Healing the Past by Nurturing the Future: trauma-aware, healing-informed care to improve support for Aboriginal and Torres Strait Islander families - implementation and evaluation study protocol.

INTRODUCTION: Complex trauma can have serious impacts on the health and well-being of Aboriginal and Torres Strait Islander families. The perinatal period represents a 'critical window' for recovery and transforming cycles of trauma into cycles of healing. The Healing the Past by Nurturing the Future (HPNF) project aims to implement and evaluate a programme of strategies to improve support for Aboriginal and Torres Strait islander families experiencing complex trauma. METHOD: The HPNF programme was codesigned over 4 years to improve awareness, support, recognition and assessment of trauma. Components include (1) a trauma-aware, healing-informed training and resource package for service providers; (2) trauma-awareness resources for parents; (3) organisational readiness assessment; (4) a database for parents and service providers to identify accessible and appropriate additional support and (5) piloting safe recognition and assessment processes. The programme will be implemented in a large rural health service in Victoria, Australia, over 12 months. Evaluation using a mixed-methods approach will assess feasibility, acceptability, cost, effectiveness and sustainability. This will include service user and provider interviews; service usage and cost auditing; and an administrative linked data study of parent and infant outcomes. ANALYSIS: Qualitative data will be analysed using reflexive thematic analysis. Quantitative and service usage outcomes will be described as counts and proportions. Evaluation of health outcomes will use interrupted time series analyses. Triangulation of data will be conducted and mapped to the Consolidated Framework for Implementation Research and Reach, Effectiveness, Adoption, Implementation and Maintenance frameworks to understand factors influencing feasibility, acceptability, effectiveness, cost and sustainability. ETHICS AND DISSEMINATION: Approval granted from St Vincent's Melbourne Ethics Committee (approval no. 239/22). Data will be disseminated according to the strategy outlined in the codesign study protocol, in-line with the National Health and Medical Research Council Aboriginal and Torres Strait Islander Research Excellence criteria.

Unsupervised Exercise in Interstitial Lung Disease: A Delphi Study to Develop a Consensus Preparticipation Screening Tool for Lymphangioleiomyomatosis.

BACKGROUND: Little research is available to provide practical guidance to health care providers for exercise preparticipation screening and referral of patients with interstitial lung diseases (ILD), including lymphangioleiomyomatosis (LAM), to participate in remote, unsupervised exercise programs. RESEARCH QUESTION: What exercise preparticipation screening steps are essential to determine whether a patient with LAM is medically appropriate to participate in a remote, unsupervised exercise program? STUDY DESIGN AND METHODS: Sixteen experts in LAM and ILD participated in a two-round modified Delphi study, ranking their level of agreement for ten statements related to unsupervised exercise training in LAM, with an a priori definition of consensus. Additionally, 60 patients with LAM completed a survey of the perceived risks and benefits of remote exercise training in LAM. RESULTS: Seven of the 10 statements reached consensus among experts. Experts agreed that an in-person clinical exercise test is indicated to screen for exercise-induced hypoxemia and prescribe supplemental oxygen therapy as indicated prior to initiating a remote exercise program. Patients with recent pneumothorax should wait to start an exercise program for at least 4 weeks until after resolution of pneumothorax and clearance by a physician. Patients with high cardiovascular risk for event during exercise, severe resting pulmonary hypertension, or risk for falls may be more appropriate for referral to a rehabilitation center. A LAM-specific remote exercise preparticipation screening tool was developed from the consensus statements and agreed upon by the panelists. INTERPRETATION: A modified Delphi study approach was useful to develop disease-specific recommendations for safety and preparticipation screening prior to unsupervised, remotely administered exercise in LAM. The primary product of this study is a clinical decision aid for providers to use when medically screening patients prior to participation in the newly launched LAMFit remote exercise program. FUNDING: This work was funded by an Established Investigator Award (LAM0130PB07-18) to MBB from The LAM Foundation.

Healing and wellbeing outcomes of services for Aboriginal people based on cultural therapeutic ways: A systematic scoping review.

