Familial hypercholesterolaemia: the Cape Town experience

Familial hypercholesterolaemia (FH), an autosomal dominantly inherited disorder characterised by elevated plasma low-density lipoprotein (LDL) cholesterol levels, tendon xanthomata and premature ischaemic heart disease, is amenable to treatment with modern medication. The clinical and biochemical details of 1 031 patients with FH were analysed. FH is the most common monogenic disorder of lipoprotein metabolism presenting to the Lipid Clinic at Groote Schuur Hospital, accounting for about 20% of consultations. The hospital classified 55% of the FH patients as white, 43% as coloured, 1.5% as Asian and 0.5% as black. In the FH cohort (whose mean age at presentation was 44 years), 80% had tendon xanthomata, 36% had arcus cornealis, and 14% had xanthelasma. Tendon xanthomata was present in almost 90% of patients by the age of 50 years. Arcus cornealis was present in about 45% by the age of 40 years, further increasing in frequency with age. Cardiovascular complications included ischaemic heart disease (43%), stroke (1.5%), transient ischaemic attacks (1.3%), and peripheral vascular disease (3.7%). The mean age of death was 55 (+13) years; 51 (+10) years in men and 61 (+12) years in women. In 46% of the cohort, a defective gene was identified by testing for locally prevalent mutations

Cognitive ability experiment with photosensitive organic molecular thin films

We present an optical experiment which permits to evaluate the information exchange necessary to self-induce cooperatively a well-organized pattern in a randomly activated molecular assembly. A low-power coherent beam carrying polarization and wavelength information is used to organize a surface relief grating on a photochromic polymer thin film which is photo-activated by a powerful incoherent beam. We demonstrate experimentally that less than 1% of the molecules possessing information cooperatively transmit it to the entire photo-activated polymer film.Comment: 16 pages, 4 figure

Familial Hypercholesterolaemia: The Cape Town Experience

Familial hypercholesterolaemia (FH), an autosomal dominantly inherited disorder characterised by elevated plasma LDL cholesterol levels, tendon xanthomata and premature ischaemic heart is amenable to treatment with modern medication. There is a paucity of clinical information on FH in South Africa. The clinical and biochemical details of 1031 patients who attended the lipid clinic at Groote Schuur Hospital with this diagnosis have been analysed. FH is the commonest monogenic disorder of lipoprotein metabolism presenting to the Lipid Clinic at Groote Schuur Hospital, accounting for about 20% of consultations. The hospital classified 55% of the FH patients as White, 43% as Coloured, 1.5% as Asian and 0.5% as Black. In the FH cohort, whose mean age at presentation was 44 years, 80% had tendon xanthomata, 36% had arcus cornealis and 14% had xanthelasma. Tendon xanthomata were present in almost 90% of patients by the age of 50 years. Arcus cornealis was present in about 45% by the age of 40 years, increasing further with age. Cardiovascular complications included ischaemic heart disease (43%), stroke (1.5%), transient ischaemic attacks (1.3%) and peripheral vascular disease (3.7%). The mean age of death was 55 (±13) years; 51 (±10) years in men and 61 (±12) years in women. In 46% of the cohort a defective gene was identified by testing for locally prevalent mutations. FH is a common, serious disease that can be diagnosed by clinical manifestations and routine laboratory tests at primary healthcare level. FH affects all ethnic groups in South Africa Effective treatment is available to prevent early and debilitating coronary disease but requires recognition and referral

Prediction of 7-year psychopathology from mother-infant joint attention behaviours: a nested case–control study

<br>Background: To investigate whether later diagnosis of psychiatric disorder can be predicted from analysis of mother-infant joint attention (JA) behaviours in social-communicative interaction at 12 months.</br> <br>Method: Using data from a large contemporary birth cohort, we examined 159 videos of a mother-infant interaction for joint attention behaviour when children were aged one year, sampled from within the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Fifty-three of the videos involved infants who were later considered to have a psychiatric disorder at seven years and 106 were same aged controls. Psychopathologies included in the case group were disruptive behaviour disorders, oppositional-conduct disorder, attention-deficit/hyperactivity disorder, pervasive development disorder, anxiety and depressive disorders. Psychiatric diagnoses were obtained using the Development and Wellbeing Assessment when the children were seven years old.</br> <br>Results: None of the three JA behaviours (shared look rate, shared attention rate and shared attention intensity) showed a significant association with the primary outcome of case–control status. Only shared look rate predicted any of the exploratory sub-diagnosis outcomes and was found to be positively associated with later oppositional-conduct disorders (OR [95% CI]: 1.5 [1.0, 2.3]; p = 0.041).</br><br>Conclusions: JA behaviours did not, in general, predict later psychopathology. However, shared look was positively associated with later oppositional-conduct disorders. This suggests that some features of JA may be early markers of later psychopathology. Further investigation will be required to determine whether any JA behaviours can be used to screen for families in need of intervention.</br&gt

Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus

Objective: Recently approved direct acting antivirals provide transformative therapies for chronic hepatitis C virus (HCV) infection. The major clinical challenge remains to identify the undiagnosed patients worldwide, many of whom live in low-income and middle-income countries, where access to nucleic acid testing remains limited. The aim of this study was to develop and validate a point-of-care (PoC) assay for the qualitative detection of HCV RNA. Design: We developed a PoC assay for the qualitative detection of HCV RNA on the PCR Genedrive instrument. We validated the Genedrive HCV assay through a case–control study comparing results with those obtained with the Abbott RealTime HCV test. Results: The PoC assay identified all major HCV genotypes, with a limit of detection of 2362 IU/mL (95% CI 1966 to 2788). Using 422 patients chronically infected with HCV and 503 controls negative for anti-HCV and HCV RNA, the Genedrive HCV assay showed 98.6% sensitivity (95% CI 96.9% to 99.5%) and 100% specificity (95% CI 99.3% to 100%) to detect HCV. In addition, melting peak ratiometric analysis demonstrated proof-of-principle for semiquantification of HCV. The test was further validated in a real clinical setting in a resource-limited country. Conclusion: We report a rapid, simple, portable and accurate PoC molecular test for HCV, with sensitivity and specificity that fulfils the recent FIND/WHO Target Product Profile for HCV decentralised testing in low-income and middle-income countries. This Genedrive HCV assay may positively impact the continuum of HCV care from screening to cure by supporting real-time treatment decisions

Not all coping strategies are created equal: a mixed methods study exploring physicians' self reported coping strategies

<p>Abstract</p> <p>Background</p> <p>Physicians experience workplace stress and draw on different coping strategies. The primary goal of this paper is to use interview data to explore physicians' self reported coping strategies. In addition, questionnaire data is utilized to explore the degree to which the coping strategies are used and are associated with feelings of emotional exhaustion, a key symptom of burnout.</p> <p>Methods</p> <p>This mixed methods study explores factors related to physician wellness within a large health region in Western Canada. This paper focuses on the coping strategies that physicians use in response to work-related stress. The qualitative component explores physicians' self reported coping strategies through open ended interviews of 42 physicians representing diverse medical specialties and settings (91% response rate). The major themes extracted from the qualitative interviews were used to construct 12 survey items that were included in the comprehensive quantitative questionnaire. Questionnaires were sent to all eligible physicians in the health region with 1178 completed surveys (40% response rate.) Questionnaire items were used to measure how often physicians draw on the various coping strategies. Feelings of burnout were also measured in the survey by 5 items from the Emotional Exhaustion subscale of the revised Maslach Burnout Inventory.</p> <p>Results</p> <p>Major themes identified from the interviews include coping strategies used at work (e.g., working through stress, talking with co-workers, taking a time out, using humor) and after work (e.g., exercise, quiet time, spending time with family). Analysis of the questionnaire data showed three often used workplace coping strategies were positively correlated with feeling emotionally exhausted (i.e., keeping stress to oneself (r = .23), concentrating on what to do next (r = .16), and going on as if nothing happened (r = .07)). Some less often used workplace coping strategies (e.g., taking a time out) and all those used after work were negatively correlated with frequency of emotional exhaustion.</p> <p>Conclusions</p> <p>Physicians' self reported coping strategies are not all created equal in terms of frequency of use and correlation with feeling emotionally exhausted from one's work. This knowledge may be integrated into practical physician stress reduction interventions.</p

The differential hormonal milieu of morning versus evening, may have an impact on muscle hypertrophic potential

Substantial gains in muscle strength and hypertrophy are clearly associated with the routine performance of resistance training. What is less evident is the optimal timing of the resistance training stimulus to elicit these significant functional and structural skeletal muscle changes. Therefore, this investigation determined the impact of a single bout of resistance training performed either in the morning or evening upon acute anabolic signalling (insulin-like growth factor-binding protein-3 (IGFBP-3), myogenic index and differentiation) and catabolic processes (cortisol). Twenty-four male participants (age 21.4±1.9yrs, mass 83.7±13.7kg) with no sustained resistance training experience were allocated to a resistance exercise group (REP). Sixteen of the 24 participants were randomly selected to perform an additional non-exercising control group (CP) protocol. REP performed two bouts of resistance exercise (80% 1RM) in the morning (AM: 0800 hrs) and evening (PM: 1800 hrs), with the sessions separated by a minimum of 72 hours. Venous blood was collected immediately prior to, and 5 min after, each resistance exercise and control sessions. Serum cortisol and IGFBP-3 levels, myogenic index, myotube width, were determined at each sampling period. All data are reported as mean ± SEM, statistical significance was set at P≤0.05. As expected a significant reduction in evening cortisol concentration was observed at pre (AM: 98.4±10.5, PM: 49.8±4.4 ng/ml, P0.05). Timing of resistance training regimen in the evening appears to augment some markers of hypertrophic potential, with elevated IGFBP-3, suppressed cortisol and a superior cellular environment. Further investigation, to further elucidate the time course of peak anabolic signalling in morning vs evening training conditions, are timely

