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To address the obesity epidemic, there is a need for novel paradigms, including those that address the timing of eating and sleep in relation to circadian rhythms. Electronic health records (EHRs) are an efficient way to identify potentially eligible participants for health research studies. Mobile health (mHealth) apps offer available and convenient data collection of health behaviors, such as timing of eating and sleep. The aim of this descriptive analysis was to report on recruitment, retention, and app use from a 6-month cohort study using a mobile app called Daily24. Using an EHR query, adult patients from three health care systems in the PaTH clinical research network were identified as potentially eligible, invited electronically to participate, and instructed to download and use the Daily24 mobile app, which focuses on eating and sleep timing. Online surveys were completed at baseline and 4 months. We described app use and identified predictors of app use, defined as 1 or more days of use, versus nonuse and usage categories (ie, immediate, consistent, and sustained) using multivariate regression analyses. Of 70,661 patients who were sent research invitations, 1021 (1.44%) completed electronic consent forms and online baseline surveys; 4 withdrew, leaving a total of 1017 participants in the analytic sample. A total of 53.79% (n=547) of the participants were app users and, of those, 75.3% (n=412), 50.1% (n=274), and 25.4% (n=139) were immediate, consistent, and sustained users, respectively. Median app use was 28 (IQR 7-75) days over 6 months. Younger age, White race, higher educational level, higher income, having no children younger than 18 years, and having used 1 to 5 health apps significantly predicted app use (vs nonuse) in adjusted models. Older age and lower BMI predicted early, consistent, and sustained use. About half (532/1017, 52.31%) of the participants completed the 4-month online surveys. A total of 33.5% (183/547), 29.3% (157/536), and 27.1% (143/527) of app users were still using the app for at least 2 days per month during months 4, 5, and 6 of the study, respectively. EHR recruitment offers an efficient (ie, high reach, low touch, and minimal participant burden) approach to recruiting participants from health care settings into mHealth research. Efforts to recruit and retain less engaged subgroups are needed to collect more generalizable data. Additionally, future app iterations should include more evidence-based features to increase participant use.

Wilson disease (WD) is a monogenic autosomal-recessive disorder of copper accumulation that leads to liver failure and/or neurological deficits. WD is caused by mutations in ATP7B, a transporter that loads Cu(I) onto newly synthesized cupro-enzymes in the trans -Golgi network (TGN) and exports excess copper out of cells by trafficking from the TGN to the plasma membrane. To date, most WD mutations have been shown to disrupt ATP7B activity and/or stability. Using a multidisciplinary approach, including clinical analysis of patients, cell-based assays, and computational studies, we characterized a patient mutation, ATP7B S⁶⁵³Y, which is stable, does not disrupt Cu(I) transport, yet renders the protein unable to exit the TGN. Bulky or charged substitutions at position 653 mimic the phenotype of the patient mutation. Molecular modeling and dynamic simulation suggest that the S653Y mutation induces local distortions within the transmembrane (TM) domain 1 and alter TM1 interaction with TM2. S653Y abolishes the trafficking-stimulating effects of a secondary mutation in the N-terminal apical targeting domain. This result indicates a role for TM1/TM2 in regulating conformations of cytosolic domains involved in ATP7B trafficking. Taken together, our experiments revealed an unexpected role for TM1/TM2 in copper-regulated trafficking of ATP7B and defined a unique class of WD mutants that are transport-competent but trafficking-defective. Understanding the precise consequences of WD-causing mutations will facilitate the development of advanced mutation-specific therapies.

Novel approaches to improving disaster response have begun to include the use of big data and information and communication technology (ICT). However, there remains a dearth of literature on the use of these technologies in disasters. We have conducted an integrative literature review on the role of ICT and big data in disasters. Included in the review were 113 studies that met our predetermined inclusion criteria. Most studies used qualitative methods (39.8%, n=45) over mixed methods (31%, n=35) or quantitative methods (29.2%, n=33). Nearly 80% (n=88) covered only the response phase of disasters and only 15% (n=17) of the studies addressed disasters in low- and middle-income countries. The 4 most frequently mentioned tools were geographic information systems, social media, patient information, and disaster modeling. We suggest testing ICT and big data tools more widely, especially outside of high-income countries, as well as in nonresponse phases of disasters (eg, disaster recovery), to increase an understanding of the utility of ICT and big data in disasters. Future studies should also include descriptions of the intended users of the tools, as well as implementation challenges, to assist other disaster response professionals in adapting or creating similar tools. (Disaster Med Public Health Preparedness. 2019;13:353–367)

The association between monovalent salts and neutral lipid bilayers is known to influence global bilayer structural properties such as headgroup conformational fluctuations and the dipole potential. The local influence of the ions, however, has been unknown due to limited structural resolution of experimental methods. Molecular dynamics simulations are used here to elucidate local structural rearrangements upon association of a series of monovalent Na + salts to a palmitoyl-oleoyl-phosphatidylcholine bilayer. We observe association of all ion types in the interfacial region. Larger anions, which are meant to rationalize data regarding a Hofmeister series of anions, bind more deeply within the bilayer than either Cl − or Na +. Although the simulations are able to reproduce experimentally measured quantities, the analysis is focused on local properties currently invisible to experiments, which may be critical to biological systems. As such, for all ion types, including Cl −, we show local ion-induced perturbations to headgroup tilt, the extent and direction of which is sensitive to ion charge and size. Additionally, we report salt-induced ordering of the water well beyond the interfacial region, which may be significant in terms of hydration repulsion between stacked bilayers.

