In utero androgen administration induces changes in gene expression and purkinje cell development in the cerebellum

Steroids play a major role in the development of the CNS with those brain areas involved in sexual behaviour having been the focus of most neuroendocrine studies to date e.g. the hypothalamus and pituitary gland (Feist and Schreck, 1996; Mong, et al., 1999; Toran-Allerand, et al., 1980). This occurs via intracellular and cell-surface receptors that regulate changes in protein synthesis (Mensah-Nyagan, et al., 1999) to modify events related to neuronal survival and synapse formation (Breedlove, 1992). Many steroidogenesis-associated enzymes have been described in the cerebellum and cortex, but the impact of steroids on their development has yet to be investigated. A steroidal fetal programming model was utilised to investigate how gene expression in these two brain regions is affected by steroid exposure during development, and examine how this may lead to a change in brain architecture and function. The main aims of this study were to identify changes in the cerebellar expression of genetic markers of steroid metabolism, using quantitative real-time polymerase chain reaction (qRT-PCR), that result from exposure to testosterone propionate (TP) during development in male sheep. The cerebellum follows a clear developmental trajectory and contains an established cytoarchitecture that enabled us to readily identify the effects of TP treatment on the developing brain by utilising histological analyses. Further alterations of gene expression in the developing male ovine cortex were also identified using microarray analysis. The results provide novel findings in regards to androgen-sensitive gene expression in the developing ovine cerebellum and cortex but perhaps the most striking result was that androgen over-exposure delays cerebellar development, which may have consequences in later life on motor and/or cognitive function

Achievement and integration factors related to the academic success and intent to persist of college freshmen and sophomores with learning disabilities

The number of students with learning disabilities (LD) attending college has increased over the past several decades, yet outcomes including graduation rates continue to lag behind those of non-disabled students. In addition to students' background characteristics and past academic achievement, Tinto's (1975; 1993) constructs of academic and social integration have been the focus of much of the research identifying factors associated with college student success and persistence. Previous research has validated the impact of academic and social integration on college student persistence and success; however, these factors have not been studied with a sample of students who have disabilities. In this investigation hierarchical multiple regression analysis was used to study the relative influence of pre-college achievement and college integration variables on the academic success and intent to persist of college freshmen and sophomores with LD, while controlling for background characteristics. Participants were 97 freshmen and sophomores with LD at a large, public university in the southwestern United States. Students completed a demographic questionnaire as well as portions of the Freshmen Year Survey (Milem & Berger, 1997) to measure integration and intent to persist. High school GPA, SAT scores, and college GPA were obtained from university records. Academic, social and total integration were not unique significant predictors of college GPA beyond background characteristics and past academic achievement. However, total integration was a significant predictor of intent to persist, accounting for 17 percent unique variance. Academic integration was a significant predictor of intent to persist accounting for 12 percent unique variance. Further, social integration was a significant predictor of intent to persist, accounting for 18 percent unique variance beyond background characteristics and past academic achievement and 7 percent unique variance in the model that also included academic integration. These findings suggest academic and social integration are promising constructs to explain the persistence of college students with LD. Implications of this study include the need for continued research on the role of academic and social integration for college students with LD, as well as on the practices of high school and college personnel in preparing students with LD for college

After-hours respiratory physiotherapy for intubated and mechanically ventilated patients with community-acquired pneumonia: An Australian perspective

Introduction: Community acquired pneumonia (CAP) is a common reason for admission to an intensive care unit for intubation and mechanical ventilation, and results in high morbidity and mortality. The primary aim of the study was to investigate availability and provision of respiratory physiotherapy, outside of normal business hours, for intubated and mechanically ventilated adults with CAP in Australian hospitals. Materials and methods: A cross-sectional, mixed methods online survey was conducted. Participants were senior intensive care unit physiotherapists from 88 public and private hospitals. Main outcome measures included presence and nature of an after-hours physiotherapy service and factors perceived to influence the need for after-hours respiratory physiotherapy intervention, when the service was available, for intubated adult patients with CAP. Data were also collected regarding respiratory intervention provided after-hours by other ICU professionals. Results: Response rate was 72% (n = 75). An after-hours physiotherapy service was provided by n = 31 (46%) hospitals and onsite after-hours physiotherapy presence was limited (22%), with a combination of onsite and on-call service reported by 19%. Treatment response (83%) was the most frequent factor for referring patients with CAP for after-hours physiotherapy intervention by the treating day-time physiotherapist. Nurses performing respiratory intervention (77%) was significantly associated with no available after-hours physiotherapy service (p = 0.04). Discussion: Physiotherapy after-hours service in Australia is limited, therefore it is common for intubated patients with CAP not to receive any respiratory physiotherapy intervention outside of normal business hours. In the absence of an after-hours physiotherapist, nurses were most likely to perform after-hours respiratory intervention to intubated patients with CAP. Conclusion: Further research is required to determine whether the frequency of respiratory physiotherapy intervention, including after-hours provision of treatment, influences outcomes for ICU patients intubated with pneumonia

