Specific quinone reductase 2 inhibitors reduce metabolic burden and reverse Alzheimer’s disease phenotype in mice

Biological aging can be described as accumulative, prolonged metabolic stress and is the major risk factor for cognitive decline and Alzheimer’s disease (AD). Recently, we identified and described a quinone reductase 2 (QR2) pathway in the brain, in which QR2 acts as a removable memory constraint and metabolic buffer within neurons. QR2 becomes overexpressed with age, and it is possibly a novel contributing factor to age-related metabolic stress and cognitive deficit. We found that, in human cells, genetic removal of QR2 produced a shift in the proteome opposing that found in AD brains while simultaneously reducing oxidative stress. We therefore created highly specific QR2 inhibitors (QR2is) to enable evaluation of chronic QR2 inhibition as a means to reduce biological age–related metabolic stress and cognitive decline. QR2is replicated results obtained by genetic removal of QR2, while local QR2i microinjection improved hippocampal and cortical-dependent learning in rats and mice. Continuous consumption of QR2is in drinking water improved cognition and reduced pathology in the brains of AD-model mice (5xFAD), with a noticeable between-sex effect on treatment duration. These results demonstrate the importance of QR2 activity and pathway function in the healthy and neurodegenerative brain and what we believe to be the great therapeutic potential of QR2is as first-in-class drugs

Implementation outcomes of cognitive behavioural therapy delivered by non-specialists for common mental disorders and substance-use disorders in low- and middle-income countries: a systematic review.

Due to severe shortages of specialist mental health personnel in low- and middle-income countries (LMICs), psychological therapies are increasingly being delivered by non-specialist health workers (NSHWs). Previous reviews have investigated the effectiveness of NSHW-delivered psychological therapies, including cognitive behavioural therapy (CBT), in LMIC settings. This systematic review aims to synthesise findings on the implementation outcomes of NSHW-delivered CBT interventions addressing common mental disorders and substance-use disorders in LMICs. Four databases were searched, yielding 3211 records, 18 of which met all inclusion criteria. We extracted and synthesised qualitative and quantitative data across eight implementation outcomes: acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, penetration and sustainability. Findings suggest that delivery of CBT-based interventions by NSHWs can be acceptable, appropriate and feasible in LMIC settings. However, more research is needed to better evaluate these and other under-reported implementation outcomes

Depression and anxiety in parents of children with intellectual and developmental disabilities: A systematic review and meta-analysis.

INTRODUCTION: Although caring for a child with intellectual and developmental disabilities (IDD) can have positive outcomes, parents may be at a greater risk of depression and anxiety, due to a number of associated stressors, such as increased caregiver demands and financial strain. This systematic review updates previous data, exploring the relationship between parenting a child with IDD and parental depression and anxiety. METHODS: Five electronic databases were searched for eligible English-language articles, published between January 2004 and July 2018. All epidemiological study designs were eligible, provided the level of depression and/or anxiety was compared between parents of children (aged <18) with and without IDD. No limit was placed on geographic location. The proportion of positive associations between parenting a child with IDD and depression/anxiety were disaggregated by disability type, geographic region, and sample size. The percentage of parents at risk of moderate depression or anxiety were calculated using recognised clinical cut-off scores for each screening tool. Meta-analyses, in which pooled effect sizes of elevated depression and anxiety symptoms were calculated, were conducted across two IDD conditions, autism and cerebral palsy. RESULTS: Of the 5,839 unique records screened, 19 studies fulfilled the inclusion criteria. The majority of studies were conducted in high-income (n = 8, 42%) or upper-middle income countries (n = 10, 53%). Of the 19 studies, 69% focused on parents of children with cerebral palsy (n = 7, 37%) or autism (n = 6, 32%). Nearly all studies found a positive association between parenting a child with IDD and depression (n = 18, 95%) and anxiety (n = 9, 90%) symptoms. Factors associated with higher levels of depression symptoms amongst parents of children with IDD included disability severity (n = 8, 78%) and lower household income (n = 4, 80%). Approximately one third (31%) of parents of children with IDD reach the clinical cut-off score for moderate depression, compared with 7% of parents of children without IDD. 31% of parents of children with IDD reach the cut-off score for moderate anxiety, compared with 14% of parents of children without IDD. The meta-analyses demonstrated moderate effect sizes for elevated depression amongst parents of children with autism and cerebral palsy. CONCLUSIONS: Results indicate elevated levels of depressive symptoms amongst parents of children with IDD. Quality concerns amongst the existing literature support the need for further research, especially in low- and middle-income countries

Prevalence of depression, anxiety and post-traumatic stress disorder in health care workers during the COVID-19 pandemic: A systematic review and meta-analysis.

