An Intact Kidney Slice Model to Investigate Vasa Recta Properties and Function in situ

Background: Medullary blood flow is via vasa recta capillaries, which possess contractile pericytes. In vitro studies using isolated descending vasa recta show that pericytes can constrict/dilate descending vasa recta when vasoactive substances are present. We describe a live kidney slice model in which pericyte-mediated vasa recta constriction/dilation can be visualized in situ. Methods: Confocal microscopy was used to image calcein, propidium iodide and Hoechst labelling in ‘live’ kidney slices, to determine tubular and vascular cell viability and morphology. DIC video-imaging of live kidney slices was employed to investigate pericyte-mediated real-time changes in vasa recta diameter. Results: Pericytes were identified on vasa recta and their morphology and density were characterized in the medulla. Pericyte-mediated changes in vasa recta diameter (10–30%) were evoked in response to bath application of vasoactive agents (norepinephrine, endothelin-1, angiotensin-II and prostaglandin E2) or by manipulating endogenous vasoactive signalling pathways (using tyramine, L-NAME, a cyclo-oxygenase (COX-1) inhibitor indomethacin, and ATP release). Conclusions: The live kidney slice model is a valid complementary technique for investigating vasa recta function in situ and the role of pericytes as regulators of vasa recta diameter. This technique may also be useful in exploring the role of tubulovascular crosstalk in regulation of medullary blood flow

Future-oriented constructs and their role in suicidal ideation and enactment

Despite the heavy focus upon risk factors for suicide, the presence or absence of protective factors are also instrumental in individuals’ vulnerability for developing suicidal ideation and behaviours. Future oriented constructs, including future thinking, future orientation, hope and optimism have been associated with suicidal ideation and behaviour; individuals who are less able to generate positive thoughts about the future, and those are less hopeful and optimistic are more likely to think about or engage in suicidal behaviours. The content and expectations of future thoughts as achievable also play a key role in their protective capacity. Within this chapter we discuss the relationships between future orientated constructs and suicidal ideation and behaviour, as well as potential mediators of these relationships, within the context of the new generation of ideation-to-action frameworks of suicidal behaviour. We also highlight challenges and opportunities for future research and intervention development for suicidal thoughts and behaviours using future oriented constructs

Impulsivity and self-harm in adolescence: a systematic review

Research supports an association between impulsivity and self-harm, yet inconsistencies in methodology across studies have complicated understanding of this relationship. This systematic review examines the association between impulsivity and self-harm in community-based adolescents aged 11-25 years and aims to integrate findings according to differing concepts and methods. Electronic searches of EMBASE, MEDLINE, PsychINFO, CINAHL, PubMed and The Cochrane Library, and manual searches of reference lists of relevant reviews, identified 4,496 articles published up to July 2015, of which 28 met inclusion criteria. Twenty-four of the studies reported an association between broadly specified impulsivity and self-harm. However, findings varied according to the conception and measurement of impulsivity and the precision with which self-harm behaviours were specified. Specifically, lifetime non-suicidal self-injury was most consistently associated with mood-based impulsivity related traits. However, cognitive facets of impulsivity (relating to difficulties maintaining focus or acting without forethought) differentiated current self-harm from past self-harm. These facets also distinguished those with thoughts of self-harm (ideation) from those who acted on thoughts (enaction). The findings suggested that mood-based impulsivity is related to the initiation of self-harm, while cognitive facets of impulsivity are associated with the maintenance of self-harm. In addition, behavioural impulsivity is most relevant to self-harm under conditions of negative affect. Collectively, the findings indicate that distinct impulsivity facets confer unique risks across the life-course of self-harm. From a clinical perspective, the review suggests that interventions focusing on reducing rash reactivity to emotions or improving self-regulation and decision-making may offer most benefit in supporting those who self-harm

Women gaze behaviour in assessing female bodies: the effects of clothing, body size, own body composition and body satisfaction

Often with minimally clothed figures depicting extreme body sizes, previous studies have shown women tend to gaze at evolutionary determinants of attractiveness when viewing female bodies, possibly for self-evaluation purposes, and their gaze distribution is modulated by own body dissatisfaction level. To explore to what extent women’s body-viewing gaze behaviour is affected by clothing type, dress size, subjective measurements of regional body satisfaction and objective measurements of own body composition (e.g., chest size, body mass index, waist-to-hip ratio), in this self-paced body attractiveness and body size judgement experiment, we compared healthy, young women’s gaze distributions when viewing female bodies in tight and loose clothing of different dress sizes. In contrast to tight clothing, loose clothing biased gaze away from the waist-hip to the leg region, and subsequently led to enhanced body attractiveness ratings and body size underestimation for larger female bodies, indicating the important role of clothing in mediating women’s body perception. When viewing preferred female bodies, women’s higher satisfaction of a specific body region was associated with an increased gaze towards neighbouring body areas, implying satisfaction might reduce the need for comparison of confident body parts; furthermore undesirable body composition measurements were correlated with a gaze avoidance process if the construct was less changeable (i.e. chest size) but a gaze comparison process if the region was more changeable (i.e. body mass index, dress size). Clearly, own body satisfaction and body composition measurements had an evident impact on women’s body-viewing gaze allocation, possibly through different cognitive processes

Prostacyclin reverses platelet stress fibre formation causing platelet aggregate instability

