Phenotypic characterization and predictive analysis of p.Asp47Asn LDL receptor mutation associated with Familial Hypercholesterolemia in a Chilean population

BackgroundFamilial hypercholesterolemia (FH) is an inherited disorder mainly caused by mutations in the LDL receptor (LDL-R) and characterized by elevation of low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease.ObjectiveIn this study, we evaluated the clinical phenotype of the p.Asp47Asn, described as an uncertain pathogenic variant, and its effect on the structure of LDL-R and ligand interactions with apolipoproteins.Methods27 children and adolescents with suspected FH diagnosis were recruited from a pediatric endocrinology outpatient clinic. Blood samples were collected after 12 h fasting for lipid profile analysis. DNA sequencing was performed for six FH-related genes by Ion Torrent PGM platform and copy number variation by MLPA. For index cases, a familial cascade screening was done restricted to the same mutation found in the index case. In silico analysis were developed to evaluate the binding capacity of LDL-R to apolipoproteins B100 and E.ResultsLipid profile in children and adolescents demonstrated higher LDL-C levels in p.Asp47Asn carriers compared to the wild type genotype. In silico analysis predicted a reduction in the binding capacity of the ligand-binding modules LA1-2 of p.Asp47Asn LDL-R for ApoB100 and ApoE, which was not produced by local structural changes or folding defects but as a consequence of a decreased apparent affinity for both apolipoproteins.ConclusionThe clinical phenotype and the structural effects of p.Asp47Asn LDL-R mutation suggest that this variant associates to FH.     

Emerging Infectious Diseases and Public Health Policy: Insights from Cambodia,Hong Kong and Indonesia

Emerging infectious diseases affect the health of animal and human populations, but the impact goes beyond health as it extends to political, economic, social and environmental domains, as well as inter‐state relations. Deeper understanding of these impacts aids public health authorities in their duties of protection and improvement of the health of their communities, promotion of healthy practices and research on disease, injury and threat prevention and mitigation. This empirical essay gathers insights from Cambodia, Hong Kong and Indonesia as they attempt to design and implement control and surveillance systems against avian influenza – an infectious disease.     

Surgical treatment for hypertrophic obstructive cardiomyopathy

INTRODUCTION AND OBJECTIVES: Five percent of the patients with hypertrophic obstructive cardiomyopathy (HOCM) have symptoms unresponsive to medical treatment and are candidates for invasive therapy. The objective of this study was to analyze our results with surgical treatment of HOCM during the last 10 years. PATIENTS AND METHOD: Between July 1993 and January 2004 26 patients with HOCM refractory to drug therapy were operated on. An extended septal myectomy was performed, in combination with anterior mitral leaflet plication in 19 cases (73%) and with mitral valve replacement in 5 (19%). Evolution of the grade of dyspnea, left ventricle outflow tract gradient (LVOTG), mitral regurgitation, and systolic anterior motion after surgery was analyzed. RESULTS: Mean follow-up was 63 (37) months. After surgery, a significant reduction in LVOTG (from 96.5 to 19.5 mmHg; P<.001), grade of mitral regurgitation (from 2.54 to 0.69; P<.001) and systolic anterior motion (from 2.92 to 0.23; P<.001) was achieved, which led to improvement in functional class. Hospital mortality and need for pacemaker implantation due to complete heart block after surgery was 3.8% (n=1). There were no cases of iatrogenic ventricular septal defect or mitro-aortic valve injury. Actuarial survival at 5 years was 96% (4%). CONCLUSIONS: Surgery in patients with HOCM yields great clinical improvements with low morbidity and mortality. Simultaneous intervention for both myocardial and valvular components of the disease allows not only reduction in the LVOTG but also correction of mitral regurgitation and abolition of systolic anterior motion.     

Response to direct‐acting antivirals for hepatitis C treatment in vertically HIV/HCV co‐infected patients

Direct‐acting antivirals (DAAs) for HCV treatment have improved tolerance and efficacy among adults, but experience in vertical transmission is scarce. In our vertically HIV/HCV co‐infected youth cohort of 58 patients, DAA achieved excellent rates of cure among naïve and pretreated individuals. Treating vertically infected seems important as 29.6% displayed advanced fibrosis at treatment initiation.     

Angina related to 5-Fluorouracil

Treatment with 5-fluorouracil is common in oncological patients. Side effects on bone marrow, skin, and mucous membranes have been reported. Cardiotoxicity, which is less predictable, can be life-threatening. Manifestations include angina, arrhythmias, infarction, heart failure and cardiogenic shock. The toxic mechanisms that might be involved have been much discussed but have not yet been clearly established. Current evidence supports the possibility of a metabolic effect in common with the cascade secondary to ischemia due to coronary disease. Based on a case report, we discuss the usual clinical presentation, treatment and prognosis. Finally we make recommendations for managing patients being treated with 5-fluorouracil.