Aboriginal Australians experience disproportionately high rates of mental health problems as the result of European colonisation, and Western evidence-based treatment has been strikingly ineffective in improving the situation. Cultural Therapeutic Ways is a culturally specific healing and wellbeing practice framework developed by the Victorian Aboriginal Child and Community Agency that focuses on culturally based practices, trauma awareness, and self-determination. Despite wide recognition of the importance of these elements in Indigenous healing and wellbeing programs, its measurable empirical impact is currently unclear. This paper summarises findings from a systematic scoping review to ascertain the published knowledge base for Cultural Therapeutic Ways and the gaps in knowledge that can inform future evaluation. Forty-two studies of programs that applied Cultural Therapeutic Ways with Indigenous participants from Australia, Canada, New Zealand, and the United States of America were identified from the literature search. Services based on Cultural Therapeutic Ways contributed to healing and wellbeing because they create safety, strengthen cultural connections, develop empowerment and provide opportunities to release emotion, and increase social and spiritual support. As the review set out to determine the published evidence base for Cultural Therapeutic Ways, other effective approaches may have been overlooked. To develop the evidence base for Cultural Therapeutic Ways, service design must clearly describe target groups, whether the program is delivered by Aboriginal people, the processes of Cultural Therapeutic Ways utilised in service delivery, and how they are blended with Western approaches. Research efforts could also productively be focused on identifying or constructing culturally appropriate outcome measures.

Minimal Detectable Changes of the HAQ-DI, PROMIS-29v2.0 Domains, and PHQ-8 in Systemic Sclerosis: A SPIN Cohort Cross-Sectional Study.

OBJECTIVE: Systemic sclerosis (SSc) is a rare, chronic, autoimmune disorder associated with disability, diminished physical function, fatigue, pain, and mental health concerns. We assessed minimal detectable changes (MDCs) of the Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient Reported Outcomes Measurement Information System-29 Profile version 2.0 (PROMIS-29v2.0) domains, and Patient Health Questionnaire-8 (PHQ-8) in SSc. METHODS: Scleroderma Patient-centered Intervention Network Cohort participants completed the HAQ-DI, PROMIS-29v2.0 domains, and PHQ-8 at baseline assessments from April 2014 until August 2023. We estimated MDC95 and MDC90 with 95% confidence intervals (CI) generated via the percentile bootstrapping method resampling 1000 times. We compared MDC estimates by age, sex and SSc subtype. RESULTS: A total of 2,571 participants were included. Most were female (N = 2,241; 87%), and 38% (N = 976) had diffuse SSc. Mean (SD) age was 54.9 (12.7) years and duration since onset of first non-Raynaud phenomenon symptom 10.8 (8.7) years. MDC95 estimate was 0.41 points (95% CI: 0.40 to 0.42) for the HAQ-DI, between 4.88 points (95% CI: 4.72 to 5.05) and 9.02 points (95% CI: 8.80 to 9.23) for the 7 PROMIS-29v2.0 domains, and 5.16 points (95% CI: 5.06 to 5.26) for the PHQ-8. MDC95 estimates were not materially different across subgroups. CONCLUSION: MDC95 and MDC90 estimates were precise and similar across age, sex and SSc subtype groups. HAQ-DI MDC95 and MDC90 were substantially larger than previous estimates of HAQ-DI minimal important difference from several small studies. Minimally important differences of all measures should be evaluated in large studies using anchor-based methods.

Overdrive is essential for targeted sperm elimination by Segregation Distorter.

Intra-genomic conflict driven by selfish chromosomes is a powerful force that shapes the evolution of genomes and species. In the male germline, many selfish chromosomes bias transmission in their own favor by eliminating spermatids bearing the competing homologous chromosomes. However, the mechanisms of targeted gamete elimination remain mysterious. Here, we show that Overdrive (Ovd), a gene required for both segregation distortion and male sterility in Drosophila pseudoobscura hybrids, is broadly conserved in Dipteran insects but dispensable for viability and fertility. In D. melanogaster, Ovd is required for targeted Responder spermatid elimination after the histone-to-protamine transition in the classical Segregation Distorter system. We propose that Ovd functions as a general spermatid quality checkpoint that is hijacked by independent selfish chromosomes to eliminate competing gametes.

