Postmenopausal Women With Greater Paracardial Fat Have More Coronary Artery Calcification Than Premenopausal Women: The Study of Women's Health Across the Nation (SWAN) Cardiovascular Fat Ancillary Study.

BackgroundVolumes of paracardial adipose tissue (PAT) and epicardial adipose tissue (EAT) are greater after menopause. Interestingly, PAT but not EAT is associated with estradiol decline, suggesting a potential role of menopause in PAT accumulation. We assessed whether volumes of heart fat depot (EAT and PAT) were associated with coronary artery calcification (CAC) in women at midlife and whether these associations were modified by menopausal status and estradiol levels.Methods and resultsEAT and PAT volumes and CAC were measured using electron beam computed tomography scans. CAC was evaluated as (1) the presence of CAC (CAC Agatston score ≥10) and (2) the extent of any CAC (log CAC Agatston score >0). The study included 478 women aged 50.9 years (58% pre- or early perimenopausal, 10% late perimenopausal, and 32% postmenopausal). EAT was significantly associated with CAC measures, and these associations were not modified by menopausal status or estradiol. In contrast, associations between PAT and CAC measures were modified by menopausal status (interaction-P≤0.01). Independent of study covariates including other adiposity measures, each 1-SD unit increase in log PAT was associated with 102% higher risk of CAC presence (P=0.04) and an 80% increase in CAC extent (P=0.008) in postmenopausal women compared with pre- or early perimenopausal women. Additional adjustment for estradiol and hormone therapy attenuated these differences. Moreover, the association between PAT and CAC extent was stronger in women with lower estradiol levels (interaction P=0.004).ConclusionsThe findings suggest that PAT is a potential menopause-specific coronary artery disease risk marker, supporting the need to monitor and target this fat depot for intervention in women at midlife

Fatal Outcome of Disseminated Strongyloidiasis despite Detectable Plasma and Cerebrospinal Levels of Orally Administered Ivermectin

Strongyloides stercoralis affects over 100 million people worldwide. Those people most susceptible to infection are those with an immunocompromising condition, such as cancer or human immunodeficiency virus (HIV). Local disease may spread throughout the body of the host, causing a condition termed disseminated strongyloidiasis. Standard treatment for Strongyloides stercoralis infection is oral ivermectin. We describe a patient with chronic lymphocytic leukemia diagnosed with disseminated strongyloidiasis two weeks after initial presentation. After repeated dosing of oral ivermectin with no clinical response, serum and cerebral spinal fluid (CSF) concentrations of ivermectin were measured to assess absorption. The peak serum concentration of 49.3 ng/mL correlated with a CSF concentration of 0.14 ng/mL. Despite these concentrations, the patient eventually succumbed to multi-system organ failure. We discuss the reasons for treatment failure and explore the utility of measuring ivermectin concentrations

Relativistic mean field approximation to the analysis of 16O(e,e'p)15N data at |Q^2|\leq 0.4 (GeV/c)^2

We use the relativistic distorted wave impulse approximation to analyze data on 16O(e,e'p)15N at |Q^2|\leq 0.4 (GeV/c)^2 that were obtained by different groups and seemed controversial. Results for differential cross-sections, response functions and A_TL asymmetry are discussed and compared to different sets of experimental data for proton knockout from p_{1/2} and p_{3/2} shells in 16O. We compare with a nonrelativistic approach to better identify relativistic effects. The present relativistic approach is found to accommodate most of the discrepancy between data from different groups, smoothing a long standing controversy.Comment: 28 pages, 7 figures (eps). Major revision made. New figures added. To be published in Phys. Rev.

