Cardiovascular Disease among Syrian refugees: a descriptive study of patients in two Médecins Sans Frontières clinics in northern Lebanon.

BACKGROUND: Literature on the burden and management of atherosclerotic cardiovascular disease (ASCVD) in humanitarian settings is limited. This study aimed to describe patient characteristics and explore both service use and use of recommended secondary prevention drugs in Syrian refugee patients with ASCVD attending two Médecins Sans Frontières (MSF) clinics in Lebanon. METHODS: This study comprised a cross-sectional survey of ASCVD patients attending either MSF clinic over a four-week period in early 2017. Using descriptive statistics, we explored patient demographic characteristics, cardiovascular risk factors and assessed ASCVD secondary prevention medication prescription and patient adherence with a 7-day self-report scale. A retrospective study of routine clinical data explored workload and trends in patient loss to follow-up. We performed logistic regression modelling to explore risk factors for loss to follow-up. RESULTS: We included 514 patients with ASCVD in the cross-sectional study, performed in 2017. Most (61.9%) were male and mean age was 60.4 years (95% CI, 59.6-61.3). Over half (58.8%) underwent revascularization and 26.1% had known cerebrovascular disease. ASCVD risk factors included 51.8% with diabetes and 72.2% with hypertension. While prescription (75.7 to 98.2%) and self-reported adherence rates (78.4 to 93.9%) for individual ASCVD secondary prevention drugs (ACE-inhibitor, statin and antiplatelet) were high, the use of all three was low at 41.3% (CI95%: 37.0-45.6). The 5-year retrospective cohort study (ending April 2017) identified 1286 patients with ASCVD and 16,618 related consultations (comprising 24% of all NCD consultations). Over one third (39.7%) of patients were lost to follow-up, with lower risk among men. CONCLUSIONS: The burden of ASCVD within MSF clinics in Lebanon is substantial. Although prescription and adherence of individual secondary prevention drugs is acceptable, overall use of the three recommended drugs is suboptimal. Loss to follow-up rates were high. Further studies are needed to evaluate innovative strategies to increase the use of the multiple recommended drugs, and to increase the retention of patients with ASCVD in the care system

Effective Population Size and the Efficacy of Selection on the X Chromosomes of Two Closely Related Drosophila Species

The prevalence of natural selection relative to genetic drift is of central interest in evolutionary biology. Depending on the distribution of fitness effects of new mutations, the importance of these evolutionary forces may differ in species with different effective population sizes. Here, we survey population genetic variation at 105 orthologous X-linked protein coding regions in Drosophila melanogaster and its sister species D. simulans, two closely related species with distinct demographic histories. We observe significantly higher levels of polymorphism and evidence for stronger selection on codon usage bias in D. simulans, consistent with a larger historical effective population size on average for this species. Despite these differences, we estimate that <10% of newly arising nonsynonymous mutations have deleterious fitness effects in the nearly neutral range (i.e., −10 < Nes < 0) in both species. The inferred distributions of fitness effects and demographic models translate into surprisingly high estimates of the fraction of “adaptive” protein divergence in both species (∼85–90%). Despite evidence for different demographic histories, differences in population size have apparently played little role in the dynamics of protein evolution in these two species, and estimates of the adaptive fraction (α) of protein divergence in both species remain high even if we account for recent 10-fold growth. Furthermore, although several recent studies have noted strong signatures of recurrent adaptive protein evolution at genes involved in immunity, reproduction, sexual conflict, and intragenomic conflict, our finding of high levels of adaptive protein divergence at randomly chosen proteins (with respect to function) suggests that many other factors likely contribute to the adaptive protein divergence signature in Drosophila

