Sokol, D K; Maloney, B; Long, J M; Ray, B; Lahiri, D K

2011-04-12

The present review highlights an association between autism, Alzheimer disease (AD), and fragile X syndrome (FXS). We propose a conceptual framework involving the amyloid-β peptide (Aβ), Aβ precursor protein (APP), and fragile X mental retardation protein (FMRP) based on experimental evidence. The anabolic (growth-promoting) effect of the secreted α form of the amyloid-β precursor protein (sAPPα) may contribute to the state of brain overgrowth implicated in autism and FXS. Our previous report demonstrated that higher plasma sAPPα levels associate with more severe symptoms of autism, including aggression. This molecular effect could contribute to intellectual disability due to repression of cell-cell adhesion, promotion of dense, long, thin dendritic spines, and the potential for disorganized brain structure as a result of disrupted neurogenesis and migration. At the molecular level, APP and FMRP are linked via the metabotropic glutamate receptor 5 (mGluR5). Specifically, mGluR5 activation releases FMRP repression of APP mRNA translation and stimulates sAPP secretion. The relatively lower sAPPα level in AD may contribute to AD symptoms that significantly contrast with those of FXS and autism. Low sAPPα and production of insoluble Aβ would favor a degenerative process, with the brain atrophy seen in AD. Treatment with mGluR antagonists may help repress APP mRNA translation and reduce secretion of sAPP in FXS and perhaps autism.

Lessons from a Rare Familial Dementia: Amyloid and Beyond

PubMed Central

Cantlon, Adam; Frigerio, Carlo Sala; Walsh, Dominic M.

2015-01-01

Here we review the similarities between a rare inherited disorder, familial British dementia (FBD), and the most common of all late-life neurological conditions, Alzheimer's diseases (AD). We describe the symptoms, pathology and genetics of FBD, the biology of the BRI2 protein and mouse models of FBD and familial Danish dementia. In particular, we focus on the evolving recognition of the importance of protein oligomers and aberrant processing of the amyloid β-protein precursor (APP) - themes that are common to both FBD and AD. The initial discovery that FBD is phenotypically similar to AD, but associated with the deposition of an amyloid peptide (ABri) distinct from the amyloid β-protein (Aβ) led many to assume that amyloid production alone is sufficient to initiate disease and that ABri is the molecular equivalent of Aβ. Parallel with work on Aβ, studies of ABri producing animal models and in vitro ABri toxicity experiments caused a revision of the amyloid hypothesis and a focus on soluble oligomers of Aβ and ABri. Contemporaneous other studies suggested that loss of the ABri precursor protein (BRI2) may underlie the cognitive deficits in FBD. In this regard it is important to note that BRI2 has been shown to interact with and regulate the processing of APP, and that mutant BRI2 leads to altered cleavage of APP. A synthesis of these results suggests that a “two-hit mechanism” better explains FBD than earlier toxic gain of function and toxic loss of function models. The lessons learned from the study of FBD imply that the molecular pathology of AD is also likely to involve both aberrant aggregation (in AD, Aβ) and altered APP processing. With regard to FBD, we propose that the C-terminal 11 amino acid of FBD-BRI2 interfere with both the normal function of BRI2 and promotes the production of cystine cross-linked toxic ABri oligomers. In this scenario, loss of BRI2 function leads to altered APP processing in as yet underappreciated ways. Given the similarities between FBD and AD it seems likely that study of the structure of ABri oligomers and FBD-induced changes in APP metabolites will further our understanding of AD. PMID:26405694

Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranes.

PubMed

Vetrivel, Kulandaivelu S; Cheng, Haipeng; Lin, William; Sakurai, Takashi; Li, Tong; Nukina, Nobuyuki; Wong, Philip C; Xu, Huaxi; Thinakaran, Gopal

2004-10-22

Alzheimer's disease-associated beta-amyloid peptides (Abeta) are generated by the sequential proteolytic processing of amyloid precursor protein (APP) by beta- and gamma-secretases. There is growing evidence that cholesterol- and sphingolipid-rich membrane microdomains are involved in regulating trafficking and processing of APP. BACE1, the major beta-secretase in neurons is a palmitoylated transmembrane protein that resides in lipid rafts. A subset of APP is subject to amyloidogenic processing by BACE1 in lipid rafts, and this process depends on the integrity of lipid rafts. Here we describe the association of all four components of the gamma-secretase complex, namely presenilin 1 (PS1)-derived fragments, mature nicastrin, APH-1, and PEN-2, with cholesterol-rich detergent insoluble membrane (DIM) domains of non-neuronal cells and neurons that fulfill the criteria of lipid rafts. In PS1(-/-)/PS2(-/-) and NCT(-/-) fibroblasts, gamma-secretase components that still remain fail to become detergent-resistant, suggesting that raft association requires gamma-secretase complex assembly. Biochemical evidence shows that subunits of the gamma-secretase complex and three TGN/endosome-resident SNAREs cofractionate in sucrose density gradients, and show similar solubility or insolubility characteristics in distinct non-ionic and zwitterionic detergents, indicative of their co-residence in membrane microdomains with similar protein-lipid composition. This notion is confirmed using magnetic immunoisolation of PS1- or syntaxin 6-positive membrane patches from a mixture of membranes with similar buoyant densities following Lubrol WX extraction or sonication, and gradient centrifugation. These findings are consistent with the localization of gamma-secretase in lipid raft microdomains of post-Golgi and endosomes, organelles previously implicated in amyloidogenic processing of APP.

Association of γ-Secretase with Lipid Rafts in Post-Golgi and Endosome Membranes*

PubMed Central

Vetrivel, Kulandaivelu S.; Cheng, Haipeng; Lin, William; Sakurai, Takashi; Li, Tong; Nukina, Nobuyuki; Wong, Philip C.; Xu, Huaxi; Thinakaran, Gopal

2005-01-01

Alzheimer’s disease-associated β-amyloid peptides (Aβ) are generated by the sequential proteolytic processing of amyloid precursor protein (APP) by β- and γ-secretases. There is growing evidence that cholesterol- and sphingolipid-rich membrane microdomains are involved in regulating trafficking and processing of APP. BACE1, the major γ-secretase in neurons is a palmi-toylated transmembrane protein that resides in lipid rafts. A subset of APP is subject to amyloidogenic processing by BACE1 in lipid rafts, and this process depends on the integrity of lipid rafts. Here we describe the association of all four components of the γ-secretase complex, namely presenilin 1 (PS1)-derived fragments, mature nicastrin, APH-1, and PEN-2, with cholesterol-rich detergent insoluble membrane (DIM) domains of non-neuronal cells and neurons that fulfill the criteria of lipid rafts. In PS1−/−/PS2−/− and NCT−/− fibroblasts, γ-secretase components that still remain fail to become detergent-resistant, suggesting that raft association requires γ-secretase complex assembly. Biochemical evidence shows that subunits of the γ-secretase complex and three TGN/endosome-resident SNAREs cofractionate in sucrose density gradients, and show similar solubility or insolubility characteristics in distinct non-ionic and zwitterionic detergents, indicative of their co-residence in membrane microdomains with similar protein-lipid composition. This notion is confirmed using magnetic immunoisolation of PS1- or syntaxin 6-positive membrane patches from a mixture of membranes with similar buoyant densities following Lubrol WX extraction or sonication, and gradient centrifugation. These findings are consistent with the localization of γ-secretase in lipid raft microdomains of post-Golgi and endosomes, organelles previously implicated in amyloidogenic processing of APP. PMID:15322084

Mobile Application to Promote Adherence to Oral Chemotherapy and Symptom Management: A Protocol for Design and Development.

PubMed

Fishbein, Joel Nathan; Nisotel, Lauren Ellen; MacDonald, James John; Amoyal Pensak, Nicole; Jacobs, Jamie Michele; Flanagan, Clare; Jethwani, Kamal; Greer, Joseph Andrew

2017-04-20

Oral chemotherapy is increasingly used in place of traditional intravenous chemotherapy to treat patients with cancer. While oral chemotherapy includes benefits such as ease of administration, convenience, and minimization of invasive infusions, patients receive less oversight, support, and symptom monitoring from clinicians. Additionally, adherence is a well-documented challenge for patients with cancer prescribed oral chemotherapy regimens. With the ever-growing presence of smartphones and potential for efficacious behavioral intervention technology, we created a mobile health intervention for medication and symptom management. The objective of this study was to develop and evaluate the usability and acceptability of a smartphone app to support adherence to oral chemotherapy and symptom management in patients with cancer. We used a 5-step development model to create a comprehensive mobile app with theoretically informed content. The research and technical development team worked together to develop and iteratively test the app. In addition to the research team, key stakeholders including patients and family members, oncology clinicians, health care representatives, and practice administrators contributed to the content refinement of the intervention. Patient and family members also participated in alpha and beta testing of the final prototype to assess usability and acceptability before we began the randomized controlled trial. We incorporated app components based on the stakeholder feedback we received in focus groups and alpha and beta testing. App components included medication reminders, self-reporting of medication adherence and symptoms, an education library including nutritional information, Fitbit integration, social networking resources, and individually tailored symptom management feedback. We are conducting a randomized controlled trial to determine the effectiveness of the app in improving adherence to oral chemotherapy, quality of life, and burden of symptoms and side effects. At every stage in this trial, we are engaging stakeholders to solicit feedback on our progress and next steps. To our knowledge, we are the first to describe the development of an app designed for people taking oral chemotherapy. The app addresses many concerns with oral chemotherapy, such as medication adherence and symptom management. Soliciting feedback from stakeholders with broad perspectives and expertise ensured that the app was acceptable and potentially beneficial for patients, caregivers, and clinicians. In our development process, we instantiated 7 of the 8 best practices proposed in a recent review of mobile health app development. Our process demonstrated the importance of effective communication between research groups and technical teams, as well as meticulous planning of technical specifications before development begins. Future efforts should consider incorporating other proven strategies in software, such as gamification, to bolster the impact of mobile health apps. Forthcoming results from our randomized controlled trial will provide key data on the effectiveness of this app in improving medication adherence and symptom management. ClinicalTrials.gov NCT02157519; https://clinicaltrials.gov/ct2/show/NCT02157519 (Archived by WebCite at http://www.webcitation.org/6prj3xfKA). ©Joel Nathan Fishbein, Lauren Ellen Nisotel, James John MacDonald, Nicole Amoyal Pensak, Jamie Michele Jacobs, Clare Flanagan, Kamal Jethwani, Joseph Andrew Greer. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 20.04.2017.

Desirable Components for a Customized, Home-Based, Digital Care-Management App for Children and Young People With Long-Term, Chronic Conditions: A Qualitative Exploration

PubMed Central

Hall, Andrew; Gelder, Carole; Friedl, Simone; Brennan, Eileen; Swallow, Veronica

2017-01-01

Background Mobile apps for mobile phones and tablet devices are widely used by children and young people aged 0-18 years with long-term health conditions, such as chronic kidney disease (CKD), and their healthy peers for social networking or gaming. They are also poised to become a major source of health guidance. However, app development processes that are coproduced, rigorously developed, and evaluated to provide tailored, condition-specific, practical advice on day-to-day care management are seldom systematic or sufficiently described to enable replication. Furthermore, attempts to extrapolate to the real world are hampered by a poor understanding of the effects of key elements of app components. Therefore, effective and cost-effective novel, digital apps that will effectively and safely support care management are critical and timely. To inform development of such an app for children with CKD, a user requirements-gathering exercise was first needed. Objective To explore the views of children with CKD, their parents, and health care professionals to inform future development of a child-focused, care-management app. Methods Using age- and developmentally appropriate methods, we interviewed 36 participants: 5-10-year-olds (n=6), 11-14-year-olds (n=6), 15-18-year-olds (n=5), mothers (n=10), fathers (n=2), and health care professionals (n=7). Data were analyzed using Framework Analysis and behavior change theories. Results Of the 27 interviews, 19 (70%) interviews were individual and 8 (30%) were joint—5 out of 8 (63%) joint interviews were with a child or young person and their parent, 1 out of 8 (13%) were with a child and both parents, and 2 out of 8 (25%) were with 2 professionals. Three key themes emerged to inform development of a software requirement specification for a future home-based, digital care-management app intervention: (1) Gaps in current online information and support, (2) Difficulties experienced by children with a long-term condition, and (3) Suggestions for a digital care-management app. Reported gaps included the fact that current online information is not usually appropriate for children as it is “dry” and “boring,” could be “scary,” and was either hard to understand or not relevant to individuals’ circumstances. For children, searching online was much less accessible than using a professional-endorsed mobile app. Children also reported difficulty explaining their condition to others, maintaining treatment adherence, coping with feeling isolated, and with trying to live a “normal” life. There was recognition that a developmentally appropriate, CKD-specific app could support the process of explaining the condition to healthy peers, reducing isolation, adhering to care-management plans, and living a “normal” life. Participants recommended a range of media and content to include in a tailored, interactive, age- and developmentally appropriate app. For example, the user would be able to enter their age and diagnosis so that only age-appropriate and condition-specific content is displayed. Conclusions Future development of a digital app that meets the identified information and support needs and preferences of children with CKD will maximize its utility, thereby augmenting CKD caregiving and optimizing outcomes. PMID:28676470

Desirable Components for a Customized, Home-Based, Digital Care-Management App for Children and Young People With Long-Term, Chronic Conditions: A Qualitative Exploration.

PubMed

Nightingale, Ruth; Hall, Andrew; Gelder, Carole; Friedl, Simone; Brennan, Eileen; Swallow, Veronica

2017-07-04

Mobile apps for mobile phones and tablet devices are widely used by children and young people aged 0-18 years with long-term health conditions, such as chronic kidney disease (CKD), and their healthy peers for social networking or gaming. They are also poised to become a major source of health guidance. However, app development processes that are coproduced, rigorously developed, and evaluated to provide tailored, condition-specific, practical advice on day-to-day care management are seldom systematic or sufficiently described to enable replication. Furthermore, attempts to extrapolate to the real world are hampered by a poor understanding of the effects of key elements of app components. Therefore, effective and cost-effective novel, digital apps that will effectively and safely support care management are critical and timely. To inform development of such an app for children with CKD, a user requirements-gathering exercise was first needed. To explore the views of children with CKD, their parents, and health care professionals to inform future development of a child-focused, care-management app. Using age- and developmentally appropriate methods, we interviewed 36 participants: 5-10-year-olds (n=6), 11-14-year-olds (n=6), 15-18-year-olds (n=5), mothers (n=10), fathers (n=2), and health care professionals (n=7). Data were analyzed using Framework Analysis and behavior change theories. Of the 27 interviews, 19 (70%) interviews were individual and 8 (30%) were joint-5 out of 8 (63%) joint interviews were with a child or young person and their parent, 1 out of 8 (13%) were with a child and both parents, and 2 out of 8 (25%) were with 2 professionals. Three key themes emerged to inform development of a software requirement specification for a future home-based, digital care-management app intervention: (1) Gaps in current online information and support, (2) Difficulties experienced by children with a long-term condition, and (3) Suggestions for a digital care-management app. Reported gaps included the fact that current online information is not usually appropriate for children as it is "dry" and "boring," could be "scary," and was either hard to understand or not relevant to individuals' circumstances. For children, searching online was much less accessible than using a professional-endorsed mobile app. Children also reported difficulty explaining their condition to others, maintaining treatment adherence, coping with feeling isolated, and with trying to live a "normal" life. There was recognition that a developmentally appropriate, CKD-specific app could support the process of explaining the condition to healthy peers, reducing isolation, adhering to care-management plans, and living a "normal" life. Participants recommended a range of media and content to include in a tailored, interactive, age- and developmentally appropriate app. For example, the user would be able to enter their age and diagnosis so that only age-appropriate and condition-specific content is displayed. Future development of a digital app that meets the identified information and support needs and preferences of children with CKD will maximize its utility, thereby augmenting CKD caregiving and optimizing outcomes. ©Ruth Nightingale, Andrew Hall, Carole Gelder, Simone Friedl, Eileen Brennan, Veronica Swallow. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 04.07.2017.

Mutations in Four Glycosyl Hydrolases Reveal a Highly Coordinated Pathway for Rhodopsin Biosynthesis and N-Glycan Trimming in Drosophila melanogaster

PubMed Central

Rosenbaum, Erica E.; Vasiljevic, Eva; Brehm, Kimberley S.; Colley, Nansi Jo

2014-01-01

As newly synthesized glycoproteins move through the secretory pathway, the asparagine-linked glycan (N-glycan) undergoes extensive modifications involving the sequential removal and addition of sugar residues. These modifications are critical for the proper assembly, quality control and transport of glycoproteins during biosynthesis. The importance of N-glycosylation is illustrated by a growing list of diseases that result from defects in the biosynthesis and processing of N-linked glycans. The major rhodopsin in Drosophila melanogaster photoreceptors, Rh1, is highly unique among glycoproteins, as the N-glycan appears to be completely removed during Rh1 biosynthesis and maturation. However, much of the deglycosylation pathway for Rh1 remains unknown. To elucidate the key steps in Rh1 deglycosylation in vivo, we characterized mutant alleles of four Drosophila glycosyl hydrolases, namely α-mannosidase-II (α-Man-II), α-mannosidase-IIb (α-Man-IIb), a β-N-acetylglucosaminidase called fused lobes (Fdl), and hexosaminidase 1 (Hexo1). We have demonstrated that these four enzymes play essential and unique roles in a highly coordinated pathway for oligosaccharide trimming during Rh1 biosynthesis. Our results reveal that α-Man-II and α-Man-IIb are not isozymes like their mammalian counterparts, but rather function at distinct stages in Rh1 maturation. Also of significance, our results indicate that Hexo1 has a biosynthetic role in N-glycan processing during Rh1 maturation. This is unexpected given that in humans, the hexosaminidases are typically lysosomal enzymes involved in N-glycan catabolism with no known roles in protein biosynthesis. Here, we present a genetic dissection of glycoprotein processing in Drosophila and unveil key steps in N-glycan trimming during Rh1 biosynthesis. Taken together, our results provide fundamental advances towards understanding the complex and highly regulated pathway of N-glycosylation in vivo and reveal novel insights into the functions of glycosyl hydrolases in the secretory pathway. PMID:24785692

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.

Development and implementation of a smartphone application to promote physical activity and reduce screen-time in adolescent boys.

PubMed

Lubans, David R; Smith, Jordan J; Skinner, Geoff; Morgan, Philip J

2014-01-01

To describe the development and implementation of a smartphone application (app) designed to promote physical activity and reduce screen-time in adolescent boys considered "at-risk" of obesity. An app was developed to support the delivery of a face-to-face school-based obesity prevention program known as the "Active Teen Leaders Avoiding Screen-time" (ATLAS) program. ATLAS was guided by self-determination theory and social cognitive theory and evaluated using a cluster randomized controlled trial with 361 boys (12.7 ± 0.5 years) in 14 secondary schools. Following the completion of the study, participants in the intervention group completed a process evaluation questionnaire and focus groups were conducted with 42 students to explore their general perceptions of the ATLAS program and their experience with the smartphone app. Barriers and challenges encountered in the development, implementation, and evaluation of the app are also described. Participation in the study was not contingent on ownership of a smartphone, but 70% of participants in the intervention group reported having access to a smartphone or tablet device. Focus group participants reported an enjoyment of the program, and felt that it had provided them with new skills, techniques, and routines for the future. However, their engagement with the smartphone app was limited, due to a variety of reasons. Barriers to the implementation and evaluation of the app included limited access to smartphone devices, technical problems with the push notifications, lack of access to usage data, and the challenges of maintaining participants' interest in using the app. Although participants reported high levels of satisfaction with the ATLAS program in general, the smartphone app was not used extensively. Additional strategies and features may be needed to enhance engagement in adolescent boys.

Developing a smartphone 'app' for public health research: the example of measuring observed smoking in vehicles.

PubMed

Patel, Vimal; Nowostawski, Mariusz; Thomson, George; Wilson, Nick; Medlin, Hamish

2013-05-01

We have developed manual methods to gather data on the point prevalence of observed smoking in road vehicles. To enable the widespread international collection of such data, we aimed to develop a smartphone application (app) for this work. We developed specifications for an app that described the: (1) variables that could be collected; (2) transfer of data to an online repository; (3) user interface (including visual schematics) and (4) processes to ensure the data authenticity from distant observers. The app functionality was trialled in roadside situations and the app was made publicly available. The smartphone app and its accompanying website were developed, tested and released over a period of 6 months. Users (n=18) who have registered themselves (and who met authentication criteria), have reported no significant problems with this application to date (observing 20 535 vehicles as of 5 July 2012). The framework, methodology and source code for this project are now freely available online and can be easily adapted for other research purposes. The prevalence of smoking in vehicles was observed in: Poland 2.7% (95% CI 2.3% to 3.1%); Australia 1.0% (95% CI 0.7% to 1.3%); New Zealand 2.9% (95% CI 2.6% to 3.2%)-similar to results using preapp methods in 2011 (3.2%, 95% CI 3.1% to 3.3%). This project indicates that it can be practical and feasible for health researchers to work together with information science researchers and software developers to create smartphone apps for field research in public health. Such apps may be used to collect observational data more widely, effectively and easily than through traditional (non-electronic) methods.

Supporting cancer patients in illness management: usability evaluation of a mobile app.

PubMed

Mirkovic, Jelena; Kaufman, David R; Ruland, Cornelia M

2014-08-13

Mobile phones and tablets currently represent a significant presence in people's everyday lives. They enable access to different information and services independent of current place and time. Such widespread connectivity offers significant potential in different app areas including health care. Our goal was to evaluate the usability of the Connect Mobile app. The mobile app enables mobile access to the Connect system, an online system that supports cancer patients in managing health-related issues. Along with symptom management, the system promotes better patient-provider communication, collaboration, and shared decision making. The Connect Mobile app enables access to the Connect system over both mobile phones and tablets. The study consisted of usability tests of a high fidelity prototype with 7 cancer patients where the objectives were to identify existing design and functionality issues and to provide patients with a real look-and-feel of the mobile system. In addition, we conducted semistructured interviews to obtain participants' feedback about app usefulness, identify the need for new system features and design requirements, and measure the acceptance of the mobile app and its features within everyday health management. The study revealed a total of 27 design issues (13 for mobile apps and 14 for tablet apps), which were mapped to source events (ie, errors, requests for help, participants' concurrent feedback, and moderator observation). We also applied usability heuristics to identify violations of usability principles. The majority of violations were related to enabling ease of input, screen readability, and glanceability (15 issues), as well as supporting an appropriate match between systems and the real world (7 issues) and consistent mapping of system functions and interactions (4 issues). Feedback from participants also showed the cancer patients' requirements for support systems and how these needs are influenced by different context-related factors, such as type of access terminal (eg, desktop computer, tablet, mobile phone) and phases of illness. Based on the observed results, we proposed design and functionality recommendations that can be used for the development of mobile apps for cancer patients to support their health management process. Understanding and addressing users' requirements is one of the main prerequisites for developing useful and effective technology-based health interventions. The results of this study outline different user requirements related to the design of the mobile patient support app for cancer patients. The results will be used in the iterative development of the Connect Mobile app and can also inform other developers and researchers in development, integration, and evaluation of mobile health apps and services that support cancer patients in managing their health-related issues.

