Glucocorticoid Receptor and Adipocyte Biology.

Glucocorticoids are steroid hormones that play a key role in metabolic adaptations during stress, such as fasting and starvation, in order to maintain plasma glucose levels. Excess and chronic glucocorticoid exposure, however, causes metabolic syndrome including insulin resistance, dyslipidemia, and hyperglycemia. Studies in animal models of metabolic disorders frequently demonstrate that suppressing glucocorticoid signaling improves insulin sensitivity and metabolic profiles. Glucocorticoids convey their signals through an intracellular glucocorticoid receptor (GR), which is a transcriptional regulator. The adipocyte is one cell type that contributes to whole body metabolic homeostasis under the influence of GR. Glucocorticoids' functions on adipose tissues are complex. Depending on various physiological or pathophysiological states as well as distinct fat depots, glucocorticoids can either increase or decrease lipid storage in adipose tissues. In rodents, glucocorticoids have been shown to reduce the thermogenic activity of brown adipocytes. However, in human acute glucocorticoid exposure, glucocorticoids act to promote thermogenesis. In this article, we will review the recent studies on the mechanisms underlying the complex metabolic functions of GR in adipocytes. These include studies of the metabolic outcomes of adipocyte specific GR knockout mice and identification of novel GR primary target genes that mediate glucocorticoid action in adipocytes

Current and emerging therapies for the treatment of pancreatic cancer

Pancreatic adenocarcinoma carries a dismal prognosis and remains a significant cause of cancer morbidity and mortality. Most patients survive less than 1 year; chemotherapeutic options prolong life minimally. The best chance for long-term survival is complete resection, which offers a 3-year survival of only 15%. Most patients who do undergo resection will go on to die of their disease. Research in chemotherapy for metastatic disease has made only modest progress and the standard of care remains the purine analog gemcitabine. For resectable pancreatic cancer, presumed micrometastases provide the rationale for adjuvant chemotherapy and chemoradiation (CRT) to supplement surgical management. Numerous randomized control trials, none definitive, of adjuvant chemotherapy and CRT have been conducted and are summarized in this review, along with recent developments in how unresectable disease can be subcategorized according to the potential for eventual curative resection. This review will also emphasize palliative care and discuss some avenues of research that show early promise

User expectations of partial driving automation capabilities and their effect on information design preferences in the vehicle

Partially automated vehicles present interface design challenges in ensuring the driver remains alert should the vehicle need to hand back control at short notice, but without exposing the driver to cognitive overload. To date, little is known about driver expectations of partial driving automation and whether this affects the information they require inside the vehicle. Twenty-five participants were presented with five partially automated driving events in a driving simulator. After each event, a semi-structured interview was conducted. The interview data was coded and analysed using grounded theory. From the results, two groupings of driver expectations were identified: High Information Preference (HIP) and Low Information Preference (LIP) drivers; between these two groups the information preferences differed. LIP drivers did not want detailed information about the vehicle presented to them, but the definition of partial automation means that this kind of information is required for safe use. Hence, the results suggest careful thought as to how information is presented to them is required in order for LIP drivers to safely using partial driving automation. Conversely, HIP drivers wanted detailed information about the system's status and driving and were found to be more willing to work with the partial automation and its current limitations. It was evident that the drivers' expectations of the partial automation capability differed, and this affected their information preferences. Hence this study suggests that HMI designers must account for these differing expectations and preferences to create a safe, usable system that works for everyone. [Abstract copyright: Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

Barriers and facilitators to HPV vaccination in primary care practices: A mixed methods study using the Consolidated Framework for Implementation Research

