Trichostatin A Blocks Aldosterone-Induced Na+ Transport And Control Of Serum- And Glucocorticoid-Inducible Kinase 1 In Cortical Collecting Duct Cells

Background and Purpose: Aldosterone stimulates epithelial Na+ channel (ENaC)-dependent Na+ retention in the cortical collecting duct (CCD) of the kidney by activating mineralocorticoid receptors that promote expression of serum and glucocorticoid-inducible kinase 1 (SGK1). This response is critical to BP homeostasis. It has previously been suggested that inhibiting lysine deacetylases (KDACs) can post-transcriptionally disrupt this response by promoting acetylation of the mineralocorticoid receptor. The present study critically evaluates this hypothesis. Experimental Approach: Electrometric and molecular methods were used to define the effects of a pan-KDAC inhibitor, trichostatin A, on the responses to a physiologically relevant concentration of aldosterone (3 nM) in murine mCCDcl1 cells. Key Results: Aldosterone augmented ENaC-induced Na+ absorption and increased SGK1 activity and abundance, as expected. In the presence of trichostatin A, these responses were suppressed. Trichostatin A-induced inhibition of KDAC was confirmed by increased acetylation of histone H3, H4, and α-tubulin. Trichostatin A did not block the electrometric response to insulin, a hormone that activates SGK1 independently of increased transcription, indicating that trichostatin A has no direct effect upon the SGK1/ENaC pathway. Conclusions and Implications: Inhibition of lysine de-acetylation suppresses aldosterone-dependent control over the SGK1–ENaC pathway but does not perturb post-transcriptional signalling, providing a physiological basis for the anti-hypertensive action of KDAC inhibition seen in vivo

Non-consumptive effects of native and invasive predators on juvenile Caribbean parrotfish

Non-consumptive effects of predators can have important impacts on aquatic food webs, but there are few data on how predators change the behaviour of Caribbean reef fishes. Such changes may include behavioural responses to the invasive predatory lionfish (Pterois volitans/P. miles). This study used an aquarium experiment to examine the behaviour of herbivorous parrotfish (Scarus iseri) in the absence of other fish (control), with a non-piscivore present, and with a predatory threat from a native grouper or lionfish. Treatments were repeated with and without additional parrotfish shelters to examine the potential effects of degraded reefs (loss of refuges). Using video, parrotfish behaviours (sheltering, swimming in open areas, foraging, aggressive conspecific interactions, bite rates, and shoaling behaviour) were recorded for groups of four parrotfish. Compared to the control, the average number of parrotfish hiding was reduced by 65 % and foraging shoals were 10 % larger when threatened by grouper, likely as a specific response to an ambush predator. When exposed to lionfish, parrotfish reduced their bite rates by 50 %, possibly to be more vigilant of this predator’s unique stalking behaviour. The absence of additional shelter had limited effects although parrotfish formed 10 % larger shoals when swimming in open water, potentially as a defensive behaviour because of a perceived lack of refuges. The reduction in parrotfish bite rates caused by lionfish may have important demographic consequences. Furthermore, parrotfishes are important grazers of macroalgae, and these behavioural changes may exacerbate the direct effects of lionfish predation and potentially affect reef benthic dynamics

A data-driven classification of outcome behaviors in those who cause concern to British public figures

Fixated individuals pose a significant threat to public figures. Previous research compares individuals labeled ‘approachers’ to those labeled ‘communicators.’ Typically, such studies compare a number of risk factors among the two groups to identify significant differences. This has impactful implications for the threat assessment and management of the pathologically fixated. The present study builds upon this established body of work by considering if more nuance can be disaggregated from a universe of cases referred to the Fixated Threat Assessment Center (FTAC). FTAC is a joint police and mental health unit in the U.K. which applies a public health approach to managing the pathologically fixated. The present study takes a deductive approach to detect profiles of cases from the data. First, we use cluster analysis to detect unmeasured subgroups of concerning behavior in the case files of 2,118 referrals to FTAC. We identify 5 patterns of concerning behavior: incoherent offline communicators, incoherent online communicators, angry/abusive communicators, concerning approachers, and problematic approachers. Second, we examine the rate of diagnosed mental disorder, the nature of concerns evoked, and case management actions taken among each of the five profiles identified. We conclude by highlighting how our results could inform triaging large volumes of cases, the allocation of limited resources, and more generally, how the success of the FTAC model has relevance across the management of grievance-fueled violence in general. (PsycInfo Database Record (c) 2021 APA, all rights reserved

Predictors of varying levels of risks posed by fixated individuals to British public figures

Concerning approaches and communications to the Royal Family and other British public figures are relatively numerous. This paper examines over 2000 such cases logged over a three-year period in the United Kingdom. Using police and health data, the paper conducts a series of bivariate and multivariate analyses to demonstrate the predictors of what types of risk are posed by an individual case (e.g., communicate only, approach, security breach). The results showed that (a) the rates of serious mental disorders are higher among this sample than the general population base rate, (b) approachers were significantly more likely than communicators to suffer from serious mental disorders, (c) approachers were significantly more likely than communicators to have a history of substance use and abuse problems, (d) approachers were significantly more likely than communicators to have a history of violent behavior against property and persons, and (e) the motivations of approachers and communicators significantly differ. The paper concludes with a consideration of the implications for threat assessment and management

Lower cardiorespiratory fitness contributes to increased insulin resistance and fasting glycaemia in middle-aged South Asian compared with European men living in the UK

