WZB117 (2-Fluoro-6-(m-hydroxybenzoyloxy) Phenyl m-Hydroxybenzoate) Inhibits GLUT1-mediated Sugar Transport by Binding Reversibly at the Exofacial Sugar Binding Site.

PubMed

Ojelabi, Ogooluwa A; Lloyd, Kenneth P; Simon, Andrew H; De Zutter, Julie K; Carruthers, Anthony

2016-12-23

WZB117 (2-fluoro-6-(m-hydroxybenzoyloxy) phenyl m-hydroxybenzoate) inhibits passive sugar transport in human erythrocytes and cancer cell lines and, by limiting glycolysis, inhibits tumor growth in mice. This study explores how WZB117 inhibits the erythrocyte sugar transporter glucose transport protein 1 (GLUT1) and examines the transporter isoform specificity of inhibition. WZB117 reversibly and competitively inhibits erythrocyte 3-O-methylglucose (3MG) uptake with K i (app) = 6 μm but is a noncompetitive inhibitor of sugar exit. Cytochalasin B (CB) is a reversible, noncompetitive inhibitor of 3MG uptake with K i (app) = 0.3 μm but is a competitive inhibitor of sugar exit indicating that WZB117 and CB bind at exofacial and endofacial sugar binding sites, respectively. WZB117 inhibition of GLUTs expressed in HEK293 cells follows the order of potency: insulin-regulated GLUT4 ≫ GLUT1 ≈ neuronal GLUT3. This may explain WZB117-induced murine lipodystrophy. Molecular docking suggests the following. 1) The WZB117 binding envelopes of exofacial GLUT1 and GLUT4 conformers differ significantly. 2) GLUT1 and GLUT4 exofacial conformers present multiple, adjacent glucose binding sites that overlap with WZB117 binding envelopes. 3) The GLUT1 exofacial conformer lacks a CB binding site. 4) The inward GLUT1 conformer presents overlapping endofacial WZB117, d-glucose, and CB binding envelopes. Interrogating the GLUT1 mechanism using WZB117 reveals that subsaturating WZB117 and CB stimulate erythrocyte 3MG uptake. Extracellular WZB117 does not affect CB binding to GLUT1, but intracellular WZB117 inhibits CB binding. These findings are incompatible with the alternating conformer carrier for glucose transport but are consistent with either a multisubunit, allosteric transporter, or a transporter in which each subunit presents multiple, interacting ligand binding sites. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human-type receptors.

PubMed

de Vries, Robert P; Tzarum, Netanel; Peng, Wenjie; Thompson, Andrew J; Ambepitiya Wickramasinghe, Iresha N; de la Pena, Alba T Torrents; van Breemen, Marielle J; Bouwman, Kim M; Zhu, Xueyong; McBride, Ryan; Yu, Wenli; Sanders, Rogier W; Verheije, Monique H; Wilson, Ian A; Paulson, James C

2017-09-01

In June 2013, the first case of human infection with an avian H6N1 virus was reported in a Taiwanese woman. Although this was a single non-fatal case, the virus continues to circulate in Taiwanese poultry. As with any emerging avian virus that infects humans, there is concern that acquisition of human-type receptor specificity could enable transmission in the human population. Despite mutations in the receptor-binding pocket of the human H6N1 isolate, it has retained avian-type (NeuAcα2-3Gal) receptor specificity. However, we show here that a single nucleotide substitution, resulting in a change from Gly to Asp at position 225 (G225D), completely switches specificity to human-type (NeuAcα2-6Gal) receptors. Significantly, G225D H6 loses binding to chicken trachea epithelium and is now able to bind to human tracheal tissue. Structural analysis reveals that Asp225 directly interacts with the penultimate Gal of the human-type receptor, stabilizing human receptor binding. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Death receptors DR6 and TROY regulate brain vascular development.

PubMed

Tam, Stephen J; Richmond, David L; Kaminker, Joshua S; Modrusan, Zora; Martin-McNulty, Baby; Cao, Tim C; Weimer, Robby M; Carano, Richard A D; van Bruggen, Nick; Watts, Ryan J

2012-02-14

Signaling events that regulate central nervous system (CNS) angiogenesis and blood-brain barrier (BBB) formation are only beginning to be elucidated. By evaluating the gene expression profile of mouse vasculature, we identified DR6/TNFRSF21 and TROY/TNFRSF19 as regulators of CNS-specific angiogenesis in both zebrafish and mice. Furthermore, these two death receptors interact both genetically and physically and are required for vascular endothelial growth factor (VEGF)-mediated JNK activation and subsequent human brain endothelial sprouting in vitro. Increasing beta-catenin levels in brain endothelium upregulate DR6 and TROY, indicating that these death receptors are downstream target genes of Wnt/beta-catenin signaling, which has been shown to be required for BBB development. These findings define a role for death receptors DR6 and TROY in CNS-specific vascular development. Copyright © 2012 Elsevier Inc. All rights reserved.

TRPC6 specifically interacts with APP to inhibit its cleavage by γ-secretase and reduce Aβ production

PubMed Central

Wang, Junfeng; Lu, Rui; Yang, Jian; Li, Hongyu; He, Zhuohao; Jing, Naihe; Wang, Xiaomin; Wang, Yizheng

2015-01-01

Generation of β-amyloid (Aβ) peptide in Alzheimer's disease involves cleavage of amyloid precursor protein (APP) by γ-secretase, a protease known to cleave several substrates, including Notch. Finding specific modulators for γ-secretase could be a potential avenue to treat the disease. Here, we report that transient receptor potential canonical (TRPC) 6 specifically interacts with APP leading to inhibition of its cleavage by γ-secretase and reduction in Aβ production. TRPC6 interacts with APP (C99), but not with Notch, and prevents C99 interaction with presenilin 1 (PS1). A fusion peptide derived from TRPC6 also reduces Aβ levels without effect on Notch cleavage. Crossing APP/PS1 mice with TRPC6 transgenic mice leads to a marked reduction in both plaque load and Aβ levels, and improvement in structural and behavioural impairment. Thus, TRPC6 specifically modulates γ-secretase cleavage of APP and preventing APP (C99) interaction with PS1 via TRPC6 could be a novel strategy to reduce Aβ formation. PMID:26581893

Structural studies of the nudix hydrolase DR1025 from deinococcus radiodurans and its ligand complexes

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

Ranatunga, Wasantha; Hill, Emma E.; Mooster, Jana L.

We have determined the crystal structure, at 1.4, of the Nudix hydrolase DR1025 from the extremely radiation resistant bacterium Deinococcus radiodurans. The protein forms an intertwined homodimer by exchanging N-terminal segments between chains. We have identified additional conserved elements of the Nudix fold, including the metal-binding motif, a kinked b-strand characterized by a proline two positions upstream of the Nudix consensus sequence, and participation of the N-terminal extension in the formation of the substrate-binding pocket. Crystal structures were also solved of DR1025 crystallized in the presence of magnesium and either a GTP analog or Ap4A (both at 1.6 resolution). Inmore » the Ap4Aco-crystal, the electron density indicated that the product of asymmetric hydrolysis, ATP, was bound to the enzyme. The GTP analog bound structure showed that GTP was bound almost identically as ATP. Neither nucleoside triphosphate was further cleaved.« less

Acceptor binding energies in GaN and AlN

NASA Astrophysics Data System (ADS)

Mireles, Francisco; Ulloa, Sergio E.

1998-08-01

We employ effective-mass theory for degenerate hole bands to calculate the acceptor binding energies for Be, Mg, Zn, Ca, C, and Si substitutional acceptors in GaN and AlN. The calculations are performed through the 6×6 Rashba-Sheka-Pikus and the Luttinger-Kohn matrix Hamiltonians for wurtzite (WZ) and zinc-blende (ZB) crystal phases, respectively. An analytic representation for the acceptor pseudopotential is used to introduce the specific nature of the impurity atoms. The energy shift due to polaron effects is also considered in this approach. The ionization energy estimates are in very good agreement with those reported experimentally in WZ GaN. The binding energies for ZB GaN acceptors are all predicted to be shallower than the corresponding impurities in the WZ phase. The binding-energy dependence upon the crystal-field splitting in WZ GaN is analyzed. Ionization levels in AlN are found to have similar ``shallow'' values to those in GaN, but with some important differences which depend on the band structure parametrizations, especially the value of the crystal-field splitting used.

Association of HLA-DR1 with the allergic response to the major mugwort pollen allergen: molecular background.

PubMed

Knapp, Bernhard; Fischer, Gottfried; Van Hemelen, Dries; Fae, Ingrid; Maillere, Bernard; Ebner, Christof; Schreiner, Wolfgang; Bohle, Barbara; Jahn-Schmid, Beatrice

2012-08-08

Mugwort pollen allergens represent the main cause of pollinosis in late summer. The major allergen, Art v 1, contains only one single immunodominant, solely HLA-DR-restricted T cell epitope (Art v 125-36). The frequency of HLA-DRB1*01 is highly increased in mugwort-allergic individuals and HLA-DR1 serves as restriction element for Art v 125-36. However, Art v 125-36 also binds to HLA-DR4 with high affinity and DR1-restricted Art v 125-36 -specific T cell receptors can be activated by HLA-DR4 molecules. To understand the predominance of HLA-DR1 in mugwort allergy in spite of the degeneracy in HLA/peptide-binding and TCR-recognition, we investigated the molecular background of Art v 125-36 /MHC/TCR interactions in the context of HLA-DR1 compared to -DR4. The majority of Art v 125-36 -specific T cell lines and clones from HLA-DR1 carrying, mugwort pollen-allergic donors reacted to synthetic and naturally processed Art v 1-peptides when presented by HLA-DR1 or HLA-DR4 expressing antigen presenting cells. However, at limiting peptide concentrations DR1 was more effective in T cell stimulation. In addition, the minimal epitope for 50% of Art v 125-36 -specific T cells was shorter for DR1 than for DR4. In vitro binding assays of Art v 125-36 mutant peptides to isolated DR1- and DR4-molecules indicated similar binding capacities and use of the same register. In silico simulation of Art v 125-36 binding to HLA-DR1 and -DR4 suggested similar binding of the central part of the peptide to either molecule, but a higher flexibility of the N- and C-terminal amino acids and detachment at the C-terminus in HLA-DR1. The predominance of HLA-DR1 in the response to Art v 125-36 may be explained by subtle conformation changes of the peptide bound to DR1 compared to DR4. Computer simulation supported our experimental data by demonstrating differences in peptide mobility within the HLA-DR complex that may influence TCR-binding. We suggest that the minor differences observed in vitro may

Exploring substrate binding and discrimination in fructose1, 6-bisphosphate and tagatose 1,6-bisphosphate aldolases.

PubMed

Zgiby, S M; Thomson, G J; Qamar, S; Berry, A

2000-03-01

Fructose 1,6-bisphosphate aldolase catalyses the reversible condensation of glycerone-P and glyceraldehyde 3-phosphate into fructose 1,6-bisphosphate. A recent structure of the Escherichia coli Class II fructose 1,6-bisphosphate aldolase [Hall, D.R., Leonard, G.A., Reed, C.D., Watt, C.I., Berry, A. & Hunter, W.N. (1999) J. Mol. Biol. 287, 383-394] in the presence of the transition state analogue phosphoglycolohydroxamate delineated the roles of individual amino acids in binding glycerone-P and in the initial proton abstraction steps of the mechanism. The X-ray structure has now been used, together with sequence alignments, site-directed mutagenesis and steady-state enzyme kinetics to extend these studies to map important residues in the binding of glyceraldehyde 3-phosphate. From these studies three residues (Asn35, Ser61 and Lys325) have been identified as important in catalysis. We show that mutation of Ser61 to alanine increases the Km value for fructose 1, 6-bisphosphate 16-fold and product inhibition studies indicate that this effect is manifested most strongly in the glyceraldehyde 3-phosphate binding pocket of the active site, demonstrating that Ser61 is involved in binding glyceraldehyde 3-phosphate. In contrast a S61T mutant had no effect on catalysis emphasizing the importance of an hydroxyl group for this role. Mutation of Asn35 (N35A) resulted in an enzyme with only 1.5% of the activity of the wild-type enzyme and different partial reactions indicate that this residue effects the binding of both triose substrates. Finally, mutation of Lys325 has a greater effect on catalysis than on binding, however, given the magnitude of the effects it is likely that it plays an indirect role in maintaining other critical residues in a catalytically competent conformation. Interestingly, despite its proximity to the active site and high sequence conservation, replacement of a fourth residue, Gln59 (Q59A) had no significant effect on the function of the enzyme. In a

Kir6.2-dependent high-affinity repaglinide binding to β-cell KATP channels

PubMed Central

Hansen, Ann Maria K; Hansen, John Bondo; Carr, Richard D; Ashcroft, Frances M; Wahl, Philip

2005-01-01

The β-cell KATP channel is composed of two types of subunit – the inward rectifier K+ channel (Kir6.2) which forms the channel pore, and the sulphonylurea receptor (SUR1), which serves as a regulatory subunit. The N-terminus of Kir6.2 is involved in transduction of sulphonylurea binding into channel closure, and deletion of the N-terminus (Kir6.2ΔN14) results in functional uncoupling of the two subunits. In this study, we investigate the interaction of the hypoglycaemic agents repaglinide and glibenclamide with SUR1 and the effect of Kir6.2 on this interaction. We further explore how the binding properties of repaglinide and glibenclamide are affected by functional uncoupling of SUR1 and Kir6.2 in Kir6.2ΔN14/SUR1 channels. All binding experiments are performed on membranes in ATP-free buffer at 37°C. Repaglinide was found to bind with low affinity (KD=59±16 nM) to SUR1 alone, but with high affinity (increased ∼150-fold) when SUR1 was co-expressed with Kir6.2 (KD=0.42±0.03 nM). Glibenclamide, tolbutamide and nateglinide all bound with marginally lower affinity to SUR1 than to Kir6.2/SUR1. Repaglinide bound with low affinity (KD=51±23 nM) to SUR1 co-expressed with Kir6.2ΔN14. In contrast, the affinity for glibenclamide, tolbutamide and nateglinide was only mildly changed as compared to wild-type channels. In whole-cell patch-clamp experiments inhibition of Kir6.2ΔN14/SUR1 currents by both repaglinide and nateglinde is abolished. The results suggest that Kir6.2 causes a conformational change in SUR1 required for high-affinity repaglinide binding, or that the high-affinity repaglinide-binding site includes contributions from both SUR1 and Kir6.2. Glibenclamide, tolbutamide and nateglinide binding appear to involve only SUR1. PMID:15678092

Efficient n-doping of graphene films by APPE (aminophenyl propargyl ether): a substituent effect.

PubMed

Kim, Youngsoo; Yoo, Je Min; Jeon, Hak Rim; Hong, Byung Hee

2013-11-14

We report the synthesis and applications of APPE (aminophenyl propargyl ether) as a novel n-type dopant for graphene. The characteristics of APPE-doped graphene films were investigated using Raman spectroscopy as well as electron transport measurements. The Raman 2D/G peak ratio decreased by more than 40%, and the minimum conductivity voltage (Dirac voltage) was shifted to -133 V as the pristine graphene was doped with APPE, indicating that the graphene was strongly n-doped. We suppose that the electron donating property of the amine group (-NH2) is the origin of such an intense n-doping effect. In contrast, a similar molecule with an electron withdrawing nitro group (-NO2) (nitrophenyl propargyl ether, NPPE) showed a slight p-doping effect. Thus, we conclude that the doping effect of a molecular framework strongly depends on the functional substituents, which can be represented by the Hammett equation. We also confirmed that the sheet resistance of the APPE doped graphene film was reduced by ∼70%, which is crucial to enhance the electrical conductivity of graphene for various electronic applications. In addition, the acetylene group of APPE appears promising to be utilized in "click chemistry" to further functionalize the π-surface of graphene for sensors and bio applications.

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

PubMed

Herrmann, Lynn Katherine; Kim, Jinsook

2017-01-01

There are thousands of fitness-related smartphone applications ("apps") available for free and purchase, but there is uncertainty if these apps help individuals achieve and maintain personal fitness. Technology usage attrition is also a concern among research studies on health technologies. Usage of three fitness apps was examined over 5 months to assess adherence and effectiveness. Initially, 64 participants downloaded three free apps available on Android and iOS and 47 remained in the study until posttest. With a one group pre-posttest design and checkpoints at months 1, 3, and 5, exercise and exercise with fitness apps were examined in the framework of the Theory of Planned Behavior (TPB) using a validated survey. Apps were selected based on their function from the Functional Triad. Perceived fitness was also measured. T -tests, sign tests, Fisher's exact tests, and linear and logistic regression were used to compare pre to posttests and users to non-users of the apps. Forty-seven participants completed both pre and posttests. Individual item scores indicated no significant change pre to posttest except for decreases observed in usefulness of using apps for exercise (attitude) (-0.78, P<0.01), peer influence on exercise (subjective norm) (-0.51, P<0.05), peer influence on exercise with apps (subjective norm) (-1.02, P<0.01), perceived difficulties in exercising with apps (perceived behavioral control) (-1.29, P<0.001), and the expected frequency of exercise with apps over the next 2 weeks (behavioral intention) (P<0.0001 in a sign test). Subscale total scores indicated significant decreases in subjective norm regarding exercise (-0.72, P<0.05), subjective norm regarding exercise with apps (-1.72, P<0.01), and perceived behavioral control over exercising with apps (-2.56, P<0.01) between pre and posttest. When comparing app users (n=32) to non-users (n=15), there was only a significant difference in subscale total scores at posttest for attitude toward exercising

Mechanism of antifungal activity of antimicrobial peptide APP, a cell-penetrating peptide derivative, against Candida albicans: intracellular DNA binding and cell cycle arrest.

PubMed

Li, Lirong; Sun, Jin; Xia, Shufang; Tian, Xu; Cheserek, Maureen Jepkorir; Le, Guowei

2016-04-01

We investigated the antifungal properties and anti-candidal mechanism of antimicrobial peptide APP. The minimum inhibitory concentration of APP was 8 μM against Candida albicans and Aspeogillus flavus, the concentration against Saccharomyces cerevisiae and Cryptococcus neoformans was 16 μM, while 32 μM inhibited Aspergilla niger and Trichopyton rubrum. APP caused slight depolarization (12.32 ± 0.87%) of the membrane potential of intact C. albicans cells when it exerted its anti-candidal activity and only caused 21.52 ± 0.48% C. albicans cell membrane damage. APP interacted with cell wall membrane, caused potassium efflux and nucleotide leakage. However, confocal fluorescence microscopy experiment and flow cytometry confirmed that FITC-labeled APP penetrated C. albicans cell membrane with 52.31 ± 1.88% cell-penetrating efficiency and accumulated in the cytoplasm. Then, APP interact with C. albicans genomic DNA and completely suppressed DNA migration above weight ratio (peptide/DNA) of 2, and significantly arrested cell cycles during the S-phase (S-phase cell population was 27.09 ± 0.73%, p < 0.05) after penetrating the cell membrane. Results indicated that APP kills C. albicans for efficient cell-penetrating efficiency, strong DNA-binding affinity and significant physiological changes inducing S-phase arrest in intracellular environment.

The S-layer Protein DR_2577 Binds Deinoxanthin and under Desiccation Conditions Protects against UV-Radiation in Deinococcus radiodurans

PubMed Central

Farci, Domenica; Slavov, Chavdar; Tramontano, Enzo; Piano, Dario

2016-01-01

Deinococcus radiodurans has the puzzling ability to withstand over a broad range of extreme conditions including high doses of ultraviolet radiation and deep desiccation. This bacterium is surrounded by a surface layer (S-layer) built of a regular repetition of several proteins, assembled to form a paracrystalline structure. Here we report that the deletion of a main constituent of this S-layer, the gene DR_2577, causes a decrease in the UVC resistance, especially in desiccated cells. Moreover, we show that the DR_2577 protein binds the carotenoid deinoxanthin, a strong protective antioxidant specific of this bacterium. A further spectroscopical characterization of the deinoxanthin-DR_2577 complex revealed features which could suggest a protective role of DR_2577. We propose that, especially under desiccation, the S-layer shields the bacterium from incident ultraviolet light and could behave as a first lane of defense against UV radiation. PMID:26909071

The S-layer Protein DR_2577 Binds Deinoxanthin and under Desiccation Conditions Protects against UV-Radiation in Deinococcus radiodurans.

PubMed

Farci, Domenica; Slavov, Chavdar; Tramontano, Enzo; Piano, Dario

2016-01-01

Deinococcus radiodurans has the puzzling ability to withstand over a broad range of extreme conditions including high doses of ultraviolet radiation and deep desiccation. This bacterium is surrounded by a surface layer (S-layer) built of a regular repetition of several proteins, assembled to form a paracrystalline structure. Here we report that the deletion of a main constituent of this S-layer, the gene DR_2577, causes a decrease in the UVC resistance, especially in desiccated cells. Moreover, we show that the DR_2577 protein binds the carotenoid deinoxanthin, a strong protective antioxidant specific of this bacterium. A further spectroscopical characterization of the deinoxanthin-DR_2577 complex revealed features which could suggest a protective role of DR_2577. We propose that, especially under desiccation, the S-layer shields the bacterium from incident ultraviolet light and could behave as a first lane of defense against UV radiation.

Establishment of HLA-DR4 Transgenic Mice for the Identification of CD4+ T Cell Epitopes of Tumor-Associated Antigens

PubMed Central

Harada, Kumiko; Michibata, Yayoi; Tsukamoto, Hirotake; Senju, Satoru; Tomita, Yusuke; Yuno, Akira; Hirayama, Masatoshi; Abu Sayem, Mohammad; Takeda, Naoki; Shibuya, Isao; Sogo, Shinji; Fujiki, Fumihiro; Sugiyama, Haruo; Eto, Masatoshi; Nishimura, Yasuharu

2013-01-01

Reports have shown that activation of tumor-specific CD4+ helper T (Th) cells is crucial for effective anti-tumor immunity and identification of Th-cell epitopes is critical for peptide vaccine-based cancer immunotherapy. Although computer algorithms are available to predict peptides with high binding affinity to a specific HLA class II molecule, the ability of those peptides to induce Th-cell responses must be evaluated. We have established HLA-DR4 (HLA-DRA*01:01/HLA-DRB1*04:05) transgenic mice (Tgm), since this HLA-DR allele is most frequent (13.6%) in Japanese population, to evaluate HLA-DR4-restricted Th-cell responses to tumor-associated antigen (TAA)-derived peptides predicted to bind to HLA-DR4. To avoid weak binding between mouse CD4 and HLA-DR4, Tgm were designed to express chimeric HLA-DR4/I-Ed, where I-Ed α1 and β1 domains were replaced with those from HLA-DR4. Th cells isolated from Tgm immunized with adjuvant and HLA-DR4-binding cytomegalovirus-derived peptide proliferated when stimulated with peptide-pulsed HLA-DR4-transduced mouse L cells, indicating chimeric HLA-DR4/I-Ed has equivalent antigen presenting capacity to HLA-DR4. Immunization with CDCA155-78 peptide, a computer algorithm-predicted HLA-DR4-binding peptide derived from TAA CDCA1, successfully induced Th-cell responses in Tgm, while immunization of HLA-DR4-binding Wilms' tumor 1 antigen-derived peptide with identical amino acid sequence to mouse ortholog failed. This was overcome by using peptide-pulsed syngeneic bone marrow-derived dendritic cells (BM-DC) followed by immunization with peptide/CFA booster. BM-DC-based immunization of KIF20A494-517 peptide from another TAA KIF20A, with an almost identical HLA-binding core amino acid sequence to mouse ortholog, successfully induced Th-cell responses in Tgm. Notably, both CDCA155-78 and KIF20A494-517 peptides induced human Th-cell responses in PBMCs from HLA-DR4-positive donors. Finally, an HLA-DR4 binding DEPDC1191-213 peptide from a new

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

PubMed

Karduck, Justine; Chapman-Novakofski, Karen

2018-01-01

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

Designing for Data with Ask Dr. Discovery: Design Approaches for Facilitating Museum Evaluation with Real-Time Data Mining

ERIC Educational Resources Information Center

Nelson, Brian C.; Bowman, Cassie; Bowman, Judd

2017-01-01

Ask Dr. Discovery is an NSF-funded study addressing the need for ongoing, large-scale museum evaluation while investigating new ways to encourage museum visitors to engage deeply with museum content. To realize these aims, we are developing and implementing a mobile app with two parts: (1) a front-end virtual scientist called Dr. Discovery (Dr. D)…

Familial Alzheimer's disease mutations in presenilin 1 do not alter levels of the secreted amyloid-beta protein precursor generated by beta-secretase cleavage.

PubMed

Zhang, Can; Browne, Andrew; Kim, Doo Yeon; Tanzi, Rudolph E

2010-02-01

Alzheimer's disease (AD) is an insidious and progressive disease with a genetically complex and heterogenous etiology. More than 200 fully penetrant mutations in the amyloid beta-protein precursor (APP), presenilin 1 (or PSEN1), and presenilin 2 (PSEN2) have been linked to early-onset familial AD (FAD). 177 PSEN1 FAD mutations have been identified so far and account for more than approximately 80% of all FAD mutations. All PSEN1 FAD mutations can increase the Abeta42:Abeta40 ratio with seemingly different and incompletely understood mechanisms. A recent study has shown that the 286 amino acid N-terminal fragment of APP (N-APP), a proteolytic product of beta-secretase-derived secreted form of APP (sAPPbeta), could bind the death receptor, DR6, and lead to neurodegeneration. Here we asked whether PSEN1 FAD mutations lead to neurodegeneration by modulating sAPPbeta levels. All four different PSEN1 FAD mutations tested (in three mammalian cell lines) did not alter sAPPbeta levels. Therefore PS1 mutations do not appear to contribute to AD pathogenesis via altered production of sAPPbeta.

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

PubMed Central

Kim, Jinsook

2017-01-01

Background There are thousands of fitness-related smartphone applications (“apps”) available for free and purchase, but there is uncertainty if these apps help individuals achieve and maintain personal fitness. Technology usage attrition is also a concern among research studies on health technologies. Methods Usage of three fitness apps was examined over 5 months to assess adherence and effectiveness. Initially, 64 participants downloaded three free apps available on Android and iOS and 47 remained in the study until posttest. With a one group pre-posttest design and checkpoints at months 1, 3, and 5, exercise and exercise with fitness apps were examined in the framework of the Theory of Planned Behavior (TPB) using a validated survey. Apps were selected based on their function from the Functional Triad. Perceived fitness was also measured. T-tests, sign tests, Fisher’s exact tests, and linear and logistic regression were used to compare pre to posttests and users to non-users of the apps. Results Forty-seven participants completed both pre and posttests. Individual item scores indicated no significant change pre to posttest except for decreases observed in usefulness of using apps for exercise (attitude) (−0.78, P<0.01), peer influence on exercise (subjective norm) (−0.51, P<0.05), peer influence on exercise with apps (subjective norm) (−1.02, P<0.01), perceived difficulties in exercising with apps (perceived behavioral control) (−1.29, P<0.001), and the expected frequency of exercise with apps over the next 2 weeks (behavioral intention) (P<0.0001 in a sign test). Subscale total scores indicated significant decreases in subjective norm regarding exercise (−0.72, P<0.05), subjective norm regarding exercise with apps (−1.72, P<0.01), and perceived behavioral control over exercising with apps (−2.56, P<0.01) between pre and posttest. When comparing app users (n=32) to non-users (n=15), there was only a significant difference in subscale total

Social anxiety apps: a systematic review and assessment of app descriptors across mobile store platforms.

PubMed

Alyami, Mohsen; Giri, Bachan; Alyami, Hussain; Sundram, Frederick

2017-08-01

The aim of this systematic review is twofold: (1) to characterise the purpose and description of available social anxiety apps and (2) to review the evidence on the effectiveness of social anxiety apps. A search was conducted on three major mobile platforms: Apple iTunes, Google Play and Windows Store. Apps were included if they addressed social anxiety and used an English language interface. A systematic review of the literature from MEDLINE, EMBASE, PsycINFO, Cochrane, Scopus and Web of Science to identify evidence-based evaluations of social anxiety apps was also undertaken. Of the 1154 apps identified, 38 apps met the inclusion criteria: iTunes (n=18), Google Play (n=16) and Windows Store (n=4). Over 60% of apps were exclusively focused on social anxiety, while the remainder targeted social anxiety and related conditions. Most developers did not provide information on their organisational affiliations or their content source. Most apps used multimedia while 17 apps used text only. Finally, although the systematic review of the literature identified 94 articles, none of which met inclusion criteria. Social anxiety apps have the potential to overcome barriers to accessing treatment; however, none of the apps identified have had studies on their effectiveness published. As the evidence base is lacking, it is therefore not currently possible to recommend their use. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Mobile Apps for Eye Care in Canada: An Analysis of the iTunes Store.

PubMed

Rodin, Alexander; Shachak, Aviv; Miller, Aaron; Akopyan, Vladimir; Semenova, Nataliya

2017-06-14

Mobile phone screens can facilitate stimulation to various components of the visual system and many mobile apps are accepted as a means of providing clinical assessments for the oculo-visual system. Although many of these apps are intended for use in clinical settings, there is a growing number of apps in eye care developed for self-tests and eye exercises for lay people. These and other features, however, have not yet been well described. Our objective was to identify, describe, and categorize mobile apps related to eye care that are available to users in the Canadian iTunes market. We conducted an extensive search of the Apple iTunes Store for apps related to eye care. We used the terms "eye," "eye care," "vision," and "eye test" and included apps that are targeted at both lay people and medical professionals. We excluded apps whose primary function is not related to eye care. Eligible apps were categorized by primary purpose, based on how they were described by their developers in the iTunes Store. Our search yielded 10,657 apps, of which 427 met our inclusion criteria. After removing duplicates, 355 unique apps were subject to further review. We assigned the eligible apps to three distinct categories: 39/355 apps (11.0%) were intended for use by medical professionals, 236 apps (66.5%, 236/355) were intended for use by lay people, and 80 apps (22.5%, 80/355) were intended for marketing eye care and eye-care products. We identified 9 subcategories of apps based on the descriptions of their primary functions. Apps for medical professionals fell into three subcategories: clinical calculators (n=6), clinical diagnostic tools (n=18), and education and networking apps for professionals (n=15). Apps for lay people fell into four subcategories: self-testing (n=153), eye exercises (n=30), patient tools and low vision aids (n=35), and apps for patient education (n=18). Mixed-use apps (n=80) were placed into two subcategories: marketing of individual practitioners or eye

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.

Monoclonal and anti-idiotypic anti-EBV/C3d receptor antibodies detect two binding sites, one for EBV and one for C3d on glycoprotein 140, the EBV/C3dR, expressed on human B lymphocytes.

PubMed

Barel, M; Fiandino, A; Delcayre, A X; Lyamani, F; Frade, R

1988-09-01

Glycoprotein (gp) 140, the EBV/C3dR of B lymphocytes, is a membrane site involved in human cell regulation. To analyze the specificities of the binding sites for EBV and for C3d on the gp 140 molecule, two distinct approaches were used. First, anti-EBV/C3dR mAb were prepared against highly purified EBV/C3dR. Nine anti-EBV/C3dR mAb were obtained. Four of these anti-EBV/C3dR mAb inhibited C3d binding but not EBV binding on gp 140, whereas four others exerted an inverse effect. These differences could not be due to differences in isotype, antibody concentration, affinity constant, and number of molecules bound on cell surface, as these parameters were identical for the nine used mAb. Second, polyclonal anti-idiotypic antibodies (Ab2) were prepared against F(ab)'2 fragments of polyclonal anti-EBV/C3dR (Ab1). Ab2 recognized the variable portion of Ab1 as controlled by immunoblotting experiments. Ab2, which did not react with the cell surface, inhibited Ab1 binding on Raji cells. Ab2 mimicked the EBV/C3dR by its properties to bind to particle-bound C3d and EBV, preventing their binding on Raji cell surface. C3d binding specificities contained in Ab2 were isolated by affinity chromatography on C3b/C3bi-Sepharose. These specificities, being the internal image of C3d binding site of EBV/C3dR, reacted with Ab1 and inhibited particle-bound C3d binding on Raji cells but did not react with EBV. Taken together, these data support strongly that gp 140, the EBV/C3dR, carried two distinct binding sites, one for EBV and one for C3d.

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

PubMed

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

2017-06-24

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

Computational studies of H5N1 hemagglutinin binding with SA-{alpha}-2, 3-Gal and SA-{alpha}-2, 6-Gal

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

Li Minyong; Wang Binghe

2006-09-01

For influenza H5N1 hemagglutinin, a switch from SA-{alpha}-2, 3-Gal to SA-{alpha}-2, 6-Gal receptor specificity is a critical step leading to the conversion from avian-to-human to human-to-human infection. Therefore, the understanding of the binding modes of SA-{alpha}-2, 3-Gal and SA-{alpha}-2, 6-Gal to H5N1 hemagglutinin will be very important for the examination of possible mutations needed for going from an avian to a human flu virus. Based on the available H5N1 hemagglutinin crystal structure, the binding profiles between H5N1 hemagglutinin and two saccharide ligands, SA-{alpha}-2, 3-Gal and SA-{alpha}-2, 6-Gal, were investigated by ab initio quantum mechanics, molecular docking, molecular mechanics, and molecularmore » dynamics simulations. It was found that SA-{alpha}-2, 3-Gal has strong multiple hydrophobic and hydrogen bond interactions in its trans conformation with H5N1 hemagglutinin, whereas the SA-{alpha}-2, 6-Gal only shows weak interactions in a different conformation (cis type)« less

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

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

Detection Of Malware Collusion With Static Dependence Analysis On Inter-App Communication

DTIC Science & Technology

2016-12-08

DETECTION OF MALWARE COLLUSION WITH STATIC DEPENDENCE ANALYSIS ON INTER-APP COMMUNICATION VIRGINIA TECH DECEMBER 2016 FINAL TECHNICAL REPORT... DEPENDENCE ANALYSIS ON INTER-APP COMMUNICATION 5a. CONTRACT NUMBER FA8750-15-2-0076 5b. GRANT NUMBER N/A 5c. PROGRAM ELEMENT NUMBER 61101E 6. AUTHOR(S...exploited. 15. SUBJECT TERMS Malware Collusion; Inter-App Communication; Static Dependence Analysis 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

Biotin-c10-AppCH2ppA is an effective new chemical proteomics probe for diadenosine polyphosphate binding proteins.

PubMed

Azhar, M Ameruddin; Wright, Michael; Kamal, Ahmed; Nagy, Judith; Miller, Andrew D

2014-07-01

Here we report on the synthesis of a synthetic, stable biotin-c10-AppCH2ppA conjugate involving an unusual Cannizzaro reaction step. This conjugate is used to bind prospective Ap4A binding proteins from Escherichia coli bacterial cell lyzates. Following binding, identities of these proteins are then determined smoothly by a process of magnetic bio-panning and electrospray mass spectrometry. Protein hits appear to be a definitive set of stress protein related targets. While this hit list may not be exclusive, and may vary with the nature of sampling conditions and organism status, nevertheless hits do appear to correspond with bona fide Ap4A-binding proteins. Therefore these hits represent a sound basis on which to construct new hypotheses concerning the cellular importance of Ap4A to bacterial cells and the potential biological significance of Ap4A-protein binding interactions. Copyright © 2014. Published by Elsevier Ltd.

A Pilot Comparison of a Smartphone App With or Without 2-Way Messaging Among Chronic Pain Patients: Who Benefits From a Pain App?

PubMed

Jamison, Robert N; Jurcik, Dylan C; Edwards, Robert R; Huang, Chuan-Chin; Ross, Edgar L

2017-08-01

The overall aim of this study was to determine the effect of introducing a smartphone pain application (app), for both Android and iPhone devices that enables chronic pain patients to assess, monitor, and communicate their status to their providers. This study recruited 105 chronic pain patients to use a smartphone pain app and half of the patients (N=52) had 2-way messaging available through the app. All patients completed baseline measures and were asked to record their progress every day for 3 months, with the opportunity to continue for 6 months. All participants were supplied a Fitbit to track daily activity. Summary line graphs were posted to each of the patients' electronic medical records and physicians were notified of their patient's progress. Ninety patients successfully downloaded the pain app. Average age of the participants was 47.1 (range, 18 to 72), 63.8% were female and 32.3% reported multiple pain sites. Adequate validity and reliability was found between the daily assessments and standardized questionnaires (r=0.50) and in repeated daily measures (pain, r=0.69; sleep, r=0.83). The app was found to be easily introduced and well tolerated. Those patients assigned to the 2-way messaging condition on average tended to use the app more and submit more daily assessments (95.6 vs. 71.6 entries), but differences between groups were not significant. Pain-app satisfaction ratings overall were high. This study highlights some of the challenges and benefits in utilizing smartphone apps to manage chronic pain patients, and provides insight into those individuals who might benefit from mHealth technology.

6. View of DR 3 antenna typical backstay concrete stanchion ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

6. View of DR 3 antenna typical back-stay concrete stanchion showing embedded anchors and structural steel leg with pin attachment. - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

Computational study of the binding mechanism between farnesoid X receptor α and antagonist N-benzyl-N-(3-(tertbutyl)-4-hydroxyphenyl)-2,6-dichloro-4-(dimethylamino) benzamide.

PubMed

Du, Juan; Qiu, Miaoxue; Guo, Lizhong; Yao, Xiaojun

2018-05-02

Farnesoid X receptor α (FXRα) is a bile acid-activated transcription factor, which plays important roles in the regulation of multiple metabolic processes. Development of FXR antagonist has revealed great potential for the treatment of metabolic disorders. The compound N-Benzyl-N-(3-(tertbutyl)-4-hydroxyphenyl)-2,6-dichloro-4-(dimethylamino). Benzamide (NDB) was recently determined as a selective antagonist of FXRα, while the detailed interaction mechanism is not well understood. In this study, the combined computational methods including molecular dynamics simulations, binding free energy calculation, and principal component analysis were utilized to investigate the effect of NDB on the dynamics behaviors and dimerization of FXRα The binding free energy calculation indicated that the protein dimerization increases NDB affinity and the binding of NDB also stabilizes the interaction between two subunits of FXRα. Further decomposition of the overall binding free energies into individual residues identifies several residues significant for NDB binding, including Leu291, Met294, Ala295, His298, Met332, Ser336, Ala452, and Leu455. It also suggests that the interactions of L289(A)-W458(B), W458(A)-L289(B), R459(A)-N461(B), and N461(A)-R459(B) are important for the dimer stabilization. This study provides a molecular basis for the understanding of binding mechanism between antagonist NDB and FXRα and valuable information for the novel FXR modulators design for the treatment of metabolic syndrome.

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

PubMed

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

2018-06-08

Mobile health services are thriving in the field of maternal and child health in China due to expansions in the field of electronic health and the introduction of the two-child policy. There are numerous maternal and child health apps in computer stores, but the exact number of apps, number of downloads, and features of these apps is not known. This study aimed to explore the use of maternal and child health apps in Android and iOS app stores and to describe the key functional features of the most popular apps, with the purpose of providing insight into further research and development of maternal and child health mobile health products. The researchers conducted a search in the 3 most popular Android app stores (Tencent MyApp, Baidu Mobile Assistant, and 360 Mobile Assistant) and the iTunes App Store in China. All apps regarding family planning (contraception and preparing for pregnancy), pregnancy and perinatal care, neonatal care and health, and development for children under 6 years were included in the initial analysis. Maternal and child health mobile apps with predominant features of product marketing, children's songs, animation, or games were excluded from the study. The 50 most frequently used apps in each of the Android stores as well as the iTunes store (a total of 78 deduplicated apps) were selected and downloaded for an in-depth analysis. A total of 5276 Android apps and 877 iOS apps developed for maternal and child health care were identified. Of the 78 most frequently used apps, 43 (55%) apps focused on one stage of MCH care, mainly targeting child care (25 apps) and before pregnancy care (11 apps), whereas 35 (45%) of the apps covered 2 or more stages, most of which (32 apps) included both pregnancy and child care services. The app features that were commonly adopted by the popular apps were health education, communication, health status self-monitoring, a diary, reminders, and counseling. Within the app feature of "health status self

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

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

PubMed Central

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

2003-01-01

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

Caffeine inhibits glucose transport by binding at the GLUT1 nucleotide-binding site

PubMed Central

Sage, Jay M.; Cura, Anthony J.; Lloyd, Kenneth P.

2015-01-01

Glucose transporter 1 (GLUT1) is the primary glucose transport protein of the cardiovascular system and astroglia. A recent study proposes that caffeine uncompetitive inhibition of GLUT1 results from interactions at an exofacial GLUT1 site. Intracellular ATP is also an uncompetitive GLUT1 inhibitor and shares structural similarities with caffeine, suggesting that caffeine acts at the previously characterized endofacial GLUT1 nucleotide-binding site. We tested this by confirming that caffeine uncompetitively inhibits GLUT1-mediated 3-O-methylglucose uptake in human erythrocytes [Vmax and Km for transport are reduced fourfold; Ki(app) = 3.5 mM caffeine]. ATP and AMP antagonize caffeine inhibition of 3-O-methylglucose uptake in erythrocyte ghosts by increasing Ki(app) for caffeine inhibition of transport from 0.9 ± 0.3 mM in the absence of intracellular nucleotides to 2.6 ± 0.6 and 2.4 ± 0.5 mM in the presence of 5 mM intracellular ATP or AMP, respectively. Extracellular ATP has no effect on sugar uptake or its inhibition by caffeine. Caffeine and ATP displace the fluorescent ATP derivative, trinitrophenyl-ATP, from the GLUT1 nucleotide-binding site, but d-glucose and the transport inhibitor cytochalasin B do not. Caffeine, but not ATP, inhibits cytochalasin B binding to GLUT1. Like ATP, caffeine renders the GLUT1 carboxy-terminus less accessible to peptide-directed antibodies, but cytochalasin B and d-glucose do not. These results suggest that the caffeine-binding site bridges two nonoverlapping GLUT1 endofacial sites—the regulatory, nucleotide-binding site and the cytochalasin B-binding site. Caffeine binding to GLUT1 mimics the action of ATP but not cytochalasin B on sugar transport. Molecular docking studies support this hypothesis. PMID:25715702

How Do Apps Work? An Analysis of Physical Activity App Users' Perceptions of Behavior Change Mechanisms.

