Recent studies reported seasonal differences in gene expression in white blood cells, adipose tissue, and inflammatory biomarkers of the immune system. There is no data on the seasonal variations of ...these biomarkers in the US general population of both children and adults. Then aim of this study is to explore the seasonal trends in complete blood count (CBC), and C-reactive protein (CRP) in a large non-institutionalized US population.
Seven cross-sectional data collected in the National Health and Nutrition Examination Survey (NHANES) during 1999-2012 were aggregated; participants reporting recent use of prescribed steroids, chemotherapy, immunomodulators and antibiotics were excluded. Linear regression models were used to compare levels of CBC and CRP between winter-spring (November-April) and summer-fall (May-October), adjusting for demographics, personal behavioral factors, and chronic disease conditions.
A total of 27,478 children and 36,644 adults (≥18 years) were included in the study. Levels of neutrophils, white blood cell count (WBC), and CRP were higher in winter-spring than summer-fall (p≤0.05). Red blood cell components were lower in winter-spring than in summer-fall, while the opposite was seen for platelets.
This large population-based study found notable seasonal variations in blood cell composition and inflammatory biomarkers, with a more pro-inflammatory immune system seen in winter-spring than summer-fall. The red blood cell patterns could have implications for the observed cardio-vascular seasonality.
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Background Stroke is a major cardiovascular disease that causes significant health and economic burden in the United States. Neighborhood community-based interventions have been shown to be both ...effective and cost-effective in preventing cardiovascular disease. There is a dearth of robust studies identifying the key determinants of cardiovascular disease and the underlying effect mechanisms at the neighborhood level. We aim to contribute to the evidence base for neighborhood cardiovascular health research. Methods and Results We created a new neighborhood health data set at the census tract level by integrating 4 types of potential predictors, including unhealthy behaviors, prevention measures, sociodemographic factors, and environmental measures from multiple data sources. We used 4 tree-based machine learning techniques to identify the most critical neighborhood-level factors in predicting the neighborhood-level prevalence of stroke, and compared their predictive performance for variable selection. We further quantified the effects of the identified determinants on stroke prevalence using a Bayesian linear regression model. Of the 5 most important predictors identified by our method, higher prevalence of low physical activity, larger share of older adults, higher percentage of non-Hispanic Black people, and higher ozone levels were associated with higher prevalence of stroke at the neighborhood level. Higher median household income was linked to lower prevalence. The most important interaction term showed an exacerbated adverse effect of aging and low physical activity on the neighborhood-level prevalence of stroke. Conclusions Tree-based machine learning provides insights into underlying drivers of neighborhood cardiovascular health by discovering the most important determinants from a wide range of factors in an agnostic, data-driven, and reproducible way. The identified major determinants and the interactive mechanism can be used to prioritize and allocate resources to optimize community-level interventions for stroke prevention.
Stroke is a chronic cardiovascular disease that puts major stresses on U.S. health and economy. The prevalence of stroke exhibits a strong geographical pattern at the state-level, where a cluster of ...southern states with a substantially higher prevalence of stroke has been called the stroke belt of the nation. Despite this recognition, the extent to which key neighborhood characteristics affect stroke prevalence remains to be further clarified.
We generated a new neighborhood health data set at the census tract level on nearly 27,000 tracts by pooling information from multiple data sources including the CDC's 500 Cities Project 2017 data release. We employed a two-stage modeling approach to understand how key neighborhood-level risk factors affect the neighborhood-level stroke prevalence in each state of the US. The first stage used a state-of-the-art Bayesian machine learning algorithm to identify key neighborhood-level determinants. The second stage applied a Bayesian multilevel modeling approach to describe how these key determinants explain the variability in stroke prevalence in each state.
Neighborhoods with a larger proportion of older adults and non-Hispanic blacks were associated with neighborhoods with a higher prevalence of stroke. Higher median household income was linked to lower stroke prevalence. Ozone was found to be positively associated with stroke prevalence in 10 states, while negatively associated with stroke in five states. There was substantial variation in both the direction and magnitude of the associations between these four key factors with stroke prevalence across the states.
When used in a principled variable selection framework, high-performance machine learning can identify key factors of neighborhood-level prevalence of stroke from wide-ranging information in a data-driven way. The Bayesian multilevel modeling approach provides a detailed view of the impact of key factors across the states. The identified major factors and their effect mechanisms can potentially aid policy makers in developing area-based stroke prevention strategies.
