Exposure to Household Air Pollution from Biomass Cookstoves and Blood Pressure Among Women in Rural Honduras: A Cross‐Sectional Study

Growing evidence links household air pollution exposure from biomass cookstoves with elevated blood pressure. We assessed cross‐sectional associations of 24‐hour mean concentrations of personal and kitchen fine particulate matter (PM2.5), black carbon (BC), and stove type with blood pressure, adjusting for confounders, among 147 women using traditional or cleaner‐burning Justa stoves in Honduras. We investigated effect modification by age and body mass index. Traditional stove users had mean (standard deviation) personal and kitchen 24‐hour PM2.5 concentrations of 126 μg/m3 (77) and 360 μg/m3 (374), while Justa stove users’ exposures were 66 μg/m3 (38) and 137 μg/m3(194), respectively. BC concentrations were similarly lower among Justa stove users. Adjusted mean systolic blood pressure was 2.5 mm Hg higher (95% CI, 0.7‐4.3) per unit increase in natural log‐transformed kitchen PM2.5 concentration; results were stronger among women of 40 years or older (5.2 mm Hg increase, 95% CI, 2.3‐8.1). Adjusted odds of borderline high and high blood pressure (categorized) were also elevated (odds ratio = 1.5, 95% CI, 1.0‐2.3). Some results included null values and are suggestive. Results suggest that reduced household air pollution, even when concentrations exceed air quality guidelines, may help lower cardiovascular disease risk, particularly among older subgroups

Exposure to Household Air Pollution from Biomass Cookstoves and Levels of Fractional Exhaled Nitric Oxide (FeNO) among Honduran Women

Household air pollution is estimated to be responsible for nearly three million premature deaths annually. Measuring fractional exhaled nitric oxide (FeNO) may improve the limited understanding of the association of household air pollution and airway inflammation. We evaluated the cross-sectional association of FeNO with exposure to household air pollution (24-h average kitchen and personal fine particulate matter and black carbon; stove type) among 139 women in rural Honduras using traditional stoves or cleaner-burning Justastoves. We additionally evaluated interaction by age. Results were generally consistent with a null association; we did not observe a consistent pattern for interaction by age. Evidence from ambient and household air pollution regarding FeNO is inconsistent, and may be attributable to differing study populations, exposures, and FeNO measurement procedures (e.g., the flow rate used to measure FeNO)

Self-Control in Cyberspace: Applying Dual Systems Theory to a Review of Digital Self-Control Tools

Many people struggle to control their use of digital devices. However, our understanding of the design mechanisms that support user self-control remains limited. In this paper, we make two contributions to HCI research in this space: first, we analyse 367 apps and browser extensions from the Google Play, Chrome Web, and Apple App stores to identify common core design features and intervention strategies afforded by current tools for digital self-control. Second, we adapt and apply an integrative dual systems model of self-regulation as a framework for organising and evaluating the design features found. Our analysis aims to help the design of better tools in two ways: (i) by identifying how, through a well-established model of self-regulation, current tools overlap and differ in how they support self-control; and (ii) by using the model to reveal underexplored cognitive mechanisms that could aid the design of new tools.Comment: 11.5 pages (excl. references), 6 figures, 1 tabl

Reductions in radiographic progression in early RA over 25-years: changing contribution from RF in 2 multi-centre UK inception cohorts

Objectives: To assess 5-year progression of erosions and Joint Space Narrowing (JSN), and their associations with RF status in two large, multi-centre early-RA cohorts spanning 25-years. Methods: Radiographic joint damage was recorded using the Sharp/van der Heijde (SvdH) method in the Early RA Study (ERAS) 1986-2001, and the Early RA Network (ERAN) 2002-2013. Mixed-effects negative-binomial regression estimated changes in radiographic damage over 5-years, including erosions and JSN separately. Rheumatoid Factor (RF), along with age, sex and baseline markers of disease activity were controlled for. Results: 1,216 patients from ERAS and 446 from ERAN had radiographic data. Compared to ERAS, ERAN patients had a lower mean total SvdH score at baseline (ERAN=6.2 vs. ERAS=10.5, p<0.001), and mean annual rate of change (ERAN=2.5 vs. ERAS=6.9 per year, p<0.001). 74% of ERAS and 27% of ERAN patients progressed ≥5 units. Lower scores at baseline in ERAN were largely driven by reductions in JSN (ERAS=3.9 vs. ERAN=1.2, p<0.001), along with erosions (ERAS=1.9 vs. ERAN=0.8, p<0.001). RF was associated with greater progression in each cohort, but the absolute difference in mean annual rate of change for RF positive patients was substantially higher for ERAS (RF+= 8.6 vs. RF-= 5.1, p<0.001), relative to ERAN (RF+= 2.0 vs. RF-= 1.9, p=0.855). Conclusion: Radiographic progression has significantly reduced between the two cohorts, associated with lower baseline damage and other factors, including changes in early DMARD use. The impact of RF status as a prognostic marker of clinically meaningful change in radiographic progression has markedly diminished in the context of more modern treatment. This article is protected by copyright. All rights reserved

Inhibitor of Differentiation (Id) Genes Are Expressed in the Steroidogenic Cells of the Ovine Ovary and Are Differentially Regulated by Members of the Transforming Growth Factor-beta Family