Modeling the role of fomites in a norovirus outbreak

Norovirus accounts for a large portion of the gastroenteritis disease burden, and outbreaks have occurred in a wide variety of environments. Understanding the role of fomites in norovirus transmission will inform behavioral interventions, such as hand washing and surface disinfection. The purpose of this study was to estimate the contribution of fomite-mediated exposures to infection and illness risks in outbreaks. A simulation model in discrete time that accounted for hand-to-porous surfaces, hand-to-nonporous surfaces, hand-to-mouth, -eyes, -nose, and hand washing events was used to predict 17 hr of simulated human behavior. Norovirus concentrations originated from monitoring contamination levels on surfaces during an outbreak on houseboats. To predict infection risk, two dose-response models (fractional Poisson and 2F1 hypergeometric) were used to capture a range of infection risks. A triangular distribution describing the conditional probability of illness given an infection was multiplied by modeled infection risks to estimate illness risks. Infection risks ranged from 70.22% to 72.20% and illness risks ranged from 21.29% to 70.36%. A sensitivity analysis revealed that the number of hand-to-mouth contacts and the number of hand washing events had strong relationships with model-predicted doses. Predicted illness risks overlapped with leisure setting and environmental attack rates reported in the literature. In the outbreak associated with the viral concentrations used in this study, attack rates ranged from 50% to 86%. This model suggests that fomites may have accounted for 25% to 82% of illnesses in this outbreak. Fomite-mediated exposures may contribute to a large portion of total attack rates in outbreaks involving multiple transmission modes. The findings of this study reinforce the importance of frequent fomite cleaning and hand washing, especially when ill persons are present.12 month embargo; published online: 04 Feb 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

DIFFERENTIAL REGULATION OF INDIVIDUAL SULFOTRANSFERASE ISOFORMS BY PHENOBARBITAL IN MALE RAT LIVER

This paper is available online at http://www.dmd.org ABSTRACT: Xenobiotics that induce the cytochromes P450 also produce changes in rat hepatic sulfotransferase (SULT) gene expression. In the present study, male Sprague-Dawley rats were treated for 3 consecutive days with doses of phenobarbital (PB) that induce cytochrome P450 2B1/2 expression. The effects of PB treatment on hepatic aryl SULT (SULT1) and hydroxysteroid SULT (SULT2) mRNA and immunoreactive protein levels and on mRNA expression of individual SULT1 and SULT2 enzyme isoforms were characterized. PB suppressed SULT1A1 mRNA levels, increased the expression of the SULT-Dopa/tyrosine isoform, and did not produce significant changes in SULT1C1 and SULT1E2 mRNA expression. In rats injected with the highest test dose of PB (100 mg/kg), hepatic SULT1A1 mRNA levels were decreased to ϳ42% of control levels and SULT-Dopa/tyrosine mRNA levels were increased to ϳ417% of vehicle-treated control levels. Like the SULT1 subfamily, individual members of the SULT2 gene subfamily were differentially affected by PB treatment. PB (35, 80, and 100 mg/kg) suppressed SULT20/21 mRNA expression to ϳ61, ϳ30, and ϳ41% of vehicle-treated control levels, respectively. In contrast, SULT60 mRNA levels were increased to ϳ162% of control levels and SULT40/41 mRNA levels were increased to ϳ416% of vehicletreated control levels in rats treated with 100 mg/kg PB. These studies support a complex role for PB-mediated effects on the SULT multigene family in rat liver. Because individual SULT1 and SULT2 enzyme isoforms are known to metabolize a variety of potentially toxic substrates, varied responses to PB among members of the SULT multigene family might have important implications for xenobiotic hepatotoxicity

Peer Influence during Adolescence: The Moderating Role of Parental Support

Although many studies show that peers influence the development of adolescent internalizing and externalizing difficulties, few have considered both internalizing and externalizing difficulties in the same study, and fewer have considered the contributions of parents. Using a longitudinal sample of 385 adolescents, the contributions of best friends\u27 internalizing and externalizing difficulties (as assessed in Grade 6; G6: M(age) = 13.64 years; 53% female; 40% ethnic or racial minority) were examined as they predicted subsequent adolescent internalizing and externalizing difficulties (at G8); in addition, the moderating role of both maternal and paternal support (at G6) was explored. Structural equation modelling revealed that best friend internalizing difficulties predicted decreases, but that best friend externalizing difficulties predicted increases in adolescents\u27 externalizing difficulties over time. Significant interactions involving both maternal and paternal support revealed that the negative impact of a G6 best friend having internalizing problems on later G8 adolescent externalizing problems was stronger at low levels of maternal and paternal support. The findings highlight the complex, and interactive, influences of friends and parents on the development of internalizing and externalizing symptomatology during adolescence, and underscore the importance of targeting both sources of social influence in research and clinical work

