Acute hypercortisolemia exerts depot-specific effects on abdominal and femoral adipose tissue function

Context Glucocorticoids have pleiotropic metabolic functions and acute glucocorticoid excess affects fatty acid metabolism, increasing systemic lipolysis. Whether glucocorticoids exert adipose tissue depot-specific effects remains unclear. Objective In vivo assessment of femoral and abdominal adipose tissue responses to acute glucocorticoid administration. Design and outcome measures Nine healthy male volunteers studied on two occasions, following a hydrocortisone infusion (0.2 mg.kg-1.min-1 for 14 hours) and saline, respectively, given in randomized double-blind order. Subjects were studied in the fasting state and following a 75g glucose drink with in vivo assessment of femoral adipose tissue blood flow (ATBF) using radioactive Xenon washout, and lipolysis and glucose uptake using the arterio-venous difference technique. In a separate study (same infusion design), 8 further healthy male subjects underwent assessment of fasting abdominal ATBF and lipolysis only. Lipolysis was assessed as the net release of non-esterified fatty acids (NEFA) from femoral and abdominal subcutaneous adipose tissue. Results Acute hypercortisolemia significantly increased basal and postprandial ATBF in femoral adipose tissue, but femoral net NEFA release did not change. In abdominal adipose tissue, hypercortisolemia induced significant increases in basal ATBF and NEFA release. Conclusions Acute hypercortisolemia induces differential lipolysis and ATBF responses in abdominal and femoral adipose tissue, suggesting depot-specific glucocorticoid effects. Abdominal, but not femoral, adipose tissue contributes to the hypercortisolemia-induced systemic NEFA increase, with likely contributions from other adipose tissue sources and intravascular triglyceride hydrolysis

Value bias of verbal memory

© 2019 Elsevier Inc. A common finding is that items associated with higher reward value are subsequently remembered better than items associated with lower value. A confounding factor is that when a higher value stimuli is presented, this typically signals to participants that it is now a particularly important time to engage in the task. When this was controlled, Madan, Fujiwara, Gerson, and Caplan (2012) still found a large value-bias of memory. Their value-learning procedure, however, explicitly pitted high- against low-value words. Our novel value-learning procedure trained words one at a time, avoiding direct competition between words, but with no difference in words signalling participants to engage in the task. Results converged on null effects of value on subsequent free recall accuracy. Re-analyses attributed Madan et al.’s value-bias to competition between choice items that were paired during learning. Value may not bias memory if it does not signal task importance or induce inter-item competition

AKR1D1 knockout mice have impaired intestinal health with evidence of gut dybiosis and increased gut permeability and have increased incidence of colon cancer in females

AKR1D1 knockout mice have impaired intestinal health with evidence of gut dybiosis and increased gut permeability and have increased incidence of colon cancer in female

Differential adipose tissue gene expression profiles in abacavir treated patients that may contribute to the understanding of cardiovascular risk: a microarray study

OBJECTIVE:To compare changes in gene expression by microarray from subcutaneous adipose tissue from HIV treatment naïve patients treated with efavirenz based regimens containing abacavir (ABC), tenofovir (TDF) or zidovidine (AZT). DESIGN:Subcutaneous fat biopsies were obtained before, at 6- and 18-24-months after treatment, and from HIV negative controls. Groups were age, ethnicity, weight, biochemical profile, and pre-treatment CD4 count matched. Microarray data was generated using the Agilent Whole Human Genome Microarray. Identification of differentially expressed genes and genomic response pathways was performed using limma and gene set enrichment analysis. RESULTS:There were significant divergences between ABC and the other two groups 6 months after treatment in genes controlling cell adhesion and environmental information processing, with some convergence at 18-24 months. Compared to controls the ABC group, but not AZT or TDF showed enrichment of genes controlling adherence junction, at 6 months and 18-24 months (adjusted p<0.05) and focal adhesions and tight junction at 6 months (p<0.5). Genes controlling leukocyte transendothelial migration (p<0.05) and ECM-receptor interactions (p = 0.04) were over-expressed in ABC compared to TDF and AZT at 6 months but not at 18-24 months. Enrichment of pathways and individual genes controlling cell adhesion and environmental information processing were specifically dysregulated in the ABC group in comparison with other treatments. There was little difference between AZT and TDF. CONCLUSION:After initiating treatment, there is divergence in the expression of genes controlling cell adhesion and environmental information processing between ABC and both TDF and AZT in subcutaneous adipose tissue. If similar changes are also taking place in other tissues including the coronary vasculature they may contribute to the increased risk of cardiovascular events reported in patients recently started on abacavir-containing regimens

What are the risks and benefits of temporarily discontinuing medications to prevent acute kidney injury? A systematic review and meta-analysis.