PubMed

Hoj, Taylor H; Covey, Emarie L; Jones, Allyn C; Haines, Amanda C; Hall, P Cougar; Crookston, Benjamin T; West, Joshua H

2017-08-03

Physical activity apps are commonly used to increase levels of activity and health status. To date, the focus of research has been to determine the potential of apps to influence behavior, to ascertain the efficacy of a limited number of apps to change behavior, and to identify the characteristics of apps that users prefer. The purpose of this study was to identify the mechanisms by which the use of physical activity apps may influence the users' physical activity behavior. This study used a cross-sectional survey of users of health-related physical activity apps during the past 6 months. An electronic survey was created in Qualtrics' Web-based survey software and deployed on Amazon Mechanical Turk. Individuals who had used at least one physical activity app in the past 6 months were eligible to respond. The final sample comprised 207 adults living in the United States. 86.0% (178/207) of respondents were between the ages of 26 and 54 years, with 51.2% (106/207) of respondents being female. Behavior change theory informed the creation of 20 survey items relating to the mechanisms of behavior change. Respondents also reported about engagement with the apps, app likeability, and physical activity behavior. Respondents reported that using a physical activity app in the past 6 months resulted in a change in their attitudes, beliefs, perceptions, and motivation. Engagement with the app (P<.001), frequency of app use (P=.03), and app price (P=.01) were related to the reported impact of the behavior change theory or mechanisms of change. The mechanisms of change were associated with self-reported physical activity behaviors (P<.001). The findings from this study provide an overview of the mechanisms by which apps may impact behavior. App developers may wish to incorporate these mechanisms in an effort to increase impact. Practitioners should consider the extent to which behavior change theory is integrated into a particular app when they consider making recommendations to

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

PubMed Central

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

2015-01-01

Background Depression is highly prevalent and causes considerable suffering and disease burden despite the existence of wide-ranging treatment options. Mobile phone apps offer the potential to help close this treatment gap by confronting key barriers to accessing support for depression. Objectives Our goal was to identify and characterize the different types of mobile phone depression apps available in the marketplace. Methods A search for depression apps was conducted on the app stores of the five major mobile phone platforms: Android, iPhone, BlackBerry, Nokia, and Windows. Apps were included if they focused on depression and were available to people who self-identify as having depression. Data were extracted from the app descriptions found in the app stores. Results Of the 1054 apps identified by the search strategy, nearly one-quarter (23.0%, 243/1054) unique depression apps met the inclusion criteria. Over one-quarter (27.7%, 210/758) of the excluded apps failed to mention depression in the title or description. Two-thirds of the apps had as their main purpose providing therapeutic treatment (33.7%, 82/243) or psychoeducation (32.1%, 78/243). The other main purpose categories were medical assessment (16.9%, 41/243), symptom management (8.2%, 20/243), and supportive resources (1.6%, 4/243). A majority of the apps failed to sufficiently describe their organizational affiliation (65.0%, 158/243) and content source (61.7%, 150/243). There was a significant relationship (χ 2 5=50.5, P<.001) between the main purpose of the app and the reporting of content source, with most medical assessment apps reporting their content source (80.5%, 33/41). A fifth of the apps featured an e-book (20.6%, 50/243), audio therapy (16.9%, 41/243), or screening (16.9%, 41/243) function. Most apps had a dynamic user interface (72.4%, 176/243) and used text as the main type of media (51.9%, 126/243), and over a third (14.4%, 35/243) incorporated more than one form of media. Conclusion

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

PubMed

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

2015-02-16

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

ADHD: Is There an App for That? A Suitability Assessment of Apps for the Parents of Children and Young People With ADHD.

PubMed

Powell, Lauren; Parker, Jack; Harpin, Valerie

2017-10-13

Attention-deficit hyperactivity disorder (ADHD) is a highly comorbid disorder that can impact significantly on the individual and their family. ADHD is managed via pharmacological and nonpharmacological interventions. Parents also gain support from parent support groups, which may include chat rooms, as well as face-to-face meetings. With the growth of technology use over recent years, parents have access to more resources that ever before. A number of mobile apps have been developed to help parents manage ADHD in their children and young people. Unfortunately many of these apps are not evidence-based, and little is known of their suitability for the parents or whether they are helpful in ADHD management. The aim of this study was to explore the (1) parents' views of the suitability of the top ten listed apps for parents of children and young people with ADHD and (2) the views of clinicians that work with them on the suitability and value of the apps. The top 10 listed apps specifically targeted toward the parents of children and young people with ADHD were identified via the Google Play (n=5) and iTunes store (n=5). Interviews were then undertaken with 7 parents of children or young people with ADHD and 6 clinicians who specialize in working with this population to explore their opinions of the 10 apps identified and what they believe the key components are for apps to be suitable and valuable for this population. Four themes emerged from clinician and parent interviews: (1) the importance of relating to the app, (2) apps that address ADHD-related difficulties, (3) how the apps can affect family relationships, and (4) apps as an educational tool. Two additional themes emerged from the clinician interviews alone: monitoring ADHD symptoms and that apps should be practical. Parents also identified an additional theme: the importance of the technology. Overall, the characteristics of the current top 10 listed apps did not appear to match well to the views of our

ADHD: Is There an App for That? A Suitability Assessment of Apps for the Parents of Children and Young People With ADHD

PubMed Central

Parker, Jack; Harpin, Valerie

2017-01-01

Background Attention-deficit hyperactivity disorder (ADHD) is a highly comorbid disorder that can impact significantly on the individual and their family. ADHD is managed via pharmacological and nonpharmacological interventions. Parents also gain support from parent support groups, which may include chat rooms, as well as face-to-face meetings. With the growth of technology use over recent years, parents have access to more resources that ever before. A number of mobile apps have been developed to help parents manage ADHD in their children and young people. Unfortunately many of these apps are not evidence-based, and little is known of their suitability for the parents or whether they are helpful in ADHD management. Objective The aim of this study was to explore the (1) parents’ views of the suitability of the top ten listed apps for parents of children and young people with ADHD and (2) the views of clinicians that work with them on the suitability and value of the apps. Methods The top 10 listed apps specifically targeted toward the parents of children and young people with ADHD were identified via the Google Play (n=5) and iTunes store (n=5). Interviews were then undertaken with 7 parents of children or young people with ADHD and 6 clinicians who specialize in working with this population to explore their opinions of the 10 apps identified and what they believe the key components are for apps to be suitable and valuable for this population. Results Four themes emerged from clinician and parent interviews: (1) the importance of relating to the app, (2) apps that address ADHD-related difficulties, (3) how the apps can affect family relationships, and (4) apps as an educational tool. Two additional themes emerged from the clinician interviews alone: monitoring ADHD symptoms and that apps should be practical. Parents also identified an additional theme: the importance of the technology. Overall, the characteristics of the current top 10 listed apps did not appear

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

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

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.

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

PubMed

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

2014-11-11

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

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

LRP-mediated clearance of Abeta is inhibited by KPI-containing isoforms of APP.

PubMed

Moir, Robert D; Tanzi, Rudolph E

2005-04-01

The pathogenesis of Alzheimer's disease (AD) involves the abnormal accumulation and deposition of beta-amyloid in cerebral blood vessels and in the brain parenchyma. Critical in modulating beta-amyloid deposition in brain is the flux of Abeta across the blood brain barrier. The low-density lipoprotein receptor-related protein (LRP), is a large endocytic receptor that mediates the efflux of Abeta out of brain and into the periphery. The first step in the LRP-mediated clearance of Abeta involves the formation of a complex between Abeta and the LRP ligands apolipoprotein E (apoE) or alpha(2)-macroglobulin (alpha(2)M). The Abeta/chaperone complexes then bind to LRP via binding sites on apoE or alpha(2)M. The efflux of Abeta/chaperone complexes out of the neuropil and into the periphery may be attenuated by LRP-ligands that compete with apoE or alpha(2)M for LRP binding. LRP is also the cell surface receptor for Kunitz Protease Inhibitor (KPI) containing isoforms of Abeta's parent protein, the amyloid protein precursor (APP). Protein and mRNA levels of KPI-containing APP isoforms (APP-KPI) are elevated in AD brain and are associated with increased Abeta production. In this study we show that soluble non-amyloidogenic APP-KPI can also inhibit the uptake of Abeta/alpha(2)M in a cell culture model of LRP mediated Abeta clearance. Clearance of Abeta/apoE complexes was not inhibited by APP-KPI. Our findings are consistent with studies showing that apoE and alpha(2)M have discrete binding sites on LRP. Most significantly, our data suggests that the elevated levels of APP-KPI in AD brain may attenuate the clearance of Abeta, the proteins own amyloidogenic catabolic product.

RG7386, a Novel Tetravalent FAP-DR5 Antibody, Effectively Triggers FAP-Dependent, Avidity-Driven DR5 Hyperclustering and Tumor Cell Apoptosis.

PubMed

Brünker, Peter; Wartha, Katharina; Friess, Thomas; Grau-Richards, Sandra; Waldhauer, Inja; Koller, Claudia Ferrara; Weiser, Barbara; Majety, Meher; Runza, Valeria; Niu, Huifeng; Packman, Kathryn; Feng, Ningping; Daouti, Sherif; Hosse, Ralf J; Mössner, Ekkehard; Weber, Thomas G; Herting, Frank; Scheuer, Werner; Sade, Hadassah; Shao, Cuiying; Liu, Bin; Wang, Peng; Xu, Gary; Vega-Harring, Suzana; Klein, Christian; Bosslet, Klaus; Umaña, Pablo

2016-05-01

Dysregulated cellular apoptosis and resistance to cell death are hallmarks of neoplastic initiation and disease progression. Therefore, the development of agents that overcome apoptosis dysregulation in tumor cells is an attractive therapeutic approach. Activation of the extrinsic apoptotic pathway is strongly dependent on death receptor (DR) hyperclustering on the cell surface. However, strategies to activate DR5 or DR4 through agonistic antibodies have had only limited clinical success. To pursue an alternative approach for tumor-targeted induction of apoptosis, we engineered a bispecific antibody (BsAb), which simultaneously targets fibroblast-activation protein (FAP) on cancer-associated fibroblasts in tumor stroma and DR5 on tumor cells. We hypothesized that bivalent binding to both FAP and DR5 leads to avidity-driven hyperclustering of DR5 and subsequently strong induction of apoptosis in tumor cells but not in normal cells. Here, we show that RG7386, an optimized FAP-DR5 BsAb, triggers potent tumor cell apoptosis in vitro and in vivo in preclinical tumor models with FAP-positive stroma. RG7386 antitumor efficacy was strictly FAP dependent, was independent of FcR cross-linking, and was superior to conventional DR5 antibodies. In combination with irinotecan or doxorubicin, FAP-DR5 treatment resulted in substantial tumor regression in patient-derived xenograft models. FAP-DR5 also demonstrated single-agent activity against FAP-expressing malignant cells, due to cross-binding of FAP and DR5 across tumor cells. Taken together, these data demonstrate that RG7386, a novel and potent antitumor agent in both mono- and combination therapies, overcomes limitations of previous DR5 antibodies and represents a promising approach to conquer tumor-associated resistance to apoptosis. Mol Cancer Ther; 15(5); 946-57. ©2016 AACR. ©2016 American Association for Cancer Research.

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

PubMed Central

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

2014-01-01

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

Circadian wheel running behavior is altered in an APP/E4 mouse model of late onset Alzheimer's disease.

PubMed

Boggs, Katelyn N; Kakalec, Peter A; Smith, Meghann L; Howell, Stefanie N; Flinn, Jane M

2017-12-01

Circadian rhythms are altered in several diseases associated with aging, one of which is Alzheimer's disease (AD). One example of a circadian rhythm is the rest-activity cycle, which can be measured in mice by monitoring their wheel-running. The present study sought to investigate differences in light phase/dark phase activity between a mouse model of late onset AD (APP/E4) and control (C57Bl6J) mice, in both the pre-plaque and post-plaques stages of the disease. To assess activity level, 24-h wheel running behavior was monitored at six months (pre-plaque) and twelve months (post-plaque) for a period of nine days. The following measures were analyzed: counts (wheel rotations) during the dark phase, counts during the light phase, hour of activity onset, and hour of activity offset. Key findings indicate that activity onset is delayed in APP/E4 mice at six and twelve months, and activity profiles for APP/E4 and C57Bl6J mice differ during the light and dark phase in such a way that APP/E4 mice run less in the early hours of the dark phase and more in the later hours of the dark phase compared to C57Bl6J mice. These findings imply that rest-activity cycle is altered in the pre-plaque stages of AD in APP/E4 mice, as they show impairments as early as six months of age. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Preference and Frequency of Mobile Phone App Use for Drug Information Among Student Pharmacists

PubMed Central

Park, Sharon K.; Purnell, Miriam C.; Freeman, Maisha Kelly; Reese, Racquel V.; Varga, Stefan

2017-01-01

Background: Health care professionals commonly use mobile devices to retrieve drug information (DI) in clinical practice. The preference and frequency of such use by student pharmacists are not well understood. Objective: To investigate the preference and frequency of mobile phone application (app) use for retrieving DI among student pharmacists. Methods: DI specialists from 3 pharmacy schools generated a 13-question survey relating to students’ preference and frequency of DI app use via their mobile phone. The survey was tested and electronically disseminated to all current P1 through P4 students from all 3 schools. Data were collected for student demographics, availability of mobile phone and DI apps, frequency of using DI apps, and whether DI apps were purchased. Data were analyzed descriptively and statistically. Results: About 74% (n = 221) of students reported using their mobile phone apps for retrieving DI. About 95% of the students used 1 to 3 apps for DI purposes and more than 85% used them a few times a week or more. About 17.6% of the students reported purchasing apps for the purpose of finding DI and that purchased apps are more accurate (27.6%), more comprehensive (36.2%), and more current (26.2%), compared with free apps. Conclusions: Student pharmacists used 1 to 3 mobile apps, at least a few times a week for DI. Some students purchased apps for DI use in addition to free subscriptions from their school. Students perceived purchased DI apps being more accurate, more comprehensive, and more up to date than the free apps.

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

Curcumin Decreases Hyperphosphorylation of Tau by Down-Regulating Caveolin-1/GSK-3β in N2a/APP695swe Cells and APP/PS1 Double Transgenic Alzheimer's Disease Mice.

PubMed

Sun, Jieyun; Zhang, Xiong; Wang, Chen; Teng, Zhipeng; Li, Yu

2017-01-01

Caveolin-1, the marker protein of membranal caveolae, is not only involved in cholesterol regulation, but also participates in the cleavage of amyloid [Formula: see text]-protein precursor (APP) and the generation of [Formula: see text]-amyloid peptide. It has been reported to be tightly related with Tau. In our previous studies, curcumin has been confirmed to play a neuroprotective role in Alzheimer's disease (AD), but its effects on Caveolin-1, Tau and their correlation, and the mechanism is still unknown. As such, in the present study, N2a/WT cells, N2a/APP695swe cell and six-month-old APP/PS1 double transgenic mice were enrolled. After curcumin treatment, the expression of Caveolin-1, Tau and their relationship was detected, and the potential mechanisms were explored. The results showed that in the N2a/APP695swe cells, curcumin not only decreased the number of caveolae, but also made their membrane to be thinner; and curcumin could decreased the expression of phosphorylated Tau (P-Tau(ser404)/Tau) and Caveolin-1 ([Formula: see text]), but the expression of phosphorylated GSK-3[Formula: see text] (P-GSK-3[Formula: see text]/GSK-3[Formula: see text] was increased ([Formula: see text]). In APP/PS1 transgenic mice, the same results were observed. Taken together, our data suggest that curcumin may play an important role in AD via reducing Caveolin-1, inactivating GSK-3[Formula: see text] and inhibiting the abnormal excessive phosphorylation of Tau, which will provide a new theory for AD treatment with curcumin.

Gaia DR1 documentation Chapter 6: Variability

NASA Astrophysics Data System (ADS)

Eyer, L.; Rimoldini, L.; Guy, L.; Holl, B.; Clementini, G.; Cuypers, J.; Mowlavi, N.; Lecoeur-Taïbi, I.; De Ridder, J.; Charnas, J.; Nienartowicz, K.

2017-12-01

This chapter describes the photometric variability processing of the Gaia DR1 data. Coordination Unit 7 is responsible for the variability analysis of over a billion celestial sources. In particular the definition, design, development, validation and provision of a software package for the data processing of photometrically variable objects. Data Processing Centre Geneva (DPCG) responsibilities cover all issues related to the computational part of the CU7 analysis. These span: hardware provisioning, including selection, deployment and optimisation of suitable hardware, choosing and developing software architecture, defining data and scientific workflows as well as operational activities such as configuration management, data import, time series reconstruction, storage and processing handling, visualisation and data export. CU7/DPCG is also responsible for interaction with other DPCs and CUs, software and programming training for the CU7 members, scientific software quality control and management of software and data lifecycle. Details about the specific data treatment steps of the Gaia DR1 data products are found in Eyer et al. (2017) and are not repeated here. The variability content of the Gaia DR1 focusses on a subsample of Cepheids and RR Lyrae stars around the South ecliptic pole, showcasing the performance of the Gaia photometry with respect to variable objects.

Denervation does not alter the number of neuronal bungarotoxin binding sites on autonomic neurons in the frog cardiac ganglion.

PubMed

Sargent, P B; Bryan, G K; Streichert, L C; Garrett, E N

1991-11-01

The binding of neuronal bungarotoxin (n-BuTX; also known as bungarotoxin 3.1, kappa-bungarotoxin, and toxin F) was analyzed in normal and denervated parasympathetic cardiac ganglia of the frog Rana pipiens, n-BuTX blocks both EPSPs and ACh potentials at 5-20 nM, as determined by intracellular recording techniques. Scatchard analysis on homogenates indicates that cardiac ganglia have two classes of binding sites for 125I-n-BuTX: a high-affinity site with an apparent dissociation constant (Kd,app) of 1.7 nM and a Bmax (number of binding sites) of 3.8 fmol/ganglion and a low-affinity site with a Kd,app of 12 microM and a Bmax of 14 pmol/ganglion. alpha-Bungarotoxin does not appear to interfere with the binding of 125I-n-BuTX to either site. The high-affinity binding site is likely to be the functional nicotinic ACh receptor (AChR), given the similarity between its affinity for 125I-n-BuTX and the concentration of n-BuTX required to block AChR function. Light microscopic autoradiographic analysis of 125I-n-BuTX binding to the ganglion cell surface reveals that toxin binding is concentrated at synaptic sites, which were identified using a synaptic vesicle-specific antibody. Scatchard analysis of autoradiographic data reveals that 125I-n-BuTX binding to the neuronal surface is saturable and has a Kd,app similar to that of the high-affinity binding site characterized in homogenates. Surface binding of 125I-n-BuTX is blocked by nicotine, carbachol, and d-tubocurarine (IC50 less than 20 microM), but not by atropine (IC50 greater than 10 mM). Denervation of the heart increases the ACh sensitivity of cardiac ganglion cells but has no effect upon the number of high-affinity binding sites for 125I-n-BuTX in tissue homogenates. Moreover, autoradiographic analysis indicates that denervation does not alter the number of 125I-n-BuTX binding sites on the ganglion cell surface. n-BuTX is as effective in reducing ganglion cell responses to ACh in denervated ganglia as it is in

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

PubMed

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

2015-09-01

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

Discovery of high-affinity BCL6-binding peptide and its structure-activity relationship

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

Sakamoto, Kotaro; Sogabe, Satoshi; Kamada, Yusuke

B cell lymphoma 6 (BCL6) is a transcriptional repressor that interacts with its corepressors BcoR and SMRT. Since this protein-protein interaction (PPI) induces activation and differentiation of B lymphocytes, BCL6 has been an attractive drug target for potential autoimmune disease treatments. Here we report a novel BCL6 inhibitory peptide, F1324 (Ac-LWYTDIRMSWRVP-OH), which we discovered using phage display technology; we also discuss this peptide's structure-activity relationship (SAR). For BCL6(5-129) binding, K{sub D} and IC{sub 50} values of F1324 were 0.57 nM and 1 nM according to the results of an SPR analysis and cell-free ELISA assay, respectively. In contrast, BcoR(Arg498-514Pro) and SMRT(Leu1422-Arg1438) exhibitedmore » relatively weak micromole-order binding to BCL6. Furthermore, Fusion protein AcGFP-F1324 transiently expressed in HEK293T cells inhibited intracellular PPI in cell-based M2H assay. By examination of the truncation and fragmentation of F1324, the C-terminal sequence WRVP, which is similar to the BcoR(509-512) sequence WVVP, was identified as being critical for BCL6 binding. In addition, subsequent single-crystal X-ray diffraction analysis of F1324/BCL6(5-129) complex revealed that the high affinity of F1324 was caused by effective interaction of its side chains while its main chain structure was similar to that of BcoR(Arg498-514Pro). To our knowledge, F1324 is the strongest BCL6-binding peptide yet reported. - Highlights: • F1324 was discovered as 5000-times higher affinity peptide to BCL6 than that of BcoR(R498-P514). • X-ray crystal structure analysis revealed the binding mode. • To our knowledge, F1324 is the strongest BCL6-binding and -inhibition peptide so far.« less

Molecular Determinants of Peptide Binding to Two Common Rhesus Macaque Major Histocompatibility Complex Class II Molecules

PubMed Central

Dzuris, John L.; Sidney, John; Horton, Helen; Correa, Rose; Carter, Donald; Chesnut, Robert W.; Watkins, David I.; Sette, Alessandro

2001-01-01

Major histocompatibility complex class II molecules encoded by two common rhesus macaque alleles Mamu-DRB1*0406 and Mamu-DRB*w201 have been purified, and quantitative binding assays have been established. The structural requirements for peptide binding to each molecule were characterized by testing panels of single-substitution analogs of the two previously defined epitopes HIV Env242 (Mamu-DRB1*0406 restricted) and HIV Env482 (Mamu-DRB*w201 restricted). Anchor positions of both macaque DR molecules were spaced following a position 1 (P1), P4, P6, P7, and P9 pattern. The specific binding motif associated with each molecule was distinct, but largely overlapping, and was based on crucial roles of aromatic and/or hydrophobic residues at P1, P6, and P9. Based on these results, a tentative Mamu class II DR supermotif was defined. This pattern is remarkably similar to a previously defined human HLA-DR supermotif. Similarities in binding motifs between human HLA and macaque Mamu-DR molecules were further illustrated by testing a panel of more than 60 different single-substitution analogs of the HLA-DR-restricted HA 307–319 epitope for binding to Mamu-DRB*w201 and HLA-DRB1*0101. The Mamu-DRB1*0406 and -DRB*w201 binding capacity of a set of 311 overlapping peptides spanning the entire simian immunodeficiency virus (SIV) genome was also evaluated. Ten peptides capable of binding both molecules were identified, together with 19 DRB1*0406 and 43 DRB*w201 selective binders. The Mamu-DR supermotif was found to be present in about 75% of the good binders and in 50% of peptides binding with intermediate affinity but only in approximately 25% of the peptides which did not bind either Mamu class II molecule. Finally, using flow cytometric detection of antigen-induced intracellular gamma interferon, we identify a new CD4+ T-lymphocyte epitope encoded within the Rev protein of SIV. PMID:11602736

Cyclo[n]pyrroles: Size and Site Specific Binding to G-Quadruplexes

PubMed Central

Baker, Erin Shammel; Lee, Jeong T.

2014-01-01

Inhibiting the enzyme telomerase by stabilizing the G-quadruplex has potential in anticancer drug design. Diprotonated cyclo[n]pyrroles represent a set of expanded porphyrin analogues with structures similar to telomestatin, a natural product known to bind to and stabilize G-quadruplexes. As a first step towards testing whether cyclo[n]pyrroles display a similar function, a series of diprotonated cyclo[n]pyrroles (where n = 6, 7 and 8) was each added to the human telomere repeat sequence d(T2AG3)4 and examined with mass spectrometry, ion mobility and molecular dynamics calculations. Nano-ESI-MS indicated that the smaller the cyclo[n]pyrrole, the stronger it binds to the telomeric sequence. It was also found that cyclo[6]pyrrole bound to d(T2AG3)4 better than octaethylporphyrin, a finding rationalized by cyclo[6]pyrrole having a +2 charge, while octaethylporphyrin bears no charge. Ion mobility measurements were used to measure the collision cross section of each d(T2AG3)4/cyclo[n]pyrrole complex. Only one peak was observed in the arrival time distributions for all complexes and the experimental cross sections indicated that only structures with d(T2AG3)4 in an antiparallel G-quadruplex arrangement and each cyclo[n]pyrrole externally stacked below the G-quartets occur under these experimental conditions. When the cyclo[n]pyrroles were intercalated or nonspecifically bound to the quadruplex or if different conformations than antiparallel were considered for d(T2AG3)4, the theoretical cross sections did not match experiment. On this basis, it is inferred that 1) external stacking represents the dominant binding mode for the interaction of cyclo[n]pyrroles with d(T2AG3)4 and 2) the overall size and charge of the cyclo[n]pyrroles play important roles in defining the binding strength. PMID:16492050

Controlling Your "App"etite: How Diet and Nutrition-Related Mobile Apps Lead to Behavior Change.

PubMed

West, Joshua H; Belvedere, Lindsay M; Andreasen, Rebecca; Frandsen, Christine; Hall, P Cougar; Crookston, Benjamin T

2017-07-10

In recent years, obesity has become a serious public health crisis in the United States. Although the problem of obesity is being addressed through a variety of strategies, the use of mobile apps is a relatively new development that could prove useful in helping people to develop healthy dietary habits. Though such apps might lead to health behavior change, especially when relevant behavior change theory constructs are integrated into them, the mechanisms by which these apps facilitate behavior change are largely unknown. The purpose of this study was to identify which behavior change mechanisms are associated with the use of diet- and nutrition-related health apps and whether the use of diet- and nutrition-related apps is associated with health behavior change. A cross-sectional survey was administered to a total of 217 participants. Participants responded to questions on demographics, use of diet and nutrition apps in the past 6 months, engagement and likability of apps, and changes in the participant's dietary behaviors. Regression analysis was used to identify factors associated with reported changes in theory and separately for reported changes in actual behavior, after controlling for potential confounding variables. The majority of study participants agreed or strongly agreed with statements regarding app use increasing their motivation to eat a healthy diet, improving their self-efficacy, and increasing their desire to set and achieve health diet goals. Additionally, majority of participants strongly agreed that using diet/nutrition apps led to changes in their behavior, namely increases in actual goal setting to eat a healthy diet (58.5%, 127/217), increases in their frequency of eating healthy foods (57.6%, 125/217), and increases in their consistency of eating healthy foods (54.4%, 118/217). Participants also responded favorably to questions related to engagement and likability of diet/nutrition apps. A number of predictors were also positively

Mobile Apps for Bipolar Disorder: A Systematic Review of Features and Content Quality

PubMed Central

Larsen, Mark Erik; Proudfoot, Judith; Christensen, Helen

2015-01-01

Background With continued increases in smartphone ownership, researchers and clinicians are investigating the use of this technology to enhance the management of chronic illnesses such as bipolar disorder (BD). Smartphones can be used to deliver interventions and psychoeducation, supplement treatment, and enhance therapeutic reach in BD, as apps are cost-effective, accessible, anonymous, and convenient. While the evidence-based development of BD apps is in its infancy, there has been an explosion of publicly available apps. However, the opportunity for mHealth to assist in the self-management of BD is only feasible if apps are of appropriate quality. Objective Our aim was to identify the types of apps currently available for BD in the Google Play and iOS stores and to assess their features and the quality of their content. Methods A systematic review framework was applied to the search, screening, and assessment of apps. We searched the Australian Google Play and iOS stores for English-language apps developed for people with BD. The comprehensiveness and quality of information was assessed against core psychoeducation principles and current BD treatment guidelines. Management tools were evaluated with reference to the best-practice resources for the specific area. General app features, and privacy and security were also assessed. Results Of the 571 apps identified, 82 were included in the review. Of these, 32 apps provided information and the remaining 50 were management tools including screening and assessment (n=10), symptom monitoring (n=35), community support (n=4), and treatment (n=1). Not even a quarter of apps (18/82, 22%) addressed privacy and security by providing a privacy policy. Overall, apps providing information covered a third (4/11, 36%) of the core psychoeducation principles and even fewer (2/13, 15%) best-practice guidelines. Only a third (10/32, 31%) cited their information source. Neither comprehensiveness of psychoeducation information (r=-.11

Mobile Apps for Bipolar Disorder: A Systematic Review of Features and Content Quality.

PubMed

Nicholas, Jennifer; Larsen, Mark Erik; Proudfoot, Judith; Christensen, Helen

2015-08-17

With continued increases in smartphone ownership, researchers and clinicians are investigating the use of this technology to enhance the management of chronic illnesses such as bipolar disorder (BD). Smartphones can be used to deliver interventions and psychoeducation, supplement treatment, and enhance therapeutic reach in BD, as apps are cost-effective, accessible, anonymous, and convenient. While the evidence-based development of BD apps is in its infancy, there has been an explosion of publicly available apps. However, the opportunity for mHealth to assist in the self-management of BD is only feasible if apps are of appropriate quality. Our aim was to identify the types of apps currently available for BD in the Google Play and iOS stores and to assess their features and the quality of their content. A systematic review framework was applied to the search, screening, and assessment of apps. We searched the Australian Google Play and iOS stores for English-language apps developed for people with BD. The comprehensiveness and quality of information was assessed against core psychoeducation principles and current BD treatment guidelines. Management tools were evaluated with reference to the best-practice resources for the specific area. General app features, and privacy and security were also assessed. Of the 571 apps identified, 82 were included in the review. Of these, 32 apps provided information and the remaining 50 were management tools including screening and assessment (n=10), symptom monitoring (n=35), community support (n=4), and treatment (n=1). Not even a quarter of apps (18/82, 22%) addressed privacy and security by providing a privacy policy. Overall, apps providing information covered a third (4/11, 36%) of the core psychoeducation principles and even fewer (2/13, 15%) best-practice guidelines. Only a third (10/32, 31%) cited their information source. Neither comprehensiveness of psychoeducation information (r=-.11, P=.80) nor adherence to best

Who are mobile app users from healthy lifestyle websites? Analysis of patterns of app use and user characteristics.

PubMed

Elavsky, Steriani; Smahel, David; Machackova, Hana

2017-12-01

The use of online communities and websites for health information has proliferated along with the use of mobile apps for managing health behaviors such as diet and exercise. The scarce evidence available to date suggests that users of these websites and apps differ in significant ways from non-users but most data come from US- and UK-based populations. In this study, we recruited users of nutrition, weight management, and fitness-oriented websites in the Czech Republic to better understand who uses mobile apps and who does not, including user sociodemographic and psychological profiles. Respondents aged 13-39 provided information on app use through an online survey (n = 669; M age = 24.06, SD = 5.23; 84% female). Among users interested in health topics, respondents using apps for managing nutrition, weight, and fitness (n = 403, 60%) were more often female, reported more frequent smartphone use, and more expert phone skills. In logistic regression models, controlling for sociodemographics, web, and phone activity, mHealth app use was predicted by levels of excessive exercise (OR 1.346, 95% CI 1.061-1.707, p < .01). Among app users, we found differences in types of apps used by gender, age, and weight status. Controlling for sociodemographics and web and phone use, drive for thinness predicted the frequency of use of apps for healthy eating (β = 0.14, p < .05), keeping a diet (β = 0.27, p < .001), and losing weight (β = 0.33, p < .001), whereas excessive exercise predicted the use of apps for keeping a diet (β = 0.18, p < .01), losing weight (β = 0.12, p < .05), and managing sport/exercise (β = 0.28, p < .001). Sensation seeking was negatively associated with the frequency of use of apps for maintaining weight (β = - 0.13, p < .05). These data unveil the user characteristics of mHealth app users from nutrition, weight management, and fitness websites, helping inform subsequent design of mHealth apps and mobile intervention strategies.

Chimeric proteins combining phosphatase and cellulose-binding activities: proof-of-concept and application in the hydrolysis of paraoxon.

PubMed

Gonçalves, Larissa M; Chaimovich, Hernan; Cuccovia, Iolanda M; Marana, Sandro R

2014-05-01

Phosphatases for organophosphate degradation and carbohydrate-binding domains (CBMs) have potential biotechnological applications. As a proof-of-concept, a soluble chimeric protein that combines acid phosphatase (AppA) from Escherichia coli and a CBM from Xanthomonas axonopodis pv. citri (AppA-CBM) was produced in E.coli. AppACBM adsorbed in microcrystalline cellulose Avicel PH101 catalyzed the hydrolysis of p-nitrophenyl phosphate (PNPP). The binding to microcrystalline cellulose displayed saturation behavior with an apparent binding constant (Kb) of 22 ± 5 mg and a maximum binding (Bmax) of 1.500 ± 0.001 enzyme units. Binding was highest at pH 2.5 and decreased above pH 6.5, as previously observed for family 2 CBMs. The Km values for PNPP of AppA-CBM and native AppA were identical (2.7 mM). To demonstrate that this strategy for protein engineering has practical applications and is largely functional, even for phosphatases exhibiting diverse folds, a chimeric protein combining human paraoxonase 1 (hPON1) and the CBM was produced. Both PON1-CBM and hPON1 had identical K_m values for paraoxon (1.3 mM). Additionally, hPON1 bound to microcrystalline cellulose with a Kb of 27 ± 3 mg, the same as that observed for AppA-CBM. These data show that the phosphatase domains are as functional in both of the chimeric proteins as they are in the native enzymes and that the CBM domain maintains the same cellulose affinity. Therefore, the engineering of chimeric proteins combining domains of phosphatases and CBMs is fully feasible, resulting in chimeric enzymes that exhibit potential for OP detoxification.

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

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

PubMed

Anderson, Kevin; Burford, Oksana; Emmerton, Lynne

2016-11-04

The availability of mobile health apps for self-care continues to increase. While little evidence of their clinical impact has been published, there is general agreement among health authorities and authors that consumers' use of health apps assist in self-management and potentially clinical decision making. A consumer's sustained engagement with a health app is dependent on the usability and functionality of the app. While numerous studies have attempted to evaluate health apps, there is a paucity of published methods that adequately recognize client experiences in the academic evaluation of apps for chronic conditions. This paper reports (1) a protocol to shortlist health apps for academic evaluation, (2) synthesis of a checklist to screen health apps for quality and reliability, and (3) a proposed method to theoretically evaluate usability of health apps, with a view towards identifying one or more apps suitable for clinical assessment. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram was developed to guide the selection of the apps to be assessed. The screening checklist was thematically synthesized with reference to recurring constructs in published checklists and related materials for the assessment of health apps. The checklist was evaluated by the authors for face and construct validity. The proposed method for evaluation of health apps required the design of procedures for raters of apps, dummy data entry to test the apps, and analysis of raters' scores. The PRISMA flow diagram comprises 5 steps: filtering of duplicate apps; eliminating non-English apps; removing apps requiring purchase, filtering apps not updated within the past year; and separation of apps into their core functionality. The screening checklist to evaluate the selected apps was named the App Chronic Disease Checklist, and comprises 4 sections with 6 questions in each section. The validity check verified classification of, and ambiguity in, wording

The Most Popular Smartphone Apps for Weight Loss: A Quality Assessment

PubMed Central

Cade, Janet E

2015-01-01

Background Advancements in mobile phone technology have led to the development of smartphones with the capability to run apps. The availability of a plethora of health- and fitness-related smartphone apps has the potential, both on a clinical and public health level, to facilitate healthy behavior change and weight management. However, current top-rated apps in this area have not been extensively evaluated in terms of scientific quality and behavioral theory evidence base. Objective The purpose of this study was to evaluate the quality of the most popular dietary weight-loss smartphone apps on the commercial market using comprehensive quality assessment criteria, and to quantify the behavior change techniques (BCTs) incorporated. Methods The top 200-rated Health & Fitness category apps from the free and paid sections of Google Play and iTunes App Store in Australia (n=800) were screened in August 2014. To be included in further analysis, an app had to focus on weight management, include a facility to record diet intake (self-monitoring), and be in English. One researcher downloaded and used the eligible apps thoroughly for 5 days and assessed the apps against quality assessment criteria which included the following domains: accountability, scientific coverage and content accuracy of information relevant to weight management, technology-enhanced features, usability, and incorporation of BCTs. For inter-rater reliability purposes, a second assessor provided ratings on 30% of the apps. The accuracy of app energy intake calculations was further investigated by comparison with results from a 3-day weighed food record (WFR). Results Across the eligible apps reviewed (n=28), only 1 app (4%) received full marks for accountability. Overall, apps included an average of 5.1 (SD 2.3) out of 14 technology-enhanced features, and received a mean score of 13.5 (SD 3.7) out of 20 for usability. The majority of apps provided estimated energy requirements (24/28, 86%) and used a food

Structure of Co(H2)n + Clusters, for n = 1-6

NASA Technical Reports Server (NTRS)

Bauschlicher, Charles W., Jr.; Maitre, Philippe

1995-01-01

The geometries and H2 binding energies have been determined for Co(H2)n (sup +), for n = 1-6. The binding energies are in good agreement with experiment. The shape of the clusters is used to explain the pairwise decrease in the binding energies. The bonding in CoH2 (sup +) and Co(H2)2 (sup +) is very similar and is enhanced by sd (sigma) hybridization. The next two H2 molecules add to the side of Co(H2)2 (sup +). These two additional H2 molecules cannot benefit from sd (sigma) hybridization and are less strongly bound. The addition of the fifth and sixth H2 molecules eliminates sd (sigma) hybridization as a mechanism for reducing Co-H2 repulsion. This coupled with the smaller Co to H2 (sigma *) donation results in another decrease in the binding energies.

Donor assists acceptor binding and catalysis of human α1,6-fucosyltransferase.

PubMed

Kötzler, Miriam P; Blank, Simon; Bantleon, Frank I; Wienke, Martin; Spillner, Edzard; Meyer, Bernd

2013-08-16

α1,6-Core-fucosyltransferase (FUT8) is a vital enzyme in mammalian physiological and pathophysiological processes such as tumorigenesis and progress of, among others, non-small cell lung cancer and colon carcinoma. It was also shown that therapeutic antibodies have a dramatically higher efficacy if the α1,6-fucosyl residue is absent. However, specific and potent inhibitors for FUT8 and related enzymes are lacking. Hence, it is crucial to elucidate the structural basis of acceptor binding and the catalytic mechanism. We present here the first structural model of FUT8 in complex with its acceptor and donor molecules. An unusually large acceptor, i.e., a hexasaccharide from the core of N-glycans, is required as minimal structure. Acceptor substrate binding of FUT8 is being dissected experimentally by STD NMR and SPR and theoretically by molecular dynamics simulations. The acceptor binding site forms an unusually large and shallow binding site. Binding of the acceptor to the enzyme is much faster and stronger if the donor is present. This is due to strong hydrogen bonding between O6 of the proximal N-acetylglucosamine and an oxygen atom of the β-phosphate of GDP-fucose. Therefore, we propose an ordered Bi Bi mechanism for FUT8 where the donor molecule binds first. No specific amino acid is present that could act as base during catalysis. Our results indicate a donor-assisted mechanism, where an oxygen of the β-phosphate deprotonates the acceptor. Knowledge of the mechanism of FUT8 is now being used for rational design of targeted inhibitors to address metastasis and prognosis of carcinomas.

Validated Smartphone-Based Apps for Ear and Hearing Assessments: A Review

PubMed Central

Pallawela, Danuk

2016-01-01

Background An estimated 360 million people have a disabling hearing impairment globally, the vast majority of whom live in low- and middle-income countries (LMICs). Early identification through screening is important to negate the negative effects of untreated hearing impairment. Substantial barriers exist in screening for hearing impairment in LMICs, such as the requirement for skilled hearing health care professionals and prohibitively expensive specialist equipment to measure hearing. These challenges may be overcome through utilization of increasingly available smartphone app technologies for ear and hearing assessments that are easy to use by unskilled professionals. Objective Our objective was to identify and compare available apps for ear and hearing assessments and consider the incorporation of such apps into hearing screening programs Methods In July 2015, the commercial app stores Google Play and Apple App Store were searched to identify apps for ear and hearing assessments. Thereafter, six databases (EMBASE, MEDLINE, Global Health, Web of Science, CINAHL, and mHealth Evidence) were searched to assess which of the apps identified in the commercial review had been validated against gold standard measures. A comparison was made between validated apps. Results App store search queries returned 30 apps that could be used for ear and hearing assessments, the majority of which are for performing audiometry. The literature search identified 11 eligible validity studies that examined 6 different apps. uHear, an app for self-administered audiometry, was validated in the highest number of peer reviewed studies against gold standard pure tone audiometry (n=5). However, the accuracy of uHear varied across these studies. Conclusions Very few of the available apps have been validated in peer-reviewed studies. Of the apps that have been validated, further independent research is required to fully understand their accuracy at detecting ear and hearing conditions. PMID

Cardiorespiratory Improvements Achieved by American College of Sports Medicine’s Exercise Prescription Implemented on a Mobile App

PubMed Central

Rospo, Gianluca; Valsecchi, Viola; Bonomi, Alberto G; Thomassen, Inge WJ; van Dantzig, Saskia; La Torre, Antonio

2016-01-01

Background Strong evidence shows that an increase in cardiorespiratory fitness (CRF) and physical activity (PA) reduces cardiovascular disease risk. Objective To test whether a scientifically endorsed program to increase CRF and PA, implemented on an easy-to-use, always-accessible mobile app would be effective in improving CRF. Methods Of 63 healthy volunteers participating, 18 tested the user interface of the Cardio-Fitness App (CF-App); and 45 underwent a 2-week intervention period, of whom 33 eventually concluded it. These were assigned into three groups. The Step-based App (Step-App) group (n=8), followed 10,000 steps/day prescription, the CF-App group (n=13), and the Supervised Cardio-Fitness (Super-CF) group (n=12), both followed a heart rate (HR)-based program according to American College of Sports Medicine (ACSM) guidelines, but either implemented on the app, or at the gym, respectively. Participants were tested for CRF, PA, resting systolic and diastolic blood pressures (SBP, DBP), resting, exercise, and recovery HR. Results CRF increased in all groups (+4.9%; P<.001). SBP decreased in all groups (-2.6 mm Hg; P=.03). DBP decrease was higher in the Super-CF group (-3.5 mm Hg) than in the Step-App group (-2.1 mm Hg; P<.001). Posttest exercise HR decreased in all groups (-3.4 bpm; P=.02). Posttest recovery HR was lower in the Super-CF group (-10.1 bpm) than in the other two groups (CF-App: -4.9 bpm, Step-App: -3.3 bpm; P<.001). The CF-App group, however, achieved these improvements with more training heart beats (P<.01). Conclusions A 10,000 steps/day target-based app improved CRF similar to an ACSM guideline-based program whether it was implemented on a mobile app or in supervised gym sessions. PMID:27339153

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

DR-78, a novel Drosophila melanogaster genomic DNA fragment highly homologous to the DNA-binding domain of thyroid hormone-retinoic acid-vitamin D receptor subfamily.

PubMed

Martín-Blanco, E; Kornberg, T B

1993-11-16

Degenerate oligodeoxyribonucleotides were designed for both ends of the DNA-binding domain of members of the nuclear receptor superfamily. PCR amplified Drosophila melanogaster DNA was purified and cloned (DR plasmids). Genomic lambda DASH clones were identified at high stringency with an amplified DR-78 plasmid DNA and isolated. The partial sequence shows a very probable open reading frame which would encode a peptide highly homologous to members of the thyroid hormone-retinoic acid-vitamin D receptor subfamily. The fragment corresponds to a single copy gene and was mapped at position 78D of chromosome three by in situ hybridization.

Interrater Reliability of mHealth App Rating Measures: Analysis of Top Depression and Smoking Cessation Apps.

PubMed

Powell, Adam C; Torous, John; Chan, Steven; Raynor, Geoffrey Stephen; Shwarts, Erik; Shanahan, Meghan; Landman, Adam B

2016-02-10

There are over 165,000 mHealth apps currently available to patients, but few have undergone an external quality review. Furthermore, no standardized review method exists, and little has been done to examine the consistency of the evaluation systems themselves. We sought to determine which measures for evaluating the quality of mHealth apps have the greatest interrater reliability. We identified 22 measures for evaluating the quality of apps from the literature. A panel of 6 reviewers reviewed the top 10 depression apps and 10 smoking cessation apps from the Apple iTunes App Store on these measures. Krippendorff's alpha was calculated for each of the measures and reported by app category and in aggregate. The measure for interactiveness and feedback was found to have the greatest overall interrater reliability (alpha=.69). Presence of password protection (alpha=.65), whether the app was uploaded by a health care agency (alpha=.63), the number of consumer ratings (alpha=.59), and several other measures had moderate interrater reliability (alphas>.5). There was the least agreement over whether apps had errors or performance issues (alpha=.15), stated advertising policies (alpha=.16), and were easy to use (alpha=.18). There were substantial differences in the interrater reliabilities of a number of measures when they were applied to depression versus smoking apps. We found wide variation in the interrater reliability of measures used to evaluate apps, and some measures are more robust across categories of apps than others. The measures with the highest degree of interrater reliability tended to be those that involved the least rater discretion. Clinical quality measures such as effectiveness, ease of use, and performance had relatively poor interrater reliability. Subsequent research is needed to determine consistent means for evaluating the performance of apps. Patients and clinicians should consider conducting their own assessments of apps, in conjunction with

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

Osmotically-induced tension and the binding of N-BAR protein to lipid vesicles.