Parent and Clinician Preferences for an Asthma App to Promote Adolescent Self-Management: A Formative Study

PubMed Central

Roberts, Courtney A; Sage, Adam J; Coyne-Beasley, Tamera; Sleath, Betsy L; Carpenter, Delesha M

2016-01-01

Background Most youth asthma apps are not designed with parent and clinician use in mind, and rarely is the app development process informed by parent or clinician input. Objective This study was conducted to generate formative data on the use, attitudes, and preferences for asthma mHealth app features among parents and clinicians, the important stakeholders who support adolescents with asthma and promote adolescent self-management skills. Methods We conducted a mixed-methods study from 2013 to 2014 employing a user-centered design philosophy to acquire feedback from a convenience sample of 20 parents and 6 clinicians. Participants were given an iPod Touch and asked to evaluate 10 features on 2 existing asthma apps. Participant experiences using the apps were collected from questionnaires and a thematic analysis of audio-recorded and transcribed (verbatim) interviews using MAXQDA. Descriptive statistics were calculated to characterize the study sample and app feature feedback. Independent samples t tests were performed to compare parent and clinician ratings of app feature usefulness (ratings: 1=not at all useful to 5=very useful). Results All parents were female (n=20), 45% were black, 20% had an income ≥US $50,000, and 45% had a bachelor’s degree or higher education. The clinician sample included 2 nurses and 4 physicians with a mean practice time of 13 years. Three main themes provided an understanding of how participants perceived their roles and use of asthma app features to support adolescent asthma self-management: monitoring and supervision, education, and communication/information sharing. Parents rated the doctor report feature highest, and clinicians rated the doctor appointment reminder highest of all evaluated app features on usefulness. The peak flow monitoring feature was the lowest ranked feature by both parents and clinicians. Parents reported higher usefulness for the doctor report (t(10)=2.7, P<.02), diary (t(10)=2.7, P<.03), and self-check quiz (t(14)=2.5, P<.02) features than clinicians. Specific participant suggestions for app enhancements (eg, a tutorial showing correct inhaler use, refill reminders, pop-up messages tied to a medication log, evidence-based management steps) were also provided. Conclusions Parent and clinician evaluations and recommendations can play an important role in the development of an asthma app designed to help support youth asthma management. Two-way asthma care communication between families and clinicians and components involving families and clinicians that support adolescent self-management should be incorporated into adolescent asthma apps. PMID:27923777

Interaction of the amyloid precursor protein-like protein 1 (APLP1) E2 domain with heparan sulfate involves two distinct binding modes

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

Dahms, Sven O., E-mail: sdahms@fli-leibniz.de; Mayer, Magnus C.; Miltenyi Biotec GmbH, Robert-Koch-Strasse 1, 17166 Teterow

2015-03-01

Two X-ray structures of APLP1 E2 with and without a heparin dodecasaccharide are presented, revealing two distinct binding modes of the protein to heparan sulfate. The data provide a mechanistic explanation of how APP-like proteins bind to heparan sulfates and how they specifically recognize nonreducing structures of heparan sulfates. Beyond the pathology of Alzheimer’s disease, the members of the amyloid precursor protein (APP) family are essential for neuronal development and cell homeostasis in mammals. APP and its paralogues APP-like protein 1 (APLP1) and APP-like protein 2 (APLP2) contain the highly conserved heparan sulfate (HS) binding domain E2, which effects variousmore » (patho)physiological functions. Here, two crystal structures of the E2 domain of APLP1 are presented in the apo form and in complex with a heparin dodecasaccharide at 2.5 Å resolution. The apo structure of APLP1 E2 revealed an unfolded and hence flexible N-terminal helix αA. The (APLP1 E2){sub 2}–(heparin){sub 2} complex structure revealed two distinct binding modes, with APLP1 E2 explicitly recognizing the heparin terminus but also interacting with a continuous heparin chain. The latter only requires a certain register of the sugar moieties that fits to a positively charged surface patch and contributes to the general heparin-binding capability of APP-family proteins. Terminal binding of APLP1 E2 to heparin specifically involves a structure of the nonreducing end that is very similar to heparanase-processed HS chains. These data reveal a conserved mechanism for the binding of APP-family proteins to HS and imply a specific regulatory role of HS modifications in the biology of APP and APP-like proteins.« less

Testing an app for reporting health concerns-Experiences from older people and home care nurses.

PubMed

Göransson, Carina; Eriksson, Irene; Ziegert, Kristina; Wengström, Yvonne; Langius-Eklöf, Ann; Brovall, Maria; Kihlgren, Annica; Blomberg, Karin

2018-06-01

To explore the experiences of using an app among older people with home-based health care and their nurses. Few information and communication technology innovations have been developed and tested for older people with chronic conditions living at home with home-based health care support. Innovative ways to support older people's health and self-care are needed. Explorative qualitative design. For 3 months to report health concerns, older people receiving home-based health care used an interactive app, which included direct access to self-care advice, graphs and a risk assessment model that sends alerts to nurses for rapid management. Interviews with older people (n = 17) and focus group discussions with home care nurses (n = 12) were conducted and analysed using thematic analysis. The findings reveal that a process occurs. Using the app, the older people participated in their care, and the app enabled learning and a new way of communication. The interaction gave a sense of security and increased self-confidence among older people. The home care nurses viewed the alerts as appropriate for the management of health concerns. However, all participants experienced challenges in using new technology and had suggestions for improvement. The use of an app appears to increase the older people's participation in their health care and offers them an opportunity to be an active partner in their care. The app as a new way to interact with home care nurses increased the feeling of security. The older people were motivated to learn to use the app and described potential use for it in the future. The use of an app should be considered as a useful information and communication technology innovation that can improve communication and accessibility for older people with home-based health care. © 2017 John Wiley & Sons Ltd.

Barriers and Facilitators for the Use of a Medical Mobile App to Prevent Work-Related Risks in Pregnancy: A Qualitative Analysis

PubMed Central

van Beukering, Monique DM; Schaafsma, Frederieke G; Frings-Dresen, Monique HW; Mol, Ben WJ; van der Post, Joris AM; Kok, Marjolein

2017-01-01

Background The number of women participating in the labor market in Europe has increased over the last several decades. At the same time, there is growing evidence that certain conditions of employment during pregnancy may have a negative influence on pregnancy outcomes. In order to better inform pregnant women, we aim to develop an app to help assess the health risk as a result of personal and work-related factors and provide personal advice for these women and their health care providers. Objective The aim of this study was to compose a thematic overview of the perceived facilitators and barriers according to pregnant women, medical professionals, and employers for the use of a mobile app in obstetrical care to prevent occupational-related pregnancy complications. Methods Two multidisciplinary focus group meetings with in total 14 participants were conducted with pregnant women, occupational physicians, general practitioners, midwives, obstetricians, and representatives of trade unions and employer organizations. Transcripts were analyzed by qualitatively coding procedures and constant comparative methods. Results We identified 24 potential facilitators and 12 potential barriers for the use of the app in 4 categories: content of the app, the app as a mean to provide information, ease of use, and external factors. The 3 main facilitators identified were the need for a good interaction between the app and the user, apps were viewed as a more practical source of information, and the information should be understandable, according to the existing guidelines, and well-dosed. The 2 main barriers for use were extensive battery and memory use of the smartphone and sending frequent push notifications. Conclusions The results of this study are important considerations in the developing process of a medical app implementing a guideline or evidence-based information in practice. PMID:28830851

Cellulose Biosynthesis: Current Views and Evolving Concepts

PubMed Central

SAXENA, INDER M.; BROWN, R. MALCOLM

2005-01-01

• Aims To outline the current state of knowledge and discuss the evolution of various viewpoints put forth to explain the mechanism of cellulose biosynthesis. • Scope Understanding the mechanism of cellulose biosynthesis is one of the major challenges in plant biology. The simplicity in the chemical structure of cellulose belies the complexities that are associated with the synthesis and assembly of this polysaccharide. Assembly of cellulose microfibrils in most organisms is visualized as a multi-step process involving a number of proteins with the key protein being the cellulose synthase catalytic sub-unit. Although genes encoding this protein have been identified in almost all cellulose synthesizing organisms, it has been a challenge in general, and more specifically in vascular plants, to demonstrate cellulose synthase activity in vitro. The assembly of glucan chains into cellulose microfibrils of specific dimensions, viewed as a spontaneous process, necessitates the assembly of synthesizing sites unique to most groups of organisms. The steps of polymerization (requiring the specific arrangement and activity of the cellulose synthase catalytic sub-units) and crystallization (directed self-assembly of glucan chains) are certainly interlinked in the formation of cellulose microfibrils. Mutants affected in cellulose biosynthesis have been identified in vascular plants. Studies on these mutants and herbicide-treated plants suggest an interesting link between the steps of polymerization and crystallization during cellulose biosynthesis. • Conclusions With the identification of a large number of genes encoding cellulose synthases and cellulose synthase-like proteins in vascular plants and the supposed role of a number of other proteins in cellulose biosynthesis, a complete understanding of this process will necessitate a wider variety of research tools and approaches than was thought to be required a few years back. PMID:15894551

Cellulose biosynthesis: current views and evolving concepts.

PubMed

Saxena, Inder M; Brown, R Malcolm

2005-07-01

To outline the current state of knowledge and discuss the evolution of various viewpoints put forth to explain the mechanism of cellulose biosynthesis. * Understanding the mechanism of cellulose biosynthesis is one of the major challenges in plant biology. The simplicity in the chemical structure of cellulose belies the complexities that are associated with the synthesis and assembly of this polysaccharide. Assembly of cellulose microfibrils in most organisms is visualized as a multi-step process involving a number of proteins with the key protein being the cellulose synthase catalytic sub-unit. Although genes encoding this protein have been identified in almost all cellulose synthesizing organisms, it has been a challenge in general, and more specifically in vascular plants, to demonstrate cellulose synthase activity in vitro. The assembly of glucan chains into cellulose microfibrils of specific dimensions, viewed as a spontaneous process, necessitates the assembly of synthesizing sites unique to most groups of organisms. The steps of polymerization (requiring the specific arrangement and activity of the cellulose synthase catalytic sub-units) and crystallization (directed self-assembly of glucan chains) are certainly interlinked in the formation of cellulose microfibrils. Mutants affected in cellulose biosynthesis have been identified in vascular plants. Studies on these mutants and herbicide-treated plants suggest an interesting link between the steps of polymerization and crystallization during cellulose biosynthesis. * With the identification of a large number of genes encoding cellulose synthases and cellulose synthase-like proteins in vascular plants and the supposed role of a number of other proteins in cellulose biosynthesis, a complete understanding of this process will necessitate a wider variety of research tools and approaches than was thought to be required a few years back.

Popular Nutrition-Related Mobile Apps: A Feature Assessment

PubMed Central

Fallaize, Rosalind; Lovegrove, Julie A; Hwang, Faustina

2016-01-01

Background A key challenge in human nutrition is the assessment of usual food intake. This is of particular interest given recent proposals of eHealth personalized interventions. The adoption of mobile phones has created an opportunity for assessing and improving nutrient intake as they can be used for digitalizing dietary assessments and providing feedback. In the last few years, hundreds of nutrition-related mobile apps have been launched and installed by millions of users. Objective This study aims to analyze the main features of the most popular nutrition apps and to compare their strategies and technologies for dietary assessment and user feedback. Methods Apps were selected from the two largest online stores of the most popular mobile operating systems—the Google Play Store for Android and the iTunes App Store for iOS—based on popularity as measured by the number of installs and reviews. The keywords used in the search were as follows: calorie(s), diet, diet tracker, dietician, dietitian, eating, fit, fitness, food, food diary, food tracker, health, lose weight, nutrition, nutritionist, weight, weight loss, weight management, weight watcher, and ww calculator. The inclusion criteria were as follows: English language, minimum number of installs (1 million for Google Play Store) or reviews (7500 for iTunes App Store), relation to nutrition (ie, diet monitoring or recommendation), and independence from any device (eg, wearable) or subscription. Results A total of 13 apps were classified as popular for inclusion in the analysis. Nine apps offered prospective recording of food intake using a food diary feature. Food selection was available via text search or barcode scanner technologies. Portion size selection was only textual (ie, without images or icons). All nine of these apps were also capable of collecting physical activity (PA) information using self-report, the global positioning system (GPS), or wearable integrations. Their outputs focused predominantly on energy balance between dietary intake and PA. None of these nine apps offered features directly related to diet plans and motivational coaching. In contrast, the remaining four of the 13 apps focused on these opportunities, but without food diaries. One app—FatSecret—also had an innovative feature for connecting users with health professionals, and another—S Health—provided a nutrient balance score. Conclusions The high number of installs indicates that there is a clear interest and opportunity for diet monitoring and recommendation using mobile apps. All the apps collecting dietary intake used the same nutrition assessment method (ie, food diary record) and technologies for data input (ie, text search and barcode scanner). Emerging technologies, such as image recognition, natural language processing, and artificial intelligence, were not identified. None of the apps had a decision engine capable of providing personalized diet advice. PMID:27480144

AaEIN3 Mediates the Downregulation of Artemisinin Biosynthesis by Ethylene Signaling Through Promoting Leaf Senescence in Artemisia annua.

PubMed

Tang, Yueli; Li, Ling; Yan, Tingxiang; Fu, Xueqing; Shi, Pu; Shen, Qian; Sun, Xiaofen; Tang, Kexuan

2018-01-01

Artemisinin is an important drug for malaria treatment, which is exclusively produced in Artemisia annua . It's important to dissect the regulatory mechanism of artemisinin biosynthesis by diverse plant hormones and transcription factors. Our study shows ethylene, a plant hormone which accelerates flower and leaf senescence and fruit ripening, suppressed the expression of genes encoding three key enzymes ADS, DBR2, CYP71AV1, and a positive regulator AaORA involved in artemisinin biosynthesis. Then we isolated the gene encoding ETHYLENE-INSENSITIVE3 (EIN3), a key transcription factor in ethylene signaling pathway, by screening the transcriptome and genome database from Artemisia annua , named AaEIN3 . Overexpressing AaEIN3 suppressed artemisinin biosynthesis, while repressing its expression with RNAi enhanced artemisinin biosynthesis in Artemisia annua , indicating AaEIN3 negatively regulates artemisinin biosynthesis. Further study showed the downregulation of artemisinin biosynthesis by ethylene required the mediation of AaEIN3. AaEIN3 could accelerate leaf senescence, and leaf senescence attenuated the expression of ADS, DBR2, CYP71AV1 , and AaORA that are involved in artemisinin biosynthesis. Collectively, our study demonstrated a negative correlation between ethylene signaling and artemisinin biosynthesis, which is ascribed to AaEIN3-induced senescence process of leaves. Our work provided novel knowledge on the regulatory network of plant hormones for artemisinin metabolic pathway.

AaEIN3 Mediates the Downregulation of Artemisinin Biosynthesis by Ethylene Signaling Through Promoting Leaf Senescence in Artemisia annua

PubMed Central

Tang, Yueli; Li, Ling; Yan, Tingxiang; Fu, Xueqing; Shi, Pu; Shen, Qian; Sun, Xiaofen; Tang, Kexuan

2018-01-01

Artemisinin is an important drug for malaria treatment, which is exclusively produced in Artemisia annua. It’s important to dissect the regulatory mechanism of artemisinin biosynthesis by diverse plant hormones and transcription factors. Our study shows ethylene, a plant hormone which accelerates flower and leaf senescence and fruit ripening, suppressed the expression of genes encoding three key enzymes ADS, DBR2, CYP71AV1, and a positive regulator AaORA involved in artemisinin biosynthesis. Then we isolated the gene encoding ETHYLENE-INSENSITIVE3 (EIN3), a key transcription factor in ethylene signaling pathway, by screening the transcriptome and genome database from Artemisia annua, named AaEIN3. Overexpressing AaEIN3 suppressed artemisinin biosynthesis, while repressing its expression with RNAi enhanced artemisinin biosynthesis in Artemisia annua, indicating AaEIN3 negatively regulates artemisinin biosynthesis. Further study showed the downregulation of artemisinin biosynthesis by ethylene required the mediation of AaEIN3. AaEIN3 could accelerate leaf senescence, and leaf senescence attenuated the expression of ADS, DBR2, CYP71AV1, and AaORA that are involved in artemisinin biosynthesis. Collectively, our study demonstrated a negative correlation between ethylene signaling and artemisinin biosynthesis, which is ascribed to AaEIN3-induced senescence process of leaves. Our work provided novel knowledge on the regulatory network of plant hormones for artemisinin metabolic pathway. PMID:29675029

Transcript profiling of the immunological interactions between Actinobacillus pleuropneumoniae serotype 7 and the host by dual RNA-seq.

PubMed

Li, Ping; Xu, Zhiwen; Sun, Xiangang; Yin, Yue; Fan, Yi; Zhao, Jun; Mao, Xiyu; Huang, Jianbo; Yang, Fan; Zhu, Ling

2017-09-12

The complexity of the pathogenic mechanism underlying the host immune response to Actinobacillus pleuropneumonia (App) makes the use of preventive measures difficult, and a more global view of the host-pathogen interactions and new insights into this process are urgently needed to reveal the pathogenic and immune mechanisms underlying App infection. Here, we infected specific pathogen-free Mus musculus with App serotype 7 by intranasal inoculation to construct an acute hemorrhagic pneumonia infection model and isolated the infected lungs for analysis of the interactions by dual RNA-seq. Four cDNA libraries were constructed, and 2428 differentially expressed genes (DEGs) of the host and 333 DEGs of App were detected. The host DEGs were mainly enriched in inflammatory signaling pathways, such as the TLR, NLR, RLR, BCR and TCR signaling pathways, resulting in large-scale cytokine up-regulation and thereby yielding a cytokine cascade for anti-infection and lung damage. The majority of the up-regulated cytokines are involved in the IL-23/IL-17 cytokine-regulated network, which is crucial for host defense against bacterial infection. The DEGs of App were mainly related to the transport and metabolism of energy and materials. Most of these genes are metabolic genes involved in anaerobic metabolism and important for challenging the host and adapting to the anaerobic stress conditions observed in acute hemorrhagic pneumonia. Some of these genes, such as adhE, dmsA, and aspA, might be potential virulence genes. In addition, the up-regulation of genes associated with peptidoglycan and urease synthesis and the restriction of major virulence genes might be immune evasion strategies of App. The regulation of metabolic genes and major virulence genes indicate that the dominant antigens might differ during the infection process and that vaccines based on these antigens might allow establishment of a precise and targeted immune response during the early phase of infection. Through an analysis of transcriptional data by dual RNA-seq, our study presents a novel global view of the interactions of App with its host and provides a basis for further study.

Development of a Mobile Clinical Prediction Tool to Estimate Future Depression Severity and Guide Treatment in Primary Care: User-Centered Design.

PubMed

Wachtler, Caroline; Coe, Amy; Davidson, Sandra; Fletcher, Susan; Mendoza, Antonette; Sterling, Leon; Gunn, Jane

2018-04-23

Around the world, depression is both under- and overtreated. The diamond clinical prediction tool was developed to assist with appropriate treatment allocation by estimating the 3-month prognosis among people with current depressive symptoms. Delivering clinical prediction tools in a way that will enhance their uptake in routine clinical practice remains challenging; however, mobile apps show promise in this respect. To increase the likelihood that an app-delivered clinical prediction tool can be successfully incorporated into clinical practice, it is important to involve end users in the app design process. The aim of the study was to maximize patient engagement in an app designed to improve treatment allocation for depression. An iterative, user-centered design process was employed. Qualitative data were collected via 2 focus groups with a community sample (n=17) and 7 semistructured interviews with people with depressive symptoms. The results of the focus groups and interviews were used by the computer engineering team to modify subsequent protoypes of the app. Iterative development resulted in 3 prototypes and a final app. The areas requiring the most substantial changes following end-user input were related to the iconography used and the way that feedback was provided. In particular, communicating risk of future depressive symptoms proved difficult; these messages were consistently misinterpreted and negatively viewed and were ultimately removed. All participants felt positively about seeing their results summarized after completion of the clinical prediction tool, but there was a need for a personalized treatment recommendation made in conjunction with a consultation with a health professional. User-centered design led to valuable improvements in the content and design of an app designed to improve allocation of and engagement in depression treatment. Iterative design allowed us to develop a tool that allows users to feel hope, engage in self-reflection, and motivate them to treatment. The tool is currently being evaluated in a randomized controlled trial. ©Caroline Wachtler, Amy Coe, Sandra Davidson, Susan Fletcher, Antonette Mendoza, Leon Sterling, Jane Gunn. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 23.04.2018.

Evaluation of a Web-Based App Demonstrating an Exclusionary Algorithmic Approach to TNM Cancer Staging

PubMed Central

2015-01-01

Background TNM staging plays a critical role in the evaluation and management of a range of different types of cancers. The conventional combinatorial approach to the determination of an anatomic stage relies on the identification of distinct tumor (T), node (N), and metastasis (M) classifications to generate a TNM grouping. This process is inherently inefficient due to the need for scrupulous review of the criteria specified for each classification to ensure accurate assignment. An exclusionary approach to TNM staging based on sequential constraint of options may serve to minimize the number of classifications that need to be reviewed to accurately determine an anatomic stage. Objective Our aim was to evaluate the usability and utility of a Web-based app configured to demonstrate an exclusionary approach to TNM staging. Methods Internal medicine residents, surgery residents, and oncology fellows engaged in clinical training were asked to evaluate a Web-based app developed as an instructional aid incorporating (1) an exclusionary algorithm that polls tabulated classifications and sorts them into ranked order based on frequency counts, (2) reconfiguration of classification criteria to generate disambiguated yes/no questions that function as selection and exclusion prompts, and (3) a selectable grid of TNM groupings that provides dynamic graphic demonstration of the effects of sequentially selecting or excluding specific classifications. Subjects were asked to evaluate the performance of this app after completing exercises simulating the staging of different types of cancers encountered during training. Results Survey responses indicated high levels of agreement with statements supporting the usability and utility of this app. Subjects reported that its user interface provided a clear display with intuitive controls and that the exclusionary approach to TNM staging it demonstrated represented an efficient process of assignment that helped to clarify distinctions between tumor, node, and metastasis classifications. High overall usefulness ratings were bolstered by supplementary comments suggesting that this app might be readily adopted for use in clinical practice. Conclusions A Web-based app that utilizes an exclusionary algorithm to prompt the assignment of tumor, node, and metastasis classifications may serve as an effective instructional aid demonstrating an efficient and informative approach to TNM staging. PMID:28410163

[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.

Polyamines in plants: biosynthesis from arginine, and metabolic, physiological, and stress-response roles

USDA-ARS?s Scientific Manuscript database

Biogenic amines in all organisms including plants affect a myriad of growth and developmental processes. Therefore, there is continued interest in understanding their (here polyamines) biosynthesis and functional roles in regulating plant metabolism, physiology and development. The role of polyamine...

User-documented food consumption data from publicly available apps: an analysis of opportunities and challenges for nutrition research.

PubMed

Maringer, Marcus; Van't Veer, Pieter; Klepacz, Naomi; Verain, Muriel C D; Normann, Anne; Ekman, Suzanne; Timotijevic, Lada; Raats, Monique M; Geelen, Anouk

2018-06-09

The need for a better understanding of food consumption behaviour within its behavioural context has sparked the interest of nutrition researchers for user-documented food consumption data collected outside the research context using publicly available nutrition apps. The study aims to characterize the scientific, technical, legal and ethical features of this data in order to identify the opportunities and challenges associated with using this data for nutrition research. A search for apps collecting food consumption data was conducted in October 2016 against UK Google Play and iTunes storefronts. 176 apps were selected based on user ratings and English language support. Publicly available information from the app stores and app-related websites was investigated and relevant data extracted and summarized. Our focus was on characteristics related to scientific relevance, data management and legal and ethical governance of user-documented food consumption data. Food diaries are the most common form of data collection, allowing for multiple inputs including generic food items, packaged products, or images. Standards and procedures for compiling food databases used for estimating energy and nutrient intakes remain largely undisclosed. Food consumption data is interlinked with various types of contextual data related to behavioural motivation, physical activity, health, and fitness. While exchange of data between apps is common practise, the majority of apps lack technical documentation regarding data export. There is a similar lack of documentation regarding the implemented terms of use and privacy policies. While users are usually the owners of their data, vendors are granted irrevocable and royalty free licenses to commercially exploit the data. Due to its magnitude, diversity, and interconnectedness, user-documented food consumption data offers promising opportunities for a better understanding of habitual food consumption behaviour and its determinants. Non-standardized or non-documented food data compilation procedures, data exchange protocols and formats, terms of use and privacy statements, however, limit possibilities to integrate, process and share user-documented food consumption data. An ongoing research effort is required, to keep pace with the technical advancements of food consumption apps, their evolving data networks and the legal and ethical regulations related to protecting app users and their personal data.

De Novo Assembly and Comparative Transcriptome Analysis Provide Insight into Lysine Biosynthesis in Toona sinensis Roem.

PubMed

Zhang, Xia; Song, Zhenqiao; Liu, Tian; Guo, Linlin; Li, Xingfeng

2016-01-01

Toona sinensis Roem is a popular leafy vegetable in Chinese cuisine and is also used as a traditional Chinese medicine. In this study, leaf samples were collected from the same plant on two development stages and then used for high-throughput Illumina RNA-sequencing (RNA-Seq). 125,884 transcripts and 54,628 unigenes were obtained through de novo assembly. A total of 25,570 could be annotated with known biological functions, which indicated that the T. sinensis leaves and shoots were undergoing multiple developmental processes especially for active metabolic processes. Analysis of differentially expressed unigenes between the two libraries showed that the lysine biosynthesis was an enriched KEGG pathway, and candidate genes involved in the lysine biosynthesis pathway in T. sinensis leaves and shoots were identified. Our results provide a primary analysis of the gene expression files of T. sinensis leaf and shoot on different development stages and afford a valuable resource for genetic and genomic research on plant lysine biosynthesis.

Fungal biosynthesis of gold nanoparticles: mechanism and scale up

PubMed Central

Kitching, Michael; Ramani, Meghana; Marsili, Enrico

2015-01-01

Gold nanoparticles (AuNPs) are a widespread research tool because of their oxidation resistance, biocompatibility and stability. Chemical methods for AuNP synthesis often produce toxic residues that raise environmental concern. On the other hand, the biological synthesis of AuNPs in viable microorganisms and their cell-free extracts is an environmentally friendly and low-cost process. In general, fungi tolerate higher metal concentrations than bacteria and secrete abundant extracellular redox proteins to reduce soluble metal ions to their insoluble form and eventually to nanocrystals. Fungi harbour untapped biological diversity and may provide novel metal reductases for metal detoxification and bioreduction. A thorough understanding of the biosynthetic mechanism of AuNPs in fungi is needed to reduce the time of biosynthesis and to scale up the AuNP production process. In this review, we describe the known mechanisms for AuNP biosynthesis in viable fungi and fungal protein extracts and discuss the most suitable bioreactors for industrial AuNP biosynthesis. PMID:25154648

Oxidative Stress and Hypoxia Contribute to Alzheimer's Disease Pathogenesis: Two Sides of the Same Coin

PubMed Central

Guglielmotto, Michela; Tamagno, Elena; Danni, Oliviero

2009-01-01

While it is well established that stroke and cerebral hypoperfusion are risk factors for Alzheimer's disease (AD), the molecular link between ischemia/hypoxia and amyloid precursor protein (APP) processing has only been recently established. Here we review the role of the release of reactive oxygen species (ROS) by the mitochondrial electron chain in response to hypoxia, providing evidence that hypoxia fosters the amyloidogenic APP processing through a biphasic mechanism that up-regulates β-secretase activity, which involves an early release of ROS and an activation of HIF-1α. PMID:19705038

Stable analogues of OSB-AMP: potent inhibitors of MenE, the o-succinylbenzoate-CoA synthetase from bacterial menaquinone biosynthesis.