Abstract Background In the United States, the effective, safe huma papilloma virus (HPV) vaccine is underused and opportunities to prevent cancer continue to be missed. National guidelines recommend completing the 2–3 dose HPV vaccine series by age 13, well before exposure to the sexually transmitted virus. Accurate characterization of the facilitators and barriers to full implementation of HPV vaccine recommendations in the primary care setting could inform effective implementation strategies. Methods We used the Consolidated Framework for Implementation Research (CFIR) to systematically investigate and characterize factors that influence HPV vaccine use in 10 primary care practices (16 providers) using a concurrent mixed methods design. The CFIR was used to guide collection and analysis of qualitative data collected through in-person semi-structured interviews with the primary care providers. We analyzed HPV vaccine use with data abstracted from medical charts. Constructs that most strongly influenced vaccine use were identified by integrating the qualitative and quantitative data. Results Of the 72 CFIR constructs assessed, seven strongly distinguished and seven weakly distinguished between providers with higher versus lower HPV vaccine coverage. The majority of strongly distinguishing constructs were facilitators and were related to characteristics of the providers (knowledge and beliefs; self-efficacy; readiness for change), their perception of the intervention (relative advantage of vaccinating younger vs. older adolescents), and their process to deliver the vaccine (executing). Additional weakly distinguishing constructs that were facilitators were from outer setting (peer pressure; financial incentives), inner setting (networks and communications and readiness for implementation) and process (planning; engaging, and reflecting and evaluating). Two strongly distinguishing constructs were barriers to use, one from the intervention (adaptability of the age of initiation) and the other from outer setting (patient needs and resources). Conclusions Using CFIR to systematically examine the use of this vaccine in independent primary care practices enabled us to identify facilitators and barriers at the provider, interpersonal and practice level that need to be addressed in future efforts to increase vaccine use in such settings. Our findings suggest that implementation strategies that target the provider and help them to address multi-level barriers to HPV vaccine use merit further investigation

Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery.

BACKGROUND: Stroke is the major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression. Recently, small trials have demonstrated that SSRIs might improve recovery after stroke, even in people who are not depressed. Systematic reviews and meta-analyses are the least biased way to bring together data from several trials. Given the promising effect of SSRIs on stroke recovery seen in small trials, a systematic review and meta-analysis is needed. OBJECTIVES: To determine whether SSRIs improve recovery after stroke, and whether treatment with SSRIs was associated with adverse effects. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (August 2011), Cochrane Depression Anxiety and Neurosis Group Trials Register (November 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 8), MEDLINE (from 1948 to August 2011), EMBASE (from 1980 to August 2011), CINAHL (from 1982 to August 2011), AMED (Allied and Complementary Medicine) (from 1985 to August 2011), PsycINFO (from 1967 to August 2011) and PsycBITE (Pyschological Database for Brain Impairment Treatment Efficacy) (March 2012). To identify further published, unpublished and ongoing trials we searched trials registers, pharmaceutical websites, reference lists, contacted experts and performed citation tracking of included studies. SELECTION CRITERIA: We included randomised controlled trials that recruited stroke survivors (ischaemic or haemorrhagic) at any time within the first year. The intervention was any SSRI, given at any dose, for any period. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. In order to be included, trials had to collect data on at least one of our primary (dependence and disability) or secondary (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early) outcomes. DATA COLLECTION AND ANALYSIS: We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. For trials in English, two review authors independently extracted data. For Chinese papers, one review author extracted data. We used standardised mean differences (SMD) to estimate treatment effects for continuous variables, and risk ratios (RR) for dichotomous effects, with their 95% confidence intervals (CIs). MAIN RESULTS: We identified 56 completed trials of SSRI versus control, of which 52 trials (4059 participants) provided data for meta-analysis. There were statistically significant benefits of SSRI on both of the primary outcomes: RR for reducing dependency at the end of treatment was 0.81 (95% CI 0.68 to 0.97) based on one trial, and for disability score, the SMD was 0.91 (95% CI 0.60 to 1.22) (22 trials involving 1343 participants) with high heterogeneity between trials (I(2) = 87%; P < 0.0001). For neurological deficit, depression and anxiety, there were statistically significant benefits of SSRIs. For neurological deficit score, the SMD was -1.00 (95% CI -1.26 to -0.75) (29 trials involving 2011 participants) with high heterogeneity between trials (I(2) = 86%; P < 0.00001). For dichotomous depression scores, the RR was 0.43 (95% CI 0.24 to 0.77) (eight trials involving 771 participants) with high heterogeneity between trials (I(2) = 77%; P < 0.0001). For continuous depression scores, the SMD was -1.91 (95% CI -2.34 to -1.48) (39 trials involving 2728 participants) with high heterogeneity between trials (I(2) = 95%; P < 0.00001). For anxiety, the SMD was -0.77 (95% CI -1.52 to -0.02) (eight trials involving 413 participants) with high heterogeneity between trials (I(2) = 92%; P < 0.00001). There was no statistically significant benefit of SSRI on cognition, death, motor deficits and leaving the trial early. For cognition, the SMD was 0.32 (95% CI -0.23 to 0.86), (seven trials involving 425 participants) with high heterogeneity between trials (I(2) = 86%; P < 0.00001). The RR for death was 0.76 (95% CI 0.34 to 1.70) (46 trials involving 3344 participants) with no heterogeneity between trials (I(2) = 0%; P = 0.85). For motor deficits, the SMD was -0.33 (95% CI -1.22 to 0.56) (two trials involving 145 participants). The RR for leaving the trial early was 1.02 (95% CI 0.86 to 1.21) in favour of control, with no heterogeneity between trials. There was a non-significant excess of seizures (RR 2.67; 95% CI 0.61 to 11.63) (seven trials involving 444 participants), a non-significant excess of gastrointestinal side effects (RR 1.90; 95% CI 0.94 to 3.85) (14 trials involving 902 participants) and a non-significant excess of bleeding (RR 1.63; 95% CI 0.20 to 13.05) (two trials involving 249 participants) in those allocated SSRIs. Data were not available on quality of life, fatigue or healthcare costs.There was no clear evidence from subgroup analyses that one SSRI was consistently superior to another, or that time since stroke or depression at baseline had a major influence on effect sizes. Sensitivity analyses suggested that effect sizes were smaller when we excluded trials at high or unclear risk of bias.Only eight trials provided data on outcomes after treatment had been completed; the effect sizes were generally in favour of SSRIs but CIs were wide. AUTHORS' CONCLUSIONS: SSRIs appeared to improve dependence, disability, neurological impairment, anxiety and depression after stroke, but there was heterogeneity between trials and methodological limitations in a substantial proportion of the trials. Large, well-designed trials are now needed to determine whether SSRIs should be given routinely to patients with stroke