A scoping review on what constitutes a good research culture.

Background: The crisis in research culture is well documented, covering issues such as a tendency for quantity over quality, unhealthy competitive environments, and assessment based on publications, journal prestige and funding. In response, research institutions need to assess their own practices to promote and advocate for change in the current research ecosystem. The purpose of the scoping review was to explore ' What does the evidence say about the 'problem' with 'poor' research culture, what are the benefits of 'good' research culture, and what does 'good' look like?' Aims: To examine the peer-reviewed and grey literature to explore the interplay between research culture, open research, career paths, recognition and rewards, and equality, diversity, and inclusion, as part of a larger programme of activity for a research institution. Methods: A scoping review was undertaken. Six databases were searched along with grey literature. Eligible literature had relevance to academic research institutions, addressed research culture, and were published between January 2017 to May 2022. Evidence was mapped and themed to specific categories. The search strategy, screening and analysis took place between April-May 2022. Results: 1666 titles and abstracts, and 924 full text articles were assessed for eligibility. Of these, 253 articles met the eligibility criteria for inclusion. A purposive sampling of relevant websites was drawn from to complement the review, resulting in 102 records included in the review. Key areas for consideration were identified across the four themes of job security, wellbeing and equality of opportunity, teamwork and interdisciplinary, and research quality and accountability. Conclusions: There are opportunities for research institutions to improve their own practice, however institutional solutions cannot act in isolation. Research institutions and research funders need to work together to build a more sustainable and inclusive research culture that is diverse in nature and supports individuals' well-being, career progression and performance.

Exploring virtual funding committee practices in the allocation of National Institute for Health and Care Research funding: A netnographic study.

Background: Funding committees, comprising members with a range of knowledge, skills, and experience, are considered integral to the decision-making process of funding organisations for recommending or allocating research funding. However, there is limited research investigating the decision-making processes, the role of members and their social interactions during funding committee meetings conducted both virtually and face-to-face. Methods: Using a mixed-methods design and following netnography principles, the study observed nine National Institute for Health and Care Research programmes funding committee meetings conducted virtually during October 2020 to December 2021; complemented by interviews with committee chairs and members (18 interviews) and NIHR staff (12 interviews); an online survey (50 responses); and documentary analysis. Personal reflections through immersive journals also formed part of the analysis. Results: Three main themes were identified from the observations, interviews, and online survey: efficiency of virtual committee meetings (importance of preparation, and the role of formality, process, and structure); understanding the effect of virtual committee meetings on well-being (effects of fatigue and apprehension, and the importance of work life balance); understanding social interactions and engagement (levels of engagement, contribution and inclusivity, awareness of unconscious bias and the value of social networking). Conclusions: Examining the decision-making practices of one funding organisation across several research programmes, across multiple committee meetings over one year has generated new insights around funding committee practices that previous studies have not been able to explore or investigate. Overall, it was observed that fair and transparent funding recommendations and outcomes can be achieved through virtual funding committees. However, whilst virtual funding committees have many benefits and opportunities, such as the potential to increase membership diversity and inclusivity, and be more environmentally sustainable, more evidence is needed to evaluate their effectiveness, with particular focus on issues of fatigue, engagement, and committee cohesion, especially when new committee members join.

mARC1 in MASLD: Modulation of lipid accumulation in human hepatocytes and adipocytes.

