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Background: Prevalence rates for both overweight and asthma have been increasing among children in developed countries over the past two decades. Some recent studies have postulated a causal relation between these but have lacked power to form a definitive conclusion. Aim: To estimate the effect of high body weight in childhood on the future risk of asthma. Methods: Medline search (1966 to October 2004), supplemented by manual search of reference lists and grey literature. Cohort studies that examined high body weight at birth or during childhood and future outcome of asthma were included. Data from each study were extracted on exposure status, clinical outcome, and study characteristics. Results: A total of 402 studies were initially identified, of which 12 met the inclusion criteria. The combined results from four studies that examined the effect of high body weight during middle childhood on the outcome of subsequent asthma showed a 50% increase in relative risk (RR 1.5, 95% CI 1.2 to 1.8). The combined results from nine studies that examined the effect of high birth weight on subsequent asthma had a pooled RR of 1.2 (95% CI 1.1 to 1.3). There was consistency among the results in sensitivity analyses examining studies containing only estimates of odds ratios, studies containing only the outcome of physician diagnosis of asthma, and studies including all definitions of high body weight. Conclusions: Children with high body weight, either at birth or later in childhood, are at increased risk for future asthma. Potential biological mechanisms include diet, gastro-oesophageal reflux, mechanical effects of obesity, atopy, and hormonal influences. Further research might elucidate the causal pathway, which could improve our understanding of the pathophysiology of asthma and perhaps lead to knowledge of potential preventive interventions.

The structure of the sodium-benzylhydantoin transport protein Mhp1 from Microbacterium liquefaciens comprises a five-helix inverted repeat, which is widespread among secondary transporters. Here, we report the crystal structure of an inward-facing conformation of Mhp1 at 3.8 angstroms resolution, complementing its previously described structures in outward-facing and occluded states. From analyses of the three structures and molecular dynamics simulations, we propose a mechanism for the transport cycle in Mhp1. Switching from the outward- to the inward-facing state, to effect the inward release of sodium and benzylhydantoin, is primarily achieved by a rigid body movement of transmembrane helices 3, 4, 8, and 9 relative to the rest of the protein. This forms the basis of an alternating access mechanism applicable to many transporters of this emerging superfamily.

The nucleobase-cation-symport-1 (NCS1) transporters are essential components of salvage pathways for nucleobases and related metabolites. Here, we report the 2.85-angstrom resolution structure of the NCS1 benzyl-hydantoin transporter, Mhp1, from Microbacterium liquefaciens. Mhp1 contains 12 transmembrane helices, 10 of which are arranged in two inverted repeats of five helices. The structures of the outward-facing open and substrate-bound occluded conformations were solved, showing how the outward-facing cavity closes upon binding of substrate. Comparisons with the leucine transporter LeuTAa and the galactose transporter vSGLT reveal that the outward- and inward-facing cavities are symmetrically arranged on opposite sides of the membrane. The reciprocal opening and closing of these cavities is synchronized by the inverted repeat helices 3 and 8, providing the structural basis of the alternating access model for membrane transport.

1. The role of land cover change as a significant component of global change has become increasingly recognized in recent decades. Large databases measuring land cover change, and the data which can potentially be used to explain the observed changes, are also becoming more commonly available. When developing statistical models to investigate observed changes, it is important to be aware that the chosen sampling strategy and modelling techniques can influence results. 2. We present a comparison of three sampling strategies and two forms of grouped logistic regression models (multinomial and ordinal) in the investigation of patterns of successional change after agricultural land abandonment in Switzerland. 3. Results indicated that both ordinal and nominal transitional change occurs in the landscape and that the use of different sampling regimes and modelling techniques as investigative tools yield different results. 4. Synthesis and applications. Our multimodel inference identified successfully a set of consistently selected indicators of land cover change, which can be used to predict further change, including annual average temperature, the number of already overgrown neighbouring areas of land and distance to historically destructive avalanche sites. This allows for more reliable decision making and planning with respect to landscape management. Although both model approaches gave similar results, ordinal regression yielded more parsimonious models that identified the important predictors of land cover change more efficiently. Thus, this approach is favourable where land cover change pattern can be interpreted as an ordinal process. Otherwise, multinomial logistic regression is a viable alternative.

PurposeWe aimed to estimate the structure of internalizing and externalizing symptoms and potential time dynamics in their association. This is understudied among adolescents, despite increasing internalizing and decreasing externalizing symptoms in recent years.MethodsWe analyzed data from US Monitoring the Future cross-sectional surveys (1991–2018) representative of school-attending adolescents (N = 304,542). Exploratory factor analysis using maximum likelihood estimation method and promax rotation resulted in a two-factor solution (factor correlation r = 0.24) that differentiated eight internalizing and seven conduct-related externalizing symptoms. Time-varying effect modification linear regression models estimated the association between standardized internalizing and externalizing symptoms factor scores over time overall and by gender.ResultsIn 2012, trends in average factor scores diverged for internalizing and externalizing factors. The average standardized internalizing factor score increased from − 0.03 in 2012 to 0.06 in 2013 and the average externalizing factor score decreased from − 0.06 in 2011 to − 0.13 in 2012. We found that for every one-unit increase in standardized internalizing factor score, standardized externalizing factor score increased by 0.224 units in 2010 (95% CI: 0.215, 0.233); the magnitude of this increase was 22.3% lower in 2018 (i.e., 0.174 units; 95% CI: 0.160, 0.188). Decoupling of internalizing and externalizing symptoms began earlier among boys (~ 1995) than among girls (~ 2010).ConclusionThe decoupling of internalizing and externalizing symptoms among adolescents suggests that changes in the prevalence of shared risk factors for adolescent psychiatric symptoms affect these dimensions in opposing directions, raising the importance of considering symptoms and their risk factors together in prevention and intervention efforts.