PubMed

Hutchison, Jaime B; Karunanayake Mudiyanselage, Aruni P K K; Weis, Robert M; Dinsmore, Anthony D

2016-02-28

The binding affinity of a curvature-sensing protein domain (N-BAR) is measured as a function of applied osmotic stress while the membrane curvature is nearly constant. Varying the osmotic stress allows us to control membrane tension, which provides a probe of the mechanism of binding. We study the N-BAR domain of the Drosophila amphiphysin and monitor its binding on 50 nm-radius vesicles composed of 90 mol% DOPC and 10 mol% PIP. We find that the bound fraction of N-BAR is enhanced by a factor of approximately 6.5 when the tension increases from zero to 2.6 mN m(-1). This tension-induced response can be explained by the hydrophobic insertion mechanism. From the data we extract a hydrophobic domain area that is consistent with known structure. These results indicate that membrane stress and strain could play a major role in the previously reported curvature-affinity of N-BAR.

Biochemical and biophysical characterization of a plant calmodulin: Role of the N- and C-lobes in calcium binding, conformational change, and target interaction.

PubMed

Astegno, Alessandra; La Verde, Valentina; Marino, Valerio; Dell'Orco, Daniele; Dominici, Paola

2016-03-01

In plants, transient elevation of intracellular Ca(2+) concentration in response to abiotic stress is responsible for glutamate decarboxylase (GAD) activation via association with calmodulin (CaM), an EF-hand protein consisting of two homologous domains (N and C). An unusual 1:2 binding mode of CaM to CaM-binding domains of GAD has long been known, however the contribution of the two CaM domains in target recognition and activation remains to be clarified. Here, we explored the coupling between physicochemical properties of Arabidopsis CaM1 (AtCaM1) and Arabidopsis GAD1 activation, focusing on each AtCaM1 lobe. We found that the four EF-loops of AtCaM1 differently contribute to the ~20 μM apparent affinity for Ca(2+) and the C-lobe shows a ~6-fold higher affinity than N-lobe (Kd(app) 5.6 μM and 32 μM for C- and N-lobes, respectively). AtCaM1 responds structurally to Ca(2+) in a manner similar to vertebrate CaM based on comparison of Ca(2+)-induced changes in hydrophobicity exposure, secondary structure, and hydrodynamic behavior. Molecular dynamics simulations of AtCaM1 apo and Ca(2+)-bound reveal that the latter state is significantly less flexible, although regions of the N-lobe remain quite flexible; this suggests the importance of N-lobe for completing the transition to the extended structure of holoprotein, consistent with data from ANS fluorescence, CD spectroscopy, and SEC analysis. Moreover, enzymatic analysis reveal that mutations in the two lobes affect GAD1 activation in similar ways and only intact AtCaM1 can fully activate GAD1. Taken together, our data provide new insights into the CaM lobes role in interactions between CaM and plant GAD. Copyright © 2015 Elsevier B.V. All rights reserved.

Toxic shock syndrome toxin 1 binds to major histocompatibility complex class II molecules.

PubMed Central

Scholl, P; Diez, A; Mourad, W; Parsonnet, J; Geha, R S; Chatila, T

1989-01-01

Toxic shock syndrome toxin 1 (TSST-1) is a 22-kDa exotoxin produced by strains of Staphylococcus aureus and implicated in the pathogenesis of toxic shock syndrome. In common with other staphylococcal exotoxins, TSST-1 has diverse immunological effects. These include the induction of interleukin 2 receptor expression, interleukin 2 synthesis, proliferation of human T lymphocytes, and stimulation of interleukin 1 synthesis by human monocytes. In the present study, we demonstrate that TSST-1 binds with saturation kinetics and with a dissociation constant of 17-43 nM to a single class of binding sites on human mononuclear cells. There was a strong correlation between the number of TSST-1 binding sites and the expression of major histocompatibility complex class II molecules, and interferon-gamma induced the expression of class II molecules as well as TSST-1 binding sites on human skin-derived fibroblasts. Monoclonal antibodies to HLA-DR, but not to HLA-DP or HLA-DQ, strongly inhibited TSST-1 binding. Affinity chromatography of 125I-labeled cell membranes over TSST-1-agarose resulted in the recovery of two bands of 35 kDa and 31 kDa that comigrated, respectively, with the alpha and beta chains of HLA-DR and that could be immunoprecipitated with anti-HLA-DR monoclonal antibodies. Binding of TSST-1 was demonstrated to HLA-DR and HLA-DQ L-cell transfectants. These results indicate that major histocompatibility complex class II molecules represent the major binding site for TSST-1 on human cells. Images PMID:2542966

Effect of Dioxygen on Copper(II) Binding to α-Synuclein

PubMed Central

Lucas, Heather R.; Lee, Jennifer C.

2010-01-01

Using the fluorescent amino acid tryptophan (Trp), we have characterized the copper(II) binding of F4W α-synuclein in the presence and absence of dioxygen at neutral pH. Variations in Trp fluorescence indicate that copper(II) binding is enhanced by the presence of dioxygen, with the apparent dissociation constant (Kd(app)) changing from 100 nM (anaerobic) to 10 nM (aerobic). To investigate the possible role of methionine oxidation, complementary work focused on synthetic peptide models of the N-terminal Cu(II)-α-syn site, MDV(F/W) and M*DV(F/W), where M*= methionine sulfoxide. Furthermore, we employed circular dichroism (CD) spectroscopy to demonstrate that the phenyl-to-indole (F→W) substitution does not alter copper(II) binding properties and to confirm the 1:1 metal-peptide binding stoichiometry. CD comparisons also revealed that Met1 oxidation does not affect the copper-peptide conformation and further suggested the possible existence of a CuII-Trp/Phe (cation-π) interaction. PMID:20064662

Theoretical study of structure, bonding, and electronic behavior of novel sandwich complexes Os3(C6H6) n ( n = 1, 2)

NASA Astrophysics Data System (ADS)

Zhou, K.; Zhao, C. B.; Huang, W. D.

2017-11-01

The correlations between structural and electronic properties of the monolayer cluster Os3 and sandwich complexes of Os3(C6H6) n ( n = 1, 2) were studied with density functional theory. Every Os adopts η2 fashion to coordinate with C6H6 in Os3(C6H6), while every Os adopts η2 and η1 fashion to coordinate with below and above C6H6 rings in Os3(C6H6)2. η2 fashion is σ donation and π back bond, and η1 fashion belong to σ bond. The first binding energy between Os3 and below C6H6 ring is-114.23 kJ/mol, which is weaker than the second binding energy with-174.16 kJ/mol between Os3(C6H6) and above C6H6 ring. The reason is that the change of spin multiplicity is different, which leads the symmetry of Os3(C6H6)2 to be broken.

The investigation of the binding of 6-mercaptopurine to site I on human serum albumin.

PubMed

Sochacka, Jolanta; Baran, Wojciech

2012-12-01

6-Mercaptopurine (6-MP) is one of a large series of purine analogues which has been found active against human leukemias. The equilibrium dialysis, circular dichroism (CD) and molecular docking were employed to study the binding of 6-MP to human serum albumin (HSA). The binding of 6-MP to HSA in the equilibrium dialysis experiment was detected by measuring the displacement of 6-MP by specific markers for site I on HSA, warfarin (RWF), phenylbutazone (PhB) and n-butyl p-aminobenzoate (ABE). It was shown, according to CD data, that binding of 6-MP to HSA leads to alteration of HSA secondary structure. Based on the findings from displacement experiment and molecular docking simulation it was found that 6-MP was located within binding cavity of subdomain IIA and the space occupied by site markers overlapped with that of 6-MP. Displacement of 6-MP by the RWF or PhB was not up the level expected for a competitive mechanism, therefore displacement of 6-MP was rather by non-cooperative than that the direct competition. Instead, in case of the interaction between ABE and 6-MP, when the little enhancement of the binding of ABE by 6-MP was found, the interaction could be via a positively cooperative mechanism.

Identification and characterization of the sodium-binding site of activated protein C.

PubMed

He, X; Rezaie, A R

1999-02-19

Activated protein C (APC) requires both Ca2+ and Na+ for its optimal catalytic function. In contrast to the Ca2+-binding sites, the Na+-binding site(s) of APC has not been identified. Based on a recent study with thrombin, the 221-225 loop is predicted to be a potential Na+-binding site in APC. The sequence of this loop is not conserved in trypsin. We engineered a Gla domainless form of protein C (GDPC) in which the 221-225 loop was replaced with the corresponding loop of trypsin. We found that activated GDPC (aGDPC) required Na+ (or other alkali cations) for its amidolytic activity with dissociation constant (Kd(app)) = 44.1 +/- 8.6 mM. In the presence of Ca2+, however, the requirement for Na+ by aGDPC was eliminated, and Na+ stimulated the cleavage rate 5-6-fold with Kd(app) = 2.3 +/- 0.3 mM. Both cations were required for efficient factor Va inactivation by aGDPC. In the presence of Ca2+, the catalytic function of the mutant was independent of Na+. Unlike aGDPC, the mutant did not discriminate among monovalent cations. We conclude that the 221-225 loop is a Na+-binding site in APC and that an allosteric link between the Na+ and Ca2+ binding loops modulates the structure and function of this anticoagulant enzyme.

Interrater Reliability of mHealth App Rating Measures: Analysis of Top Depression and Smoking Cessation Apps

PubMed Central

Chan, Steven; Raynor, Geoffrey Stephen; Shwarts, Erik; Shanahan, Meghan; Landman, Adam B

2016-01-01

Background There are over 165,000 mHealth apps currently available to patients, but few have undergone an external quality review. Furthermore, no standardized review method exists, and little has been done to examine the consistency of the evaluation systems themselves. Objective We sought to determine which measures for evaluating the quality of mHealth apps have the greatest interrater reliability. Methods We identified 22 measures for evaluating the quality of apps from the literature. A panel of 6 reviewers reviewed the top 10 depression apps and 10 smoking cessation apps from the Apple iTunes App Store on these measures. Krippendorff’s alpha was calculated for each of the measures and reported by app category and in aggregate. Results The measure for interactiveness and feedback was found to have the greatest overall interrater reliability (alpha=.69). Presence of password protection (alpha=.65), whether the app was uploaded by a health care agency (alpha=.63), the number of consumer ratings (alpha=.59), and several other measures had moderate interrater reliability (alphas>.5). There was the least agreement over whether apps had errors or performance issues (alpha=.15), stated advertising policies (alpha=.16), and were easy to use (alpha=.18). There were substantial differences in the interrater reliabilities of a number of measures when they were applied to depression versus smoking apps. Conclusions We found wide variation in the interrater reliability of measures used to evaluate apps, and some measures are more robust across categories of apps than others. The measures with the highest degree of interrater reliability tended to be those that involved the least rater discretion. Clinical quality measures such as effectiveness, ease of use, and performance had relatively poor interrater reliability. Subsequent research is needed to determine consistent means for evaluating the performance of apps. Patients and clinicians should consider conducting their

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

PubMed

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

2015-07-27

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

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.

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.

Gamification for health promotion: systematic review of behaviour change techniques in smartphone apps

PubMed Central

Lumsden, J; Rivas, C; Steed, L; Thiyagarajan, A; Sohanpal, R; Caton, H; Griffiths, C J; Munafò, M R; Taylor, S; Walton, R T

2016-01-01

Objective Smartphone games that aim to alter health behaviours are common, but there is uncertainty about how to achieve this. We systematically reviewed health apps containing gaming elements analysing their embedded behaviour change techniques. Methods Two trained researchers independently coded apps for behaviour change techniques using a standard taxonomy. We explored associations with user ratings and price. Data sources We screened the National Health Service (NHS) Health Apps Library and all top-rated medical, health and wellness and health and fitness apps (defined by Apple and Google Play stores based on revenue and downloads). We included free and paid English language apps using ‘gamification’ (rewards, prizes, avatars, badges, leaderboards, competitions, levelling-up or health-related challenges). We excluded apps targeting health professionals. Results 64 of 1680 (4%) health apps included gamification and met inclusion criteria; only 3 of these were in the NHS Library. Behaviour change categories used were: feedback and monitoring (n=60, 94% of apps), reward and threat (n=52, 81%), and goals and planning (n=52, 81%). Individual techniques were: self-monitoring of behaviour (n=55, 86%), non-specific reward (n=49, 82%), social support unspecified (n=48, 75%), non-specific incentive (n=49, 82%) and focus on past success (n=47, 73%). Median number of techniques per app was 14 (range: 5–22). Common combinations were: goal setting, self-monitoring, non-specific reward and non-specific incentive (n=35, 55%); goal setting, self-monitoring and focus on past success (n=33, 52%). There was no correlation between number of techniques and user ratings (p=0.07; rs=0.23) or price (p=0.45; rs=0.10). Conclusions Few health apps currently employ gamification and there is a wide variation in the use of behaviour change techniques, which may limit potential to improve health outcomes. We found no correlation between user rating (a possible proxy for health benefits

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

Crystal structure of the UBR-box from UBR6/FBXO11 reveals domain swapping mediated by zinc binding.

PubMed

Muñoz-Escobar, Juliana; Kozlov, Guennadi; Gehring, Kalle

2017-10-01

The UBR-box is a 70-residue zinc finger domain present in the UBR family of E3 ubiquitin ligases that directly binds N-terminal degradation signals in substrate proteins. UBR6, also called FBXO11, is an UBR-box containing E3 ubiquitin ligase that does not bind N-terminal signals. Here, we present the crystal structure of the UBR-box domain from human UBR6. The dimeric crystal structure reveals a unique form of domain swapping mediated by zinc coordination, where three independent protein chains come together to regenerate the topology of the monomeric UBR-box fold. Analysis of the structure suggests that the absence of N-terminal residue binding arises from the lack of an amino acid binding pocket. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

Role of transcription factor Sp1 and RNA binding protein HuR in the down-regulation of Dr+ Escherichia coli receptor protein Decay Accelerating Factor (DAF or CD55) by Nitric oxide

PubMed Central

Banadakoppa, Manu; Liebenthal, Daniel; Nowak, David E; Urvil, Petri; Yallampalli, Uma; Wilson, Gerald M; Kishor, Aparna; Yallampalli, Chandra

2012-01-01

We previously reported that nitric oxide (NO) reduces the rate of bacteremia and maternal mortality in pregnant rats with uterine infection by Escherichia coli expressing the Dr Fimbria (Dr+). The epithelial invasion of Dr+ E. coli is dependent on the expression level of its cellular receptor decay accelerating factor (DAF). NO reduces the rate of bacteremia by down-regulating the expression of DAF. In this study, we elucidated the role of transcription factor Sp1 and RNA binding protein HuR in the down-regulation of human DAF by NO. We generated a series of deletion mutant constructs of DAF gene 5′-untranslated region and mapped NO-response region upstream to the core promoter region of the DAF gene. One of the several Sp1 binding sites in the DAF 5′-untranslated region was located within the NO-response region. The binding of Sp1 to this site was inhibited by NO. Furthermore, NO also promoted the degradation of DAF mRNA. The 3′-untranslated region of DAF harbors an AU-rich element and this element destabilized the mRNA transcript. The NO promoted the rapid degradation of DAF mRNA by inhibiting the binding of mRNA stabilizing protein HuR to this AU-rich region. The inhibition of binding of HuR to AU-rich region was due to the S-nitrosylation of one or more cysteine residues by NO. Thus, these data reveal the molecular mediators of transcriptional and post-transcriptional regulation of DAF by NO with implications in pathophysiology related to DAF. PMID:23176121

Gaia DR2 documentation Chapter 6: Spectroscopy

NASA Astrophysics Data System (ADS)

Sartoretti, P.; Blomme, R.; David, M.; Seabroke, G.

2018-04-01

This chapter of the Gaia DR2 documentation describes the processing and validation of the Radial Velocity Spectrometer (RVS) data. A more detailed description of the processing is provided in Sartoretti et al. (2018) and of the validation in Katz et al. (2018). A description of the RVS instrument is provided in Cropper et al. (2018).

Attention Deficit Hyperactivity Disorder: Is There an App for That? Suitability Assessment of Apps for Children and Young People With ADHD

PubMed Central

Parker, Jack; Robertson, Naomi; Harpin, Valerie

2017-01-01

Background Attention-deficit/hyperactivity disorder (ADHD) is a complex highly comorbid disorder, which can have a huge impact on those with ADHD, their family, and the community around them. ADHD is currently managed using pharmacological and nonpharmacological interventions. However, with advances in technology and an increase in the use of mobile apps, managing ADHD can be augmented using apps specifically designed for this population. However, little is known regarding the suitability and usability of currently available apps. Objective The aim of this study was to explore the suitability of the top 10 listed apps for children and young people with ADHD and clinicians who work with them. It is hypothesized that mobile apps designed for this population could be more suitably designed for this population. Methods The top 10 listed apps that are specifically targeted toward children and young people with ADHD in the United Kingdom were identified via the Google Play (n=5) and iTunes store (n=5). Interviews were then undertaken with 5 clinicians who specialize in treating this population and 5 children and young people with ADHD themselves, to explore their opinions of the 10 apps identified and what they believe the key components are for apps to be suitable for this population. Results Five themes emerged from clinician and young people interviews: the accessibility of the technology, the importance of relating to apps, addressing ADHD symptoms and related difficulties, age appropriateness, and app interaction. Three additional themes emerged from the clinician interviews alone: monitoring symptoms, side effects and app effect on relationships, and the impact of common comorbid conditions. The characteristics of the apps did not appear to match well with the views of our sample. Conclusions These findings suggest that the apps may not be suitable in meeting the complex needs associated with this condition. Further research is required to explore the value of apps

Role of transcription factor Sp1 and RNA binding protein HuR in the downregulation of Dr+ Escherichia coli receptor protein decay accelerating factor (DAF or CD55) by nitric oxide.

PubMed

Banadakoppa, Manu; Liebenthal, Daniel; Nowak, David E; Urvil, Petri; Yallampalli, Uma; Wilson, Gerald M; Kishor, Aparna; Yallampalli, Chandra

2013-02-01

We previously reported that nitric oxide (NO) reduces the rate of bacteremia and maternal mortality in pregnant rats with uterine infection by Escherichia coli expressing the Dr Fimbria (Dr(+) ). The epithelial invasion of Dr(+) E. coli is dependent on the expression level of its cellular receptor decay accelerating factor (DAF). NO reduces the rate of bacteremia by downregulating the expression of DAF. In this study, we elucidated the role of transcription factor Sp1 and RNA binding protein HuR in the downregulation of human DAF by NO. We generated a series of deletion mutant constructs of DAF gene 5'-untranslated region and mapped the NO-response region upstream to the core promoter region of the DAF gene. One of the several Sp1 binding sites in the DAF 5'-untranslated region was located within the NO-response region. The binding of Sp1 to this site was inhibited by NO. Furthermore, NO also promoted the degradation of DAF mRNA. The 3'-untranslated region of DAF harbors an AU-rich element and this element destabilized the mRNA transcript. NO promoted the rapid degradation of DAF mRNA by inhibiting the binding of mRNA stabilizing protein HuR to this AU-rich region. The inhibition of binding of HuR to the AU-rich region was due to the S-nitrosylation of one or more cysteine residues by NO. Thus, these data reveal the molecular mediators of transcriptional and post-transcriptional regulation of DAF by NO with implications in pathophysiology related to DAF. © 2012 The Authors Journal compilation © 2012 FEBS.

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

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.

STARD6 on steroids: solution structure, multiple timescale backbone dynamics and ligand binding mechanism

NASA Astrophysics Data System (ADS)

Létourneau, Danny; Bédard, Mikaël; Cabana, Jérôme; Lefebvre, Andrée; Lehoux, Jean-Guy; Lavigne, Pierre

2016-06-01

START domain proteins are conserved α/β helix-grip fold that play a role in the non-vesicular and intracellular transport of lipids and sterols. The mechanism and conformational changes permitting the entry of the ligand into their buried binding sites is not well understood. Moreover, their functions and the identification of cognate ligands is still an active area of research. Here, we report the solution structure of STARD6 and the characterization of its backbone dynamics on multiple time-scales through 15N spin-relaxation and amide exchange studies. We reveal for the first time the presence of concerted fluctuations in the Ω1 loop and the C-terminal helix on the microsecond-millisecond time-scale that allows for the opening of the binding site and ligand entry. We also report that STARD6 binds specifically testosterone. Our work represents a milestone for the study of ligand binding mechanism by other START domains and the elucidation of the biological function of STARD6.

Increased BMP6 levels in the brains of Alzheimer's disease patients and APP transgenic mice are accompanied by impaired neurogenesis.

PubMed

Crews, Leslie; Adame, Anthony; Patrick, Christina; Delaney, Alexandra; Pham, Emiley; Rockenstein, Edward; Hansen, Lawrence; Masliah, Eliezer

2010-09-15

During aging and in the progression of Alzheimer's disease (AD), synaptic plasticity and neuronal integrity are disturbed. In addition to the alterations in plasticity in mature neurons, the neurodegenerative process in AD has been shown to be accompanied by alterations in neurogenesis. Members of the bone morphogenetic protein (BMP) family of growth factors have been implicated as important regulators of neurogenesis and neuronal cell fate determination during development; however, their role in adult neurogenesis and in AD is less clear. We show here by qRT-PCR analysis that BMP6 mRNA levels were significantly increased in the hippocampus of human patients with AD and in APP transgenic mice compared to controls. Immunoblot and immunohistochemical analyses confirmed that BMP6 protein levels were increased in human AD brains and APP transgenic mouse brains compared to controls and accumulated around hippocampal plaques. The increased levels of BMP6 were accompanied by defects in hippocampal neurogenesis in AD patients and APP transgenic mice. In support of a role for BMP6 in defective neurogenesis in AD, we show in an in vitro model of adult neurogenesis that treatment with amyloid-β(1-42) protein (Aβ) resulted in increased expression of BMP6, and that exposure to recombinant BMP6 resulted in reduced proliferation with no toxic effects. Together, these results suggest that Aβ-associated increases in BMP6 expression in AD may have deleterious effects on neurogenesis in the hippocampus, and therapeutic approaches could focus on normalization of BMP6 levels to protect against AD-related neurogenic deficits.

Changes in pH and NADPH regulate the DNA binding activity of neuronal PAS domain protein 2, a mammalian circadian transcription factor.

PubMed

Yoshii, Katsuhiro; Tajima, Fumihisa; Ishijima, Sumio; Sagami, Ikuko

2015-01-20

Neuronal PAS domain protein 2 (NPAS2) is a core clock transcription factor that forms a heterodimer with BMAL1 to bind the E-box in the promoter of clock genes and is regulated by various environmental stimuli such as heme, carbon monoxide, and NAD(P)H. In this study, we investigated the effects of pH and NADPH on the DNA binding activity of NPAS2. In an electrophoretic mobility shift (EMS) assay, the pH of the reaction mixture affected the DNA binding activity of the NPAS2/BMAL1 heterodimer but not that of the BMAL1/BMAL1 homodimer. A change in pH from 7.0 to 7.5 resulted in a 1.7-fold increase in activity in the absence of NADPH, and NADPH additively enhanced the activity up to 2.7-fold at pH 7.5. The experiments using truncated mutants revealed that N-terminal amino acids 1-61 of NPAS2 were sufficient to sense the change in both pH and NADPH. We further analyzed the kinetics of formation and DNA binding of the NPAS2/BMAL1 heterodimer at various pH values. In the absence of NADPH, a change in pH from 6.5 to 8.0 decreased the KD(app) value of the E-box from 125 to 22 nM, with an 8-fold increase in the maximal level of DNA binding for the NPAS2/BMAL1 heterodimer. The addition of NADPH resulted in a further decrease in KD(app) to 9 nM at pH 8.0. Furthermore, NPAS2-dependent transcriptional activity in a luciferase assay using NIH3T3 cells also increased with the pH of the culture medium. These results suggest that NPAS2 has a role as a pH and metabolite sensor in regulating circadian rhythms.

An antagonistic monoclonal antibody (B-N6) specific for the human neurotensin receptor-1.

PubMed

Ovigne, J M; Vermot-Desroches, C; Lecron, J C; Portier, M; Lupker, J; Pecceu, F; Wijdenes, J

1998-06-01

The neuropeptide neurotensin (NT) interacts with two types of human receptors (hNTR) termed hNTR-1 and hNTR-2. This study describes a monoclonal antibody (MAb) specific for hNTR-1, B-N6. This MAb binds specifically to hNTR-1, but not to hNTR-2 transfected CHO cells. B-N6 and NT display a reciprocal competition and react in a similar way to trypsin, suggesting that the B-N6 epitope is at or close to the NT binding site on the third extracellular loop. Unlike B-N6, NT induces hNTR-1 internalization. Although neither NT-FITC nor B-N6 binding was detected by flow cytometry on different human cells, specific mRNA expression for hNTR-1 was detected in these cells. In CHO cells expressing hNTR-1 and a luciferase gene coupled to the krox24 reporter, B-N6 and the antagonist SR 48692 inhibited NT-induced intracellular activation of krox24 in a dose-dependent manner. From these results it is concluded that B-N6 is an antagonistic anti-hNTR-1 MAb.

Agonistic Human Monoclonal Antibodies against Death Receptor 4 (DR4) | NCI Technology Transfer Center | TTC

Cancer.gov

The National Cancer Institute is seeking parties interested in licensing human monoclonal antibodies (mAbs) that bind to death receptor 4 ("DR4"). The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and its functional receptors, DR4 and DR5, have been recognized as promising targets for cancer treatment.

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.

Mobile Phone Apps for the Prevention of Unintended Pregnancy: A Systematic Review and Content Analysis

PubMed Central

Lebrun, Victoria; Muessig, Kathryn E

2016-01-01

Background Over 50% of pregnancies in the United States are unintended, meaning that the pregnancy is mistimed, unplanned, or unwanted. Unintended pregnancy increases health risks for mother and child, leads to high economic costs for society, and increases social disparities. Mobile phone ownership is rapidly increasing, providing opportunities to reach at-risk populations with reproductive health information and tailored unintended pregnancy prevention interventions through mobile phone apps. However, apps that offer support for unintended pregnancy prevention remain unevaluated. Objective To identify, describe, and evaluate mobile phone apps that purport to help users prevent unintended pregnancy. Methods We conducted an extensive search of the Apple iTunes and Android Google Play stores for apps that explicitly included or advertised pregnancy prevention or decision-making support in the context of fertility information/tracking, birth control reminders, contraceptive information, pregnancy decision-making, abortion information or counseling, sexual communication/negotiation, and pregnancy tests. We excluded apps that targeted medical professionals or that cost more than US $1.99. Eligible apps were downloaded and categorized by primary purpose. Data extraction was performed on a minimum of 143 attributes in 3 domains: (1) pregnancy prevention best practices, (2) contraceptive methods and clinical services, and (3) user interface. Apps were assigned points for their inclusion of features overall and for pregnancy prevention best practices and contraceptive information. Results Our search identified 6805 app descriptions in iTunes and Google Play. Of these, 218 unique apps met inclusion criteria and were included in the review. Apps were grouped into 9 categories: fertility trackers (n=72), centers and resources (n=38), birth control reminders (n=35), general sexual and reproductive health (SRH) information (n=17), SRH information targeted specifically to young

Mobile Phone Apps for the Prevention of Unintended Pregnancy: A Systematic Review and Content Analysis.

PubMed

Mangone, Emily Rose; Lebrun, Victoria; Muessig, Kathryn E

2016-01-19

Over 50% of pregnancies in the United States are unintended, meaning that the pregnancy is mistimed, unplanned, or unwanted. Unintended pregnancy increases health risks for mother and child, leads to high economic costs for society, and increases social disparities. Mobile phone ownership is rapidly increasing, providing opportunities to reach at-risk populations with reproductive health information and tailored unintended pregnancy prevention interventions through mobile phone apps. However, apps that offer support for unintended pregnancy prevention remain unevaluated. To identify, describe, and evaluate mobile phone apps that purport to help users prevent unintended pregnancy. We conducted an extensive search of the Apple iTunes and Android Google Play stores for apps that explicitly included or advertised pregnancy prevention or decision-making support in the context of fertility information/tracking, birth control reminders, contraceptive information, pregnancy decision-making, abortion information or counseling, sexual communication/negotiation, and pregnancy tests. We excluded apps that targeted medical professionals or that cost more than US $1.99. Eligible apps were downloaded and categorized by primary purpose. Data extraction was performed on a minimum of 143 attributes in 3 domains: (1) pregnancy prevention best practices, (2) contraceptive methods and clinical services, and (3) user interface. Apps were assigned points for their inclusion of features overall and for pregnancy prevention best practices and contraceptive information. Our search identified 6805 app descriptions in iTunes and Google Play. Of these, 218 unique apps met inclusion criteria and were included in the review. Apps were grouped into 9 categories: fertility trackers (n=72), centers and resources (n=38), birth control reminders (n=35), general sexual and reproductive health (SRH) information (n=17), SRH information targeted specifically to young adults (YA) (n=16), contraceptive

Gamification for health promotion: systematic review of behaviour change techniques in smartphone apps.

PubMed

Edwards, E A; Lumsden, J; Rivas, C; Steed, L; Edwards, L A; Thiyagarajan, A; Sohanpal, R; Caton, H; Griffiths, C J; Munafò, M R; Taylor, S; Walton, R T

2016-10-04

Smartphone games that aim to alter health behaviours are common, but there is uncertainty about how to achieve this. We systematically reviewed health apps containing gaming elements analysing their embedded behaviour change techniques. Two trained researchers independently coded apps for behaviour change techniques using a standard taxonomy. We explored associations with user ratings and price. We screened the National Health Service (NHS) Health Apps Library and all top-rated medical, health and wellness and health and fitness apps (defined by Apple and Google Play stores based on revenue and downloads). We included free and paid English language apps using 'gamification' (rewards, prizes, avatars, badges, leaderboards, competitions, levelling-up or health-related challenges). We excluded apps targeting health professionals. 64 of 1680 (4%) health apps included gamification and met inclusion criteria; only 3 of these were in the NHS Library. Behaviour change categories used were: feedback and monitoring (n=60, 94% of apps), reward and threat (n=52, 81%), and goals and planning (n=52, 81%). Individual techniques were: self-monitoring of behaviour (n=55, 86%), non-specific reward (n=49, 82%), social support unspecified (n=48, 75%), non-specific incentive (n=49, 82%) and focus on past success (n=47, 73%). Median number of techniques per app was 14 (range: 5-22). Common combinations were: goal setting, self-monitoring, non-specific reward and non-specific incentive (n=35, 55%); goal setting, self-monitoring and focus on past success (n=33, 52%). There was no correlation between number of techniques and user ratings (p=0.07; r s =0.23) or price (p=0.45; r s =0.10). Few health apps currently employ gamification and there is a wide variation in the use of behaviour change techniques, which may limit potential to improve health outcomes. We found no correlation between user rating (a possible proxy for health benefits) and game content or price. Further research is

Theory-Based Design and Development of a Socially Connected, Gamified Mobile App for Men About Breastfeeding (Milk Man)

PubMed Central

White, Becky K; Martin, Annegret; White, James A; Burns, Sharyn K; Maycock, Bruce R; Giglia, Roslyn C

2016-01-01

Background Despite evidence of the benefits of breastfeeding, <15% of Australian babies are exclusively breastfed to the recommended 6 months. The support of the father is one of the most important factors in breastfeeding success, and targeting breastfeeding interventions to the father has been a successful strategy in previous research. Mobile technology offers unique opportunities to engage and reach populations to enhance health literacy and healthy behavior. Objective The objective of our study was to use previous research, formative evaluation, and behavior change theory to develop the first evidence-based breastfeeding app targeted at men. We designed the app to provide men with social support and information aiming to increase the support men can offer their breastfeeding partners. Methods We used social cognitive theory to design and develop the Milk Man app through stages of formative research, testing, and iteration. We held focus groups with new and expectant fathers (n=18), as well as health professionals (n=16), and used qualitative data to inform the design and development of the app. We tested a prototype with fathers (n=4) via a think-aloud study and the completion of the Mobile Application Rating Scale (MARS). Results Fathers and health professionals provided input through the focus groups that informed the app development. The think-aloud walkthroughs identified 6 areas of functionality and usability to be addressed, including the addition of a tutorial, increased size of text and icons, and greater personalization. Testers rated the app highly, and the average MARS score for the app was 4.3 out of 5. Conclusions To our knowledge, Milk Man is the first breastfeeding app targeted specifically at men. The development of Milk Man followed a best practice approach, including the involvement of a multidisciplinary team and grounding in behavior change theory. It tested well with end users during development. Milk Man is currently being trialed as part

Theory-Based Design and Development of a Socially Connected, Gamified Mobile App for Men About Breastfeeding (Milk Man).

PubMed

White, Becky K; Martin, Annegret; White, James A; Burns, Sharyn K; Maycock, Bruce R; Giglia, Roslyn C; Scott, Jane A

2016-06-27

Despite evidence of the benefits of breastfeeding, <15% of Australian babies are exclusively breastfed to the recommended 6 months. The support of the father is one of the most important factors in breastfeeding success, and targeting breastfeeding interventions to the father has been a successful strategy in previous research. Mobile technology offers unique opportunities to engage and reach populations to enhance health literacy and healthy behavior. The objective of our study was to use previous research, formative evaluation, and behavior change theory to develop the first evidence-based breastfeeding app targeted at men. We designed the app to provide men with social support and information aiming to increase the support men can offer their breastfeeding partners. We used social cognitive theory to design and develop the Milk Man app through stages of formative research, testing, and iteration. We held focus groups with new and expectant fathers (n=18), as well as health professionals (n=16), and used qualitative data to inform the design and development of the app. We tested a prototype with fathers (n=4) via a think-aloud study and the completion of the Mobile Application Rating Scale (MARS). Fathers and health professionals provided input through the focus groups that informed the app development. The think-aloud walkthroughs identified 6 areas of functionality and usability to be addressed, including the addition of a tutorial, increased size of text and icons, and greater personalization. Testers rated the app highly, and the average MARS score for the app was 4.3 out of 5. To our knowledge, Milk Man is the first breastfeeding app targeted specifically at men. The development of Milk Man followed a best practice approach, including the involvement of a multidisciplinary team and grounding in behavior change theory. It tested well with end users during development. Milk Man is currently being trialed as part of the Parent Infant Feeding Initiative (ACTRN

Nitric oxide sensitizes tumor cells to TRAIL-induced apoptosis via inhibition of the DR5 transcription repressor Yin Yang 1.

PubMed

Huerta-Yepez, Sara; Vega, Mario; Escoto-Chavez, Saul E; Murdock, Benjamin; Sakai, Toshiyuki; Baritaki, Stavroula; Bonavida, Benjamin

2009-02-01

Treatment of TRAIL-resistant tumor cells with the nitric oxide donor DETANONOate sensitizes the tumor cells to TRAIL-induced apoptosis concomitantly with DR5 upregulation. The mechanism of sensitization was examined based on the hypothesis that DETANONOate inhibits a transcription repressor Yin Yang 1 (YY1) that negatively regulates DR5 transcription. Treatment of the prostate carcinoma cell lines with DETANONOate inhibited both NF-kappaB and YY1 DNA-binding activities concomitantly with upregulation of DR5 expression. The direct role of YY1 in the regulation of TRAIL resistance was demonstrated in cells treated with YY1 siRNA resulting in TRAIL-induced apoptosis. The role of YY1 in the transcriptional regulation of DR5 was examined in cells treated with a DR5 luciferase reporter system (pDR5) and two constructs, namely, the pDR5/-605 construct with a deletion of the putative YY1 DNA-binding region (-1224 to -605) and a construct pDR5-YY1 with a mutation of the YY1 DNA-binding site. A significant (3-fold) augmentation of luciferase activity over baseline transfection with pDR5 was observed in cells transfected with the modified constructs. ChIP analysis corroborated the YY1 binding to the DR5 promoter. In vivo, tissues from nude mice bearing the PC-3 xenograft and treated with DETANONOate showed inhibition of YY1 and upregulation of DR5. The present findings demonstrate that YY1 negatively regulates DR5 transcription and expression and these correlated with resistance to TRAIL-induced apoptosis. DETANONOate inhibits both NF-kappaB and YY1 and in combination with TRAIL reverses tumor cell resistance to TRAIL apoptosis.

One-pot synthesis and sigma receptor binding studies of novel spirocyclic-2,6-diketopiperazine derivatives.

PubMed

Ghandi, Mehdi; Sherafat, Fatemeh; Sadeghzadeh, Masoud; Alirezapour, Behrouz

2016-06-01

New spirocyclic-2,6-diketopiperazine derivatives containing benzylpiperidine and cycloalkane moieties were synthesized by a one-pot two-step sequential Ugi/intramolecular N-amidation process in moderate to good yields. The in vitro ligand-binding profile studies performed on the sigma-1 and sigma-2 receptors revealed that the σ1 affinities and subtype selectivities of three spirocyclic piperidine derivatives are generally comparable to those of spirocycloalkane analogues. Compared to the low σ1 affinities obtained for cycloalkyl-substituted spirocyclic-2,6-diketopiperazines with n=2, those with n=1 proved to have optimal fitting with σ2 subtype by exhibiting higher affinities. Moreover, the best binding affinity and subtype selectivity was identified for compound 3c with Kiσ1=5.9±0.5nM and Kiσ2=563±21nM as well as 95-fold σ1/σ2 selectivity ratio, respectively. Copyright © 2016. Published by Elsevier Ltd.

Mobile App for Treatment of Stress Urinary Incontinence: A Cost-Effectiveness Analysis.

PubMed

Sjöström, Malin; Lindholm, Lars; Samuelsson, Eva

2017-05-08

Mobile apps can increase access to care, facilitate self-management, and improve adherence to treatment. Stress urinary incontinence (SUI) affects 10-35% of women and, currently, an app with instructions for pelvic floor muscle training (PFMT) is available as first-line treatment. A previous randomized controlled study demonstrated that the app benefitted symptom severity and quality of life (QoL); in this study we investigate the cost-effectiveness of the app. The objective of this study was to evaluate the health economy of the app for treating SUI. This deterministic cost-utility analysis, with a 1-year societal perspective, compared the app treatment with no treatment. Health economic data were collected alongside a randomized controlled trial performed in Sweden from March 2013 to October 2014. This study included 123 community-dwelling women participants of 18 years and above, with stress urinary incontinence ≥1 time per week. Participants were self-assessed with validated questionnaires and 2-day leakage diaries, and then randomized to 3 months of treatment (app group, n=62) or no treatment (controls, n=61). The app focused on pelvic floor muscle training, prescribed 3 times daily. We continuously registered treatment delivery costs. Data were collected on each participant's training time, incontinence aids, and laundry at baseline and at a 3-month follow-up. We measured quality of life with the International Consultation on Incontinence Modular Questionnaire on Lower Urinary Tract Symptoms and Quality of Life, and calculated the quality-adjusted life years (QALYs) gained. Data from the 3-month follow-up were extrapolated to 1 year for the calculations. Our main outcome was the incremental cost-effectiveness ratios compared between app and control groups. One-way and multiway sensitivity analyses were performed. The mean age of participants was 44.7 years (SD 9.4). Annual costs were €547.0 for the app group and €482.4 for the control group. Annual

Reviews Toy: Air swimmers Book: Their Arrows will Darken the Sun: The Evolution and Science of Ballistics Book: Physics Experiments for your Bag Book: Quantum Physics for Poets Equipment: SEP colour wheel kit Equipment: SEP colour mixing kit Software: USB DrDAQ App: iHandy Level Equipment: Photonics Explorer kit Web Watch

NASA Astrophysics Data System (ADS)

2012-01-01

WE RECOMMEND Air swimmers Helium balloon swims like a fish Their Arrows will Darken the Sun: The Evolution and Science of Ballistics Ballistics book hits the spot Physics Experiments for your Bag Handy experiments for your lessons Quantum Physics for Poets Book shows the economic importance of physics SEP colour wheel kit Wheels investigate colour theory SEP colour mixing kit Cheap colour mixing kit uses red, green and blue LEDs iHandy Level iPhone app superbly measures angles Photonics Explorer kit Free optics kit given to schools WORTH A LOOK DrDAQ DrDAQ software gets an upgrade WEB WATCH Websites show range of physics

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

PubMed

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

2018-01-24

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

Evidence against roles for phorbol binding protein Munc13-1, ADAM adaptor Eve-1, or vesicle trafficking phosphoproteins Munc18 or NSF as phospho-state-sensitive modulators of phorbol/PKC-activated Alzheimer APP ectodomain shedding

PubMed Central

Ikin, Annat F; Causevic, Mirsada; Pedrini, Steve; Benson, Lyndsey S; Buxbaum, Joseph D; Suzuki, Toshiharu; Lovestone, Simon; Higashiyama, Shigeki; Mustelin, Tomas; Burgoyne, Robert D; Gandy, Sam

2007-01-01

Background Shedding of the Alzheimer amyloid precursor protein (APP) ectodomain can be accelerated by phorbol esters, compounds that act via protein kinase C (PKC) or through unconventional phorbol-binding proteins such as Munc13-1. We have previously demonstrated that application of phorbol esters or purified PKC potentiates budding of APP-bearing secretory vesicles at the trans-Golgi network (TGN) and toward the plasma membrane where APP becomes a substrate for enzymes responsible for shedding, known collectively as α-secretase(s). However, molecular identification of the presumptive "phospho-state-sensitive modulators of ectodomain shedding" (PMES) responsible for regulated shedding has been challenging. Here, we examined the effects on APP ectodomain shedding of four phorbol-sensitive proteins involved in regulation of vesicular membrane trafficking of APP: Munc13-1, Munc18, NSF, and Eve-1. Results Overexpression of either phorbol-sensitive wildtype Munc13-1 or phorbol-insensitive Munc13-1 H567K resulted in increased basal APP ectodomain shedding. However, in contrast to the report of Roßner et al (2004), phorbol ester-dependent APP ectodomain shedding from cells overexpressing APP and Munc13-1 wildtype was indistinguishable from that observed following application of phorbol to cells overexpressing APP and Munc13-1 H567K mutant. This pattern of similar effects on basal and stimulated APP shedding was also observed for Munc18 and NSF. Eve-1, an ADAM adaptor protein reported to be essential for PKC-regulated shedding of pro-EGF, was found to play no obvious role in regulated shedding of sAPPα. Conclusion Our results indicate that, in the HEK293 system, Munc13-1, Munc18, NSF, and EVE-1 fail to meet essential criteria for identity as PMES for APP. PMID:18067682

Evidence against roles for phorbol binding protein Munc13-1, ADAM adaptor Eve-1, or vesicle trafficking phosphoproteins Munc18 or NSF as phospho-state-sensitive modulators of phorbol/PKC-activated Alzheimer APP ectodomain shedding.