PubMed

Lu, Xuequan; Zhou, Rong; Sharma, Indrajeet; Li, Xiaokai; Kumar, Gyanendra; Swaminathan, Subramanyam; Tonge, Peter J; Tan, Derek S

2012-01-02

MenE, the o-succinylbenzoate (OSB)-CoA synthetase from bacterial menaquinone biosynthesis, is a promising new antibacterial target. Sulfonyladenosine analogues of the cognate reaction intermediate, OSB-AMP, have been developed as inhibitors of the MenE enzymes from Mycobacterium tuberculosis (mtMenE), Staphylococcus aureus (saMenE) and Escherichia coli (ecMenE). Both a free carboxylate and a ketone moiety on the OSB side chain are required for potent inhibitory activity. OSB-AMS (4) is a competitive inhibitor of mtMenE with respect to ATP (K(i) =5.4±0.1 nM) and a noncompetitive inhibitor with respect to OSB (K(i) =11.2±0.9 nM). These data are consistent with a Bi Uni Uni Bi Ping-Pong kinetic mechanism for these enzymes. In addition, OSB-AMS inhibits saMenE with K(i)(app) =22±8 nM and ecMenE with K(i)(OSB) =128±5 nM. Putative active-site residues, Arg222, which may interact with the OSB aromatic carboxylate, and Ser302, which may bind the OSB ketone oxygen, have been identified through computational docking of OSB-AMP with the unliganded crystal structure of saMenE. A pH-dependent interconversion of the free keto acid and lactol forms of the inhibitors is also described, along with implications for inhibitor design. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

ESUPPO: Next Generation

DTIC Science & Technology

2017-12-01

sessions were correlated quantitatively by the web-based survey , identifying the need to update eSUPPO with specific icons such as Innovation...focus groups and surveys , assesses how well the mobile app meets the needs of the Supply Corps community. The analysis begins by understanding the...the app. After a complete analysis of eSUPPO’s current “As-Is” processes, the study takes the information gathered from both the survey and focus

Assessment of soil health and fertility indicators with mobile phone imagery

NASA Astrophysics Data System (ADS)

Aitkenhead, Matt; Gwatkin, Richard; Coull, Malcolm; Donnelly, David

2015-04-01

Work on rapid soil assessment in the field has led to many hand-held sensors for soil monitoring (e.g. NIR, FTIR, XRF). Recent work by a research team at the James Hutton Institute has led to an integrated framework of mobile phones, apps and server-side processing. One example of this is the SOCIT app for estimating soil organic matter and carbon using geolocated mobile phone camera imagery. The SOCIT app is only applicable for agricultural soils in Scotland, and our intention is to expand this work both geographically and in functional ability. Ongoing work for the development of a prototype app for estimating soil characteristics across Europe using mobile phone imagery and the JRC LUCAS dataset will be described. Additionally, we will demonstrate recent work in estimating a number of soil health indicators from more detailed analysis of soil photographs. Accuracy levels achieved for estimating soil organic matter and organic carbon content, pH, structure, cation exchange capacity and texture vary and are not as good as those achieved with laboratory analysis, but are suitable for rapid field-based assessment. Issues relating to this work include colour stabilisation and calibration, integration with data on site characteristics, data processing, model development and the ethical use of data captured by others, and each of these topics will also be discussed.

Loss of function of ATXN1 increases amyloid beta-protein levels by potentiating beta-secretase processing of beta-amyloid precursor protein.

PubMed

Zhang, Can; Browne, Andrew; Child, Daniel; Divito, Jason R; Stevenson, Jesse A; Tanzi, Rudolph E

2010-03-19

Alzheimer disease (AD) is a devastating neurodegenerative disease with complex and strong genetic inheritance. Four genes have been established to either cause familial early onset AD (APP, PSEN1, and PSEN2) or to increase susceptibility for late onset AD (APOE). To date approximately 80% of the late onset AD genetic variance remains elusive. Recently our genome-wide association screen identified four novel late onset AD candidate genes. Ataxin 1 (ATXN1) is one of these four AD candidate genes and has been indicated to be the disease gene for spinocerebellar ataxia type 1, which is also a neurodegenerative disease. Mounting evidence suggests that the excessive accumulation of Abeta, the proteolytic product of beta-amyloid precursor protein (APP), is the primary AD pathological event. In this study, we ask whether ATXN1 may lead to AD pathogenesis by affecting Abeta and APP processing utilizing RNA interference in a human neuronal cell model and mouse primary cortical neurons. We show that knock-down of ATXN1 significantly increases the levels of both Abeta40 and Abeta42. This effect could be rescued with concurrent overexpression of ATXN1. Moreover, overexpression of ATXN1 decreased Abeta levels. Regarding the underlying molecular mechanism, we show that the effect of ATXN1 expression on Abeta levels is modulated via beta-secretase cleavage of APP. Taken together, ATXN1 functions as a genetic risk modifier that contributes to AD pathogenesis through a loss-of-function mechanism by regulating beta-secretase cleavage of APP and Abeta levels.

Loss of Function of ATXN1 Increases Amyloid β-Protein Levels by Potentiating β-Secretase Processing of β-Amyloid Precursor Protein*

PubMed Central

Zhang, Can; Browne, Andrew; Child, Daniel; DiVito, Jason R.; Stevenson, Jesse A.; Tanzi, Rudolph E.

2010-01-01

Alzheimer disease (AD) is a devastating neurodegenerative disease with complex and strong genetic inheritance. Four genes have been established to either cause familial early onset AD (APP, PSEN1, and PSEN2) or to increase susceptibility for late onset AD (APOE). To date ∼80% of the late onset AD genetic variance remains elusive. Recently our genome-wide association screen identified four novel late onset AD candidate genes. Ataxin 1 (ATXN1) is one of these four AD candidate genes and has been indicated to be the disease gene for spinocerebellar ataxia type 1, which is also a neurodegenerative disease. Mounting evidence suggests that the excessive accumulation of Aβ, the proteolytic product of β-amyloid precursor protein (APP), is the primary AD pathological event. In this study, we ask whether ATXN1 may lead to AD pathogenesis by affecting Aβ and APP processing utilizing RNA interference in a human neuronal cell model and mouse primary cortical neurons. We show that knock-down of ATXN1 significantly increases the levels of both Aβ40 and Aβ42. This effect could be rescued with concurrent overexpression of ATXN1. Moreover, overexpression of ATXN1 decreased Aβ levels. Regarding the underlying molecular mechanism, we show that the effect of ATXN1 expression on Aβ levels is modulated via β-secretase cleavage of APP. Taken together, ATXN1 functions as a genetic risk modifier that contributes to AD pathogenesis through a loss-of-function mechanism by regulating β-secretase cleavage of APP and Aβ levels. PMID:20097758

Autism, Alzheimer disease, and fragile X

PubMed Central

Sokol, D.K.; Maloney, B.; Long, J.M.; Ray, B.

2011-01-01

The present review highlights an association between autism, Alzheimer disease (AD), and fragile X syndrome (FXS). We propose a conceptual framework involving the amyloid-β peptide (Aβ), Aβ precursor protein (APP), and fragile X mental retardation protein (FMRP) based on experimental evidence. The anabolic (growth-promoting) effect of the secreted α form of the amyloid-β precursor protein (sAPPα) may contribute to the state of brain overgrowth implicated in autism and FXS. Our previous report demonstrated that higher plasma sAPPα levels associate with more severe symptoms of autism, including aggression. This molecular effect could contribute to intellectual disability due to repression of cell–cell adhesion, promotion of dense, long, thin dendritic spines, and the potential for disorganized brain structure as a result of disrupted neurogenesis and migration. At the molecular level, APP and FMRP are linked via the metabotropic glutamate receptor 5 (mGluR5). Specifically, mGluR5 activation releases FMRP repression of APP mRNA translation and stimulates sAPP secretion. The relatively lower sAPPα level in AD may contribute to AD symptoms that significantly contrast with those of FXS and autism. Low sAPPα and production of insoluble Aβ would favor a degenerative process, with the brain atrophy seen in AD. Treatment with mGluR antagonists may help repress APP mRNA translation and reduce secretion of sAPP in FXS and perhaps autism. PMID:21482951

Modern use of smartphone applications in the perioperative management in microsurgical breast reconstruction

PubMed Central

Rozen, Warren Matthew; Marsh, Daniel; Chow, Whitney T.H.; Vickers, Tobias; Khan, Lubna; Miller, George S.; Hunter-Smith, David J.; Ramakrishnan, Venkat V.

2016-01-01

Background Advances in mobile telecommunication, improved mobile internet and affordability have led to a significant increase in smartphone use within medicine. The capability of instant messaging, photography, videography, word processing, drawing and internet access allow significant potential in this small portable device. Smartphone use within medicine has grown tremendously worldwide given its affordability, improved internet and capabilities. Methods We have searched for apps specifically helpful in the perioperative care of microsurgical breast reconstructive patients. Results The useful apps have been subdivided: (I) communication apps—multimedia messaging, WhatsApp, PicSafeMedi: allow efficient communication via text, picture and video messages leading to earlier assessment and definitive management of free flaps; (II) storage apps—Notability, Elogbook: electronic storage of patient notes and logbooks of case which can be shared with others if required; (III) educational apps—FlapApp, Touch Surgery, PubMed on tap: step by step guides to surgical procedures to aid learning and medical journal database; (IV) flap monitoring app—SilpaRamanitor: free flap monitoring app based on photographic analysis for earlier detection of compromised flaps. Conclusions There has been remarkable growth in smartphones use among surgeons. Apps are being developed for every conceivable use. The future will be in wearable smart devices that allow continuous monitoring with the potential to instigate change should deviations from the norm occur. The smart watch is the start of this digital revolution. PMID:27047783

beta. -Amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues

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

Selkoe, D.J.; Podlisny, M.B.; Joachim, C.L.

1988-10-01

Progressive cerebral deposition of extracellular filaments composed of the {beta}-amyloid protein ({beta}AP) is a constant feature of Alzheimer disease (AD). Since the gene on chromosome 21 encoding the {beta}AP precursor ({beta}APP) is not known to be altered in AD, transcriptional or posttranslational changes may underlie accelerated {beta}AP deposition. Using two antibodies to the predicted carboxyl terminus of {beta}APP, the authors have identified the native {beta}APP in brain and nonneural human tissues as a 110- to 135-kDa protein complex that is insoluble in buffer and found in various membrane-rich subcellular fractions. These proteins are relatively uniformly distributed in adult brain, abundantmore » in fetal brain, and detected in nonneural tissues that contain {beta}APP mRNA. Similarly sized proteins occur in rat, cow, and monkey brain and in cultured human HL-60 and HeLa cells; the precise patterns in the 110- to 135-kDa range are heterogeneous among various tissues and cell lines. They conclude that the highly conserved {beta}APP molecule occurs in mammalian tissues as a heterogeneous group of membrane-associated proteins of {approx} 120 kDa. Detection of the nonamyloidogenic carboxyl terminus within plaques suggests that proteolytic processing of the {beta}APP into insoluble filaments occurs locally in cortical regions that develop {beta}-amyloid deposits with age.« less

Development, preliminary usability and accuracy testing of the EBMT 'eGVHD App' to support GvHD assessment according to NIH criteria-a proof of concept.

PubMed

Schoemans, H; Goris, K; Durm, R V; Vanhoof, J; Wolff, D; Greinix, H; Pavletic, S; Lee, S J; Maertens, J; Geest, S D; Dobbels, F; Duarte, R F

2016-08-01

The EBMT Complications and Quality of Life Working Party has developed a computer-based algorithm, the 'eGVHD App', using a user-centered design process. Accuracy was tested using a quasi-experimental crossover design with four expert-reviewed case vignettes in a convenience sample of 28 clinical professionals. Perceived usefulness was evaluated by the technology acceptance model (TAM) and User satisfaction by the Post-Study System Usability Questionnaire (PSSUQ). User experience was positive, with a median of 6 TAM points (interquartile range: 1) and beneficial median total, and subscale PSSUQ scores. The initial standard practice assessment of the vignettes yielded 65% correct results for diagnosis and 45% for scoring. The 'eGVHD App' significantly increased diagnostic and scoring accuracy to 93% (+28%) and 88% (+43%), respectively (both P<0.05). The same trend was observed in the repeated analysis of case 2: accuracy improved by using the App (+31% for diagnosis and +39% for scoring), whereas performance tended to decrease once the App was taken away. The 'eGVHD App' could dramatically improve the quality of care and research as it increased the performance of the whole user group by about 30% at the first assessment and showed a trend for improvement of individual performance on repeated case evaluation.

Selective deletion of apolipoprotein E in astrocytes ameliorates the spatial learning and memory deficits in Alzheimer's disease (APP/PS1) mice by inhibiting TGF-β/Smad2/STAT3 signaling.

PubMed

Zheng, Jin-Yu; Sun, Jian; Ji, Chun-Mei; Shen, Lin; Chen, Zhong-Jun; Xie, Peng; Sun, Yuan-Zhao; Yu, Ru-Tong

2017-06-01

Astrocytes and apolipoprotein E (apoE) play critical roles in cognitive function, not only under physiological conditions but also in some pathological situations, particularly in the pathological progression of Alzheimer's disease (AD). The regulatory mechanisms underlying the effect of apoE, derived from astrocytes, on cognitive deficits during AD pathology development are unclear. In this study, we generated amyloid precursor protein/apoE knockout (APP/apoE KO ) and APP/glial fibrillary acidic protein (GFAP)-apoE KO mice (the AD mice model used in this study was based on the APP-familial Alzheimer disease overexpression) to investigate the role of apoE, derived from astrocytes, in AD pathology and cognitive function. To explore the mechanism, we investigated the amyloidogenic process related transforming growth factor β/mothers against decapentaplegic homolog 2/signal transducer and activator of transcription 3 (TGF-β/Smad2/STAT3) signaling pathway and further confirmed by administering TGF-β-overexpression adeno-associated virus (specific to astrocytes) to APP/GFAP-apoE KO mice and TGF-β-inhibition adeno-associated virus (specific to astrocytes) to APP/WT mice. Whole body deletion of apoE significantly ameliorated the spatial learning and memory impairment, reduced amyloid β-protein production and inhibited astrogliosis in APP/apoE KO mice, as well as specific deletion apoE in astrocytes in APP/GFAP-apoE KO mice. Moreover, amyloid β-protein accumulation was increased due to promotion of amyloidogenesis of APP, and astrogliosis was upregulated by activation of TGF-β/Smad2/STAT3 signaling. Furthermore, the overexpression of TGF-β in astrocytes in APP/GFAP-apoE KO mice abrogated the effects of apoE knockout. In contrast, repression of TGF-β in astrocytes of APP/WT mice exerted a therapeutic effect similar to apoE knockout. These data suggested that apoE derived from astrocytes contributes to the risk of AD through TGF-β/Smad2/STAT3 signaling activation. These findings enhance our understanding of the role of apoE, derived from astrocytes, in AD and suggest it to be a potential biomarker and therapeutic target for AD. Copyright © 2017 Elsevier Inc. All rights reserved.

New target prediction and visualization tools incorporating open source molecular fingerprints for TB Mobile 2.0

PubMed Central

2014-01-01

Background We recently developed a freely available mobile app (TB Mobile) for both iOS and Android platforms that displays Mycobacterium tuberculosis (Mtb) active molecule structures and their targets with links to associated data. The app was developed to make target information available to as large an audience as possible. Results We now report a major update of the iOS version of the app. This includes enhancements that use an implementation of ECFP_6 fingerprints that we have made open source. Using these fingerprints, the user can propose compounds with possible anti-TB activity, and view the compounds within a cluster landscape. Proposed compounds can also be compared to existing target data, using a näive Bayesian scoring system to rank probable targets. We have curated an additional 60 new compounds and their targets for Mtb and added these to the original set of 745 compounds. We have also curated 20 further compounds (many without targets in TB Mobile) to evaluate this version of the app with 805 compounds and associated targets. Conclusions TB Mobile can now manage a small collection of compounds that can be imported from external sources, or exported by various means such as email or app-to-app inter-process communication. This means that TB Mobile can be used as a node within a growing ecosystem of mobile apps for cheminformatics. It can also cluster compounds and use internal algorithms to help identify potential targets based on molecular similarity. TB Mobile represents a valuable dataset, data-visualization aid and target prediction tool. PMID:25302078

New target prediction and visualization tools incorporating open source molecular fingerprints for TB Mobile 2.0.

PubMed

Clark, Alex M; Sarker, Malabika; Ekins, Sean

2014-01-01

We recently developed a freely available mobile app (TB Mobile) for both iOS and Android platforms that displays Mycobacterium tuberculosis (Mtb) active molecule structures and their targets with links to associated data. The app was developed to make target information available to as large an audience as possible. We now report a major update of the iOS version of the app. This includes enhancements that use an implementation of ECFP_6 fingerprints that we have made open source. Using these fingerprints, the user can propose compounds with possible anti-TB activity, and view the compounds within a cluster landscape. Proposed compounds can also be compared to existing target data, using a näive Bayesian scoring system to rank probable targets. We have curated an additional 60 new compounds and their targets for Mtb and added these to the original set of 745 compounds. We have also curated 20 further compounds (many without targets in TB Mobile) to evaluate this version of the app with 805 compounds and associated targets. TB Mobile can now manage a small collection of compounds that can be imported from external sources, or exported by various means such as email or app-to-app inter-process communication. This means that TB Mobile can be used as a node within a growing ecosystem of mobile apps for cheminformatics. It can also cluster compounds and use internal algorithms to help identify potential targets based on molecular similarity. TB Mobile represents a valuable dataset, data-visualization aid and target prediction tool.

Docosahexaenoic Acid Reduces Amyloid β Production via Multiple Pleiotropic Mechanisms*

PubMed Central

Grimm, Marcus O. W.; Kuchenbecker, Johanna; Grösgen, Sven; Burg, Verena K.; Hundsdörfer, Benjamin; Rothhaar, Tatjana L.; Friess, Petra; de Wilde, Martijn C.; Broersen, Laus M.; Penke, Botond; Péter, Mária; Vígh, László; Grimm, Heike S.; Hartmann, Tobias

2011-01-01

Alzheimer disease is characterized by accumulation of the β-amyloid peptide (Aβ) generated by β- and γ-secretase processing of the amyloid precursor protein (APP). The intake of the polyunsaturated fatty acid docosahexaenoic acid (DHA) has been associated with decreased amyloid deposition and a reduced risk in Alzheimer disease in several epidemiological trials; however, the exact underlying molecular mechanism remains to be elucidated. Here, we systematically investigate the effect of DHA on amyloidogenic and nonamyloidogenic APP processing and the potential cross-links to cholesterol metabolism in vivo and in vitro. DHA reduces amyloidogenic processing by decreasing β- and γ-secretase activity, whereas the expression and protein levels of BACE1 and presenilin1 remain unchanged. In addition, DHA increases protein stability of α-secretase resulting in increased nonamyloidogenic processing. Besides the known effect of DHA to decrease cholesterol de novo synthesis, we found cholesterol distribution in plasma membrane to be altered. In the presence of DHA, cholesterol shifts from raft to non-raft domains, and this is accompanied by a shift in γ-secretase activity and presenilin1 protein levels. Taken together, DHA directs amyloidogenic processing of APP toward nonamyloidogenic processing, effectively reducing Aβ release. DHA has a typical pleiotropic effect; DHA-mediated Aβ reduction is not the consequence of a single major mechanism but is the result of combined multiple effects. PMID:21324907

Downstream reactions and engineering in the microbially reconstituted pathway for Taxol.

PubMed

Jiang, Ming; Stephanopoulos, Gregory; Pfeifer, Blaine A

2012-05-01

Taxol (a trademarked product of Bristol-Myers Squibb) is a complex isoprenoid natural product which has displayed potent anticancer activity. Originally isolated from the Pacific yew tree (Taxus brevifolia), Taxol has been mass-produced through processes reliant on plant-derived biosynthesis. Recently, there have been alternative efforts to reconstitute the biosynthetic process through technically convenient microbial hosts, which offer unmatched growth kinetics and engineering potential. Such an approach is made challenging by the need to successfully introduce the significantly foreign enzymatic steps responsible for eventual biosynthesis. Doing so, however, offers the potential to engineer more efficient and economical production processes and the opportunity to design and produce tailored analog compounds with enhanced properties. This mini review will specifically focus on heterologous biosynthesis as it applies to Taxol with an emphasis on the challenges associated with introducing and reconstituting the downstream reaction steps needed for final bioactivity.

PhzA/B catalyzes the formation of the tricycle in phenazine biosynthesis.

USDA-ARS?s Scientific Manuscript database

Phenazines are redox-active bacterial secondary metabolites that participate in important biological processes such as the generation of toxic reactive oxygen species and the reduction of environmental iron. Their biosynthesis from chorismic acid depends on enzymes encoded by the phz operon, but man...

Evidence-Based mHealth Chronic Disease Mobile App Intervention Design: Development of a Framework.

PubMed

Wilhide Iii, Calvin C; Peeples, Malinda M; Anthony Kouyaté, Robin C

2016-02-16

Mobile technology offers new capabilities that can help to drive important aspects of chronic disease management at both an individual and population level, including the ability to deliver real-time interventions that can be connected to a health care team. A framework that supports both development and evaluation is needed to understand the aspects of mHealth that work for specific diseases, populations, and in the achievement of specific outcomes in real-world settings. This framework should incorporate design structure and process, which are important to translate clinical and behavioral evidence, user interface, experience design and technical capabilities into scalable, replicable, and evidence-based mobile health (mHealth) solutions to drive outcomes. The purpose of this paper is to discuss the identification and development of an app intervention design framework, and its subsequent refinement through development of various types of mHealth apps for chronic disease. The process of developing the framework was conducted between June 2012 and June 2014. Informed by clinical guidelines, standards of care, clinical practice recommendations, evidence-based research, best practices, and translated by subject matter experts, a framework for mobile app design was developed and the refinement of the framework across seven chronic disease states and three different product types is described. The result was the development of the Chronic Disease mHealth App Intervention Design Framework. This framework allowed for the integration of clinical and behavioral evidence for intervention and feature design. The application to different diseases and implementation models guided the design of mHealth solutions for varying levels of chronic disease management. The framework and its design elements enable replicable product development for mHealth apps and may provide a foundation for the digital health industry to systematically expand mobile health interventions and validate their effectiveness across multiple implementation settings and chronic diseases.

Technology-Assisted Behavioral Intervention to Extend Sleep Duration: Development and Design of the Sleep Bunny Mobile App.

PubMed

Baron, Kelly Glazer; Duffecy, Jennifer; Reid, Kathryn; Begale, Mark; Caccamo, Lauren

2018-01-10

Despite the high prevalence of short sleep duration (29.2% of adults sleep <6 hours on weekdays), there are no existing theory-based behavioral interventions to extend sleep duration. The popularity of wearable sleep trackers provides an opportunity to engage users in interventions. The objective of this study was to outline the theoretical foundation and iterative process of designing the "Sleep Bunny," a technology-assisted sleep extension intervention including a mobile phone app, wearable sleep tracker, and brief telephone coaching. We conducted a two-step process in the development of this intervention, which was as follows: (1) user testing of the app and (2) a field trial that was completed by 2 participants with short sleep duration and a cardiovascular disease risk factor linked to short sleep duration (body mass index [BMI] >25). All participants had habitual sleep duration <6.5 hours verified by 7 days of actigraphy. A total of 6 individuals completed initial user testing in the development phase, and 2 participants completed field testing. Participants in the user testing and field testing responded to open-ended surveys about the design and utility of the app. Participants in the field testing completed the Epworth Sleepiness Scale and also wore an actigraph for a 1-week baseline period and during the 4-week intervention period. The feedback suggests that users enjoyed the wearable sleep tracker and found the app visually pleasing, but they suggested improvements to the notification and reminder features of the app. The 2 participants who completed the field test demonstrated significant improvements in sleep duration and daytime sleepiness. Further testing is needed to determine effects of this intervention in populations at risk for the mental and physical consequences of sleep loss. ©Kelly Glazer Baron, Jennifer Duffecy, Kathryn Reid, Mark Begale, Lauren Caccamo. Originally published in JMIR Mental Health (http://mental.jmir.org), 10.01.2018.

The Prenylflavonoid Xanthohumol Reduces Alzheimer-Like Changes and Modulates Multiple Pathogenic Molecular Pathways in the Neuro2a/APPswe Cell Model of AD.