Advancing the global physical activity agenda: recommendations for future research by the 2020 WHO physical activity and sedentary behavior guidelines development group.

Funder: Public Health Agency of CanadaFunder: Government of NorwayBACKGROUND: In July, 2019, the World Health Organization (WHO) commenced work to update the 2010 Global Recommendations on Physical Activity for Health and established a Guideline Development Group (GDG) comprising expert public health scientists and practitioners to inform the drafting of the 2020 Guidelines on Physical Activity and Sedentary Behavior. The overall task of the GDG was to review the scientific evidence and provide expert advice to the WHO on the amount of physical activity and sedentary behavior associated with optimal health in children and adolescents, adults, older adults (> 64 years), and also specifically in pregnant and postpartum women and people living with chronic conditions or disabilities. METHODS: The GDG reviewed the available evidence specific to each sub-population using systematic protocols and in doing so, identified a number of gaps in the existing literature. These proposed research gaps were discussed and verified by expert consensus among the entire GDG. RESULTS: Evidence gaps across population sub-groups included a lack of information on: 1) the precise shape of the dose-response curve between physical activity and/or sedentary behavior and several of the health outcomes studied; 2) the health benefits of light-intensity physical activity and of breaking up sedentary time with light-intensity activity; 3) differences in the health effects of different types and domains of physical activity (leisure-time; occupational; transportation; household; education) and of sedentary behavior (occupational; screen time; television viewing); and 4) the joint association between physical activity and sedentary time with health outcomes across the life course. In addition, we acknowledge the need to conduct more population-based studies in low- and middle-income countries and in people living with disabilities and/or chronic disease, and to identify how various sociodemographic factors (age, sex, race/ethnicity, socioeconomic status) modify the health effects of physical activity, in order to address global health disparities. CONCLUSIONS: Although the 2020 WHO Guidelines for Physical Activity and Sedentary Behavior were informed by the most up-to-date research on the health effects of physical activity and sedentary time, there is still substantial work to be done in advancing the global physical activity agenda

World Health Organization 2020 guidelines on physical activity and sedentary behaviour.

Funder: The Public Health Agency of Canada and the Government of Norway provided financial support, without which this work could not have been completedOBJECTIVES: To describe new WHO 2020 guidelines on physical activity and sedentary behaviour. METHODS: The guidelines were developed in accordance with WHO protocols. An expert Guideline Development Group reviewed evidence to assess associations between physical activity and sedentary behaviour for an agreed set of health outcomes and population groups. The assessment used and systematically updated recent relevant systematic reviews; new primary reviews addressed additional health outcomes or subpopulations. RESULTS: The new guidelines address children, adolescents, adults, older adults and include new specific recommendations for pregnant and postpartum women and people living with chronic conditions or disability. All adults should undertake 150-300 min of moderate-intensity, or 75-150 min of vigorous-intensity physical activity, or some equivalent combination of moderate-intensity and vigorous-intensity aerobic physical activity, per week. Among children and adolescents, an average of 60 min/day of moderate-to-vigorous intensity aerobic physical activity across the week provides health benefits. The guidelines recommend regular muscle-strengthening activity for all age groups. Additionally, reducing sedentary behaviours is recommended across all age groups and abilities, although evidence was insufficient to quantify a sedentary behaviour threshold. CONCLUSION: These 2020 WHO guidelines update previous WHO recommendations released in 2010. They reaffirm messages that some physical activity is better than none, that more physical activity is better for optimal health outcomes and provide a new recommendation on reducing sedentary behaviours. These guidelines highlight the importance of regularly undertaking both aerobic and muscle strengthening activities and for the first time, there are specific recommendations for specific populations including for pregnant and postpartum women and people living with chronic conditions or disability. These guidelines should be used to inform national health policies aligned with the WHO Global Action Plan on Physical Activity 2018-2030 and to strengthen surveillance systems that track progress towards national and global targets

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H