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Regulation of AMPA receptor (AMPAR) function is a fundamental mechanism controlling synaptic strength during long-term potentiation/depression and homeostatic scaling. AMPAR function and membrane ...trafficking is controlled by protein–protein interactions, as well as by posttranslational modifications. Phosphorylation of the GluA1 AMPAR subunit at S845 and S831 play especially important roles during synaptic plasticity. Recent controversy has emerged regarding the extent to which GluA1 phosphorylation may contribute to synaptic plasticity. Here we used a variety of methods to measure the population of phosphorylated GluA1-containing AMPARs in cultured primary neurons and mouse forebrain. Phosphorylated GluA1 represents large fractions from 12% to 50% of the total population under basal and stimulated conditions in vitro and in vivo. Furthermore, a large fraction of synapses are positive for phospho-GluA1–containing AMPARs. Our results support the large body of research indicating a prominent role of GluA1 phosphorylation in synaptic plasticity.
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Kringle 5, the fifth fragment of plasminogen, is known to be important for inhibiting the proliferation and migration of vascular endothelial cell (VEC), while not having any effects on normal ...endothelial cells. Therefore, it may be a potential tumor therapy candidate. However, the ligand of the Kringle 5 in VEC has not yet been identified. In this study, the possible ligand of Kringle 5 in vitro was screened and validated using Ph.D.-7 phage display peptide library with molecular docking, along with surface plasma resonance (SPR). After four rounds of panning, the specific clones of Kringle 5 were confirmed using enzyme-linked immunosorbent assay (ELISA). The gene sequence analysis showed that they expressed the common amino sequence IGNSNTL. Then, using a NCBI BLAST, 103 matching sequences were found. Following the molecular docking evaluation and considering the acting function and pathway of the plasminogen Kringle 5 in the human body, the most promising candidate was determined to be voltage-dependent anion channel-1 (VDAC-1), which was able to bind to Kringle 5 at -822.65 J·mol-1 of the binding energy at the residues of Lys12, Thr19, Ser57, Thr188, Arg139, Asn214, Ser240 and Lys274. A strong dose-dependent interaction occurred between the VDAC-1 and Kringle 5 (binding constant 2.43 × 103 L·mol-1) in SPR observation. Therefore, this study proposed that VDAC-1 was a potential ligand of plasminogen Kringle 5, and also demonstrated that the screening and validation of protein ligand using phage display peptide library with the molecular docking, along with SPR, was a practicable application.
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Aim： Aquaporins （AQPs） are the water-channels that play important roles in brain water homeostasis and in cerebral edema induced by brain injury. In this study we investigated the relationship ...between AQPs and a neuroprotective agent curcumin that was effective in the treatment of brain edema in mice with intracerebral hemorrhage （ICH）. Methods： ICH was induced in mice by autologous blood infusion. The mice immediately received curcumin （75, 150, and 300 mg/kg, ip）. The Rotarod test scores, brain water content and brain expression of AQPs were measured post ICH. Cultured primary mouse astrocytes were used for in vitro experiments. The expression of AQP1, AQP4 and AQP9 and NF-KB p65 were detected using Western blotting or immunochemistry staining. Results： Curcumin administration dose-dependently reduced the cerebral edema at d 3 post ICH, and significantly attenuated the neurological deficits at d 5 post ICH. Furthermore, curcumin dose-dependently decreased the gene and protein expression of AQP4 and AQPg, but not AQP1 post ICH. Treatment of the cultured astrocytes with Fe2＋ （10-100μmol/L） dose-dependently increased the expression and nuclear translocation of NF-kB p65 and the expression of AQP4 and AQP9, which were partly blocked by co-treatment with curcumin （20 pmol/L） orthe NF-kB inhibitor PDTC （10 pmol/L）. Conclusion： Curcumin effectively attenuates brain edema in mice with ICH through inhibition of the NF-kB pathway and subsequently the expression of AQP4 and AQP9. Curcumin may serve as a potential therapeutic agent for ICH.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Design Cushing’s disease (CD) is a rare clinical syndrome characterized by chronic exposure to hypercortisolism due to an adrenocorticotropic hormone-secreting pituitary adenoma. The adverse effects ...of chronic exposure to hypercortisolism on the human brain remain unclear. The purpose of this study was to assess the prevalence of cerebral microbleeds (CMBs) in CD patients and their associations with clinical characteristics. Methods In this study, 48 active CD patients, 39 remitted CD patients, and 52 healthy control (HC) subjects underwent MRI. CD patients also underwent neuropsychological testing and clinical examinations. The number, locations, and volumes of CMBs were assessed on quantitative susceptibility mapping (QSM) images and with the Microbleed Anatomical Rating Scale. The correlation between CMBs and clinical characteristics was explored. Results The prevalence of CMBs among active and remitted CD patients was higher than that among HCs (16.3%, 20.5%, and 3.3%, respectively). Moreover, the age of CD patients with CMBs were much younger than HCs with CMBs. Furthermore, the increased number of CMBs in active CD patients was associated with increased cerebrospinal fluid (CSF) volumes in remitted CD patients. Conclusions Chronic exposure to hypercortisolism may be relevant to CMBs and significantly correlated with altered brain volumes in CD.
