The Region Specific Influence of Estradiol on In-Vivo Lipolysis in Subcutaneous Adipose Tissue in Overweight-to-Moderately-Obese Premenopausal Women

Premenopausal women demonstrate preferential accumulation of adiposity in the gynoid region, a distribution which shifts towards the abdominal region after the menopausal transition. Although estrogen is implicated as a major player in determining body fat distribution the mechanisms behind estrogenic action(s) in adipose tissue of women are still unclear. The global aim of this project was to determine if local estrogen influences regional adiposity in premenopausal women. Specifically, we investigated the influence of local estradiol on adipose tissue lipolysis as well as estrogen receptor content and adipocyte size in abdominal and gluteal subcutaneous adipose tissue of overweight-to-moderately-obese premenopausal women.    Eighteen overweight-to-moderately-obese Caucasian (CA, n=9) and African American (AA, n=9) women were recruited. Between 15 and 17 of these women took part in each of the three studies. We found the influence of estradiol on lipolysis to be adipose tissue depot specific and treatment dependent, with estradiol perfusion blunting the response to lipolytic stimulation under some conditions while potentiating this response in others. Furthermore, we found differences in abdominal and gluteal estrogen receptor alpha and estrogen receptor beta protein content, potentially revealing region specific actions of estrogen through these estrogen receptors in adipose tissue. Finally, we found racial differences in adipose tissue morphology, as indicated by variations in adipocyte diameter populations in CA and AA women (higher proportion of medium size adipocytes in abdominal and gluteal subcutaneous adipose tissue of CA and higher proportion of small adipocytes in gluteal region of AA) which could underlie the increased chronic disease risk in AA compared to CA women for a given body mass index (BMI).   Our findings indicate depot specific influence of estradiol on lipid mobilization may play a role in the predominant gluteal-femoral body fat distribution of premenopausal women. It is possible that depot specific effects of estradiol may be a result of regional differences in estrogen receptor content. Racial divergence in adipocyte morphology is an adipose tissue characteristic potentially underlying differing disease risk between CA and AA women of similar BMI. The integration of these results provides insight towards a more complete understanding of regional adiposity in overweight-to-obese premenopausal women, but future studies must be conducted to uncover the interaction between estrogen receptor content and local estrogen action as well as the direct physiological consequences of these findings.  Ph.D

Association of overweight and obesity with health status, weight management, and exercise behaviors among individuals with type 2 diabetes mellitus or with cardiometabolic risk factors

James R Gavin, III1, Helena W Rodbard2, Kathleen M Fox3, Susan Grandy4 for the SHIELD Study Group1Emory University School of Medicine, Atlanta, GA, USA; 2Endocrine and Metabolic Consultants, Rockville, MD, USA; 3Strategic Healthcare Solutions, LLC, Monkton, MD, USA; 4AstraZeneca LP, Wilmington, DE, USAObjectives: This investigation evaluated the role of obesity in health status and behaviors for weight management and exercise among individuals with type 2 diabetes mellitus (T2DM) or cardiometabolic risk factors.Methods: Self-reported health status, exercise behaviors, and weight management were assessed in the SHIELD study for respondents with T2DM or high risk (HR) for diabetes (ie, ≥3 of the following: abdominal obesity, body mass index [BMI] ≥28 kg/m2, self-reported diagnosis of dyslipidemia, hypertension, or history of cardiovascular disease). Respondents were stratified into three BMI categories: <25 kg/m2 (underweight or normal weight), 25.0−29.9 kg/m2 (overweight), and ≥30 kg/m2 (obese), with comparisons made using analysis of variance. Comparisons between T2DM and HR were made using chi-square tests.Results: T2DM (n = 3,918) and HR (n = 5,464) groups were similar for age (mean = 59 years), race (≥85% white), and obesity. Overweight (31%) or obese T2DM (18%) respondents were significantly less likely to report excellent health compared with overweight or obese HR respondents (42% and 30%, respectively), p < 0.001. There were no differences between T2DM and HR groups for exercise behaviors. More obese respondents (20% T2DM, 21% HR) were “contemplating exercising”, and fewer (21%−23%) were currently “exercising regularly” compared with overweight and normal weight respondents, p < 0.001. More obese respondents (78% T2DM, 83% HR) attempted weight management than normal (28%−35%) or overweight (57%−61%) respondents, p < 0.001.Conclusions: Obesity was negatively associated with self-perception of current health, exercising regularly, and weight maintenance for those with or at risk for diabetes.Keywords: overweight, obesity, type 2 diabetes mellitus, exercise, weight managemen

Perspectives on “Giving Back”: A Conversation Between Researcher and Refugee

Our chapter—“Perspectives on ‘giving back’: A conversation between researcher and refugee”—offers personal reflections on the ethics of research with refugees and what it means for researchers to “give back” to refugee participants beyond “policy impact”. Written as a dialogue between an academic and a Rohingya refugee youth leader, we explore the blurry lines between academic work and advocacy when the issues of refugee protection are pressing, as well as the appropriateness of researchers giving monetary donations and volunteering for refugee causes as payback for data. In this chapter, we also examine what it means to build trust and relationships between researchers and refugees, and how too often researchers fail to develop meaningful research interactions with refugee participants who share their time, energy and personal stories of vulnerability

Performance of verbal autopsy methods in estimating HIV-associated mortality among adults in South Africa