PubMed

Huang, Xianfeng; Wang, Jing; Chen, Xiao; Liu, Pan; Wang, Shujin; Song, Fangchen; Zhang, Zaijun; Zhu, Feiqi; Huang, Xinfeng; Liu, Jianjun; Song, Guoqiang; Spencer, Peter S; Yang, Xifei

2018-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has proved refractory to drug treatment. Given evidence of neuroprotection in animal models of ischemic stroke, we assessed the prenylflavonoid xanthohumol from the Common Hop ( Humulus lupulus L.) for therapeutic potential in murine neuroblastoma N2a cells stably expressing human Swedish mutant amyloid precursor protein (N2a/APP), a well-characterized cellular model of AD. The ELISA and Western-blot analysis revealed that xanthohumol (Xn) inhibited Aβ accumulation and APP processing, and that Xn ameliorated tau hyperphosphorylation via PP2A, GSK3β pathways in N2a/APP cells. The amelioration of tau hyperphosphorylation by Xn was also validated on HEK293/Tau cells, another cell line with tau hyperphosphorylation. Proteomic analysis (2D-DIGE-coupled MS) revealed a total of 30 differentially expressed lysate proteins in N2a/APP vs. wild-type (WT) N2a cells (N2a/WT), and a total of 21 differentially expressed proteins in lysates of N2a/APP cells in the presence or absence of Xn. Generally, these 51 differential proteins could be classified into seven main categories according to their functions, including: endoplasmic reticulum (ER) stress-associated proteins; oxidative stress-associated proteins; proteasome-associated proteins; ATPase and metabolism-associated proteins; cytoskeleton-associated proteins; molecular chaperones-associated proteins, and others. We used Western-blot analysis to validate Xn-associated changes of some key proteins in several biological/pathogenic processes. Taken together, we show that Xn reduces AD-related changes in stably transfected N2a/APP cells. The underlying mechanisms involve modulation of multiple pathogenic pathways, including those involved in ER stress, oxidative stress, proteasome molecular systems, and the neuronal cytoskeleton. These results suggest Xn may have potential for the treatment of AD and/or neuropathologically related neurodegenerative diseases.

Exposure to As-, Cd-, and Pb-mixture induces Aβ, amyloidogenic APP processing and cognitive impairments via oxidative stress-dependent neuroinflammation in young rats.

PubMed

Ashok, Anushruti; Rai, Nagendra Kumar; Tripathi, Sachin; Bandyopadhyay, Sanghamitra

2015-01-01

Environmental pollutants act as risk factors for Alzheimer's disease (AD), mainly affecting the aging population. We investigated early manifestations of AD-like pathology by a mixture of arsenic (As), cadmium (Cd), and lead (Pb), reported to impair neurodevelopment. We treated rats with As+Cd+Pb at their concentrations detected in groundwater of India, ie, 0.38, 0.098, and 0.22 ppm or 10 times of each, respectively, from gestation-05 to postnatal day-180. We identified dose-dependent increase in amyloid-beta (Aβ) in frontal cortex and hippocampus as early as post-weaning. The effect was strongly significant during early-adulthood, reaching levels comparable to an Aβ-infused AD-like rat model. The metals activated the proamyloidogenic pathway, mediated by increase in amyloid precursor protein (APP), and subsequent beta secretase (BACE) and presenilin (PS)-mediated APP-processing. Investigating the mechanism of Aβ-induction revealed an augmentation in oxidative stress-dependent neuroinflammation that stimulated APP expression through interleukin-responsive-APP-mRNA 5'-untranslated region. We then examined the effects of individual metals and binary mixtures in comparison with the tertiary. Among individual metals, Pb triggered maximum induction of Aβ, whereas individual As or Cd had a relatively non-significant effect on Aβ despite enhanced APP, owing to reduced induction of BACE and PS. Interestingly, when combined the metals demonstrated synergism, with a major contribution by As. The synergistic effect was significant and consistent in tertiary mixture, resulting in the augmentation of Aβ. Eventually, increase in Aβ culminated in cognitive impairments in the young rats. Together, our data demonstrate that exposure to As+Cd+Pb induces premature manifestation of AD-like pathology that is synergistic, and oxidative stress and inflammation dependent. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Zinc and Copper Differentially Modulate Amyloid Precursor Protein Processing by γ-Secretase and Amyloid-β Peptide Production.

PubMed

Gerber, Hermeto; Wu, Fang; Dimitrov, Mitko; Garcia Osuna, Guillermo M; Fraering, Patrick C

2017-03-03

Recent evidence suggests involvement of biometal homeostasis in the pathological mechanisms in Alzheimer's disease (AD). For example, increased intracellular copper or zinc has been linked to a reduction in secreted levels of the AD-causing amyloid-β peptide (Aβ). However, little is known about whether these biometals modulate the generation of Aβ. In the present study we demonstrate in both cell-free and cell-based assays that zinc and copper regulate Aβ production by distinct molecular mechanisms affecting the processing by γ-secretase of its Aβ precursor protein substrate APP-C99. We found that Zn 2+ induces APP-C99 dimerization, which prevents its cleavage by γ-secretase and Aβ production, with an IC 50 value of 15 μm Importantly, at this concentration, Zn 2+ also drastically raised the production of the aggregation-prone Aβ43 found in the senile plaques of AD brains and elevated the Aβ43:Aβ40 ratio, a promising biomarker for neurotoxicity and AD. We further demonstrate that the APP-C99 histidine residues His-6, His-13, and His-14 control the Zn 2+ -dependent APP-C99 dimerization and inhibition of Aβ production, whereas the increased Aβ43:Aβ40 ratio is substrate dimerization-independent and involves the known Zn 2+ binding lysine Lys-28 residue that orientates the APP-C99 transmembrane domain within the lipid bilayer. Unlike zinc, copper inhibited Aβ production by directly targeting the subunits presenilin and nicastrin in the γ-secretase complex. Altogether, our data demonstrate that zinc and copper differentially modulate Aβ production. They further suggest that dimerization of APP-C99 or the specific targeting of individual residues regulating the production of the long, toxic Aβ species, may offer two therapeutic strategies for preventing AD. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Evidence-Based mHealth Chronic Disease Mobile App Intervention Design: Development of a Framework

PubMed Central

Peeples, Malinda M; Anthony Kouyaté, Robin C

2016-01-01

Background Mobile technology offers new capabilities that can help to drive important aspects of chronic disease management at both an individual and population level, including the ability to deliver real-time interventions that can be connected to a health care team. A framework that supports both development and evaluation is needed to understand the aspects of mHealth that work for specific diseases, populations, and in the achievement of specific outcomes in real-world settings. This framework should incorporate design structure and process, which are important to translate clinical and behavioral evidence, user interface, experience design and technical capabilities into scalable, replicable, and evidence-based mobile health (mHealth) solutions to drive outcomes. Objective The purpose of this paper is to discuss the identification and development of an app intervention design framework, and its subsequent refinement through development of various types of mHealth apps for chronic disease. Methods The process of developing the framework was conducted between June 2012 and June 2014. Informed by clinical guidelines, standards of care, clinical practice recommendations, evidence-based research, best practices, and translated by subject matter experts, a framework for mobile app design was developed and the refinement of the framework across seven chronic disease states and three different product types is described. Results The result was the development of the Chronic Disease mHealth App Intervention Design Framework. This framework allowed for the integration of clinical and behavioral evidence for intervention and feature design. The application to different diseases and implementation models guided the design of mHealth solutions for varying levels of chronic disease management. Conclusions The framework and its design elements enable replicable product development for mHealth apps and may provide a foundation for the digital health industry to systematically expand mobile health interventions and validate their effectiveness across multiple implementation settings and chronic diseases. PMID:26883135

WhatsApp Messenger as an Adjunctive Tool for Telemedicine: An Overview.

PubMed

Giordano, Vincenzo; Koch, Hilton; Godoy-Santos, Alexandre; Dias Belangero, William; Esteves Santos Pires, Robinson; Labronici, Pedro

2017-07-21

The advent of telemedicine has allowed physicians to deliver medical treatment to patients from a distance. Mobile apps such as WhatsApp Messenger, an instant messaging service, came as a novel concept in all fields of social life, including medicine. The use of instant messaging services has been shown to improve communication within medical teams by providing means for quick teleconsultation, information sharing, and starting treatment as soon as possible. The aim of this study was to perform a comprehensive systematic review of present literature on the use of the WhatsApp Messenger app as an adjunctive health care tool for medical doctors. Searches were performed in PubMed, EMBASE, and the Cochrane Library using the term "whatsapp*" in articles published before January 2016. A bibliography of all relevant original articles that used the WhatsApp Messenger app was created. The level of evidence of each study was determined according to the Oxford Levels of Evidence ranking system produced by the Oxford Centre for Evidence-Based Medicine. The impact and the indications of WhatsApp Messenger are discussed in order to understand the extent to which this app currently functions as an adjunctive tool for telemedicine. The database search identified a total of 30 studies in which the term "whatsapp*" was used. Each article's list of references was evaluated item-by-item. After literature reviews, letters to the editor, and low-quality studies were excluded, a total of 10 studies were found to be eligible for inclusion. Of these studies, 9 had been published in the English language and 1 had been published in Spanish. Five were published by medical doctors. The pooled data presents compelling evidence that the WhatsApp Messenger app is a promising system, whether used as a communication tool between health care professionals, as a means of communication between health care professionals and the general public, or as a learning tool for providing health care information to professionals or to the general population. However, high-quality and properly evaluated research is needed, as are improvements in descriptions of the methodology and the study processes. These improvements will allow WhatsApp Messenger to be categorically defined as an effective telemedicine tool in many different fields of health care. ©Vincenzo Giordano, Hilton Koch, Alexandre Godoy-Santos, William Dias Belangero, Robinson Esteves Santos Pires, Pedro Labronici. Originally published in the Interactive Journal of Medical Research (http://www.i-jmr.org/), 21.07.2017.

Transcriptional Regulation and Transport of Terpenoid Indole Alkaloid in Catharanthus roseus: Exploration of New Research Directions

PubMed Central

Liu, Jiaqi; Cai, Junjun; Wang, Rui; Yang, Shihai

2016-01-01

As one of the model medicinal plants for exploration of biochemical pathways and molecular biological questions on complex metabolic pathways, Catharanthus roseus synthesizes more than 100 terpenoid indole alkaloids (TIAs) used for clinical treatment of various diseases and for new drug discovery. Given that extensive studies have revealed the major metabolic pathways and the spatial-temporal biosynthesis of TIA in C. roseus plant, little is known about subcellular and inter-cellular trafficking or long-distance transport of TIA end products or intermediates, as well as their regulation. While these transport processes are indispensable for multi-organelle, -tissue and -cell biosynthesis, storage and their functions, great efforts have been made to explore these dynamic cellular processes. Progress has been made in past decades on transcriptional regulation of TIA biosynthesis by transcription factors as either activators or repressors; recent studies also revealed several transporters involved in subcellular and inter-cellular TIA trafficking. However, many details and the regulatory network for controlling the tissue-or cell-specific biosynthesis, transport and storage of serpentine and ajmalicine in root, catharanthine in leaf and root, vindoline specifically in leaf and vinblastine and vincristine only in green leaf and their biosynthetic intermediates remain to be determined. This review is to summarize the progress made in biosynthesis, transcriptional regulation and transport of TIAs. Based on analysis of organelle, tissue and cell-type specific biosynthesis and progresses in transport and trafficking of similar natural products, the transporters that might be involved in transport of TIAs and their synthetic intermediates are discussed; according to transcriptome analysis and bioinformatic approaches, the transcription factors that might be involved in TIA biosynthesis are analyzed. Further discussion is made on a broad context of transcriptional and transport regulation in order to guide our future research. PMID:28036025

Paleoproterozoic sterol biosynthesis and the rise of oxygen

NASA Astrophysics Data System (ADS)

Gold, David A.; Caron, Abigail; Fournier, Gregory P.; Summons, Roger E.

2017-03-01

Natural products preserved in the geological record can function as ‘molecular fossils’, providing insight into organisms and physiologies that existed in the deep past. One important group of molecular fossils is the steroidal hydrocarbons (steranes), which are the diagenetic remains of sterol lipids. Complex sterols with modified side chains are unique to eukaryotes, although simpler sterols can also be synthesized by a few bacteria. Sterol biosynthesis is an oxygen-intensive process; thus, the presence of complex steranes in ancient rocks not only signals the presence of eukaryotes, but also aerobic metabolic processes. In 1999, steranes were reported in 2.7 billion year (Gyr)-old rocks from the Pilbara Craton in Australia, suggesting a long delay between photosynthetic oxygen production and its accumulation in the atmosphere (also known as the Great Oxidation Event) 2.45-2.32 Gyr ago. However, the recent reappraisal and rejection of these steranes as contaminants pushes the oldest reported steranes forward to around 1.64 Gyr ago (ref. 6). Here we use a molecular clock approach to improve constraints on the evolution of sterol biosynthesis. We infer that stem eukaryotes shared functionally modern sterol biosynthesis genes with bacteria via horizontal gene transfer. Comparing multiple molecular clock analyses, we find that the maximum marginal probability for the divergence time of bacterial and eukaryal sterol biosynthesis genes is around 2.31 Gyr ago, concurrent with the most recent geochemical evidence for the Great Oxidation Event. Our results therefore indicate that simple sterol biosynthesis existed well before the diversification of living eukaryotes, substantially predating the oldest detected sterane biomarkers (approximately 1.64 Gyr ago), and furthermore, that the evolutionary history of sterol biosynthesis is tied to the first widespread availability of molecular oxygen in the ocean-atmosphere system.

Paleoproterozoic sterol biosynthesis and the rise of oxygen.

PubMed

Gold, David A; Caron, Abigail; Fournier, Gregory P; Summons, Roger E

2017-03-16

Natural products preserved in the geological record can function as 'molecular fossils', providing insight into organisms and physiologies that existed in the deep past. One important group of molecular fossils is the steroidal hydrocarbons (steranes), which are the diagenetic remains of sterol lipids. Complex sterols with modified side chains are unique to eukaryotes, although simpler sterols can also be synthesized by a few bacteria. Sterol biosynthesis is an oxygen-intensive process; thus, the presence of complex steranes in ancient rocks not only signals the presence of eukaryotes, but also aerobic metabolic processes. In 1999, steranes were reported in 2.7 billion year (Gyr)-old rocks from the Pilbara Craton in Australia, suggesting a long delay between photosynthetic oxygen production and its accumulation in the atmosphere (also known as the Great Oxidation Event) 2.45-2.32 Gyr ago. However, the recent reappraisal and rejection of these steranes as contaminants pushes the oldest reported steranes forward to around 1.64 Gyr ago (ref. 6). Here we use a molecular clock approach to improve constraints on the evolution of sterol biosynthesis. We infer that stem eukaryotes shared functionally modern sterol biosynthesis genes with bacteria via horizontal gene transfer. Comparing multiple molecular clock analyses, we find that the maximum marginal probability for the divergence time of bacterial and eukaryal sterol biosynthesis genes is around 2.31 Gyr ago, concurrent with the most recent geochemical evidence for the Great Oxidation Event. Our results therefore indicate that simple sterol biosynthesis existed well before the diversification of living eukaryotes, substantially predating the oldest detected sterane biomarkers (approximately 1.64 Gyr ago), and furthermore, that the evolutionary history of sterol biosynthesis is tied to the first widespread availability of molecular oxygen in the ocean-atmosphere system.

Management of the General Process of Parenteral Nutrition Using mHealth Technologies: Evaluation and Validation Study.

PubMed

Cervera Peris, Mercedes; Alonso Rorís, Víctor Manuel; Santos Gago, Juan Manuel; Álvarez Sabucedo, Luis; Wanden-Berghe, Carmina; Sanz-Valero, Javier

2018-04-03

Any system applied to the control of parenteral nutrition (PN) ought to prove that the process meets the established requirements and include a repository of records to allow evaluation of the information about PN processes at any time. The goal of the research was to evaluate the mobile health (mHealth) app and validate its effectiveness in monitoring the management of the PN process. We studied the evaluation and validation of the general process of PN using an mHealth app. The units of analysis were the PN bags prepared and administered at the Son Espases University Hospital, Palma, Spain, from June 1 to September 6, 2016. For the evaluation of the app, we used the Poststudy System Usability Questionnaire and subsequent analysis with the Cronbach alpha coefficient. Validation was performed by checking the compliance of control for all operations on each of the stages (validation and transcription of the prescription, preparation, conservation, and administration) and by monitoring the operative control points and critical control points. The results obtained from 387 bags were analyzed, with 30 interruptions of administration. The fulfillment of stages was 100%, including noncritical nonconformities in the storage control. The average deviation in the weight of the bags was less than 5%, and the infusion time did not present deviations greater than 1 hour. The developed app successfully passed the evaluation and validation tests and was implemented to perform the monitoring procedures for the overall PN process. A new mobile solution to manage the quality and traceability of sensitive medicines such as blood-derivative drugs and hazardous drugs derived from this project is currently being deployed. ©Mercedes Cervera Peris, Víctor Manuel Alonso Rorís, Juan Manuel Santos Gago, Luis Álvarez Sabucedo, Carmina Wanden-Berghe, Javier Sanz-Valero. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 03.04.2018.

Novel insights into the effect of nitrogen on storage protein biosynthesis and protein body development in wheat caryopsis.

PubMed

Yu, Xurun; Chen, Xinyu; Wang, Leilei; Yang, Yang; Zhu, Xiaowei; Shao, Shanshan; Cui, Wenxue; Xiong, Fei

2017-04-01

Molecular and cytological mechanisms concerning the effects of nitrogen on wheat (Triticum aestivum L.) storage protein biosynthesis and protein body development remain largely elusive. We used transcriptome sequencing, proteomics techniques, and light microscopy to investigate these issues. In total, 2585 differentially expressed genes (DEGs) and 57 differentially expressed proteins (DEPs) were found 7 days after anthesis (DAA), and 2456 DEGs and 64 DEPs were detected 18 DAA after nitrogen treatment. Gene ontology terms related to protein biosynthesis processes enriched these numbers by 678 and 582 DEGs at 7 and 18 DAA, respectively. Further, 25 Kyoto Encyclopedia of Genes and Genomes pathways were involved in protein biosynthesis at both 7 and 18 DAA. DEPs related to storage protein biosynthesis contained gliadin and glutenin subunits, most of which were up-regulated after nitrogen treatment. Quantitative real-time PCR analysis indicated that some gliadin and glutenin subunit encoding genes were differentially expressed at 18 DAA. Structural observation revealed that wheat endosperm accumulated more and larger protein bodies after nitrogen treatment. Collectively, our findings suggest that nitrogen treatment enhances storage protein content, endosperm protein body quantity, and partial processing quality by altering the expression levels of certain genes involved in protein biosynthesis pathways and storage protein expression at the proteomics level. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Assay Methods for ACS Activity and ACS Phosphorylation by MAP Kinases In Vitro and In Vivo.

PubMed

Han, Xiaomin; Li, Guojing; Zhang, Shuqun

2017-01-01

Ethylene, a gaseous phytohormone, has profound effects on plant growth, development, and adaptation to the environment. Ethylene-regulated processes begin with the induction of ethylene biosynthesis. There are two key steps in ethylene biosynthesis. The first is the biosynthesis of 1-aminocyclopropane-1-carboxylic acid (ACC) from S-Adenosyl-Methionine (SAM), a common precursor in many metabolic pathways, which is catalyzed by ACC synthase (ACS). The second is the oxidative cleavage of ACC to form ethylene under the action of ACC oxidase (ACO). ACC biosynthesis is the committing and generally the rate-limiting step in ethylene biosynthesis. As a result, characterizing the cellular ACS activity and understanding its regulation are important. In this chapter, we detail the methods used to measure, (1) the enzymatic activity of both recombinant and native ACS proteins, and (2) the phosphorylation of ACS protein by mitogen-activated protein kinases (MAPKs) in vivo and in vitro.

Crush the Crave: Development and Formative Evaluation of a Smartphone App for Smoking Cessation.

PubMed

Baskerville, Neill B; Struik, Laura L; Dash, Darly

2018-03-02

Emerging evidence supports the use of smartphone apps for smoking cessation, especially in young adults given their high smoking rates and high smartphone ownership rates. Although evaluative evidence is encouraging for supporting smoking cessation, there remains a paucity of research describing the design and development processes of mobile health (mHealth) interventions. The aim of this paper was to describe the process of developing Crush the Crave (CTC), an evidence-informed app to support smoking cessation in young adults, and the results of a formative evaluation of app usage behavior, as part of a broader program of research that seeks to establish the effectiveness of the CTC app. The Spiral Technology Action Research (STAR) 5-cycle model (listen, plan, do, act, and study) was employed to guide the development, implementation, and dissemination of CTC. The approach to development and formative evaluation included focus groups with young adult smokers (n=78) across 2 phases, analysis of the content of existing apps, 2 sessions with content experts, and Google Analytics to assess user behavior during a 12-month pilot. LISTEN-focus groups revealed young adult smoker preferences of (1) positive reinforcement, (2) personalization, (3) social support, (4) quit support, (5) tracking the behavior, and (6) tracking quit benefits. PLAN-informed by evidence for smoking cessation, young adult preferences and an assessment of popular cessation apps, content experts produced a mind map and a storyboard describing app content and structure. DO-focus groups with young adult smokers provided feedback on the first version of the app with opinions on content and suggestions for improvement such as providing alerts and distractions from craving. ACT-refinements were made, and app content was organized using the 4 key design components informed by principles of persuasive technology for behavior change: credibility, task support, dialogue support, and social support. CTC was launched in April 2013 and piloted from the period July 2013 to June 2014 where 1987 Android users had 18,567 sessions, resulting in 59,384 page views and 89.58% (1780/1987) of users returning within the same day to use CTC. STUDY-a pragmatic randomized controlled trial of CTC was launched in August 2014 to demonstrate that including mHealth technology as a population-based intervention can help young adult smokers to quit. The results of this phase will be presented in a subsequent publication. CTC is one of the first smoking cessation apps designed to meet the needs of young adult smokers. The development was informed by the inclusion of young adults in the design and the systematic application of multiple stakeholder input, scientific evidence, and theory. The STAR model approach was followed from the beginning of intervention development, which should facilitate optimization of mHealth interventions in the future. ClinicalTrials.gov NCT01983150; http://clinicaltrials.gov/ct2/show/NCT01983150 (Archived by WebCite at http://www.webcitation.org/6VGyc0W0i). ©Neill B Baskerville, Laura L Struik, Darly Dash. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 02.03.2018.

Crush the Crave: Development and Formative Evaluation of a Smartphone App for Smoking Cessation

PubMed Central

2018-01-01

Background Emerging evidence supports the use of smartphone apps for smoking cessation, especially in young adults given their high smoking rates and high smartphone ownership rates. Although evaluative evidence is encouraging for supporting smoking cessation, there remains a paucity of research describing the design and development processes of mobile health (mHealth) interventions. Objective The aim of this paper was to describe the process of developing Crush the Crave (CTC), an evidence-informed app to support smoking cessation in young adults, and the results of a formative evaluation of app usage behavior, as part of a broader program of research that seeks to establish the effectiveness of the CTC app. Methods The Spiral Technology Action Research (STAR) 5-cycle model (listen, plan, do, act, and study) was employed to guide the development, implementation, and dissemination of CTC. The approach to development and formative evaluation included focus groups with young adult smokers (n=78) across 2 phases, analysis of the content of existing apps, 2 sessions with content experts, and Google Analytics to assess user behavior during a 12-month pilot. Results LISTEN—focus groups revealed young adult smoker preferences of (1) positive reinforcement, (2) personalization, (3) social support, (4) quit support, (5) tracking the behavior, and (6) tracking quit benefits. PLAN—informed by evidence for smoking cessation, young adult preferences and an assessment of popular cessation apps, content experts produced a mind map and a storyboard describing app content and structure. DO—focus groups with young adult smokers provided feedback on the first version of the app with opinions on content and suggestions for improvement such as providing alerts and distractions from craving. ACT—refinements were made, and app content was organized using the 4 key design components informed by principles of persuasive technology for behavior change: credibility, task support, dialogue support, and social support. CTC was launched in April 2013 and piloted from the period July 2013 to June 2014 where 1987 Android users had 18,567 sessions, resulting in 59,384 page views and 89.58% (1780/1987) of users returning within the same day to use CTC. STUDY—a pragmatic randomized controlled trial of CTC was launched in August 2014 to demonstrate that including mHealth technology as a population-based intervention can help young adult smokers to quit. The results of this phase will be presented in a subsequent publication. Conclusions CTC is one of the first smoking cessation apps designed to meet the needs of young adult smokers. The development was informed by the inclusion of young adults in the design and the systematic application of multiple stakeholder input, scientific evidence, and theory. The STAR model approach was followed from the beginning of intervention development, which should facilitate optimization of mHealth interventions in the future. Trial Registration ClinicalTrials.gov NCT01983150; http://clinicaltrials.gov/ct2/show/NCT01983150 (Archived by WebCite at http://www.webcitation.org/6VGyc0W0i) PMID:29500157

Trans fatty acids enhance amyloidogenic processing of the Alzheimer amyloid precursor protein (APP).