Objectives. To evaluate the relationship between changes in county jail incarceration rates and subsequent county mortality rates across the United States. Methods. We analyzed county jail incarceration rates from the Bureau of Justice Statistics from 1987 to 2016 for 1884 counties and mortality rates from the National Vital Statistics System. We fit 1-year-lagged quasi-Poisson 2-way fixed-effects models, controlling for unmeasured stable county characteristics, and measured time-varying confounders, including county poverty and crime rates. Results. A within-county increase in jail incarceration rates from the first to second quartile was associated with a 2.5% increase in mortality rates, adjusting for confounders (risk ratio [RR] = 1.03; 95% confidence interval [CI] = 1.02, 1.03). This association followed a dose–response relationship and was stronger for mortality among those aged 15 to 34 years (RR = 1.07; 95% CI = 1.06, 1.09). Conclusions. Within-county increases in jail incarceration rates are associated with increases in subsequent mortality rates after adjusting for important confounders. Public Health Implications. Our findings add to the growing body of empirical evidence of the harms of mass incarceration. The criminal justice reform and decarceration movements can use these findings as they develop strategies to end mass incarceration.

Understanding how an amino acid sequence folds into a functional, three-dimensional structure has proved to be a formidable challenge in biological research, especially for transmembrane proteins with multiple alpha helical domains. Mechanistic folding studies on helical membrane proteins have been limited to unusually stable, single domain proteins such as bacteriorhodopsin. Here, we extend such work to flexible, multidomain proteins and one of the most widespread membrane transporter families, the major facilitator superfamily, thus showing that more complex membrane proteins can be successfully refolded to recover native substrate binding. We determine the unfolding free energy of the two-domain, Escherichia coli galactose transporter, GalP; a bacterial homologue of human glucose transporters. GalP is reversibly unfolded by urea. Urea causes loss of substrate binding and a significant reduction in alpha helical content. Full recovery of helical structure and substrate binding occurs in dodecylmaltoside micelles, and the unfolding free energy can be determined. A linear dependence of this free energy on urea concentration allows the free energy of unfolding in the absence of urea to be determined as +2.5 kcal·mol⁻¹. Urea has often been found to be a poor denaturant for transmembrane helical structures. We attribute the denaturation of GalP helices by urea to the dynamic nature of the transporter structure allowing denaturant access via the substrate binding pocket, as well as to helical structure that extends beyond the membrane. This study gives insight into the final, critical folding step involving recovery of ligand binding for a multidomain membrane transporter.

Although it is apparent that providing useful information has a positive effect on transit riders, no studies to date have investigated bus operators’ reactions to real-time arrival information and other potential rider information tools. In this study, the project team surveyed 253 bus operators to determine their views and values concerning the existing use of real-time information and to ask about future transit rider information applications. Almost all operators (93 and 91 % on two separate questions) were positive or neutral to the provision of real-time information. In addition, operators were receptive to building other new information applications, with all applications in the survey being supported by at least 60 % of the bus operators. The two most widely supported potential applications in the survey were additional tools to help blind and deaf-blind riders (89 % of bus operators favored) and an application that would aid riders in identifying physical stop, shelter and bus issues such as graffiti, broken parts or a need for lights (88 % of bus operators). Applications displaying data about past performance or current bus capacity received the least support (66 and 61 % respectively). This research gives a better understanding of the impact of rider information tools on bus operators, including the views and values of the operators, and the harms and benefits of such tools.

Objectives. We evaluated the protective effectiveness of speed humps in reducing child pedestrian injuries in residential neighborhoods. Methods. We conducted a matched case–control study over a 5-year period among children seen in a pediatric emergency department after being struck by an automobile. Results. A multivariate conditional logistic regression analysis showed that speed humps were associated with lower odds of children being injured within their neighborhood (adjusted odds ratio [OR] = 0.47) and being struck in front of their home (adjusted OR = 0.40). Ethnicity (but not socioeconomic status) was independently associated with child pedestrian injuries and was adjusted for in the regression model. Conclusions. Our findings suggest that speed humps make children’s living environments safer.

Background. GB virus C (GBV-C) infection is transmitted by blood exposure and associated with lower human immunodeficiency virus (HIV) load and slower HIV disease progression. Few studies describe predictors of acute GBV-C infection following transfusion in HIV-infected patients. Methods. We used a limited-access database from the National Heart Lung and Blood Institute's Viral Activation Transfusion Study, a randomized controlled trial of leukoreduced versus nonleukoreduced transfusions received by HIV-infected, transfusion-naive patients. Blood samples from 489 subjects were tested for GBV-C markers in pretransfusion and posttransfusion samples. We estimated the risk of acquiring GBV-C RNA and predictors of GBV-C acquisition, using pooled logistic regression. Results. GBV-C RNA was detected ≤120 days following the first transfusion in 22 (7.5%) of 294 subjects who were GBV-C negative before transfusion. The risk of GBV-C RNA acquisition increased with each unit transfused (odds ratio, 1.09; 95% confidence interval, 1.06—1.11). Lower baseline HIV load and use of antiretroviral therapy were associated with subsequent GBV-C RNA acquisition, after control for units of blood transfused. Leukoreduced status of transfused units was not associated with GBV-C transmission. Conclusions. Blood transfusion is associated with a significant risk of GBV-C acquisition among HIV-infected patients. Transmission of GBV-C by blood transfusion was inversely related to HIV load.