BACKGROUND: Mutations in the gene MTARC1 (mitochondrial amidoxime-reducing component 1) protect carriers from metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. MTARC1 encodes the mARC1 enzyme, which is localized to the mitochondria and has no known MASH-relevant molecular function. Our studies aimed to expand on the published human genetic mARC1 data and to observe the molecular effects of mARC1 modulation in preclinical MASH models. METHODS AND RESULTS: We identified a novel human structural variant deletion in MTARC1, which is associated with various biomarkers of liver health, including alanine aminotransferase levels. Phenome-wide Mendelian Randomization analyses additionally identified novel putatively causal associations between MTARC1 expression, and esophageal varices and cardiorespiratory traits. We observed that protective MTARC1 variants decreased protein accumulation in in vitro overexpression systems and used genetic tools to study mARC1 depletion in relevant human and mouse systems. Hepatocyte mARC1 knockdown in murine MASH models reduced body weight, liver steatosis, oxidative stress, cell death, and fibrogenesis markers. mARC1 siRNA treatment and overexpression modulated lipid accumulation and cell death consistently in primary human hepatocytes, hepatocyte cell lines, and primary human adipocytes. mARC1 depletion affected the accumulation of distinct lipid species and the expression of inflammatory and mitochondrial pathway genes/proteins in both in vitro and in vivo models. CONCLUSIONS: Depleting hepatocyte mARC1 improved metabolic dysfunction-associated steatotic liver disease-related outcomes. Given the functional role of mARC1 in human adipocyte lipid accumulation, systemic targeting of mARC1 should be considered when designing mARC1 therapies. Our data point to plasma lipid biomarkers predictive of mARC1 abundance, such as Ceramide 22:1. We propose future areas of study to describe the precise molecular function of mARC1, including lipid trafficking and subcellular location within or around the mitochondria and endoplasmic reticulum.

Postoperative Recovery of Quality-of-Life Following Ureteroscopy for Nephrolithiasis: The Impact on Pain Intensity and Interference and the Ability to Participate in Social Roles.

OBJECTIVE: To prospectively capture patient-reported outcomes to assess the recovery profile of ureteroscopy (URS). MATERIALS AND METHODS: Adults undergoing URS for renal/ureteral stones were eligible for inclusion (11/2020-8/2022). Patients prospectively completed PROMIS - Pain Intensity, - Pain Interference, and - Ability to participate in social roles and activities in-person preoperatively (POD 0) and via email on POD 1, 7, 14, and 30. Scores are reported as T-scores (normalized to U.S. population, mean=50) with a change of 5 (0.5 SD) considered clinically significant. RESULTS: One hundred and seventy-eight participants enrolled at POD 0 (POD 1 =87, POD 7 =83, POD 14 =70, POD30 =67). There was a worsening of quality of life from day 0 to day 1 and day 0 to 7. All dimensions then improved with an increase in scores from day 0 to day 14 and day 0 to day 30. On multivariable analysis, the presence of a preoperative ureteral stent (OR 0.14) and use of semirigid URS (OR 0.33) were associated with a reduced odds for severe pain interference at day 1. The use of semirigid URS (OR 0.20) was associated with a reduced odds for severe worsening in the ability to participate in social roles at day 1. CONCLUSION: Ability to participate in social roles declines immediately postoperatively, while pain intensity and interference sharply increase. There is a gradual improvement until POD 30. Findings suggest preoperative stents may influence postoperative recovery. Results offer meaningful insight to assist in counseling and setting expectation for patients postoperatively.

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination.

Kinetic studies on the intramolecular hydroamination of protected variants of 2,2-diphenylpent-4-en-1-amine were carried out under a variety of conditions with cationic gold catalysts supported by phosphine ligands. The impact of ligand on gold, protecting group on nitrogen, and solvent and additive on reaction rates was determined. The most effective reactions utilized more Lewis basic ureas, and more electron-withdrawing phosphines. A DCM/alcohol cooperative effect was quantified, and a continuum of isotope effects was measured with low KIE's in the absence of deuterated alcoholic solvent, increasing to large solvent KIE's when comparing reactions in pure MeOH to those in pure MeOH-d4. The effects are interpreted both within the context of a classic gold π-activation/protodeauration mechanism and a general acid-catalyzed mechanism without intermediate gold alkyls.

Online survey exploring researcher experiences of research funding processes in the UK: the effort and burden of applying for funding and fulfilling reporting requirements.

