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Tissue-specific mitochondrial pathway remodeling linked to longevity in honeybee queens

by Clément Joël Lucien Chevret, José Francisco Echegaray, Alexander Walton, Maryam Lo, Olav Rueppell, Hélène Lemieux

Mitochondrial metabolism plays a critical role in determining lifespan across animal taxa. In our study, we used the Western honeybee (Apis mellifera) as a model, capitalizing on the stark lifespan difference between queens, which often live more than two years, and summer workers, which survive only about 30 days, despite sharing the same genetic background. We investigated mitochondrial function in head tissue, thoracic muscle, and abdominal fat tissue of queens and workers, comparing early (7 days) and late adult stages (28–30 days in workers; 2 years in queens). No significant differences in mitochondrial flux control ratio for the NADH- Succinate- and glycerophosphate (Gp) pathways were found in thoracic muscles across castes or age groups. In head and abdominal fat tissues, early-life queens showed reduced reliance on NADH-linked pathways for maximal respiratory flux compared to workers. The decrease in the NADH-pathway was compensated by an increase in the Gp-pathway contribution. Queens exhibited reduced phosphorylation-pathway control over OXPHOS compared to workers, both in head tissue during early life and in abdominal fat tissue later in life. These findings reveal caste- and tissue-specific patterns of mitochondrial regulation that may contribute to dramatic lifespan divergence observed in eusocial insects. They suggest that early-life metabolic flexibility could play an important role in shaping life history evolution in Apis mellifera.

Prevalence and factors associated with pre-diabetes and undiagnosed diabetes in Cambodia: cross-sectional study based on the World Health Survey Plus 2023

Por: Chhim · S. · Ku · G. V. · Kowal · P. · Te · V. · Sorithisey · M. · Ngor · C. · Walton · P. · Maung · K. T. · Ng · N. · Naidoo · N. · Por · I. · Klipstein-Grobusch · K. · Chhea · C. · Sopheab · H.
Objective

This study aimed to determine the prevalence and factors associated with pre-diabetes and undiagnosed type 2 diabetes (UDD) in Cambodia.

Design

This analysis used data from the WHO World Health Survey Plus, which was collected using a cross-sectional design with a GIS-based, three-stage sampling approach. Multiple logistic regression was used to identify key associated factors, based on a significance level of p

Setting

Data were collected from all 25 provinces in Cambodia between 12 March 2023 and 31 May 2023.

Participants

4427 individuals aged 18 years or older, residing in the selected household for at least 6 months in the past year.

Primary outcome measures

Pre-diabetes (Haemoglobin A1c (HbA1c) 5.7%–6.4%) and UDD (HbA1c≥6.5%), without prior knowledge of having type 2 diabetes (T2D).

Results

The weighted prevalences of pre-diabetes and UDD were 26.4% (95% CI 24.0% to 29.0%) and 9.3% (95% CI 7.9% to 11.0%). Pre-diabetes prevalence was higher in urban areas compared with rural areas (adjusted OR, aOR=1.2, 95% CI 1.0 to 1.4), males (aOR=1.7, 95% CI 1.3 to 2.3), individuals aged 40–49 (aOR=1.8, 95% CI 1.4 to 2.4), individuals aged 50+ years group (aOR=2.9, 95% CI 2.3 to 3.6) compared with the 18–39 years group, overweight individuals (aOR=1.7, 95% CI 1.4 to 2.0), obese (aOR=2.1, 95% CI 1.5 to 3.0) and those with elevated total triglycerides (aOR=1.3, 95% CI 1.1 to 1.5). Similar risk factors were identified for UDD, with the addition of hypertension (aOR=1.6, 95% CI 1.3 to 2.0) and high waist circumference (aOR=2.0, 95% CI 1.5 to 2.7).

Conclusions

The high prevalence of pre-diabetes and UDD in Cambodia is a pressing public health concern. Urgent and intensive interventions are needed to effectively prevent and manage T2D, particularly among urban residents, older persons and individuals with metabolic risk factors.