AIMS/HYPOTHESIS: This study aimed to determine the extent to which increased insulin resistance and fasting glycaemia in South Asian men, compared with white European men, living in the UK, was due to lower cardiorespiratory fitness (maximal oxygen uptake [[Formula: see text]]) and physical activity. METHODS: One hundred South Asian and 100 age- and BMI-matched European men without diagnosed diabetes, aged 40–70 years, had fasted blood taken for measurement of glucose concentration, HOMA-estimated insulin resistance (HOMA(IR)), plus other risk factors, and underwent assessment of physical activity (using accelerometry), [Formula: see text], body size and composition, and demographic and other lifestyle factors. For 13 South Asian and one European man, HbA(1c) levels were >6.5% (>48 mmol/mol), indicating potential undiagnosed diabetes; these men were excluded from the analyses. Linear regression models were used to determine the extent to which body size and composition, fitness and physical activity variables explained differences in HOMA(IR) and fasting glucose between South Asian and European men. RESULTS: HOMA(IR) and fasting glucose were 67% (p < 0.001) and 3% (p < 0.018) higher, respectively, in South Asians than Europeans. Lower [Formula: see text], lower physical activity and greater total adiposity in South Asians individually explained 68% (95% CI 45%, 91%), 29% (11%, 46%) and 52% (30%, 80%), respectively, and together explained 83% (50%, 119%) (all p < 0.001) of the ethnic difference in HOMA(IR). Lower [Formula: see text] and greater total adiposity, respectively, explained 61% (9%, 111%) and 39% (9%, 76%) (combined effect 63% [8%, 115%]; all p < 0.05) of the ethnic difference in fasting glucose. CONCLUSIONS/INTERPRETATION: Lower cardiorespiratory fitness is a key factor associated with the excess insulin resistance and fasting glycaemia in middle-aged South Asian, compared with European, men living in the UK. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-013-2969-y) contains peer-reviewed but unedited supplementary material, which is available to authorised users

Assessment of abdominal fat compartments using DXA in premenopausal women from anorexia nervosa to morbid obesity

Objective: The purpose of this study was to test a newly developed DXA method for abdominal fat depot quantification in subjects with AN, normal weight, and obesity using CT as a gold standard. Design and Methods 135 premenopausal women (overweight/obese: n=89, normal-weight: n=27, AN: n=19); abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT) areas determined on CT and DXA. Results: There were strong correlations between DXA and CT measurements of abdominal fat compartments in all groups with the strongest correlation coefficients in the normal-weight and overweight/obese groups. Correlations of DXA and CT VAT measurements were strongest in the obese group and weakest in the AN group. DXA abdominal fat depots were higher in all groups compared to CT, with the largest % mean difference in the AN group and smallest in the obese group. Conclusions: A new DXA technique is able to assess abdominal fat compartments including VAT in premenopausal women across a large weight spectrum However, DXA measurements of abdominal fat were higher than CT, and this percent bias was most pronounced in the AN subjects and decreased with increasing weight, suggesting that this technique may be more useful in obese individuals

Neoliberalisation and 'lad cultures' in higher education

This paper links HE neoliberalisation and ‘lad cultures’, drawing on interviews and focus groups with women students. We argue that retro-sexist ‘laddish’ forms of masculine competitiveness and misogyny have been reshaped by neoliberal rationalities to become modes of consumerist sexualised audit. We also suggest that neoliberal frameworks scaffold an individualistic and adversarial culture among young people that interacts with perceived threats to men’s privilege and intensifies attempts to put women in their place through misogyny and sexual harassment. Furthermore, ‘lad cultures’, sexism and sexual harassment in higher education may be invisibilised by institutions to preserve marketability in a neoliberal context. In response, we ask if we might foster dialogue and partnership between feminist and anti-marketisation politics

What happens when 55% of acute psychiatric beds are closed in six days: an unexpected naturalistic observational study.

OBJECTIVE: The sudden closure of 30 out of 54 acute psychiatric beds in Cornwall presented a stressful challenge to staff but also a natural experiment on how a service dealt with this situation. We aimed to evaluate the outcomes of patients needing to leave the closed ward, how bed occupancy rates were affected and the impact on admission rates. DESIGN: A service evaluation of the impact of the ward closure. SETTING: A comprehensive secondary NHS mental health service in Cornwall serving 550,000 population. MAIN OUTCOME MEASURES: The destination of the patients needing to leave the acute unit, the effect of the closure on bed occupancy, admission rates and serious untoward incidents. RESULTS: Of 26 patients needing to be moved from the acute ward, only 10 needed an acute psychiatric bed. None of the seven patients who had been on the ward longer than nine weeks needed an acute unit. Admission rates fell over the subsequent three months. There was no increase in serious incidents due to the closure. CONCLUSIONS: This naturalistic event suggests that many patients on acute units could be cared for elsewhere, especially recovery/rehabilitation care environments, if political and financial urgency is present. Admission rates are responsive to the pressure on beds

Decision making and risk management in adventure sports coaching

Adventure sport coaches practice in environments that are dynamic and high in risk, both perceived and actual. The inherent risks associated with these activities, individuals’ responses and the optimal exploitation of both combine to make the processes of risk management more complex and hazardous than the traditional sports where risk management is focused almost exclusively on minimization. Pivotal to this process is the adventure sports coaches’ ability to make effective judgments regarding levels of risk, potential benefits and possible consequences. The exact nature of this decision making process should form the basis of coaching practice and coach education in this complex and dynamic field. This positional paper examines decision making by the adventure sports coach in these complex, challenging environments and seeks to stimulate debate whilst offering a basis for future research into this topic