PubMed

Ikin, Annat F; Causevic, Mirsada; Pedrini, Steve; Benson, Lyndsey S; Buxbaum, Joseph D; Suzuki, Toshiharu; Lovestone, Simon; Higashiyama, Shigeki; Mustelin, Tomas; Burgoyne, Robert D; Gandy, Sam

2007-12-09

Shedding of the Alzheimer amyloid precursor protein (APP) ectodomain can be accelerated by phorbol esters, compounds that act via protein kinase C (PKC) or through unconventional phorbol-binding proteins such as Munc13-1. We have previously demonstrated that application of phorbol esters or purified PKC potentiates budding of APP-bearing secretory vesicles at the trans-Golgi network (TGN) and toward the plasma membrane where APP becomes a substrate for enzymes responsible for shedding, known collectively as alpha-secretase(s). However, molecular identification of the presumptive "phospho-state-sensitive modulators of ectodomain shedding" (PMES) responsible for regulated shedding has been challenging. Here, we examined the effects on APP ectodomain shedding of four phorbol-sensitive proteins involved in regulation of vesicular membrane trafficking of APP: Munc13-1, Munc18, NSF, and Eve-1. Overexpression of either phorbol-sensitive wildtype Munc13-1 or phorbol-insensitive Munc13-1 H567K resulted in increased basal APP ectodomain shedding. However, in contrast to the report of Rossner et al (2004), phorbol ester-dependent APP ectodomain shedding from cells overexpressing APP and Munc13-1 wildtype was indistinguishable from that observed following application of phorbol to cells overexpressing APP and Munc13-1 H567K mutant. This pattern of similar effects on basal and stimulated APP shedding was also observed for Munc18 and NSF. Eve-1, an ADAM adaptor protein reported to be essential for PKC-regulated shedding of pro-EGF, was found to play no obvious role in regulated shedding of sAPPalpha. Our results indicate that, in the HEK293 system, Munc13-1, Munc18, NSF, and EVE-1 fail to meet essential criteria for identity as PMES for APP.

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.

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.

A Pilot Comparison of a Smartphone App With or Without 2-Way Messaging Among Chronic Pain Patients

PubMed Central

Jurcik, Dylan C.; Edwards, Robert R.; Huang, Chuan-Chin; Ross, Edgar L.

2017-01-01

Objectives: The overall aim of this study was to determine the effect of introducing a smartphone pain application (app), for both Android and iPhone devices that enables chronic pain patients to assess, monitor, and communicate their status to their providers. Methods: This study recruited 105 chronic pain patients to use a smartphone pain app and half of the patients (N=52) had 2-way messaging available through the app. All patients completed baseline measures and were asked to record their progress every day for 3 months, with the opportunity to continue for 6 months. All participants were supplied a Fitbit to track daily activity. Summary line graphs were posted to each of the patients’ electronic medical records and physicians were notified of their patient’s progress. Results: Ninety patients successfully downloaded the pain app. Average age of the participants was 47.1 (range, 18 to 72), 63.8% were female and 32.3% reported multiple pain sites. Adequate validity and reliability was found between the daily assessments and standardized questionnaires (r=0.50) and in repeated daily measures (pain, r=0.69; sleep, r=0.83). The app was found to be easily introduced and well tolerated. Those patients assigned to the 2-way messaging condition on average tended to use the app more and submit more daily assessments (95.6 vs. 71.6 entries), but differences between groups were not significant. Pain-app satisfaction ratings overall were high. Discussion: This study highlights some of the challenges and benefits in utilizing smartphone apps to manage chronic pain patients, and provides insight into those individuals who might benefit from mHealth technology. PMID:27898460

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.

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.

Download Alert: Understanding Gastroenterology Patients' Perspectives on Health-Related Smartphone Apps

PubMed Central

Zia, Jasmine K; Le, Thai; Munson, Sean; Heitkemper, Margaret M; Demiris, George

2015-01-01

Objectives: The aims of this study were to understand patients' willingness to use different types of health-related smartphone apps and to explore their attitudes on the overall value, usability, feasibility, credibility, intrusiveness, and obtrusiveness of these apps. Methods: Questionnaires were distributed to adult patients presenting to gastroenterology clinics at an academic medical center. The 25-question survey consisted of 5-point Likert-type scale statements, multiple-choice questions, and open-ended questions. Results: Participants were mainly White (N=94, 78%) and smartphone owners (N=125, 93%). The mean age was 40.8 years (N=121, s.d.=13.2). Participants were willing to use most types of apps unless it monitored their location or social networking activity. Half were less willing to use an app if it required a visible accessory. Most participants were willing to use a health-related app up to 5 min a day indefinitely but unwilling to pay out-of-pocket for it. Participants generally disagreed that an app would be hard to learn how to use, interfere with their daily routine, or be embarrassing to use in public. Overall, participants felt that health-related apps could help them and their doctors better manage their medical problems, but were neutral in trusting their quality. Most worried that personal information used for an app would fall into the wrong hands. Conclusion: Gastroenterology patients were willing to use and valued most types of health-related apps. They perceived this technology as feasible, usable, and relatively unobtrusive unless a visible accessory was required. However, many were concerned about their privacy. PMID:26133109

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

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

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.

A Mobile App to Stabilize Daily Functional Activity of Breast Cancer Patients in Collaboration With the Physician: A Randomized Controlled Clinical Trial.

PubMed

Egbring, Marco; Far, Elmira; Roos, Malgorzata; Dietrich, Michael; Brauchbar, Mathis; Kullak-Ublick, Gerd A; Trojan, Andreas

2016-09-06

The well-being of breast cancer patients and reporting of adverse events require close monitoring. Mobile apps allow continuous recording of disease- and medication-related symptoms in patients undergoing chemotherapy. The aim of the study was to evaluate the effects of a mobile app on patient-reported daily functional activity in a supervised and unsupervised setting. We conducted a randomized controlled study of 139 breast cancer patients undergoing chemotherapy. Patient status was self-measured using Eastern Cooperative Oncology Group scoring and Common Terminology Criteria for Adverse Events. Participants were randomly assigned to a control group, an unsupervised group that used a mobile app to record data, or a supervised group that used the app and reviewed data with a physician. Primary outcome variables were change in daily functional activity and symptoms over three outpatient visits. Functional activity scores declined in all groups from the first to second visit. However, from the second to third visit, only the supervised group improved, whereas the others continued to decline. Overall, the supervised group showed no significant difference from the first (median 90.85, IQR 30.67) to third visit (median 84.76, IQR 18.29, P=.72). Both app-using groups reported more distinct adverse events in the app than in the questionnaire (supervised: n=1033 vs n=656; unsupervised: n=852 vs n=823), although the unsupervised group reported more symptoms overall (n=4808) in the app than the supervised group (n=4463). The mobile app was associated with stabilized daily functional activity when used under collaborative review. App-using participants could more frequently report adverse events, and those under supervision made fewer and more precise entries than unsupervised participants. Our findings suggest that patient well-being and awareness of chemotherapy adverse effects can be improved by using a mobile app in collaboration with the treating physician. Clinical

A Mobile App to Stabilize Daily Functional Activity of Breast Cancer Patients in Collaboration With the Physician: A Randomized Controlled Clinical Trial

PubMed Central

Egbring, Marco; Far, Elmira; Roos, Malgorzata; Dietrich, Michael; Brauchbar, Mathis; Kullak-Ublick, Gerd A

2016-01-01

Background The well-being of breast cancer patients and reporting of adverse events require close monitoring. Mobile apps allow continuous recording of disease- and medication-related symptoms in patients undergoing chemotherapy. Objective The aim of the study was to evaluate the effects of a mobile app on patient-reported daily functional activity in a supervised and unsupervised setting. Methods We conducted a randomized controlled study of 139 breast cancer patients undergoing chemotherapy. Patient status was self-measured using Eastern Cooperative Oncology Group scoring and Common Terminology Criteria for Adverse Events. Participants were randomly assigned to a control group, an unsupervised group that used a mobile app to record data, or a supervised group that used the app and reviewed data with a physician. Primary outcome variables were change in daily functional activity and symptoms over three outpatient visits. Results Functional activity scores declined in all groups from the first to second visit. However, from the second to third visit, only the supervised group improved, whereas the others continued to decline. Overall, the supervised group showed no significant difference from the first (median 90.85, IQR 30.67) to third visit (median 84.76, IQR 18.29, P=.72). Both app-using groups reported more distinct adverse events in the app than in the questionnaire (supervised: n=1033 vs n=656; unsupervised: n=852 vs n=823), although the unsupervised group reported more symptoms overall (n=4808) in the app than the supervised group (n=4463). Conclusions The mobile app was associated with stabilized daily functional activity when used under collaborative review. App-using participants could more frequently report adverse events, and those under supervision made fewer and more precise entries than unsupervised participants. Our findings suggest that patient well-being and awareness of chemotherapy adverse effects can be improved by using a mobile app in

Validation of a smartphone app to map social networks of proximity

PubMed Central

Larsen, Mark E.; Townsend, Samuel; Christensen, Helen

2017-01-01

Social network analysis is a prominent approach to investigate interpersonal relationships. Most studies use self-report data to quantify the connections between participants and construct social networks. In recent years smartphones have been used as an alternative to map networks by assessing the proximity between participants based on Bluetooth and GPS data. While most studies have handed out specially programmed smartphones to study participants, we developed an application for iOS and Android to collect Bluetooth data from participants’ own smartphones. In this study, we compared the networks estimated with the smartphone app to those obtained from sociometric badges and self-report data. Participants (n = 21) installed the app on their phone and wore a sociometric badge during office hours. Proximity data was collected for 4 weeks. A contingency table revealed a significant association between proximity data (ϕ = 0.17, p<0.0001), but the marginal odds were higher for the app (8.6%) than for the badges (1.3%), indicating that dyads were more often detected by the app. We then compared the networks that were estimated using the proximity and self-report data. All three networks were significantly correlated, although the correlation with self-reported data was lower for the app (ρ = 0.25) than for badges (ρ = 0.67). The scanning rates of the app varied considerably between devices and was lower on iOS than on Android. The association between the app and the badges increased when the network was estimated between participants whose app recorded more regularly. These findings suggest that the accuracy of proximity networks can be further improved by reducing missing data and restricting the interpersonal distance at which interactions are detected. PMID:29261782

Smartphone Apps for Measuring Human Health and Climate Change Co-Benefits: A Comparison and Quality Rating of Available Apps

PubMed Central

Sullivan, Rachel K; Marsh, Samantha; Halvarsson, Jakob; Holdsworth, Michelle; Waterlander, Wilma; Poelman, Maartje P; Salmond, Jennifer Ann; Christian, Hayley; Koh, Lenny SC; Cade, Janet E; Spence, John C; Woodward, Alistair

2016-01-01

Background Climate change and the burden of noncommunicable diseases are major global challenges. Opportunities exist to investigate health and climate change co-benefits through a shift from motorized to active transport (walking and cycling) and a shift in dietary patterns away from a globalized diet to reduced consumption of meat and energy dense foods. Given the ubiquitous use and proliferation of smartphone apps, an opportunity exists to use this technology to capture individual travel and dietary behavior and the associated impact on the environment and health. Objective The objective of the study is to identify, describe the features, and rate the quality of existing smartphone apps which capture personal travel and dietary behavior and simultaneously estimate the carbon cost and potential health consequences of these actions. Methods The Google Play and Apple App Stores were searched between October 19 and November 6, 2015, and a secondary Google search using the apps filter was conducted between August 8 and September 18, 2016. Eligible apps were required to estimate the carbon cost of personal behaviors with the potential to include features to maximize health outcomes. The quality of included apps was assessed by 2 researchers using the Mobile Application Rating Scale (MARS). Results Out of 7213 results, 40 apps were identified and rated. Multiple travel-related apps were identified, however no apps solely focused on the carbon impact or health consequences of dietary behavior. None of the rated apps provided sufficient information on the health consequences of travel and dietary behavior. Some apps included features to maximize participant engagement and encourage behavior change towards reduced greenhouse gas emissions. Most apps were rated as acceptable quality as determined by the MARS; 1 was of poor quality and 10 apps were of good quality. Interrater reliability of the 2 evaluators was excellent (ICC=0.94, 95% CI 0.87-0.97). Conclusions Existing

Apps for Hearing Science and Care.

PubMed

Paglialonga, Alessia; Tognola, Gabriella; Pinciroli, Francesco

2015-09-01

Our research aims at the identification and assessment of applications (referred to as apps) in the hearing health care domain. This research forum article presents an overview of the current availability, affordability, and variety of hearing-related apps. The available apps were reviewed by searching on the leading platforms (iOS, Android, Windows Phone stores) using the keywords hearing, audiology, audio, auditory, speech, language, tinnitus, hearing loss, hearing aid, hearing sys tem, cochlear implant, implantable device, auditory training, hearing rehabilitation, and assistive technology/tool/device. O n the bas is of the offered services, apps were classified into 4 application domains: (a) screening and assessment, (b) intervention and rehabilitation, (c) education and information, and (d) assistive tools. A large variety of apps are available in the hearing health care domain. These cover a wide range of services for people with hearing or communication problems as well as for hearing professionals, families, or informal caregivers. This evolution can potentially bring along considerable advantages and improved outcomes in the field of hearing health care. Nevertheless, potential risks and threats (e.g., safety, quality, effectiveness, privacy, and regulation) should not be overlooked. Significant research—particularly in terms of assessment and guidance—is still needed for the informed, aware, and safe adoption of hearing-related apps by patients and professionals.

Valuable Features in Mobile Health Apps for Patients and Consumers: Content Analysis of Apps and User Ratings

PubMed Central

2015-01-01

Background The explosion of mobile phones with app capabilities coupled with increased expectations of the patient-consumers’ role in managing their care presents a unique opportunity to use mobile health (mHealth) apps. Objectives The aim of this paper is to identify the features and characteristics most-valued by patient-consumers (“users”) that contribute positively to the rating of an app. Methods A collection of 234 apps associated with reputable health organizations found in the medical, health, and fitness categories of the Apple iTunes store and Google Play marketplace was assessed manually for the presence of 12 app features and characteristics. Regression analysis was used to determine which, if any, contributed positively to a user’s rating of the app. Results Analysis of these 12 features explained 9.3% (R 2=.093 n=234, P<.001) of the variation in an app’s rating, with only 5 reaching statistical significance. Of the 5 reaching statistical significance, plan or orders, export of data, usability, and cost contributed positively to a user’s rating, while the tracker feature detracted from it. Conclusions These findings suggest that users appreciate features that save time over current methods and identify an app as valuable when it is simple and intuitive to use, provides specific instructions to better manage a condition, and shares data with designated individuals. Although tracking is a core function of most health apps, this feature may detract from a user’s experience when not executed properly. Further investigation into mHealth app features is worthwhile given the inability of the most common features to explain a large portion of an app’s rating. In the future, studies should focus on one category in the app store, specific diseases, or desired behavior change, and methods should include measuring the quality of each feature, both through manual assessment and evaluation of user reviews. Additional investigations into understanding

Selecting "App"ealing and "App"ropriate Book Apps for Beginning Readers

ERIC Educational Resources Information Center

Cahill, Maria; McGill-Franzen, Anne

2013-01-01

Beginning with a brief rationale for selecting quality digital picture book apps for beginning readers, the authors describe the elements of digital picture books and provide a brief review of the instructional benefits of digital picture book use for beginning readers. They then present a detailed taxonomy for selecting quality picture book apps.…

Type 1 diabetes risk for HLA-DR3 haplotypes depends on genotypic context: Association of DPB1 and HLA class I loci among DR3 and DR4 matched Italian patients and controls

PubMed Central

Noble, Janelle A.; Martin, Adelle; Valdes, Ana M.; Lane, Julie A.; Galgani, Andrea; Petrone, Antonio; Lorini, Renata; Pozzilli, Paolo; Buzzetti, Raffaella; Erlich, Henry A.

2008-01-01

Patients with high-risk HLA-DR-DQ genotypes for type 1 diabetes (T1D) were compared to HLA-matched controls to evaluate T1D risk for other HLA loci, including HLA-A, -B, -Cw, and DPB1. Patients (n=133) with high-risk genotypes (DR3/DR3, DR3/DR4, DR4/DR4) were selected from the Lazio (Rome) region of Italy. Screening of more than 9000 subjects from the Lazio region and northern Italy yielded 162 controls with high- T1D-risk haplotypes. Although the overall distributions were not significantly different, allele frequency differences were discovered between the controls from Lazio and those from Northern Italy for some alleles previously shown to affect T1D risk, such as A*3002, DPB1*0301, and DPB1*0402. Therefore, Lazio patient data were compared both to the Lazio subset of controls (n=53) and to the entire group of controls for association analyses. Significant allele frequency differences between patients and DR-DQ-matched controls were found for specific alleles at all loci. Data for the DR3/DR3 subset of patients and controls showed an increase of Cw*0702 in patients. Reduced patient, compared to control, frequencies were seen for several alleles, including A*0101, B*0801, and Cw*0701, all found on the highly-conserved, extended DR3 haplotype known as 8.1 in DR3/DR3, but not DR3/DR4, subgroup. DPB1*0101, often found on 8.1 haplotypes, was also less frequent in DR3/DR3 patients than controls. Analysis of family-based data from the HBDI repository was consistent with the observed results from the Italian subjects, suggesting the presence of a T1D-protective locus at or near A*0101 and a second T1D-protective locus at or near DPB1*0101. These data suggest that T1D risk conferred by the 8.1 haplotype is genotype dependent. PMID:18486765

A Diabetes Mobile App With In-App Coaching From a Certified Diabetes Educator Reduces A1C for Individuals With Type 2 Diabetes.

PubMed

Kumar, Shefali; Moseson, Heidi; Uppal, Jaspreet; Juusola, Jessie L

2018-06-01

Purpose There are currently many diabetes apps available, but there is limited evidence demonstrating clinical impact. The purpose of this study is to evaluate the impact of a diabetes mobile app with in-app coaching by a certified diabetes educator on glycemic control for individuals with type 2 diabetes. Methods A 12 week-long single-arm intent-to-treat trial evaluated the impact of a diabetes mobile app and coaching program (One Drop | Mobile With One Drop | Experts), which facilitated tracking of self-care and included an in-app diabetes education program, on A1C for individuals with type 2 diabetes and an A1C ≥7.5% (58 mmol/mol). An online study platform (Achievement Studies, Evidation Health Inc, San Mateo, CA) was used to screen, consent, and enroll participants; collect study data; and track participants' progress throughout the study. Baseline and study end A1C measurements as well as questionnaire data from participants were collected. Results Participants (n = 146) were 52 ± 9 years old, 71% female, 25% black or Hispanic, diagnosed with diabetes for 11 ± 7 years, and with a mean baseline A1C of 9.87% ± 2.0 (84 mmol/mol). In adjusted repeated measures models, mean A1C improved by -0.86% among study completers (n = 127), -0.96% among active users of the app and coaching program (n = 93), and -1.32% among active users with a baseline A1C ≥9.0% (75 mmol/mol) (n = 53). Conclusions This program was associated with a clinically meaningful and significant reduction in A1C and can potentially increase access to effective diabetes self-management education and support for individuals with diabetes.

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

PubMed Central

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

2011-01-01

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

Smartphone and medical related App use among medical students and junior doctors in the United Kingdom (UK): a regional survey.

PubMed

Payne, Karl Frederick Braekkan; Wharrad, Heather; Watts, Kim

2012-10-30

Smartphone usage has spread to many settings including that of healthcare with numerous potential and realised benefits. The ability to download custom-built software applications (apps) has created a new wealth of clinical resources available to healthcare staff, providing evidence-based decisional tools to reduce medical errors.Previous literature has examined how smartphones can be utilised by both medical student and doctor populations, to enhance educational and workplace activities, with the potential to improve overall patient care. However, this literature has not examined smartphone acceptance and patterns of medical app usage within the student and junior doctor populations. An online survey of medical student and foundation level junior doctor cohorts was undertaken within one United Kingdom healthcare region. Participants were asked whether they owned a Smartphone and if they used apps on their Smartphones to support their education and practice activities. Frequency of use and type of app used was also investigated. Open response questions explored participants' views on apps that were desired or recommended and the characteristics of apps that were useful. 257 medical students and 131 junior doctors responded, equating to a response rate of 15.0% and 21.8% respectively. 79.0% (n=203/257) of medical students and 74.8% (n=98/131) of junior doctors owned a smartphone, with 56.6% (n=115/203) of students and 68.4% (n=67/98) of doctors owning an iPhone.The majority of students and doctors owned 1-5 medical related applications, with very few owning more than 10, and iPhone owners significantly more likely to own apps (Chi sq, p<0.001). Both populations showed similar trends of app usage of several times a day. Over 24 hours apps were used for between 1-30 minutes for students and 1-20 minutes for doctors, students used disease diagnosis/management and drug reference apps, with doctors favouring clinical score/calculator apps. This study found a high level

Smartphone and medical related App use among medical students and junior doctors in the United Kingdom (UK): a regional survey

PubMed Central

2012-01-01

Background Smartphone usage has spread to many settings including that of healthcare with numerous potential and realised benefits. The ability to download custom-built software applications (apps) has created a new wealth of clinical resources available to healthcare staff, providing evidence-based decisional tools to reduce medical errors. Previous literature has examined how smartphones can be utilised by both medical student and doctor populations, to enhance educational and workplace activities, with the potential to improve overall patient care. However, this literature has not examined smartphone acceptance and patterns of medical app usage within the student and junior doctor populations. Methods An online survey of medical student and foundation level junior doctor cohorts was undertaken within one United Kingdom healthcare region. Participants were asked whether they owned a Smartphone and if they used apps on their Smartphones to support their education and practice activities. Frequency of use and type of app used was also investigated. Open response questions explored participants’ views on apps that were desired or recommended and the characteristics of apps that were useful. Results 257 medical students and 131 junior doctors responded, equating to a response rate of 15.0% and 21.8% respectively. 79.0% (n=203/257) of medical students and 74.8% (n=98/131) of junior doctors owned a smartphone, with 56.6% (n=115/203) of students and 68.4% (n=67/98) of doctors owning an iPhone. The majority of students and doctors owned 1–5 medical related applications, with very few owning more than 10, and iPhone owners significantly more likely to own apps (Chi sq, p<0.001). Both populations showed similar trends of app usage of several times a day. Over 24hours apps were used for between 1–30 minutes for students and 1–20 minutes for doctors, students used disease diagnosis/management and drug reference apps, with doctors favouring clinical score

The PpaA/AerR regulators of photosynthesis gene expression from anoxygenic phototrophic proteobacteria contain heme-binding SCHIC domains.

PubMed

Moskvin, Oleg V; Gilles-Gonzalez, Marie-Alda; Gomelsky, Mark

2010-10-01

The SCHIC domain of the B12-binding domain family present in the Rhodobacter sphaeroides AppA protein binds heme and senses oxygen. Here we show that the predicted SCHIC domain PpaA/AerR regulators also bind heme and respond to oxygen in vitro, despite their low sequence identity with AppA.

ReadyVax: A new mobile vaccine information app.

PubMed

Bednarczyk, Robert A; Frew, Paula M; Salmon, Daniel A; Whitney, Ellen; Omer, Saad B

2017-05-04

Vaccine information of varying quality is available through many different sources. We describe the creation, release and utilization of ReadyVax, a new mobile smartphone app providing access to trustworthy, evidence-based vaccine information for a target audience of healthcare providers, pharmacists, and patients (including parents of children). We describe the information content and technical development of ReadyVax. Between the hard launch of the app on February 12, 2015 and October 8, 2016, the app has been downloaded by 5,142 unique users, with 6,841 total app sessions initiated, comprising a total of 15,491 screen views (2.3 screens/session on average). ReadyVax has been downloaded by users in 102 different countries; most users (52%) are from the United States. We are continuing outreach efforts to increase app use, and planning for development of an Android-compatible version of ReadyVax, to increase the available market for the app.

ReadyVax: A new mobile vaccine information app

PubMed Central

Bednarczyk, Robert A.; Frew, Paula M.; Salmon, Daniel A.; Whitney, Ellen; Omer, Saad B.

2017-01-01

Abstract Vaccine information of varying quality is available through many different sources. We describe the creation, release and utilization of ReadyVax, a new mobile smartphone app providing access to trustworthy, evidence-based vaccine information for a target audience of healthcare providers, pharmacists, and patients (including parents of children). We describe the information content and technical development of ReadyVax. Between the hard launch of the app on February 12, 2015 and October 8, 2016, the app has been downloaded by 5,142 unique users, with 6,841 total app sessions initiated, comprising a total of 15,491 screen views (2.3 screens/session on average). ReadyVax has been downloaded by users in 102 different countries; most users (52%) are from the United States. We are continuing outreach efforts to increase app use, and planning for development of an Android-compatible version of ReadyVax, to increase the available market for the app. PMID:28059610

APP Regulates Microglial Phenotype in a Mouse Model of Alzheimer's Disease

PubMed Central

Manocha, Gunjan D.; Floden, Angela M.; Rausch, Keiko; Kulas, Joshua A.; McGregor, Brett A.; Rojanathammanee, Lalida; Puig, Kelley R.; Puig, Kendra L.; Karki, Sanjib; Nichols, Michael R.; Darland, Diane C.; Porter, James E.

2016-01-01

Prior work suggests that amyloid precursor protein (APP) can function as a proinflammatory receptor on immune cells, such as monocytes and microglia. Therefore, we hypothesized that APP serves this function in microglia during Alzheimer's disease. Although fibrillar amyloid β (Aβ)-stimulated cytokine secretion from both wild-type and APP knock-out (mAPP−/−) microglial cultures, oligomeric Aβ was unable to stimulate increased secretion from mAPP−/− cells. This was consistent with an ability of oligomeric Aβ to bind APP. Similarly, intracerebroventricular infusions of oligomeric Aβ produced less microgliosis in mAPP−/− mice compared with wild-type mice. The mAPP−/− mice crossed to an APP/PS1 transgenic mouse line demonstrated reduced microgliosis and cytokine levels and improved memory compared with wild-type mice despite robust fibrillar Aβ plaque deposition. These data define a novel function for microglial APP in regulating their ability to acquire a proinflammatory phenotype during disease. SIGNIFICANCE STATEMENT A hallmark of Alzheimer's disease (AD) brains is the accumulation of amyloid β (Aβ) peptide within plaques robustly invested with reactive microglia. This supports the notion that Aβ stimulation of microglial activation is one source of brain inflammatory changes during disease. Aβ is a cleavage product of the ubiquitously expressed amyloid precursor protein (APP) and is able to self-associate into a wide variety of differently sized and structurally distinct multimers. In this study, we demonstrate both in vitro and in vivo that nonfibrillar, oligomeric forms of Aβ are able to interact with the parent APP protein to stimulate microglial activation. This provides a mechanism by which metabolism of APP results in possible autocrine or paracrine Aβ production to drive the microgliosis associated with AD brains. PMID:27511018

How a mobile app supports the learning and practice of newly qualified doctors in the UK: an intervention study.

PubMed

Bullock, Alison; Dimond, Rebecca; Webb, Katie; Lovatt, Joseph; Hardyman, Wendy; Stacey, Mark

2015-04-08

The transition from medical school to the workplace can be demanding, with high expectations placed on newly qualified doctors. The provision of up-to-date and accurate information is essential to support doctors at a time when they are managing increased responsibility for patient care. In August 2012, the Wales Deanery issued the Dr.Companion© software with five key medical textbooks (the iDoc app) to newly qualified doctors (the intervention). The aim of the study was to examine how a smartphone app with key medical texts was used in clinical workplace settings by newly qualified doctors in relation to other information sources and to report changes over time. Participants (newly qualified - Foundation Year 1 - doctors) completed a baseline questionnaire before downloading the iDoc app to their own personal smartphone device. At the end of Foundation Year 1 participants (n = 125) completed exit questionnaires one year later. We used Wilcoxon Signed Rank test to analyse matched quantitative data. We report significant changes in our participants' use of workplace information resources over the year. Respondents reduced their use of hard-copy and electronic versions of texts on PCs but made more use of senior medical staff. There was no significant difference in the use of peers and other staff as information sources. We found a significant difference in how doctors felt about using a mobile device containing textbooks in front of patients and senior medical staff in the workplace. Our study indicates that a mobile app enabling timely, internet-free access to key textbooks supports the learning and practice of newly qualified doctors. Although participants changed their use of other resources in the workplace, they continued to consult with seniors. Rather than over-reliance on technology, these findings suggest that the app was used strategically to complement, not replace discussion with members of the medical team. Participants' uncertainty about using a

Direct ex vivo detection of HLA-DR3-restricted cytomegalovirus- and Mycobacterium tuberculosis-specific CD4+ T cells.

PubMed

Bronke, Corine; Palmer, Nanette M; Westerlaken, Geertje H A; Toebes, Mireille; van Schijndel, Gijs M W; Purwaha, Veenu; van Meijgaarden, Krista E; Schumacher, Ton N M; van Baarle, Debbie; Tesselaar, Kiki; Geluk, Annemieke

2005-09-01

In order to detect epitope-specific CD4+ T cells in mycobacterial or viral infections in the context of human class II major histocompatibility complex protein human leukocyte antigen (HLA)-DR3, two HLA-DR3 tetrameric molecules were successfully produced. One contained an immunodominant HLA-DR3-restricted T-cell epitope derived from the 65-kDa heat-shock protein of Mycobacterium tuberculosis, peptide 1-13. For the other tetramer, we used an HLA-DR3-restricted T-cell epitope derived from cytomegalovirus (CMV) pp65 lower matrix protein, peptide 510-522, which induced high levels of interferon (IFN)-gamma-producing CD4+ T cells in three of four HLA-DR3-positive CMV-seropositive individuals up to 0.84% of CD4+ T cells by intracellular cytokine staining. In peripheral blood mononuclear cells from M. tuberculosis-exposed, Mycobacterium bovis bacille Calmette-Guérin (BCG)-vaccinated, or CMV-seropositive individuals, we were able to directly detect with both tetramers epitope-specific T cells up to 0.62% and 0.45% of the CD4+ T-cell population reactive to M. tuberculosis and CMV, respectively. After a 6-day culture with peptide p510-522, the frequency of CMV-specific tetramer-binding T cells was expanded up to 9.90% tetramer+ CFSElow (5,6-carboxyfluorescein diacetate succinimidyl ester) cells within the CD4+ T-cell population, further confirming the specificity of the tetrameric molecules. Thus, HLA-DR3/peptide tetrameric molecules can be used to investigate HLA-DR3-restricted antigen-specific CD4+ T cells in clinical disease or after vaccination.

Smartphone Apps for Measuring Human Health and Climate Change Co-Benefits: A Comparison and Quality Rating of Available Apps.

PubMed

Sullivan, Rachel K; Marsh, Samantha; Halvarsson, Jakob; Holdsworth, Michelle; Waterlander, Wilma; Poelman, Maartje P; Salmond, Jennifer Ann; Christian, Hayley; Koh, Lenny Sc; Cade, Janet E; Spence, John C; Woodward, Alistair; Maddison, Ralph

2016-12-19

Climate change and the burden of noncommunicable diseases are major global challenges. Opportunities exist to investigate health and climate change co-benefits through a shift from motorized to active transport (walking and cycling) and a shift in dietary patterns away from a globalized diet to reduced consumption of meat and energy dense foods. Given the ubiquitous use and proliferation of smartphone apps, an opportunity exists to use this technology to capture individual travel and dietary behavior and the associated impact on the environment and health. The objective of the study is to identify, describe the features, and rate the quality of existing smartphone apps which capture personal travel and dietary behavior and simultaneously estimate the carbon cost and potential health consequences of these actions. The Google Play and Apple App Stores were searched between October 19 and November 6, 2015, and a secondary Google search using the apps filter was conducted between August 8 and September 18, 2016. Eligible apps were required to estimate the carbon cost of personal behaviors with the potential to include features to maximize health outcomes. The quality of included apps was assessed by 2 researchers using the Mobile Application Rating Scale (MARS). Out of 7213 results, 40 apps were identified and rated. Multiple travel-related apps were identified, however no apps solely focused on the carbon impact or health consequences of dietary behavior. None of the rated apps provided sufficient information on the health consequences of travel and dietary behavior. Some apps included features to maximize participant engagement and encourage behavior change towards reduced greenhouse gas emissions. Most apps were rated as acceptable quality as determined by the MARS; 1 was of poor quality and 10 apps were of good quality. Interrater reliability of the 2 evaluators was excellent (ICC=0.94, 95% CI 0.87-0.97). Existing apps capturing travel and dietary behavior and the

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

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

PubMed Central

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

2013-01-01

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

[Reproduction,genotype identification and evaluation of APP/PS1 transgenic mice].

PubMed

Tan, Long; Li, Hai-Qiang; Li, Yi-Bo; Liu, Wei; Pang, Wei; Jiang, Yu-Gang

2018-02-08

To identify the genotype of (APP/PS1) transgenic mice and evaluate the changing of cognitive and behavioral fu nctions, provide an effective animal model for the Alzheimer's disease (AD) research. Male APP/PS1 transgenic mice mated with female APP/PS1 transgenic mice, and the genotype of their filial mice was identified by PCR. The APP +/PS1 + mice were assigned into AD model group (AD group, n =8), and the APP/PS1 mice were assigned into control group (CT group, n =8). The Morris water maze test was carried out to detect the capacity of learning and memory of mice. After that, the mice were sacrificed and the brain tissues were sampled and stained by HE and congo red for the pathological examination. ①A APP/PS1 genome DNA about 360 bp size was detected. The methods of feeding and breeding were successful to attain APP/PS1 transgenic mice.②Statistical significance was found in the differences of the capacity of learning and memory between 7-month-old APP/PS1 positive mice and negative mice ( P <0.05).③The results of HE stain showed that the structure and cellular morphology of hippocampus of AD mice were obviously abnormal. The results of congo red stain showed that positive amyloid plaque was observed in brains of AD mice. APP/PS1 transgenic mice present typical symptoms and behaviors of Alzheimer's disease. The transgenic mouse is an effective tool for the research and prevention of AD.

Enriched endogenous n-3 polyunsaturated fatty acids alleviate cognitive and behavioral deficits in a mice model of Alzheimer's disease.

PubMed

Wu, Kefeng; Gao, Xiang; Shi, Baoyan; Chen, Shiyu; Zhou, Xin; Li, Zhidong; Gan, Yuhong; Cui, Liao; Kang, Jing Xuan; Li, Wende; Huang, Ren

2016-10-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accompanied by memory deficits and neuropsychiatric dysfunction. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have seemly therapeutic potential in AD, but the benefit of n-3 PUFAs is still in debates. Here, we employed a transgenic mice carry fat-1 gene to encode n-3 desaturase from Caenorhabditis elegans, which increase endogenous n-3 PUFAs by converting n-6 PUFAs to n-3 PUFAs crossed with amyloid precursor protein (APP) Tg mice to evaluate the protective effects of endogenous n-3 PUFAs on cognitive and behavioral deficits of APP Tg mice. We fed APP, APP/fat-1 and fat-1 mice with n-6 PUFAs rich diet. Brain tissues were collected at 3, 9 and 12 months for fatty acid and gene expression analysis, histology and protein assays. Morris Water Maze Test, open field test and elevated plus maze test were performed to measure the behavior capability. From the results, the expression of fat-1 transgene increased cortical n-3: n-6 PUFAs ratio and n-3 PUFAs concentrations, and sensorimotor dysfunction and cognitive deficits in AD were significantly less severe in APP/fat-1 mice with endogenous n-3 PUFAs than in APP mice controls. The protection against disturbance of spontaneous motor activity and cognitive deficits in AD was strongly correlated with increased n-3: n-6 PUFAs ratio and endogenous n-3 PUFAs, reduced APP generation, inhibited amyloid β peptide aggregation, suppressed nuclear factor-kappa B and astroglia activation, and reduced death of neurons in the cortex of APP/fat-1 mice compared with APP mice controls. In conclusion, our study demonstrates that an available medication with the maintenance of enriched n-3 PUFAs in the brain could slow down cognitive decline and prevent neuropsychological disorder in AD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2014-09-09

Facebook is the most popular social network site, with over 1 billion users globally. There are millions of apps available within Facebook, many of which address health and health behavior change. Facebook may represent a promising channel to reach smokers with cessation interventions via apps. To date, there have been no published reports about Facebook apps for smoking cessation. The purpose of this study was to review the features and functionality of Facebook apps for smoking cessation and to determine the extent to which they adhere to evidence-based guidelines for tobacco dependence treatment. In August 2013, we searched Facebook and three top Internet search engines using smoking cessation keywords to identify relevant Facebook apps. Resultant apps were screened for eligibility (smoking cessation-related, English language, and functioning). Eligible apps were reviewed by 2 independent coders using a standardized coding scheme. Coding included content features (interactive, informational, and social) and adherence to an established 20-item index (possible score 0-40) derived from the US Public Health Service's Clinical Practice Guidelines for Treating Tobacco Use and Dependence. We screened 22 apps for eligibility; of these, 12 underwent full coding. Only 9 apps were available on Facebook. Facebook apps fell into three broad categories: public pledge to quit (n=3), quit-date-based calculator/tracker (n=4), or a multicomponent quit smoking program (n=2). All apps incorporated interactive, informational, and social features except for two quit-date-based calculator/trackers apps (lacked informational component). All apps allowed app-related posting within Facebook (ie, on self/other Facebook profile), and four had a within-app "community" feature to enable app users to communicate with each other. Adherence index summary scores among Facebook apps were low overall (mean 15.1, SD 7.8, range 7-30), with multicomponent apps scoring the highest. There are few

Evaluating Instructional Apps Using the App Checklist for Educators (ACE)

ERIC Educational Resources Information Center

Lubniewski, Kathryn L.; McArthur, Carol L.; Harriott, Wendy

2018-01-01

The use of iPads and apps has become common in K-12 inclusive classrooms. Special education teachers frequently use this tool to support instruction. Data from electronic surveys were used to determine criteria that teachers identified as important for choosing apps for classroom use. Using this information, the authors developed an App Checklist…

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

PubMed

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

2012-05-14

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

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.

Calcium ion binding to a soil fulvic acid using a donnan potential model

USGS Publications Warehouse

Marinsky, J.A.; Mathuthu, A.; Ephraim, J.H.; Reddy, M.M.

1999-01-01

Calcium ion binding to a soil fulvic acid (Armadale Bh Horizon) was evaluated over a range of calcium ion concentrations, from pH 3.8 to 7.3, using potentiometric titrations and calcium ion electrode measurements. Fulvic acid concentration was constant (100 milligrams per liter) and calcium ion concentration varied up to 8 X 10-4 moles per liter. Experiments discussed here included: (1) titrations of fulvic acid-calcium ion containing solutions with sodium hydroxide; and (2) titrations of fully neutralized fulvic acid with calcium chloride solutions. Apparent binding constants (expressed as the logarithm of the value, log ??app) vary with solution pH, calcium ion concentration, degree of acid dissociation, and ionic strength (from log ??app = 2.5 to 3.9) and are similar to those reported by others. Fulvic acid charge, and the associated Donnan Potential, influences calcium ion-fulvic acid ion pair formation. A Donnan Potential corrrection term allowed calculation of intrinsic calcium ion-fulvic acid binding constants. Intrinsic binding constants vary from 1.2 to 2.5 (the average value is about log??= 1.6) and are similar to, but somewhat higher than, stability constants for calcium ion-carboxylic acid monodentate complexes. ?? by Oldenbourg Wissenschaftsverlag, Mu??nchen.

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

Insight into inhibition of the human amyloid beta protein precursor (APP: PDB ID ) using (E)-N-(pyridin-2-ylmethylene)arylamine (LR) models: structure elucidation of a family of ZnX2-LR complexes.

PubMed

Basu Baul, Tushar S; Kundu, Sajal; Singh, Palwinder; Shaveta; Guedes da Silva, M Fátima C

2015-02-07

The amyloid beta precursor protein (APP) and its neurotoxic cleavage product amyloid beta (Aβ) are a cause of Alzheimer's disease and appear essential for neuronal development and cell homeostasis. Proteolytic processing of APP is influenced by metal ions and protein ligands, however the structural and functional mechanism of APP regulation is not known so far. In this context, molecular modeling studies were performed to understand the molecular behavior of (E)-N-(pyridin-2-ylmethylene)arylamines (LR) with an E2 domain of the APP in its complex with zinc (APP; PDB ID: ). Docking results indeed confirmed that the LR interacts with Zn in the binding site of the protein between two α-helical chains. In view of these findings, LR was further investigated for complexation reactions with Zn(2+) in order to establish the structural models in solution and in the solid state. Five new Zn(2+) complexes of compositions viz. [Zn(Br)2(L2-Me)] (), [Zn(Br)2(L2-OMe)] (), [Zn(i)2(L2-OMe)] (), [Zn(NO3)2(L2-OMe)(H2O)] () and [Zn(L4-Me)2(H2O)2](NO3)2 () were synthesized and their structures were ascertained by microanalysis, IR and (1)H NMR spectroscopy, and single-crystal X-ray diffraction. The zinc atom in complex exhibits a distorted tetrahedral geometry while the crystal structures of complexes and show distorted square pyramidal geometries. The zinc cation in and has an octahedral coordination environment, but in the zinc coordination geometry is less distorted. The Zn(ii) cations take part in one ( and ) or two () 5-membered metallacycles imposed by the NN or NNO chelation modes of LR. The significant intermolecular ππ interactions are also discussed.

Security Recommendations for mHealth Apps: Elaboration of a Developer's Guide.

PubMed

Morera, Enrique Pérez; de la Torre Díez, Isabel; Garcia-Zapirain, Begoña; López-Coronado, Miguel; Arambarri, Jon

2016-06-01

Being the third fastest-growing app category behind games and utilities, mHealth apps are changing the healthcare model, as medicine today involves the data they compile and analyse, information known as Big Data. However, the majority of apps are lacking in security when gathering and dealing with the information, which becomes a serious problem. This article presents a guide regarding security solution, intended to be of great use for developers of mHealth apps. In August 2015 current mobile health apps were sought out in virtual stores such as Android Google Play, Apple iTunes App Store etc., in order to classify them in terms of usefulness. After this search, the most widespread weaknesses in the field of security in the development of these mobile apps were examined, based on sources such as the "OWASP Mobile Security Project, the initiative recently launched by the Office of Civil Rights (OCR), and other articles of scientific interest. An informative, elemental guide has been created for the development of mHealth apps. It includes information about elements of security and its implementation on different levels for all types of mobile health apps based on the data that each app manipulates, the associated calculated risk as a result of the likelihood of occurrence and the threat level resulting from its vulnerabilities - high level (apps for monitoring, diagnosis, treatment and care) from 6 ≤ 9, medium level (calculator, localizer and alarm) from 3 ≤ 6 and low level (informative and educational apps) from 0 ≤ 3. The guide aims to guarantee and facilitate security measures in the development of mobile health applications by programmers unconnected to the ITC and professional health areas.

Enhanced Human-Type Receptor Binding by Ferret-Transmissible H5N1 with a K193T Mutation.

PubMed

Peng, Wenjie; Bouwman, Kim M; McBride, Ryan; Grant, Oliver C; Woods, Robert J; Verheije, Monique H; Paulson, James C; de Vries, Robert P

2018-05-15

All human influenza pandemics have originated from avian influenza viruses. Although multiple changes are needed for an avian virus to be able to transmit between humans, binding to human-type receptors is essential. Several research groups have reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets. Upon detailed analysis, we have found that these mutants exhibit significant differences in fine receptor specificity compared to human H1N1 and H3N2 and retain avian-type receptor binding. We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer. In this binding mode, the glycan projects over the 190 helix at the top of the receptor-binding pocket, which in H5N1 would create a stearic clash with lysine at position 193. Thus, we hypothesized that a K193T mutation would improve binding to branched N-linked receptors. Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses. IMPORTANCE Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans. Fortunately, H5N1 viruses do not transmit between humans because they do not bind to human-type receptors. In 2012, three seminal papers have shown how these viruses can be engineered to transmit between ferrets, the human model for influenza virus infection. Receptor binding, among others, was changed, and the viruses now bind to human-type receptors. Receptor specificity was still markedly different compared to that of human influenza viruses. Here we report an additional mutation in ferret

Starting the Conversation - A Childhood Obesity Knowledge Project Using an App.