Toward utilization of data for program management and evaluation: quality assessment of five years of health management information system data in Rwanda

Background: Health data can be useful for effective service delivery, decision making, and evaluating existing programs in order to maintain high quality of healthcare. Studies have shown variability in data quality from national health management information systems (HMISs) in sub-Saharan Africa which threatens utility of these data as a tool to improve health systems. The purpose of this study is to assess the quality of Rwanda's HMIS data over a 5-year period. Methods: The World Health Organization (WHO) data quality report card framework was used to assess the quality of HMIS data captured from 2008 to 2012 and is a census of all 495 publicly funded health facilities in Rwanda. Factors assessed included completeness and internal consistency of 10 indicators selected based on WHO recommendations and priority areas for the Rwanda national health sector. Completeness was measured as percentage of non-missing reports. Consistency was measured as the absence of extreme outliers, internal consistency between related indicators, and consistency of indicators over time. These assessments were done at the district and national level. Results: Nationally, the average monthly district reporting completeness rate was 98% across 10 key indicators from 2008 to 2012. Completeness of indicator data increased over time: 2008, 88%; 2009, 91%; 2010, 89%; 2011, 90%; and 2012, 95% (p<0.0001). Comparing 2011 and 2012 health events to the mean of the three preceding years, service output increased from 3% (2011) to 9% (2012). Eighty-three percent of districts reported ratios between related indicators (ANC/DTP1, DTP1/DTP3) consistent with HMIS national ratios. Conclusion and policy implications Our findings suggest that HMIS data quality in Rwanda has been improving over time. We recommend maintaining these assessments to identify remaining gaps in data quality and that results are shared publicly to support increased use of HMIS data

Codesigning a systemic discharge intervention for inpatient mental health settings (MINDS): a protocol for integrating realist evaluation and an engineering-based systems approach

© 2023 The Author(s). Published by BMJ. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Introduction: Transition following discharge from mental health hospital is high risk in terms of relapse, readmission and suicide. Discharge planning supports transition and reduces risk. It is a complex activity involving interacting systemic elements. The codesigning a systemic discharge intervention for inpatient mental health settings (MINDS) study aims to improve the process for people being discharged, their carers/supporters and staff who work in mental health services, by understanding, co-designing and evaluating implementation of a systemic approach to discharge planning. Methods and analysis: The MINDS study integrates realist research and an engineering-informed systems approach across three stages. Stage 1 applies realist review and evaluation using a systems approach to develop programme theories of discharge planning. Stage 2 uses an Engineering Better Care framework to codesign a novel systemic discharge intervention, which will be subjected to process and economic evaluation in stage 3. The programme theories and resulting care planning approach will be refined throughout the study ready for a future clinical trial. MINDS is co-led by an expert by experience, with researchers with lived experience co-leading each stage. Ethics and dissemination: MINDS stage 1 has received ethical approval from Yorkshire & The Humber—Bradford Leeds (Research Ethics Committee (22/YH/0122). Findings from MINDS will be disseminated via high-impact journal publications and conference presentations, including those with service user and mental health professional audiences. We will establish routes to engage with public and service user communities and National Health Service professionals including blogs, podcasts and short videos. Trial registration number: MINDS is funded by the National Institute of Health Research (NIHR 133013) https://fundingawards.nihr.ac.uk/award/NIHR133013. The realist review protocol is registered on PROSPERO. PROSPERO registration number: CRD42021293255.Peer reviewe

