Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al

Effects of Subjective Memory Complaints (SMCs) and Social Capital on Self-Rated Health (SRH) in a Semirural Malaysian Population

Daniel Reidpath - ORCID: 0000-0002-8796-0420 https://orcid.org/0000-0002-8796-0420Subjective memory complaints (SMCs) and social capital were known to be related to self-rated health (SRH). Despite this, no studies have examined the potential interaction of SMC and social capital on SRH. Using data from a cross-sectional health survey of men and women aged 56 years and above (n = 6,421), we examined how SMCs and social capital explained SRH in a population of community-dwelling older adults in a semirural area in Malaysia. We also evaluated whether SRH’s relationship with SMCs is moderated by social capital. The association of SMC and social capital with poor SRH was investigated using multivariable logistic regression. Social capital (OR = 0.86, 95% CI = 0.82–0.89), mild SMC (OR = 1.70, 95% CI = 1.50–1.94), and moderate SMC (OR = 1.90, 95% CI = 1.63–2.20) were found to be associated with poor SRH after adjustment for sociodemographic factors and depression in the initial regression model. SMC was found to have partial interaction effects with social capital which was included in the subsequent regression model. Unlike individuals with no SMC and mild SMC, those who reported moderate SMC did not show decreasing probabilities of poor SRH despite increasing levels of social capital. Nevertheless, this analysis suggests that social capital and SMC are independent predictors of poor SRH. Further research needs to be targeted at improving the understanding on how social capital and SMC moderate and interact with the perception of health in older adults.https://doi.org/10.1155/2019/915180

Are Ethnic and Gender Specific Equations Needed to Derive Fat Free Mass from Bioelectrical Impedance in Children of South Asian, Black African-Caribbean and White European Origin? Results of the Assessment of Body Composition in Children Study

Background Bioelectrical impedance analysis (BIA) is a potentially valuable method for assessing lean mass and body fat levels in children from different ethnic groups. We examined the need for ethnic- and gender-specific equations for estimating fat free mass (FFM) from BIA in children from different ethnic groups and examined their effects on the assessment of ethnic differences in body fat. Methods Cross-sectional study of children aged 8–10 years in London Primary schools including 325 South Asians, 250 black African-Caribbeans and 289 white Europeans with measurements of height, weight and arm-leg impedance (Z; Bodystat 1500). Total body water was estimated from deuterium dilution and converted to FFM. Multilevel models were used to derive three types of equation {A: FFM = linear combination(height+weight+Z); B: FFM = linear combination(height2/Z); C: FFM = linear combination(height2/Z+weight)}. Results Ethnicity and gender were important predictors of FFM and improved model fit in all equations. The models of best fit were ethnicity and gender specific versions of equation A, followed by equation C; these provided accurate assessments of ethnic differences in FFM and FM. In contrast, the use of generic equations led to underestimation of both the negative South Asian-white European FFM difference and the positive black African-Caribbean-white European FFM difference (by 0.53 kg and by 0.73 kg respectively for equation A). The use of generic equations underestimated the positive South Asian-white European difference in fat mass (FM) and overestimated the positive black African-Caribbean-white European difference in FM (by 4.7% and 10.1% respectively for equation A). Consistent results were observed when the equations were applied to a large external data set. Conclusions Ethnic- and gender-specific equations for predicting FFM from BIA provide better estimates of ethnic differences in FFM and FM in children, while generic equations can misrepresent these ethnic differences

A pilot randomized controlled study of the mental health first aid elearning course with UK medical students

Background: Medical students face many barriers to seeking out professional help for their mental health, including stigma relating to mental illness, and often prefer to seek support and advice from fellow students. Improving medical students’ mental health literacy and abilities to support someone experiencing a mental health problem could reduce barriers to help seeking and improve mental health in this population. Mental Health First Aid (MHFA) is an evidence-based intervention designed to improve mental health literacy and ability to respond to someone with a mental health problem. This pilot randomised controlled trial aims to evaluate the MHFA eLearning course in UK medical students. Methods: Fifty-five medical students were randomised to receive six weeks access to the MHFA eLearning course (n = 27) or to a no-access control group (n = 28). Both groups completed baseline (pre-randomisation) and follow-up (six weeks post-randomisation) online questionnaires measuring recognition of a mental health problem, mental health first aid intentions, confidence to help a friend experiencing a mental health problem, and stigmatising attitudes. Course feedback was gathered at follow-up. Results: More participants were lost follow-up in the MHFA group (51.9%) compared to control (21.4%). Both intention-to-treat (ITT) and non-ITT analyses showed that the MHFA intervention improved mental health first aid intentions (p = <.001) and decreased stigmatising attitudes towards people with mental health problems (p = .04). While ITT analysis found no significant Group x Time interaction for confidence to help a friend, the non-ITT analysis did show the intervention improved confidence to help a friend with mental health problems (p =<.001), and improved mental health knowledge (p = .003). Medical students in the intervention group reported a greater number of actual mental health first aid actions at follow-up (p = .006). Feedback about the MHFA course was generally positive, with participants stating it helped improve their knowledge and confidence to help someone. Conclusion: This pilot study demonstrated the potential for the MHFA eLearning course to improve UK medical students’ mental health first aid skills, confidence to help a friend and stigmatising attitudes. It could be useful in supporting their own and others’ mental health while studying and in their future healthcare careers

A comparison of time taken to return to baseline erectile function following focal and whole gland ablative therapies for localized prostate cancer: A systematic review

