Mobile Technology Intervention for Weight Loss in Rural Men: Protocol for a Pilot Pragmatic Randomised Controlled Trial

INTRODUCTION: Men who are overweight or obese in the rural Midwestern USA are an unrepresented, at-risk group exhibiting rising rates of cardiovascular disease, poor access to preventive care and poor lifestyle behaviours that contribute to sedentary lifestyle and unhealthy diet. Self-monitoring of eating and activity has demonstrated efficacy for weight loss. Use of mobile technologies for self-monitoring eating and activity may address rural men\u27s access disparities to preventive health resources and support weight loss. Our pilot trial will assess the feasibility and acceptability of two mobile applications for weight loss in rural men to inform a future, full-scale trial. METHODS AND ANALYSIS: A 6-month randomised controlled trial with contextual evaluation will randomise 80 men using a 1:1 ratio to either a Mobile Technology Plus (MT+) intervention or a basic Mobile Technology (MT) intervention in rural, midlife men (aged 40-69 years). The MT+ intervention consists of a smartphone self-monitoring application enhanced with discussion group (Lose-It premium), short message service text-based support and Wi-Fi scale. The MT group will receive only a self-monitoring application (Lose-It basic). Feasibility and acceptability will be evaluated using number of men recruited and retained, and evaluative focus group feedback. We seek to determine point estimates and variability of outcome measures of weight loss (kg and % body weight) and improved dietary and physical activity behaviours (Behavioral Risk Factor Surveillance System (BRFSS) physical activity and fruit and vegetable consumption surveys, data from Lose-It! application (kcal/day, steps/day)). Community capacity will be assessed using standard best practice methods. Descriptive content analysis will evaluate intervention acceptability and contextual sensitivity. ETHICS AND DISSEMINATION: This protocol was approved by the University of Nebraska Medical Center Institutional Review Board (IRB# 594-17-EP). Dissemination of findings will occur through ClinicalTrials.gov and publish pilot data to inform the design of a larger clinical trial. TRIAL REGISTRATION NUMBER: NCT03329079; preresults. Protocol V.10, study completion date 31 August 2020. Roles and responsibilities funder: NIH/NINR Health Disparities Section 1R15NR017522-01

Chronic exposure to arsenic in the drinking water alters the expression of immune response genes in mouse lung

This paper is not subject to U.S. copyright. The definitive version was published in Environmental Health Perspectives 117 (2009): 1108-1115, doi:10.1289/ehp.0800199.Chronic exposure to drinking water arsenic is a significant worldwide environmental health concern. Exposure to As is associated with an increased risk of lung disease, which may make it a unique toxicant, because lung toxicity is usually associated with inhalation rather than ingestion. The goal of this study was to examine mRNA and protein expression changes in the lungs of mice exposed chronically to environmentally relevant concentrations of As in the food or drinking water, specifically examining the hypothesis that As may preferentially affect gene and protein expression related to immune function as part of its mechanism of toxicant action. C57BL/6J mice fed a casein-based AIN-76A defined diet were exposed to 10 or 100 ppb As in drinking water or food for 5–6 weeks. Whole genome transcriptome profiling of animal lungs revealed significant alterations in the expression of many genes with functions in cell adhesion and migration, channels, receptors, differentiation and proliferation, and, most strikingly, aspects of the innate immune response. Confirmation of mRNA and protein expression changes in key genes of this response revealed that genes for interleukin 1β, interleukin 1 receptor, a number of toll-like receptors, and several cytokines and cytokine receptors were significantly altered in the lungs of As-exposed mice. These findings indicate that chronic low-dose As exposure at the current U.S. drinking-water standard can elicit effects on the regulation of innate immunity, which may contribute to altered disease risk, particularly in lung.This work was supported by National Institute of Environmental Health Science grant P42 ES007373 [J.W.H., Superfund Basic Research Program (SBRP) project 2]. C.D.K., A.P.N., and J.A.G. were supported by graduate and postdoctoral fellowships from P42 ES007373 (SBRP, Training Core). C.D.K. was also supported by National Institutes of Health training grant predoctoral fellowship T32-DF007301. P.L.E. and D.J.W. were supported by Cystic Fibrosis Foundation Research grant HL081289

The JWST Galactic Center Survey -- A White Paper

The inner hundred parsecs of the Milky Way hosts the nearest supermassive black hole, largest reservoir of dense gas, greatest stellar density, hundreds of massive main and post main sequence stars, and the highest volume density of supernovae in the Galaxy. As the nearest environment in which it is possible to simultaneously observe many of the extreme processes shaping the Universe, it is one of the most well-studied regions in astrophysics. Due to its proximity, we can study the center of our Galaxy on scales down to a few hundred AU, a hundred times better than in similar Local Group galaxies and thousands of times better than in the nearest active galaxies. The Galactic Center (GC) is therefore of outstanding astrophysical interest. However, in spite of intense observational work over the past decades, there are still fundamental things unknown about the GC. JWST has the unique capability to provide us with the necessary, game-changing data. In this White Paper, we advocate for a JWST NIRCam survey that aims at solving central questions, that we have identified as a community: i) the 3D structure and kinematics of gas and stars; ii) ancient star formation and its relation with the overall history of the Milky Way, as well as recent star formation and its implications for the overall energetics of our galaxy's nucleus; and iii) the (non-)universality of star formation and the stellar initial mass function. We advocate for a large-area, multi-epoch, multi-wavelength NIRCam survey of the inner 100\,pc of the Galaxy in the form of a Treasury GO JWST Large Program that is open to the community. We describe how this survey will derive the physical and kinematic properties of ~10,000,000 stars, how this will solve the key unknowns and provide a valuable resource for the community with long-lasting legacy value.Comment: This White Paper will be updated when required (e.g. new authors joining, editing of content). Most recent update: 24 Oct 202

Exploring mechanisms of protein influence on calcium oxalate kidney stone formation.