The Pancreas Is Altered by In Utero Androgen Exposure: Implications for Clinical Conditions Such as Polycystic Ovary Syndrome (PCOS)

Using an ovine model of polycystic ovary syndrome (PCOS), (pregnant ewes injected with testosterone propionate (TP) (100 mg twice weekly) from day (d)62 to d102 of d147 gestation (maternal injection – MI-TP)), we previously reported female offspring with normal glucose tolerance but hyperinsulinemia. We therefore examined insulin signalling and pancreatic morphology in these offspring using quantitative (Q) RT-PCR and western blotting. In addition the fetal pancreatic responses to MI-TP, and androgenic and estrogenic contributions to such responses (direct fetal injection (FI) of TP (20 mg) or diethylstilbestrol (DES) (20 mg) at d62 and d82 gestation) were assessed at d90 gestation. Fetal plasma was assayed for insulin, testosterone and estradiol, pancreatic tissue was cultured, and expression of key β-cell developmental genes was assessed by QRT-PCR. In female d62MI-TP offspring insulin signalling was unaltered but there was a pancreatic phenotype with increased numbers of β-cells (

A smartphone-based test for the assessment of attention deficits in delirium: A case-control diagnostic test accuracy study in older hospitalised patients.

BACKGROUND: Delirium is a common and serious acute neuropsychiatric syndrome which is often missed in routine clinical care. Inattention is the core cognitive feature. Diagnostic test accuracy (including cut-points) of a smartphone Delirium App (DelApp) for assessing attention deficits was assessed in older hospital inpatients. METHODS: This was a case-control study of hospitalised patients aged ≥65 years with delirium (with or without pre-existing cognitive impairment), who were compared to patients with dementia without delirium, and patients without cognitive impairment. Reference standard delirium assessment, which included a neuropsychological test battery, was based on Diagnostic and Statistical Manual of Mental Disorders-5 criteria. A separate blinded assessor administered the DelApp arousal assessment (score 0-4) and attention task (0-6) yielding an overall score of 0 to 10 (lower scores indicate poorer performance). Analyses included receiver operating characteristic curves and sensitivity and specificity. Optimal cut-points for delirium detection were determined using Youden's index. RESULTS: A total of 187 patients were recruited, mean age 83.8 (range 67-98) years, 152 (81%) women; n = 61 with delirium; n = 61 with dementia without delirium; and n = 65 without cognitive impairment. Patients with delirium performed poorly on the DelApp (median score = 4/10; inter-quartile range 3.0, 5.5) compared to patients with dementia (9.0; 5.5, 10.0) and those without cognitive impairment (10.0; 10.0, 10.0). Area under the curve for detecting delirium was 0.89 (95% Confidence Interval 0.84, 0.94). At an optimal cut-point of ≤8, sensitivity was 91.7% (84.7%, 98.7%) and specificity 74.2% (66.5%, 81.9%) for discriminating delirium from the other groups. Specificity was 68.3% (56.6%, 80.1%) for discriminating delirium from dementia (cut-point ≤6). CONCLUSION: Patients with delirium (with or without pre-existing cognitive impairment) perform poorly on the DelApp compared to patients with dementia and those without cognitive impairment. A cut-point of ≤8/10 is suggested as having optimal sensitivity and specificity. The DelApp is a promising tool for assessment of attention deficits associated with delirium in older hospitalised adults, many of whom have prior cognitive impairment, and should be further validated in representative patient cohorts

Anderson's ethical vulnerability: animating feminist responses to sexual violence

Pamela Sue Anderson argues for an ethical vulnerability which “activates an openness to becoming changed” that “can make possible a relational accountability to one another on ethical matters”. In this essay I pursue Anderson’s solicitation that there is a positive politics to be developed from acknowledging and affirming vulnerability. I propose that this politics is one which has a specific relevance for animating the terms of feminist responses to sexual violence, something which has proved difficult for feminist theorists and activists alike. I will demonstrate the contribution of Anderson’s work to such questions by examining the way in which “ethical vulnerability” as a framework can illuminate the intersectional feminist character of Tarana Burke’s grassroots Me Too movement when compared with the mainstream, viral version of the movement. I conclude by arguing that Anderson’s “ethical vulnerability” contains ontological insights which can allay both activist and academic concerns regarding how to respond to sexual violence