Anatomic versus reverse total shoulder replacement for patients with osteoarthritis and intact rotator cuff: the RAPSODI-UK randomised controlled trial protocol

Por: Rodrick · H. L. · Dias · J. · Watts · A. C. · Walton · M. J. · Brealey · S. · Page · R. · Foster · N. E. · Boland · K. · Cunningham · L. J. · Fairhurst · C. · Geoghegan · J. · Greenwood · W. · Hewitt · C. · Kirwan · C. · Leggett · H. · McDaid · C. · Parkes · M. · Parrott · S. · Powell · R.
Introduction

Shoulder osteoarthritis most commonly affects older adults, causing pain, reduced function and quality of life. Total shoulder replacements (TSRs) are indicated once other non-surgical options no longer provide adequate pain relief. Two main types of TSRs are widely used: anatomic TSR (aTSR) and reverse TSR (rTSR). It is not clear whether one TSR type provides better short- or long-term outcomes for patients, and which, if either, is more cost-effective for the National Health Service (NHS).

Methods and analysis

RAPSODI-UK is a multi-centre, pragmatic, two-parallel arm, superiority randomised controlled trial comparing the clinical- and cost-effectiveness of aTSR versus rTSR for adults aged 60+ with a primary diagnosis of osteoarthritis, an intact rotator cuff and bone stock suitable for TSR. Participants in both arms of the trial will receive usual post-operative rehabilitation. We aim to recruit 430 participants from approximately 28 NHS sites across the UK. The primary outcome is the Shoulder Pain and Disability Index (SPADI) at 2 years post-randomisation. Outcomes will be collected at 3, 6, 12, 18 and 24 months after randomisation. Secondary outcomes include the pain and function subscales of the SPADI, the Oxford Shoulder Score, health-related quality of life (EQ-5D-5L), complications, range of movement and strength, revisions and mortality. The between-group difference in the primary outcome will be derived from a constrained longitudinal data analysis model. We will also undertake a full health economic evaluation and conduct qualitative interviews to explore perceptions of acceptability of the two types of TSR and experiences of recovery with a sample of participants.

Ethics and dissemination

Ethics committee approval for this trial was obtained (London - Queen Square Research Ethics Committee, Rec Reference 22/LO/0617) on 4 October 2022. The results of the main trial will be submitted for publication in a peer-reviewed journal and using other professional and media outlets.

Trial registration number

ISRCTN12216466.

Preferences and predictors driving opioid-involved polysubstance use profiles and trajectories: a prospective cohort study protocol

Por: Campbell · M. · Lafayette · J. I. · Vallejo Vasquez · K. · Rivard · A. · Diamond · J. · Nguyen · C. · Caputo · D. · Lothumalla · S. · Rodriguez · C. R. · Tomlinson · D. C. · Bonar · E. E. · Goldstick · J. E. · Walton · M. · Lee · S. · Menke · N. · Lin · L. · Coughlin · L. N.
Introduction

Polysubstance use (PSU), particularly opioid-involved and stimulant-involved PSU, is a growing issue in the USA. PSU increases the risk of negative health consequences, including infectious diseases, worsening physical and mental health conditions, and overdose-related deaths. These consequences occur in the context of varying health risk behaviours, substance-related preferences, and treatment engagements among people with PSU. To inform improvements in prevention, harm reduction, and substance use disorder (SUD) treatment, additional research is needed to comprehensively understand the current context and drivers of PSU preferences, motivations, and behaviours.

Methods and analysis

Herein, we describe the protocol for a prospective cohort study designed to capture detailed patterns, profiles, and trajectories of PSU, with the aim of comprehensively examining the drivers of PSU behaviours and SUD treatment utilisation. Adults (ages 18–75; n=400) who engage in PSU will be recruited from healthcare institutions, an established participant database maintained by an adjacent SUD research team, and online advertisements. Study assessments will capture dynamic patterns, choice preferences, and motivators of PSU via behavioural economic (BE) measures, detailed Timeline Follow-Back (TLFB) interviews, and self-administered surveys. The assessment timeline will include a baseline survey and TLFB interview, weekly TLFB interviews for 4 weeks post-baseline, and follow-up surveys and TLFB interviews at 4-, 8-, and 12-months post-baseline.

Ethics and dissemination

The study is funded through the National Institutes of Health Helping to End Addiction Long-term (HEAL) initiative and was approved by the University of Michigan Medical Institutional Review Board. Findings will be disseminated to academic, clinical, and community partners through the Michigan Innovations in Addiction Care through Research and Education programme. Results from this study will inform actionable and practical insights relevant to the delivery of personalised care in the context of PSU.

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