OBJECTIVE: To explore researchers' experiences of funding processes, the effort and burden involved in applying for funding, obtaining funding and/or fulfilling reporting requirements with a UK health and social care research funder. DESIGN/SETTING: A cross-sectional online survey study with open (free-text) and closed questions (August to November 2021). PARTICIPANTS: Researchers with experience of applying for/obtaining funding and/or experience of fulfilling reporting requirements for UK health and social care research funded between January 2018 and June 2021. RESULTS: The survey was completed by 182 researchers, of which 176 had experience with applying for/obtaining funding, and 143 had experience with fulfilling reporting requirements during the timeframe. The majority of the 176 respondents (58%) completed between 7 and 13 key processes in order to submit an application and 69% felt that it was critically important to undertake these key processes. Respondents (n=143) reported submitting an average of 17 reports as part of research monitoring to a range of organisations (eg, funders, Higher Education Institutions). However, only 33% of respondents felt it was critically important to provide the requested reporting information to the different organisations. Thematic analysis of free-text questions on application and reporting identified themes relating to process inefficiencies including streamlining and alignment of systems, lack of understanding of processes including a need for improved communication and feedback from organisations with clear explanations about what information is needed, when and why, the support required by respondents and the time, effort and impact on workload and well-being. CONCLUSIONS: Through this study, we were able to identify funding processes that are considered by some to be effortful, but necessary, as well as those that were perceived as unnecessary, complex and repetitive, and may waste some researchers time and effort and impact on well-being. Possible solutions to increase efficiency and enhance value in these processes were identified.

The association of resilience and positive mental health in systemic sclerosis: A Scleroderma Patient-centered Intervention Network (SPIN) cohort cross-sectional study.

OBJECTIVE: A previous study using Scleroderma Patient-centered Intervention Network (SPIN) Cohort data identified five classes of people with systemic sclerosis (also known as scleroderma) based on patient-reported somatic (fatigue, pain, sleep) and mental health (anxiety, depression) symptoms and compared indicators of disease severity between classes. Across four classes ("low", "normal", "high", "very high"), there were progressively worse somatic and mental health outcomes and greater disease severity. The fifth ("high/low") class, however, was characterized by high disease severity, fatigue, pain, and sleep but low mental health symptoms. We evaluated resilience across classes and compared resilience between classes. METHODS: Cross-sectional study. SPIN Cohort participants completed the 10-item Connor-Davidson-Resilience Scale (CD-RISC) and PROMIS v2.0 domains between August 2022 and January 2023. We used latent profile modeling to identify five classes as in the previous study and multiple linear regression to compare resilience levels across classes, controlling for sociodemographic and disease variables. RESULTS: Mean CD-RISC score (N = 1054 participants) was 27.7 (standard deviation = 7.3). Resilience decreased progressively across "low" to "normal" to "high" to "very high" classes (mean 4.7 points per step). Based on multiple regression, the "high/low" class exhibited higher resilience scores than the "high" class (6.0 points, 95% confidence interval [CI] 4.9 to 7.1 points; standardized mean difference = 0.83, 95% CI 0.67 to 0.98). CONCLUSIONS: People with worse disease severity and patient-reported outcomes reported substantially lower resilience, except a class of people with high disease severity, fatigue, pain, and sleep disturbance but positive mental health and high resilience.

Compliance of Adolescent Friendly Health Clinics with National and International Standards: Quantitative findings from the i-Saathiya study.