Clinical practice guidelines for BRCA1 and BRCA2 genetic testing

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices

SIRT1 Is Essential for Normal Cognitive Function and Synaptic Plasticity

Conservation of normal cognitive functions relies on the proper performance of the nervous system at the cellular and molecular level. The mammalian NAD(+)-dependent deacetylase, SIRT1, impacts different processes potentially involved in the maintenance of brain integrity such as chromatin remodeling, DNA repair, cell survival and neurogenesis. Here we show that SIRT1 is expressed in neurons of the hippocampus, a key structure in learning and memory. Using a combination of behavioral and electrophysiological paradigms we analyzed the effects of SIRT1 deficiency and overexpression on mouse learning and memory as well as on synaptic plasticity. We demonstrated that the absence of SIRT1 impaired cognitive abilities, including immediate memory, classical conditioning and spatial learning. In addition, we found that the cognitive deficits in SIRT1 knockout mice were associated with defects in synaptic plasticity without alterations in basal synaptic transmission or NMDA receptor function. Brains of SIRT1-KO mice exhibited normal morphology and dendritic spine structure but display a decrease in dendritic branching, branch length and complexity of neuronal dendritic arbors. Also, a decrease in ERK1/2 phosphorylation and altered expression of hippocampal genes involved in synaptic function, lipid metabolism and myelination were detected in SIRT1-KO mice. In contrast, mice with high levels of SIRT1 expression in brain exhibited regular synaptic plasticity and memory. We conclude that SIRT1 is indispensable for normal learning, memory and synaptic plasticity in mice

Prospective association between total and specific dietary polyphenol intakes and cardiovascular disease risk in the Nutrinet-Sante french cohort

Background: Epidemiological and experimental evidence support a protective effect of dietary polyphenols on chronic diseases, but high quality longitudinal data are needed, including details on categories of polyphenols. Our objective was to investigate the prospective association between total and individual classes and subclasses of dietary polyphenols and the risk of major cardiovascular disease in the NutriNet-Sante cohort. Methods: A total of 84,158 participants, who completed at least three 24 h dietary records, were included between May 2009 and June 2017. Individual polyphenols intakes were obtained by matching food consumption data from the 24 h dietary records with the Phenol-Explorer polyphenol composition database. Multivariable Cox proportional hazards models were used to characterize the associations between dietary polyphenols and the incidence of cardiovascular diseases, comparing tertile T3 vs. T1 of classes and subclasses of polyphenols. Results: Over a median of 4.9 years of follow-up, 602 major cardiovascular events were diagnosed. Intakes of anthocyanins, catechins, and flavonols were strongly inversely associated with cardiovascular disease risk (anthocyanins: Hazard Ratio (HR)(for a 1-point increment of 10 mg/day) = 0.98 (0.96-0.99, p = 0.03, HRT3vs.(T1) = 0.66 (0.52-0.83), p(trend) = 0.0003; catechins: HRfor a 1-point increment of 10 mg/day = 0.98 (0.96-0.99), p = 0.02, HRT3vs. (T1) = 0.74 (0.60-0.91), p(trend) = 0.004; flavonols: HRfor a 1-point increment of 10 mg/day = 0.94 (0.90-0.99), p = 0.02, HRT3vs.(T1) = 0.75 (0.61-0.94), p(trend) = 0.006). Intakes of dihydrochalcones, proanthocyaninidins, dihydroflavonols, hydroxybenzoic acids, and stilbenes were also associated with a decrease (13%, 19%, 24%, 24%, and 27%, respectively) in cardiovascular disease risk, when comparing tertile T3 to T1. Conclusions: Higher intakes of polyphenols, especially of anthocyanins, catechins, and flavonols, were associated with a statistically significant decreased cardiovascular disease risk

Prospective association between consumption frequency of organic food and body weight change, risk of overweight or obesity: results from the NutriNet-Sante Study

A lower BMI has been reported among consumers of organic foods, but this relationship has never been examined in a prospective design study. Our aim was to prospectively investigate the association between frequency of organic food consumption and weight change. We analysed data from 62 224 participants of the NutriNet-Sante cohort (78 % women, mean age=45 years) with information on consumption frequency of organic foods, dietary intake and repeated anthropometric data. For sixteen products, participants reported their consumption frequency of labelled organic foods (never, occasionally, most of the time). An organic score (OS) with a maximum of thirty-two points was computed. The associations of the OS (modeled as quartiles (Q)) with change in BMI during follow-up (on average 31 years) and with the risk of overweight and obesity were estimated by ANCOVA and multivariable logistic regression. A lower BMI increase was observed across quartiles of the OS (mean difference Q4 v. Q1=-016 (95 % CI -032, -001). An increase in the OS was associated with a lower risk of overweight and obesity (among non-overweight and non-obese participants at inclusion): OR for Q4 v. Q1 were 077 (95 % CI 068, 086) and 069 (95 % CI 058, 082), respectively. Concerning obesity risk, the association was stronger among participants with higher adherence to nutritional guidelines. This study supports a strong protective role of consumption frequency of organic foods with regard to the risk of overweight and obesity that depends on overall dietary quality. Upon confirmation, these results may contribute to fine-tune nutritional guidelines by accounting for farming practices in food production