Opposing roles for AMPK in regulating distinct mitophagy pathways.

Mitophagy degrades damaged mitochondria, but we show here that it can also target functional mitochondria. This latter scenario occurs during programmed mitophagy and involves the mitophagy receptors NIX and BNIP3. Although AMP-activated protein kinase (AMPK), the energy-sensing protein kinase, can influence damaged-induced mitophagy, its role in programmed mitophagy is unclear.

A qualitative study of the general practice experience of diagnosing and managing long COVID: Challenges and practical recommendations.

Background And Objectives: Patients with prolonged symptoms following COVID-19 infection(s) will increasingly present to general practice. Our research objective was to understand the general practice experience of diagnosing and managing long COVID and to explore recommendations for contributing to the safety and quality of the long COVID response.

Method: A two-hour qualitative session involving 11 project stakeholders was held in March 2023.

Locally adaptive inversions in structured populations.

Inversions have been proposed to facilitate local adaptation, by linking together locally coadapted alleles at different loci. Prior work addressing this question theoretically has considered the spread of inversions in "continent-island" scenarios in which there is a unidirectional flow of maladapted migrants into the island population. In this setting, inversions capturing locally adaptive haplotypes are most likely to invade when selection is weak, because stronger local selection (i) more effectively purges maladaptive alleles and (ii) generates linkage disequilibrium between adaptive alleles, thus lessening the advantage of inversions.

Gametic selection favours polyandry and selfing.

Competition among pollen or sperm (gametic selection) can cause evolution. Mating systems shape the intensity of gametic selection by determining the competitors involved, which can in turn cause the mating system itself to evolve. We model the bidirectional relationship between gametic selection and mating systems, focusing on variation in female mating frequency (monandry-polyandry) and self-fertilisation (selfing-outcrossing).

Differences in integrated assessment and management of non-communicable diseases (NCDs) for people with HIV across the WHO European region.

Objectives: We aimed to assess the extent of integration of non-communicable disease (NCD) assessment and management in HIV clinics across Europe.

Methods: A structured electronic questionnaire with 41 multiple-choice and rating-scale questions assessing NCD assessment and management was sent to 88 HIV clinics across the WHO European Region during March-May 2023. One response per clinic was collected.

Use of greyscale and Doppler ultrasound in initial evaluation and follow-up of neurovascular malformations in children.

Pediatric intracranial arteriovenous shunts are rare vascular malformations that can be diagnosed prenatally or postnatally, as an incidental finding or due to complications. We propose a review of cerebral vascular malformations in newborns and infants with special emphasis on neurosonography and Doppler ultrasound as the first diagnostic method. Sonography can thus contribute in the planning of further studies that are always necessary, and in post-therapy follow-up.

Scottish Index of Multiple Deprivation (SIMD) indicators as predictors of mortality among patients hospitalised with COVID-19 disease in the Lothian Region, Scotland during the first wave: a cohort study.

Background: Sars-CoV-2, the causative agent of COVID-19, has led to more than 226,000 deaths in the UK and multiple risk factors for mortality including age, sex and deprivation have been identified. This study aimed to identify which individual indicators of the Scottish Index of Multiple Deprivation (SIMD), an area-based deprivation index, were predictive of mortality.

Methods: This was a prospective cohort study of anonymised electronic health records of 710 consecutive patients hospitalised with Covid-19 disease between March and June 2020 in the Lothian Region of Southeast Scotland.

Strengths and weaknesses of the MABC-2 as a diagnostic tool for developmental coordination disorder: An online survey of occupational therapists and physiotherapists.

The Movement Assessment Battery for Children-2 (MABC-2) is the most widely used instrument for aiding the diagnosis of developmental coordination disorder (DCD). Despite being shown to have strong validity and reliability, it has received criticism for aspects of its scoring system, the lack of formal training, and its susceptibility to overlook higher functioning DCD children. To aid the development of future diagnostic tools and/or iterations of the MABC-2, the present study attempted to draw upon the experience of key stakeholders and determine the strengths and weaknesses of the MABC-2.

Performance status: A key factor in predicting mortality in the first wave of COVID-19 in South-East Scotland.

Background: COVID-19 mortality risk factors have been established in large cohort studies; long-term mortality outcomes are less documented.

Methods: We performed multivariable logistic regression to identify factors associated with in-patient mortality and intensive care unit (ICU) admission in symptomatic COVID-19 patients admitted to hospitals in South-East Scotland from 1st March to 30th June 2020. One-year mortality was reviewed.

Differential roles and regulation of the protein kinases PAK4, PAK5 and PAK6 in melanoma cells.

The protein kinases PAK4, PAK5 and PAK6 comprise a family of ohnologues. In multiple cancers including melanomas PAK5 most frequently carries non-synonymous mutations; PAK6 and PAK4 have fewer; and PAK4 is often amplified. To help interpret these genomic data, initially we compared the cellular regulation of the sister kinases and their roles in melanoma cells.