PubMed

Grimm, Marcus O W; Rothhaar, Tatjana L; Grösgen, Sven; Burg, Verena K; Hundsdörfer, Benjamin; Haupenthal, Viola J; Friess, Petra; Kins, Stefan; Grimm, Heike S; Hartmann, Tobias

2012-10-01

Hydrogenation of oils and diary products of ruminant animals leads to an increasing amount of trans fatty acids in the human diet. Trans fatty acids are incorporated in several lipids and accumulate in the membrane of cells. Here we systematically investigate whether the regulated intramembrane proteolysis of the amyloid precursor protein (APP) is affected by trans fatty acids compared to the cis conformation. Our experiments clearly show that trans fatty acids compared to cis fatty acids increase amyloidogenic and decrease nonamyloidogenic processing of APP, resulting in an increased production of amyloid beta (Aβ) peptides, main components of senile plaques, which are a characteristic neuropathological hallmark for Alzheimer's disease (AD). Moreover, our results show that oligomerization and aggregation of Aβ are increased by trans fatty acids. The mechanisms identified by this in vitro study suggest that the intake of trans fatty acids potentially increases the AD risk or causes an earlier onset of the disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Sleep apps: what role do they play in clinical medicine?

PubMed

Lorenz, Christopher P; Williams, Adrian J

2017-11-01

Today's smartphones boast more computing power than the Apollo Guidance Computer. Given the ubiquity and popularity of smartphones, are we already carrying around miniaturized sleep labs in our pockets? There is still a lack of validation studies for consumer sleep technologies in general and apps for monitoring sleep in particular. To overcome this gap, multidisciplinary teams are needed that focus on feasibility work at the intersection of software engineering, data science and clinical sleep medicine. To date, no smartphone app for monitoring sleep through movement sensors has been successfully validated against polysomnography, despite the role and validity of actigraphy in sleep medicine having been well established. Missing separation of concerns, not methodology, poses the key limiting factor: The two essential steps in the monitoring process, data collection and scoring, are chained together inside a black box due to the closed nature of consumer devices. This leaves researchers with little room for influence nor can they access raw data. Multidisciplinary teams that wield complete power over the sleep monitoring process are sorely needed.

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.

Microbial consortia in meat processing environments

NASA Astrophysics Data System (ADS)

Alessandria, V.; Rantsiou, K.; Cavallero, M. C.; Riva, S.; Cocolin, L.

2017-09-01

Microbial contamination in food processing plants can play a fundamental role in food quality and safety. The description of the microbial consortia in the meat processing environment is important since it is a first step in understanding possible routes of product contamination. Furthermore, it may contribute in the development of sanitation programs for effective pathogen removal. The purpose of this study was to characterize the type of microbiota in the environment of meat processing plants: the microbiota of three different meat plants was studied by both traditional and molecular methods (PCR-DGGE) in two different periods. Different levels of contamination emerged between the three plants as well as between the two sampling periods. Conventional methods of killing free-living bacteria through antimicrobial agents and disinfection are often ineffective against bacteria within a biofilm. The use of gas-discharge plasmas potentially can offer a good alternative to conventional sterilization methods. The purpose of this study was to measure the effectiveness of Atmospheric Pressure Plasma (APP) surface treatments against bacteria in biofilms. Biofilms produced by three different L. monocytogenes strains on stainless steel surface were subjected to three different conditions (power, exposure time) of APP. Our results showed how most of the culturable cells are inactivated after the Plasma exposure but the RNA analysis by qPCR highlighted the entrance of the cells in the viable-but non culturable (VBNC) state, confirming the hypothesis that cells are damaged after plasma treatment, but in a first step, still remain alive. The understanding of the effects of APP on the L. monocytogenes biofilm can improve the development of sanitation programs with the use of APP for effective pathogen removal.

Disruption of transporters affiliated with enantio-pyochelin biosynthesis gene cluster of Pseudomonas protegens Pf-5 has pleiotropic effects

USDA-ARS?s Scientific Manuscript database

Pseudomonas protegens Pf-5 (formerly Pseudomonas fluorescens) is a biocontrol bacterium that produces the siderophore enantio-pyochelin under conditions of iron starvation in a process that is often accompanied by the secretion of its biosynthesis intermediates, salicylic acid and dihydroaeruginoic ...

Supporting Cancer Patients in Illness Management: Usability Evaluation of a Mobile App

PubMed Central

Kaufman, David R; Ruland, Cornelia M

2014-01-01

Background Mobile phones and tablets currently represent a significant presence in people’s everyday lives. They enable access to different information and services independent of current place and time. Such widespread connectivity offers significant potential in different app areas including health care. Objective Our goal was to evaluate the usability of the Connect Mobile app. The mobile app enables mobile access to the Connect system, an online system that supports cancer patients in managing health-related issues. Along with symptom management, the system promotes better patient-provider communication, collaboration, and shared decision making. The Connect Mobile app enables access to the Connect system over both mobile phones and tablets. Methods The study consisted of usability tests of a high fidelity prototype with 7 cancer patients where the objectives were to identify existing design and functionality issues and to provide patients with a real look-and-feel of the mobile system. In addition, we conducted semistructured interviews to obtain participants’ feedback about app usefulness, identify the need for new system features and design requirements, and measure the acceptance of the mobile app and its features within everyday health management. Results The study revealed a total of 27 design issues (13 for mobile apps and 14 for tablet apps), which were mapped to source events (ie, errors, requests for help, participants' concurrent feedback, and moderator observation). We also applied usability heuristics to identify violations of usability principles. The majority of violations were related to enabling ease of input, screen readability, and glanceability (15 issues), as well as supporting an appropriate match between systems and the real world (7 issues) and consistent mapping of system functions and interactions (4 issues). Feedback from participants also showed the cancer patients’ requirements for support systems and how these needs are influenced by different context-related factors, such as type of access terminal (eg, desktop computer, tablet, mobile phone) and phases of illness. Based on the observed results, we proposed design and functionality recommendations that can be used for the development of mobile apps for cancer patients to support their health management process. Conclusions Understanding and addressing users’ requirements is one of the main prerequisites for developing useful and effective technology-based health interventions. The results of this study outline different user requirements related to the design of the mobile patient support app for cancer patients. The results will be used in the iterative development of the Connect Mobile app and can also inform other developers and researchers in development, integration, and evaluation of mobile health apps and services that support cancer patients in managing their health-related issues. PMID:25119490

Comparative Proteomic Analysis Reveals Proteins Putatively Involved in Toxin Biosynthesis in the Marine Dinoflagellate Alexandrium catenella

PubMed Central

Wang, Da-Zhi; Gao, Yue; Lin, Lin; Hong, Hua-Sheng

2013-01-01

Alexandrium is a neurotoxin-producing dinoflagellate genus resulting in paralytic shellfish poisonings around the world. However, little is known about the toxin biosynthesis mechanism in Alexandrium. This study compared protein profiles of A. catenella collected at different toxin biosynthesis stages (non-toxin synthesis, initial toxin synthesis and toxin synthesizing) coupled with the cell cycle, and identified differentially expressed proteins using 2-DE and MALDI-TOF-TOF mass spectrometry. The results showed that toxin biosynthesis of A. catenella occurred within a defined time frame in the G1 phase of the cell cycle. Proteomic analysis indicated that 102 protein spots altered significantly in abundance (P < 0.05), and 53 proteins were identified using database searching. These proteins were involved in a variety of biological processes, i.e., protein modification and biosynthesis, metabolism, cell division, oxidative stress, transport, signal transduction, and translation. Among them, nine proteins with known functions in paralytic shellfish toxin-producing cyanobacteria, i.e., methionine S-adenosyltransferase, chloroplast ferredoxin-NADP+ reductase, S-adenosylhomocysteinase, adenosylhomocysteinase, ornithine carbamoyltransferase, inorganic pyrophosphatase, sulfotransferase (similar to), alcohol dehydrogenase and arginine deiminase, varied significantly at different toxin biosynthesis stages and formed an interaction network, indicating that they might be involved in toxin biosynthesis in A. catenella. This study is the first step in the dissection of the behavior of the A. catenella proteome during different toxin biosynthesis stages and provides new insights into toxin biosynthesis in dinoflagellates. PMID:23340676

Optimization and evaluation of alkaline potassium permanganate pretreatment of corncob.

PubMed

Ma, Lijuan; Cui, Youzhi; Cai, Rui; Liu, Xueqiang; Zhang, Cuiying; Xiao, Dongguang

2015-03-01

Alkaline potassium permanganate solution (APP) was applied to the pretreatment of corncob with a simple and effective optimization of APP concentration, reaction time, temperature and solid to liquid ratio (SLR). The optimized pretreatment conditions were at 2% (w/v) potassium permanganate with SLR of 1:10 treating for 6h at 50°C. This simple one-step treatment resulted in significant 94.56% of the cellulose and 81.47% of the hemicellulose recoveries and 46.79% of the lignin removal of corncob. The reducing sugar in the hydrolysate from APP-pretreated corncob was 8.39g/L after 12h enzymatic hydrolysis, which was 1.44 and 1.29 folds higher than those from raw and acid pretreated corncobs. Physical characteristics, crystallinity and structure of the pretreated corncob were analyzed and assessed by SEM, XRD and FTIR. The APP pretreatment process was novel and enhanced enzymatic hydrolysis of lignocellulose by affecting composition and structural features. Copyright © 2014 Elsevier Ltd. All rights reserved.

[The personal digital assistant: A tool for supporting mental health rehabilitation].

PubMed

Charbonneau, Karine; Lalande, Mélissa; Briand, Catherine

2015-10-01

People living with mental illness may manifest cognitive and social-emotional difficulties leading to several challenges in their daily lives. Using technological aids may help to compensate for some of these difficulties. The objective of this study was to document the effects and issues of the use of mobile technology applications (apps) with people with mental illness during the rehabilitation process. Using an exploratory qualitative evaluative approach, 12 participants were engaged in ongoing brief interviews in which they discussed their use of a variety of apps that met their rehabilitation needs. A thematic analysis (descriptive interpretive) was used to uncover the effects and issues of the integration of apps in participants' daily life. The apps helped participants to overcome their cognitive difficulties, facilitated the management of their daily tasks and socialization, and prevented boredom. However, several issues related to the context, the technology, and the person need to be considered. The findings prompt one to consider the therapist's role in the integration of personal digital assistants in psychosocial rehabilitation.

Apple App Store as a Business Model Supporting U.S. Navy Requirements

DTIC Science & Technology

2011-10-25

credit card identity information for charging the required $99/year fee. Actual payment of the fee is handled by putting the developer program...required for the App Store. Applications are submitted via iTunes Connect (http://itunesconnect.apple.com). Table 1 gives a list of the...still being processed by the iTunes Connect system.  Invalid Binary—Appears when a binary is received through the Application Loader and has been

Entity Resolution Workflow Installation Process and User Guide

DTIC Science & Technology

2013-07-01

Program Files\\PostgreSQL\\9.1\\data superuser ( postgres ), service account ( postgres ) password : "password" Port #: 5432 Add an environment variable...in this report. • Run the script found in <GG_HOME>\\ globalgraph-dist-1.4.6-final\\schema- ddl\\postgresSetup.bat. This script will set up Postgres ...Username: postgres DB Admin PWD: password GlobalGraph App User: gguser GlobalGraph App PWD: password • Restart the Postgres service using the Windows

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"

Paralytic shellfish toxin biosynthesis in cyanobacteria and dinoflagellates: A molecular overview.

PubMed

Wang, Da-Zhi; Zhang, Shu-Fei; Zhang, Yong; Lin, Lin

2016-03-01

Paralytic shellfish toxins (PSTs) are a group of water soluble neurotoxic alkaloids produced by two different kingdoms of life, prokaryotic cyanobacteria and eukaryotic dinoflagellates. Owing to the wide distribution of these organisms, these toxic secondary metabolites account for paralytic shellfish poisonings around the world. On the other hand, their specific binding to voltage-gated sodium channels makes these toxins potentially useful in pharmacological and toxicological applications. Much effort has been devoted to the biosynthetic mechanism of PSTs, and gene clusters encoding 26 proteins involved in PST biosynthesis have been unveiled in several cyanobacterial species. Functional analysis of toxin genes indicates that PST biosynthesis in cyanobacteria is a complex process including biosynthesis, regulation, modification and export. However, less is known about the toxin biosynthesis in dinoflagellates owing to our poor understanding of the massive genome and unique chromosomal characteristics [1]. So far, few genes involved in PST biosynthesis have been identified from dinoflagellates. Moreover, the proteins involved in PST production are far from being totally explored. Thus, the origin and evolution of PST biosynthesis in these two kingdoms are still controversial. In this review, we summarize the recent progress on the characterization of genes and proteins involved in PST biosynthesis in cyanobacteria and dinoflagellates, and discuss the standing evolutionary hypotheses concerning the origin of toxin biosynthesis as well as future perspectives in PST biosynthesis. Paralytic shellfish toxins (PSTs) are a group of potent neurotoxins which specifically block voltage-gated sodium channels in excitable cells and result in paralytic shellfish poisonings (PSPs) around the world. Two different kingdoms of life, cyanobacteria and dinoflagellates are able to produce PSTs. However, in contrast with cyanobacteria, our understanding of PST biosynthesis in dinoflagellates is extremely limited owing to their unique features. The origin and evolution of PST biosynthesis in these two kingdoms are still controversial. High-throughput omics technologies, such as genomics, transcriptomics and proteomics provide powerful tools for the study of PST biosynthesis in cyanobacteria and dinoflagellates, and have shown their powerful potential with regard to revealing genes and proteins involved in PST biosynthesis in two kingdoms. This review summarizes the recent progress in PST biosynthesis in cyanobacteria and dinoflagellates with focusing on the novel insights from omics technologies, and discusses the evolutionary relationship of toxin biosynthesis genes between these two kingdoms. Copyright © 2015 Elsevier B.V. All rights reserved.

Biosynthesis of Lincosamide Antibiotics: Reactions Associated with Degradation and Detoxification Pathways Play a Constructive Role.

PubMed

Zhang, Daozhong; Tang, Zhijun; Liu, Wen

2018-06-19

Natural products typically are small molecules produced by living organisms. These products possess a wide variety of biological activities and thus have historically played a critical role in medicinal chemistry and chemical biology either as chemotherapeutic agents or as useful tools. Natural products are not synthesized for use by human beings; rather, living organisms produce them in response to various biochemical processes and environmental concerns, both internal and external. These processes/concerns are often dynamic and thus motivate the diversification, optimization, and selection of small molecules in line with changes in biological function. Consequently, the interactions between living organisms and their environments serve as an engine that drives coevolution of natural products and their biological functions and ultimately programs the constant theme of small-molecule development in nature based on biosynthesis generality and specificity. Following this theme, we herein review the biosynthesis of lincosamide antibiotics and dissect the process through which nature creates an unusual eight-carbon aminosugar (lincosamide) and then functionalizes this common high-carbon chain-containing sugar core with diverse l-proline derivatives and sulfur appendages to form individual members, including the clinically useful anti-infective agent lincomycin A and its naturally occurring analogues celesticetin and Bu-2545. The biosynthesis of lincosamide antibiotics is unique in that it results from an intersection of anabolic and catabolic chemistry. Many reactions that are usually involved in degradation and detoxification play a constructive role in biosynthetic processes. Formation of the trans-4-propyl-l-proline residue in lincomycin A biosynthesis requires an oxidation-associated degradation-like pathway composed of heme peroxidase-catalyzed ortho-hydroxylation and non-heme 2,3-dioxygenase-catalyzed extradiol cleavage for l-tyrosine processing prior to the building-up process. Mycothiol (MSH) and ergothioneine (EGT), two small-molecule thiols that are known for their redox-relevant roles in protection against various endogenous and exogenous stresses, function through two unusual S-glycosylations to mediate an eight-carbon aminosugar transfer, activation, and modification during the molecular assembly and tailoring processes in lincosamide antibiotic biosynthesis. Related intermediates include an MSH S-conjugate, mercapturic acid, and a thiomethyl product, which are reminiscent of intermediates found in thiol-mediated detoxification metabolism. In these biosynthetic pathways, "old" protein folds can result in "new" enzymatic activity, such as the DinB-2 fold protein for thiol exchange between EGT and MSH, the γ-glutamyltranspeptidase homologue for C-C bond cleavage, and the pyridoxal-5'-phosphate-dependent enzyme for diverse S-functionalization, generating interest in how nature develops remarkably diverse biochemical functions using a limited range of protein scaffolds. These findings highlight what we can learn from natural product biosynthesis, the recognition of its generality and specificity, and the natural theme of the development of bioactive small molecules, which enables the diversification process to advance and expand small-molecule functions.

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.

Original Chemical Series of Pyrimidine Biosynthesis Inhibitors That Boost the Antiviral Interferon Response

PubMed Central

Lucas-Hourani, Marianne; Dauzonne, Daniel; Munier-Lehmann, Hélène; Khiar, Samira; Nisole, Sébastien; Dairou, Julien; Helynck, Olivier; Afonso, Philippe V.

2017-01-01

ABSTRACT De novo pyrimidine biosynthesis is a key metabolic pathway involved in multiple biosynthetic processes. Here, we identified an original series of 3-(1H-indol-3-yl)-2,3-dihydro-4H-furo[3,2-c]chromen-4-one derivatives as a new class of pyrimidine biosynthesis inhibitors formed by two edge-fused polycyclic moieties. We show that identified compounds exhibit broad-spectrum antiviral activity and immunostimulatory properties, in line with recent reports linking de novo pyrimidine biosynthesis with innate defense mechanisms against viruses. Most importantly, we establish that pyrimidine deprivation can amplify the production of both type I and type III interferons by cells stimulated with retinoic acid-inducible gene 1 (RIG-I) ligands. Altogether, our results further expand the current panel of pyrimidine biosynthesis inhibitors and illustrate how the production of antiviral interferons is tightly coupled to this metabolic pathway. Functional and structural similarities between this new chemical series and dicoumarol, which was reported before to inhibit pyrimidine biosynthesis at the dihydroorotate dehydrogenase (DHODH) step, are discussed. PMID:28807907

A novel pathway for the biosynthesis of heme in Archaea: genome-based bioinformatic predictions and experimental evidence.

PubMed

Storbeck, Sonja; Rolfes, Sarah; Raux-Deery, Evelyne; Warren, Martin J; Jahn, Dieter; Layer, Gunhild

2010-12-13

Heme is an essential prosthetic group for many proteins involved in fundamental biological processes in all three domains of life. In Eukaryota and Bacteria heme is formed via a conserved and well-studied biosynthetic pathway. Surprisingly, in Archaea heme biosynthesis proceeds via an alternative route which is poorly understood. In order to formulate a working hypothesis for this novel pathway, we searched 59 completely sequenced archaeal genomes for the presence of gene clusters consisting of established heme biosynthetic genes and colocalized conserved candidate genes. Within the majority of archaeal genomes it was possible to identify such heme biosynthesis gene clusters. From this analysis we have been able to identify several novel heme biosynthesis genes that are restricted to archaea. Intriguingly, several of the encoded proteins display similarity to enzymes involved in heme d(1) biosynthesis. To initiate an experimental verification of our proposals two Methanosarcina barkeri proteins predicted to catalyze the initial steps of archaeal heme biosynthesis were recombinantly produced, purified, and their predicted enzymatic functions verified.

Original Chemical Series of Pyrimidine Biosynthesis Inhibitors That Boost the Antiviral Interferon Response.

PubMed

Lucas-Hourani, Marianne; Dauzonne, Daniel; Munier-Lehmann, Hélène; Khiar, Samira; Nisole, Sébastien; Dairou, Julien; Helynck, Olivier; Afonso, Philippe V; Tangy, Frédéric; Vidalain, Pierre-Olivier

2017-10-01

De novo pyrimidine biosynthesis is a key metabolic pathway involved in multiple biosynthetic processes. Here, we identified an original series of 3-(1 H -indol-3-yl)-2,3-dihydro-4 H -furo[3,2- c ]chromen-4-one derivatives as a new class of pyrimidine biosynthesis inhibitors formed by two edge-fused polycyclic moieties. We show that identified compounds exhibit broad-spectrum antiviral activity and immunostimulatory properties, in line with recent reports linking de novo pyrimidine biosynthesis with innate defense mechanisms against viruses. Most importantly, we establish that pyrimidine deprivation can amplify the production of both type I and type III interferons by cells stimulated with retinoic acid-inducible gene 1 (RIG-I) ligands. Altogether, our results further expand the current panel of pyrimidine biosynthesis inhibitors and illustrate how the production of antiviral interferons is tightly coupled to this metabolic pathway. Functional and structural similarities between this new chemical series and dicoumarol, which was reported before to inhibit pyrimidine biosynthesis at the dihydroorotate dehydrogenase (DHODH) step, are discussed. Copyright © 2017 Lucas-Hourani et al.

A Novel Pathway for the Biosynthesis of Heme in Archaea: Genome-Based Bioinformatic Predictions and Experimental Evidence

PubMed Central

Storbeck, Sonja; Rolfes, Sarah; Raux-Deery, Evelyne; Warren, Martin J.; Jahn, Dieter; Layer, Gunhild

2010-01-01

Heme is an essential prosthetic group for many proteins involved in fundamental biological processes in all three domains of life. In Eukaryota and Bacteria heme is formed via a conserved and well-studied biosynthetic pathway. Surprisingly, in Archaea heme biosynthesis proceeds via an alternative route which is poorly understood. In order to formulate a working hypothesis for this novel pathway, we searched 59 completely sequenced archaeal genomes for the presence of gene clusters consisting of established heme biosynthetic genes and colocalized conserved candidate genes. Within the majority of archaeal genomes it was possible to identify such heme biosynthesis gene clusters. From this analysis we have been able to identify several novel heme biosynthesis genes that are restricted to archaea. Intriguingly, several of the encoded proteins display similarity to enzymes involved in heme d 1 biosynthesis. To initiate an experimental verification of our proposals two Methanosarcina barkeri proteins predicted to catalyze the initial steps of archaeal heme biosynthesis were recombinantly produced, purified, and their predicted enzymatic functions verified. PMID:21197080

Control of Aβ release from human neurons by differentiation status and RET signaling.

PubMed

Scholz, Diana; Chernyshova, Yana; Leist, Marcel

2013-01-01

Few studies have compared the processing of endogenous human amyloid precursor protein (APP) in younger and older neurons. Here, we characterized LUHMES cells as a human model to study Alzheimer's disease-related processes during neuronal maturation and aging. Differentiated LUHMES expressed and spontaneously processed APP via the secretase pathways, and they secreted amyloid β (Aβ) peptide. This was inhibited by cholesterol depletion or secretase inhibition, but not by block of tau phosphorylation. In vitro aged cells increased Aβ secretion without upregulation of APP or secretases. We identified the medium constituent glial cell line-derived neurotrophic factor (GDNF) as responsible for this effect. GDNF-triggered Aβ release was associated with rapid upregulation of the GDNF coreceptor "rearranged during transfection" (RET). Other direct (neurturin) or indirect (nerve growth factor) RET activators also increased Aβ, whereas different neurotrophins were ineffective. Downstream of RET, we found activation of protein kinase B (AKT) to be involved. Accordingly, inhibitors of the AKT regulator phosphatidylinositol-3-kinase completely blocked GDNF-triggered AKT phosphorylation and Aβ increase. This suggests that RET signaling affects Aβ release from aging neurons. Copyright © 2013 Elsevier Inc. All rights reserved.

Youth Codesign of a Mobile Phone App to Facilitate Self-Monitoring and Management of Mood Symptoms in Young People With Major Depression, Suicidal Ideation, and Self-Harm.

PubMed

Hetrick, Sarah Elisabeth; Robinson, Jo; Burge, Eloise; Blandon, Ryan; Mobilio, Bianca; Rice, Simon M; Simmons, Magenta B; Alvarez-Jimenez, Mario; Goodrich, Simon; Davey, Christopher G

2018-01-23

Effective treatment of depression in young people is critical, given its prevalence, impacts, and link to suicide. Clinical practice guidelines point to the need for regular monitoring of depression symptom severity and the emergence of suicidal ideation to track treatment progress and guide intervention delivery. Yet, this is seldom integrated in clinical practice. The objective of this study was to address the gap between guidelines about monitoring and real-world practice by codesigning an app with young people that allows for self-monitoring of mood and communication of this monitoring with a clinician. We engaged young people aged 18 to 25 years who had experienced depression, suicidal ideation including those who self-harm, as well as clinicians in a codesign process. We used a human-centered codesign design studio methodology where young people designed the features of the app first individually and then as a group. This resulted in a minimal viable product design, represented through low-fidelity hand-drawn wireframes. Clinicians were engaged throughout the process via focus groups. The app incorporated a mood monitoring feature with innovative design aspects that allowed customization, and was named a "well-being tracker" in response to the need for a positive approach to this function. Brief personalized interventions designed to support young people in the intervals between face-to-face appointments were embedded in the app and were immediately available via pop-ups generated by a back-end algorithm within the well-being tracker. Issues regarding the safe incorporation of alerts generated by the app into face-to-face clinical services were raised by clinicians (ie, responding in a timely manner) and will need to be addressed during the full implementation of the app into clinical services. The potential to improve outcomes for young people via technology-based enhancement to interventions is enormous. Enhancing communication between young people and their clinicians about symptoms and treatment progress and increasing access to timely and evidence-based interventions are desirable outcomes. To achieve positive outcomes for young people using technology- (app) based interventions, it is critical to understand and incorporate, in a meaningful way, the expectations and motivations of both young people and clinicians. ©Sarah Elisabeth Hetrick, Jo Robinson, Eloise Burge, Ryan Blandon, Bianca Mobilio, Simon M Rice, Magenta B Simmons, Mario Alvarez-Jimenez, Simon Goodrich, Christopher G Davey. Originally published in JMIR Mental Health (http://mental.jmir.org), 23.01.2018.