PubMed

Appel, Hoa B; Huang, Bu; Cole, Allison; James, Rosalina; Ai, Amy L

2014-04-01

Starting the Conversation was a pilot project to test an intervention for childhood obesity, a major public health epidemic, using a free smartphone application (app). The primary aim was to assess students' knowledge of nutritional indicators, physical exercise and use of screen time before and after the intervention. The study was conducted in 2011-2012. The sample, recruited from seven high schools in Snohomish County, Washington, was 65.3% minority participants. Of the 118 participants in the sample (n=118), 79 handwrote their responses (n=78) and 36 responded via the app (n=39). We compared the frequency and types of physical exercise, frequency of screen time, and nutritional variables of high school students. Participants used the cell phone app or a handwritten log to record their daily entries for 20 days. Both males (n=43) and females (n=75) grades 9-12 used the app or handwritten entries. Participants who used the app ate less fast food and exercised more, as compared with those who recorded their entries by hand. Screen time usage decreased over the course of the study, based on a comparison of the post-survey level and the pre-survey level. Knowledge of recommended daily consumption of vegetables increased post-test in the app group and knowledge of water consumption increased significantly in both groups. There was no significant difference in BMI pre and post-test. Patterns of nutritional intake, physical exercise and knowledge of these issues varied pre and post-test. It is critical to further examine factors associated with lack of physical activity and food intake patterns of youth using social media to further address the childhood obesity epidemic. Future research should focus on specific ethnic subgroups and an intervention at the school level aimed at the students with BMI ≥ 95 th percentile.

Autoinhibition of ETV6 DNA Binding Is Established by the Stability of Its Inhibitory Helix

PubMed Central

De, Soumya; Okon, Mark; Graves, Barbara J.; McIntosh, Lawrence P.

2017-01-01

The ETS transcriptional repressor ETV6 (or TEL) is autoinhibited by an α-helix that sterically blocks its DNA-binding ETS domain. The inhibitory helix is marginally stable and unfolds when ETV6 binds to either specific or non-specific DNA. Using NMR spectroscopy, we show that folding of the inhibitory helix requires a buried charge–dipole interaction with helix H1 of the ETS domain. This interaction also contributes directly to autoinhibition by precluding a highly conserved dipole-enhanced hydrogen bond between the phosphodiester backbone of bound DNA and the N terminus of helix H1. To probe further the thermodynamic basis of autoinhibition, ETV6 variants were generated with amino acid substitutions introduced along the solvent exposed surface of the inhibitory helix. These changes were designed to increase the intrinsic helical propensity of the inhibitory helix without perturbing its packing interactions with the ETS domain. NMR-monitored amide hydrogen exchange measurements confirmed that the stability of the folded inhibitory helix increases progressively with added helix-promoting substitutions. This also results in progressively reinforced autoinhibition and decreased DNA-binding affinity. Surprisingly, locking the inhibitory helix onto the ETS domain by a disulfide bridge severely impairs, but does not abolish DNA binding. Weak interactions still occur via an interface displaced from the canonical ETS domain DNA-binding surface. Collectively, these studies establish a direct thermodynamic linkage between inhibitory helix stability and ETV6 autoinhibition, and demonstrate that helix unfolding does not strictly precede DNA binding. Modulating inhibitory helix stability provides a potential route for the in vivo regulation of ETV6 activity. PMID:26920109

Improving specific activity and thermostability of Escherichia coli phytase by structure-based rational design.

PubMed

Wu, Tzu-Hui; Chen, Chun-Chi; Cheng, Ya-Shan; Ko, Tzu-Ping; Lin, Cheng-Yen; Lai, Hui-Lin; Huang, Ting-Yung; Liu, Je-Ruei; Guo, Rey-Ting

2014-04-10

Escherichia coli phytase (EcAppA) which hydrolyzes phytate has been widely applied in the feed industry, but the need to improve the enzyme activity and thermostability remains. Here, we conduct rational design with two strategies to enhance the EcAppA performance. First, residues near the substrate binding pocket of EcAppA were modified according to the consensus sequence of two highly active Citrobacter phytases. One out of the eleven mutants, V89T, exhibited 17.5% increase in catalytic activity, which might be a result of stabilized protein folding. Second, the EcAppA glycosylation pattern was modified in accordance with the Citrobacter phytases. An N-glycosylation motif near the substrate binding site was disrupted to remove spatial hindrance for phytate entry and product departure. The de-glycosylated mutants showed 9.6% increase in specific activity. On the other hand, the EcAppA mutants that adopt N-glycosylation motifs from CbAppA showed improved thermostability that three mutants carrying single N-glycosylation motif exhibited 5.6-9.5% residual activity after treatment at 80°C (1.8% for wild type). Furthermore, the mutant carrying all three glycosylation motifs exhibited 27% residual activity. In conclusion, a successful rational design was performed to obtain several useful EcAppA mutants with better properties for further applications. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Review and Evaluation of Mindfulness-Based iPhone Apps

PubMed Central

Kavanagh, David J; Hides, Leanne; Stoyanov, Stoyan R

2015-01-01

Background There is growing evidence for the positive impact of mindfulness on wellbeing. Mindfulness-based mobile apps may have potential as an alternative delivery medium for training. While there are hundreds of such apps, there is little information on their quality. Objective This study aimed to conduct a systematic review of mindfulness-based iPhone mobile apps and to evaluate their quality using a recently-developed expert rating scale, the Mobile Application Rating Scale (MARS). It also aimed to describe features of selected high-quality mindfulness apps. Methods A search for “mindfulness” was conducted in iTunes and Google Apps Marketplace. Apps that provided mindfulness training and education were included. Those containing only reminders, timers or guided meditation tracks were excluded. An expert rater reviewed and rated app quality using the MARS engagement, functionality, visual aesthetics, information quality and subjective quality subscales. A second rater provided MARS ratings on 30% of the apps for inter-rater reliability purposes. Results The “mindfulness” search identified 700 apps. However, 94 were duplicates, 6 were not accessible and 40 were not in English. Of the remaining 560, 23 apps met inclusion criteria and were reviewed. The median MARS score was 3.2 (out of 5.0), which exceeded the minimum acceptable score (3.0). The Headspace app had the highest average score (4.0), followed by Smiling Mind (3.7), iMindfulness (3.5) and Mindfulness Daily (3.5). There was a high level of inter-rater reliability between the two MARS raters. Conclusions Though many apps claim to be mindfulness-related, most were guided meditation apps, timers, or reminders. Very few had high ratings on the MARS subscales of visual aesthetics, engagement, functionality or information quality. Little evidence is available on the efficacy of the apps in developing mindfulness. PMID:26290327

Review and Evaluation of Mindfulness-Based iPhone Apps.

PubMed

Mani, Madhavan; Kavanagh, David J; Hides, Leanne; Stoyanov, Stoyan R

2015-08-19

There is growing evidence for the positive impact of mindfulness on wellbeing. Mindfulness-based mobile apps may have potential as an alternative delivery medium for training. While there are hundreds of such apps, there is little information on their quality. This study aimed to conduct a systematic review of mindfulness-based iPhone mobile apps and to evaluate their quality using a recently-developed expert rating scale, the Mobile Application Rating Scale (MARS). It also aimed to describe features of selected high-quality mindfulness apps. A search for "mindfulness" was conducted in iTunes and Google Apps Marketplace. Apps that provided mindfulness training and education were included. Those containing only reminders, timers or guided meditation tracks were excluded. An expert rater reviewed and rated app quality using the MARS engagement, functionality, visual aesthetics, information quality and subjective quality subscales. A second rater provided MARS ratings on 30% of the apps for inter-rater reliability purposes. The "mindfulness" search identified 700 apps. However, 94 were duplicates, 6 were not accessible and 40 were not in English. Of the remaining 560, 23 apps met inclusion criteria and were reviewed. The median MARS score was 3.2 (out of 5.0), which exceeded the minimum acceptable score (3.0). The Headspace app had the highest average score (4.0), followed by Smiling Mind (3.7), iMindfulness (3.5) and Mindfulness Daily (3.5). There was a high level of inter-rater reliability between the two MARS raters. Though many apps claim to be mindfulness-related, most were guided meditation apps, timers, or reminders. Very few had high ratings on the MARS subscales of visual aesthetics, engagement, functionality or information quality. Little evidence is available on the efficacy of the apps in developing mindfulness.

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…

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.

easyHealthApps: e-Health Apps dynamic generation for smartphones & tablets.

PubMed

Paschou, Mersini; Sakkopoulos, Evangelos; Tsakalidis, Athanasios

2013-06-01

Mobile phones and especially smartphones have been embraced by a rapidly increasing number of people worldwide and this trend is expected to evolve even more in the years to come. There are numerous smartphone Apps that record critical medical data in an effort to solve a particular health issue each time. We studied such applications and not surprisingly, we have found that development and design effort is often repeated. Software patterns have been detected to exist, however re-usability has not been enforced. This leads to lost programming manpower and to increased probability of repeating bugs in Apps. Moreover, at the moment smartphone e-Health Apps demand time, effort and costs for development. Unfortunately even simple data recording Apps are practically impossible to be produced by multiple health domain users who are not developers. In this work, we propose, design and implement a simple and integrated solution which gives healthcare professionals and researchers the ability to create their own data intensive smartphone applications, independent of the desired healthcare domain. The proposed approach applies efficient software techniques that hide development from the users and enable App creation through a simple Web User Interface. The Apps produced are in native format and it is possible to dynamically receive m-Health business logic and the chosen UI. Evaluation of the proposed solution has shown that the generated Apps are functionally and UI equivalent to human-coded Apps according to a number of comparison parameters. Furthermore, e-Health professionals show particular interest in developing Apps on their own for a particular domain they focus on.

Low Quality of Free Coaching Apps With Respect to the American College of Sports Medicine Guidelines: A Review of Current Mobile Apps

PubMed Central

Bian, Jiang; Leavitt, Trevor; Bromwell, Jennifer; Harris III, Charles; Vincent, Heather

2015-01-01

Background Low physical activity level is a significant contributor to chronic disease, weight dysregulation, and mortality. Nearly 70% of the American population is overweight, and 35% is obese. Obesity costs an estimated US$ 147 billion annually in health care, and as many as 95 million years of life. Although poor nutritional habits remain the major culprit, lack of physical activity significantly contributes to the obesity epidemic and related lifestyle diseases. Objective Over the past 10 years, mobile devices have become ubiquitous, and there is an ever-increasing number of mobile apps that are being developed to facilitate physical activity, particularly for active people. However, no systematic assessment has been performed about their quality with respect to following the parameters of sound fitness principles and scientific evidence, or suitability for a variety of fitness levels. The aim of this paper is to fill this gap and assess the quality of mobile coaching apps on iOS mobile devices. Methods A set of 30 popular mobile apps pertaining to physical activity programming was identified and reviewed on an iPhone device. These apps met the inclusion criteria and provided specific prescriptive fitness and exercise programming content. The content of these apps was compared against the current guidelines and fitness principles established by the American College of Sports Medicine (ACSM). A weighted scoring method based on the recommendations of the ACSM was developed to generate subscores for quality of programming content for aerobic (0-6 scale), resistance (0-6 scale), and flexibility (0-2 scale) components using the frequency, intensity, time, and type (FITT) principle. An overall score (0-14 scale) was generated from the subscores to represent the overall quality of a fitness coaching app. Results Only 3 apps scored above 50% on the aerobic component (mean 0.7514, SD 1.2150, maximum 4.1636), 4 scored above 50% on the resistance/strength component (mean

Low Quality of Free Coaching Apps With Respect to the American College of Sports Medicine Guidelines: A Review of Current Mobile Apps.

PubMed

Modave, François; Bian, Jiang; Leavitt, Trevor; Bromwell, Jennifer; Harris Iii, Charles; Vincent, Heather

2015-07-24

Low physical activity level is a significant contributor to chronic disease, weight dysregulation, and mortality. Nearly 70% of the American population is overweight, and 35% is obese. Obesity costs an estimated US$ 147 billion annually in health care, and as many as 95 million years of life. Although poor nutritional habits remain the major culprit, lack of physical activity significantly contributes to the obesity epidemic and related lifestyle diseases. Over the past 10 years, mobile devices have become ubiquitous, and there is an ever-increasing number of mobile apps that are being developed to facilitate physical activity, particularly for active people. However, no systematic assessment has been performed about their quality with respect to following the parameters of sound fitness principles and scientific evidence, or suitability for a variety of fitness levels. The aim of this paper is to fill this gap and assess the quality of mobile coaching apps on iOS mobile devices. A set of 30 popular mobile apps pertaining to physical activity programming was identified and reviewed on an iPhone device. These apps met the inclusion criteria and provided specific prescriptive fitness and exercise programming content. The content of these apps was compared against the current guidelines and fitness principles established by the American College of Sports Medicine (ACSM). A weighted scoring method based on the recommendations of the ACSM was developed to generate subscores for quality of programming content for aerobic (0-6 scale), resistance (0-6 scale), and flexibility (0-2 scale) components using the frequency, intensity, time, and type (FITT) principle. An overall score (0-14 scale) was generated from the subscores to represent the overall quality of a fitness coaching app. Only 3 apps scored above 50% on the aerobic component (mean 0.7514, SD 1.2150, maximum 4.1636), 4 scored above 50% on the resistance/strength component (mean 1.4525, SD 1.2101, maximum 4

Anxiety: There is an app for that. A systematic review of anxiety apps.

PubMed

Sucala, Madalina; Cuijpers, Pim; Muench, Frederick; Cardoș, Roxana; Soflau, Radu; Dobrean, Anca; Achimas-Cadariu, Patriciu; David, Daniel

2017-06-01

Smartphones and mobile devices have become ubiquitous, and with the rapid advance of technology, the number of health applications (apps) that are available for consumers on these devices is constantly growing. In particular, there has been a recent proliferation of anxiety apps. However, there has been no review of the quality or content of these anxiety apps and little is known about their purpose, the features they contain, and their empirical support. The goal of this systematic review was to assess the commercially available anxiety apps. A list of anxiety apps was collected in January 2017, using the Power Search function of iTunes and Google Play. Of 5,078 identified apps, 52 met our inclusion criteria (i.e., being defined as an anxiety/worry relief app, and offering psychological techniques aimed primarily at reducing anxiety) and were further reviewed. The majority (67.3%) of the currently available anxiety apps were found to lack the involvement of health care professionals in their development, and very few (3.8%) of them have been rigorously tested. At the moment, although anxiety apps have the potential to enhance access to mental health care, there is a marked discrepancy between the wealth of commercially available apps, and the paucity of data regarding their efficacy and effectiveness. Although the great promise of apps is their ability to increasing access to evidence-based mental health, the field is not quite there yet and the full potential of apps for treating anxiety has yet to be exploited. © 2017 Wiley Periodicals, Inc.

Neurobiology of nAChRs and cognition: A mini review of Dr. Jerry J. Buccafusco's contributions over a 25 year career

PubMed Central

Terry, Alvin V.; Decker, Michael W.

2011-01-01

This review highlights some of the many contributions of the late Dr. Jerry J. Buccafusco to the neurobiology of nicotinic acetylcholine receptors (nAChRs) and cognition over a 25 year period. The article is written by two of Dr. Buccafusco's professional colleagues, one from academia and one from the pharmaceutical industry. While Dr. Buccafusco's expertise in the cholinergic field was extensive, his insights into the practical relevance of his work (with a long-term goal of formulating new drug development strategies) were unique, and a great asset to both the basic science community and pharmaceutical companies. In 1988, Dr. Buccafusco's laboratory was the first to report the cognitive enhancing action of low doses of nicotine in non-human primates. Since that time he studied a large number of novel pro-cognitive agents from several pharmacological classes in rodents as well as monkeys. Based on years of observing paradoxical effects of nicotinic ligands in vitro and in vivo, Dr. Buccafusco made the provocative argument that it might be possible to develop new chemical entities (with pro-cognitive actions) that have the ability to desensitize nAChRs without producing an antecedent agonist action. Some of his more recent work focused on development of single molecular entities that act on multiple CNS targets (including nAChRs) to enhance cognition, provide neuroprotection, and/or provide additional therapeutic actions (e.g., antipsychotic effects). Dr. Buccafusco's influence will live on in the work of the numerous graduate students, postdoctoral fellows, and junior faculty that he mentored over the years who now serve in prestigious positions throughout the world. PMID:21684265

Amino acid polymorphisms in the fibronectin-binding repeats of fibronectin-binding protein A affect bond strength and fibronectin conformation.

PubMed

Casillas-Ituarte, Nadia N; Cruz, Carlos H B; Lins, Roberto D; DiBartola, Alex C; Howard, Jessica; Liang, Xiaowen; Höök, Magnus; Viana, Isabelle F T; Sierra-Hernández, M Roxana; Lower, Steven K

2017-05-26

The Staphylococcus aureus cell surface contains cell wall-anchored proteins such as fibronectin-binding protein A (FnBPA) that bind to host ligands ( e.g. fibronectin; Fn) present in the extracellular matrix of tissue or coatings on cardiac implants. Recent clinical studies have found a correlation between cardiovascular infections caused by S. aureus and nonsynonymous SNPs in FnBPA. Atomic force microscopy (AFM), surface plasmon resonance (SPR), and molecular simulations were used to investigate interactions between Fn and each of eight 20-mer peptide variants containing amino acids Ala, Asn, Gln, His, Ile, and Lys at positions equivalent to 782 and/or 786 in Fn-binding repeat-9 of FnBPA. Experimentally measured bond lifetimes (1/ k off ) and dissociation constants ( K d = k off / k on ), determined by mechanically dissociating the Fn·peptide complex at loading rates relevant to the cardiovascular system, varied from the lowest-affinity H782A/K786A peptide (0.011 s, 747 μm) to the highest-affinity H782Q/K786N peptide (0.192 s, 15.7 μm). These atomic force microscopy results tracked remarkably well to metadynamics simulations in which peptide detachment was defined solely by the free-energy landscape. Simulations and SPR experiments suggested that an Fn conformational change may enhance the stability of the binding complex for peptides with K786I or H782Q/K786I ( K d app = 0.2-0.5 μm, as determined by SPR) compared with the lowest-affinity double-alanine peptide ( K d app = 3.8 μm). Together, these findings demonstrate that amino acid substitutions in Fn-binding repeat-9 can significantly affect bond strength and influence the conformation of Fn upon binding. They provide a mechanistic explanation for the observation of nonsynonymous SNPs in fnbA among clinical isolates of S. aureus that cause endovascular infections. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Characterizing user engagement with health app data: a data mining approach.

PubMed

Serrano, Katrina J; Coa, Kisha I; Yu, Mandi; Wolff-Hughes, Dana L; Atienza, Audie A

2017-06-01

The use of mobile health applications (apps) especially in the area of lifestyle behaviors has increased, thus providing unprecedented opportunities to develop health programs that can engage people in real-time and in the real-world. Yet, relatively little is known about which factors relate to the engagement of commercially available apps for health behaviors. This exploratory study examined behavioral engagement with a weight loss app, Lose It! and characterized higher versus lower engaged groups. Cross-sectional, anonymized data from Lose It! were analyzed (n = 12,427,196). This dataset was randomly split into 24 subsamples and three were used for this study (total n = 1,011,008). Classification and regression tree methods were used to identify subgroups of user engagement with one subsample, and descriptive analyses were conducted to examine other group characteristics associated with engagement. Data mining validation methods were conducted with two separate subsamples. On average, users engaged with the app for 29 days. Six unique subgroups were identified, and engagement for each subgroup varied, ranging from 3.5 to 172 days. Highly engaged subgroups were primarily distinguished by the customization of diet and exercise. Those less engaged were distinguished by weigh-ins and the customization of diet. Results were replicated in further analyses. Commercially-developed apps can reach large segments of the population, and data from these apps can provide insights into important app features that may aid in user engagement. Getting users to engage with a mobile health app is critical to the success of apps and interventions that are focused on health behavior change.

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

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

PubMed

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

2016-05-01

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

Teaching medicine with the help of "Dr. House".

PubMed

Jerrentrup, Andreas; Mueller, Tobias; Glowalla, Ulrich; Herder, Meike; Henrichs, Nadine; Neubauer, Andreas; Schaefer, Juergen R

2018-01-01

TV series such as "House MD", "Grey´s Anatomy" or "Emergency Room" are well perceived by medical students. Seminars featuring medical TV series such as "House MD" might serve as door-opener to attract medical students to learn more about rare diseases. The TV series "House MD" is troublesome for the main character Dr. House is an excellent diagnostician but at the same time a rather misanthropic person. Therefore, lecturing medicine with the help of "House MD" requires constant evaluation. From 2008 to 2016 we are using the well-known TV series "House MD" continuously to attract medical students and teach them about rare diseases as well as diagnostic strategies. We collected from 213 students a detailed questionnaire assessing their learning experience. 76.6% of our students (n = 157) reported to watching medical dramas on a regular basis. The Dr. House seminar was compared to traditional seminars and our students reported an improved learning effect (69.9%), better concentration (89.7%), higher motivation to participate (88.7%), and more fun (86.7%) (all p<0.001). The students see Dr. House's behavior quite critically. Likert assessment on a 5-point scale identified strong disagreement with Dr. House´s interpersonal skills in dealing with his colleagues (median = 1) and patients (median = 1). At the same time, the students strongly agreed with his outstanding diagnostic (median = 5) and therapeutic capabilities (median = 4). Medical students visiting a Dr. House teaching seminar are highly motivated to learn more about rare diseases. They were positively influenced by TV series such as Dr. House to improve their diagnostic and clinical skills. At the same time, they are critical enough not to see Dr. House as a role model for their own personality. Well performed medical TV shows such as Dr. House can successfully be used in an educational setting to motivate medical students to come into seminars to learn more about rare diseases.

Characterization of binding of N'-nitrosonornicotine to protein

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

Hughes, M.F.

1986-01-01

The NADPH-dependent activation of the carcinogenic nitrosamine, N'-nitrosonornicotine (NNN) to a reactive intermediate which binds covalently to protein was assessed using male Sprague-Dawley rat liver and lung microsomes. The NADPH-dependent covalent binding of (/sup 14/C)NNN to liver and lung microsomes was linear with time up to 90 and 45 min, respectively and was also linear with protein concentrations up to 3.0 and 2.0 mg/ml, respectively. The apparent K/sub m/ and V/sub max/ of the NADPH-dependent binding to liver microsomes were determined from the initial velocities. Addition of the thiols glutathione, cystein, N-acetylcysteine or 2-mercapthoethanol significantly decreased the non-NADPH-dependent binding tomore » liver microsomal protein, but did not affect the NADPH-dependent binding. Glutathione was required in order to observe any NADPH-dependent binding to lung microsomal protein. In lung microsomes, SKF-525A significantly decreased the NADPH-dependent binding by 79%. Replacement of an air atmosphere with N/sub 2/ or CO:O/sub 2/ (8:2) significantly decreased the NADPH-dependent binding of (/sup 14/C)NNN to liver microsomal protein by 40% or 27% respectively. Extensive covalent binding of (/sup 14/C)NNN to liver and muscle microsomal protein occurred in the absence of an NADPH-generating system, in the presence of 50% methanol and also to bovine serum albumin, indicating a nonenzymatic reaction. These data indicate that cytochrome P-450 is at least in part responsible for the metabolic activation of the carcinogen NNN, but also suggest additional mechanisms of activation.« less

Using WhatsApp and Facebook Online Social Groups for Smoking Relapse Prevention for Recent Quitters: A Pilot Pragmatic Cluster Randomized Controlled Trial.

PubMed

Cheung, Yee Tak Derek; Chan, Ching Han Helen; Lai, Chi-Keung Jonah; Chan, Wai Fung Vivian; Wang, Man Ping; Li, Ho Cheung William; Chan, Sophia Siu Chee; Lam, Tai-Hing

2015-10-22

Quit attempters often have episodes of smoking relapse before they eventually quit. Interactive text messaging through mobile phones has been shown to increase abstinence. This service can be potentially applied on the platform of a social networking service to help quitters maintain abstinence. Our aim was to determine if the group discussion and reminders via the WhatsApp or Facebook social group were effective to prevent smoking relapse in quitters who had stopped smoking recently. This was a single-blinded, parallel, 3-arm pilot cluster randomized controlled trial allocating recent quitters, who had completed an 8-week treatment and reported abstinence for at least 7 days, to WhatsApp (n=42), Facebook (n=40), and a control group (n=54). The 2 intervention groups participated in a 2-month online group discussion with either WhatsApp or Facebook moderated by a trained smoking cessation counselor and received a self-help booklet on smoking cessation. The control group only received the booklet. The primary outcome was the 2- and 6-month relapse rates, defined as the proportion of participants who smoked at least 5 cigarettes in 3 consecutive days. Fewer participants in the WhatsApp group (17%, 7/42) reported relapse than the control group (42.6%, 23/54) at 2-month (OR 0.27, 95% CI 0.10-0.71) and 6-month (40.5%, 17/42 vs 61.1%, 33/54; OR 0.43, 95% CI 0.19-0.99) follow-ups. The Facebook group (30.0%, 12/40) had an insignificantly lower relapse rate than the control group (42.6%, 23/54) at 2-month (OR 0.58, 95% CI 0.24-1.37) and 6-month (52.5%, 13/40 vs 61.1%, 33/54; OR 0.70, 95% CI 0.31-1.61) follow-ups. The WhatsApp social groups had more moderators' posts (median 60, IQR 25 vs median 32, IQR 7; P=.05) and participants' posts (median 35, IQR 50 vs median 6, IQR 9; P=.07) than their Facebook counterparts, but the difference was insignificant. The intervention via the WhatsApp social group was effective in reducing relapse probably because of enhanced discussion and

Delivery of Instructions via Mobile Social Media App Increases Quality of Bowel Preparation.

PubMed

Kang, Xiaoyu; Zhao, Lina; Leung, Felix; Luo, Hui; Wang, Limei; Wu, Ji; Guo, Xiaoyang; Wang, Xiangping; Zhang, Linhui; Hui, Na; Tao, Qin; Jia, Hui; Liu, Zhiguo; Chen, Zhangqin; Liu, Junjun; Wu, Kaichun; Fan, Daiming; Pan, Yanglin; Guo, Xuegang

2016-03-01

Bowel preparation is closely linked to the quality of colonoscopy. We investigated whether delivery of instructions via a social media app increases the quality of colonoscopy by improving adequacy of bowel preparation. We performed a prospective study at 3 endoscopic centers in China of 770 colonoscopy outpatients (18-80 years old) with convenient access to Wechat (a widely used mobile social media app) from May through November 2014. Patients were randomly assigned to groups that received standard education along with delivery of interactive information via Wechat (n = 387) or standard education (controls, n = 383). The primary outcome was proportion of patients with adequate bowel preparation (Ottawa score <6). Secondary outcomes included rates of adenoma detection and cecal intubation, cecal intubation time, rates of incomplete compliance with instructions, and patient willingness to repeat bowel preparation. Demographic features were comparable between the groups. A higher proportion of patients in the group that received social media instruction had adequate bowel preparation than the control group (82.2% vs 69.5%, P < .001). Among patients with successful colonoscopies, the group that received social media instruction had lower mean total and segmental Ottawa scores (P < .05). A higher proportion of patients receiving social media instruction also had cecal intubation (97.2% vs 93.2% in controls, P = .014) and were found to have adenomas (18.6% vs 12.0% in controls, P = .012). Instruction via a mobile social media app, in conjunction with regular instruction, increases subjective measures of adequacy of bowel preparation. Use of the app significantly increased the proportion of patients with successful cecal intubation and in whom adenomas were detected, indicating increased quality of colonoscopy. ClinicalTrials.gov number: NCT02140827. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

The Cytoscape app article collection

PubMed Central

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

2014-01-01

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

A Guide to Help Consumers Choose Apps and Avoid App Overload

ERIC Educational Resources Information Center

Schuster, Ellen; Zimmerman, Lynda

2014-01-01

Mobile technology has transformed the way consumers access and use information. The exponential growth of mobile apps makes finding suitable, easy-to-use nutrition and health-related apps challenging. A guide for consumers helps them ask important questions before downloading apps. The guide can be adapted for other Extension disciplines.

Health App Use Among Individuals With Symptoms of Depression and Anxiety: A Survey Study With Thematic Coding

PubMed Central

Rubanovich, Caryn Kseniya; Mohr, David C

2017-01-01

Background Researchers have largely turned to commercial app stores, randomized trials, and systematic reviews to make sense of the mHealth landscape. Few studies have approached understanding by collecting information from target end users. The end user perspective is critical as end user interest in and use of mHealth technologies will ultimately drive the efficacy of these tools. Objective The purpose of this study was to obtain information from end users of mHealth technologies to better understand the physical and mental health apps people use and for what purposes. Methods People with depressive or anxious symptoms (N=176) seeking entry into a trial of mental health and well-being apps for Android devices completed online questionnaires assessing depression and anxiety (Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7), past and current mental health treatment-seeking behavior, overall mobile device use, and use of mobile health apps. Participants reported the physical health and mental health apps on their devices and their reasons for using them. Data were extracted from the participant self-reports and apps and app purposes were coded in order to categorize them. Results Participants were largely white, middle-aged females from the Midwest region of the United States recruited via a health care organization and Web-based advertising (135 female, 41 male, mean age 38.64 years, age range 19-75 years.) Over three-quarters (137/176, 77.8%) of participants indicated having a health app on their device. The top 3 kinds of apps were exercise, fitness, and pedometers or heart rate monitoring apps (93/176, 52.8%); diet, food, or calorie counting apps (65/177, 36.9%); and mental health/wellness apps (46/177, 26.1%). The mean number of mobile physical and mental health apps on a participant’s phone was 2.15 (SD 3.195). Of 176 participants, 107 (60.8%) specifically reported the top 5 health apps that they used and their purposes. Across the 107

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

PubMed Central

2014-01-01

Background Facebook is the most popular social network site, with over 1 billion users globally. There are millions of apps available within Facebook, many of which address health and health behavior change. Facebook may represent a promising channel to reach smokers with cessation interventions via apps. To date, there have been no published reports about Facebook apps for smoking cessation. Objective The purpose of this study was to review the features and functionality of Facebook apps for smoking cessation and to determine the extent to which they adhere to evidence-based guidelines for tobacco dependence treatment. Methods In August 2013, we searched Facebook and three top Internet search engines using smoking cessation keywords to identify relevant Facebook apps. Resultant apps were screened for eligibility (smoking cessation-related, English language, and functioning). Eligible apps were reviewed by 2 independent coders using a standardized coding scheme. Coding included content features (interactive, informational, and social) and adherence to an established 20-item index (possible score 0-40) derived from the US Public Health Service’s Clinical Practice Guidelines for Treating Tobacco Use and Dependence. Results We screened 22 apps for eligibility; of these, 12 underwent full coding. Only 9 apps were available on Facebook. Facebook apps fell into three broad categories: public pledge to quit (n=3), quit-date–based calculator/tracker (n=4), or a multicomponent quit smoking program (n=2). All apps incorporated interactive, informational, and social features except for two quit-date–based calculator/trackers apps (lacked informational component). All apps allowed app-related posting within Facebook (ie, on self/other Facebook profile), and four had a within-app “community” feature to enable app users to communicate with each other. Adherence index summary scores among Facebook apps were low overall (mean 15.1, SD 7.8, range 7-30), with

Reading apps for children: Readability from the design perspective

NASA Astrophysics Data System (ADS)

Mohammed, Wasan Abdulwahab; Husni, Husniza

2017-10-01

Electronic reading for young children opens new avenues especially with the advance of modern reading devices. The readability of mobile learning applications has received extensive attention by the designers and developers. The reason for such concern is due to its importance in determining usability related issues especially in the design context for children. In many cases, children find it difficult to interact with mobile reading apps. This is because apps for reading and for entertainment require different features. As such, this study sets out three objectives: 1) to evaluate five reading apps for young children from design perspectives; 2) to examine the readability for current existing mobile apps for reading and 3) to propose and evaluate mobile apps UI guideline for readability. Readability indices, observation and interview were conducted on 6 - 8 years old students. The obtained result showed that certain reading apps provide better reading experience for children than others. Some of the reasons are mostly related to the design characteristics embedded within the app. In addition, the use of animation was found to stimulate children reading experience as it is believed to offer the interactivity elements to gain their interest and willingness to read. These findings are believed to provide the recommendations and insights for designers of reading apps for children.

Clinician perceptions of using a smartphone app with prolonged exposure therapy.

PubMed

Kuhn, Eric; Eftekhari, Afsoon; Hoffman, Julia E; Crowley, Jill J; Ramsey, Kelly M; Reger, Greg M; Ruzek, Josef I

2014-11-01

Clinician perceptions of clinical innovations affect their adoption and spread. This study investigated mental health clinicians' (n = 163) perceptions of a patient-facing smartphone application (app) for prolonged exposure (PE) therapy for posttraumatic stress disorder, before its public release. After reading a description of the app, participants rated perceptions of it based on diffusion of innovations theory constructs. Perceptions were generally favorable regarding the app's relative advantage over existing PE practices, compatibility with their values and needs, and complexity. Age (<40 years), smartphone ownership, and having used apps in care related to more favorable perceptions. Smartphone ownership, relative advantage, and complexity significantly predicted intention to use the app if it were available. These findings suggest that clinicians are receptive to using a PE app and that dissemination efforts should target sub-groups of PE clinicians to maximize adoption.

The influence of repressor DNA binding site architecture on transcriptional control.

PubMed

Park, Dan M; Kiley, Patricia J

2014-08-26

How the architecture of DNA binding sites dictates the extent of repression of promoters is not well understood. Here, we addressed the importance of the number and information content of the three direct repeats (DRs) in the binding and repression of the icdA promoter by the phosphorylated form of the global Escherichia coli repressor ArcA (ArcA-P). We show that decreasing the information content of the two sites with the highest information (DR1 and DR2) eliminated ArcA binding to all three DRs and ArcA repression of icdA. Unexpectedly, we also found that DR3 occupancy functions principally in repression, since mutation of this low-information-content site both eliminated DNA binding to DR3 and significantly weakened icdA repression, despite the fact that binding to DR1 and DR2 was intact. In addition, increasing the information content of any one of the three DRs or addition of a fourth DR increased ArcA-dependent repression but perturbed signal-dependent regulation of repression. Thus, our data show that the information content and number of DR elements are critical architectural features for maintaining a balance between high-affinity binding and signal-dependent regulation of icdA promoter function in response to changes in ArcA-P levels. Optimization of such architectural features may be a common strategy to either dampen or enhance the sensitivity of DNA binding among the members of the large OmpR/PhoB family of regulators as well as other transcription factors. In Escherichia coli, the response regulator ArcA maintains homeostasis of redox carriers under O2-limiting conditions through a comprehensive repression of carbon oxidation pathways that require aerobic respiration to recycle redox carriers. Although a binding site architecture comprised of a variable number of sequence recognition elements has been identified within the promoter regions of ArcA-repressed operons, it is unclear how this variable architecture dictates transcriptional regulation. By

NKG2D and CD94 bind to multimeric alpha2,3-linked N-acetylneuraminic acid.

PubMed

Imaizumi, Yuzo; Higai, Koji; Suzuki, Chiho; Azuma, Yutaro; Matsumoto, Kojiro

2009-05-08

Killer lectin-like receptors on natural killer cells mediate cytotoxicity through glycans on target cells including the sialyl Lewis X antigen (sLeX). We investigated whether NK group 2D (NKG2D) and CD94 can bind to sialylated N-linked glycans, using recombinant glutathione S-transferase-fused extracellular lectin-like domains of NKG2D (rNKG2Dlec) and CD94 (rCD94lec). Both rNKG2Dlec and rCD94lec bound to plates coated with high-sLeX-expressing transferrin secreted by HepG2 cells (HepTF). The binding of rNKG2Dlec and rCD94lec to HepTF was markedly suppressed by treatment of HepTF with neuraminidase and in the presence of N-acetylneuraminic acid. Moreover, rNKG2Dlec and rCD94lec bound to alpha2,3-sialylated human alpha(1)-acid glycoprotein (AGP) but not to alpha2,6-sialylated AGP. Mutagenesis revealed that (152)Y of NKG2D and (144)F and (160)N of CD94 were critical for HepTF binding. This is the first report that NKG2D and CD94 bind to alpha2,3-sialylated but not to alpha2,6-sialylated multi-antennary N-glycans.

Just a fad? Gamification in health and fitness apps.

PubMed

Lister, Cameron; West, Joshua H; Cannon, Ben; Sax, Tyler; Brodegard, David

2014-08-04

Gamification has been a predominant focus of the health app industry in recent years. However, to our knowledge, there has yet to be a review of gamification elements in relation to health behavior constructs, or insight into the true proliferation of gamification in health apps. The objective of this study was to identify the extent to which gamification is used in health apps, and analyze gamification of health and fitness apps as a potential component of influence on a consumer's health behavior. An analysis of health and fitness apps related to physical activity and diet was conducted among apps in the Apple App Store in the winter of 2014. This analysis reviewed a sample of 132 apps for the 10 effective game elements, the 6 core components of health gamification, and 13 core health behavior constructs. A regression analysis was conducted in order to measure the correlation between health behavior constructs, gamification components, and effective game elements. This review of the most popular apps showed widespread use of gamification principles, but low adherence to any professional guidelines or industry standard. Regression analysis showed that game elements were associated with gamification (P<.001). Behavioral theory was associated with gamification (P<.05), but not game elements, and upon further analysis gamification was only associated with composite motivational behavior scores (P<.001), and not capacity or opportunity/trigger. This research, to our knowledge, represents the first comprehensive review of gamification use in health and fitness apps, and the potential to impact health behavior. The results show that use of gamification in health and fitness apps has become immensely popular, as evidenced by the number of apps found in the Apple App Store containing at least some components of gamification. This shows a lack of integrating important elements of behavioral theory from the app industry, which can potentially impact the efficacy of

Just a Fad? Gamification in Health and Fitness Apps

PubMed Central

2014-01-01

Background Gamification has been a predominant focus of the health app industry in recent years. However, to our knowledge, there has yet to be a review of gamification elements in relation to health behavior constructs, or insight into the true proliferation of gamification in health apps. Objective The objective of this study was to identify the extent to which gamification is used in health apps, and analyze gamification of health and fitness apps as a potential component of influence on a consumer’s health behavior. Methods An analysis of health and fitness apps related to physical activity and diet was conducted among apps in the Apple App Store in the winter of 2014. This analysis reviewed a sample of 132 apps for the 10 effective game elements, the 6 core components of health gamification, and 13 core health behavior constructs. A regression analysis was conducted in order to measure the correlation between health behavior constructs, gamification components, and effective game elements. Results This review of the most popular apps showed widespread use of gamification principles, but low adherence to any professional guidelines or industry standard. Regression analysis showed that game elements were associated with gamification (P<.001). Behavioral theory was associated with gamification (P<.05), but not game elements, and upon further analysis gamification was only associated with composite motivational behavior scores (P<.001), and not capacity or opportunity/trigger. Conclusions This research, to our knowledge, represents the first comprehensive review of gamification use in health and fitness apps, and the potential to impact health behavior. The results show that use of gamification in health and fitness apps has become immensely popular, as evidenced by the number of apps found in the Apple App Store containing at least some components of gamification. This shows a lack of integrating important elements of behavioral theory from the app industry

There's an App for That? Highlighting the Difficulty in Finding Clinically Relevant Smartphone Applications.

PubMed

Wiechmann, Warren; Kwan, Daniel; Bokarius, Andrew; Toohey, Shannon L

2016-03-01

The use of personal mobile devices in the medical field has grown quickly, and a large proportion of physicians use their mobile devices as an immediate resource for clinical decision-making, prescription information and other medical information. The iTunes App Store (Apple, Inc.) contains approximately 20,000 apps in its "Medical" category, providing a robust repository of resources for clinicians; however, this represents only 2% of the entire App Store. The App Store does not have strict criteria for identifying content specific to practicing physicians, making the identification of clinically relevant content difficult. The objective of this study is to quantify the characteristics of existing medical applications in the iTunes App Store that could be used by emergency physicians, residents, or medical students. We found applications related to emergency medicine (EM) by searching the iTunes App Store for 21 terms representing core content areas of EM, such as "emergency medicine," "critical care," "orthopedics," and "procedures." Two physicians independently reviewed descriptions of these applications in the App Store and categorized each as the following: Clinically Relevant, Book/Published Source, Non-English, Study Tools, or Not Relevant. A third physician reviewer resolved disagreements about categorization. Descriptive statistics were calculated. We found a total of 7,699 apps from the 21 search terms, of which 17.8% were clinical, 9.6% were based on a book or published source, 1.6% were non-English, 0.7% were clinically relevant patient education resources, and 4.8% were study tools. Most significantly, 64.9% were considered not relevant to medical professionals. Clinically relevant apps make up approximately 6.9% of the App Store's "Medical" Category and 0.1% of the overall App Store. Clinically relevant apps represent only a small percentage (6.9%) of the total App volume within the Medical section of the App Store. Without a structured search

Using Smartphones and Health Apps to Change and Manage Health Behaviors: A Population-Based Survey

PubMed Central

Dombrowski, Stephan U; Oedekoven, Monika; O´Sullivan, Julie L; Kanzler, Melanie; Kuhlmey, Adelheid; Gellert, Paul

2017-01-01

Background Chronic conditions are an increasing challenge for individuals and the health care system. Smartphones and health apps are potentially promising tools to change health-related behaviors and manage chronic conditions. Objective The aim of this study was to explore (1) the extent of smartphone and health app use, (2) sociodemographic, medical, and behavioral correlates of smartphone and health app use, and (3) associations of the use of apps and app characteristics with actual health behaviors. Methods A population-based survey (N=4144) among Germans, aged 35 years and older, was conducted. Sociodemographics, presence of chronic conditions, health behaviors, quality of life, and health literacy, as well as the use of the Internet, smartphone, and health apps were assessed by questionnaire at home visit. Binary logistic regression models were applied. Results It was found that 61.25% (2538/4144) of participants used a smartphone. Compared with nonusers, smartphone users were younger, did more research on the Internet, were more likely to work full-time and more likely to have a university degree, engaged more in physical activity, and less in low fat diet, and had a higher health-related quality of life and health literacy. Among smartphone users, 20.53% (521/2538) used health apps. App users were younger, less likely to be native German speakers, did more research on the Internet, were more likely to report chronic conditions, engaged more in physical activity, and low fat diet, and were more health literate compared with nonusers who had a smartphone. Health apps focused on smoking cessation (232/521, 44.5%), healthy diet (201/521, 38.6%), and weight loss (121/521, 23.2%). The most common app characteristics were planning (264/521, 50.7%), reminding (188/521, 36.1%), prompting motivation (179/521 34.4%), and the provision of information (175/521, 33.6%). Significant associations were found between planning and the health behavior physical activity

Using Smartphones and Health Apps to Change and Manage Health Behaviors: A Population-Based Survey.

PubMed

Ernsting, Clemens; Dombrowski, Stephan U; Oedekoven, Monika; O Sullivan, Julie L; Kanzler, Melanie; Kuhlmey, Adelheid; Gellert, Paul

2017-04-05

Chronic conditions are an increasing challenge for individuals and the health care system. Smartphones and health apps are potentially promising tools to change health-related behaviors and manage chronic conditions. The aim of this study was to explore (1) the extent of smartphone and health app use, (2) sociodemographic, medical, and behavioral correlates of smartphone and health app use, and (3) associations of the use of apps and app characteristics with actual health behaviors. A population-based survey (N=4144) among Germans, aged 35 years and older, was conducted. Sociodemographics, presence of chronic conditions, health behaviors, quality of life, and health literacy, as well as the use of the Internet, smartphone, and health apps were assessed by questionnaire at home visit. Binary logistic regression models were applied. It was found that 61.25% (2538/4144) of participants used a smartphone. Compared with nonusers, smartphone users were younger, did more research on the Internet, were more likely to work full-time and more likely to have a university degree, engaged more in physical activity, and less in low fat diet, and had a higher health-related quality of life and health literacy. Among smartphone users, 20.53% (521/2538) used health apps. App users were younger, less likely to be native German speakers, did more research on the Internet, were more likely to report chronic conditions, engaged more in physical activity, and low fat diet, and were more health literate compared with nonusers who had a smartphone. Health apps focused on smoking cessation (232/521, 44.5%), healthy diet (201/521, 38.6%), and weight loss (121/521, 23.2%). The most common app characteristics were planning (264/521, 50.7%), reminding (188/521, 36.1%), prompting motivation (179/521 34.4%), and the provision of information (175/521, 33.6%). Significant associations were found between planning and the health behavior physical activity, between feedback or monitoring and physical

Involvement of a bifunctional, paired-like DNA-binding domain and a transpositional enhancer in Sleeping Beauty transposition.