Prostacyclin (PGI2) modulates platelet activation to regulate haemostasis. Evidence has emerged to suggest that thrombi are dynamic structures with distinct areas of differing platelet activation. It was hypothesised that PGI2 could reverse platelet spreading by actin cytoskeletal modulation, leading to reduced capability of platelet aggregates to withstand a high shear environment. Our data demonstrates that post-flow of PGI2 over activated and spread platelets on fibrinogen, identified a significant reduction in platelet surface area under high shear. Exploration of the molecular mechanisms underpinning this effect revealed that PGI2 reversed stress fibre formation in adherent platelets, reduced platelet spreading, whilst simultaneously promoting actin nodule formation. The effects of PGI2 on stress fibres were mimicked by the adenylyl cyclase activator forskolin and prevented by inhibitors of protein kinase A (PKA). Stress fibre formation is a RhoA dependent process and we found that treatment of adherent platelets with PGI2 caused inhibitory phosphorylation of RhoA, reduced RhoA GTP-loading and reversal of myosin light chain phosphorylation. Phospho-RhoA was localised in actin nodules with PKA type II and a number of other phosphorylated PKA substrates. This study demonstrates that PGI2 can reverse key platelet functions after their initial activation and identifies a novel mechanism for controlling thrombosis

Optimisation of medications used in residential aged care facilities: a systematic review and meta-analysis of randomised controlled trials

Background: Frail older adults living in residential aged care facilities (RACFs) usually experience comorbidities and are frequently prescribed multiple medications. This increases the potential risk of inappropriate prescribing and its negative consequences. Thus, optimising prescribed medications in RACFs is a challenge for healthcare providers. Objective: Our aim was to systematically review interventions that increase the appropriateness of medications used in RACFs and the outcomes of these interventions. Methods: Systematic review and meta-analysis of randomised control trials (RCTs) and cluster randomised control trials (cRCTs) were performed by searching specified databases (MEDLINE, PubMed, Google scholar, PsycINFO) for publications from inception to May 2019 based on defined inclusion criteria. Data were extracted, study quality was assessed and statistically analysed using RevMan v5.3. Medication appropriateness, hospital admissions, mortality, falls, quality of life (QoL), Behavioural and Psychological Symptoms of Dementia (BPSD), adverse drug events (ADEs) and cognitive function could be meta-analysed. Results: A total of 25 RCTs and cRCTs comprising 19,576 participants met the inclusion criteria. The studies tested various interventions including medication review (n = 13), staff education (n = 9), multi-disciplinary case conferencing (n = 4) and computerised clinical decision support systems (n = 2). There was an effect of interventions on medication appropriateness (RR 0.71; 95% confidence interval (CI): 0.60,0.84) (10 studies), and on medication appropriateness scales (standardised mean difference = − 0.67; 95% CI: − 0.97, − 0.36) (2 studies). There were no apparent effects on hospital admission (RR 1.00; 95% CI: 0.93, 1.06), mortality (RR 0.98; 95% CI: 0.86, 1.11), falls (RR 1.06; 95% CI: 0.89,1.26), ADEs (RR 1.04; 95% CI: 0.96,1.13), QoL (standardised mean difference = 0.16; 95% CI:-0.13, 0.45), cognitive function (weighted mean difference = 0.69; 95% CI: − 1.25, 2.64) and BPSD (RR 0.68; 95% CI: 0.44,1.06) (2 studies). Conclusion: Modest improvements in medication appropriateness were observed in the studies included in this systematic review. However, the effect on clinical measures was limited to drive strong conclusions

Universal Alcohol/Drug Screening in Prenatal Care: A Strategy for Reducing Racial Disparities? Questioning the Assumptions

Agencies and organizations promoting universal screening for alcohol and drug use in prenatal care argue that universal screening will reduce White versus Black racial disparities in reporting to Child Protective Services (CPS) at delivery. Yet, no published research has assessed the impact of universal screening on reporting disparities or explored plausible mechanisms. This review defines two potential mechanisms: Equitable Surveillance and Effective Treatment and identifies assumptions underlying each mechanism. It reviews published literature relating to each assumption. Research relating to assumptions underlying each mechanism is primarily inconclusive or contradictory. Thus, available research does not support the claim that universal screening for alcohol and drug use in prenatal care reduces racial disparities in CPS reporting at delivery. Reducing these reporting disparities requires more than universal screening

Comparative analysis of bones, mites, soil chemistry, nematodes and soil micro-Eukaryotes from a suspected homicide to estimate the post-mortem interval

Criminal investigations of suspected murder cases require estimating the post-mortem interval (PMI, or time after death) which is challenging for longer periods. Here we present the case of human remains found in a Swiss forest. We have used a multidisciplinary approach involving the analysis of bones, soil chemical characteristics, mites and nematodes (by microscopy) and micro-Eukaryotes (by Illumina high throughput sequencing). We analysed soil samples collected beneath the remains of the head, upper and lower body and “control” samples taken a few meters away. The PMI estimated on hair 14C-data via bomb peak radiocarbon dating gave a time range of 1 to 2 years before the finding of the remains on site. Cluster analyses for chemical constituents, nematodes, mites and micro- Eukaryotes revealed two clusters 1) head and upper body and 2) lower body and controls. From mite evidence, we conclude that the body was likely to have been brought to the site after death. However, chemical analyses, nematode community analyses and the analyses of micro-Eukaryotes indicate that decomposition took place at least partly on site. This study illustrates the usefulness of combining several lines of evidence for the study of homicide cases to better calibrate PMI inference tools