Calcium oxalate monohydrate (COM) crystals are the primary constituent of most kidney stones, but urine proteins in stone matrix are believed to be critical elements for stone formation from these crystals. Recent data have shown that hundreds of proteins appear in the stone matrix with no explanation for inclusion of so many proteins. We have proposed a stone formation model with protein stimulated COM aggregation based on polyanion-polycation aggregation, which is supported by finding that matrix is highly enriched in strongly anionic and strongly cationic proteins. Many other proteins may be drawn to such aggregates due to their limited solubility in water or charge effects. Finding similar protein enrichment in both polyarginine (pR) induced aggregates of urine proteins and COM stone matrix would support this hypothesis. Purified proteins (PP) were obtained from random urine samples of six healthy adults by ultradiafiltration. Protein aggregation was induced by adding pR to PP solutions at two concentrations; 0.25 and 0.5 µg pR/µg of PP. Samples of each fraction and the original PP mixture were lyophilized and analyzed by tandem mass spectrometry. Aggregates induced by pR addition to PP samples collected a protein mixture that mimicked the protein distribution observed in COM matrix, supporting our hypothesis. The apparently discordant behavior of certain abundant anionic proteins preferentially joining the pR aggregate, when they had demonstrated reduced abundance in COM stone matrix, suggests that this model was overdriven to aggregate. The reversal of aggregate preference of albumin at low pR addition supports this interpretation

Effect of Chronic Hyperoxic Exposure on Duroquinone Reduction in Adult Rat Lungs

NAD(P)H:quinone oxidoreductase 1 (NQO1) plays a dominant role in the reduction of the quinone compound 2,3,5,6-tetramethyl-1,4-benzoquinone (duroquinone, DQ) to durohydroquinone (DQH2) on passage through the rat lung. Exposure of adult rats to 85% O2 for ≥7 days stimulates adaptation to the otherwise lethal effects of \u3e95% O2. The objective of this study was to examine whether exposure of adult rats to hyperoxia affected lung NQO1 activity as measured by the rate of DQ reduction on passage through the lung. We measured DQH2 appearance in the venous effluent during DQ infusion at different concentrations into the pulmonary artery of isolated perfused lungs from rats exposed to room air or to 85% O2. We also evaluated the effect of hyperoxia on vascular transit time distribution and measured NQO1 activity and protein in lung homogenate. The results demonstrate that exposure to 85% O2 for 21 days increases lung capacity to reduce DQ to DQH2 and that NQO1 is the dominant DQ reductase in normoxic and hyperoxic lungs. Kinetic analysis revealed that 21-day hyperoxia exposure increased the maximum rate of pulmonary DQ reduction, Vmax, and the apparent Michaelis-Menten constant for DQ reduction, Kma. The increase in Vmax suggests a hyperoxia-induced increase in NQO1 activity of lung cells accessible to DQ from the vascular region, consistent qualitatively but not quantitatively with an increase in lung homogenate NQO1 activity in 21-day hyperoxic lungs. The increase in Kma could be accounted for by ∼40% increase in vascular transit time heterogeneity in 21-day hyperoxic lungs

Heterogeneous stock rats: a new model to study the genetics of renal phenotypes

Chronic kidney disease is a growing medical concern, with an estimated 25.6 million people in the United States exhibiting some degree of kidney injury and/or decline in kidney function. Animal models provide great insight into the study of the genetics of complex diseases. In particular, heterogeneous stock (HS) rats represent a unique genetic resource enabling rapid fine-mapping of complex traits. However, they have not been explored as a model to study renal phenotypes. To evaluate the usefulness of HS rats in the genetics of renal traits, a time course evaluation (weeks 8–40) was performed for several renal phenotypes. As expected, a large degree of variation was seen for most renal traits. By week 24, three (of 40) rats exhibited marked proteinuria that increased gradually until week 40 and ranged from 33.7 to 80.2 mg/24 h. Detailed histological analysis confirmed renal damage in these rats. In addition, several rats consistently exhibited significant hematuria (5/41). Interestingly, these rats were not the same rats that exhibited proteinuria, indicating that susceptibility to different types of kidney injury is likely segregating within the HS population. One HS rat exhibited unilateral renal agenesis (URA), which was accompanied by a significant degree of proteinuria and glomerular and tubulointerstitial injury. The parents of this HS rat were identified and bred further. Additional offspring of this pair were observed to exhibit URA at frequency between 40% and 60%. In summary, these novel data demonstrate that HS rats exhibit variation in proteinuria and other kidney-related traits, confirming that the model harbors susceptibility alleles for kidney injury and providing the basis for further genetic studies