OBJECTIVES: To systematically review erectile function (EF) outcomes following primary whole gland (WG) and focal ablative therapies for localized prostate cancer to ascertain whether the treatment modality or intended treatment volume affects the time taken to recover baseline EF. METHOD AND MATERIALS: A systematic review was performed according to the preferred reporting items for systematic review and meta-analysis statement. Inclusion criteria were men with localized prostate cancer treated with primary, ablative therapy. Primary outcome was the return to baseline EF measured with objective, validated symptoms scores. Secondary outcome was use of phosphodiesterase inhibitors or erectile aids. Meta-analysis was not performed owing to heterogenous outcome measures. RESULTS: Of 222 articles identified in February 2017, 55 studies which reported EF after ablative therapy were identified but only 17 used validated outcome measures and met inclusion criteria. WG cryotherapy was used in 2 studies, WG high-intensity focused ultrasound (HIFU) in 5, focal cryotherapy in 2, focal HIFU in 3, focal phototherapy or laser therapy in 4, vascular-targeted photodynamic therapy in 3, and irreversible electroporation in 2. WG cryotherapy was associated with a significant decline in EF at 6 months with minimal improvement at 36 months. Baseline IIEF-15 of patients undergoing focal HIFU fell 30 points at 1 month but returned to baseline by 6 months. The remaining focal therapies demonstrated minimal or no effect on EF, but the men in these studies had small foci of disease. The review is limited by lack of randomized studies and heterogenous outcome measures. CONCLUSIONS: Most studies assessing the outcomes of focal therapy on sexual function were not of high quality, used heterogenous outcomes, and had relatively short follow up, highlighting the need for more robustly designed studies using validated patient reported outcome measures  for comparison. However, FT in general resulted in less effect on EF than WG ablation

Link Between Dietary Sodium Intake, Cognitive Function, and Dementia Risk in Middle-Aged and Older Adults: A Systematic Review

Daniel Reidpath - ORCID: 0000-0002-8796-0420 https://orcid.org/0000-0002-8796-0420Background: A key focus for dementia risk-reduction is the prevention of socio-demographic, lifestyle, and nutritional risk factors. High sodium intake is associated with hypertension and cardiovascular disease (both are linked to dementia), generating numerous recommendations for salt reduction to improve cardiovascular health. Objective: This systematic review aimed to assess, in middle- and older-aged people, the relationship between dietary sodium intake and cognitive outcomes including cognitive function, risk of cognitive decline, or dementia. Methods: Six databases (PubMed, EMBASE, CINAHL, Psych info, Web of Science, and Cochrane Library) were searched from inception to 1 March 2020. Data extraction included information on study design, population characteristics, sodium reduction strategy (trials) or assessment of dietary sodium intake (observational studies), measurement of cognitive function or dementia, and summary of main results. Risk-of-bias assessments were performed using the National Heart, Lung, and Blood Institute (NHLBI) assessment tool. Results: Fifteen studies met the inclusion criteria including one clinical trial, six cohorts, and eight cross-sectional studies. Studies reported mixed associations between sodium levels and cognition. Results from the only clinical trial showed that a lower sodium intake was associated with improved cognition over six months. In analysis restricted to only high-quality studies, three out of four studies found that higher sodium intake was associated with impaired cognitive function. Conclusion: There is some evidence that high salt intake is associated with poor cognition. However, findings are mixed, likely due to poor methodological quality, and heterogeneous dietary, analytical, and cognitive assessment methods and design of the studies. Reduced sodium intake may be a potential target for intervention. High quality prospective studies and clinical trials are needed.https://doi.org/10.3233/JAD-19133976pubpub

What's wrong with John? A randomised controlled trial of Mental Health First Aid (MHFA) training with nursing students

BACKGROUND: The prevalence of mental health problems have been found to be higher among university students compared to their non-student peers. Nursing students in particular face a range of additional stressors which may impact their undergraduate performance and their careers. Mental Health First Aid (MHFA) aims to increase mental health literacy and to reduce stigma and may positively impact on the student population. This paper describes a MHFA randomised controlled trial targeting nursing students at a large Australian university. This study aimed to measure the impact of the MHFA course on mental health literacy, mental health first aid intentions, confidence in helping someone with a mental health problem and stigmatising attitudes including social distance. METHODS: Participants were first year nursing students (n = 181) randomly allocated to the intervention (n = 92) or control (n = 89) group. Intervention group participants received the standardised MHFA course for nursing students. Online self-report questionnaires were completed at three time intervals: baseline (one week prior to the intervention: T1) (n = 140), post intervention (T2) (n = 120), and two months post intervention (T3) (n = 109). Measures included demographics, mental health knowledge, recognition of depression, confidence in helping, mental health first aid intentions and stigmatising attitudes including social distance. Repeated measures ANOVA was computed to measure if the impact of time (T1, T2, T3) and group (intervention and control) on the outcome variables. RESULTS: There was a significant improvement among intervention compared to control group participants across the three time periods for knowledge scores (p &lt; 0.001), confidence in helping (p &lt; 0.001), mental health first aid intentions (p &lt; 0.001), total personal stigma (p &lt; 0.05), personal dangerous/unpredictable stigma (p &lt; 0.05) and social distance (p &lt; 0.05) scores. CONCLUSION: MHFA is useful training to embed in university courses and has the potential to enhance mental health literacy and reduce stigmatising attitudes and social distance. While this course has particular salience for nursing and other health science students, there are broader benefits to the general university population that should be considered and opportunities accordingly explored for all students to complete the course. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12614000861651 . Retrospectively registered 11 August 2014