OBJECTIVE: Indian adolescents experience several health challenges requiring acceptable, equitable, appropriate and effective healthcare services. Our objective was to assess the compliance of Adolescent Friendly Health Clinics (AFHCs) in two of India's largest states, using both national benchmarks (under Rashtriya Kishor Swasthya Karyakram-RKSK) and global standards (by WHO). DESIGN: Cross-sectional study comprising structured observations and interactions (November 2021 to June 2022). SETTING: Fourteen AFHCs across all levels of health system were included from two districts of Maharashtra (n=8) and Madhya Pradesh (n=6). These AFHCs were observed using checklist, and few items of checklist were verified by interactions with AFHC's health workers (medical officers/auxillary nurse midwives/counsellors) handlings adolescents. The developed checklist included 57 items based on adapted global standards and 25 items using national benchmarks. RESULT: High compliance of AFHCs with RKSK's benchmarks was attributed to various items including the accessibility through local transport (n=14, 100%), clean surroundings (n=11, 78.5%), presence of signage (n=10, 71.4%), convenient operating days and time (n=11, 78.5%), and secure storage of records (n=13, 92.9%). Concurrently, items that showed low compliance encompassed, the availability of Information, Education and communication (IEC) resources, which were deficient in 57.1% of AFHCs (n=8). Similarly, designated areas for clinical services (n=10, 71.4%) and commodity disbursement (n=9, 64.3%) lacked in more than half of the recruited AFHCs. Additionally, lack of guidelines for referrals (n=13, 92.9%), as well as standard operating procedures to ensure equity, non-judgemental attitude, competence, confidentiality and referral as per WHO standards. CONCLUSION: Evidence spotlights the strengths and gaps in AFHCs, aligning with, government's priorities on adolescent health. Addressing the identified gaps is crucial to creating healthcare facilities that are adolescent-friendly, easily accessible and effectively navigate adolescent health challenges. This concerted effort would contribute to their development and transformation, playing a pivotal role in India's progress.

Ultra-low dose chest CT with silver filter and deep learning reconstruction significantly reduces radiation dose and retains quantitative information in the investigation and monitoring of lymphangioleiomyomatosis (LAM).

PURPOSE: Frequent CT scans to quantify lung involvement in cystic lung disease increases radiation exposure. Beam shaping energy filters can optimize imaging properties at lower radiation dosages. The aim of this study is to investigate whether use of SilverBeam filter and deep learning reconstruction algorithm allows for reduced radiation dose chest CT scanning in patients with lymphangioleiomyomatosis (LAM). MATERIAL AND METHODS: In a single-center prospective study, 60 consecutive patients with LAM underwent chest CT at standard and ultra-low radiation doses. Standard dose scan was performed with standard copper filter and ultra-low dose scan was performed with SilverBeam filter. Scans were reconstructed using a soft tissue kernel with deep learning reconstruction (AiCE) technique and using a soft tissue kernel with hybrid iterative reconstruction (AIDR3D). Cyst scores were quantified by semi-automated software. Signal-to-noise ratio (SNR) was calculated for each reconstruction. Data were analyzed by linear correlation, paired t-test, and Bland-Altman plots. RESULTS: Patients averaged 49.4 years and 100% were female with mean BMI 26.6 ± 6.1 kg/m2. Cyst score measured by AiCE reconstruction with SilverBeam filter correlated well with that of AIDR3D reconstruction with standard filter, with a 1.5% difference, and allowed for an 85.5% median radiation dosage reduction (0.33 mSv vs. 2.27 mSv, respectively, p < 0.001). Compared to standard filter with AIDR3D, SNR for SilverBeam AiCE images was slightly lower (3.2 vs. 3.1, respectively, p = 0.005). CONCLUSION: SilverBeam filter with deep learning reconstruction reduces radiation dosage of chest CT, while maintaining accuracy of cyst quantification as well as image quality in cystic lung disease. CLINICAL RELEVANCE STATEMENT: Radiation dosage from chest CT can be significantly reduced without sacrificing image quality by using silver filter in combination with a deep learning reconstructive algorithm. KEY POINTS: • Deep learning reconstruction in chest CT had no significant effect on cyst quantification when compared to conventional hybrid iterative reconstruction. • SilverBeam filter reduced radiation dosage by 85.5% compared to standard dose chest CT. • SilverBeam filter in coordination with deep learning reconstruction maintained image quality and diagnostic accuracy for cyst quantification when compared to standard dose CT with hybrid iterative reconstruction.

Moderators of Loneliness Trajectories in People with Systemic Sclerosis During the COVID-19 Pandemic: A SPIN COVID-19 Cohort Longitudinal Study.