Randomised controlled trial of intravenous nafamostat mesylate in COVID pneumonitis: Phase 1b/2a experimental study to investigate safety, Pharmacokinetics and Pharmacodynamics.

Background: Many repurposed drugs have progressed rapidly to Phase 2 and 3 trials in COVID19 without characterisation of Pharmacokinetics /Pharmacodynamics including safety data. One such drug is nafamostat mesylate.

Methods: We present the findings of a phase Ib/IIa open label, platform randomised controlled trial of intravenous nafamostat in hospitalised patients with confirmed COVID-19 pneumonitis.

Evaluation of new or repurposed treatments for COVID-19: protocol for the phase Ib/IIa DEFINE trial platform.

Introduction: COVID-19 is a new viral-induced pneumonia caused by infection with a novel coronavirus, SARS-CoV-2. At present, there are few proven effective treatments. This early-phase experimental medicine protocol describes an overarching and adaptive trial designed to provide safety data in patients with COVID-19, pharmacokinetic (PK)/pharmacodynamic (PD) information and exploratory biological surrogates of efficacy, which may support further development and deployment of candidate therapies in larger scale trials of patients positive for COVID-19.

Equity for excellence in academic institutions: a manifesto for change.

Higher academic institutions in the UK need to drive improvements in equity, diversity, and inclusion (EDI) through sustainable practical interventions. A broad view of inclusivity is based on an intersectional approach that considers race, geographical location, caring responsibilities, disability, neurodiversity, religion, and LGBTQIA+ identities. We describe the establishment of a diverse stakeholder group to develop practical grass-roots recommendations through which improvements can be advanced.

Evaluation of cross-grazing deer with sheep or cattle, as means to reduces anthelmintic usage to control gastrointestinal and pulmonary nematodes in farmed red deer (Cervus elaphus) in New Zealand.

Recent reports indicate that gastrointestinal nematodes (GIN) are contributing to significant losses in deer productivity and that anthelmintic resistance has become an issue of concern for deer farmers in New Zealand. The aim of this study was to evaluate cross-grazing of deer with sheep or cattle as an aid for control of gastrointestinal and pulmonary nematode parasites of farmed red deer (Cervus elaphus) in New Zealand. This was a field study replicated over two years (2012 and 2013) for 16 weeks each year at two locations (Massey University, Palmerston North and Invermay AgResearch Centre, Mosgiel).

Diagnostic performance of the combined nasal and throat swab in patients admitted to hospital with suspected COVID-19.

Background: Accurate diagnosis in patients with suspected coronavirus disease 2019 (COVID-19) is essential to guide treatment and limit spread of the virus. The combined nasal and throat swab is used widely, but its diagnostic performance is uncertain.

Methods: In a prospective, multi-centre, cohort study conducted in secondary and tertiary care hospitals in Scotland, we evaluated the combined nasal and throat swab with reverse transcriptase-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in consecutive patients admitted to hospital with suspected COVID-19.

Glucocorticoid receptor Thr524 phosphorylation by MINK1 induces interactions with 14-3-3 protein regulators.

The glucocorticoid receptor (GR) is a ligand-dependent transcription factor that plays a central role in inflammation. The GR activity is also modulated via protein-protein interactions, including binding of 14-3-3 proteins induced by GR phosphorylation. However, the specific phosphorylation sites on the GR that trigger these interactions and their functional consequences are less clear.

X-linked meiotic drive can boost population size and persistence.

X-linked meiotic drivers cause X-bearing sperm to be produced in excess by male carriers, leading to female-biased sex ratios. Here, we find general conditions for the spread and fixation of X-linked alleles. Our conditions show that the spread of X-linked alleles depends on sex-specific selection and transmission rather than the time spent in each sex.

Association of Coffee Intake With Survival in Patients With Advanced or Metastatic Colorectal Cancer.

Importance: Several compounds found in coffee possess antioxidant, anti-inflammatory, and insulin-sensitizing effects, which may contribute to anticancer activity. Epidemiological studies have identified associations between increased coffee consumption and decreased recurrence and mortality of colorectal cancer. The association between coffee consumption and survival in patients with advanced or metastatic colorectal cancer is unknown.

Does location matter? Characterisation of the anatomic locations, molecular profiles, and clinical features of gliomas.

Background: Neuroanatomic locations of gliomas may influence clinical presentations, molecular profiles, and patients' prognoses.

Methods: We investigated our institutional cancer registry to include patients with glioma over a 10-year period. Statistical tests were used to compare demographic, genetic, and clinical characteristics among patients with gliomas in different locations.

Inequitable access to an outpatient parenteral antimicrobial therapy service: linked cross-sectional study.

Study Aim: To assess whether Outpatient Parenteral Antimicrobial Therapy (OPAT) is provided equitably across gender and social groups in a tertiary care setting.

Background: OPAT is a widely used and growing approach in high income countries to early discharge or admission avoidance for patients requiring intravenous antimicrobials. There is however a risk that equitable access to healthcare could be eroded unintentionally by expansion of outpatient or ambulatory approaches such as this.