41 research outputs found

    Social contact networks and mixing among students in K-12 schools in Pittsburgh, PA

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    Students attending schools play an important role in the transmission of influenza. In this study, we present a social network analysis of contacts among 1,828 students in eight different schools in urban and suburban areas in and near Pittsburgh, Pennsylvania, United States of America, including elementary, elementary-middle, middle, and high schools. We collected social contact information of students who wore wireless sensor devices that regularly recorded other devices if they are within a distance of 3 meters. We analyzed these networks to identify patterns of proximal student interactions in different classes and grades, to describe community structure within the schools, and to assess the impact of the physical environment of schools on proximal contacts. In the elementary and middle schools, we observed a high number of intra-grade and intra-classroom contacts and a relatively low number of inter-grade contacts. However, in high schools, contact networks were well connected and mixed across grades. High modularity of lower grades suggests that assumptions of homogeneous mixing in epidemic models may be inappropriate; whereas lower modularity in high schools suggests that homogenous mixing assumptions may be more acceptable in these settings. The results suggest that interventions targeting subsets of classrooms may work better in elementary schools than high schools. Our work presents quantitative measures of age-specific, school-based contacts that can be used as the basis for constructing models of the transmission of infections in schools

    Astrocytes regulate GLP-1 receptor-mediated effects on energy balance

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    © 2016 the authors. Astrocytes are well established modulators of extracellular glutamate, but their direct influence on energy balance-relevant behaviors is largely understudied. As the anorectic effects of glucagon-like peptide-1 receptor (GLP-1R) agonists are partly mediated by central modulation of glutamatergic signaling, we tested the hypothesis that astrocytic GLP-1R signaling regulates energy balance in rats. Central or peripheral administration of a fluorophore-labeled GLP-1R agonist, exendin-4, localizes within astrocytes and neurons in the nucleus tractus solitarius (NTS), a hindbrain nucleus critical for energy balance control. This effect is mediated by GLP-1R, as the uptake of systemically administered fluorophore-tagged exendin-4 was blocked by central pretreatment with the competitive GLP-1R antagonist exendin-(9–39). Ex vivo analyses show prolonged exendin-4-induced activation (live cell calcium signaling) of NTS astrocytes and neurons; these effects are also attenuated by exendin-(9–39), indicating mediation by the GLP-1R. In vitro analyses show that the application of GLP-1R agonists increases cAMP levels in astrocytes. Immunohistochemical analyses reveal that endogenous GLP-1 axons form close synaptic apposition with NTS astrocytes. Finally, pharmacological inhibition of NTS astrocytes attenuates the anorectic and body weight-suppressive effects of intra-NTS GLP-1R activation. Collectively, data demonstrate a role for NTS astrocytic GLP-1R signaling in energy balance control

    Lying in Wait: The Resurgence of Dengue Virus After the Zika Epidemic in Brazil

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    After the Zika virus (ZIKV) epidemic in the Americas in 2016, both Zika and dengue incidence declined to record lows in many countries in 2017-2018, but in 2019 dengue resurged in Brazil, causing ~2.1 million cases. In this study we use epidemiological, climatological and genomic data to investigate dengue dynamics in recent years in Brazil. First, we estimate dengue virus force of infection (FOI) and model mosquito-borne transmission suitability since the early 2000s. Our estimates reveal that DENV transmission was low in 2017-2018, despite conditions being suitable for viral spread. Our study also shows a marked decline in dengue susceptibility between 2002 and 2019, which could explain the synchronous decline of dengue in the country, partially as a result of protective immunity from prior ZIKV and/or DENV infections. Furthermore, we performed phylogeographic analyses using 69 newly sequenced genomes of dengue virus serotype 1 and 2 from Brazil, and found that the outbreaks in 2018-2019 were caused by local DENV lineages that persisted for 5-10 years, circulating cryptically before and after the Zika epidemic. We hypothesize that DENV lineages may circulate at low transmission levels for many years, until local conditions are suitable for higher transmission, when they cause major outbreaks

    Ablation of intact hypothalamic and/or hindbrain TrkB signaling leads to perturbations in energy balance

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    Objective: Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), play a paramount role in the central regulation of energy balance. Despite the substantial body of genetic evidence implicating BDNF- or TrkB-deficiency in human obesity, the critical brain region(s) contributing to the endogenous role of BDNF/TrkB signaling in metabolic control remain unknown. Methods: We assessed the importance of intact hypothalamic or hindbrain TrkB signaling in central regulation of energy balance by generating Nkx2.1-Ntrk2−/− and Phox2b-Ntrk2+/− mice, respectively, and comparing metabolic parameters (body weight, adiposity, food intake, energy expenditure and glucose homeostasis) under high-fat diet or chow fed conditions. Results: Our data show that when fed a high-fat diet, male and female Nkx2.1-Ntrk2−/− mice have significantly increased body weight and adiposity that is likely driven by reduced locomotor activity and core body temperature. When maintained on a chow diet, female Nkx2.1-Ntrk2−/− mice exhibit an increased body weight and adiposity phenotype more robust than in males, which is accompanied by hyperphagia that precedes the onset of a body weight difference. In addition, under both diet conditions, Nkx2.1-Ntrk2−/− mice show increased blood glucose, serum insulin and leptin levels. Mice with complete hindbrain TrkB-deficiency (Phox2b-Ntrk2−/−) are perinatal lethal, potentially indicating a vital role for TrkB in visceral motor neurons that control cardiovascular, respiratory, and digestive functions during development. Phox2b-Ntrk2+/− heterozygous mice are similar in body weight, adiposity and glucose homeostasis parameters compared to wild type littermate controls when maintained on a high-fat or chow diet. Interestingly, despite the absence of a body weight difference, Phox2b-Ntrk2+/− heterozygous mice exhibit pronounced hyperphagia. Conclusion: Taken together, our findings suggest that the hypothalamus is a key brain region involved in endogenous BDNF/TrkB signaling and central metabolic control and that endogenous hindbrain TrkB likely plays a role in modulating food intake and survival of mice. Our findings also show that female mice lacking TrkB in the hypothalamus have a more robust metabolic phenotype

    Contact matrices among the grades for each school*.

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    <p>* Each cell represents number of contacts between the grades per pair of students. The contacts with total duration less than 5 minutes are ignored. Each column and row corresponds to a grade and 0 is used for Kindergarten. C: Charter school; P: Public school; ES: Elementary school; EM: Elementary-middle school; MS: Middle school; HS: High school.</p

    Contact network measurements and their standard deviations (and standard errors) for school contact networks<sup>*</sup>.

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    <p>Contact network measurements and their standard deviations (and standard errors) for school contact networks<sup><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151139#t002fn001" target="_blank">*</a></sup>.</p
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