Association of the PHACTR1/EDN1 genetic locus with spontaneous coronary artery dissection

Background: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. Objectives: This study sought to test the association between the rs9349379 genotype and SCAD. Methods: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. Results: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. Conclusions: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Not the same old thing: Establishing the unique contribution of drinking identity as a predictor of alcohol consumption and problems over time

Drinking identity – how much individuals view themselves as drinkers– is a promising cognitive factor that predicts problem drinking. Implicit and explicit measures of drinking identity have been developed (the former assesses more reflexive/automatic cognitive processes; the latter more reflective/controlled cognitive processes): each predicts unique variance in alcohol consumption and problems. However, implicit and explicit identity’s utility and uniqueness as a predictor relative to cognitive factors important for problem drinking screening and intervention has not been evaluated. Thus, the current study evaluated implicit and explicit drinking identity as predictors of consumption and problems over time. Baseline measures of drinking identity, social norms, alcohol expectancies, and drinking motives were evaluated as predictors of consumption and problems (evaluated every three months over two academic years) in a sample of 506 students (57% female) in their first or second year of college. Results found that baseline identity measures predicted unique variance in consumption and problems over time. Further, when compared to each set of cognitive factors, the identity measures predicted unique variance in consumption and problems over time. Findings were more robust for explicit, versus, implicit identity and in models that did not control for baseline drinking. Drinking identity appears to be a unique predictor of problem drinking relative to social norms, alcohol expectancies, and drinking motives. Intervention and theory could benefit from including and considering drinking identity

Evaluating the relationship between explicit and implicit drinking identity centrality and hazardous drinking

Drinking identity strength (how strongly one views oneself as a drinker) is a promising risk factor for hazardous drinking. A critical next step is to investigate whether the centrality of drinking identity (i.e., the relative importance of drinking vs. other identity domains, like well-being, relationships, education) also plays a role. Thus, we developed explicit and implicit measures of drinking identity centrality and evaluated them as predictors of hazardous drinking after controlling for explicit drinking identity strength. Two studies were conducted (Ns = 360 and 450, respectively). Participants, who self-identified as full-time students, completed measures of explicit identity strength, explicit and implicit centrality, and the Alcohol Use Disorders Identification Test (AUDIT). Study 1a evaluated two variants of the implicit measure (short- vs. long-format of the Multi-category Implicit Association Test), Study 1b only included the long form and also assessed alcohol consumption. In Study 1a, implicit and explicit centrality measures were positively and significantly associated with AUDIT scores after controlling for explicit drinking identity strength. There were no significant differences in the implicit measure variants, but the long format had slightly higher internal consistency. In Study 1b, results replicated for explicit, but not implicit, centrality. These studies provide preliminary evidence that drinking identity centrality may be an important factor for predicting hazardous drinking. Future research should improve its measurement and evaluate implicit and explicit centrality in experimental and longitudinal studies

Alcohol use and coping in a cross-sectional study of African American homicide survivors

The loss of a loved one to homicide is associated with considerable distress, often in the form of posttraumatic stress disorder (PTSD) and complicated grief (CG), and alcohol misuse. Yet alcohol-related problems and loss from a homicide are issues that disproportionally affect African Americans. The present study investigated alcohol use in a sample of 54 African American homicide survivors. Although there was a low prevalence of hazardous drinking, alcohol use was associated with higher levels of PTSD, complicated grief, and depression severity. In addition, scores on the Alcohol Use Disorders Identification Test (AUDIT) were correlated with active emotional coping and avoidant emotional coping. In analyses of PTSD symptom clusters, emotional numbing and hyperarousal symptoms were significantly correlated with AUDIT total score

Self-control, implicit alcohol associations, and the (lack of) prediction of consumption in an alcohol taste test with college student heavy episodic drinkers.