Collecting data on daily habits across a population of individuals is challenging. Mobile-based circadian ecological momentary assessment (cEMA) is a powerful frame for observing the impact of daily living on long-term health. In this paper, we (1) describe the design, testing, and rationale for specifications of a mobile-based cEMA app to collect timing of eating and sleeping data and (2) compare cEMA and survey data collected as part of a 6-month observational cohort study. The ultimate goal of this paper is to summarize our experience and lessons learned with the Daily24 mobile app and to highlight the pros and cons of this data collection modality. Design specifications for the Daily24 app were drafted by the study team based on the research questions and target audience for the cohort study. The associated backend was optimized to provide real-time data to the study team for participant monitoring and engagement. An external 8-member advisory board was consulted throughout the development process, and additional test users recruited as part of a qualitative study provided feedback through in-depth interviews. After ≥4 days of at-home use, 37 qualitative study participants provided feedback on the app. The app generally received positive feedback from test users for being fast and easy to use. Test users identified several bugs and areas where modifications were necessary to in-app text and instructions and also provided feedback on the engagement strategy. Data collected through the mobile app captured more variability in eating windows than data collected through a one-time survey, though at a significant cost. Researchers should consider the potential uses of a mobile app beyond the initial data collection when deciding whether the time and monetary expenditure are advisable for their situation and goals.

Using 237 all-atom double bilayer simulations, we examined the thermodynamic and structural changes that occur as a phosphatidylcholine lipid bilayer stack is dehydrated. The simulated system represents a micropatch of lipid multilayer systems that are studied experimentally using surface force apparatus, atomic force microscopy and osmotic pressure studies. In these experiments, the hydration level of the system is varied, changing the separation between the bilayers, in order to understand the forces that the bilayers feel as they are brought together. These studies have found a curious, strongly repulsive force when the bilayers are very close to each other, which has been termed the “hydration force,” though the origins of this force are not clearly understood. We computationally reproduce this repulsive, relatively free energy change as bilayers come together and make qualitative conclusions as to the enthalpic and entropic origins of the free energy change. This analysis is supported by data showing structural changes in the waters, lipids and salts that have also been seen in experimental work. Increases in solvent ordering as the bilayers are dehydrated are found to be essential in causing the repulsion as the bilayers come together.

Protegrins (PG) are important in defending host tissues, preventing infection via an attack on the membrane surface of invading microorganisms. Protegrins have powerful antibiotic abilities, but the molecular-level mechanisms underlying the interactions of their β-sheet motifs with the membrane are not known. Protegrin-1 (PG-1) is composed of 18 amino acids with a high content of basic residues and two disulfide bonds. Here we focused on the stability of PG-1 at the amphipathic interface in lipid bilayers and on the details of the peptide-membrane interactions. We simulated all-atom models of the PG-1 monomer with explicit water and lipid bilayers composed of both homogeneous POPC (palmitoyl-oleyl-phosphatidylcholine) lipids and a mixture of POPC/POPG (palmitoyl-oleyl-phosphatidylglycerol) (4:1) lipids. We observed that local thinning of the lipid bilayers mediated by the peptide is enhanced in the lipid bilayer containing POPG, consistent with experimental results of selective membrane targeting. The β-hairpin motif of PG-1 is conserved in both lipid settings, whereas it is highly bent in aqueous solution. The conformational dynamics of PG-1, especially the highly charged β-hairpin turn region, are found to be mostly responsible for disturbing the membrane. Even though the eventual membrane disruption requires PG-1 oligomers, our simulations clearly show the first step of the monomeric effects. The thinning effects in the bilayer should relate to pore/channel formation in the lipid bilayer and thus be responsible for further defects in the membrane caused by oligomer.

The position and extent of movement of a charged peptide within a membrane bilayer provides much controversy. In our study, we have examined the nature of the highly charged helix-turn-helix motif (S3b and S4) to address how a highly charged peptide is stabilized within a bilayer in the presence of various transmembrane electrical potentials. Our double-bilayer simulation results show how the variation of the salt concentrations between the inner and outer bath establishes a transmembrane potential. Our results also show that important features of the peptide affected by changes in electrical potential are the center of mass depth, the swivel/kink degrees of conformation, and the hydrogen-bonding patterns. As the voltage gradient across the bilayer increased, the center of mass of the peptide shifted in a direction toward the outer bath. The peptide also has a higher percent helical content and the swivel/kink conformation is more rigid for nonpolarized systems where no voltage drop occurred between salt baths. Our results also provide some suggestions for how this domain may be affected by environmental changes as part of the voltage sensor in a K-channel.

It is commonly believed that binding affinity can be estimated by consideration of local changes of ligand and protein. This paper discusses a set of molecular dynamics simulations of intestinal fatty acid binding protein addressing the protein's response to presence or absence of different ligands. A 5-ns simulation was performed of the protein without a ligand, and three simulations (one 5-ns and two 2-ns) were performed with different fatty acids bound. The results indicate that, although the basic protein structure is unchanged by the presence of the ligand, other properties are significantly affected by ligand binding. For example, zero-time covariance patterns between protein, bound waters, and ligand vary between the different simulations. Moreover, the interaction energies between ligand and specific residues indicate that different ligands are stabilized in different ways. In sum, the results suggest that binding thermodynamics within this system will need to be calculated not from a subset of nearby protein:ligand interactions, but will depend on a knowledge of the motions coupling together water, protein, and ligand.

The Symposium ‘Frontiers in membrane and membrane protein biophysics: experiments and theory’, held this year at the University of California, Irvine (August 19–20), celebrated the 70th Birthday of Stephen H. White by bringing together distinguished experimentalists and theoreticians to discuss the state of the art and future challenges in the field of membrane and membrane protein biophysics. The meeting and this special issue highlight the highly interdisciplinary nature of membrane and membrane protein biophysics, and the tremendous contributions that S. H. White and his lab have brought to the field.