Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Fasting glucose versus oral glucose tolerance test for detection of glucose intolerance in obese children Glicemia de ayuno versus prueba de tolerancia oral a la glucosa en la detección de intolerancia a la glucosa en niños y adolescentes obesos

Background: Recently, the cut-off point for normal fasting glucose (FG) level, was decreased to 100 mg/dl. Aim: To determine the frequency of abnormal carbohydrate abnormalities in children with obesity and evaluate if the fasting glucose level is a useful tool for the screening of glucose intolerance (GI). Patients and methods: Children and adolescents, referred for evaluation of obesity were evaluated with an oral glucose tolerance test (OGTT) and FG. The sensitivity of FG for detection of GI, using the 100 and 110 mg/dl cut-off point, was evaluated. Results: We studied 186 patients (125 females) aged 12.1 (range: 5.4-19.3) years with a body mass index (BMI) of 29.9 (18.3-44.6) kg/mt 2 and a BMI Z score of 2.1 (1.7-3.2). Seven patients (3.8%) had abnormalities in the carbohydrate metabolism. The sensitivity of FG for the detection of GI using the 100 and 110 mg/dl cut-off values was 42.9 and 14.3%, respectively. Receiver operating characteristic (ROC) curves showed that the optimal

Hemolytic-uremic syndrome in Chile: clinical features, evolution and prognostic factors

Background: Hemolytic-uremic syndrome (HUS) is characterized by acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia. Aim: To describe the characteristics of patients with the diagnosis of HUS in Chile, and to identify the most reliable early predictors of morbidity and mortality. Material and methods: The clinical records of patients with HUS aged less than 15 years, attended between January 1990 and December 2003 in 15 hospitals, were reviewed. Demographic, clinical, biochemical, hematological parameters, morbidity and mortality were analyzed. Results: A cohort of 587 patients aged 2 to 8 years, 48% males, was analyzed. Ninety two percent had diarrhea. At the moment of diagnosis, anuria was observed in 39% of the patients, hypertension in 45% and seizures in 17%. Forty two percent required renal replacement therapy (RRT) and peritoneal dialysis was used in the majority of cases (78%). The most frequently isolated etiological agent was Escherichia coli. Mortality rate was 2.9% in the acute phase of the disease and there was a positive correlation between mortality and anuria, seizures, white blood cell count (WCC) >20.000/mm3 and requirements of renal replacement therapy (p <0.05). Twelve percent of patients evolved to chronic renal failure and the risk factors during the acute phase were the need for renal replacement therapy, anuria, WCC >20.000/mm3, seizures and hypertension. Conclusions: The present study emphasizes important clinical and epidemiological aspects of HUS in a Chilean pediatric population

Snowmass 2021 CMB-S4 White Paper

This Snowmass 2021 White Paper describes the Cosmic Microwave Background Stage 4 project CMB-S4, which is designed to cross critical thresholds in our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. We provide an overview of the science case, the technical design, and project plan

Snowmass 2021 CMB-S4 White Paper

This Snowmass 2021 White Paper describes the Cosmic Microwave Background Stage 4 project CMB-S4, which is designed to cross critical thresholds in our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. We provide an overview of the science case, the technical design, and project plan