The high levels of problematic drinking in college students make clear the need for improvement in the prediction of problematic drinking. We conducted a laboratory-based experiment that investigated whether implicit measures of alcohol-related associations, self-control, and their interaction predicted drinking. Although a few studies have evaluated self-control as a moderator of the relationship between implicit measures of alcohol-related associations and drinking, this study extended that work by using a previously-validated manipulation that included a more (vs. less) cognitively demanding task and incentive to restrain drinking and by evaluating multiple validated measures of alcohol-related associations. Experimental condition was expected to moderate the relationship between implicit measures of alcohol-related associations and drinking, with a more positive relationship between alcohol-related associations and drinking among participants who completed the more (vs. less) cognitive demanding task. Secondary aims were to evaluate how individual differences in control factors (implicit theories about willpower and working memory capacity) might further moderate those relationships. One hundred and five U.S. undergraduate heavy episodic drinkers completed baseline measures of: drinking patterns, three Implicit Association Tests (evaluating drinking identity, alcohol excite, alcohol approach associations) and their explicit measure counterparts, implicit theories about willpower, and working memory capacity. Participants were randomized to complete a task that was more (vs. less) cognitively demanding and were given an incentive to restrain their drinking. They then completed an alcohol taste test. Results were not consistent with expectations. Despite using a previously validated manipulation, there was no evidence that one condition was more demanding than the other, and none of the predicted interactions reached statistical significance. The findings raise questions about the relation between self-control, implicit measures of alcohol-related associations, and drinking, as well as the conditions under which implicit measures of alcohol-related associations predict alcohol consumption in the laboratory

The associations between posttraumatic stress disorder and delay discounting, future orientation, and reward availability: A behavioral economic model

The theoretical framework of behavioral economics, a metatheory that integrates operant learning and economic theory, has only recently been applied to posttraumatic stress disorder (PTSD). A behavioral economic theory of PTSD reflects an expansion of prior behavioral conceptualization of PTSD, which described PTSD in terms of respondent and operant conditioning. In the behavioral economic framework of PTSD, negatively reinforced avoidance behavior is overvalued, in part due to deficits in environmental reward, and may be conceptualized as a form of reinforcer pathology (i.e., excessive preference for and valuation of an immediate reinforcer). We investigated cross-sectional relationships between PTSD severity and several constructs rooted in this behavioral economic framework, including future orientation, reward availability, and delay discounting in a sample of 110 military personnel/veterans (87.2% male) who had served combat deployments following September 11, 2001. Total PTSD severity was inversely related to environmental reward availability, β = -.49, ΔR = 0.24, p \u3c .001; hedonic reward availability, β = -.32, ΔR = 0.10, p = .001; and future orientation, β = -.20, ΔR = 0.04, p = .032, but not delay discounting, r = -.05, p = .633. An examination of individual symptom clusters did not suggest that avoidance symptoms were uniquely associated with these behavioral economic constructs. The findings offer support for a behavioral economic model of PTSD in which there is a lack of positive reinforcement as well as a myopic focus on the present

Cardiovascular and Limb Outcomes in Patients With Diabetes and Peripheral Artery Disease: The EUCLID Trial.

BACKGROUND Diabetes confers an increased risk for atherosclerotic cardiovascular disease, but less is known about the independent risk diabetes confers on major cardiovascular and limb events in patients with symptomatic peripheral artery disease (PAD) on contemporary management. OBJECTIVES The authors sought to assess the risk of cardiovascular and limb events in patients with PAD and diabetes as compared with those with PAD alone. METHODS In the EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) trial, 13,885 patients with symptomatic PAD were evaluated with a primary endpoint of an adjudicated composite of major adverse cardiovascular events (MACE) (cardiovascular death, myocardial infarction, ischemic stroke) followed over a median of ∼30 months. The diabetes subgroup was analyzed compared with the subgroup without diabetes, and further examined for diabetes-specific factors such as glycosylated hemoglobin (HbA) that might affect risk for major cardiovascular and limb outcomes. RESULTS A total of 5,345 patients (38.5%) had diabetes; the majority (n = 5,134 [96.1%]) had type 2 diabetes. The primary endpoint occurred in 15.9% of patients with PAD and diabetes as compared with 10.4% of those without diabetes (absolute risk difference 5.5%; adjusted hazard ratio: 1.56; 95% confidence interval [CI]: 1.41 to 1.72; p < 0.001). Every 1% increase in HbA was associated with a 14.2% increased relative risk for MACE (95% CI: 1.09 to 1.20; p < 0.0001). CONCLUSIONS Patients with PAD and diabetes are at high risk for cardiovascular and limb ischemic events, even on contemporary therapies. Every 1% increase in HbA was associated with a 14.2% increased relative risk for MACE (95% CI: 1.09 to 1.20; p < 0.0001). (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease [EUCLID]; NCT01732822)