Endomicroscopic and transcriptomic analysis of impaired barrier function and malabsorption in environmental enteropathy

Introduction: Environmental enteropathy (EE) is associated with growth failure, micronutrient malabsorption and impaired responses to oral vaccines. We set out to define cellular mechanisms of impaired barrier function in EE and explore protective mechanisms. Methods: We studied 49 adults with environmental enteropathy in Lusaka, Zambia using confocal laser endomicroscopy (CLE); histology, immunohistochemistry and mRNA sequencing of small intestinal biopsies; and correlated these with plasma lipopolysaccharide (LPS) and a zinc uptake test. Results: CLE images (median 134 for each study) showed virtually ubiquitous small intestinal damage. Epithelial defects, imaged by histology and claudin 4 immunostaining, were predominantly seen at the tips of villi and corresponded with leakage imaged in vivo by CLE. In multivariate analysis, circulating log-transformed LPS was correlated with cell shedding events (β = 0.83; P = 0.035) and with serum glucagon-like peptide-2 (β = -0.13; P = 0.007). Zinc uptake from a test dose of 25mg was attenuated in 30/47 (64%) individuals and in multivariate analysis was reduced by HIV, but positively correlated with GLP-2 (β = 2.72; P = 0.03). There was a U-shaped relationship between circulating LPS and villus surface area. Transcriptomic analysis identified 23 differentially expressed genes in severe enteropathy, including protective peptides and proteins. Conclusions: Confocal endomicroscopy, claudin 4 immunostaining and histology identify epithelial defects which are probably sites of bacterial translocation, in the presence of which increased epithelial surface area increases the burden of translocation. GLP 2 and other protective peptides may play an important role in mucosal protection in EE

A systematic review of participatory scenario planning to envision mountain social-ecological systems futures

Mountain social-ecological systems (MtSES) provide crucial ecosystem services to over half of humanity. However, populations living in these highly varied regions are now confronted by global change. It is critical that they are able to anticipate change to strategically manage resources and avoid potential conflict. Yet, planning for sustainable, equitable transitions for the future is a daunting task, considering the range of uncertainties and the unique character of MtSES. Participatory scenario planning (PSP) can help MtSES communities by critically reflecting on a wider array of innovative pathways for adaptive transformation. Although the design of effective approaches has been widely discussed, how PSP has been employed in MtSES has yet to be examined. Here, we present the first systematic global review of single- and multiscalar, multisectoral PSP undertaken in MtSES, in which we characterize the process, identify strengths and gaps, and suggest effective ways to apply PSP in MtSES. We used a nine-step process to help guide the analysis of 42 studies from 1989 screened articles. Our results indicate a steady increase in relevant studies since 2006, with 43% published between 2015 and 2017. These studies encompass 39 countries, with over 50% in Europe. PSP in MtSES is used predominantly to build cooperation, social learning, collaboration, and decision support, yet meeting these objectives is hindered by insufficient engagement with intended end users. MtSES PSP has focused largely on envisioning themes of governance, economy, land use change, and biodiversity, but has overlooked themes such as gender equality, public health, and sanitation. There are many avenues to expand and improve PSP in MtSES: to other regions, sectors, across a greater diversity of stakeholders, and with a specific focus on MtSES paradoxes. Communicating uncertainty, monitoring and evaluating impacts, and engendering more comparative approaches can further increase the utility of PSP for addressing MtSES challenges, with lessons for other complex social-ecological systems