BACKGROUND: Many individuals with systemic sclerosis (SSc) are at heightened risk for COVID-19 related morbidity and isolation due to interstitial lung disease, frailty, and immunosuppressant use. Minimal research has explored loneliness predictors in individuals with chronic illnesses during COVID-19. This study evaluated moderators of loneliness trajectories in individuals with SSc during COVID-19. METHODS: Longitudinal data were analyzed across 30 timepoints from April 2020 to May 2022 from 775 adults in the Scleroderma Patient-centered Intervention Network (SPIN) COVID-19 Cohort. Hierarchical linear modeling evaluated cross-level moderators of loneliness trajectories, including marital status, baseline number of household members, number of virtual or telephone one-on-one or virtual group conversations, number of hours spent enjoying in-person household conversations or activities, and satisfaction with quality of in-person household conversations (all in the past week). Level-1 moderation analyses assessed effects of conversation, activity, and satisfaction means and slopes over time. RESULTS: Baseline values were not statistically significant moderators of loneliness trajectories. Higher mean (averaged over time) virtual or telephone one-on-one and in-person household conversations, in-person household activity, and in-person household conversation satisfaction were associated with lower loneliness trajectories (ps < .05). The relationship between in-person household conversation satisfaction and loneliness trajectory was statistically significantly but minimally attenuated over time (p < .001). CONCLUSIONS: For people with SSc, higher mean conversation, activity, and satisfaction variables were associated with lower levels of loneliness during the pandemic, but changes in these social variables were generally not predictive of changes in loneliness.

Role of histone variants H2BC1 and H2AZ.2 in H2AK119ub nucleosome organization and Polycomb gene silencing.

Ubiquitination of histone H2A at lysine 119 residue (H2AK119ub) plays critical roles in a wide range of physiological processes, including Polycomb gene silencing 1,2 , replication 3-5 , DNA damage repair 6-10 , X inactivation 11,12 , and heterochromatin organization 13,14 . However, the underlying mechanism and structural basis of H2AK119ub remains largely elusive. In this study, we report that H2AK119ub nucleosomes have a unique composition, containing histone variants H2BC1 and H2AZ.2, and importantly, this composition is required for H2AK119ub and Polycomb gene silencing. Using the UAB domain of RSF1, we purified H2AK119ub nucleosomes to a sufficient amount and purity. Mass spectrometry analyses revealed that H2AK119ub nucleosomes contain the histone variants H2BC1 and H2AZ.2. A cryo-EM study resolved the structure of native H2AK119ub nucleosomes to a 2.6A resolution, confirming H2BC1 in one subgroup of H2AK119ub nucleosomes. Tandem GST-UAB pulldown, Flag-H2AZ.2, and HA-H2BC1 immunoprecipitation revealed that H2AK119ub nucleosomes could be separated into distinct subgroups, suggesting their composition heterogeneity and potential dynamic organization. Knockout or knockdown of H2BC1 or H2AZ.2 reduced cellular H2AK119ub levels, establishing H2BC1 and H2AZ.2 as critical determinants of H2AK119ub. Furthermore, genomic binding profiles of H2BC1 and H2AZ.2 overlapped significantly with H2AK119ub binding, with the most significant overlapping in the gene body and intergenic regions. Finally, assays in developing embryos reveal an interaction of H2AZ.2, H2BC1, and RING1A in vivo . Thus, this study revealed, for the first time, that the H2AK119ub nucleosome has a unique composition, and this composition is required for H2AK119ub and Polycomb gene silencing.

The estimated health impact of alcohol interventions in New Zealand: A modelling study.