PubMed

Izsvák, Zsuzsanna; Khare, Dheeraj; Behlke, Joachim; Heinemann, Udo; Plasterk, Ronald H; Ivics, Zoltán

2002-09-13

Sleeping Beauty (SB) is the most active Tc1/mariner-like transposon in vertebrate species. Each of the terminal inverted repeats (IRs) of SB contains two transposase-binding sites (DRs). This feature, termed the IR/DR structure, is conserved in a group of Tc1-like transposons. The DNA-binding region of SB transposase, similar to the paired domain of Pax proteins, consists of two helix-turn-helix subdomains (PAI + RED = PAIRED). The N-terminal PAI subdomain was found to play a dominant role in contacting the DRs. Transposase was able to bind to mutant sites retaining the 3' part of the DRs; thus, primary DNA binding is not sufficient to determine the specificity of the transposition reaction. The PAI subdomain was also found to bind to a transpositional enhancer-like sequence within the left IR of SB, and to mediate protein-protein interactions between transposase subunits. A tetrameric form of the transposase was detected in solution, consistent with an interaction between the IR/DR structure and a transposase tetramer. We propose a model in which the transpositional enhancer and the PAI subdomain stabilize complexes formed by a transposase tetramer bound at the IR/DR. These interactions may result in enhanced stability of synaptic complexes, which might explain the efficient transposition of Sleeping Beauty in vertebrate cells.

Apps Developed by Academics

ERIC Educational Resources Information Center

Shing, Sophia; Yuan, Benjamin

2016-01-01

In the days of the digital Wild West, developers from all backgrounds have joined in the gold rush trying to profit from the almost unbridled spending of well-to-do parents on educational products. In 2016, the Apple App Store had over 80,000 educational apps. The proliferation of educational apps has happened at a furious pace and more apps are…

Gamification in Stress Management Apps: A Critical App Review

PubMed Central

Christmann, Corinna A; Bleser, Gabriele

2017-01-01

Background In today’s society, stress is more and more often a cause of disease. This makes stress management an important target of behavior change programs. Gamification has been suggested as one way to support health behavior change. However, it remains unclear to which extend available gamification techniques are integrated in stress management apps, and if their occurrence is linked to the use of elements from behavior change theory. Objective The aim of this study was to investigate the use of gamification techniques in stress management apps and the cooccurrence of these techniques with evidence-based stress management methods and behavior change techniques. Methods A total of 62 stress management apps from the Google Play Store were reviewed on their inclusion of 17 gamification techniques, 15 stress management methods, and 26 behavior change techniques. For this purpose, an extended taxonomy of gamification techniques was constructed and applied by 2 trained, independent raters. Results Interrater-reliability was high, with agreement coefficient (AC)=.97. Results show an average of 0.5 gamification techniques for the tested apps and reveal no correlations between the use of gamification techniques and behavior change techniques (r=.17, P=.20), or stress management methods (r=.14, P=.26). Conclusions This leads to the conclusion that designers of stress management apps do not use gamification techniques to influence the user’s behaviors and reactions. Moreover, app designers do not exploit the potential of combining gamification techniques with behavior change theory. PMID:28592397

Binding Patterns Associated Aß-HSP60 p458 Conjugate to HLA-DR-DRB Allele of Human in Alzheimer's Disease: An In Silico Approach.

PubMed

Padmadas, Naveen; Panda, Pritam Kumar; Durairaj, Sudarsanam

2018-03-01

Alzheimer's disease (AD) is a complex, irreversible, progressive brain disorder, which diminishes memory in a slow pace and thinking skills; ranked third by experts. It is a complex disorder that involves numerous cellular and subcellular alterations. The pathogenesis of AD is still unknown, but for better understanding, we proposed an in silico analysis to find out the binding patterns associated with HSP60. Several experimental conclusions have been drawn to understand the actual mechanism behind the forming of aggregation due to misfolding. Protein misfolding disorder is experimentally identified by the accumulation of protein aggregates at the intracellular or extracellular region of brain that adversely affects the cell functioning by disrupting the connection between the cells and ultimately leading to cell death. To unravel the mystery behind the mechanism of AD through computational approach, the current proposal shows the designing of Aß-HSP60 p458 conjugate followed by secondary structure analysis, which is further targeted to HLA-DR-DRB allele of human. The antigenicity of Aß (1-42) peptide is the major concern in our study predicted through PVS server, which provides an insight into the immunogenic behavior of Aß peptide. The mechanism involved in the interaction of HSP60-Aß conjugate with HLA-DR-DRB allele considering the fact that Aß (1-42) is highly immunogenic in human and interactions evoked highly robust T-cell response through MHC class II binding predictions. It was assisted by molecular dynamics simulation of predicted HSP60 structure followed by validation through Ramachandran plot analysis and protein-protein interaction of Aß (1-42) with HSP60.

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

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

Using smartphone apps in STD interviews to find sexual partners.

PubMed

Pennise, Melissa; Inscho, Roxana; Herpin, Kate; Owens, John; Bedard, Brenden A; Weimer, Anita C; Kennedy, Byron S; Younge, Mary

2015-01-01

Smartphone applications (apps) are increasingly used to facilitate casual sexual relationships, increasing the risk of sexually transmitted diseases (STDs). In STD investigations, traditional contact elicitation methods can be enhanced with smartphone technology during field interviews. In 2013, the Monroe County Department of Public Health conducted a large, multi-infection STD investigation among men who have sex with men (MSM) using both index case and cluster interviews. When patients indicated meeting sexual partners online, disease intervention specialists (DISs) had access to smartphone apps and were able to elicit partners through access to inboxes and profiles where traditional contact information was lacking. Social network mapping was used to display the extent of the investigation and the impact of access to smartphones on the investigation. A total of 14 index patient interviews and two cluster interviews were conducted; 97 individuals were identified among 117 sexual dyads. On average, eight partners were elicited per interview (range: 1-31). The seven individuals who used apps to find partners had an average of three Internet partners (range: 1-5). Thirty-six individuals either had a new STD (n=7) or were previously known to be HIV-positive (n=29). Of the 117 sexual dyads, 21 (18%) originated either online (n=8) or with a smartphone app (n=13). Of those originating online or with a smartphone app, six (29%) partners were located using the smartphone and two (10%) were notified of their exposure via a website. Three of the new STD/HIV cases were among partners who met online. Smartphone technology used by DISs in the field improved contact elicitation and resulted in successful partner notification and case finding.

Free energy simulations reveal a double mutant avian H5N1 virus hemagglutinin with altered receptor binding specificity.

PubMed

Das, Payel; Li, Jingyuan; Royyuru, Ajay K; Zhou, Ruhong

2009-08-01

Historically, influenza pandemics have been triggered when an avian influenza virus or a human/avian reassorted virus acquires the ability to replicate efficiently and become transmissible in the human population. Most critically, the major surface glycoprotein hemagglutinin (HA) must adapt to the usage of human-like (alpha-2,6-linked) sialylated glycan receptors. Therefore, identification of mutations that can switch the currently circulating H5N1 HA receptor binding specificity from avian to human might provide leads to the emergence of pandemic H5N1 viruses. To define such mutations in the H5 subtype, here we provide a computational framework that combines molecular modeling with extensive free energy simulations. Our results show that the simulated binding affinities are in good agreement with currently available experimental data. Moreover, we predict that one double mutation (V135S and A138S) in HA significantly enhances alpha-2,6-linked receptor recognition by the H5 subtype. Our simulations indicate that this double mutation in H5N1 HA increases the binding affinity to alpha-2,6-linked sialic acid receptors by 2.6 +/- 0.7 kcal/mol per HA monomer that primarily arises from the electrostatic interactions. Further analyses reveal that introduction of this double mutation results in a conformational change in the receptor binding pocket of H5N1 HA. As a result, a major rearrangement occurs in the hydrogen-bonding network of HA with the human receptor, making the human receptor binding pattern of double mutant H5N1 HA surprisingly similar to that observed in human H1N1 HA. These large scale molecular simulations on single and double mutants thus provide new insights into our understanding toward human adaptation of the avian H5N1 virus. 2009 Wiley Periodicals, Inc.

Characterization of local polarity and hydrophobic binding sites of beta-lactoglobulin by using N-terminal specific fluorescence labeling.

PubMed

Dong, Su-Ying; Zhao, Zhen-Wen; Ma, Hui-Min

2006-01-01

Because of wide ligand-binding ability and significant industrial interest of beta-lactoglobulin (beta-LG), its binding properties have been extensively studied. However, there still exists a controversy as to where a ligand binds, since at least two potential hydrophobic binding sites in beta-LG have been postulated for ligand binding: an internal one (calyx) and an external one (near the N-terminus). In this work, the local polarity and hydrophobic binding sites of beta-LG have been characterized by using N-terminal specific fluorescence labeling combined with a polarity-sensitive fluorescent probe 3-(4-chloro-6-hydrazino- 1,3,5-triazinylamino)-7-(dimethylamino)-2-methylphenazine (CHTDP). The polarity within the calyx is found to be extremely low, which is explained in terms of superhydrophobicity possibly resulting from its nanostructure, and the polarity is increased with the destruction of the calyx by heat treatment. However, the polarity of the N-terminal domain in native beta-LG is decreased after thermal denaturation. This polarity trend toward decreasing instead of increasing shows that beta-LG may have no definite external hydrophobic binding site. The hydrophobic binding of a ligand such as CHTDP at the surface of the protein is probably achieved via appropriate assembling of corresponding hydrophobic residues rather than via a fixed external hydrophobic binding site. Also, the ligand-binding location in beta-LG is found to be relevant to not only experimental conditions (pH < or = 6.2 or pH > 7.1) but also binding mechanisms (hydrophobic affinity or electrostatic interaction).

Apps for IMproving FITness and Increasing Physical Activity Among Young People: The AIMFIT Pragmatic Randomized Controlled Trial

PubMed Central

Jiang, Yannan; Whittaker, Robyn; Maddison, Ralph

2015-01-01

app intervention (n=16), or the control group (n=18). The mean age of participants was 15.7 (SD 1.2) years; participants were mostly NZ Europeans (61%, 31/51) and 57% (29/51) were female. Overall retention rate was 96% (49/51). There was no significant intervention effect on the primary outcome using either of the apps. Compared to the control, time to complete the fitness test was –28.4 seconds shorter (95% CI –66.5 to 9.82, P=.20) for the immersive app group and –24.7 seconds (95% CI –63.5 to 14.2, P=.32) for the nonimmersive app group. No significant intervention effects were found for secondary outcomes. Conclusions Although apps have the ability to increase reach at a low cost, our pragmatic approach using readily available commercial apps as a stand-alone instrument did not have a significant effect on fitness. However, interest in future use of PA apps is promising and highlights a potentially important role of these tools in a multifaceted approach to increase fitness, promote PA, and consequently reduce the adverse health outcomes associated with insufficient activity. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN12613001030763; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12613001030763 (Archived by WebCite at http://www.webcitation.org/6aasfJVTJ). PMID:26316499

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

There’s an App for That: Content Analysis of Paid Health and Fitness Apps

PubMed Central

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

2012-01-01

Background The introduction of Apple’s iPhone provided a platform for developers to design third-party apps, which greatly expanded the functionality and utility of mobile devices for public health. Objective This study provides an overview of the developers’ written descriptions of health and fitness apps and appraises each app’s potential for influencing behavior change. Methods Data for this study came from a content analysis of health and fitness app descriptions available on iTunes during February 2011. The Health Education Curriculum Analysis Tool (HECAT) and the Precede-Proceed Model (PPM) were used as frameworks to guide the coding of 3336 paid apps. Results Compared to apps with a cost less than US $0.99, apps exceeding US $0.99 were more likely to be scored as intending to promote health or prevent disease (92.55%, 1925/3336 vs 83.59%, 1411/3336; P<.001), to be credible or trustworthy (91.11%, 1895/3336 vs 86.14%, 1454/3349; P<.001), and more likely to be used personally or recommended to a health care client (72.93%, 1517/2644 vs 66.77%, 1127/2644; P<.001). Apps related to healthy eating, physical activity, and personal health and wellness were more common than apps for substance abuse, mental and emotional health, violence prevention and safety, and sexual and reproductive health. Reinforcing apps were less common than predisposing and enabling apps. Only 1.86% (62/3336) of apps included all 3 factors (ie, predisposing, enabling, and reinforcing). Conclusions Development efforts could target public health behaviors for which few apps currently exist. Furthermore, practitioners should be cautious when promoting the use of apps as it appears most provide health-related information (predisposing) or make attempts at enabling behavior, with almost none including all theoretical factors recommended for behavior change. PMID:22584372

Psych-related iPhone apps.

PubMed

Harrison, Anthony Mark; Goozee, Rhianna

2014-02-01

iPhone apps are a widely utilised technology that have recently been identified as a useful medium for health research, clinical interventions and education. While some researchers have discussed advances in app technology, others promote specific apps that are not free to access. To our knowledge, no study has conducted a review of current, free iPhone apps related to psychology, psychiatry and mental health. Therefore, we conducted a pilot, web-based review exploring free iPhone apps using a replicable search strategy within the iTunes Store search function. A selection of apps were selected and subjectively assessed in terms of their usability, utility, graphics, and associated costs for the consumer. We concluded that the apps reviewed, though novel, are limited in their scope and utility. We also note a significant gap in more scientific, evidence-based app technology, and pose some pertinent ethical questions when developing future psych-related apps.

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

PubMed

Lewis, Thomas Lorchan; Wyatt, Jeremy C

2015-08-19

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

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

PubMed Central

Wyatt, Jeremy C

2015-01-01

Background One factor when assessing the quality of mobile apps is quantifying the impact of a given app on a population. There is currently no metric which can be used to compare the population impact of a mobile app across different health care disciplines. Objective The objective of this study is to create a novel metric to characterize the impact of a mobile app on a population. Methods We developed the simple novel metric, app usage factor (AUF), defined as the logarithm of the product of the number of active users of a mobile app with the median number of daily uses of the app. The behavior of this metric was modeled using simulated modeling in Python, a general-purpose programming language. Three simulations were conducted to explore the temporal and numerical stability of our metric and a simulated app ecosystem model using a simulated dataset of 20,000 apps. Results Simulations confirmed the metric was stable between predicted usage limits and remained stable at extremes of these limits. Analysis of a simulated dataset of 20,000 apps calculated an average value for the app usage factor of 4.90 (SD 0.78). A temporal simulation showed that the metric remained stable over time and suitable limits for its use were identified. Conclusions A key component when assessing app risk and potential harm is understanding the potential population impact of each mobile app. Our metric has many potential uses for a wide range of stakeholders in the app ecosystem, including users, regulators, developers, and health care professionals. Furthermore, this metric forms part of the overall estimate of risk and potential for harm or benefit posed by a mobile medical app. We identify the merits and limitations of this metric, as well as potential avenues for future validation and research. PMID:26290093

1. View of three detection radar (DR) antennas. DR 1 ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. View of three detection radar (DR) antennas. DR 1 (structure no. 735) on left, DR 2 (structure no. 736) in center, and DR 3 (structure no. 737) looking north 30 degrees west, with tracking radar (large radome) and satcom (satellite communication) system in small radome in view between DR 2 and DR 3 antennae. - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

Homogeneous bioluminescence competitive binding assay for folate based on a coupled glucose-6-phosphate dehydrogenase--bacterial luciferase enzyme system.

PubMed

Huang, W; Feltus, A; Witkowski, A; Daunert, S

1996-05-01

A homogeneous bioluminescence competitive binding assay for folate was developed by using a coupled enzyme system of glucose-6-phosphate dehydrogenase (G6PDH) and bacterial luciferase. A highly substituted G6PDH-folate conjugate was prepared by employing an N-hydroxysuccinimide/carbodiimide method. Folate binding protein inhibits the activity of the conjugate. In the presence of folate, there is a competition between folate and the G6PDH-folate conjugate for the binding site of the folate binding protein, and the activity of the conjugate is recovered. Thus, the concentration of folate can be related to the activity of the G6PDH-folate conjugate, which is directly related to the bioluminescence produced by the coupled enzyme reaction. Using this assay, dose-response curves with a detection limit of 2.5 x 10(-8) M folate were obtained, which is an improvement of an order of magnitude with respect to an assay that monitors G6PDH activity spectrophotometrically. The assay was validated using vitamin tablets and a cell culture medium.

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

Developing smartphone apps for behavioural studies: The AlcoRisk app case study.

PubMed

Smith, Anthony; de Salas, Kristy; Lewis, Ian; Schüz, Benjamin

2017-08-01

Smartphone apps have emerged as valuable research tools to sample human behaviours at their time of occurrence within natural environments. Human behaviour sampling methods, such as Ecological Momentary Assessment (EMA), aim to facilitate research that is situated in ecologically valid real world environments rather than laboratory environments. Researchers have trialled a range of EMA smartphone apps to sample human behaviours such as dieting, physical activity and smoking. Software development processes for EMA smartphones apps, however, are not widely documented with little guidance provided for the integration of complex multidisciplinary behavioural and technical fields. In this paper, the AlcoRisk app for studying alcohol consumption and risk taking tendencies is presented alongside a software development process that integrates these multidisciplinary fields. The software development process consists of three stages including requirements analysis, feature and interface design followed by app implementation. Results from a preliminary feasibility study support the efficacy of the AlcoRisk app's software development process. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-03-01

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

PilN binding modulates the structure and binding partners of the Pseudomonas aeruginosa type IVa pilus protein PilM

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

McCallum, Matthew; Tammam, Stephanie; Little, Dustin J.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that expresses type IVa pili. The pilus assembly system, which promotes surface-associated twitching motility and virulence, is composed of inner and outer membrane subcomplexes, connected by an alignment subcomplex composed of PilMNOP. PilM binds to the N terminus of PilN, and we hypothesize that this interaction causes functionally significant structural changes in PilM. To characterize this interaction, we determined the crystal structures of PilM and a PilM chimera where PilM was fused to the first 12 residues of PilN (PilM·PilN(1–12)). Structural analysis, multiangle light scattering coupled with size exclusion chromatography, and bacterial two-hybridmore » data revealed that PilM forms dimers mediated by the binding of a novel conserved motif in the N terminus of PilM, and binding PilN abrogates this binding interface, resulting in PilM monomerization. Structural comparison of PilM with PilM·PilN(1–12) revealed that upon PilN binding, there is a large domain closure in PilM that alters its ATP binding site. Using biolayer interferometry, we found that the association rate of PilN with PilM is higher in the presence of ATP compared with ADP. Bacterial two-hybrid data suggested the connectivity of the cytoplasmic and inner membrane components of the type IVa pilus machinery in P. aeruginosa, with PilM binding to PilB, PilT, and PilC in addition to PilN. Pull-down experiments demonstrated direct interactions of PilM with PilB and PilT. As a result, we propose a working model in which dynamic binding of PilN facilitates functionally relevant structural changes in PilM.« less

PilN binding modulates the structure and binding partners of the Pseudomonas aeruginosa type IVa pilus protein PilM

DOE PAGES

McCallum, Matthew; Tammam, Stephanie; Little, Dustin J.; ...

2016-03-28

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that expresses type IVa pili. The pilus assembly system, which promotes surface-associated twitching motility and virulence, is composed of inner and outer membrane subcomplexes, connected by an alignment subcomplex composed of PilMNOP. PilM binds to the N terminus of PilN, and we hypothesize that this interaction causes functionally significant structural changes in PilM. To characterize this interaction, we determined the crystal structures of PilM and a PilM chimera where PilM was fused to the first 12 residues of PilN (PilM·PilN(1–12)). Structural analysis, multiangle light scattering coupled with size exclusion chromatography, and bacterial two-hybridmore » data revealed that PilM forms dimers mediated by the binding of a novel conserved motif in the N terminus of PilM, and binding PilN abrogates this binding interface, resulting in PilM monomerization. Structural comparison of PilM with PilM·PilN(1–12) revealed that upon PilN binding, there is a large domain closure in PilM that alters its ATP binding site. Using biolayer interferometry, we found that the association rate of PilN with PilM is higher in the presence of ATP compared with ADP. Bacterial two-hybrid data suggested the connectivity of the cytoplasmic and inner membrane components of the type IVa pilus machinery in P. aeruginosa, with PilM binding to PilB, PilT, and PilC in addition to PilN. Pull-down experiments demonstrated direct interactions of PilM with PilB and PilT. As a result, we propose a working model in which dynamic binding of PilN facilitates functionally relevant structural changes in PilM.« less

Methods for Evaluating the Content, Usability, and Efficacy of Commercial Mobile Health Apps

PubMed Central

Silfee, Valerie J; Waring, Molly E; Boudreaux, Edwin D; Sadasivam, Rajani S; Mullen, Sean P; Carey, Jennifer L; Hayes, Rashelle B; Ding, Eric Y; Bennett, Gary G; Pagoto, Sherry L

2017-01-01

Commercial mobile apps for health behavior change are flourishing in the marketplace, but little evidence exists to support their use. This paper summarizes methods for evaluating the content, usability, and efficacy of commercially available health apps. Content analyses can be used to compare app features with clinical guidelines, evidence-based protocols, and behavior change techniques. Usability testing can establish how well an app functions and serves its intended purpose for a target population. Observational studies can explore the association between use and clinical and behavioral outcomes. Finally, efficacy testing can establish whether a commercial app impacts an outcome of interest via a variety of study designs, including randomized trials, multiphase optimization studies, and N-of-1 studies. Evidence in all these forms would increase adoption of commercial apps in clinical practice, inform the development of the next generation of apps, and ultimately increase the impact of commercial apps. PMID:29254914

Gamification in Stress Management Apps: A Critical App Review.

PubMed

Hoffmann, Alexandra; Christmann, Corinna A; Bleser, Gabriele

2017-06-07

In today's society, stress is more and more often a cause of disease. This makes stress management an important target of behavior change programs. Gamification has been suggested as one way to support health behavior change. However, it remains unclear to which extend available gamification techniques are integrated in stress management apps, and if their occurrence is linked to the use of elements from behavior change theory. The aim of this study was to investigate the use of gamification techniques in stress management apps and the cooccurrence of these techniques with evidence-based stress management methods and behavior change techniques. A total of 62 stress management apps from the Google Play Store were reviewed on their inclusion of 17 gamification techniques, 15 stress management methods, and 26 behavior change techniques. For this purpose, an extended taxonomy of gamification techniques was constructed and applied by 2 trained, independent raters. Interrater-reliability was high, with agreement coefficient (AC)=.97. Results show an average of 0.5 gamification techniques for the tested apps and reveal no correlations between the use of gamification techniques and behavior change techniques (r=.17, P=.20), or stress management methods (r=.14, P=.26). This leads to the conclusion that designers of stress management apps do not use gamification techniques to influence the user's behaviors and reactions. Moreover, app designers do not exploit the potential of combining gamification techniques with behavior change theory. ©Alexandra Hoffmann, Corinna A Christmann, Gabriele Bleser. Originally published in JMIR Serious Games (http://games.jmir.org), 07.06.2017.

Opiate receptor binding properties of morphine-, dihydromorphine-, and codeine 6-O-sulfate ester congeners.

PubMed

Crooks, Peter A; Kottayil, Santosh G; Al-Ghananeem, Abeer M; Byrn, Stephen R; Butterfield, D Allan

2006-08-15

A series of 3-O-acyl-6-O-sulfate esters of morphine, dihydromorphine, N-methylmorphinium iodide, codeine, and dihydrocodeine were prepared and evaluated for their ability to bind to mu-, delta-, kappa(1)-, kappa(2)-, and kappa(3)-opiate receptors. Several compounds exhibited good affinity for the mu-opiate receptor. Morphine-3-O-propionyl-6-O-sulfate had four times greater affinity than morphine at the mu-opiate receptor and was the most selective compound at this receptor subtype.

Health App Use Among Individuals With Symptoms of Depression and Anxiety: A Survey Study With Thematic Coding.

PubMed

Rubanovich, Caryn Kseniya; Mohr, David C; Schueller, Stephen M

2017-06-23

Researchers have largely turned to commercial app stores, randomized trials, and systematic reviews to make sense of the mHealth landscape. Few studies have approached understanding by collecting information from target end users. The end user perspective is critical as end user interest in and use of mHealth technologies will ultimately drive the efficacy of these tools. The purpose of this study was to obtain information from end users of mHealth technologies to better understand the physical and mental health apps people use and for what purposes. People with depressive or anxious symptoms (N=176) seeking entry into a trial of mental health and well-being apps for Android devices completed online questionnaires assessing depression and anxiety (Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7), past and current mental health treatment-seeking behavior, overall mobile device use, and use of mobile health apps. Participants reported the physical health and mental health apps on their devices and their reasons for using them. Data were extracted from the participant self-reports and apps and app purposes were coded in order to categorize them. Participants were largely white, middle-aged females from the Midwest region of the United States recruited via a health care organization and Web-based advertising (135 female, 41 male, mean age 38.64 years, age range 19-75 years.) Over three-quarters (137/176, 77.8%) of participants indicated having a health app on their device. The top 3 kinds of apps were exercise, fitness, and pedometers or heart rate monitoring apps (93/176, 52.8%); diet, food, or calorie counting apps (65/177, 36.9%); and mental health/wellness apps (46/177, 26.1%). The mean number of mobile physical and mental health apps on a participant's phone was 2.15 (SD 3.195). Of 176 participants, 107 (60.8%) specifically reported the top 5 health apps that they used and their purposes. Across the 107 participants, a total of 285 apps were

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

The Coags Uncomplicated App: Fulfilling Educational Gaps Around Diagnosis and Laboratory Testing of Coagulation Disorders.

PubMed

Kessler, Craig; Peerschke, Ellinor I; Chitlur, Meera B; Kulkarni, Roshni; Holot, Natalia; Cooper, David L

2017-04-18

Patients with coagulation disorders may present to a variety of physician specialties; however, accurate and efficient diagnosis can be challenging for physicians not specialized in hematology, due to identified gaps in knowledge around appropriate laboratory assays and interpretation of test results. Coags Uncomplicated was developed to fill this unmet educational need by increasing practical knowledge of coagulation disorders among nonexpert physicians and other health care professionals (HCPs) in a point-of-care (POC) setting. The aim of this study was to assess patterns of use of the mobile app Coags Uncomplicated, a tool designed to support education regarding accurate and efficient diagnosis of bleeding disorders. App metrics were obtained by tracking registered user data. Additionally, a survey was distributed to registered users, to assess circumstances and frequency of use. The most common specialties of 7596 registered US users were hematology-oncology (n=1534, 20.19%), hematology (n=1014, 13.35%), and emergency medicine (n=1222, 16.09%); most identified as physicians (n=4082, 53.74%). Specialties accounting for the greatest numbers of screen views were hematology-oncology (99,390 views), hematology (47,808 views), emergency medicine (23,121 views), and internal medicine (22,586 views). The most common diagnostic endpoints reached were disseminated intravascular coagulation (DIC; 2713 times), liver disease effect (2108 times), and vitamin K deficiency (1584 times). Of 3424 users asked to take the survey, 262 responded (7.65%); most were physicians in direct clinical care (71%) and specialized in hematology-oncology (39%) or emergency medicine (21%). Most frequent use was reported by hematologists (69%, ≥6 times) and hematologists-oncologists (38%, ≥6 times). Most physicians (89.2%) reported using the app for patient-case-related education around appropriate use of laboratory tests in diagnostic evaluation. Physicians rated Lab Value Analyzer (mean 4

Entropy as a Driver of Selectivity for Inhibitor Binding to Histone Deacetylase 6.

PubMed

Porter, Nicholas J; Wagner, Florence F; Christianson, David W

2018-05-18

Among the metal-dependent histone deacetylases, the class IIb isozyme HDAC6 is remarkable because of its role in the regulation of microtubule dynamics in the cytosol. Selective inhibition of HDAC6 results in microtubule hyperacetylation, leading to cell cycle arrest and apoptosis, which is a validated strategy for cancer chemotherapy and the treatment of other disorders. HDAC6 inhibitors generally consist of a Zn 2+ -binding group such as a hydroxamate, a linker, and a capping group; the capping group is a critical determinant of isozyme selectivity. Surprisingly, however, even "capless" inhibitors exhibit appreciable HDAC6 selectivity. To probe the chemical basis for this selectivity, we now report high-resolution crystal structures of HDAC6 complexed with capless cycloalkyl hydroxamate inhibitors 1-4. Each inhibitor hydroxamate group coordinates to the catalytic Zn 2+ ion with canonical bidentate geometry. Additionally, the olefin moieties of compounds 2 and 4 bind in an aromatic crevice between the side chains of F583 and F643. Reasoning that similar binding could be achieved in the representative class I isozyme HDAC8, we employed isothermal titration calorimetry to study the thermodynamics of inhibitor binding. These measurements indicate that the entropy of inhibitor binding is generally positive for binding to HDAC6 and negative for binding to HDAC8, resulting in ≤313-fold selectivity for binding to HDAC6 relative to HDAC8. Thus, favorable binding entropy contributes to HDAC6 selectivity. Notably, cyclohexenyl hydroxamate 2 represents a promising lead for derivatization with capping groups that may further enhance its impressive 313-fold thermodynamic selectivity for HDAC6 inhibition.

The "Aachen fall prevention App" - a Smartphone application app for the self-assessment of elderly patients at risk for ground level falls.

PubMed

Rasche, Peter; Mertens, Alexander; Bröhl, Christina; Theis, Sabine; Seinsch, Tobias; Wille, Matthias; Pape, Hans-Christoph; Knobe, Matthias

2017-01-01

Fall incidents are a major problem for patients and healthcare. The "Aachen Fall Prevention App" (AFPA) represents the first mobile Health (mHealth) application (app) empowering older patients (persons 50+ years) to self-assess and monitor their individual fall risk. Self-assessment is based on the "Aachen Fall Prevention Scale," which consists of three steps. First, patients answer ten standardized yes-no questions (positive criterion ≥ 5 "Yes" responses). Second, a ten-second test of free standing without compensatory movement is performed (positive criterion: compensatory movement). Finally, during the third step, patients rate their subjective fall risk on a 10-point Likert scale, based on the results of steps one and two. The purpose of this app is (1) to offer a low-threshold service through which individuals can independently monitor their individual fall risk and (2) to collect data about how a patient-centered mHealth app for fall risk assessment is used in the field. The results represent the first year of an ongoing field study. From December 2015 to December 2016, 197 persons downloaded the AFPA (iOS ™ and Android ™ ; free of charge). N  = 111 of these persons voluntarily shared their data and thereby participated in the field study. Data from a final number of n  = 79 persons were analyzed due to exclusion criteria (age, missing objective fall risk, missing self-assessment). The objective fall risk and the self-assessed subjective risk measured by the AFPA showed a significant positive relationship. The "Aachen Fall Prevention App" (AFPA) is an mHealth app released for iOS and Android. This field study revealed the AFPA as a promising tool to raise older adults' awareness of their individual fall risk by means of a low-threshold patient-driven fall risk assessment tool.

Cannabis Mobile Apps: A Content Analysis.

PubMed

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

2015-08-12

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

Use of eluted peptide sequence data to identify the binding characteristics of peptides to the insulin-dependent diabetes susceptibility allele HLA-DQ8 (DQ 3.2).

PubMed

Godkin, A; Friede, T; Davenport, M; Stevanovic, S; Willis, A; Jewell, D; Hill, A; Rammensee, H G

1997-06-01

HLA-DQ8 (A1*0301, B1*0302) and -DQ2 (A1*0501, B1*0201) are both associated with diseases such as insulin-dependent diabetes mellitus and coeliac disease. We used the technique of pool sequencing to look at the requirements of peptides binding to HLA-DQ8, and combined these data with naturally sequenced ligands and in vitro binding assays to describe a novel motif for HLA-DQ8. The motif, which has the same basic format as many HLA-DR molecules, consists of four or five anchor regions, in the positions from the N-terminus of the binding core of n, n + 3, n + 5/6 and n + 8, i.e. P1, P4, P6/7 and P9. P1 and P9 require negative or polar residues, with mainly aliphatic residues at P4 and P6/7. The features of the HLA-DQ8 motif were then compared to a pool sequence of peptides eluted from HLA-DQ2. A consensus motif for the binding of a common peptide which may be involved in disease pathogenesis is described. Neither of the disease-associated alleles HLA-DQ2 and -DQ8 have Asp at position 57 of the beta-chain. This Asp, if present, may form a salt bridge with an Arg at position 79 of the alpha-chain and so alter the binding specificity of P9. HLA-DQ2 and -DQ8 both appear to prefer negatively charged amino acids at P9. In contrast, HLA-DQ7 (A1*0301, B1*0301), which is not associated with diabetes, has Asp at beta 57, allowing positively charged amino acids at P9. This analysis of the sequence features of DQ-binding peptides suggests molecular characteristics which may be useful to predict epitopes involved in disease pathogenesis.

Behavior change techniques in popular alcohol reduction apps: content analysis.

PubMed

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

2015-05-14

Mobile phone apps have the potential to reduce excessive alcohol consumption cost-effectively. Although hundreds of alcohol-related apps are available, there is little information about the behavior change techniques (BCTs) they contain, or the extent to which they are based on evidence or theory and how this relates to their popularity and user ratings. Our aim was to assess the proportion of popular alcohol-related apps available in the United Kingdom that focus on alcohol reduction, identify the BCTs they contain, and explore whether BCTs or the mention of theory or evidence is associated with app popularity and user ratings. We searched the iTunes and Google Play stores with the terms "alcohol" and "drink", and the first 800 results were classified into alcohol reduction, entertainment, or blood alcohol content measurement. Of those classified as alcohol reduction, all free apps and the top 10 paid apps were coded for BCTs and for reference to evidence or theory. Measures of popularity and user ratings were extracted. Of the 800 apps identified, 662 were unique. Of these, 13.7% (91/662) were classified as alcohol reduction (95% CI 11.3-16.6), 53.9% (357/662) entertainment (95% CI 50.1-57.7), 18.9% (125/662) blood alcohol content measurement (95% CI 16.1-22.0) and 13.4% (89/662) other (95% CI 11.1-16.3). The 51 free alcohol reduction apps and the top 10 paid apps contained a mean of 3.6 BCTs (SD 3.4), with approximately 12% (7/61) not including any BCTs. The BCTs used most often were "facilitate self-recording" (54%, 33/61), "provide information on consequences of excessive alcohol use and drinking cessation" (43%, 26/61), "provide feedback on performance" (41%, 25/61), "give options for additional and later support" (25%, 15/61) and "offer/direct towards appropriate written materials" (23%, 14/61). These apps also rarely included any of the 22 BCTs frequently used in other health behavior change interventions (mean 2.46, SD 2.06). Evidence was mentioned by 16

Behavior Change Techniques in Popular Alcohol Reduction Apps: Content Analysis

PubMed Central

Garnett, Claire; Brown, James; West, Robert; Michie, Susan

2015-01-01

Background Mobile phone apps have the potential to reduce excessive alcohol consumption cost-effectively. Although hundreds of alcohol-related apps are available, there is little information about the behavior change techniques (BCTs) they contain, or the extent to which they are based on evidence or theory and how this relates to their popularity and user ratings. Objective Our aim was to assess the proportion of popular alcohol-related apps available in the United Kingdom that focus on alcohol reduction, identify the BCTs they contain, and explore whether BCTs or the mention of theory or evidence is associated with app popularity and user ratings. Methods We searched the iTunes and Google Play stores with the terms “alcohol” and “drink”, and the first 800 results were classified into alcohol reduction, entertainment, or blood alcohol content measurement. Of those classified as alcohol reduction, all free apps and the top 10 paid apps were coded for BCTs and for reference to evidence or theory. Measures of popularity and user ratings were extracted. Results Of the 800 apps identified, 662 were unique. Of these, 13.7% (91/662) were classified as alcohol reduction (95% CI 11.3-16.6), 53.9% (357/662) entertainment (95% CI 50.1-57.7), 18.9% (125/662) blood alcohol content measurement (95% CI 16.1-22.0) and 13.4% (89/662) other (95% CI 11.1-16.3). The 51 free alcohol reduction apps and the top 10 paid apps contained a mean of 3.6 BCTs (SD 3.4), with approximately 12% (7/61) not including any BCTs. The BCTs used most often were “facilitate self-recording” (54%, 33/61), “provide information on consequences of excessive alcohol use and drinking cessation” (43%, 26/61), “provide feedback on performance” (41%, 25/61), “give options for additional and later support” (25%, 15/61) and “offer/direct towards appropriate written materials” (23%, 14/61). These apps also rarely included any of the 22 BCTs frequently used in other health behavior change

Effects of a home care mobile app on the outcomes of discharged patients with a stoma: a randomized controlled trial.

PubMed

Wang, Qing-Qing; Zhao, Jing; Huo, Xiao-Rong; Wu, Ling; Yang, Li-Fang; Li, Ju-Yun; Wang, Jie

2018-05-18

The aim of this study is to explore the effects of a home care mobile app on the outcomes of stoma patients who discharged from hospital. Patients with a newly formed stoma experience many difficulties after surgery. Mobile application (app) has the potential to help patients self-manage their diseases and adjust to the changes in their lives and is a convenient way to ensure the continuity of care. However, there is a lack of studies about the effects of a mobile app on the transitional care for improving discharged stoma-related health outcomes. A randomized controlled trial. 203 patients with a permanent stoma in tertiary hospitals in China were randomly assigned into two groups. Patients in the control group (n=103) received routine discharge care. Patients in the intervention group (n=100) received home care via a mobile app besides routine care. The psychosocial adjustment level, self-efficacy scale and stoma complications incidence were measured in the follow-up period and compared between the two groups. Data was collected at four time points: before intervention (baseline), at 1, 3 and 6 months after discharge. The psychosocial adjustment level and stoma self-efficacy score of the intervention group were significantly higher than those of the control group respectively at 1, 3 and 6-month follow-up (all P<0.05). The incidence of stoma complications in the intervention group were tending to reduce at 1, 3 and 6 months after discharge. The findings indicated that follow-up care at home via a mobile app can effectively improve the psychosocial adjustment level, self-efficacy scale and other related outcomes of stoma patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Effects of N-acetylimidazole on oxytocin binding in bovine mammary tissue

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

Zhao, X.; Gorewit, R.C.; Currie, W.B.

1990-01-01

The effects of N-acetylimidazole on specific binding of oxytocin to microsomal fractions of bovine mammary gland were studied. N-acetylimidazole suppressed oxytocin binding, with time and concentration dependence. Decreased oxytocin binding activity appeared to be due to decreased affinity of the hormone for its receptor. Acetylation of oxytocin, rather than of oxytocin receptors, seemed to be responsible for the decreased binding.

Relationship between potential aggregation-prone regions and HLA-DR-binding T-cell immune epitopes: implications for rational design of novel and follow-on therapeutic antibodies.

PubMed

Kumar, Sandeep; Mitchell, Mark A; Rup, Bonita; Singh, Satish K

2012-08-01

Aggregation and unwanted immunogenicity are hurdles to avoid in successful commercial development of antibody-based therapeutics. In this article, the relationship between aggregation-prone regions (APRs), capable of forming cross-β motifs/amyloid fibrils, and major histocompatibility complex class II-restricted human leukocyte antigen (HLA)-DR-binding T-cell immune epitopes (TcIEs) is analyzed using amino acid sequences of 25 therapeutic antibodies, 55 TcIEs recognized by T-regulatory cells (tregitopes), 1000 randomly generated 15-residue-long peptides, 2257 human self-TcIEs (autoantigens), and 11 peptides in HLA-peptide cocrystal structures. Sequence analyses from these diverse sources consistently show a high level of correlation between APRs and TcIEs: approximately one-third of TcIEs contain APRs, but the majority of APRs occur within TcIE regions (TcIERs). Tregitopes also contain APRs. Most APR-containing TcIERs can bind multiple HLA-DR alleles, suggesting that aggregation-driven adverse immune responses could impact a broad segment of patient population. This article has identified common molecular sequence-structure loci that potentially contribute toward both manufacturability and safety profiles of the therapeutic antibodies, thereby laying a foundation for simultaneous optimization of these attributes in novel and follow-on candidates. Incidence of APRs within TcIERs is not special to biotherapeutics, self-TcIEs from human proteins, involved in various diseases, also contain predicted APRs and experimentally proven amyloid-fibril-forming peptide sequence portions. Copyright © 2012 Wiley Periodicals, Inc.

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.

Discovery of and Interest in Health Apps Among Those With Mental Health Needs: Survey and Focus Group Study.

PubMed

Schueller, Stephen M; Neary, Martha; O'Loughlin, Kristen; Adkins, Elizabeth C

2018-06-11

A large number of health apps are available directly to consumers through app marketplaces. Little information is known, however, about how consumers search for these apps and which factors influence their uptake, adoption, and long-term use. The aim of this study was to understand what people look for when they search for health apps and the aspects and features of those apps that consumers find appealing. Participants were recruited from Northwestern University's Center for Behavioral Intervention Technologies' research registry of individuals with mental health needs. Most participants (n=811) completed a survey asking about their use and interest in health and mental health apps. Local participants were also invited to participate in focus groups. A total of 7 focus groups were conducted with 30 participants that collected more detailed information about their use and interest in health and mental health apps. Survey participants commonly found health apps through social media (45.1%, 366/811), personal searches (42.7%, 346/811), or word of mouth (36.9%, 299/811), as opposed to professional sources such as medical providers (24.6%, 200/811). From the focus groups, common themes related to uptake and use of health apps included the importance of personal use before adoption, specific features that users found desirable, and trusted sources either developing or promoting the apps. As the number of mental health and health apps continue to increase, it is imperative to better understand the factors that impact people's adoption and use of such technologies. Our findings indicated that a number of factors-ease of use, aesthetics, and individual experience-drove adoption and use and highlighted areas of focus for app developers and disseminators. ©Stephen M Schueller, Martha Neary, Kristen O'Loughlin, Elizabeth C Adkins. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 11.06.2018.

Adoption, Acceptability, and Effectiveness of a Mobile Health App for Personalized Prostate Cancer Survivorship Care: Protocol for a Realist Case Study of the Ned App

PubMed Central

Cafazzo, Joseph A; Feifer, Andrew

2017-01-01

Background By 2030, prostate cancer will be the most commonly diagnosed cancer in North America. To mitigate this impending challenge, comprehensive support mechanisms for disease- and treatment-specific changes in health and well-being must be proactively designed and thoughtfully implemented for streamlined survivorship care. mHealth apps have been lauded as a promising complement to current outpatient treatment and monitoring strategies, but have not yet been widely used to support prostate cancer survivorship needs. A realist evaluation is needed to examine the impact of such apps on the prostate cancer survivorship experience. Objective We seek to gain an understanding of how an mHealth app for prostate cancer survivorship care called Ned (No Evident Disease) is adopted and accepted by patients, caregivers, and clinicians. We also aim to determine the effect of Ned on health-related quality of life, satisfaction with cancer care, unmet needs, self-efficacy, and prostate cancer-related levels of anxiety. Methods The Ned case study is a 12-month mixed-methods embedded single-case study with a nested within-group pre-post comparison of health outcomes. We will give 400 patients, 200 caregivers, and 10 clinicians access to Ned. Participants will be asked to complete study assessments at baseline, 2 months, 6 months, and 12 months. We will conduct 30 semistructured qualitative interviews with patients (n=20) and their caregivers (n=10) poststudy to gain insight into their experience with the app. Results We recruited our first survivor in October 2017 and anticipate completing this study by May 2019. Conclusions This will, to our knowledge, be the first realist case study to evaluate an app for prostate cancer survivorship care. Prostate cancer survivors are set to increase in number and longevity, heightening the need for integrated survivorship solutions to provide them with optimal and durable outcomes. The knowledge gained from this study will comprehensively

Plausibility of Menstrual Cycle Apps Claiming to Support Conception.

