Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports on the most up-to-date statistics related to heart disease, stroke, and cardiovas...

Heart Disease and Stroke Statistics—2020 Update: A Report From the American Heart Association

Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascul...

Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association.

The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs).The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2022 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population and an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, and the global burden of cardiovascular disease and healthy life expectancy.Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics.The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions. 

https://www.ahajournals.org/doi/pdf/10.1161/CIR.0000000000001052

Heart Disease and Stroke Statistics—2022 Update: A Report From the American Heart Association

1757 Identification of Ocular Sebaceous Neoplasia with Evaluation for Mismatch Repair Proteins L Schoenfield, J Anthony, R Djohan, I Lalak, M Levine, P Ng, J Perry, A Singh, T Plesec. Cleveland Clinic, Cleveland, OH. Background: Recognizing sebaceous carcinoma is important because of its risk for metastasis and tumor death. Histopathology alone is often difficult because fresh tissue for oil red-O stain is not always available. Several immunohistochemical stains (IHC) have been evaluated but often the diagnosis is elusive. Furthermore, the diagnosis of a sebaceous adenoma or carcinoma raises the possibility of Lynch syndrome, a cancer predisposition syndrome. Mismatch repair protein(MMR) abnormalities are a feature of Lynch syndrome, and they can be detected with IHC for the MLH1, MSH2, PMS2, and MSH6 proteins. Design: 14 sebaceous carcinomas and 3 adenomas from the eyelid (17 specimens) from 14 patients were evaluated for oil red-O when possible as well as IHC for AR, EMA, BER-EP4, CAM5.2 for diagnosis. MMR for MLH1, MSH2, PMS2, and MSH6 by IHC were evaluated as a possible screening panel for Lynch syndrome. Two patients already had other tissue tested by PCR for microsatellite instability (MSI) for Lynch syndrome. Results: Oil red-O was done on 6 of 17 specimens and positive in 5 of the 6 (83%). AR was positive in 2 of 3 adenomas (67%) and 5 of 14 carcinomas (36%). EMA was positive in 2 of 3 adenomas (67%) and 11 of 14 carcinomas (79%). BER-EP4 was negative in all 3 adenomas and positive in 7 of 14 carcinomas (50%). CAM5.2 was positive in 1 of 3 adenomas (33%) and 8 of 14 carcinomas (57%). All 17 specimens(100%) showed positive nuclear staining for MLH1 and PMS2, indicative of normal protein expression. In 14 of 17 specimens from 12 patients, MSH2 and MSH6 were also normal. 3 specimens from 2 patients that had rare positive cells for MSH2 and MSH6. Both patients had previous colonic tumors tested for MSI and were found to be MSI-H, indicative of possible Lynch syndrome. Conclusions: Diagnosing sebaceous carcinoma is important prognostically but sometimes challenging with routine histopathology. In our experience androgen receptor (AR) was found to be confirmatory in only 36% of cases and not dependent on the size of the tumor available. The other IHC stains were of marginal benefit and not specific. While none of the cases showed complete loss of expression of a MMR protein, there were 2 patients in with only rare positive cells who had known MSI-H tumors in the colon, suggestive of Lynch syndrome. Additional studies of these eyelid tumors may elucidate the possible role of using them for screening for Lynch syndrome.

When the Pancreas

The scientific landscape surrounding amyotrophic lateral sclerosis (ALS) continues to shift as the number of genes associated with the disease risk and pathogenesis, and the cellular processes involved, continues to grow. Despite decades of intense research and over 50 potentially causative or disease-modifying genes identified, etiology remains unexplained and treatment options remain limited for the majority of ALS patients. Various factors have contributed to the slow progress in understanding and developing therapeutics for this disease. Here, we review the genetic basis of ALS, highlighting factors that have contributed to the elusiveness of genetic heritability. The most commonly mutated ALS-linked genes are reviewed with an emphasis on disease-causing mechanisms. The cellular processes involved in ALS pathogenesis are discussed, with evidence implicating their involvement in ALS summarized. Past and present therapeutic strategies and the benefits and limitations of the model systems available to ALS researchers are discussed with future directions for research that may lead to effective treatment strategies outlined.

/pdf/als-genetics-mechanisms-and-therapeutics-where-are-we-now-g2xe5fjrbn.pdf

ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?

Hundreds of genetic variants have been associated with Body Mass Index (BMI) through genome-wide association studies (GWAS) using observational cohorts. However, the genetic contribution to efficient weight loss in response to dietary intervention remains unknown. We perform a GWAS in two large low-caloric diet intervention cohorts of obese participants. Two loci close to NKX6.3/MIR486 and RBSG4 are identified in the Canadian discovery cohort (n = 1166) and replicated in the DiOGenes cohort (n = 789). Modulation of HGTX (NKX6.3 ortholog) levels in Drosophila melanogaster leads to significantly altered triglyceride levels. Additional tissue-specific experiments demonstrate an action through the oenocytes, fly hepatocyte-like cells that regulate lipid metabolism. Our results identify genetic variants associated with the efficacy of weight loss in obese subjects and identify a role for NKX6.3 in lipid metabolism, and thereby possibly weight control. Individuals show large variability in their capacity to lose weight and maintain this weight. Here, the authors perform GWAS in two weight loss intervention cohorts and identify two genetic loci associated with weight loss that are taken forward for Bayesian fine-mapping and functional assessment in flies.

/pdf/genome-wide-gene-based-analyses-of-weight-loss-interventions-22vthpwrzs.pdf

Victoria Shenton

Papers

Genome-wide gene-based analyses of weight loss interventions identify a potential role for NKX6.3 in metabolism.

PGC1α Controls Sucrose Taste Sensitization in Drosophila