The Prostate Imaging Reporting and Data System (PI-RADS) has good ability to identify the nature of lesions on prostate magnetic resonance imaging (MRI). However, some lesions are still reported as ...PI-RADS 4 and 5 but are biopsy-proven benign. Herein, we aimed to summarize the reasons for the negative prostate biopsy of patients who were assessed as PI-RADS 4 and 5 by biparameter MRI. We retrospectively sorted out the prostate MRI, treatment, and follow-up results of patients who underwent a biparameter MRI examination of the prostate in The First Affiliated Hospital of Nanjing Medical University (Nanjing, China) from August 2019 to June 2021 with PI-RADS 4 and 5 but a negative biopsy. We focused on reviewing the MRI characteristics. A total of 467 patients underwent transperineal prostate biopsy. Among them, biopsy pathology of 93 cases were negative. After follow-up, 90 patients were ruled out of prostate cancer. Among the 90 cases, 40 were considered to be overestimated PI-RADS after review. A total of 22 cases were transition zone (TZ) lesions with regular appearance and clear boundaries, and 3 cases were symmetrical lesions. Among 15 cases, the TZ nodules penetrated the peripheral zone (PZ) and were mistaken for the origin of PZ. A total of 17 cases of lesions were difficult to distinguish from prostate cancer. Among them, 5 cases were granulomatous inflammation (1 case of prostate tuberculosis). A total of 33 cases were ambiguous lesions, whose performance was between PI-RADS 3 and 4. In summary, the reasons for "false-positive MRI diagnosis" included PI-RADS overestimation, ambiguous images giving higher PI-RADS, diseases that were really difficult to distinguish, and missed lesion in the initial biopsy; and the first two accounted for the most.
Hurricane Sandy caused extensive physical and economic damage; the long-term mental health consequences are unknown. Flooding is a central component of hurricane exposure, influencing mental health ...through multiple pathways that unfold over months after flooding recedes. Here we assess the concordance in self-reported and Federal Emergency Management (FEMA) flood exposure after Hurricane Sandy and determine the associations between flooding and anxiety, depression, and post-traumatic stress disorder (PTSD). Self-reported flood data and mental health symptoms were obtained through validated questionnaires from New York City and Long Island residents (N = 1231) following Sandy. Self-reported flood data was compared to FEMA data obtained from the FEMA Modeling Task Force Hurricane Sandy Impact Analysis. Multivariable logistic regressions were performed to determine the relationship between flooding exposure and mental health outcomes. There were significant discrepancies between self-reported and FEMA flood exposure data. Self-reported dichotomous flooding was positively associated with anxiety (ORadj: 1.5 95% CI: 1.1-1.9), depression (ORadj: 1.7 1.3-2.2), and PTSD (ORadj: 2.5 1.8-3.4), while self-reported continuous flooding was associated with depression (ORadj: 1.1 1.01-1.12) and PTSD (ORadj: 1.2 1.1-1.2). Models with FEMA dichotomous flooding (ORadj: 2.1 1.5-2.8) or FEMA continuous flooding (ORadj: 1.1 1.1-1.2) were only significantly associated with PTSD. Associations between mental health and flooding vary according to type of flood exposure measure utilized. Future hurricane preparedness and recovery efforts must integrate micro and macro-level flood exposures in order to accurately determine flood exposure risk during storms and realize the long-term importance of flooding on these three mental health symptoms.
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