PubMed

Freis, Alexander; Freundl-Schütt, Tanja; Wallwiener, Lisa-Maria; Baur, Sigfried; Strowitzki, Thomas; Freundl, Günter; Frank-Herrmann, Petra

2018-01-01

The interval of peak fertility during the menstrual cycle is of limited duration, and the day of ovulation varies, even in women with fairly regular cycles. Therefore, menstrual cycle apps identifying the "fertile window" for women trying to conceive must be quite precise. A deviation of a few days may lead the couple to focus on less- or non-fertile days for sexual intercourse and thus may be worse than random intercourse. The aim of the present investigation was to develop a scoring system for rating available apps for determining the fertile window and secondarily pilot test 12 apps currently available in both German and English (consisting of 6 calendar-based apps: Clue Menstruations- und Zykluskalender, Flo Menstruationskalender, Maya-Mein Periodentracker, Menstruationskalender Pro, Period Tracker Deluxe, and WomanLog-Pro-Kalender; 2 calculothermal apps: Ovy and Natural Cycles; and 4 symptothermal apps: myNFP, Lady Cycle, Lily, and OvuView). The calendar-based apps were investigated by entering several series of cycles with varying lengths, whereas the symptom-based apps were examined by entering data of cycles with known temperature rise, cervical mucus pattern, and clinical ovulation. The main criteria for evaluating the cycle apps were as follows: (1) What methods/parameters were used to determine the fertile window? (2) What study results exist concerning that underlying method/parameters? (3) What study results exist concerning the app itself? (4) Was there a qualified counseling service? The calendar-based apps predicted the fertile days based on data of previous cycles. They obtained zero points in our scoring system, as they did not comply with any of the evaluated criteria. Calculothermal apps had similar deficits for predicting the most fertile days and produced suboptimal results (Ovy 3/30 points and Natural Cycles 2/30 points). The symptothermal apps determined the fertile days based on parameters of the current cycle: Lady Cycle scored 20

Plausibility of Menstrual Cycle Apps Claiming to Support Conception

PubMed Central

Freis, Alexander; Freundl-Schütt, Tanja; Wallwiener, Lisa-Maria; Baur, Sigfried; Strowitzki, Thomas; Freundl, Günter; Frank-Herrmann, Petra

2018-01-01

The interval of peak fertility during the menstrual cycle is of limited duration, and the day of ovulation varies, even in women with fairly regular cycles. Therefore, menstrual cycle apps identifying the “fertile window” for women trying to conceive must be quite precise. A deviation of a few days may lead the couple to focus on less- or non-fertile days for sexual intercourse and thus may be worse than random intercourse. The aim of the present investigation was to develop a scoring system for rating available apps for determining the fertile window and secondarily pilot test 12 apps currently available in both German and English (consisting of 6 calendar-based apps: Clue Menstruations- und Zykluskalender, Flo Menstruationskalender, Maya-Mein Periodentracker, Menstruationskalender Pro, Period Tracker Deluxe, and WomanLog-Pro-Kalender; 2 calculothermal apps: Ovy and Natural Cycles; and 4 symptothermal apps: myNFP, Lady Cycle, Lily, and OvuView). The calendar-based apps were investigated by entering several series of cycles with varying lengths, whereas the symptom-based apps were examined by entering data of cycles with known temperature rise, cervical mucus pattern, and clinical ovulation. The main criteria for evaluating the cycle apps were as follows: (1) What methods/parameters were used to determine the fertile window? (2) What study results exist concerning that underlying method/parameters? (3) What study results exist concerning the app itself? (4) Was there a qualified counseling service? The calendar-based apps predicted the fertile days based on data of previous cycles. They obtained zero points in our scoring system, as they did not comply with any of the evaluated criteria. Calculothermal apps had similar deficits for predicting the most fertile days and produced suboptimal results (Ovy 3/30 points and Natural Cycles 2/30 points). The symptothermal apps determined the fertile days based on parameters of the current cycle: Lady Cycle scored 20

Smartphone use in neurosurgery? APP-solutely!

PubMed Central

Zaki, Michael; Drazin, Doniel

2014-01-01

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

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.

Enhancing Pharmacy Student Learning and Perceptions of Medical Apps

PubMed Central

Aungst, Timothy Dy; Brown, Nicole V; Cui, Yan; Tam, Leonard

2016-01-01

Background The use of mobile apps in health care is growing. Current and future practitioners must be equipped with the skills to navigate and utilize apps in patient care, yet few strategies exist for training health care professional students on the usage of apps. Objective To characterize first-year pharmacy student use of medical apps, evaluate first-year pharmacy student's perception of skills in finding, evaluating, and using medical apps before and after a focused learning experience, and assess student satisfaction and areas for improvement regarding the learning experience. Methods Students listened to a recorded, Web-based lecture on finding, evaluating, and using mobile apps in patient care. A 2-hour, interactive workshop was conducted during which students were led by an instructor through a discussion on strategies for finding and using apps in health care. The students practiced evaluating 6 different health care–related apps. Surveys were conducted before and after the focused learning experience to assess students' perceptions of medical apps and current use and perspectives on satisfaction with the learning experience and role of technology in health care. Results This educational intervention is the first described formal, interactive method to educate student pharmacists on medical apps. With a 99% response rate, surveys conducted before and after the learning experience displayed perceived improvement in student skills related to finding (52/119, 44% before vs 114/120, 95% after), evaluating (18/119, 15% before vs 112/120, 93% after), and using medical apps in patient care (31/119, 26% before vs 108/120, 90% after) and the health sciences classroom (38/119, 32% before vs 104/120, 87% after). Students described satisfaction with the educational experience and agreed that it should be repeated in subsequent years (89/120, 74% agreed or strongly agreed). Most students surveyed possessed portable electronic devices (107/119, 90% mobile phone) and

Enhancing Pharmacy Student Learning and Perceptions of Medical Apps.

PubMed

Rodis, Jennifer; Aungst, Timothy Dy; Brown, Nicole V; Cui, Yan; Tam, Leonard

2016-05-12

The use of mobile apps in health care is growing. Current and future practitioners must be equipped with the skills to navigate and utilize apps in patient care, yet few strategies exist for training health care professional students on the usage of apps. To characterize first-year pharmacy student use of medical apps, evaluate first-year pharmacy student's perception of skills in finding, evaluating, and using medical apps before and after a focused learning experience, and assess student satisfaction and areas for improvement regarding the learning experience. Students listened to a recorded, Web-based lecture on finding, evaluating, and using mobile apps in patient care. A 2-hour, interactive workshop was conducted during which students were led by an instructor through a discussion on strategies for finding and using apps in health care. The students practiced evaluating 6 different health care-related apps. Surveys were conducted before and after the focused learning experience to assess students' perceptions of medical apps and current use and perspectives on satisfaction with the learning experience and role of technology in health care. This educational intervention is the first described formal, interactive method to educate student pharmacists on medical apps. With a 99% response rate, surveys conducted before and after the learning experience displayed perceived improvement in student skills related to finding (52/119, 44% before vs 114/120, 95% after), evaluating (18/119, 15% before vs 112/120, 93% after), and using medical apps in patient care (31/119, 26% before vs 108/120, 90% after) and the health sciences classroom (38/119, 32% before vs 104/120, 87% after). Students described satisfaction with the educational experience and agreed that it should be repeated in subsequent years (89/120, 74% agreed or strongly agreed). Most students surveyed possessed portable electronic devices (107/119, 90% mobile phone) and agreed with the concept of medical apps

Apps in sleep medicine.

PubMed

Stippig, Andreas; Hübers, Ulrich; Emerich, Markus

2015-03-01

Users of mobile devices such as iPhones or iPads are offered a wide range of applications (apps) regarding sleep and sleep medicine. This article will give an overview about the apps that are available. Moreover, it will present how they work and determine if they can be used in therapy. The apps' competence to count snoring noises had to be evaluated. This was done with a three-piece test set-up to analyze the apps' ability to distinguish between snoring sounds and disturbing noises such as cars driving past the window, conversations in the bedroom, or even just the rustling of sheets and blankets. The tested apps monitor and record snoring noises well as long as they are used in a soundproof environment. In a real-life environment with various disturbing noises, the apps show difficulties in telling snoring sounds and other noises apart. The tested apps are not accurate enough to replace the common diagnostic standard in therapy. However, they can be a helpful addition. Especially, singles could use them who do not know if their snoring has improved with an OA and do not have anybody to ask.

Using WhatsApp and Facebook Online Social Groups for Smoking Relapse Prevention for Recent Quitters: A Pilot Pragmatic Cluster Randomized Controlled Trial

PubMed Central

Chan, Ching Han Helen; Lai, Chi-Keung Jonah; Chan, Wai Fung Vivian; Wang, Man Ping; Li, Ho Cheung William; Chan, Sophia Siu Chee; Lam, Tai-Hing

2015-01-01

Background Quit attempters often have episodes of smoking relapse before they eventually quit. Interactive text messaging through mobile phones has been shown to increase abstinence. This service can be potentially applied on the platform of a social networking service to help quitters maintain abstinence. Objective Our aim was to determine if the group discussion and reminders via the WhatsApp or Facebook social group were effective to prevent smoking relapse in quitters who had stopped smoking recently. Methods This was a single-blinded, parallel, 3-arm pilot cluster randomized controlled trial allocating recent quitters, who had completed an 8-week treatment and reported abstinence for at least 7 days, to WhatsApp (n=42), Facebook (n=40), and a control group (n=54). The 2 intervention groups participated in a 2-month online group discussion with either WhatsApp or Facebook moderated by a trained smoking cessation counselor and received a self-help booklet on smoking cessation. The control group only received the booklet. The primary outcome was the 2- and 6-month relapse rates, defined as the proportion of participants who smoked at least 5 cigarettes in 3 consecutive days. Results Fewer participants in the WhatsApp group (17%, 7/42) reported relapse than the control group (42.6%, 23/54) at 2-month (OR 0.27, 95% CI 0.10-0.71) and 6-month (40.5%, 17/42 vs 61.1%, 33/54; OR 0.43, 95% CI 0.19-0.99) follow-ups. The Facebook group (30.0%, 12/40) had an insignificantly lower relapse rate than the control group (42.6%, 23/54) at 2-month (OR 0.58, 95% CI 0.24-1.37) and 6-month (52.5%, 13/40 vs 61.1%, 33/54; OR 0.70, 95% CI 0.31-1.61) follow-ups. The WhatsApp social groups had more moderators’ posts (median 60, IQR 25 vs median 32, IQR 7; P=.05) and participants’ posts (median 35, IQR 50 vs median 6, IQR 9; P=.07) than their Facebook counterparts, but the difference was insignificant. Conclusions The intervention via the WhatsApp social group was effective in reducing

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

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

Uptake of an Incentive-Based mHealth App: Process Evaluation of the Carrot Rewards App

PubMed Central

Oh, Paul; Alter, David; Leahey, Tricia; Kwan, Matthew; Faulkner, Guy

2017-01-01

Background Behavioral economics has stimulated renewed interest in financial health incentives worldwide. The Carrot Rewards app was developed as part of a public-private partnership to reward Canadians with loyalty points (eg, movies and groceries) for downloading the app, referring friends, and completing an average of 1 to 2 educational health quizzes per week (“micro-learning”), with long-term objectives of increasing health knowledge and encouraging healthy behaviors. Objective The main objective of this study was to evaluate uptake of a loyalty points-based mHealth app during the exclusive 3-month launch period in British Columbia (BC), Canada. The secondary aims were to describe the health and sociodemographic characteristics of users, as well as participation levels (eg, proportion of quizzes completed and friends referred). Methods The app was promoted via loyalty program email campaigns (1.64 million emails). Number of downloads and registrations (users enter age, gender, and valid BC postal code to register) were collected. Additional sociodemographics were inferred by linking postal codes with census data at the local health area (LHA) level. Health risk assessments were also deployed. Participation levels were collected over 3 months and descriptive data were presented. Results In 3 months, 67,464 individuals downloaded the app; in its first week, Carrot Rewards was the most downloaded health app in Canada. Among valid users (n=57,885; at least one quiz completed), the majority were female (62.96%; 36,446/57,885) and aged 18 to 34 years (54.34%; 31,459/57,885). More than half of the users (52.40%; 30,332/57,885) resided in LHAs where the median personal income was below the provincial average (Can $28,765). Furthermore, 64.42% (37,291/57,885) of users lived in metropolitan (ie, urban) LHAs, compared with 56.17% of the general BC population. The most prevalent risk factors were “not” meeting physical activity guidelines (72.70%; 31

Cannabis Mobile Apps: A Content Analysis

PubMed Central

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

2015-01-01

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

Mobile apps in cardiology: review.

PubMed

Martínez-Pérez, Borja; de la Torre-Díez, Isabel; López-Coronado, Miguel; Herreros-González, Jesús

2013-07-24

Cardiovascular diseases are the deadliest diseases worldwide, with 17.3 million deaths in 2008 alone. Among them, heart-related deaths are of the utmost relevance; a fact easily proven by the 7.25 million deaths caused by ischemic heart disease alone in that year. The latest advances in smartphones and mHealth have been used in the creation of thousands of medical apps related to cardiology, which can help to reduce these mortality rates. The aim of this paper is to study the literature on mobile systems and applications currently available, as well as the existing apps related to cardiology from the leading app stores and to then classify the results to see what is available and what is missing, focusing particularly on commercial apps. Two reviews have been developed. One is a literature review of mobile systems and applications, retrieved from several databases and systems such as Scopus, PubMed, IEEE Xplore, and Web of Knowledge. The other is a review of mobile apps in the leading app stores, Google play for Android and Apple's App Store for iOS. Search queries up to May 2013 located 406 papers and 710 apps related to cardiology and heart disease. The most researched section in the literature associated with cardiology is related to mobile heart (and vital signs) monitoring systems and the methods involved in the classification of heart signs in order to detect abnormal functions. Other systems with a significant number of papers are mobile cardiac rehabilitation systems, blood pressure measurement, and systems for the detection of heart failure. The majority of apps for cardiology are heart monitors and medical calculators. Other categories with a high number of apps are those for ECG education and interpretation, cardiology news and journals, blood pressure tracking, heart rate monitoring using an external device, and CPR instruction. There are very few guides on cardiac rehabilitation and apps for the management of the cardiac condition, and there were no

The AppScale Cloud Platform

PubMed Central

Krintz, Chandra

2013-01-01

AppScale is an open source distributed software system that implements a cloud platform as a service (PaaS). AppScale makes cloud applications easy to deploy and scale over disparate cloud fabrics, implementing a set of APIs and architecture that also makes apps portable across the services they employ. AppScale is API-compatible with Google App Engine (GAE) and thus executes GAE applications on-premise or over other cloud infrastructures, without modification. PMID:23828721

Mobile medical apps for patient education: a graded review of available dermatology apps.

PubMed

Masud, Aisha; Shafi, Shahram; Rao, Babar K

2018-02-01

The utilization of mobile applications (apps) as educational resources for patients highlights the need for an objective method of evaluating the quality of health care-related mobile apps. In this study, a quantified rubric was developed to objectively grade publicly available dermatology mobile apps with the primary focus of patient education. The rubric included 5 criteria thought to be most important in evaluating the adequacy of these apps in relaying health information to patients: educational objectives, content, accuracy, design, and conflict of interest. A 4-point scale was applied to each criterion. The use of this objective rubric could have implications in the evaluation and recommendation of mobile health care apps as a vital educational resource for patients.

SnoN co-repressor binds and represses smad7 gene promoter.

PubMed

Briones-Orta, Marco A; Sosa-Garrocho, Marcela; Moreno-Alvarez, Paola; Fonseca-Sánchez, Miguel A; Macías-Silva, Marina

2006-03-17

SnoN and Ski oncoproteins are co-repressors for Smad proteins and repress TGF-beta-responsive gene expression. The smad7 gene is a TGF-beta target induced by Smad signaling, and its promoter contains the Smad-binding element (SBE) required for a positive regulation by the TGF-beta/Smad pathway. SnoN and Ski co-repressors also bind SBE but regulate negatively smad7 gene. Ski along with Smad4 binds and represses the smad7 promoter, whereas the repression mechanism by SnoN is not clear. Ski and SnoN overexpression inhibits smad7 reporter expression induced through TGF-beta signaling. Using chromatin immunoprecipitation assays, we found that SnoN binds smad7 promoter at the basal condition, whereas after a short TGF-beta treatment for 15-30 min SnoN is downregulated and no longer bound smad7 promoter. Interestingly, after a prolonged TGF-beta treatment SnoN is upregulated and returns to its position on the smad7 promoter, functioning probably as a negative feedback control. Thus, SnoN also seems to regulate negatively the TGF-beta-responsive smad7 gene by binding and repressing its promoter in a similar way to Ski.

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

PubMed

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

2017-06-01

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

iPhone app adherence to expert-recommended guidelines for pediatric obesity prevention.

PubMed

Wearing, Jessica R; Nollen, Nikki; Befort, Christie; Davis, Ann M; Agemy, Carolina K

2014-04-01

Pediatric obesity is a serious and prevalent problem. Smartphone technology, which is becoming increasingly available to children of diverse backgrounds, presents a unique opportunity to instill healthy behaviors before the onset of obesity. Past studies have examined the use of smartphone applications as tools of health behavior modification for adults. The present study examines the content of children's exercise and nutrition smartphone apps. Sixty-two iPhone apps were identified and coded by two independent raters for adherence to expert-recommended behaviors (e.g., five fruits/vegetables per day) and strategies (e.g., self-monitoring diet/physical activity) for the prevention of pediatric obesity. App behavioral and strategy index scores were uniformly low. Apps were more likely to address expert-recommended behaviors for the prevention of pediatric obesity (93.5%), whereas few apps addressed recommended strategies (20.9%). The most common behaviors addressed included physical activity (53.2%) and fruit/vegetable consumption (48.3%). Other important behaviors (e.g., screen time [1.6%] and family meals together [1.6%]) were rarely addressed. Current children's diet and exercise apps could be improved with increased adherence to expert-recommended guidelines, especially expert-recommended strategies.

iPhone App Adherence to Expert-Recommended Guidelines for Pediatric Obesity Prevention

PubMed Central

Wearing, Jessica R.; Befort, Christie; Davis, Ann M.; Agemy, Carolina K.

2014-01-01

Abstract Background: Pediatric obesity is a serious and prevalent problem. Smartphone technology, which is becoming increasingly available to children of diverse backgrounds, presents a unique opportunity to instill healthy behaviors before the onset of obesity. Past studies have examined the use of smartphone applications as tools of health behavior modification for adults. The present study examines the content of children's exercise and nutrition smartphone apps. Method: Sixty-two iPhone apps were identified and coded by two independent raters for adherence to expert-recommended behaviors (e.g., five fruits/vegetables per day) and strategies (e.g., self-monitoring diet/physical activity) for the prevention of pediatric obesity. Results: App behavioral and strategy index scores were uniformly low. Apps were more likely to address expert-recommended behaviors for the prevention of pediatric obesity (93.5%), whereas few apps addressed recommended strategies (20.9%). The most common behaviors addressed included physical activity (53.2%) and fruit/vegetable consumption (48.3%). Other important behaviors (e.g., screen time [1.6%] and family meals together [1.6%]) were rarely addressed. Conclusions: Current children's diet and exercise apps could be improved with increased adherence to expert-recommended guidelines, especially expert-recommended strategies. PMID:24655230

Supporting Homework Compliance in Cognitive Behavioural Therapy: Essential Features of Mobile Apps

PubMed Central

Tang, Wei

2017-01-01

Cognitive behavioral therapy (CBT) is one of the most effective psychotherapy modalities used to treat depression and anxiety disorders. Homework is an integral component of CBT, but homework compliance in CBT remains problematic in real-life practice. The popularization of the mobile phone with app capabilities (smartphone) presents a unique opportunity to enhance CBT homework compliance; however, there are no guidelines for designing mobile phone apps created for this purpose. Existing literature suggests 6 essential features of an optimal mobile app for maximizing CBT homework compliance: (1) therapy congruency, (2) fostering learning, (3) guiding therapy, (4) connection building, (5) emphasis on completion, and (6) population specificity. We expect that a well-designed mobile app incorporating these features should result in improved homework compliance and better outcomes for its users. PMID:28596145

The heparin-binding site in tetranectin is located in the N-terminal region and binding does not involve the carbohydrate recognition domain.

PubMed Central

Lorentsen, R H; Graversen, J H; Caterer, N R; Thogersen, H C; Etzerodt, M

2000-01-01

Tetranectin is a homotrimeric plasma and extracellular-matrix protein that binds plasminogen and complex sulphated polysaccharides including heparin. In terms of primary and tertiary structure, tetranectin is related to the collectin family of Ca(2+)-binding C-type lectins. Tetranectin is encoded in three exons. Exon 3 encodes the carbohydrate recognition domain, which binds to kringle 4 in plasminogen at low levels of Ca(2+). Exon 2 encodes an alpha-helix, which is necessary and sufficient to govern the trimerization of tetranectin by assembling into a triple-helical coiled-coil structural element. Here we show that the heparin-binding site in tetranectin resides not in the carbohydrate recognition domain but within the N-terminal region, comprising the 16 amino acid residues encoded by exon 1. In particular, the lysine residues in the decapeptide segment KPKKIVNAKK (tetranectin residues 6-15) are shown to be of primary importance in heparin binding. PMID:10727405

The heparin-binding site in tetranectin is located in the N-terminal region and binding does not involve the carbohydrate recognition domain.

PubMed

Lorentsen, R H; Graversen, J H; Caterer, N R; Thogersen, H C; Etzerodt, M

2000-04-01

Tetranectin is a homotrimeric plasma and extracellular-matrix protein that binds plasminogen and complex sulphated polysaccharides including heparin. In terms of primary and tertiary structure, tetranectin is related to the collectin family of Ca(2+)-binding C-type lectins. Tetranectin is encoded in three exons. Exon 3 encodes the carbohydrate recognition domain, which binds to kringle 4 in plasminogen at low levels of Ca(2+). Exon 2 encodes an alpha-helix, which is necessary and sufficient to govern the trimerization of tetranectin by assembling into a triple-helical coiled-coil structural element. Here we show that the heparin-binding site in tetranectin resides not in the carbohydrate recognition domain but within the N-terminal region, comprising the 16 amino acid residues encoded by exon 1. In particular, the lysine residues in the decapeptide segment KPKKIVNAKK (tetranectin residues 6-15) are shown to be of primary importance in heparin binding.

Structural and functional characterization of cargo-binding sites on the μ4-subunit of adaptor protein complex 4.

PubMed

Ross, Breyan H; Lin, Yimo; Corales, Esteban A; Burgos, Patricia V; Mardones, Gonzalo A

2014-01-01

Adaptor protein (AP) complexes facilitate protein trafficking by playing key roles in the selection of cargo molecules to be sorted in post-Golgi compartments. Four AP complexes (AP-1 to AP-4) contain a medium-sized subunit (μ1-μ4) that recognizes YXXØ-sequences (Ø is a bulky hydrophobic residue), which are sorting signals in transmembrane proteins. A conserved, canonical region in μ subunits mediates recognition of YXXØ-signals by means of a critical aspartic acid. Recently we found that a non-canonical YXXØ-signal on the cytosolic tail of the Alzheimer's disease amyloid precursor protein (APP) binds to a distinct region of the μ4 subunit of the AP-4 complex. In this study we aimed to determine the functionality of both binding sites of μ4 on the recognition of the non-canonical YXXØ-signal of APP. We found that substitutions in either binding site abrogated the interaction with the APP-tail in yeast-two hybrid experiments. Further characterization by isothermal titration calorimetry showed instead loss of binding to the APP signal with only the substitution R283D at the non-canonical site, in contrast to a decrease in binding affinity with the substitution D190A at the canonical site. We solved the crystal structure of the C-terminal domain of the D190A mutant bound to this non-canonical YXXØ-signal. This structure showed no significant difference compared to that of wild-type μ4. Both differential scanning fluorimetry and limited proteolysis analyses demonstrated that the D190A substitution rendered μ4 less stable, suggesting an explanation for its lower binding affinity to the APP signal. Finally, in contrast to overexpression of the D190A mutant, and acting in a dominant-negative manner, overexpression of μ4 with either a F255A or a R283D substitution at the non-canonical site halted APP transport at the Golgi apparatus. Together, our analyses support that the functional recognition of the non-canonical YXXØ-signal of APP is limited to the non

Structural and Functional Characterization of Cargo-Binding Sites on the μ4-Subunit of Adaptor Protein Complex 4

PubMed Central

Ross, Breyan H.; Lin, Yimo; Corales, Esteban A.; Burgos, Patricia V.; Mardones, Gonzalo A.

2014-01-01

Adaptor protein (AP) complexes facilitate protein trafficking by playing key roles in the selection of cargo molecules to be sorted in post-Golgi compartments. Four AP complexes (AP-1 to AP-4) contain a medium-sized subunit (μ1-μ4) that recognizes YXXØ-sequences (Ø is a bulky hydrophobic residue), which are sorting signals in transmembrane proteins. A conserved, canonical region in μ subunits mediates recognition of YXXØ-signals by means of a critical aspartic acid. Recently we found that a non-canonical YXXØ-signal on the cytosolic tail of the Alzheimer's disease amyloid precursor protein (APP) binds to a distinct region of the μ4 subunit of the AP-4 complex. In this study we aimed to determine the functionality of both binding sites of μ4 on the recognition of the non-canonical YXXØ-signal of APP. We found that substitutions in either binding site abrogated the interaction with the APP-tail in yeast-two hybrid experiments. Further characterization by isothermal titration calorimetry showed instead loss of binding to the APP signal with only the substitution R283D at the non-canonical site, in contrast to a decrease in binding affinity with the substitution D190A at the canonical site. We solved the crystal structure of the C-terminal domain of the D190A mutant bound to this non-canonical YXXØ-signal. This structure showed no significant difference compared to that of wild-type μ4. Both differential scanning fluorimetry and limited proteolysis analyses demonstrated that the D190A substitution rendered μ4 less stable, suggesting an explanation for its lower binding affinity to the APP signal. Finally, in contrast to overexpression of the D190A mutant, and acting in a dominant-negative manner, overexpression of μ4 with either a F255A or a R283D substitution at the non-canonical site halted APP transport at the Golgi apparatus. Together, our analyses support that the functional recognition of the non-canonical YXXØ-signal of APP is limited to the non

Vig r 6, the cytokinin-specific binding protein from mung bean (Vigna radiata) sprouts, cross-reacts with Bet v 1-related allergens and binds IgE from birch pollen allergic patients’ sera

PubMed Central

Guhsl, Eva Elisabeth; Hofstetter, Gerlinde; Hemmer, Wolfgang; Ebner, Christof; Vieths, Stefan; Vogel, Lothar; Breiteneder, Heimo; Radauer, Christian

2014-01-01

Scope Birch pollen associated allergy to mung bean sprouts is caused by cross-reactivity between the birch pollen allergen Bet v 1 and the mung bean allergen Vig r 1. We aimed to determine the allergenicity of the cytokinin-specific binding protein from mung bean (Vig r 6), another allergen related to Bet v 1 with only 31% sequence identity. Methods and results Bet v 1, Gly m 4, Vig r 1, and Vig r 6 were produced in Escherichia coli. In an ELISA, 73 and 32% of Bet v 1-sensitized birch-allergic patients’ sera (n = 60) showed IgE binding to Vig r 1 and Vig r 6, respectively. Of 19 patients who reported allergic reactions or had positive prick-to-prick tests to mung bean sprouts, 79% showed IgE binding to Vig r 1 and 63% showed IgE binding to Vig r 6. Bet v 1 completely inhibited IgE binding to both mung bean allergens. Vig r 6 showed partial cross-reactivity with Vig r 1 and activated basophils sensitized with mung bean allergic patients’ sera. Conclusion We demonstrated IgE cross-reactivity despite low sequence identity between Vig r 6 and other Bet v 1-related allergens. Thus, IgE binding to Vig r 6 may contribute to birch pollinosis-associated mung bean sprout allergy. PMID:23996905

A qualitative study of user perceptions of mobile health apps.

PubMed

Peng, Wei; Kanthawala, Shaheen; Yuan, Shupei; Hussain, Syed Ali

2016-11-14

Mobile apps for health exist in large numbers today, but oftentimes, consumers do not continue to use them after a brief period of initial usage, are averse toward using them at all, or are unaware that such apps even exist. The purpose of our study was to examine and qualitatively determine the design and content elements of health apps that facilitate or impede usage from the users' perceptive. In 2014, six focus groups and five individual interviews were conducted in the Midwest region of the U.S. with a mixture of 44 smartphone owners of various social economic status. The participants were asked about their general and health specific mobile app usage. They were then shown specific features of exemplar health apps and prompted to discuss their perceptions. The focus groups and interviews were audio recorded, transcribed verbatim, and coded using the software NVivo. Inductive thematic analysis was adopted to analyze the data and nine themes were identified: 1) barriers to adoption of health apps, 2) barriers to continued use of health apps, 3) motivators, 4) information and personalized guidance, 5) tracking for awareness and progress, 6) credibility, 7) goal setting, 8) reminders, and 9) sharing personal information. The themes were mapped to theories for interpretation of the results. This qualitative research with a diverse pool of participants extended previous research on challenges and opportunities of health apps. The findings provide researchers, app designers, and health care providers insights on how to develop and evaluate health apps from the users' perspective.

Developing mental health mobile apps: Exploring adolescents' perspectives.

PubMed

Kenny, Rachel; Dooley, Barbara; Fitzgerald, Amanda

2016-06-01

Mobile applications or 'apps' have significant potential for use in mental health interventions with adolescents. However, there is a lack of research exploring end users' needs from such technologies. The aim of this study was to explore adolescents' needs and concerns in relation to mental health mobile apps. Five focus groups were conducted with young people aged 15-16 years (N = 34, 60% male). Participants were asked about their views in relation to the use of mental health mobile technologies and were asked to give their responses to a mental health app prototype. Participants identified (1) safety, (2) engagement, (3) functionality, (4) social interaction, (5) awareness, (6) accessibility, (7) gender and (8) young people in control as important factors. Understanding end users' needs and concerns in relation to this topic will inform the future development of youth-oriented mental health apps that are acceptable to young people. © The Author(s) 2014.

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

PubMed

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

2016-11-01

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

Mobile Videoconferencing Apps for Telemedicine.

PubMed

Zhang, Kai; Liu, Wei-Li; Locatis, Craig; Ackerman, Michael

2016-01-01

The quality and performance of several videoconferencing applications (apps) tested on iOS (Apple, Cupertino, CA) and Android (Google, Mountain View, CA) mobile platforms using Wi-Fi (802.11), third-generation (3G), and fourth-generation (4G) cellular networks are described. The tests were done to determine how well apps perform compared with videoconferencing software installed on computers or with more traditional videoconferencing using dedicated hardware. The rationale for app assessment and the testing methodology are described. Findings are discussed in relation to operating system platform (iOS or Android) for which the apps were designed and the type of network (Wi-Fi, 3G, or 4G) used. The platform, network, and apps interact, and it is impossible to discuss videoconferencing experienced on mobile devices in relation to one of these factors without referencing the others. Apps for mobile devices can vary significantly from other videoconferencing software or hardware. App performance increased over the testing period due to improvements in network infrastructure and how apps manage bandwidth.

Mobile Videoconferencing Apps for Telemedicine

PubMed Central

Liu, Wei-Li; Locatis, Craig; Ackerman, Michael

2016-01-01

Abstract Introduction: The quality and performance of several videoconferencing applications (apps) tested on iOS (Apple, Cupertino, CA) and Android™ (Google, Mountain View, CA) mobile platforms using Wi-Fi (802.11), third-generation (3G), and fourth-generation (4G) cellular networks are described. Materials and Methods: The tests were done to determine how well apps perform compared with videoconferencing software installed on computers or with more traditional videoconferencing using dedicated hardware. The rationale for app assessment and the testing methodology are described. Results: Findings are discussed in relation to operating system platform (iOS or Android) for which the apps were designed and the type of network (Wi-Fi, 3G, or 4G) used. The platform, network, and apps interact, and it is impossible to discuss videoconferencing experienced on mobile devices in relation to one of these factors without referencing the others. Conclusions: Apps for mobile devices can vary significantly from other videoconferencing software or hardware. App performance increased over the testing period due to improvements in network infrastructure and how apps manage bandwidth. PMID:26204322

Experimental binding energies for the metal complexes [Mg(CH3OH)n](2+), [Ca(CH3OH)n](2+), and [Sr(CH3OH)n](2+) for n in the range 4-20.

PubMed

Bruzzi, E; Stace, A J

2014-10-09

A supersonic source of clusters has been used to prepare neutral complexes of methanol in association with an alkaline earth metal atom. From these complexes the following metal-containing dications have been generated through electron ionization: [Mg(CH3OH)n](2+), [Ca(CH3OH)n](2+), and [Sr(CH3OH)n](2+), and for n in the range 4-20, kinetic energy release measurements following the evaporation of a single molecule have been undertaken using a high resolution mass spectrometer. Using finite heat bath theory, these data have been transformed into binding energies for individual methanol molecules attached to each of the three cluster systems. In the larger complexes (n > 6) the results exhibit a consistent trend, whereby the experimental binding energy data for all three metal ions are similar, suggesting that the magnitude of the charge rather than charge density influences the strength of the interaction. From a comparison with data recorded previously for (CH3OH)nH(+) it is found that the 2+ charge on a metal ion has an effect on the binding energy of molecules in complexes containing up to 20 solvent molecules. The results recorded for [Ca(CH3OH)n](2+) show evidence of a very marked transition between n = 6 and 7, which is thought to coincide with the completion of a primary solvation shell and the onset of molecules starting to occupy a second and most probably a third shell.

Mobile Apps in Cardiology: Review

PubMed Central

2013-01-01

Background Cardiovascular diseases are the deadliest diseases worldwide, with 17.3 million deaths in 2008 alone. Among them, heart-related deaths are of the utmost relevance; a fact easily proven by the 7.25 million deaths caused by ischemic heart disease alone in that year. The latest advances in smartphones and mHealth have been used in the creation of thousands of medical apps related to cardiology, which can help to reduce these mortality rates. Objective The aim of this paper is to study the literature on mobile systems and applications currently available, as well as the existing apps related to cardiology from the leading app stores and to then classify the results to see what is available and what is missing, focusing particularly on commercial apps. Methods Two reviews have been developed. One is a literature review of mobile systems and applications, retrieved from several databases and systems such as Scopus, PubMed, IEEE Xplore, and Web of Knowledge. The other is a review of mobile apps in the leading app stores, Google play for Android and Apple’s App Store for iOS. Results Search queries up to May 2013 located 406 papers and 710 apps related to cardiology and heart disease. The most researched section in the literature associated with cardiology is related to mobile heart (and vital signs) monitoring systems and the methods involved in the classification of heart signs in order to detect abnormal functions. Other systems with a significant number of papers are mobile cardiac rehabilitation systems, blood pressure measurement, and systems for the detection of heart failure. The majority of apps for cardiology are heart monitors and medical calculators. Other categories with a high number of apps are those for ECG education and interpretation, cardiology news and journals, blood pressure tracking, heart rate monitoring using an external device, and CPR instruction. There are very few guides on cardiac rehabilitation and apps for the management of the

Semi-empirical quantum evaluation of peptide - MHC class II binding

NASA Astrophysics Data System (ADS)

González, Ronald; Suárez, Carlos F.; Bohórquez, Hugo J.; Patarroyo, Manuel A.; Patarroyo, Manuel E.

2017-01-01

Peptide presentation by the major histocompatibility complex (MHC) is a key process for triggering a specific immune response. Studying peptide-MHC (pMHC) binding from a structural-based approach has potential for reducing the costs of investigation into vaccine development. This study involved using two semi-empirical quantum chemistry methods (PM7 and FMO-DFTB) for computing the binding energies of peptides bonded to HLA-DR1 and HLA-DR2. We found that key stabilising water molecules involved in the peptide binding mechanism were required for finding high correlation with IC50 experimental values. Our proposal is computationally non-intensive, and is a reliable alternative for studying pMHC binding interactions.

Ligand binding to the human MT2 melatonin receptor: The role of residues in transmembrane domains 3, 6, and 7

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

Mazna, Petr; Berka, Karel; Jelinkova, Irena

To better understand the mechanism of interactions between G-protein-coupled melatonin receptors and their ligands, our previously reported homology model of human MT2 receptor with docked 2-iodomelatonin was further refined and used to select residues within TM3, TM6, and TM7 potentially important for receptor-ligand interactions. Selected residues were mutated and radioligand-binding assay was used to test the binding affinities of hMT2 receptors transiently expressed in HEK293 cells. Our data demonstrate that residues N268 and A275 in TM6 as well as residues V291 and L295 in TM7 are essential for 2-iodomelatonin binding to the hMT2 receptor, while TM3 residues M120, G121, V124,more » and I125 may participate in binding of other receptor agonists and/or antagonists. Presented data also hint at possible specific interaction between the side-chain of Y188 in second extracellular loop and N-acetyl group of 2-iodomelatonin.« less

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

The binding interaction of imazapyr with cucurbit[n]uril (n = 6-8): Combined experimental and molecular modeling study

NASA Astrophysics Data System (ADS)

Mokhtar, Maali Saad; Suliman, FakhrEldin O.; Elbashir, Abdalla A.

2018-04-01

The inclusion complexes of imazapyr (IMA) with cucurbit[n]uril, CB[n] (n = 6-8), have been investigated. Fluorescence spectroscopy, MALDI-TOF, and 1HNMR were used to investigate and characterize the inclusion complexation of IMA and CB[n] in solutions. Whereas the solid state complexes have been characterized by Fourier transform infrared spectroscopy (FTIR), and powder X-ray diffraction (PXRD). IMA was found to form 1:1 complexes with CB[n] with association constants ranging from 5.80 × 102-2.65 × 103. The guest molecule IMA was found to encapsulate into the larger cavities of CB[7] and CB[8], whereas with CB[6] the molecule remains outside the cavity. Molecular dynamic (MD) simulations were used to follow the inclusion process at an atomistic level to study the mechanism and stability of inclusion. The results obtained showed that inclusion complexes of IMA with both CB[7] and CB[8] are highly stable in aqueous media, but the CB[6] smaller cavity size prohibited the formation of an inclusion complex with IMA. The results clearly show that in addition to hydrophobic effects the presence of hydrogen bonding has added greatly to the stability of these complexes.

Diet app use by sports dietitians: a survey in five countries.

PubMed

Jospe, Michelle R; Fairbairn, Kirsty A; Green, Peter; Perry, Tracy L

2015-01-22

Despite the hundreds of diet apps available for use on smartphones (mobile phones), no studies have examined their use as tools for dietary assessment and tracking in sports nutrition. The aim is to examine the prevalence and perceptions of using smartphone diet apps for dietary assessment and tracking among sports dietitians. A cross-sectional online survey to examine the use and perception of diet apps was developed and distributed to sports dietitians in Australia, Canada, New Zealand, the United Kingdom, and the United States (US). The overall response rate from the 1709 sports dietitians invited to participate was 10.3% (n=180). diet apps were used by 32.4% (57/176) of sports dietitians to assess and track the dietary intake of athletes. Sports dietitians from the US were more likely to use smartphone diet apps than sports dietitians from other countries (OR=5.61, 95% CI 1.84-17.08, P=.002). Sports dietitians used 28 different diet apps, with 56% (32/57) choosing MyFitnessPal. Overall, sports dietitians held a positive perception of smartphone diet apps, with the majority of respondents viewing diet apps as "better" (25/53, 47%) or "equivalent" (22/53, 41%) when compared with traditional dietary assessment methods. Nearly one-third of sports dietitians used mobile phone diet apps in sports nutrition practice, and viewed them as useful in helping to assess and track the dietary intake of athletes.

Diet App Use by Sports Dietitians: A Survey in Five Countries

PubMed Central

Fairbairn, Kirsty A; Green, Peter; Perry, Tracy L

2015-01-01

Background Despite the hundreds of diet apps available for use on smartphones (mobile phones), no studies have examined their use as tools for dietary assessment and tracking in sports nutrition. Objective The aim is to examine the prevalence and perceptions of using smartphone diet apps for dietary assessment and tracking among sports dietitians. Methods A cross-sectional online survey to examine the use and perception of diet apps was developed and distributed to sports dietitians in Australia, Canada, New Zealand, the United Kingdom, and the United States (US). Results The overall response rate from the 1709 sports dietitians invited to participate was 10.3% (n=180). diet apps were used by 32.4% (57/176) of sports dietitians to assess and track the dietary intake of athletes. Sports dietitians from the US were more likely to use smartphone diet apps than sports dietitians from other countries (OR=5.61, 95% CI 1.84-17.08, P=.002). Sports dietitians used 28 different diet apps, with 56% (32/57) choosing MyFitnessPal. Overall, sports dietitians held a positive perception of smartphone diet apps, with the majority of respondents viewing diet apps as “better” (25/53, 47%) or “equivalent” (22/53, 41%) when compared with traditional dietary assessment methods. Conclusions Nearly one-third of sports dietitians used mobile phone diet apps in sports nutrition practice, and viewed them as useful in helping to assess and track the dietary intake of athletes. PMID:25616274

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

PubMed

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

2018-02-02

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

Mental and Emotional Self-Help Technology Apps: Cross-Sectional Study of Theory, Technology, and Mental Health Behaviors.

