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Little is understood about the relationship between glycated haemoglobin and future functional health in the general population. In this work, we aimed to assess if glycaemic control is associated with future physical and mental functional health at 18-month follow-up in a UK general population, in those with and without diabetes. This work was a cross-sectional study. Between 1995 and 1997, participants of the European Prospective Investigation into Cancer, Norfolk, attended a health check including blood testing for haemoglobin A1c (HbA1c) and completed a health and lifestyle questionnaire. Eighteen months later, self-reported physical and mental functional health were assessed using short form-36 (SF-36). Outcomes of interest included physical and mental component summary (PCS and MCS, respectively) scores of the SF-36. A total of 7343 participants (56% women, mean (SD) 58.1 ± 9.5 years) were eligible to be included, of whom 167 had prevalent diabetes. In our linear regression analysis, a higher HbA1c (mmol/mol) was found to be associated with a poorer PCS score (coefficient -0.15 ( p < 0.0001)) at follow-up. After adjustment for comorbid conditions, including obesity, this association was no longer statistically significant. A higher HbA1c (mmol/mol) was associated with a better MCS score at follow-up; this finding was significant when adjusted for comorbid conditions (coefficient 0.029 ( p < 0.05)). Our findings suggest that the association between a higher HbA1c and poorer physical functional health is explained by a higher BMI and comorbidity status in a general population. While higher HbA1c was found to be associated with higher mental functional health at follow-up, the magnitude of this association was small. Healthy responder bias and unmeasured confounding variables may have influenced this result; thus, it should be interpreted with caution.

Elite and semielite athletes commonly experience mental health concerns and disorders. Compared with men athletes, women athletes are at greater risk of a range of psychological stressors that contribute to health concerns and mental health disorders, which can impact their career satisfaction and longevity. In order to address and improve the mental health of women athletes, it is necessary to simultaneously tackle the gender specific psychosocial stressors that contribute to mental health outcomes. This narrative review examines the gender-specific stressors that affect mental health and well-being in women athletes, some of which are modifiable. Psychosocial stressors identified include exposure to violence, be it psychological, physical or sexual in nature, which can result in a myriad of acute and long-lasting symptoms; and inequities as reflected in pay disparities, under-representation in the media, fewer opportunities in leadership positions and implications associated with family planning and motherhood. Strategies to promote mental health in women athletes should be considered, and where possible, should proactively address gender-specific stressors likely to influence mental health in order to maximise positive outcomes in women athletes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Heterozygous de novo mutations in EEF1A2, encoding the tissue-specific translation elongation factor eEF1A2, have been shown to cause neurodevelopmental disorders including often severe epilepsy and intellectual disability. The mutational profile is unusual; ~50 different missense mutations have been identified but no obvious loss of function mutations, though large heterozygous deletions are known to be compatible with life. A key question is whether the heterozygous missense mutations operate through haploinsufficiency or a gain of function mechanism, an important prerequisite for design of therapeutic strategies. In order both to address this question and to provide a novel model for neurodevelopmental disorders resulting from mutations in EEF1A2, we created a new mouse model of the D252H mutation. This mutation causes the eEF1A2 protein to be expressed at lower levels in brain but higher in muscle in the mice. We compared both heterozygous and homozygous D252H and null mutant mice using behavioural and motor phenotyping alongside molecular modelling and analysis of binding partners. Although the proteomic analysis pointed to a loss of function for the D252H mutant protein, the D252H homozygous mice were more severely affected than null homozygotes on the same genetic background. Mice that are heterozygous for the missense mutation show no behavioural abnormalities but do have sex-specific deficits in body mass and motor function. The phenotyping of our novel mouse lines, together with analysis of molecular modelling and interacting proteins, suggest that the D252H mutation results in a gain of function., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Researchers, policy makers, and practitioners increasingly pay attention to sport and physical activity as a means and context for refugee wellbeing and integration, influenced by wider political and policy concerns about forced migration. Considering this growing scholarly and policy attention, it is timely to take stock of, and critically reflect on, recent developments in this field of research. This paper offers an integrative, critical review of the scientific literature on the topic. It critically synthesizes what is known about the sport and physical activity experiences of people with refugee and forced migrant backgrounds, and identifies key issues and directions for future research in this field. This review of contemporary academic literature comprises 83 publications derived from fourteen languages published between 1996 and 2019. It shows a substantial increase in the volume of published research on the topic in recent years (2017-2019). Published research is concentrated primarily in Western countries around the themes of health promotion, integration and social inclusion, and barriers and facilitators to participation in sport and physical activity. The findings foreground the use of policy categories, deficit approaches, and intersectionalities as three pressing challenges in this area of research. Based on this synthesis, the authors identify four research gaps that require attention in future research: the experiential (embodied emotional) dimensions of sport and physical activity, the need to decolonize research, the space for innovative methodologies, and research ethics., (Copyright © 2019 Spaaij, Broerse, Oxford, Luguetti, McLachlan, McDonald, Klepac, Lymbery, Bishara and Pankowiak.)