OBJECTIVE: The COVID-19 pandemic has placed health care workers under psychological stress. Previous reviews show a high prevalence of mental disorders among health care workers, but these need updating and inclusion of studies written in Chinese. The aim of this systematic review and meta-analysis was to provide updated prevalence estimates for depression, anxiety and post-traumatic stress disorder (PTSD) among health care workers during the COVID-19 pandemic, benefitting from the inclusion of studies published in Chinese. METHODS: Systematic search of EMBASE, MEDLINE, PsycINFO, Global Health, Web of Science, CINAHL, Google Scholar and the Chinese databases SinoMed, WanfangMed, CNKI and CQVIP, for studies conducted between December 2019 and August 2020 on the prevalence of depression, anxiety and PTSD in health care workers during the COVID-19 pandemic. Studies published in both English and Chinese were included. RESULTS: Data on the prevalence of moderate depression, anxiety and PTSD was pooled across 65 studies involving 97,333 health care workers across 21 countries. The pooled prevalence of depression was 21.7% (95% CI, 18.3%-25.2%), of anxiety 22.1% (95% CI, 18.2%-26.3%), and of PTSD 21.5% (95% CI, 10.5%-34.9%). Prevalence estimates are also provided for a mild classification of each disorder. Pooled prevalence estimates of depression and anxiety were highest in studies conducted in the Middle-East (34.6%; 28.9%). Subgroup and meta-regression analyses were conducted across covariates, including sampling method and outcome measure. CONCLUSIONS: This systematic review and meta-analysis has identified a high prevalence of moderate depression, anxiety and PTSD among health care workers during the COVID-19 pandemic. Appropriate support is urgently needed. The response would benefit from additional research on which interventions are effective at mitigating these risks

Disability and mental health among Syrian refugees in Sultanbeyli, Istanbul: 2019 Survey Report

Evidence suggests that refugee populations are at an increased risk of disability, especially mental health issues. There is, however, insufficient data regarding the prevalence and lived experience of Syrian refugees with disabilities in Istanbul. This study aims to provide reliable data on disability and mental health, with which to inform service provision, policy, and advocacy

Better Health, Better Lives? 10-Years on From the World Health Organization's Declaration on the Health of Children With Intellectual Disabilities.

It is now 10 years since the European Declaration on the Health of Children and Young People with Intellectual Disabilities and their Families: Better Health - Better Lives was adopted by the World Health Organization. Through discussions with key informants and an online literature review, we reflect on actions and progress made in line with this Declaration to improve the health and wellbeing of children with intellectual disabilities and their families. Despite finding positive examples of policy, legislation and practice in support of children with intellectual disabilities, there are clear gaps and areas for improvement. Countries must continue to take action, as supported by the World Health Organization and other such organisations, in order to support children with intellectual disabilities in realising their fundamental human rights

Disabled people and the impact of COVID-19: four urgent messages for the government

Tom Shakespeare, Nicholas Watson, Richard Brunner, Jane Cullingworth, Shaffa Hameed, Charlotte Pearson, Nathaniel Scherer and Veronika Reichenberger report on in-depth qualitative interviews conducted with 69 disabled people in England and Scotland, and with 28 key informants from infrastructure organisations in the voluntary and statutory sectors, about the impact of COVID-19, and measures taken to control it. They discuss the dislocations it has caused in everyday life; the failures of social care; the use of new technologies; and participants’ views on leadership and communication

Disabled people and COVID-19: four urgent messages for the government

Tom Shakespeare (LSHTM), Nicholas Watson, Richard Brunner, Jane Cullingworth (University of Glasgow), Shaffa Hameed (LSHTM), Charlotte Pearson (University of Glasgow), Nathaniel Scherer and Veronika Reichenberger (LSHTM) report on in-depth qualitative interviews conducted with 69 disabled people in England and Scotland, and with 28 key informants from infrastructure organisations in the voluntary and statutory sectors, about the impact of COVID-19, and measures taken to control it. They discuss the dislocations it has caused in everyday life; the failures of social care; the use of new technologies; and participants’ views on leadership and communication

Cambodia and Bangadesh Water, Sanitation and Hygiene Policy Analysis: Using the EquiFrame to understand how WASH policies and program documents capture the rights of people with disabilities and women and girls. Briefing note 2

This briefing note is supported by the Australian Aid program Water for Women Fund. It synthesises Scherer,N.;Mactaggart,I.; Huggett, C.; Pheng, P.; Rahman, M.-u.; Biran, A.; Wilbur, J. (2021), The Inclusion of Rights of People with Disabilities and Women and Girls in Water, Sanitation, and Hygiene Policy Documents and Programs of Bangladesh and Cambodia: Content Analysis Using EquiFrame. International Journal of Environrmental Research and Public Health (1)

Are the rights of people with disabilities included in international guidance on WASH during the COVID-19 pandemic? Briefing note

This briefing note is supported by the Australian Aid program Water for Women Fund. It draws on the article, currently under peer review: Scherer, N., Mactaggart, I., Huggett, C, Pheng, P., Rahman, M., Wilbur, J., Are the rights of people with disabilities included in international guidance on WASH during the COVID-19 pandemic? Content analysis using EquiFrame; BMJ Open 2021