PubMed

Crookston, Benjamin T; West, Joshua H; Hall, P Cougar; Dahle, Kaitana Martinez; Heaton, Thomas L; Beck, Robin N; Muralidharan, Chandni

2017-10-17

Mental and emotional self-help apps have emerged as potential mental illness prevention and treatment tools. The health behavior theory mechanisms by which these apps influence mental health-related behavior change have not been thoroughly examined. The objective of this study was to examine the association between theoretical behavior change mechanisms and use of mental and emotional self-help apps and whether the use of such apps is associated with mental health behaviors. This study utilized a cross-sectional survey of 150 users of mental or emotional health apps in the past 6 months. Survey questions included theory-based items, app engagement and likeability items, and behavior change items. Stata version 14 was used to calculate all statistics. Descriptive statistics were calculated for each of the demographic, theory, engagement, and behavior variables. Multiple regression analysis was used to identify factors associated with reported changes in theory and separately for reported changes in actual behavior after controlling for potentially confounding variables. Participants reported that app use increased their motivation, desire to set goals, confidence, control, and intentions to be mentally and emotionally healthy. Engagement (P<.001) was positively associated with the reported changes in theory items, whereas perceived behavior change was positively associated with theory (P<.001), engagement (P=.004), frequency of use of apps (P=.01), and income (P=.049). Participants reported that app use increased their motivation, desire to set goals, confidence, control, and intentions to be mentally and emotionally healthy. This increase in perceptions, beliefs, and attitudes surrounding their mental and emotional health was considerably associated with perceived change in behavior. There was a positive association between the level of engagement with the app and the impact on theory items. Future efforts should consider the value of impacting key theoretical

Health App Use Among US Mobile Phone Users: Analysis of Trends by Chronic Disease Status

PubMed Central

2017-01-01

Background Mobile apps hold promise for serving as a lifestyle intervention in public health to promote wellness and attenuate chronic conditions, yet little is known about how individuals with chronic illness use or perceive mobile apps. Objective The objective of this study was to explore behaviors and perceptions about mobile phone–based apps for health among individuals with chronic conditions. Methods Data were collected from a national cross-sectional survey of 1604 mobile phone users in the United States that assessed mHealth use, beliefs, and preferences. This study examined health app use, reason for download, and perceived efficacy by chronic condition. Results Among participants, having between 1 and 5 apps was reported by 38.9% (314/807) of respondents without a condition and by 6.6% (24/364) of respondents with hypertension. Use of health apps was reported 2 times or more per day by 21.3% (172/807) of respondents without a condition, 2.7% (10/364) with hypertension, 13.1% (26/198) with obesity, 12.3% (20/163) with diabetes, 12.0% (32/267) with depression, and 16.6% (53/319) with high cholesterol. Results of the logistic regression did not indicate a significant difference in health app download between individuals with and without chronic conditions (P>.05). Compared with individuals with poor health, health app download was more likely among those with self-reported very good health (odds ratio [OR] 3.80, 95% CI 2.38-6.09, P<.001) and excellent health (OR 4.77, 95% CI 2.70-8.42, P<.001). Similarly, compared with individuals who report never or rarely engaging in physical activity, health app download was more likely among those who report exercise 1 day per week (OR 2.47, 95% CI 1.6-3.83, P<.001), 2 days per week (OR 4.77, 95% CI 3.27-6.94, P<.001), 3 to 4 days per week (OR 5.00, 95% CI 3.52-7.10, P<.001), and 5 to 7 days per week (OR 4.64, 95% CI 3.11-6.92, P<.001). All logistic regression results controlled for age, sex, and race or ethnicity

Cognitive Factors of Using Health Apps: Systematic Analysis of Relationships Among Health Consciousness, Health Information Orientation, eHealth Literacy, and Health App Use Efficacy

PubMed Central

Cho, Jaehee

2014-01-01

Background Interest in smartphone health apps has been increasing recently. However, we have little understanding of the cognitive and motivational factors that influence the extent of health-app use. Objective This study aimed to examine the effects of four cognitive factors—health consciousness, health information orientation, eHealth literacy, and health-app use efficacy—on the extent of health-app use. It also explored the influence of two different use patterns—information and information-behavior use of health apps—with regard to the relationships among the main study variables. Methods We collected and analyzed 765 surveys in South Korea. According to the results, there was a negligible gender difference: males (50.6%, 387/765) and females (49.4%, 378/765). All participants were adults whose ages ranged from 19 to 59. In order to test the proposed hypotheses, we used a path analysis as a specific form of structural equation modeling. Results Through a path analysis, we discovered that individuals’ health consciousness had a direct effect on their use of health apps. However, unlike the initial expectations, the effects of health information orientation and eHealth literacy on health-app use were mediated by health-app use efficacy. Conclusions The results from the path analysis addressed a significant direct effect of health consciousness as well as strong mediating effects of health-app use efficacy. These findings contribute to widening our comprehension of the new, digital dimensions of health management, particularly those revolving around mobile technology. PMID:24824062

Relevance of Trust Marks and CE Labels in German-Language Store Descriptions of Health Apps: Analysis

PubMed Central

Hillebrand, Uta; von Jan, Ute

2018-01-01

Background In addition to mandatory CE marking (“CE” representing Conformité Européenne, with the CE marking being a symbol of free marketability in the European Economic Area) for medical devices, there are various seals, initiatives, action groups, etc, in the health app context. However, whether manufacturers use them to distinguish their apps and attach relevance to them is unclear. Objective The objective was to take a snapshot of quality seals, regulatory marks, and other orientation aids available on the German app market and to determine whether manufacturers deem such labels relevant enough to apply them to their apps, namely as reflected by mentions in app description texts in a typical app store (ie, Apple’s App Store). Methods A full survey of the metadata of 103,046 apps from Apple’s German App Store in the Medicine and Health & Fitness categories was carried out. For apps with German-language store descriptions (N=8767), these were automatically searched for the occurrence of relevant keywords and validated manually (N=41). In addition, the websites of various app seal providers were checked for assigned seals. Results Few manufacturers referenced seals in the descriptions (5/41), although this would have been expected more often based on the seals we were able to identify from the seal providers’ Web pages, and there were 34 of 41 that mentioned CE status in the descriptions. Two apps referenced an app directory curated by experts; however, this is not an alternative to CE marks and seals of approval. Conclusions Currently, quality seals seem to be irrelevant for manufacturers. In line with regulatory requirements, mentions of medical device status are more frequent; however, neither characteristic is effective for identifying high-quality apps. To improve this situation, a possibly legally obligatory, standardized reporting system should be implemented. PMID:29695374

The Empowering Role of Mobile Apps in Behavior Change Interventions: The Gray Matters Randomized Controlled Trial.

PubMed

Hartin, Phillip J; Nugent, Chris D; McClean, Sally I; Cleland, Ian; Tschanz, JoAnn T; Clark, Christine J; Norton, Maria C

2016-08-02

Health education and behavior change programs targeting specific risk factors have demonstrated their effectiveness in reducing the development of future diseases. Alzheimer disease (AD) shares many of the same risk factors, most of which can be addressed via behavior change. It is therefore theorized that a behavior change intervention targeting these risk factors would likely result in favorable rates of AD prevention. The objective of this study was to reduce the future risk of developing AD, while in the short term promoting vascular health, through behavior change. The study was an interventional randomized controlled trial consisting of subjects who were randomly assigned into either treatment (n=102) or control group (n=42). Outcome measures included various blood-based biomarkers, anthropometric measures, and behaviors related to AD risk. The treatment group was provided with a bespoke "Gray Matters" mobile phone app designed to encourage and facilitate behavior change. The app presented evidence-based educational material relating to AD risk and prevention strategies, facilitated self-reporting of behaviors across 6 behavioral domains, and presented feedback on the user's performance, calculated from reported behaviors against recommended guidelines. This paper explores the rationale for a mobile phone-led intervention and details the app's effect on behavior change and subsequent clinical outcomes. Via the app, the average participant submitted 7.3 (SD 3.2) behavioral logs/day (n=122,719). Analysis of these logs against primary outcome measures revealed that participants who improved their high-density lipoprotein cholesterol levels during the study duration answered a statistically significant higher number of questions per day (mean 8.30, SD 2.29) than those with no improvement (mean 6.52, SD 3.612), t97.74=-3.051, P=.003. Participants who decreased their body mass index (BMI) performed significantly better in attaining their recommended daily goals

[Dr Stockmann and Dr Snow--two heroes of public health].

PubMed

Nylenna, Magne

2003-12-23

Dr Thomas Stockmann, the main character of An enemy of the people by Henrik Ibsen (1828-1906), has been described as a hero of public health. In spite of his idealism and high principles, he was, however, not able to do anything about the contaminated water supply of the baths in the town where he lived. Important differences may be noticed if we compare the fictional Dr Stockmann with Dr John Snow (1813-58), a real hero of public health famous for his handling of a cholera epidemic in London in 1854. While Dr Snow carried out extensive investigations of the relation between water supply and illness and still was humble when presenting his findings, the fictional Dr Stockmann took only one sample of water for examination and was bombastic in his conclusion. And while Dr Snow had a simple suggestion for solving the problem, Dr Stockmann seemed more eager to dramatize the situation. Scientific documentation and a practical attitude to problem solving continue to be important in order to achieve results in the field of public health.

Vig r 6, the cytokinin-specific binding protein from mung bean (Vigna radiata) sprouts, cross-reacts with Bet v 1-related allergens and binds IgE from birch pollen allergic patients' sera.

PubMed

Guhsl, Eva Elisabeth; Hofstetter, Gerlinde; Hemmer, Wolfgang; Ebner, Christof; Vieths, Stefan; Vogel, Lothar; Breiteneder, Heimo; Radauer, Christian

2014-03-01

Birch pollen associated allergy to mung bean sprouts is caused by cross-reactivity between the birch pollen allergen Bet v 1 and the mung bean allergen Vig r 1. We aimed to determine the allergenicity of the cytokinin-specific binding protein from mung bean (Vig r 6), another allergen related to Bet v 1 with only 31% sequence identity. Bet v 1, Gly m 4, Vig r 1, and Vig r 6 were produced in Escherichia coli. In an ELISA, 73 and 32% of Bet v 1-sensitized birch-allergic patients' sera (n = 60) showed IgE binding to Vig r 1 and Vig r 6, respectively. Of 19 patients who reported allergic reactions or had positive prick-to-prick tests to mung bean sprouts, 79% showed IgE binding to Vig r 1 and 63% showed IgE binding to Vig r 6. Bet v 1 completely inhibited IgE binding to both mung bean allergens. Vig r 6 showed partial cross-reactivity with Vig r 1 and activated basophils sensitized with mung bean allergic patients' sera. We demonstrated IgE cross-reactivity despite low sequence identity between Vig r 6 and other Bet v 1-related allergens. Thus, IgE binding to Vig r 6 may contribute to birch pollinosis-associated mung bean sprout allergy. © 2013 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

An Android Communication App Forensic Taxonomy.

PubMed

Azfar, Abdullah; Choo, Kim-Kwang Raymond; Liu, Lin

2016-09-01

Due to the popularity of Android devices and applications (apps), Android forensics is one of the most studied topics within mobile forensics. Communication apps, such as instant messaging and Voice over IP (VoIP), are one popular app category used by mobile device users, including criminals. Therefore, a taxonomy outlining artifacts of forensic interest involving the use of Android communication apps will facilitate the timely collection and analysis of evidentiary materials from such apps. In this paper, 30 popular Android communication apps were examined, where a logical extraction of the Android phone images was collected using XRY, a widely used mobile forensic tool. Various information of forensic interest, such as contact lists and chronology of messages, was recovered. Based on the findings, a two-dimensional taxonomy of the forensic artifacts of the communication apps is proposed, with the app categories in one dimension and the classes of artifacts in the other dimension. Finally, the artifacts identified in the study of the 30 communication apps are summarized using the taxonomy. It is expected that the proposed taxonomy and the forensic findings in this paper will assist forensic investigations involving Android communication apps. © 2016 American Academy of Forensic Sciences.

SUBFIELD AND LAYER-SPECIFIC DEPLETION IN CALBINDIN-D28K, CALRETININ AND PARVALBUMIN IMMUNOREACTIVITY IN THE DENTATE GYRUS OF APP/PS1 TRANSGENIC MICE

PubMed Central

Popovi, Miroljub; Caballero-Bleda, María; Kadish, Inga; van Groen, Thomas

2008-01-01

The depletion of neuronal calcium binding proteins deprives neurons of the capacity to buffer high levels of intracellular Ca2+ and this leaves them vulnerable to pathological processes, such as those present in Alzheimer’s disease (AD). The aim of the present study was to investigate the expression of the calcium binding proteins, calbindin-D28K, calretinin and parvalbumin in the dentate gyrus (DG) of APP/PS1 transgenic mice and their non-Tg littermates, as well as the relation with the deposition of human Aβ. We measured the expression of these three proteins at seven different rostro-caudal levels, and in the molecular, granular and polymorphic layers of the DG. We found that, except in the most caudal part of the DG, there is a substantial loss of calbindin-D28K immunoreactivity in all three layers of the DG in APP/PS1 mice compared to the non-Tg mice. Significant loss of calretinin immunoreactivity is present in most of the polymorphic layer of the DG of APP/PS1 mice compared to the non-Tg mice, as well as in the rostral and intermediate part of the inner molecular layer. Compared to the non-Tg mice parvalbumin immunoreactivity is significantly reduced throughout the whole polymorphic layer as well as in the rostral and intermediate part of the granular layer of DG in APP/PS1 mice. The relatively preservation of calbindin immunoreactivity in the caudal part of molecular and granular layers as well as calretinin immunoreactivity in the caudal part of polymorphic layer of the DG is likely related to the lower Aβ expression in those parts of DG. The present data suggest an involvement of calcium-dependent pathways in the pathogenesis of AD and indicate that there exists a subfield and layer-specific decrease in immunoreactivity which is related to the type of calcium-binding protein in APP/PS1 mice. Moreover, it seems that APP expression affects more the calbindin expression then parvalbumin and calretinin expression in the DG of APP/PS1 transgenic mice. PMID

UNDERSTANDING POLYSPECIFICITY WITHIN THE SUBSTRATE-BINDING CAVITY OF THE HUMAN MULTIDRUG RESISTANCE P-GLYCOPROTEIN

PubMed Central

Martinez, Lorena; Arnaud, Ophélie; Henin, Emilie; Tao, Houchao; Chaptal, Vincent; Doshi, Rupak; Andrieu, Thibaud; Dussurgey, Sébastien; Tod, Michel; Di Pietro, Attilio; Zhang, Qinghai; Chang, Geoffrey; Falson, Pierre

2015-01-01

Human P-glycoprotein (P-gp) controls drugs bioavailability by pumping out of the cells many structurally-unrelated drugs. The x-ray structure of the mouse P-gp ortholog was solved with two SSS- and one RRR-enantiomers of the selenohexapeptide inhibitor QZ59, found within the putative drug-binding pocket of the membrane domain outer leaflet. This offered the first opportunity to localize the well-known H- and R- drug-substrate sites in light of QZ59 inhibition mechanisms that were characterized here in cellulo and modelled towards Hoechst 33342 and daunorubicin transport. We found that QZ59-SSS competes efficiently with both substrates, displaying KI,app values of 0.15 and 0.3 μM, respectively 13 and 2 times lower than corresponding Km,app. In contrast, QZ59-RRR non-competitively inhibited daunorubicin transport with moderate efficacy (KI,app = 1.9 μM) and displayed a mixed-type inhibition towards Hoechst 33342 transport, resulting from a mainly non-competitive (Ki2,app = 1.6 μM) and a poor but significant competitive tendency (Ki1,app = 5 μM). These results suppose a positional overlap of QZ59 – drug-transport sites, total for the SSS enantiomer and partial for the RRR one. Crystal structures analysis suggests that the H site overlaps both QZ59-SSS locations while the R-site overlaps the most embedded one. PMID:24219411

Myelin-reactive “type B” T cells and T cells specific for low-affinity MHC-binding myelin peptides escape tolerance in HLA-DR transgenic mice

PubMed Central

Kawamura, Kazuyuki; McLaughlin, Katherine A.; Weissert, Robert; Forsthuber, Thomas G.

2009-01-01

Genes of the major histocompatibility complex (MHC) show the strongest genetic association with multiple sclerosis (MS) but the underlying mechanisms have remained unresolved. Here, we asked whether the MS-associated MHC class II molecules, HLA-DRB1*1501, HLA-DRB5*0101, and HLA-DRB1*0401 contribute to autoimmune central nervous system (CNS) demyelination by promoting pathogenic T cell responses to human myelin basic protein (hMBP), using three transgenic (Tg) mouse lines expressing these MHC molecules. Unexpectedly, profound T cell tolerance to the high-affinity MHC-binding hMBP82-100 epitope was observed in all Tg mouse lines. T cell tolerance to hMBP82-100 was abolished upon backcrossing the HLA-DR Tg mice to MBP-deficient mice. In contrast, T cell tolerance was incomplete for low-affinity MHC-binding hMBP epitopes. Furthermore, hMBP82-100-specific “type B” T cells escaped tolerance in HLA-DRB5*0101 Tg mice. Importantly, T cells specific for low-affinity MHC-binding hMBP epitopes and hMBP82-100-specific “type B” T cells were highly encephalitogenic. Collectively, the results show that MS-associated MHC class II molecules are highly efficient at inducing T cell tolerance to high-affinity MHC-binding epitope, whereas autoreactive T cells specific for the low-affinity MHC-binding epitopes and “type B” T cells can escape the induction of T cell tolerance and may promote MS. PMID:18713991

Nurses' perceptions and problems in the usability of a medication safety app.

PubMed

Ankem, Kalyani; Cho, Sookyung; Simpson, Diana

2017-10-16

The majority of medication apps support medication adherence. Equally, if not more important, is medication safety. Few apps report on medication safety, and fewer studies have been conducted with these apps. The usability of a medication safety app was tested with nurses to reveal their perceptions of the graphical user interface and to discover problems they encountered in using the app. Usability testing of the app was conducted with RN-BSN students and informatics students (n = 18). Perceptions of the graphical components were gathered in pretest and posttest questionnaires, and video recordings of the usability testing were transcribed. The significance of the difference in mean performance time for 8 tasks was tested, and qualitative analysis was deployed to identify problems encountered and to rate the severity of each problem. While all participants perceived the graphical user interface as easy to understand, nurses took significantly more time to complete certain tasks. More nurses found the medication app to be lacking in intuitiveness of user interface design, in capability to match real-world data, and in providing optimal information architecture. To successfully integrate mobile devices in healthcare, developers must address the problems that nurses encountered in use of the app.

Characterization of the Igf-II Binding Site of the IGF-II/MAN-6-P Receptor Extracellular Domain.

NASA Astrophysics Data System (ADS)

Garmroudi, Farideh

1995-01-01

substituting threonine for isoleucine at position 1621, which is located in the N-terminal half of repeat 11, and was found to abrogate IGF-II binding. Collectively, our work indicates that repeat 11 of the IGF-II/Man-6-P receptor's extracellular domain encompasses the elements both for binding and cross-linking to IGF-II.

Supporting Homework Compliance in Cognitive Behavioural Therapy: Essential Features of Mobile Apps.

PubMed

Tang, Wei; Kreindler, David

2017-06-08

Cognitive behavioral therapy (CBT) is one of the most effective psychotherapy modalities used to treat depression and anxiety disorders. Homework is an integral component of CBT, but homework compliance in CBT remains problematic in real-life practice. The popularization of the mobile phone with app capabilities (smartphone) presents a unique opportunity to enhance CBT homework compliance; however, there are no guidelines for designing mobile phone apps created for this purpose. Existing literature suggests 6 essential features of an optimal mobile app for maximizing CBT homework compliance: (1) therapy congruency, (2) fostering learning, (3) guiding therapy, (4) connection building, (5) emphasis on completion, and (6) population specificity. We expect that a well-designed mobile app incorporating these features should result in improved homework compliance and better outcomes for its users. ©Wei Tang, David Kreindler. Originally published in JMIR Mental Health (http://mental.jmir.org), 08.06.2017.

Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II recepter HLA-DR1

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

Mullen, M.; Haan, K.M.; Longnecker, R.

Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes long-term latent infections, and is associated with a variety of human tumors. The EBV gp42 glycoprotein binds MHC class II molecules, playing a critical role in infection of B lymphocytes. EBV gp42 belongs to the C-type lectin superfamily, with homology to NK receptors of the immune system. We report the crystal structure of gp42 bound to the human MHC class II molecule HLA-DR1. The gp42 binds HLA-DR1 using a surface site that is distinct from the canonical lectin and NK receptor ligand binding sites. At the canonical ligand binding site, gp42 forms amore » large hydrophobic groove, which could interact with other ligands necessary for EBV entry, providing a mechanism for coupling MHC recognition and membrane fusion.« less

Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants

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

Zhu, Xueyong; Viswanathan, Karthik; Raman, Rahul

Avian H5N1 influenza viruses continue to spread in wild birds and domestic poultry with sporadic infection in humans. Receptor binding specificity changes are a prerequisite for H5N1 viruses and other zoonotic viruses to be transmitted among humans. Previous reported hemagglutinin (HA) mutants from ferret-transmissible H5N1 viruses of A/Viet Nam/1203/04 and A/Indonesia/5/05 showed slightly increased, but still very weak, binding to human receptors. From mutagenesis and glycan array studies, we previously identified two H5N1 HA mutants that could more effectively switch receptor specificity to human-like α2-6 linked sialosides with avidity comparable to wild-type H5 HA binding to avian-like α2-3 linked sialosides.more » Here, crystal structures of these two H5 HA mutants free and in complex with human and avian glycan receptor analogues reveal the structural basis for their preferential binding to human receptors. These findings suggest continuous surveillance should be maintained to monitor and assess human-to-human transmission potential of H5N1 viruses.« less

Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants

DOE PAGES

Zhu, Xueyong; Viswanathan, Karthik; Raman, Rahul; ...

2015-11-01

Avian H5N1 influenza viruses continue to spread in wild birds and domestic poultry with sporadic infection in humans. Receptor binding specificity changes are a prerequisite for H5N1 viruses and other zoonotic viruses to be transmitted among humans. Previous reported hemagglutinin (HA) mutants from ferret-transmissible H5N1 viruses of A/Viet Nam/1203/04 and A/Indonesia/5/05 showed slightly increased, but still very weak, binding to human receptors. From mutagenesis and glycan array studies, we previously identified two H5N1 HA mutants that could more effectively switch receptor specificity to human-like α2-6 linked sialosides with avidity comparable to wild-type H5 HA binding to avian-like α2-3 linked sialosides.more » Here, crystal structures of these two H5 HA mutants free and in complex with human and avian glycan receptor analogues reveal the structural basis for their preferential binding to human receptors. These findings suggest continuous surveillance should be maintained to monitor and assess human-to-human transmission potential of H5N1 viruses.« less

Brain energy metabolism and neuroinflammation in ageing APP/PS1-21 mice using longitudinal 18F-FDG and 18F-DPA-714 PET imaging.

PubMed

Takkinen, Jatta S; López-Picón, Francisco R; Al Majidi, Rana; Eskola, Olli; Krzyczmonik, Anna; Keller, Thomas; Löyttyniemi, Eliisa; Solin, Olof; Rinne, Juha O; Haaparanta-Solin, Merja

2017-08-01

Preclinical animal model studies of brain energy metabolism and neuroinflammation in Alzheimer's disease have produced conflicting results, hampering both the elucidation of the underlying disease mechanism and the development of effective Alzheimer's disease therapies. Here, we aimed to quantify the relationship between brain energy metabolism and neuroinflammation in the APP/PS1-21 transgenic mouse model of Alzheimer's disease using longitudinal in vivo 18 F-FDG and 18 F-DPA-714) PET imaging and ex vivo brain autoradiography. APP/PS1-21 (TG, n = 9) and wild type control mice (WT, n = 9) were studied longitudinally every third month from age 6 to 15 months with 18 F-FDG and 18 F-DPA-714 with a one-week interval between the scans. Additional TG (n = 52) and WT (n = 29) mice were used for ex vivo studies. In vivo, the 18 F-FDG SUVs were lower and the 18 F-DPA-714 binding ratios relative to the cerebellum were higher in the TG mouse cortex and hippocampus than in WT mice at age 12 to 15 months ( p < 0.05). The ex vivo cerebellum binding ratios supported the results of the in vivo 18 F-DPA-714 studies but not the 18 F-FDG studies. This longitudinal PET study demonstrated decreased energy metabolism and increased inflammation in the brains of APP/PS1-21 mice compared to WT mice.

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 Suicide Prevention: Review of Virtual Stores and Literature

PubMed Central

Castillo, Gema; Arambarri, Jon; López-Coronado, Miguel; Franco, Manuel A

2017-01-01

Background The best manner to prevent suicide is to recognize suicidal signs and signals, and know how to respond to them. Objective We aim to study the existing mobile apps for suicide prevention in the literature and the most commonly used virtual stores. Methods Two reviews were carried out. The first was done by searching the most commonly used commercial app stores, which are iTunes and Google Play. The second was a review of mobile health (mHealth) apps in published articles within the last 10 years in the following 7 scientific databases: Science Direct, Medline, PsycINFO, Embase, The Cochrane Library, IEEE Xplore, and Google Scholar. Results A total of 124 apps related to suicide were found in the cited virtual stores but only 20 apps were specifically designed for suicide prevention. All apps were free and most were designed for Android. Furthermore, 6 relevant papers were found in the indicated scientific databases; in these studies, some real experiences with physicians, caregivers, and families were described. The importance of these people in suicide prevention was indicated. Conclusions The number of apps regarding suicide prevention is small, and there was little information available from literature searches, indicating that technology-based suicide prevention remains understudied. Many of the apps provided no interactive features. It is important to verify the accuracy of the results of different apps that are available on iOS and Android. The confidence generated by these apps can benefit end users, either by improving their health monitoring or simply to verify their body condition. PMID:29017992

A Systematic Review of Cognitive Behavioral Therapy and Behavioral Activation Apps for Depression

PubMed Central

McGrath, Patrick J.; Wozney, Lori; Wheaton, Mike; Conrod, Jill; Rozario, Sharlene

2016-01-01

Depression is a common mental health condition for which many mobile apps aim to provide support. This review aims to identify self-help apps available exclusively for people with depression and evaluate those that offer cognitive behavioural therapy (CBT) or behavioural activation (BA). One hundred and seventeen apps have been identified after searching both the scientific literature and the commercial market. 10.26% (n = 12) of these apps identified through our search offer support that seems to be consistent with evidence-based principles of CBT or BA. Taking into account the non existence of effectiveness/efficacy studies, and the low level of adherence to the core ingredients of the CBT/BA models, the utility of these CBT/BA apps are questionable. The usability of reviewed apps is highly variable and they rarely are accompanied by explicit privacy or safety policies. Despite the growing public demand, there is a concerning lack of appropiate CBT or BA apps, especially from a clinical and legal point of view. The application of superior scientific, technological, and legal knowledge is needed to improve the development, testing, and accessibility of apps for people with depression. PMID:27135410

Use of transcriptomic data for extending a model of the AppA/PpsR system in Rhodobacter sphaeroides.

PubMed

Pandey, Rakesh; Armitage, Judith P; Wadhams, George H

2017-12-28

Photosynthetic (PS) gene expression in Rhodobacter sphaeroides is regulated in response to changes in light and redox conditions mainly by PrrB/A, FnrL and AppA/PpsR systems. The PrrB/A and FnrL systems activate the expression of them under anaerobic conditions while the AppA/PpsR system represses them under aerobic conditions. Recently, two mathematical models have been developed for the AppA/PpsR system and demonstrated how the interaction between AppA and PpsR could lead to a phenotype in which PS genes are repressed under semi-aerobic conditions. These models have also predicted that the transition from aerobic to anaerobic growth mode could occur via a bistable regime. However, they lack experimentally quantifiable inputs and outputs. Here, we extend one of them to include such quantities and combine all relevant micro-array data publically available for a PS gene of this bacterium and use that to parameterise the model. In addition, we hypothesise that the AppA/PpsR system alone might account for the observed trend of PS gene expression under semi-aerobic conditions. Our extended model of the AppA/PpsR system includes the biological input of atmospheric oxygen concentration and an output of photosynthetic gene expression. Following our hypothesis that the AppA/PpsR system alone is sufficient to describe the overall trend of PS gene expression we parameterise the model and suggest that the rate of AppA reduction in vivo should be faster than its oxidation. Also, we show that despite both the reduced and oxidised forms of PpsR binding to the PS gene promoters in vitro, binding of the oxidised form as a repressor alone is sufficient to reproduce the observed PS gene expression pattern. Finally, the combination of model parameters which fit the biological data well are broadly consistent with those which were previously determined to be required for the system to show (i) the repression of PS genes under semi-aerobic conditions, and (ii) bistability. We found

Mixed-Methods Analysis of Factors Impacting Use of a Postoperative mHealth App

PubMed Central

Scott, Aaron R; Alore, Elizabeth A; Naik, Aanand D; Berger, David H

2017-01-01

Background Limited communication and care coordination following discharge from hospitals may contribute to surgical complications. Smartphone apps offer a novel mechanism for communication and care coordination. However, factors which may affect patient app use in a postoperative, at-home setting are poorly understood. Objective The objectives of this study were to (1) gauge interest in smartphone app use among patients after colorectal surgery and (2) better understand factors affecting patient app use in a postoperative, at-home setting. Methods A prospective feasibility study was performed at a hospital that principally serves low socioeconomic status patients. After colorectal surgery, patients were enrolled and given a smartphone app, which uses previously validated content to provide symptom-based recommendations. Patients were instructed to use the app daily for 14 days after discharge. Demographics and usability data were collected at enrollment. Usability was measured with the System Usability Scale (SUS). At follow-up, the SUS was repeated and patients underwent a structured interview covering ease of use, willingness to use, and utility of use. Two members of the research team independently reviewed the field notes from follow-up interviews and extracted the most consistent themes. Chart and app log reviews identified clinical endpoints. Results We screened 115 patients, enrolled 20 patients (17.4%), and completed follow-up interviews with 17 patients (85%). Reasons for nonenrollment included: failure to meet inclusion criteria (47/115, 40.9%), declined to participate (26/115, 22.6%), and other reasons (22/115, 19.1%). There was no difference in patient ratings between usability at first-use and after extended use, with SUS scores greater than the 95th percentile at both time points. Despite high usability ratings, 6/20 (30%) of patients never used the app at home after hospital discharge and 2/20 (10%) only used the app once. Interviews revealed three

The effectiveness of a suicide prevention app for indigenous Australian youths: study protocol for a randomized controlled trial.

PubMed

Shand, Fiona L; Ridani, Rebecca; Tighe, Joe; Christensen, Helen

2013-11-20

Indigenous Australian youth (aged 15 to 34) have up to four times the risk of suicide compared with their non-Indigenous counterparts. Barriers to help-seeking include shame, feared loss of autonomy and negative attitudes towards healthcare providers. The use of mobile devices and apps continues to rise amongst young people, thus presenting opportunities to utilize these aids in overcoming help-seeking barriers. Apps have been shown to assist in several health-related areas, including weight loss and smoking cessation, although no apps have as yet been evaluated for suicide prevention. Moreover, there is a lack of research that scientifically evaluates suicide prevention interventions within Indigenous communities. In this study, a recently developed self-help app will be evaluated in a randomized controlled trial. The intervention is based on acceptance and commitment therapy and mindfulness-based cognitive behavioural therapy. It is aimed at participants who have suicidal thoughts but who are not actively suicidal. In total, 150 participants will be randomly allocated to the intervention-condition (N = 75) or to the wait-list control condition (N = 75). Questionnaires will be completed at baseline, post-test and 6 weeks follow-up. The primary outcome measure is a reduction in frequency and intensity of suicidal thoughts. Secondary outcome measures are the reduction of depression, anxiety and impulsivity. This study is the first to evaluate the effectiveness of a self-help app for suicidal thoughts amongst young Indigenous people. Several limitations and strengths of the design are discussed. Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613000104752.

A Context-Sensing Mobile Phone App (Q Sense) for Smoking Cessation: A Mixed-Methods Study.

PubMed

Naughton, Felix; Hopewell, Sarah; Lathia, Neal; Schalbroeck, Rik; Brown, Chloë; Mascolo, Cecilia; McEwen, Andy; Sutton, Stephen

2016-09-16

A major cause of lapse and relapse to smoking during a quit attempt is craving triggered by cues from a smoker's immediate environment. To help smokers address these cue-induced cravings when attempting to quit, we have developed a context-aware smoking cessation app, Q Sense, which uses a smoking episode-reporting system combined with location sensing and geofencing to tailor support content and trigger support delivery in real time. We sought to (1) assess smokers' compliance with reporting their smoking in real time and identify reasons for noncompliance, (2) assess the app's accuracy in identifying user-specific high-risk locations for smoking, (3) explore the feasibility and user perspective of geofence-triggered support, and (4) identify any technological issues or privacy concerns. An explanatory sequential mixed-methods design was used, where data collected by the app informed semistructured interviews. Participants were smokers who owned an Android mobile phone and were willing to set a quit date within one month (N=15). App data included smoking reports with context information and geolocation, end-of-day (EoD) surveys of smoking beliefs and behavior, support message ratings, and app interaction data. Interviews were undertaken and analyzed thematically (N=13). Quantitative and qualitative data were analyzed separately and findings presented sequentially. Out of 15 participants, 3 (20%) discontinued use of the app prematurely. Pre-quit date, the mean number of smoking reports received was 37.8 (SD 21.2) per participant, or 2.0 (SD 2.2) per day per participant. EoD surveys indicated that participants underreported smoking on at least 56.2% of days. Geolocation was collected in 97.0% of smoking reports with a mean accuracy of 31.6 (SD 16.8) meters. A total of 5 out of 9 (56%) eligible participants received geofence-triggered support. Interaction data indicated that 50.0% (137/274) of geofence-triggered message notifications were tapped within 30 minutes of

Structural Characterization of the E2 Domain of APL-1, a C. Elegans Homolog of Human Amyloid Precursor Protein, and its Heparin Binding Site

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

Hoopes, J.; Liu, X; Xu, X

2010-01-01

The amyloid {beta}-peptide deposit found in the brain tissue of patients with Alzheimer disease is derived from a large heparin-binding protein precursor APP. The biological function of APP and its homologs is not precisely known. Here we report the x-ray structure of the E2 domain of APL-1, an APP homolog in Caenorhabditis elegans, and compare it to the human APP structure. We also describe the structure of APL-1 E2 in complex with sucrose octasulfate, a highly negatively charged disaccharide, which reveals an unexpected binding pocket between the two halves of E2. Based on the crystal structure, we are able tomore » map, using site-directed mutagenesis, a surface groove on E2 to which heparin may bind. Our biochemical data also indicate that the affinity of E2 for heparin is influenced by pH: at pH 5, the binding appears to be much stronger than that at neutral pH. This property is likely caused by histidine residues in the vicinity of the mapped heparin binding site and could be important for the proposed adhesive function of APL-1.« less

Delineating distinct heme-scavenging and -binding functions of domains in MF6p/helminth defense molecule (HDM) proteins from parasitic flatworms.

PubMed

Martínez-Sernández, Victoria; Mezo, Mercedes; González-Warleta, Marta; Perteguer, María J; Gárate, Teresa; Romarís, Fernanda; Ubeira, Florencio M

2017-05-26

MF6p/FhHDM-1 is a small protein secreted by the parasitic flatworm (trematode) Fasciola hepatica that belongs to a broad family of heme-binding proteins (MF6p/helminth defense molecules (HDMs)). MF6p/HDMs are of interest for understanding heme homeostasis in trematodes and as potential targets for the development of new flukicides. Moreover, interest in these molecules has also increased because of their immunomodulatory properties. Here we have extended our previous findings on the mechanism of MF6p/HDM-heme interactions and mapped the protein regions required for heme binding and for other biological functions. Our data revealed that MF6p/FhHDM-1 forms high-molecular-weight complexes when associated with heme and that these complexes are reorganized by a stacking procedure to form fibril-like and granular nanostructures. Furthermore, we showed that MF6p/FhHDM-1 is a transitory heme-binding protein as protein·heme complexes can be disrupted by contact with an apoprotein ( e.g. apomyoglobin) with higher affinity for heme. We also demonstrated that (i) the heme-binding region is located in the MF6p/FhHDM-1 C-terminal moiety, which also inhibits the peroxidase-like activity of heme, and (ii) MF6p/HDMs from other trematodes, such as Opisthorchis viverrini and Paragonimus westermani , also bind heme. Finally, we observed that the N-terminal, but not the C-terminal, moiety of MF6p/HDMs has a predicted structural analogy with cell-penetrating peptides and that both the entire protein and the peptide corresponding to the N-terminal moiety of MF6p/FhHDM-1 interact in vitro with cell membranes in hemin-preconditioned erythrocytes. Our findings suggest that MF6p/HDMs can transport heme in trematodes and thereby shield the parasite from the harmful effects of heme. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Computer-assisted prediction of HLA-DR binding and experimental analysis for human promiscuous Th1-cell peptides in the 24 kDa secreted lipoprotein (LppX) of Mycobacterium tuberculosis.

PubMed

Al-Attiyah, R; Mustafa, A S

2004-01-01

The secreted 24 kDa lipoprotein (LppX) is an antigen that is specific for Mycobacterium tuberculosis complex and M. leprae. The present study was carried out to identify the promiscuous T helper 1 (Th1)-cell epitopes of the M. tuberculosis LppX (MT24, Rv2945c) antigen by using 15 overlapping synthetic peptides (25 mers overlapping by 10 residues) covering the sequence of the complete protein. The analysis of Rv2945c sequence for binding to 51 alleles of nine serologically defined HLA-DR molecules, by using a virtual matrix-based prediction program (propred), showed that eight of the 15 peptides of Rv2945c were predicted to bind promiscuously to >/=10 alleles from more than or equal to three serologically defined HLA-DR molecules. The Th1-cell reactivity of all the peptides was assessed in antigen-induced proliferation and interferon-gamma (IFN-gamma)-secretion assays with peripheral blood mononuclear cells (PBMCs) from 37 bacille Calmette-Guérin (BCG)-vaccinated healthy subjects. The results showed that 17 of the 37 donors, which represented an HLA-DR-heterogeneous group, responded to one or more peptides of Rv2945c in the Th1-cell assays. Although each peptide stimulated PBMCs from one or more donors in the above assays, the best positive responses (12/17 (71%) responders) were observed with the peptide p14 (aa 196-220). This suggested a highly promiscuous presentation of p14 to Th1 cells. In addition, the sequence of p14 is completely identical among the LppX of M. tuberculosis, M. bovis and M. leprae, which further supports the usefulness of Rv2945c and p14 in the subunit vaccine design against both tuberculosis and leprosy.

Free mobile apps on depression for Indian users: A brief overview and critique.

PubMed

Kumar, Satish; Mehrotra, Seema

2017-08-01

The present study aimed at identifying the nature of mobile apps available to Indian android phone users who might search for free apps to help them deal with depression. The specific objectives were to examine the available interactive self-care apps in terms of guidance provided to users to make decisions regarding use of app, inclusion of elements that encourage professional help-seeking, guidance regarding managing psychological crisis and the range of therapeutic strategies incorporated. Using the search term 'depression', 278 apps were identified in the first step and these spanned a wide range of categories. Information on coping with depression and stand alone screening tools formed the two largest types of free apps. Features of interactive self-care apps (N = 33) were reviewed further and this exercise showed that less than 10% of the apps incorporated explicit delineation of their scope or initial screening for suitability. Guidance regarding managing suicidal crisis were incorporated in only about 12% of the interactive apps. Slightly more than one third of these apps included content aimed at encouraging professional help seeking when needed or an explicit mention of their theoretical or empirical basis. Monitoring moods, thoughts and behaviors were the commonest therapeutic strategies incorporated in these apps, in addition, to a wide range of other strategies such as behavioral activation, identifying and correcting cognitive errors, mindfulness exercises, cultivation of gratitude, and medication management. The challenges for a potential user of these apps are discussed and ways to address the same are highlighted. Copyright © 2017 Elsevier B.V. All rights reserved.

Acemannan increases NF-κB/DNA binding and IL-6/-8 expression by selectively binding Toll-like receptor-5 in human gingival fibroblasts.

PubMed

Thunyakitpisal, Pasutha; Ruangpornvisuti, Vithaya; Kengkwasing, Pattrawadee; Chokboribal, Jaroenporn; Sangvanich, Polkit

2017-04-01

Acemannan, an acetylated polymannose from Aloe vera, has immunomodulatory effects. We investigated whether acemannan induces IL-6 and -8 expression and NF-κB/DNA binding in human gingival fibroblasts. IL-6 and -8 expression levels were assessed via RT-PCR and ELISA. The NF-κB p50/p65-DNA binding was determined. The structures of acemannan mono-pentamers and Toll-like receptor 5 (TLR5) were simulated. The binding energies between acemannan and TLR5 were identified. We found that acemannan significantly stimulated IL-6/-8 expression at both the mRNA and protein level and significantly increased p50/DNA binding. Preincubation with an anti-TLR5 neutralizing antibody abolished acemannan-induced IL-6/-8 expression and p50/DNA binding, and co-incubation of acemannan with Bay11-7082, a specific NF- κB inhibitor, abolished IL-6/-8 expression. The computer modeling indicated that monomeric/dimeric single stranded acemannan molecules interacted with the TLR5 flagellin recognition sites with a high binding affinity. We conclude that acemannan induces IL-6/-8 expression, and p50/DNA binding in gingival fibroblasts, at least partly, via a TLR5/NF-κB-dependent signaling pathway. Furthermore, acemannan selectively binds with TLR5 ectodomain flagellin recognition sites. Copyright © 2017 Elsevier Ltd. All rights reserved.

Usability and Acceptability of a Mobile Comprehensive HIV Prevention App for Men Who Have Sex With Men: A Pilot Study

PubMed Central

Driggers, Robert; Stekler, Joanne D; Siegler, Aaron; Goldenberg, Tamar; McDougal, Sarah J; Caucutt, Jason; Jones, Jeb; Stephenson, Rob

2017-01-01

Background Men who have sex with men (MSM) are the group most impacted by the human immunodeficiency virus (HIV) epidemic and the only subgroup in the United States among which new HIV diagnoses are not decreasing. To achieve the US National HIV/AIDS (acquired immunodeficiency syndrome) Strategy goals of reducing new diagnoses by 25%, high (eg, 30-50%) coverage of multiple HIV prevention interventions is needed in both urban and rural areas. Mobile phone “apps” are an important channel through which prevention services could be provided at scale and at low marginal cost. Objective The aim of this study was to evaluate the usability and acceptability of a theory-based Android mobile phone app for HIV prevention. Methods The app included self-assessment tools; prevention recommendations; commodity (condoms, HIV self-tests) ordering; reminders to MSM for basic HIV prevention services, HIV testing, condom use, screening for preexposure prophylaxis (PrEP) and nonoccupational postexposure prophylaxis (nPEP); and prevention and treatment provider locators. The study recruited HIV-negative, Android-using MSM in Atlanta and Seattle who were asked to use the app for 4 months and complete a post-use survey. We measured the use of the app and its features, ordering of commodities, self-report of establishing an HIV testing plan, being HIV tested in the community, and starting PrEP or using nPEP. Usability was assessed using the system usability scale (SUS). Results A total of 121 MSM were enrolled (59.5%, 72/121 from Atlanta; 40.5%, 49/121 from Seattle). Median age was 28. Nearly half (48.8%, 59/121) were nonwhite, and most (85.9%, 104/121) were gay-identified. Most had tested for HIV in the past (85.1%, 103/121), and 52 (43.0%, 52/121) had a plan to test for HIV regularly. Men used the app for an average of 17.7 minutes over the first 4 months. Over the 4-month period, over half ordered condoms (63.6%, 77/121) and HIV test kits (52.8%, 64/121) on the app. Eight of 86 (9

DR3 regulation of apoptosis of naive T-lymphocytes in children with acute infectious mononucleosis.

PubMed

Filatova, Elena Nikolaevna; Anisenkova, Elena Viktorovna; Presnyakova, Nataliya Borisovna; Utkin, Oleg Vladimirovich

2016-09-01

Acute infectious mononucleosis (AIM) is a widespread viral disease that mostly affects children. Development of AIM is accompanied by a change in the ratio of immune cells. This is provided by means of different biological processes including the regulation of apoptosis of naive T-cells. One of the potential regulators of apoptosis of T-lymphocytes is a death receptor 3 (DR3). We have studied the role of DR3 in the regulation of apoptosis of naive CD4 + (nTh) and CD8 + (nCTL) T-cells in healthy children and children with AIM. In healthy children as well as in children with AIM, the activation of DR3 is accompanied by inhibition of apoptosis of nTh. In healthy children, the stimulation of DR3 resulted in the increase in apoptosis of nCTL. On the contrary, in children with AIM, the level of apoptosis of nCTL decreased after DR3 activation, which is a positive contribution to the antiviral immune response. In children with AIM, nCTL are characterized by reduced level of apoptosis as compared with healthy children. These results indicate that DR3 can be involved in the reduction of sensitivity of nCTL to apoptosis in children with AIM.