The multi-subunit eEF1 complex plays a crucial role in de novo protein synthesis. The central functional component of the complex is eEF1A, which occurs as two independently encoded variants with reciprocal expression patterns: whilst eEF1A1 is widely expressed, eEF1A2 is found only in neurons and muscle. Heterozygous mutations in the gene encoding eEF1A2, EEF1A2, have recently been shown to cause epilepsy, autism, and intellectual disability. The remaining subunits of the eEF1 complex, eEF1Bα, eEF1Bδ, eEF1Bγ, and valyl-tRNA synthetase (VARS), together form the GTP exchange factor for eEF1A and are ubiquitously expressed, in keeping with their housekeeping role. However, mutations in the genes encoding these subunits EEF1B2 (eEF1Bα), EEF1D (eEF1Bδ), and VARS (valyl-tRNA synthetase) have also now been identified as causes of neurodevelopmental disorders. In this review, we describe the mutations identified so far in comparison with the degree of normal variation in each gene, and the predicted consequences of the mutations on the functions of the proteins and their isoforms. We discuss the likely effects of the mutations in the context of the role of protein synthesis in neuronal development., (© 2018 Crown copyright. Human Mutation © 2018 Wiley Periodicals, Inc.)

Background: Many effects of statins on non-cardiovascular disease (non-CVD) outcomes have been reported., Purpose: To evaluate the quantity, validity, and credibility of evidence regarding associations between statins and non-CVD outcomes and the effects of statins on these outcomes., Data Sources: MEDLINE and EMBASE (English terms only, inception to 28 May 2018)., Study Selection: Meta-analyses (published in English) of observational studies and of randomized controlled trials (RCTs) that examined non-CVD outcomes of statin intake., Data Extraction: Two investigators extracted data from meta-analyses and individual studies. Credibility assessments based on summary effect sizes from a random-effects model, between-study heterogeneity, 95% prediction interval, small-study effect, excess significance, and credibility ceilings were devised to classify evidence., Data Synthesis: This review explored 278 unique non-CVD outcomes from 112 meta-analyses of observational studies and 144 meta-analyses of RCTs. For observational studies, no convincing (class I) evidence, 2 highly suggestive (class II) associations (decreased cancer mortality in patients with cancer and decreased exacerbation in patients with chronic obstructive pulmonary disease), 21 suggestive (class III) associations, and 42 weak (class IV) associations were identified. One outcome from the RCTs (decreased all-cause mortality in patients with chronic kidney disease) attained a sufficient amount of evidence with no hints of bias. For adverse events, observational studies showed suggestive evidence that statins increase the risk for diabetes and myopathy. Among the RCTs, no statistically significant effects were found on myopathy, myalgia, or rhabdomyolysis., Limitations: Studies with relevant data and outcomes not included in the meta-analyses may have been missed. Credibility assessments relied on several assumptions and arbitrary thresholds., Conclusion: The absence of convincing evidence of an association between statins and non-CVD outcomes supports leaving the current recommendations unchanged., Primary Funding Source: None.

De novo heterozygous missense mutations in the gene encoding translation elongation factor eEF1A2 have recently been found to give rise to neurodevelopmental disorders. Children with mutations in this gene have developmental delay, epilepsy, intellectual disability and often autism; the most frequently occurring mutation is G70S. It has been known for many years that complete loss of eEF1A2 in mice causes motor neuron degeneration and early death; on the other hand heterozygous null mice are apparently normal. We have used CRISPR/Cas9 gene editing in the mouse to mutate the gene encoding eEF1A2, obtaining a high frequency of biallelic mutations. Whilst many of the resulting founder (F0) mice developed motor neuron degeneration, others displayed phenotypes consistent with a severe neurodevelopmental disorder, including sudden unexplained deaths and audiogenic seizures. The presence of G70S protein was not sufficient to protect mice from neurodegeneration in G70S/- mice, showing that the mutant protein is essentially non-functional.

The facile syntheses and the structures of five new Cu(I) alkynyl clusters, [Cu(12)(hfac)(8)(C[triple chemical bond]CnPr)(4)(thf)(6)]xTHF (1), [Cu(12)(hfac)(8)(C[triple chemical bond]CtBu)(4)] (2), [Cu(12)(hfac)(8)(C[triple chemical bond]CSiMe(3))(4)] (3), [Cu(10)(hfac)(6)(C[triple chemical bond]CtBu)(4)(diethyl ether)]/[Cu(10)(hfac)(6)(C[triple chemical bond]CtBu)(3)(C[triple chemical bond]CnPr)(diethyl ether)] (4) and [Cu(10)(hfac)(6)(C[triple chemical bond]CtBu)(4)(diethyl ether)] (5) are reported, in which hfacH=1,1,1,5,5,5-hexafluoropentan-2,4-dione. The first independent molecule found in the crystals of 4 (4 a) proved to be chemically identical to 5. The Cu(10) and Cu(12) cores in these clusters are based on a central "square" Cu(4)C(4) unit. Whilst the connectivities of the Cu(10) or Cu(12) units remain identical the geometries vary considerably and depend on the bulk of the alkynyl group, weak coordination of ether molecules to copper atoms in the core and CuO intramolecular contacts formed between Cu-hfac units on the periphery of the cluster. Similar intermolecular contacts and interlocking of Cu-hfac units are formed in the simple model complex [Cu(2)(hfac)(2)(HC[triple chemical bond]CtBu)] (6). When linear alkynes, C(n)H(2n+1)C[triple chemical bond]CH, are used in the synthesis and non-coordinating solvents are used in the workup, further association of the Cu(4)C(4) cores occurs and clusters with more than eighteen copper atoms are isolated.