AIMS: To estimate the health impacts of key modelled alcohol interventions among Maori (indigenous peoples) and non-Maori in New Zealand (NZ). DESIGN: Multi-stage life-table intervention modelling study. We modelled two scenarios: (1) business-as-usual (BAU); and (2) an intervention package scenario that included a 50% alcohol tax increase, outlet density reduction from 63 to five outlets per 100 000 people, outlet hours reduction from 112 to 50 per week and a complete ban on all forms of alcohol marketing. SETTING AND PARTICIPANTS: The model's population replicates the 2018 NZ population by ethnicity (Maori/non-Maori), age and sex. MEASUREMENTS: Alcohol consumption was estimated using nationally representative survey data combined with sales data and corrected for tourist and unrecorded consumption. Disease incidence, prevalence and mortality were calculated using Ministry of Health data. We used dose-response relationships between alcohol and illness from the 2016 Global Burden of Disease study and calculated disability rates for each illness. Changes in consumption were based on the following effect sizes: total intervention package [-30.3%, standard deviation (SD) = 0.02); tax (-7.60%, SD = 0.01); outlet density (-8.64%, SD = 0.01); outlet hours (-9.24%, SD = 0.01); and marketing (-8.98%, SD = 0.02). We measured health gain using health-adjusted life years (HALYs) and life expectancy. FINDINGS: Compared with the BAU scenario, the total alcohol intervention package resulted in 726 000 [95% uncertainty interval (UI) = 492 000-913 000] HALYs gained during the life-time of the modelled population. Maori experienced greater HALY gains compared with non-Maori (0.21, 95% UI = 0.14-0.26 and 0.16, 95% UI = 0.11-0.20, respectively). When modelled individually, each alcohol intervention within the intervention package produced similar health gains (~200 000 HALYs per intervention) owing to the similar effect sizes. CONCLUSIONS: Modelled interventions for increased alcohol tax, reduced availability of alcohol and a ban on alcohol marketing among Maori and non-Maori in New Zealand (NZ) suggest substantial population-wide health gains and reduced health inequities between Maori and non-Maori.

Food tax policies in Pacific Island Countries and Territories: systematic policy review.

OBJECTIVE: To systematically identify and review food taxation policy changes in Pacific Island Countries and Territories (PICTs). DESIGN: Food taxation polices, regarding excise taxes and tariffs applied from 2000 to 2020 in twenty-two PICTs, and their key characteristics were reviewed. The search was conducted using databases, government legal repositories and broad-based search engines. Identified documents for screening included legislation, reports, academic literature, news articles and grey literature. Key informants were contacted from each PICT to retrieve further data and confirm results. Results were analysed by narrative synthesis. SETTING: Noncommunicable diseases (NCD) are the leading cause of premature death in PICTs and in many jurisdictions globally. An NCD crisis has been declared in the Pacific, and food taxation policy has been recommended to address the dietary risk factors associated with. Progress is unclear. RESULTS: Of the twenty-two PICTs included in the study, fourteen had food taxation policies and five introduced excise taxes. Processed foods, sugar and salt were the main target of excise taxes. A total of eighty-four food taxation policy changes were identified across all food groups. There was a total of 279 taxes identified by food group, of which 85 % were tariffs and 15 % were excise taxes. Individual tax rates varied substantially. The predominant tax design was ad valorem, and this was followed by volumetric. CONCLUSIONS: A quarter of PICTs have introduced food excise taxes from 2000 to 2020. Further excise taxes, specifically tiered or nutrient-specific designs, could be introduced and more systematically applied to a broader range of unhealthy foods.

Sexual, reproductive and mental health among young men (10-24) in low-and-middle income countries: a scoping review.

Background: The relationship between SRH and mental health among men is not well documented, especially in the 10-24 age group. This scoping review aimed to investigate what is known about the association between SRH and mental health among young men (10-24) in LMICs. Methods: Embase, APA PsycInfo, MEDLINE(R) ALL, ASSIA and the Cochrane Library of Database of Systematic Reviews were searched from the year of establishment up to August 2022. The review was reported using the PRISMA-ScR checklist. Results: A total of (n = 2636) studies were identified from the five databases. After the completion of screening, only ten studies (n = 8 cross-sectional, n = 1 mixed methods and n = 1 qualitative) met the eligibility criteria and were included in the review. The findings suggest that there is a reciprocal relationship between mental health and SRH. Sperm concentration and total sperm count were found to be lower in depressed men. Poor mental health was associated with early sexual debut, higher rates of sexual activity and an increased number of sexual partners. Poor mental health was also found among men who had sex with men (MSM). In addition, we found a relationship between sexual abuse, sexual coercion and poor mental health. Conclusion: The findings of this unique study indicate that poor mental health is associated with poor SRH outcomes and vice versa among young men (10-24) living in LMICs. However, further research will be needed to establish the temporal relationship between SRH and mental health outcomes.