Early accumulation of intracellular fibrillar oligomers and late congophilic amyloid angiopathy in mice expressing the Osaka intra-Aβ APP mutation

PubMed Central

Kulic, L; McAfoose, J; Welt, T; Tackenberg, C; Späni, C; Wirth, F; Finder, V; Konietzko, U; Giese, M; Eckert, A; Noriaki, K; Shimizu, T; Murakami, K; Irie, K; Rasool, S; Glabe, C; Hock, C; Nitsch, R M

2012-01-01

Pathogenic amyloid-β peptide precursor (APP) mutations clustered around position 693 of APP—position 22 of the Aβ sequence—are commonly associated with congophilic amyloid angiopathy (CAA) and intracerebral hemorrhages. In contrast, the Osaka (E693Δ) intra-Aβ APP mutation shows a recessive pattern of inheritance that leads to AD-like dementia despite low brain amyloid on in vivo positron emission tomography imaging. Here, we investigated the effects of the Osaka APP mutation on Aβ accumulation and deposition in vivo using a newly generated APP transgenic mouse model (E22ΔAβ) expressing the Osaka mutation together with the Swedish (K670N/M671L) double mutation. E22ΔAβ mice exhibited reduced α-processing of APP and early accumulation of intraneuronal fibrillar Aβ oligomers associated with cognitive deficits. In line with our in vitro findings that recombinant E22Δ-mutated Aβ peptides form amyloid fibrils, aged E22ΔAβ mice showed extracellular CAA deposits in leptomeningeal cerebellar and cortical vessels. In vitro results from thioflavin T aggregation assays with recombinant Aβ peptides revealed a yet unknown antiamyloidogenic property of the E693Δ mutation in the heterozygous state and an inhibitory effect of E22Δ Aβ42 on E22Δ Aβ40 fibrillogenesis. Moreover, E22Δ Aβ42 showed a unique aggregation kinetics lacking exponential fibril growth and poor seeding effects on wild-type Aβ aggregation. These results provide a possible explanation for the recessive trait of inheritance of the Osaka APP mutation and the apparent lack of amyloid deposition in E693Δ mutation carriers. PMID:23149447

The Sargassum Early Advisory System (SEAS)

NASA Astrophysics Data System (ADS)

Armstrong, D.; Gallegos, S. C.

2016-02-01

The Sargassum Early Advisory System (SEAS) web-app was designed to automatically detect Sargassum at sea, forecast movement of the seaweed, and alert users of potential landings. Inspired to help address the economic hardships caused by large landings of Sargassum, the web app automates and enhances the manual tasks conducted by the SEAS group of Texas A&M University at Galveston. The SEAS web app is a modular, mobile-friendly tool that automates the entire workflow from data acquisition to user management. The modules include: 1) an Imagery Retrieval Module to automatically download Landsat-8 Operational Land Imagery (OLI) from the United States Geological Survey (USGS), 2) a Processing Module for automatic detection of Sargassum in the OLI imagery, and subsequent mapping of theses patches in the HYCOM grid, producing maps that show Sargassum clusters; 3) a Forecasting engine fed by the HYbrid Coordinate Ocean Model (HYCOM) model currents and winds from weather buoys; and 4) a mobile phone optimized geospatial user interface. The user can view the last known position of Sargassum clusters, trajectory and location projections for the next 24, 72 and 168 hrs. Users can also subscribe to alerts generated for particular areas. Currently, the SEAS web app produces advisories for Texas beaches. The forecasted Sargassum landing locations are validated by reports from Texas beach managers. However, the SEAS web app was designed to easily expand to other areas, and future plans call for extending the SEAS web app to Mexico and the Caribbean islands. The SEAS web app development is led by NASA, with participation by ASRC Federal/Computer Science Corporation, and the Naval Research Laboratory, all at Stennis Space Center, and Texas A&M University at Galveston.

Development and Pilot Testing of the Eating4two Mobile Phone App to Monitor Gestational Weight Gain.

PubMed

Knight-Agarwal, Catherine; Davis, Deborah Lee; Williams, Lauren; Davey, Rachel; Cox, Robert; Clarke, Adam

2015-06-05

The number of pregnant women with a body mass index (BMI) of 30kg/m(2) or more is increasing, which has important implications for antenatal care. Various resource-intensive interventions have attempted to assist women in managing their weight gain during pregnancy with limited success. A mobile phone app has been proposed as a convenient and cost-effective alternative to face-to-face interventions. This paper describes the process of developing and pilot testing the Eating4Two app, which aims to provide women with a simple gestational weight gain (GWG) calculator, general dietary information, and the motivation to achieve a healthy weight gain during pregnancy. The project involved the development of app components, including a graphing function that allows the user to record their weight throughout the pregnancy and to receive real-time feedback on weight gain progress and general information on antenatal nutrition. Stakeholder consultation was used to inform development. The app was pilot tested with 10 pregnant women using a mixed method approach via an online survey, 2 focus groups, and 1 individual interview. The Eating4Two app took 7 months to develop and evaluate. It involved several disciplines--including nutrition and dietetics, midwifery, public health, and information technology--at the University of Canberra. Participants found the Eating4Two app to be a motivational tool but would have liked scales or other markers on the graph that demonstrated exact weight gain. They also liked the nutrition information; however, many felt it should be formatted in a more user friendly way. The Eating4Two app was viewed by participants in our study as an innovative support system to help motivate healthy behaviors during pregnancy and as a credible resource for accessing nutrition-focused information. The feedback provided by participants will assist with refining the current prototype for use in a clinical intervention trial.

Development and Pilot Testing of the Eating4two Mobile Phone App to Monitor Gestational Weight Gain

PubMed Central

Davis, Deborah Lee; Williams, Lauren; Davey, Rachel; Cox, Robert; Clarke, Adam

2015-01-01

Background The number of pregnant women with a body mass index (BMI) of 30kg/m2 or more is increasing, which has important implications for antenatal care. Various resource-intensive interventions have attempted to assist women in managing their weight gain during pregnancy with limited success. A mobile phone app has been proposed as a convenient and cost-effective alternative to face-to-face interventions. Objective This paper describes the process of developing and pilot testing the Eating4Two app, which aims to provide women with a simple gestational weight gain (GWG) calculator, general dietary information, and the motivation to achieve a healthy weight gain during pregnancy. Methods The project involved the development of app components, including a graphing function that allows the user to record their weight throughout the pregnancy and to receive real-time feedback on weight gain progress and general information on antenatal nutrition. Stakeholder consultation was used to inform development. The app was pilot tested with 10 pregnant women using a mixed method approach via an online survey, 2 focus groups, and 1 individual interview. Results The Eating4Two app took 7 months to develop and evaluate. It involved several disciplines--including nutrition and dietetics, midwifery, public health, and information technology--at the University of Canberra. Participants found the Eating4Two app to be a motivational tool but would have liked scales or other markers on the graph that demonstrated exact weight gain. They also liked the nutrition information; however, many felt it should be formatted in a more user friendly way. Conclusions The Eating4Two app was viewed by participants in our study as an innovative support system to help motivate healthy behaviors during pregnancy and as a credible resource for accessing nutrition-focused information. The feedback provided by participants will assist with refining the current prototype for use in a clinical intervention trial. PMID:26048313

Development and Implementation of a Smartphone Application to Promote Physical Activity and Reduce Screen-Time in Adolescent Boys

PubMed Central

Lubans, David R.; Smith, Jordan J.; Skinner, Geoff; Morgan, Philip J.

2014-01-01

Purpose: To describe the development and implementation of a smartphone application (app) designed to promote physical activity and reduce screen-time in adolescent boys considered “at-risk” of obesity. Methods: An app was developed to support the delivery of a face-to-face school-based obesity prevention program known as the “Active Teen Leaders Avoiding Screen-time” (ATLAS) program. ATLAS was guided by self-determination theory and social cognitive theory and evaluated using a cluster randomized controlled trial with 361 boys (12.7 ± 0.5 years) in 14 secondary schools. Following the completion of the study, participants in the intervention group completed a process evaluation questionnaire and focus groups were conducted with 42 students to explore their general perceptions of the ATLAS program and their experience with the smartphone app. Barriers and challenges encountered in the development, implementation, and evaluation of the app are also described. Results: Participation in the study was not contingent on ownership of a smartphone, but 70% of participants in the intervention group reported having access to a smartphone or tablet device. Focus group participants reported an enjoyment of the program, and felt that it had provided them with new skills, techniques, and routines for the future. However, their engagement with the smartphone app was limited, due to a variety of reasons. Barriers to the implementation and evaluation of the app included limited access to smartphone devices, technical problems with the push notifications, lack of access to usage data, and the challenges of maintaining participants’ interest in using the app. Conclusion: Although participants reported high levels of satisfaction with the ATLAS program in general, the smartphone app was not used extensively. Additional strategies and features may be needed to enhance engagement in adolescent boys. PMID:24904909

Implementation of the HealthKick intervention in primary schools in low-income settings in the Western Cape Province, South Africa: a process evaluation.

PubMed

de Villiers, Anniza; Steyn, Nelia P; Draper, Catherine E; Hill, Jillian; Dalais, Lucinda; Fourie, Jean; Lombard, Carl; Barkhuizen, Gerhard; Lambert, Estelle V

2015-08-22

The HealthKick intervention, introduced at eight primary schools in low-income settings in the Western Cape Province, South Africa, aimed to promote healthy lifestyles among learners, their families and school staff. Eight schools from similar settings without any active intervention served as controls. The Action Planning Process (APP) guided school staff through a process that enabled them to assess areas for action; identify specific priorities; and set their own goals regarding nutrition and physical activity at their schools. Educators were introduced to the APP and trained to undertake this at their schools by holding workshops. Four action areas were covered, which included the school nutrition environment; physical activity and sport environment; staff health; and chronic disease and diabetes awareness. Intervention schools also received a toolkit comprising an educator's manual containing planning guides, printed resource materials and a container with physical activity equipment. To facilitate the APP, a champion was identified at each school to drive the APP and liaise with the project team. Over the three-years a record was kept of activities planned and those accomplished. At the end of the intervention, focus group discussions were held with school staff at each school to capture perceptions about the APP and intervention activities. Overall uptake of events offered by the research team was 65.6% in 2009, 75% in 2010 and 62.5% in 2011. Over the three-year intervention, the school food and nutrition environment action area scored the highest, with 55.5% of planned actions being undertaken. In the chronic disease and diabetes awareness area 54.2% actions were completed, while in the school physical activity and sport environment and staff health activity areas 25.9 and 20% were completed respectively. According to educators, the low level of implementation of APP activities was because of a lack of parental involvement, time and available resources, poor physical environment at schools and socio-economic considerations. The implementation of the HealthKick intervention was not as successful as anticipated. Actions required for future interventions include increased parental involvement, greater support from the Department of Basic Education and assurance of sufficient motivation and 'buy-in' from schools.

Bringing Health and Fitness Data Together for Connected Health Care: Mobile Apps as Enablers of Interoperability

PubMed Central

2015-01-01

Background A transformation is underway regarding how we deal with our health. Mobile devices make it possible to have continuous access to personal health information. Wearable devices, such as Fitbit and Apple’s smartwatch, can collect data continuously and provide insights into our health and fitness. However, lack of interoperability and the presence of data silos prevent users and health professionals from getting an integrated view of health and fitness data. To provide better health outcomes, a complete picture is needed which combines informal health and fitness data collected by the user together with official health records collected by health professionals. Mobile apps are well positioned to play an important role in the aggregation since they can tap into these official and informal health and data silos. Objective The objective of this paper is to demonstrate that a mobile app can be used to aggregate health and fitness data and can enable interoperability. It discusses various technical interoperability challenges encountered while integrating data into one place. Methods For 8 years, we have worked with third-party partners, including wearable device manufacturers, electronic health record providers, and app developers, to connect an Android app to their (wearable) devices, back-end servers, and systems. Results The result of this research is a health and fitness app called myFitnessCompanion, which enables users to aggregate their data in one place. Over 6000 users use the app worldwide to aggregate their health and fitness data. It demonstrates that mobile apps can be used to enable interoperability. Challenges encountered in the research process included the different wireless protocols and standards used to communicate with wireless devices, the diversity of security and authorization protocols used to be able to exchange data with servers, and lack of standards usage, such as Health Level Seven, for medical information exchange. Conclusions By limiting the negative effects of health data silos, mobile apps can offer a better holistic view of health and fitness data. Data can then be analyzed to offer better and more personalized advice and care. PMID:26581920

Bringing Health and Fitness Data Together for Connected Health Care: Mobile Apps as Enablers of Interoperability.

PubMed

Gay, Valerie; Leijdekkers, Peter

2015-11-18

A transformation is underway regarding how we deal with our health. Mobile devices make it possible to have continuous access to personal health information. Wearable devices, such as Fitbit and Apple's smartwatch, can collect data continuously and provide insights into our health and fitness. However, lack of interoperability and the presence of data silos prevent users and health professionals from getting an integrated view of health and fitness data. To provide better health outcomes, a complete picture is needed which combines informal health and fitness data collected by the user together with official health records collected by health professionals. Mobile apps are well positioned to play an important role in the aggregation since they can tap into these official and informal health and data silos. The objective of this paper is to demonstrate that a mobile app can be used to aggregate health and fitness data and can enable interoperability. It discusses various technical interoperability challenges encountered while integrating data into one place. For 8 years, we have worked with third-party partners, including wearable device manufacturers, electronic health record providers, and app developers, to connect an Android app to their (wearable) devices, back-end servers, and systems. The result of this research is a health and fitness app called myFitnessCompanion, which enables users to aggregate their data in one place. Over 6000 users use the app worldwide to aggregate their health and fitness data. It demonstrates that mobile apps can be used to enable interoperability. Challenges encountered in the research process included the different wireless protocols and standards used to communicate with wireless devices, the diversity of security and authorization protocols used to be able to exchange data with servers, and lack of standards usage, such as Health Level Seven, for medical information exchange. By limiting the negative effects of health data silos, mobile apps can offer a better holistic view of health and fitness data. Data can then be analyzed to offer better and more personalized advice and care.

Barriers and Facilitators for the Use of a Medical Mobile App to Prevent Work-Related Risks in Pregnancy: A Qualitative Analysis.

PubMed

Velu, Adeline V; van Beukering, Monique Dm; Schaafsma, Frederieke G; Frings-Dresen, Monique Hw; Mol, Ben Wj; van der Post, Joris Am; Kok, Marjolein

2017-08-22

The number of women participating in the labor market in Europe has increased over the last several decades. At the same time, there is growing evidence that certain conditions of employment during pregnancy may have a negative influence on pregnancy outcomes. In order to better inform pregnant women, we aim to develop an app to help assess the health risk as a result of personal and work-related factors and provide personal advice for these women and their health care providers. The aim of this study was to compose a thematic overview of the perceived facilitators and barriers according to pregnant women, medical professionals, and employers for the use of a mobile app in obstetrical care to prevent occupational-related pregnancy complications. Two multidisciplinary focus group meetings with in total 14 participants were conducted with pregnant women, occupational physicians, general practitioners, midwives, obstetricians, and representatives of trade unions and employer organizations. Transcripts were analyzed by qualitatively coding procedures and constant comparative methods. We identified 24 potential facilitators and 12 potential barriers for the use of the app in 4 categories: content of the app, the app as a mean to provide information, ease of use, and external factors. The 3 main facilitators identified were the need for a good interaction between the app and the user, apps were viewed as a more practical source of information, and the information should be understandable, according to the existing guidelines, and well-dosed. The 2 main barriers for use were extensive battery and memory use of the smartphone and sending frequent push notifications. The results of this study are important considerations in the developing process of a medical app implementing a guideline or evidence-based information in practice. ©Adeline V Velu, Monique DM van Beukering, Frederieke G Schaafsma, Monique HW Frings-Dresen, Ben WJ Mol, Joris AM van der Post, Marjolein Kok. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 22.08.2017.

Biosynthesis and intracellular movement of the melanosomal membrane glycoprotein gp75, the human b (brown) locus product

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

Vijayasaradhi, S.; Doskoch, P.M.; Houghton, A.N.

1991-10-01

A 75-kDa melanosomal glycoprotein (gp75) is the product of a gene that maps to the b (brown) locus, a genetic locus that determines coat color in the mouse. The b locus is conserved (88% identity) between mouse and human. The mouse monoclonal antibody TA99 was used to study the biosynthesis and processing of gp75. gp75 was synthesized as a 55-kDa polypeptide, glycosylated by addition and processing of five or more Asn-linked carbohydrate chains through the cis and trans Golgi, and transported to melanosomes as a mature 75-kDa form. Synthesis and processing of gp75 was rapid (T{sub 1/2} < 30 min),more » and early steps in processing were required for efficient export of gp75 was quite stable in the melanosome. Studies with inhibitors of steps in oligosaccharide processing showed that alternative forms of gp75 were generated during trimming reactions by mannosidase IA/IB and that further maturation resulted in the two mature forms of gp75. The authors purpose that the kinetics of biosynthesis and processing reflect events in the biogenesis and maturation of melanosomes.« less

Feasibility and impact study of a reward-based mobile application to improve adolescents' snacking habits.

PubMed

De Cock, Nathalie; Van Lippevelde, Wendy; Vangeel, Jolien; Notebaert, Melissa; Beullens, Kathleen; Eggermont, Steven; Deforche, Benedicte; Maes, Lea; Goossens, Lien; Verbeken, Sandra; Moens, Ellen; Vervoort, Leentje; Braet, Caroline; Huybregts, Lieven; Kolsteren, Patrick; Van Camp, John; Lachat, Carl

2018-04-02

Adolescents' snacking habits are driven by both explicit reflective and implicit hedonic processes. Hedonic pathways and differences in sensitivity to food rewards in addition to reflective determinants should be considered. The present study evaluated the feasibility and impact of a mobile phone-delivered intervention, incorporating explicit reflective and implicit rewarding strategies, on adolescents' snack intake. Adolescents (n 988; mean age 14·9 (sd 0·70) years, 59·4 % boys) completed a non-randomized clustered controlled trial. Adolescents (n 416) in the intervention schools (n 3) were provided with the intervention application for four weeks, while adolescents (n 572) in the control schools (n 3) followed the regular curriculum. Outcomes were differences in healthy snacking ratio and key determinants (awareness, intention, attitude, self-efficacy, habits and knowledge). Process evaluation data were collected via questionnaires and through log data of the app. No significant positive intervention effects on the healthy snack ratio (b=-3·52 (se 1·82), P>0·05) or targeted determinants were observed. Only 268 adolescents started using the app, of whom only fifty-five (20·5 %) still logged in after four weeks. Within the group of users, higher exposure to the app was not significantly associated with positive intervention effects. App satisfaction ratings were low in both high and low user groups. Moderation analyses revealed small positive intervention effects on the healthy snack ratio in high compared with low reward-sensitive boys (b=1·38 (se 0·59), P<0·05). The intervention was not able to improve adolescents' snack choices, due to low reach and exposure. Future interventions should consider multicomponent interventions, teacher engagement, exhaustive participatory app content development and tailoring.

Iron overload accelerates neuronal amyloid-β production and cognitive impairment in transgenic mice model of Alzheimer's disease.

PubMed

Becerril-Ortega, Javier; Bordji, Karim; Fréret, Thomas; Rush, Travis; Buisson, Alain

2014-10-01

Iron dyshomeostasis is proving increasingly likely to be involved in the pathology of Alzheimer's disease (AD); yet, its mechanism is not well understood. Here, we investigated the AD-related mechanism(s) of iron-sulfate exposure in vitro and in vivo, using cultured primary cortical neurons and APP/PS1 AD-model mice, respectively. In both systems, we observed iron-induced disruptions of amyloid precursor protein (APP) processing, neuronal signaling, and cognitive behavior. Iron overload increased production of amyloidogenic KPI-APP and amyloid beta. Further, this APP misprocessing was blocked by MK-801 in vitro, suggesting the effect was N-methyl-D-aspartate receptor (NMDAR) dependent. Calcium imaging confirmed that 24 hours iron exposure led to disrupted synaptic signaling by augmenting GluN2B-containing NMDAR expression-GluN2B messenger RNA and protein levels were increased and promoting excessing extrasynaptic NMDAR signaling. The disrupted GluN2B expression was concurrent with diminished expression of the splicing factors, sc35 and hnRNPA1. In APP/PS1 mice, chronic iron treatment led to hastened progression of cognitive impairment with the novel object recognition discrimination index, revealing a deficit at the age of 4 months, concomitant with augmented GluN2B expression. Together, these data suggest iron-induced APP misprocessing and hastened cognitive decline occur through inordinate extrasynaptic NMDAR activation. Copyright © 2014 Elsevier Inc. All rights reserved.

Functional Roles of the Interaction of APP and Lipoprotein Receptors

PubMed Central

Pohlkamp, Theresa; Wasser, Catherine R.; Herz, Joachim

2017-01-01

The biological fates of the key initiator of Alzheimer’s disease (AD), the amyloid precursor protein (APP), and a family of lipoprotein receptors, the low-density lipoprotein (LDL) receptor-related proteins (LRPs) and their molecular roles in the neurodegenerative disease process are inseparably interwoven. Not only does APP bind tightly to the extracellular domains (ECDs) of several members of the LRP group, their intracellular portions are also connected through scaffolds like the one established by FE65 proteins and through interactions with adaptor proteins such as X11/Mint and Dab1. Moreover, the ECDs of APP and LRPs share common ligands, most notably Reelin, a regulator of neuronal migration during embryonic development and modulator of synaptic transmission in the adult brain, and Agrin, another signaling protein which is essential for the formation and maintenance of the neuromuscular junction (NMJ) and which likely also has critical, though at this time less well defined, roles for the regulation of central synapses. Furthermore, the major independent risk factors for AD, Apolipoprotein (Apo) E and ApoJ/Clusterin, are lipoprotein ligands for LRPs. Receptors and ligands mutually influence their intracellular trafficking and thereby the functions and abilities of neurons and the blood-brain-barrier to turn over and remove the pathological product of APP, the amyloid-β peptide. This article will review and summarize the molecular mechanisms that are shared by APP and LRPs and discuss their relative contributions to AD. PMID:28298885

Characterization of the biosynthesis, processing, and sorting of human HBP/CAP37/azurocidin.

PubMed

Lindmark, A; Garwicz, D; Rasmussen, P B; Flodgaard, H; Gullberg, U

1999-10-01

Azurocidin is a multifunctional endotoxin-binding serine protease homolog synthesized during the promyelocytic stage of neutrophil development. To characterize the biosynthesis and processing of azurocidin, cDNA encoding human preproazurocidin was stably transfected to the rat basophilic leukemia cell line RBL-1 and the murine myeloblast-like cell line 32D cl3; cell lines previously utilized to study the related proteins cathepsin G and proteinase 3. After 30 min of pulse radiolabeling, two forms of newly synthesized proazurocidin (34.5 and 37 kDa), differing in carbohydrate content but with protein cores of identical sizes, were recognized. With time, the 34.5-kDa form disappeared, while the 37-kDa form was further processed proteolytically, as judged by digestion with N-glycosidase F. Conversion of high-mannose oligosaccharides into complex forms was shown by acquisition of complete resistance to endoglycosidase H. Radiosequence analysis demonstrated that the amino-terminal seven amino acid propeptide of proazurocidin was removed in a stepwise manner during processing; initial removal of five amino acids was followed by cleavage of a dipeptide. Presence of the protease inhibitors Gly-Phe-diazomethyl ketone, bestatin, or leupeptin inhibited only the cleavage of the dipeptide, thus indicating the involvement of at least two amino-terminal processing enzymes. Translocation of azurocidin to granules was shown by subcellular fractionation. Similar results, with efficient biosynthesis, processing, and targeting to granules in both cell lines, were obtained with a mutant form of human preproazurocidin lacking the amino-terminal heptapropeptide. In conclusion, this investigation is an important addition to our previous studies on related azurophil granule proteins, and provides novel information concerning the biosynthesis and distinctive amino-terminal processing of human azurocidin.

Fungal biosynthesis of gold nanoparticles: mechanism and scale up.