Inhibitor of Differentiation (Id) proteins act during embryogenesis and development to repress gene transcription required for lineage commitment, whilst promoting cell growth. Growth factors belonging to the transforming growth factor beta (TGFβ) superfamily of signaling molecules, notably the bone morphogenetic proteins (BMPs) and activin, can regulate Id expression in these tissues. Id expression and function in adult physiology is less well determined and we hypothesized a role for Id proteins in the adult mammalian ovary. Immunohistochemistry for Id1, Id2, Id3 and Id4 in the sheep ovary revealed consistent expression in granulosa and thecal cells of ovarian follicles throughout development. In atretic follicles Id proteins were selectively down-regulated in thecal cells (P<0.0001). Additionally Id1 was universally up-regulated in the cumulus cells adjacent to the oocyte. Immunohistochemistry for phospho (p)-smad 1/5/8 signalling components (stimulated by BMPs) showed a punctate pattern of expression whereas p-smad 2/3 (stimulated by activin) was ubiquitously expressed in follicles. Neither pathway however displayed differential staining in line with Id1 cumulus specific expression, suggesting a more complex relationship between Id1 expression and TGFβ signaling in these cells. Nevertheless, in vitro, stimulation of ovine granulosa cells with BMP6 or activin A led to a respective increase and decrease in Id1 (P<0.0001), Id2 (P<0.0001), Id3 (P<0.0001) and Id4 (P<0.05) transcripts and Id1 gene expression was further manipulated by the oocyte-secreted factors BMP15 and GDF9 (P<0.001). These data confirm that TGFβ signaling can regulate Id gene expression in the sheep ovarian follicle and suggest a functional role for the Id family in the mammalian ovary

Exposure to household air pollution from biomass cookstoves and blood pressure among women in rural Honduras: A crossâ sectional study

Growing evidence links household air pollution exposure from biomass cookstoves with elevated blood pressure. We assessed crossâ sectional associations of 24â hour mean concentrations of personal and kitchen fine particulate matter (PM2.5), black carbon (BC), and stove type with blood pressure, adjusting for confounders, among 147 women using traditional or cleanerâ burning Justa stoves in Honduras. We investigated effect modification by age and body mass index. Traditional stove users had mean (standard deviation) personal and kitchen 24â hour PM2.5 concentrations of 126 μg/m3 (77) and 360 μg/m3 (374), while Justa stove usersâ exposures were 66 μg/m3 (38) and 137 μg/m3 (194), respectively. BC concentrations were similarly lower among Justa stove users. Adjusted mean systolic blood pressure was 2.5 mm Hg higher (95% CI, 0.7â 4.3) per unit increase in natural logâ transformed kitchen PM2.5 concentration; results were stronger among women of 40 years or older (5.2 mm Hg increase, 95% CI, 2.3â 8.1). Adjusted odds of borderline high and high blood pressure (categorized) were also elevated (odds ratio = 1.5, 95% CI, 1.0â 2.3). Some results included null values and are suggestive. Results suggest that reduced household air pollution, even when concentrations exceed air quality guidelines, may help lower cardiovascular disease risk, particularly among older subgroups.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146816/1/ina12507.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146816/2/ina12507_am.pd

Inhibiting Androgen Receptor Splice Variants With Cysteine-Selective Irreversible Covalent Inhibitors To Treat Prostate Cancer

Androgen receptor (AR) and its splice variants (AR-SVs) promote prostate cancer (PCa) growth by orchestrating transcriptional reprogramming. Mechanisms by which the low complexity and intrinsically disordered primary transactivation domain (AF-1) of AR and AR-SVs regulate transcriptional programming in PCa remains poorly defined. Using omics, live and fixed fluorescent microscopy of cells, and purified AF-1 and AR-V7 recombinant proteins we show here that AF-1 and the AR-V7 splice variant form molecular condensates by liquid-liquid phase separation (LLPS) that exhibit disorder characteristics such as rapid intracellular mobility, coactivator interaction, and euchromatin induction. The LLPS and other disorder characteristics were reversed by a class of small-molecule-selective AR-irreversible covalent antagonists (SARICA) represented herein by UT-143 that covalently and selectively bind to C406 and C327 in the AF-1 region. Interfering with LLPS formation with UT-143 or mutagenesis resulted in chromatin condensation and dissociation of AR-V7 interactome, all culminating in a transcriptionally incompetent complex. Biochemical studies suggest that C327 and C406 in the AF-1 region are critical for condensate formation, AR-V7 function, and UT-143\u27s irreversible AR inhibition. Therapeutically, UT-143 possesses drug-like pharmacokinetics and metabolism properties and inhibits PCa cell proliferation and tumor growth. Our work provides critical information suggesting that clinically important AR-V7 forms transcriptionally competent molecular condensates and covalently engaging C327 and C406 in AF-1, dissolves the condensates, and inhibits its function. The work also identifies a library of AF-1-binding AR and AR-SV-selective covalent inhibitors for the treatment of PCa

Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918

The H1N1 subtype of influenza A virus has caused substantial morbidity and mortality in humans, first documented in the global pandemic of 1918 and continuing to the present day. Despite this disease burden, the evolutionary history of the A/H1N1 virus is not well understood, particularly whether there is a virological basis for several notable epidemics of unusual severity in the 1940s and 1950s. Using a data set of 71 representative complete genome sequences sampled between 1918 and 2006, we show that segmental reassortment has played an important role in the genomic evolution of A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate from the 1947 epidemic acquired novel PB2 and HA genes through intra-subtype reassortment, which may explain the abrupt antigenic evolution of this virus. Similarly, the 1951 influenza epidemic may also have been associated with reassortant A/H1N1 viruses. Intra-subtype reassortment therefore appears to be a more important process in the evolution and epidemiology of H1N1 influenza A virus than previously realized