OBJECTIVES: To summarise evidence on temporary discontinuation of medications to prevent acute kidney injury (AKI). DESIGN: Systematic review and meta-analysis of randomised and non-randomised studies. PARTICIPANTS: Adults taking diuretics, ACE inhibitors (ACEI), angiotensin receptor blockers (ARB), direct renin inhibitors, non-steroidal anti-inflammatories, metformin or sulfonylureas, experiencing intercurrent illnesses, radiological or surgical procedures. INTERVENTIONS: Temporary discontinuation of any of the medications of interest. PRIMARY AND SECONDARY OUTCOME MEASURES: Risk of AKI. Secondary outcome measures were estimated glomerular filtration rate and creatinine post-AKI, urea, systolic and diastolic blood pressure, death, clinical outcomes and biomarkers. RESULTS: 6 studies were included (1663 participants), 3 randomised controlled trials (RCTs) and 3 prospective cohort studies. The mean age ranged from 65 to 73 years, and the proportion of women ranged from 31% to 52%. All studies were in hospital settings; 5 evaluated discontinuation of medication prior to coronary angiography and 1 prior to cardiac surgery. 5 studies evaluated discontinuation of ACEI and ARBs and 1 small cohort study looked at discontinuation of non-steroidal anti-inflammatory drugs. No studies evaluated discontinuation of medication in the community following an acute intercurrent illness. There was an increased risk of AKI of around 15% in those in whom medication was continued compared with those in whom it was discontinued (relative risk (RR) 1.17, 95% CI 0.99 to 1.38; 5 studies). When only results from RCTs were pooled, the increase in risk was almost 50% (RR 1.48, 95% CI 0.84 to 2.60; 3 RCTs), but the CI was wider. There was no difference between groups for any secondary outcomes. CONCLUSIONS: There is low-quality evidence that withdrawal of ACEI/ARBs prior to coronary angiography and cardiac surgery may reduce the incidence of AKI. There is no evidence of the impact of drug cessation interventions on AKI incidence during intercurrent illness in primary or secondary care. TRIAL REGISTRATION NUMBER: PROSPERO CRD42015023210

Physiological Factors of Female Runners With and Without Stress Fracture Histories: A Pilot Study.

BACKGROUND: Female runners are at increased risk of stress fractures (SFs) compared with men. Literature is lacking with regard to best practice for preventing and treating SFs in women. The purpose of the study was to compare physiological measures and running-related factors between women of various ages and running abilities with and without a history of running-related SFs. HYPOTHESIS: Women with and without SF histories will differ with regard to medical and menstrual history, bone health, body composition, nutrition, and running history. STUDY DESIGN: Prospective cohort study. LEVEL OF EVIDENCE: Level 2. METHODS: A total of 20 female runners with SF histories were matched based on age and running distance with 20 women without SF histories. Data included medical, menstrual, running, injury, and nutritional histories; blood histology related to nutritional, hormonal, and bone-related risk factors; and bone density, fat, and lean tissue using dual energy x-ray absorptiometry. Paired RESULTS: Women with SF histories had lower hip bone mineral density compared with women without SF histories ( CONCLUSION: Female runners with low hip bone mineral density, menstrual changes during peak training, and elevated bone turnover markers may be at increased risk of SF. CLINICAL RELEVANCE: Female runners need routine screening for risks associated with SF occurrence. As bone mineral density and bone turnover markers are not routinely assessed in this population, important risk factors may be missed

Adopting a Citizen Science Approach in Translational Experimental Medicine Research in Non-Alcoholic Fatty Liver Disease: A Study Protocol

Citizen science approaches are widely and successfully used in biological, environmental, and ecological sciences; however, they are rarely applied in other domains, such as translational health research, notably in the field of liver disease and metabolism. We have designed a study that aims to explore the application of the citizen science approach in a translational experimental medicine study on non-alcoholic fatty liver disease (NAFLD) and a 12-week lifestyle and weight loss program. In this methodological paper, we describe the process of involving citizen scientists in the study. We will recruit a convenience sample of 31 participants (with and without NAFLD) and a half-dozen citizen scientists (members of the public). Citizen scientists will work alongside clinical and non-clinical researchers in a translational experimental medicine study on NAFLD. Citizen scientists will be involved in the co-design and/or review of data collection tools (e.g., semi-structured open-ended questionnaire surveys and semi-structured wellbeing diaries completed by the participants), co-analysis of data on participants’ experiences and motivations, co-drafts of research findings and papers, and suggestions for policy recommendations. Citizen scientists will be trained in the research tasks they will undertake, and will be either co-authors or their names will be mentioned in the acknowledgements in research paper(s) based on the level of research contributions. Lessons learned from implementing citizen science in this study will help to reveal the advantages, limitations, and implications of involving citizen scientists in the translational medicine research. Knowing citizen scientists’ motivations, expectations, training needs, and overall experience of involvement in this study could provide insights, which could inform the planning and conduct of future translational research studies. Involving citizen scientists in translational medicine research is an important step in extending research opportunities for members of the public; however, there may be methodological challenges, which may be identified and resolved by more research studies