A rapid and inexpensive viability assay for zoospores and zoosporangia of Batrachochytrium dendrobatidis

The fungus Batrachochytrium dendrobatidis is causing global amphibian declines. Here we describe a simple, rapid and inexpensive methylene blue staining protocol to determine B. dendrobatidis viability, regardless of life-stage. The viability of cells in suspension or adherent monolayers can be determined using either manual microscopy counting or colorimetric assay

Sex on the brain! Associations between sexual activity and cognitive function in older age

Background: the relationship between cognition and sexual activity in healthy older adults is under-researched. A limited amount of research in this area has shown that sexual activity is associated with better cognition in older men. The current study explores the possible mediating factors in this association in men and women, and attempts to provide an explanation in terms of physiological influences on cognitive function. Methods: using newly available data from Wave 6 of the English Longitudinal Study of Ageing, the current study explored associations between sexual activity and cognition in adults aged 50–89 (n = 6,833). Two different tests of cognitive function were analysed: number sequencing, which broadly relates to executive function, and word recall, which broadly relates to memory. Results: after adjusting for age, education, wealth, physical activity, depression, cohabiting, self-rated health, loneliness and quality of life, there were significant associations between sexual activity and number sequencing and recall in men. However, in women there was a significant association between sexual activity and recall, but not number sequencing. Conclusions: possible mediators of these associations (e.g. neurotransmitters) are discussed. The cross-sectional nature of the analysis is limiting, but provides a promising avenue for future explorations and longitudinal studies. The findings have implications for the promotion of sexual counselling in healthcare settings, where maintaining a healthy sex life in older age could be instrumental in improving cognitive function and well-being