PubMed

Kitching, Michael; Ramani, Meghana; Marsili, Enrico

2015-11-01

Gold nanoparticles (AuNPs) are a widespread research tool because of their oxidation resistance, biocompatibility and stability. Chemical methods for AuNP synthesis often produce toxic residues that raise environmental concern. On the other hand, the biological synthesis of AuNPs in viable microorganisms and their cell-free extracts is an environmentally friendly and low-cost process. In general, fungi tolerate higher metal concentrations than bacteria and secrete abundant extracellular redox proteins to reduce soluble metal ions to their insoluble form and eventually to nanocrystals. Fungi harbour untapped biological diversity and may provide novel metal reductases for metal detoxification and bioreduction. A thorough understanding of the biosynthetic mechanism of AuNPs in fungi is needed to reduce the time of biosynthesis and to scale up the AuNP production process. In this review, we describe the known mechanisms for AuNP biosynthesis in viable fungi and fungal protein extracts and discuss the most suitable bioreactors for industrial AuNP biosynthesis. © 2014 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Lysine Succinylation Contributes to Aflatoxin Production and Pathogenicity in Aspergillus flavus*

PubMed Central

Ren, Silin; Yang, Mingkun; Yue, Yuewei; Ge, Feng; Li, Yu; Guo, Xiaodong; Zhang, Jia; Zhang, Feng; Nie, Xinyi; Wang, Shihua

2018-01-01

Aspergillus flavus (A. flavus) is a ubiquitous saprophytic and pathogenic fungus that produces the aflatoxin carcinogen, and A. flavus can have tremendous economic and health impacts worldwide. Increasing evidence demonstrates that lysine succinylation plays an important regulatory role in metabolic processes in both bacterial and human cells. However, little is known about the extent and function of lysine succinylation in A. flavus. Here, we performed a global succinylome analysis of A. flavus using high accuracy nano-LC-MS/MS in combination with the enrichment of succinylated peptides from digested cell lysates and subsequent peptide identification. In total, 985 succinylation sites on 349 succinylated proteins were identified in this pathogen. Bioinformatics analysis revealed that the succinylated proteins were involved in various biological processes and were particularly enriched in the aflatoxin biosynthesis process. Site-specific mutagenesis and biochemical studies showed that lysine succinylation on the norsolorinic acid reductase NorA (AflE), a key enzyme in aflatoxins biosynthesis, can affect the production of sclerotia and aflatoxins biosynthesis in A. flavus. Together, our findings reveal widespread roles for lysine succinylation in regulating metabolism and aflatoxins biosynthesis in A. flavus. Our data provide a rich resource for functional analyses of lysine succinylation and facilitate the dissection of metabolic networks in this pathogen. PMID:29298838

Experiences of Indian Health Workers Using WhatsApp for Improving Aseptic Practices With Newborns: Exploratory Qualitative Study.

PubMed

Pahwa, Parika; Lunsford, Sarah; Livesley, Nigel

2018-03-01

Quality improvement (QI) involves the following 4 steps: (1) forming a team to work on a specific aim, (2) analyzing the reasons for current underperformance, (3) developing changes that could improve care and testing these changes using plan-do-study-act cycles (PDSA), and (4) implementing successful interventions to sustain improvements. Teamwork and group discussion are key for effective QI, but convening in-person meetings with all staff can be challenging due to workload and shift changes. Mobile technologies can support communication within a team when face-to-face meetings are not possible. WhatsApp, a mobile messaging platform, was implemented as a communication tool by a neonatal intensive care unit (NICU) team in an Indian tertiary hospital seeking to reduce nosocomial infections in newborns. This exploratory qualitative study aimed to examine experiences with WhatsApp as a communication tool among improvement team members and an external coach to improve adherence to aseptic protocols. Ten QI team members and the external coach were interviewed on communication processes and approaches and thematically analyzed. The WhatsApp transcript for the implementation period was also included in the analysis. WhatsApp was effective for disseminating information, including guidance on QI and clinical practice, and data on performance indicators. It was not effective as a platform for group discussion to generate change ideas or analyze the performance indicator data. The decision of who to include in the WhatsApp group and how members engaged in the group may have reinforced existing hierarchies. Using WhatsApp created a work environment in which members were accessible all the time, breaking down barriers between personal and professional time. The continual influx of messages was distracting to some respondents, and how respondents managed these messages (eg, using the silent function) may have influenced their perceptions of WhatsApp. The coach used WhatsApp to share information, schedule site visits, and prompt action on behalf of the team. WhatsApp is a productive communication tool that can be used by teams and coaches to disseminate information and prompt action to improve the quality of care, but cannot replace in-person meetings. ©Parika Pahwa, Sarah Lunsford, Nigel Livesley. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 01.03.2018.

Experiences of Indian Health Workers Using WhatsApp for Improving Aseptic Practices With Newborns: Exploratory Qualitative Study

PubMed Central

Livesley, Nigel

2018-01-01

Background Quality improvement (QI) involves the following 4 steps: (1) forming a team to work on a specific aim, (2) analyzing the reasons for current underperformance, (3) developing changes that could improve care and testing these changes using plan-do-study-act cycles (PDSA), and (4) implementing successful interventions to sustain improvements. Teamwork and group discussion are key for effective QI, but convening in-person meetings with all staff can be challenging due to workload and shift changes. Mobile technologies can support communication within a team when face-to-face meetings are not possible. WhatsApp, a mobile messaging platform, was implemented as a communication tool by a neonatal intensive care unit (NICU) team in an Indian tertiary hospital seeking to reduce nosocomial infections in newborns. Objective This exploratory qualitative study aimed to examine experiences with WhatsApp as a communication tool among improvement team members and an external coach to improve adherence to aseptic protocols. Methods Ten QI team members and the external coach were interviewed on communication processes and approaches and thematically analyzed. The WhatsApp transcript for the implementation period was also included in the analysis. Results WhatsApp was effective for disseminating information, including guidance on QI and clinical practice, and data on performance indicators. It was not effective as a platform for group discussion to generate change ideas or analyze the performance indicator data. The decision of who to include in the WhatsApp group and how members engaged in the group may have reinforced existing hierarchies. Using WhatsApp created a work environment in which members were accessible all the time, breaking down barriers between personal and professional time. The continual influx of messages was distracting to some respondents, and how respondents managed these messages (eg, using the silent function) may have influenced their perceptions of WhatsApp. The coach used WhatsApp to share information, schedule site visits, and prompt action on behalf of the team. Conclusions WhatsApp is a productive communication tool that can be used by teams and coaches to disseminate information and prompt action to improve the quality of care, but cannot replace in-person meetings. PMID:29496651

A Digital Tool to Promote Alcohol and Drug Use Screening, Brief Intervention, and Referral to Treatment Skill Translation: A Mobile App Development and Randomized Controlled Trial Protocol

PubMed Central

2017-01-01

Background Translation of knowledge and skills from classroom settings to clinical practice is a major challenge in healthcare training, especially for behavioral interventions. For example, screening, brief intervention, and referral to treatment (SBIRT) is a highly-promoted approach to identifying and treating individuals at risk for alcohol or drug problems, yet effective, routine use of SBIRT has lagged. Objective The objective of this paper is to describe the development, pilot testing, and trial protocol of a mobile app based on the theory of planned behavior (TPB) to promote SBIRT skill translation and application. Methods Intended for use after classroom training occurs, the mobile app has three primary functions designed to increase behavioral intent to deliver SBIRT: (1) review skills (ie, address knowledge and beliefs about SBIRT), (2) apply skills with patients (ie, build confidence and perceived behavioral control), and (3) report performance data (ie, increase accountability and social norms and/or influence). The app includes depression and anxiety screening tools due to high comorbidity with substance use. A randomized controlled trial (RCT) is in progress among health and social service learners (N=200) recruited from 3 universities and 6 different training programs in nursing, social work, internal medicine, psychiatry, and psychology. Participants are randomized to SBIRT classroom instruction alone or classroom instruction plus app access prior to beginning their field placement rotations. TPB-based data are collected via Qualtrics or via the mobile app pre-post and SBIRT utilization, weekly for 10 weeks. Key outcomes include the frequency of and self-reported confidence in delivery of SBIRT. Results Beta testing with advanced practice nursing students (N=22) indicated that the app and its associated assessment tools were acceptable and useful. The system usability scale (SUS) mean was 65.8 (n=19), which indicated that the SBIRT app was acceptable but could benefit from improvement. Indeed, modifications were implemented prior to starting the trial. Enrollment of trial participants began in September 2016. Results are expected by December 2017. Conclusions This report describes the process of TPB-based app development and testing, and the protocol for a RCT to determine the effectiveness of the app in enhancing skill translation. If effective, this approach could improve SBIRT implementation, fidelity, and clinical outcomes. PMID:28420604

“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

Thymoquinone-rich fraction nanoemulsion (TQRFNE) decreases Aβ40 and Aβ42 levels by modulating APP processing, up-regulating IDE and LRP1, and down-regulating BACE1 and RAGE in response to high fat/cholesterol diet-induced rats.

PubMed

Ismail, Norsharina; Ismail, Maznah; Azmi, Nur Hanisah; Bakar, Muhammad Firdaus Abu; Yida, Zhang; Abdullah, Maizaton Atmadini; Basri, Hamidon

2017-11-01

Though the causes of Alzheimer's disease (AD) are yet to be understood, much evidence has suggested that excessive amyloid-β (Aβ) accumulation due to abnormal amyloid-β precursor protein (APP) processing and Aβ metabolism are crucial processes towards AD pathogenesis. Hence, approaches aiming at APP processing and Aβ metabolism are currently being actively pursued for the management of AD. Studies suggest that high cholesterol and a high fat diet have harmful effects on cognitive function and may instigate the commencement of AD pathogenesis. Despite the neuropharmacological attributes of black cumin seed (Nigella sativa) extracts and its main active compound, thymoquinone (TQ), limited records are available in relation to AD research. Nanoemulsion (NE) is exploited as drug delivery systems due to their capacity of solubilising non-polar active compounds and is widely examined for brain targeting. Herewith, the effects of thymoquinone-rich fraction nanoemulsion (TQRFNE), thymoquinone nanoemulsion (TQNE) and their counterparts' conventional emulsion in response to high fat/cholesterol diet (HFCD)-induced rats were investigated. Particularly, the Aβ generation; APP processing, β-secretase 1 (BACE1), γ-secretases of presenilin 1 (PSEN1) and presenilin 2 (PSEN2), Aβ degradation; insulin degrading enzyme (IDE), Aβ transportation; low density lipoprotein receptor-related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE) were measured in brain tissues. TQRFNE reduced the brain Aβ fragment length 1-40 and 1-42 (Aβ40 and Aβ42) levels, which would attenuate the AD pathogenesis. This reduction could be due to the modulation of β- and γ-secretase enzyme activity, and the Aβ degradation and transportation in/out of the brain. The findings show the mechanistic actions of TQRFNE in response to high fat and high cholesterol diet associated to Aβ generation, degradation and transportation in the rat's brain tissue. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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.

Acceptance of a Mobile Application Supporting Nurses Workflow at Patient Bedside: Results from a Pilot Study.

PubMed

Ehrler, Frederic; Ducloux, Pascal; Wu, Danny T Y; Lovis, Christian; Blondon, Katherine

2018-01-01

Supporting caregivers' workflow with mobile applications (apps) is a growing trend. At the bedside, apps can provide new ways to support the documentation process rather than using a desktop computer in a nursing office. Although these applications show potential, few existing reports have studied the real impact of such solutions. At the University Hospitals of Geneva, we developed BEDside Mobility, a mobile application supporting nurses' daily workflow. In a pilot study, the app was trialed in two wards for a period of one month. We collected data of the actual usage of the app and asked the users to complete a tailored technology acceptance model questionnaire at the end of the study period. Results show that participation remain stable with time with participants using in average the tool for almost 29 minutes per day. The technology acceptance questionnaires revealed a high usability of the app and good promotion from the institution although users did not perceive any increase in productivity. Overall, intent of use was divergent between promoters and antagonist. Furthermore, some participants considered the tool as an addition to their workload. This evaluation underlines the importance of helping all end users perceive the benefits of a new intervention since coworkers strong influence each other.

Caspase-9 mediates synaptic plasticity and memory deficits of Danish dementia knock-in mice: caspase-9 inhibition provides therapeutic protection.

PubMed

Tamayev, Robert; Akpan, Nsikan; Arancio, Ottavio; Troy, Carol M; D'Adamio, Luciano

2012-12-10

Mutations in either Aβ Precursor protein (APP) or genes that regulate APP processing, such as BRI2/ITM2B and PSEN1/PSEN2, cause familial dementias. Although dementias due to APP/PSEN1/PSEN2 mutations are classified as familial Alzheimer disease (FAD) and those due to mutations in BRI2/ITM2B as British and Danish dementias (FBD, FDD), data suggest that these diseases have a common pathogenesis involving toxic APP metabolites. It was previously shown that FAD mutations in APP and PSENs promote activation of caspases leading to the hypothesis that aberrant caspase activation could participate in AD pathogenesis. Here, we tested whether a similar mechanism applies to the Danish BRI2/ITM2B mutation. We have generated a genetically congruous mouse model of FDD, called FDD(KI), which presents memory and synaptic plasticity deficits. We found that caspase-9 is activated in hippocampal synaptic fractions of FDD(KI) mice and inhibition of caspase-9 activity rescues both synaptic plasticity and memory deficits. These data directly implicate caspase-9 in the pathogenesis of Danish dementia and suggest that reducing caspase-9 activity is a valid therapeutic approach to treating human dementias.

Caspase-9 mediates synaptic plasticity and memory deficits of Danish dementia knock-in mice: caspase-9 inhibition provides therapeutic protection

PubMed Central

2012-01-01

Background Mutations in either Aβ Precursor protein (APP) or genes that regulate APP processing, such as BRI2/ITM2B and PSEN1/PSEN2, cause familial dementias. Although dementias due to APP/PSEN1/PSEN2 mutations are classified as familial Alzheimer disease (FAD) and those due to mutations in BRI2/ITM2B as British and Danish dementias (FBD, FDD), data suggest that these diseases have a common pathogenesis involving toxic APP metabolites. It was previously shown that FAD mutations in APP and PSENs promote activation of caspases leading to the hypothesis that aberrant caspase activation could participate in AD pathogenesis. Results Here, we tested whether a similar mechanism applies to the Danish BRI2/ITM2B mutation. We have generated a genetically congruous mouse model of FDD, called FDDKI, which presents memory and synaptic plasticity deficits. We found that caspase-9 is activated in hippocampal synaptic fractions of FDDKI mice and inhibition of caspase-9 activity rescues both synaptic plasticity and memory deficits. Conclusion These data directly implicate caspase-9 in the pathogenesis of Danish dementia and suggest that reducing caspase-9 activity is a valid therapeutic approach to treating human dementias. PMID:23217200

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.

Cloning and bioinformatic analysis of lovastatin biosynthesis regulatory gene lovE.

PubMed

Huang, Xin; Li, Hao-ming

2009-08-05

Lovastatin is an effective drug for treatment of hyperlipidemia. This study aimed to clone lovastatin biosynthesis regulatory gene lovE and analyze the structure and function of its encoding protein. According to the lovastatin synthase gene sequence from genebank, primers were designed to amplify and clone the lovastatin biosynthesis regulatory gene lovE from Aspergillus terrus genomic DNA. Bioinformatic analysis of lovE and its encoding animo acid sequence was performed through internet resources and software like DNAMAN. Target fragment lovE, almost 1500 bp in length, was amplified from Aspergillus terrus genomic DNA and the secondary and three-dimensional structures of LovE protein were predicted. In the lovastatin biosynthesis process lovE is a regulatory gene and LovE protein is a GAL4-like transcriptional factor.

A Mobile App Development Guideline for Hospital Settings: Maximizing the Use of and Minimizing the Security Risks of "Bring Your Own Devices" Policies

PubMed Central

Pelletier, Alexandra; Sunthara, Gajen; Gujral, Nitin; Mittal, Vandna; Bourgeois, Fabienne C

2016-01-01

Background Hospitals today are introducing new mobile apps to improve patient care and workflow processes. Mobile device adoption by hospitals fits with present day technology behavior; however, requires a deeper look into hospital device policies and the impact on patients, staff, and technology development. Should hospitals spend thousands to millions of dollars to equip all personnel with a mobile device that is only used in a hospital environment? Allowing health care professionals to use personal mobile devices at work, known as bring-your-own-device (BYOD), has the potential to support both the hospital and its employees to deliver effective and efficient care. Objective The objectives of this research were to create a mobile app development guideline for a BYOD hospital environment, apply the guideline to the development of an in-house mobile app called TaskList, pilot the TaskList app within Boston Children’s Hospital (BCH), and refine the guideline based on the app pilot. TaskList is an Apple operating system (iOS)-based app designed for medical residents to monitor, create, capture, and share daily collaborative tasks associated with patients. Methods To create the BYOD guidelines, we developed TaskList that required the use of mobile devices among medical resident. The TaskList app was designed in four phases: (1) mobile app guideline development, (2) requirements gathering and developing of TaskList fitting the guideline, (3) deployment of TaskList using BYOD with end-users, and (4) refinement of the guideline based on the TaskList pilot. Phase 1 included understanding the existing hospital BYOD policies and conducting Web searches to find best practices in software development for a BYOD environment. Phase 1 also included gathering subject matter input from the Information Services Department (ISD) at BCH. Phase 2 involved the collaboration between the Innovation Acceleration Program at BCH, the ISD Department and the TaskList Clinical team in understanding what features should be built into the app. Phase 3 involved deployment of TaskList on a clinical floor at BCH. Lastly, Phase 4 gathered the lessons learned from the pilot to refine the guideline. Results Fourteen practical recommendations were identified to create the BCH Mobile Application Development Guideline to safeguard custom applications in hospital BYOD settings. The recommendations were grouped into four categories: (1) authentication and authorization, (2) data management, (3) safeguarding app environment, and (4) remote enforcement. Following the guideline, the TaskList app was developed and then was piloted with an inpatient ward team. Conclusions The Mobile Application Development guideline was created and used in the development of TaskList. The guideline is intended for use by developers when addressing integration with hospital information systems, deploying apps in BYOD health care settings, and meeting compliance standards, such as Health Insurance Portability and Accountability Act (HIPAA) regulations. PMID:27169345

A Mobile App Development Guideline for Hospital Settings: Maximizing the Use of and Minimizing the Security Risks of "Bring Your Own Devices" Policies.

PubMed

Al Ayubi, Soleh U; Pelletier, Alexandra; Sunthara, Gajen; Gujral, Nitin; Mittal, Vandna; Bourgeois, Fabienne C

2016-05-11

Hospitals today are introducing new mobile apps to improve patient care and workflow processes. Mobile device adoption by hospitals fits with present day technology behavior; however, requires a deeper look into hospital device policies and the impact on patients, staff, and technology development. Should hospitals spend thousands to millions of dollars to equip all personnel with a mobile device that is only used in a hospital environment? Allowing health care professionals to use personal mobile devices at work, known as bring-your-own-device (BYOD), has the potential to support both the hospital and its employees to deliver effective and efficient care. The objectives of this research were to create a mobile app development guideline for a BYOD hospital environment, apply the guideline to the development of an in-house mobile app called TaskList, pilot the TaskList app within Boston Children's Hospital (BCH), and refine the guideline based on the app pilot. TaskList is an Apple operating system (iOS)-based app designed for medical residents to monitor, create, capture, and share daily collaborative tasks associated with patients. To create the BYOD guidelines, we developed TaskList that required the use of mobile devices among medical resident. The TaskList app was designed in four phases: (1) mobile app guideline development, (2) requirements gathering and developing of TaskList fitting the guideline, (3) deployment of TaskList using BYOD with end-users, and (4) refinement of the guideline based on the TaskList pilot. Phase 1 included understanding the existing hospital BYOD policies and conducting Web searches to find best practices in software development for a BYOD environment. Phase 1 also included gathering subject matter input from the Information Services Department (ISD) at BCH. Phase 2 involved the collaboration between the Innovation Acceleration Program at BCH, the ISD Department and the TaskList Clinical team in understanding what features should be built into the app. Phase 3 involved deployment of TaskList on a clinical floor at BCH. Lastly, Phase 4 gathered the lessons learned from the pilot to refine the guideline. Fourteen practical recommendations were identified to create the BCH Mobile Application Development Guideline to safeguard custom applications in hospital BYOD settings. The recommendations were grouped into four categories: (1) authentication and authorization, (2) data management, (3) safeguarding app environment, and (4) remote enforcement. Following the guideline, the TaskList app was developed and then was piloted with an inpatient ward team. The Mobile Application Development guideline was created and used in the development of TaskList. The guideline is intended for use by developers when addressing integration with hospital information systems, deploying apps in BYOD health care settings, and meeting compliance standards, such as Health Insurance Portability and Accountability Act (HIPAA) regulations.

Smart dental practice: capitalising on smart mobile technology.

PubMed

Plangger, K; Bredican, J; Mills, A J; Armstrong, J

2015-08-14

To keep pace with consumer adoption of smart mobile devices, such as smartphones and tablets, and the applications ('apps') developed for these devices, dental professionals should consider how this technology could be used to simultaneously improve both patient service experiences and dental practice management. Using U-Commerce as a theoretical lens, this article discusses the potential value of smart mobile technology to the dental practice context, with a particular focus on the unique and customisable capabilities of apps. To take full advantage of this technology, a process is outlined for identifying and designing bespoke dental apps that takes into account the unique advantages of these devices. Dental practices, with increasing financial and competitive pressures, may improve the efficiency and profitability of operations and better manage patients, employees and stakeholders by integrating smart mobile technology.

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.

Bioactive Oligosaccharide Natural Products

PubMed Central

McCranie, Emilianne K.; Bachmann, Brian O.

2016-01-01

Oligosaccharide natural products target a wide spectrum of biological processes including disruption of cell wall biosynthesis, interference of bacterial translation, and inhibition of human α-amylase. Correspondingly, oligosaccharides possess potential for development as treatments of such diverse diseases as bacterial infections and type II diabetes. Despite their potent and selective activities and potential clinical relevance, isolated bioactive secondary metabolic oligosaccharides are less prevalent than other classes of natural products and their biosynthesis has received comparatively less attention. This review highlights the unique modes of action and biosynthesis of four classes of bioactive oligosaccharides: the orthosomycins, moenomycins, saccharomicins, and acarviostatins. PMID:24883430

Defining Lipid Transport Pathways in Animal Cells

NASA Astrophysics Data System (ADS)

Pagano, Richard E.; Sleight, Richard G.

1985-09-01

A new technique for studying the metabolism and intracellular transport of lipid molecules in living cells based on the use of fluorescent lipid analogs is described. The cellular processing of various intermediates (phosphatidic acid and ceramide) and end products (phosphatidylcholine and phosphatidylethanolamine) in lipid biosynthesis is reviewed and a working model for compartmentalization during lipid biosynthesis is presented.

Developing tools for investigating the multiple roles of ethylene: Identification and mapping genes for ethylene biosynthesis and reception in barley

USDA-ARS?s Scientific Manuscript database

The plant hormone ethylene is important to many plant processes from germination through senescence, including responses to in vitro growth and plant regeneration. Knowledge of the number of genes, and of their function, that are involved in ethylene biosynthesis and reception is necessary to determ...

Aging process alters hippocampal and cortical secretase activities of Wistar rats.

PubMed

Bertoldi, Karine; Cechinel, Laura Reck; Schallenberger, Bruna; Meireles, Louisiana; Basso, Carla; Lovatel, Gisele Agustini; Bernardi, Lisiane; Lamers, Marcelo Lazzaron; Siqueira, Ionara Rodrigues

2017-01-15

A growing body of evidence has demonstrated amyloid plaques in aged brain; however, little attention has been given to amyloid precursor protein (APP) processing machinery during the healthy aging process. The amyloidogenic and non-amyloidogenic pathways, represented respectively by β- and α-secretases (BACE and TACE), are responsible for APP cleavage. Our working hypothesis is that the normal aging process could imbalance amyloidogenic and non-amyloidogenic pathways specifically BACE and TACE activities. Besides, although it has been showed that exercise can modulate secretase activities in Alzheimer Disease models the relationship between exercise effects and APP processing during healthy aging process is rarely studied. Our aim was to investigate the aging process and the exercise effects on cortical and hippocampal BACE and TACE activities and aversive memory performance. Young adult and aged Wistar rats were subjected to an exercise protocol (20min/day for 2 weeks) and to inhibitory avoidance task. Biochemical parameters were evaluated 1h and 18h after the last exercise session in order to verify transitory and delayed exercise effects. Aged rats exhibited impaired aversive memory and diminished cortical TACE activity. Moreover, an imbalance between TACE and BACE activities in favor of BACE activity was observed in aged brain. Moderate treadmill exercise was unable to alter secretase activities in any brain areas or time points evaluated. Our results suggest that aging-related aversive memory decline is partly linked to decreased cortical TACE activity. Additionally, an imbalance between secretase activities can be related to the higher vulnerability to neurodegenerative diseases induced by aging. Copyright © 2016 Elsevier B.V. All rights reserved.

Methods for studying reaction kinetics in gas chromatography, exemplified by using the 1-chloro-2,2-dimethylaziridine interconversion reaction.