Aaron S. Karat - ORCID 0000-0001-9643-664X https://orcid.org/0000-0001-9643-664XIntroduction Verbal autopsy (VA) can be integrated into civil registration and vital statistics systems, but its accuracy in determining HIV-associated causes of death (CoD) is uncertain. We assessed the sensitivity and specificity of VA questions in determining HIV status and antiretroviral therapy (ART) initiation and compared HIV-associated mortality fractions assigned by different VA interpretation methods.Methods Using the WHO 2012 instrument with added ART questions, VA was conducted for deaths among adults with known HIV status (356 HIV positive and 103 HIV negative) in South Africa. CoD were assigned using physiciancertified VA (PCVA) and computer-coded VA (CCVA) methods and compared with documented HIV statusResults The sensitivity of VA questions in detecting HIV status and ART initiation was 84.3% (95% CI 80 to 88) and 91.0% (95% CI 86 to 95); 283/356 (79.5%) HIV-positive individuals were assigned HIV-associated CoD by PCVA, 166 (46.6%) by InterVA-4.03, 201 (56.5%) by InterVA-5, and 80 (22.5%) and 289 (81.2%) by SmartVA-Analyze V.1.1.1 and V.1.2.1. Agreement between PCVA and older CCVA methods was poor (chance-corrected concordance [CCC] <0; cause-specific mortality fraction [CSMF] accuracy ≤56%) but better between PCVA and updated methods (CCC 0.21–0.75; CSMF accuracy 65%–98%). All methods were specific (specificity 87% to 96%) in assigning HIV-associated CoD.Conclusion All CCVA interpretation methods underestimated the HIV-associated mortality fraction compared with PCVA; InterVA-5 and SmartVA-Analyze V.1.2.1 performed better than earlier versions. Changes to VA methods and classification systems are needed to track progress towards targets for reducing HIV-associated mortality,This study was funded by a grant from the Bill & Melinda Gates Foundation (OPP1083118).http://dx.doi.org/10.1136/bmjgh-2018-0008333pubpub

Reversible lysine fatty acylation of an anchoring protein mediates adipocyte adrenergic signaling.

N-myristoylation on glycine is an irreversible modification that has long been recognized to govern protein localization and function. In contrast, the biological roles of lysine myristoylation remain ill-defined. We demonstrate that the cytoplasmic scaffolding protein, gravin-α/A kinase–anchoring protein 12, is myristoylated on two lysine residues embedded in its carboxyl-terminal protein kinase A (PKA) binding domain. Histone deacetylase 11 (HDAC11) docks to an adjacent region of gravin-α and demyristoylates these sites. In brown and white adipocytes, lysine myristoylation of gravin-α is required for signaling via β(2)- and β(3)-adrenergic receptors (β-ARs), which are G protein–coupled receptors (GPCRs). Lysine myristoylation of gravin-α drives β-ARs to lipid raft membrane microdomains, which results in PKA activation and downstream signaling that culminates in protective thermogenic gene expression. These findings define reversible lysine myristoylation as a mechanism for controlling GPCR signaling and highlight the potential of inhibiting HDAC11 to manipulate adipocyte phenotypes for therapeutic purposes

Standardized Direct Observation Assessment Tool: Using a Training Video.

BACKGROUND: We developed a DVD training tool to educate physicians evaluating emergency residents on accurate Standardized Direct Observation Assessment Tool (SDOT) application. OBJECTIVE: Our goal was to assess whether this training video improved attendings\u27 and senior residents\u27 SDOT use. METHODS: Participants voluntarily completed SDOT evaluations based on a scripted test video. A DVD with positive and negative scenarios of proper SDOT use was viewed. It included education on appropriate recording of 26 behaviors. The test scenario was viewed again and follow-up SDOTs submitted. Performances by attendings and residents on the pre- and post-test SDOTs were compared. RESULTS: Twenty-six attendings and 26 senior residents participated. Prior SDOT experience was noted for 8 attendings and 11 residents. For 20 anchors, participants recorded observed behaviors with statistically significant difference on one each of the pretest (no. 20; p = 0.034) and post-test (no. 14; p = 0.041) SDOTs. On global competency assessments, pretest medical knowledge (p = 0.016) differed significantly between groups. The training intervention changed one anchor (no. 5; p = 0.035) and one global assessment (systems-based practice; p = 0.031) more negatively for residents. Recording SDOTs with exact agreement occurred 48.73% for attendings pretest and 54.41% post-test; resident scores were 45.86% and 49.55%, respectively. DVD exposure slightly raised attending scores (p = 0.289) and significantly lowered resident scores (p = 0.046). CONCLUSIONS: Exposure to an independently developed SDOT training video tended to raise attending scores, though without significance, while at the same time lowered senior resident scores statistically significantly. Emergency attendings\u27 and senior residents\u27 SDOT scoring rarely differed with significance; about half of anchor behaviors were recorded with exact agreement. This suggests senior residents, with appropriate education, may participate in SDOT assessment

Thank You to Our 2019 Peer Reviewers

On behalf of the journal, AGU, and the scientific community, the editors would like to sincerely thank those who reviewed the manuscripts for Geophysical Research Letters in 2019. The hours reading and commenting on manuscripts not only improve the manuscripts but also increase the scientific rigor of future research in the field. We particularly appreciate the timely reviews in light of the demands imposed by the rapid review process at Geophysical Research Letters. With the revival of the “major revisions” decisions, we appreciate the reviewers’ efforts on multiple versions of some manuscripts. With the advent of AGU’s data policy, many reviewers have helped immensely to evaluate the accessibility and availability of data associated with the papers they have reviewed, and many have provided insightful comments that helped to improve the data presentation and quality. We greatly appreciate the assistance of the reviewers in advancing open science, which is a key objective of AGU’s data policy. Many of those listed below went beyond and reviewed three or more manuscripts for our journal, and those are indicated in italics.Key PointThe editors thank the 2019 peer reviewersPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162718/2/grl60415.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162718/1/grl60415_am.pd