PubMed

Krupcík, J; Mydlová, J; Májek, P; Simon, P; Armstrong, D W

2008-04-04

In this paper, methods are described that are used for studying first-order reaction kinetics by gas chromatography. Basic theory is summarized and illustrated using the interconversion of 1-chloro-2,2-dimethylaziridine enantiomers as a representative example. For the determination of the kinetic and thermodynamic activation data of interconversion the following methods are reviewed: (i) classical kinetic methods where samples of batch-wise kinetic studies are analyzed by enantioselective gas chromatography, (ii) stopped-flow methods performed on one chiral column, (iii) stopped-flow methods performed on an achiral column or empty capillary coupled in series with two chiral columns, (iv) on-flow method performed on an achiral column coupled in series with two chiral columns, and (v) reaction gas chromatography, known as a dynamic gas chromatography, where the interconversion is performed on chiral column during the separation process. The determination of kinetic and thermodynamic activation data by methods (i) through (iv) is straightforward as the experimental data needed for the evaluation (particularly the concentration of reaction constituents) are accessible from the chromatograms. The evaluation of experiments from reaction chromatography method (v) is complex as the concentration bands of reaction constituents are overlapped. The following procedures have been developed to determination peak areas of reaction constituents in such complex chromatograms: (i) methods based on computer-assisted simulations of chromatograms where the kinetic activation parameters for the interconversion of enantiomers are obtained by iterative comparison of experimental and simulated chromatograms, (ii) stochastic methods based on the simulation of Gaussian distribution functions and using a time-dependent probability density function, (iii) approximation function and unified equation, (iv) computer-assisted peak deconvolution methods. Evaluation of the experimental data permits the calculation of apparent rate constants for both the interconversion of the first eluted (k (A-->B)(app)) as well as the second eluted (k(B-->A)(app)) enantiomer. The mean value for all the rate constants (from all the reviewed methods) was found for 1-chloro-2,2-dimethylaziridine A-->B enantiomer interconversion at 100 degrees C: k (A-->B)(app)=21.2 x 10(-4)s(-1) with a standard deviation sigma=10.7 x 10(-4). Evaluating data for reaction chromatography at 100 degrees C {k (app)=k(A-->B)(app)=k(B-->A)(app)=13.9 x 10(-4)s(-1), sigma=3.0 x 10(-4)s(-1)} shows that differences between k(A-->B)(app) and k(B-->A)(app) are the same within experimental error. It was shown both theoretically and experimentally that the Arrhenius activation energy (E(a)) calculated from Arrhenius plots (lnk(app) versus 1/T) is proportional to the enthalpy of activation {E(a)=DeltaH+RT}. Statistical treatment of Gibbs activation energy values gave: DeltaG (app)=110.5kJmol(-1), sigma=2.4kJmol(-1), DeltaG (A-->B)(app)=110.5kJmol(-1), sigma=2.2kJmol(-1), DeltaG (B-->A)(app)=110.3kJmol(-1), sigma=2.8kJmol(-1). This shows that the apparent Gibbs energy barriers for the interconversion of 1-chloro-2,2-dimethylaziridine enantiomers are equal DeltaG (app)=DeltaG(A-->B)(app)=DeltaG(B-->A)(app) and within the given precision of measurement independent of the experimental method used.

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

Biosynthesis of human myeloperoxidase.

PubMed

Nauseef, William M

2018-03-15

Members of Chordata peroxidase subfamily [1] expressed in mammals, including myeloperoxidase (MPO), eosinophil peroxidase (EPO), lactoperoxidase (LPO), and thyroid peroxidase (TPO), express conserved motifs around the heme prosthetic group essential for their activity, a calcium-binding site, and at least two covalent bonds linking the heme group to the protein backbone. Although most studies of the biosynthesis of these peroxidases have focused on MPO, many of the features described occur during biosynthesis of other members of the protein subfamily. Whereas MPO biosynthesis includes events typical for proteins generated in the secretory pathway, the importance and consequences of heme insertion are events uniquely associated with peroxidases. This Review summarizes decades of work elucidating specific steps in the biosynthetic pathway of human MPO. Discussion includes cotranslational glycosylation and subsequent modifications of the N-linked carbohydrate sidechains, contributions by molecular chaperones in the endoplasmic reticulum, cleavage of the propeptide from proMPO, and proteolytic processing of protomers and dimerization to yield mature MPO. Parallels between the biosynthesis of MPO and TPO as well as the impact of inherited mutations in the MPO gene on normal biosynthesis will be summarized. Lastly, specific gaps in our knowledge revealed by this review of our current understanding will be highlighted. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

User Needs in the Development of a Health App Ecosystem for Self-Management of Cystic Fibrosis: User-Centered Development Approach.

PubMed

Floch, Jacqueline; Zettl, Annabel; Fricke, Lena; Weisser, Tina; Grut, Lisbet; Vilarinho, Thomas; Stav, Erlend; Ascolese, Antonio; Schauber, Cornelia

2018-05-08

Digital self-management in cystic fibrosis (CF) is foreseen as a means toward better understanding of the disease and its treatment and better adherence to the treatment. Mobile apps hold the potential to provide access to information, motivate, and strengthen compliance. However, to deliver high-quality apps, the development should be based on thorough knowledge about user needs. Empirical research on the user-centered development of mobile apps for health care is, however, still limited. The aim of this research is to develop and evaluate an app ecosystem for self-management in CF. It targets not only those directly affected by CF but also parents and health care professionals involved in the treatment. This paper covers the first step of the design process that aims to analyze the context and the user requirements. The primary research question is as follows: what digital support has the potential to usefully support persons with CF and their caregivers in the CF care? To answer this question, we address two preliminary questions: what important factors in everyday life affect the care of persons with CF? and how is the CF care delivered today and what are the limitations of CF care services? The overall research adopts a user-centered design approach in which future users are involved in the development process from the very beginning to ensure that the apps developed best suit the potential users. The research presented in the paper follows an interpretative case study research strategy seeking to understand the concerns and needs of persons with CF and their caregivers. Data were collected through semistructured qualitative interviews involving 74 participants in seven European countries and from internet forums. The results of the analysis phase show a strong need for individuality of the digital support, as well as for its adaptability to different contexts. The paper presents the concerns and needs of the participants in the study and extracts a set of relevant features for a self-management app ecosystem. Education, enzyme dosage calculation, nutrition management, treatment organization, health diary, treatment follow-up, practical guidelines for treatment, communication with doctors, and communication with peers are foreseen as useful features. The results indicate the readiness for self-management in the CF care even in countries that provide well-functioning health care services for CF care. The large diversity of user requirements identified reflects the crucial role user integration plays in developing apps for a chronic condition such as CF. The need for personalization stemming from the individuality of the patients and the need for communication with health care professionals support the idea of an app ecosystem for the self-management of CF. ©Jacqueline Floch, Annabel Zettl, Lena Fricke, Tina Weisser, Lisbet Grut, Thomas Vilarinho, Erlend Stav, Antonio Ascolese, Cornelia Schauber. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 08.05.2018.

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

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.

Qualitative assessment of user experiences of a novel smart phone application designed to support flexible intensive insulin therapy in type 1 diabetes.

PubMed

Knight, Brigid A; McIntyre, H David; Hickman, Ingrid J; Noud, Marina

2016-09-15

Modern flexible multiple daily injection (MDI) therapy requires people with diabetes to manage complex mathematical calculations to determine insulin doses on a day to day basis. Automated bolus calculators assist with these calculations, add additional functionality to protect against hypoglycaemia and enhance the record keeping process, however uptake and use depends on the devices meeting the needs of the user. We aimed to obtain user feedback on the usability of a mobile phone bolus calculator application in adults with T1DM to inform future development of mobile phone diabetes support applications. Adults with T1DM who had previously received education in flexible MDI therapy were invited to participate. Eligible respondents attended app education and one month later participated in a focus group to provide feedback on the features of the app in relation to usability for patient-based flexible MDI and future app development. Seven adults participated in the app training and follow up interview. App features that support dose adjustment to reduce hypoglycaemia risk and features that enable greater efficiency in dose calculation, record keeping and report generation were highly valued. Adults who are self managing flexible MDI found the Rapidcalc mobile phone app to be a useful self-management tool and additional features to further improve usability, such as connectivity with BG meter and food databases, shortcut options to economise data entry and web based storage of data, were identified. Further work is needed to ascertain specific features and benefit for those with lower health literacy.

[Future trend medical apps. From the apps store directly into medical practice?].

PubMed

Gehring, H; Pramann, O; Imhoff, M; Albrecht, U-V

2014-12-01

In day to day medical care, patients, nursing staff and doctors currently face a bewildering and rapidly growing number of health-related apps running on various "smart" devices and there are also uncountable possibilities for the use of such technology. Concerning regulation, a risk-based approach is applied for development and use (including safety and security considerations) of medical and health-related apps. Considering safety-related issues as well as organizational matters, this is a sensible approach but requires honest self-assessment as well as a high degree of responsibility, networking and good quality management by all those involved. This cannot be taken for granted. Apart from regulatory aspects it is important to not only consider what is reasonable, helpful or profitable. Quality aspects, safety matters, data protection and privacy as well as liability issues must also be considered but are often not adequately respected. If software quality is compromised, this endangers patient safety as well as data protection, privacy and data integrity. This can for example result in unwanted advertising or unauthorized access to the stored data by third parties; therefore, local, regional and international regulatory measures need to be applied in order to ensure safe use of medical apps in all possible areas, including the operating room (OR) with its highly specialized demands. Lawmakers need to include impulses from all stakeholders in their considerations and this should include input from existing private initiatives that already deal with the use and evaluation of apps in a medical context. Of course, this process needs to respect pre-existing national, European as well as international (harmonized) standards.

Bioaccessibility of PAHs and PAH derivatives in a fuel soot assessed by an in vitro digestive model with absorptive sink: Effects of aging the soot in a soil-water mixture.

PubMed

Zhang, Yanyan; Pignatello, Joseph J; Tao, Shu

2018-02-15

Aging soot in soil under neutral aqueous condition for 30days significantly (p<0.05) reduced the apparent gastrointestinal bioaccessibility (B app ) of polycyclic aromatic hydrocarbons (PAHs) and PAH derivatives (d-PAHs) natively present in a composite fuel soot sample. B app was determined under fasting conditions by a previously developed in vitro digestive model that includes silicone sheet as a third phase absorptive sink in the small intestinal stage. Redistribution of contaminants from soot to soil, determined in independent experiments, was too small to affect B app . Prior uptake by soot of a commercial humic acid representing dissolved soil organic matter had no impact on B app . We identified two causes for the reduction in B app by soil and found they were approximately additive. One is an aging time-independent "matrix effect" attributable to competitive sorption by the soil of labile contaminant that is desorbed from the soot during the digestion test. The other is the dissolution of soluble substances from the soot during the aging process that increases soot surface area and nanoporosity. The increased surface area and nanoporosity drive contaminants from labile to nonlabile states in the soot and decrease the desorption into the digestive fluid, the former contributing most to the reduction in B app . The present study shows that mixing of raw soot with soil has important effects, both aging and non-aging, on the bioaccessibility of soot-borne contaminants. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

The impact of a mobile application-based treatment for urinary incontinence in adult women: Design of a mixed-methods randomized controlled trial in a primary care setting.

PubMed

Loohuis, Anne M M; Wessels, Nienke J; Jellema, Petra; Vermeulen, Karin M; Slieker-Ten Hove, Marijke C; van Gemert-Pijnen, Julia E W C; Berger, Marjolein Y; Dekker, Janny H; Blanker, Marco H

2018-02-02

We aim to assess whether a purpose-developed mobile application (app) is non-inferior regarding effectiveness and cost-effective when used to treat women with urinary incontinence (UI), as compared to care as usual in Dutch primary care. Additionally, we will explore the expectations and experiences of patients and care providers regarding app usage. A mixed-methods study will be performed, combining a pragmatic, randomized-controlled, non-inferiority trial with an extensive process evaluation. Women aged ≥18 years, suffering from UI ≥ 2 times per week and with access to a smartphone or tablet are eligible to participate. The primary outcome will be the change in UI symptom scores at 4 months after randomization, as assessed by the International Consultation on Incontinence Modular Questionnaire UI Short Form. Secondary outcomes will be the change in UI symptom scores at 12 months, as well as the patient-reported global impression of improvement, quality of life, change in sexual functioning, UI episodes per day, and costs at 4 and 12 months. In parallel, we will perform an extensive process evaluation to assess the expectations and experiences of patients and care providers regarding app usage, making use of interviews, focus group sessions, and log data analysis. This study will assess both the effectiveness and cost-effectiveness of app-based treatment for UI. The combination with the process evaluation, which will be performed in parallel, should also give valuable insights into the contextual factors that influence the effectiveness of such a treatment. © 2018 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.

Students paperwork tracking system (SPATRASE)

NASA Astrophysics Data System (ADS)

Ishak, I. Y.; Othman, M. B.; Talib, Rahmat; Ilyas, M. A.

2017-09-01

This paper focused on a system for tracking the status of the paperwork using the Near Field Communication (NFC) technology and mobile apps. Student paperwork tracking system or known as SPATRASE was developed to ease the user to track the location status of the paperwork. The current problem faced by the user is the process of approval paperwork takes around a month or more. The process took around a month to get full approval from the department because of many procedures that need to be done. Nevertheless, the user cannot know the location status of the paperwork immediately because of the inefficient manual system. The submitter needs to call the student affairs department to get the information about the location status of the paperwork. Thus, this project was purposed as an alternative to solve the waiting time of the paperwork location status. The prototype of this system involved the hardware and software. The project consists of NFC tags, RFID Reader, and mobile apps. At each checkpoint, the RFID Reader was placed on the secretary desk. While the system involved the development of database using Google Docs that linked to the web server. After that, the submitter received the URL link and be directed to the web server and mobile apps. This system is capable of checking their location status tracking using mobile apps and Google Docs. With this system, it makes the tracking process become efficient and reliable to know the paperwork at the exact location. Thus, it is preventing the submitter to call the department all the time. Generally, this project is fully functional and we hope it can help Universiti Tun Hussein Onn Malaysia (UTHM) to overcome the problem of paperwork missing and location of the paperwork.

49 CFR Appendix A to Part 580 - Secure Printing Processes and Other Secure Processes

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 7 2014-10-01 2014-10-01 false Secure Printing Processes and Other Secure Processes A Appendix A to Part 580 Transportation Other Regulations Relating to Transportation (Continued... DISCLOSURE REQUIREMENTS Pt. 580, App. A Appendix A to Part 580—Secure Printing Processes and Other Secure...

49 CFR Appendix A to Part 580 - Secure Printing Processes and Other Secure Processes

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 false Secure Printing Processes and Other Secure Processes A Appendix A to Part 580 Transportation Other Regulations Relating to Transportation (Continued... DISCLOSURE REQUIREMENTS Pt. 580, App. A Appendix A to Part 580—Secure Printing Processes and Other Secure...

49 CFR Appendix A to Part 580 - Secure Printing Processes and Other Secure Processes

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 7 2011-10-01 2011-10-01 false Secure Printing Processes and Other Secure Processes A Appendix A to Part 580 Transportation Other Regulations Relating to Transportation (Continued... DISCLOSURE REQUIREMENTS Pt. 580, App. A Appendix A to Part 580—Secure Printing Processes and Other Secure...

49 CFR Appendix A to Part 580 - Secure Printing Processes and Other Secure Processes

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 7 2013-10-01 2013-10-01 false Secure Printing Processes and Other Secure Processes A Appendix A to Part 580 Transportation Other Regulations Relating to Transportation (Continued... DISCLOSURE REQUIREMENTS Pt. 580, App. A Appendix A to Part 580—Secure Printing Processes and Other Secure...

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

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.

Transgenic analysis reveals LeACS-1 as a positive regulator of ethylene-induced shikonin biosynthesis in Lithospermum erythrorhizon hairy roots.

PubMed

Fang, Rongjun; Wu, Fengyao; Zou, Ailan; Zhu, Yu; Zhao, Hua; Zhao, Hu; Liao, Yonghui; Tang, Ren-Jie; Yang, Tongyi; Pang, Yanjun; Wang, Xiaoming; Yang, Rongwu; Qi, Jinliang; Lu, Guihua; Yang, Yonghua

2016-03-01

The phytohormone ethylene (ET) is a crucial signaling molecule that induces the biosynthesis of shikonin and its derivatives in Lithospermum erythrorhizon shoot cultures. However, the molecular mechanism and the positive regulators involved in this physiological process are largely unknown. In this study, the function of LeACS-1, a key gene encoding the 1-aminocyclopropane-1-carboxylic acid synthase for ET biosynthesis in L. erythrorhizon hairy roots, was characterized by using overexpression and RNA interference (RNAi) strategies. The results showed that overexpression of LeACS-1 significantly increased endogenous ET concentration and shikonin production, consistent with the up-regulated genes involved in ET biosynthesis and transduction, as well as the genes related to shikonin biosynthesis. Conversely, RNAi of LeACS-1 effectively decreased endogenous ET concentration and shikonin production and down-regulated the expression level of above genes. Correlation analysis showed a significant positive linear relationship between ET concentration and shikonin production. All these results suggest that LeACS-1 acts as a positive regulator of ethylene-induced shikonin biosynthesis in L. erythrorhizon hairy roots. Our work not only gives new insights into the understanding of the relationship between ET and shikonin biosynthesis, but also provides an efficient genetic engineering target gene for secondary metabolite production in non-model plant L. erythrorhizon.

ATP synthesis in the energy metabolism pathway: a new perspective for manipulating CdSe quantum dots biosynthesized in Saccharomyces cerevisiae.

PubMed

Zhang, Rong; Shao, Ming; Han, Xu; Wang, Chuan; Li, Yong; Hu, Bin; Pang, Daiwen; Xie, Zhixiong

2017-01-01

Due to a growing trend in their biomedical application, biosynthesized nanomaterials are of great interest to researchers nowadays with their biocompatible, low-energy consumption, economic, and tunable characteristics. It is important to understand the mechanism of biosynthesis in order to achieve more efficient applications. Since there are only rare studies on the influences of cellular energy levels on biosynthesis, the influence of energy is often overlooked. Through determination of the intracellular ATP concentrations during the biosynthesis process, significant changes were observed. In addition, ATP synthesis deficiency caused great decreases in quantum dots (QDs) biosynthesis in the Δ atp1 , Δ atp2 , Δ atp14 , and Δ atp17 strains. With inductively coupled plasma-atomic emission spectrometry and atomic absorption spectroscopy analyses, it was found that ATP affected the accumulation of the seleno-precursor and helped with the uptake of Cd and the formation of QDs. We successfully enhanced the fluorescence intensity 1.5 or 2 times through genetic modification to increase ATP or SeAM (the seleno analog of S -adenosylmethionine, the product that would accumulate when ATP is accrued). This work explains the mechanism for the correlation of the cellular energy level and QDs biosynthesis in living cells, demonstrates control of the biosynthesis using this mechanism, and thus provides a new manipulation strategy for the biosynthesis of other nanomaterials to widen their applications.

ATP synthesis in the energy metabolism pathway: a new perspective for manipulating CdSe quantum dots biosynthesized in Saccharomyces cerevisiae

PubMed Central

Zhang, Rong; Shao, Ming; Han, Xu; Wang, Chuan; Li, Yong; Hu, Bin; Pang, Daiwen; Xie, Zhixiong

2017-01-01

Due to a growing trend in their biomedical application, biosynthesized nanomaterials are of great interest to researchers nowadays with their biocompatible, low-energy consumption, economic, and tunable characteristics. It is important to understand the mechanism of biosynthesis in order to achieve more efficient applications. Since there are only rare studies on the influences of cellular energy levels on biosynthesis, the influence of energy is often overlooked. Through determination of the intracellular ATP concentrations during the biosynthesis process, significant changes were observed. In addition, ATP synthesis deficiency caused great decreases in quantum dots (QDs) biosynthesis in the Δatp1, Δatp2, Δatp14, and Δatp17 strains. With inductively coupled plasma-atomic emission spectrometry and atomic absorption spectroscopy analyses, it was found that ATP affected the accumulation of the seleno-precursor and helped with the uptake of Cd and the formation of QDs. We successfully enhanced the fluorescence intensity 1.5 or 2 times through genetic modification to increase ATP or SeAM (the seleno analog of S-adenosylmethionine, the product that would accumulate when ATP is accrued). This work explains the mechanism for the correlation of the cellular energy level and QDs biosynthesis in living cells, demonstrates control of the biosynthesis using this mechanism, and thus provides a new manipulation strategy for the biosynthesis of other nanomaterials to widen their applications. PMID:28579774

Production of microbial polyester by fermentation of recombinant microorganisms.

PubMed

Lee, S Y; Choi, J I

2001-01-01

Polyhydroxyalkanoates (PHAs) can be produced from renewable sources and are biodegradable with similar material properties and processibility to conventional plastic materials. With recent advances in our understanding of the biochemistry and genetics of PHA biosynthesis and cloning of the PHA biosynthesis genes from a number of different bacteria, many different recombinant bacteria have been developed to improve PHA production for commercial applications. For enhancing PHA synthetic capacity, homologous or heterologous expression of the PHA biosynthetic enzymes has been attempted. Several genes that allow utilization of various substrates were transformed into PHA producers, or non-PHA producers utilizing inexpensive carbon substrate were transformed with the PHA biosynthesis genes. Novel PHAs have been synthesized by introducing a new PHA biosynthesis pathway or a new PHA synthase gene. In this article, recent advances in the production of PHA by recombinant bacteria are described.

Investigation into the use of smartphone as a machine vision device for engineering metrology and flaw detection, with focus on drilling

NASA Astrophysics Data System (ADS)

Razdan, Vikram; Bateman, Richard

2015-05-01

This study investigates the use of a Smartphone and its camera vision capabilities in Engineering metrology and flaw detection, with a view to develop a low cost alternative to Machine vision systems which are out of range for small scale manufacturers. A Smartphone has to provide a similar level of accuracy as Machine Vision devices like Smart cameras. The objective set out was to develop an App on an Android Smartphone, incorporating advanced Computer vision algorithms written in java code. The App could then be used for recording measurements of Twist Drill bits and hole geometry, and analysing the results for accuracy. A detailed literature review was carried out for in-depth study of Machine vision systems and their capabilities, including a comparison between the HTC One X Android Smartphone and the Teledyne Dalsa BOA Smart camera. A review of the existing metrology Apps in the market was also undertaken. In addition, the drilling operation was evaluated to establish key measurement parameters of a twist Drill bit, especially flank wear and diameter. The methodology covers software development of the Android App, including the use of image processing algorithms like Gaussian Blur, Sobel and Canny available from OpenCV software library, as well as designing and developing the experimental set-up for carrying out the measurements. The results obtained from the experimental set-up were analysed for geometry of Twist Drill bits and holes, including diametrical measurements and flaw detection. The results show that Smartphones like the HTC One X have the processing power and the camera capability to carry out metrological tasks, although dimensional accuracy achievable from the Smartphone App is below the level provided by Machine vision devices like Smart cameras. A Smartphone with mechanical attachments, capable of image processing and having a reasonable level of accuracy in dimensional measurement, has the potential to become a handy low-cost Machine vision system for small scale manufacturers, especially in field metrology and flaw detection.

Potential Alternatives for Advanced Energy Material Processing in High Performance Li-ion Batteries (LIBs) via Atmospheric Pressure Plasma Treatment

NASA Astrophysics Data System (ADS)

Duh, Jenq-Gong; Chuang, Shang-I.; Lan, Chun-Kai; Yang, Hao; Chen, Hsien-Wei

2015-09-01

A new processing technique by atmospheric pressure plasma (APP) jet treatment of LIBs was introduced. Ar/N2 plasma enhanced the high-rate anode performance of Li4Ti5O12. Oxygen vacancies were discovered and nitrogen doping were achieved by the surface reaction between pristine Li4Ti5O12 and plasma reactive species (N* and N2+). Electrochemical impedance spectra confirm that plasma modification increases Li ions diffusivity and reduces internal charge-transfer resistance, leading to a superior capacity (132 mAh/g) and excellent stability with negligible capacity decay over 100 cycles under 10C rate. Besides 2D material surface treatment, a specially designed APP generator that are feasible to modify 3D TiO2 powders is proposed. The rate capacity of 20 min plasma treated TiO2 exhibited 20% increment. Plasma diagnosis revealed that excited Ar and N2 was contributed to TiO2 surface reduction as companied by formation of oxygen vacancy. A higher amount of oxygen vacancy increased the chance for excited nitrogen doped onto surface of TiO2 particle. These findings promote the understanding of APP on processing anode materials in high performance LIBs.

Sustainable aggregate production planning in the chemical process industry - A benchmark problem and dataset.

PubMed

Brandenburg, Marcus; Hahn, Gerd J

2018-06-01

Process industries typically involve complex manufacturing operations and thus require adequate decision support for aggregate production planning (APP). The need for powerful and efficient approaches to solve complex APP problems persists. Problem-specific solution approaches are advantageous compared to standardized approaches that are designed to provide basic decision support for a broad range of planning problems but inadequate to optimize under consideration of specific settings. This in turn calls for methods to compare different approaches regarding their computational performance and solution quality. In this paper, we present a benchmarking problem for APP in the chemical process industry. The presented problem focuses on (i) sustainable operations planning involving multiple alternative production modes/routings with specific production-related carbon emission and the social dimension of varying operating rates and (ii) integrated campaign planning with production mix/volume on the operational level. The mutual trade-offs between economic, environmental and social factors can be considered as externalized factors (production-related carbon emission and overtime working hours) as well as internalized ones (resulting costs). We provide data for all problem parameters in addition to a detailed verbal problem statement. We refer to Hahn and Brandenburg [1] for a first numerical analysis based on and for future research perspectives arising from this benchmarking problem.

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.

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.