Community Mortality due to Respiratory Syncytial Virus in Argentina: Population-based surveillance study

Background. Many deaths in infants from low-middle income countries (LMICs) occur at home or upon arrival to health facilities. Although acute lower respiratory tract illness plays an important role in community mortality, the accuracy of mortality rates due to respiratory syncytial virus (RSV) remains unknown. Methods. An active surveillance study among children aged under 5 years old (U5) was performed in Buenos Aires, Argentina, between January and December 2019, to define the burden and role of RSV in childhood community mortality. Results. A total of 63 families of children U5 participated in the study. Based on a combined approach of tissue sampling, verbal autopsies, and expert’s analysis, RSV infection was found in the causal chain of 11 from 12 cases with positive molecular biology results in respiratory samples. The estimated mortality rate due to RSV among infants was 0.27 deaths/1000 live births. The mean age of RSV-related household deaths was 2.8 months of age (standard deviation [SD] 1.7), and 8/12 were male infants (66.7%). Dying at home from RSV was associated with Streptococcus pneumoniae and/or Moraxella catarrhalis lung coinfection (75%), living in slums and settlement (odds ratio [OR], 17.09; 95% confidence interval [CI], 1.3–219.2), and other underlying comorbidities (OR, 14.87; 95% CI, 1.3–164.6). Conclusions. Infant community mortality rates due to RSV are higher than those reported in industrialized countries and similar to those reported in hospital-based studies in the same catchment population.Fil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Bianchi, Alejandra Silvina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Diaz Grigaites, Sebastian. Gobierno de la Provincia de Buenos Aires. Ministerio Publico. Ministerio Publico Fiscal. Instituto de Ciencias Forenses de Lomas de Zamora.; ArgentinaFil: de la Iglesia Niveyro, Paola Ximena. Hospital Italiano; ArgentinaFil: Nuño, Alejandra. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Valle, Sandra. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Afarian, Gabriela. Gobierno de la Provincia de Buenos Aires. Ministerio Publico. Ministerio Publico Fiscal. Instituto de Ciencias Forenses de Lomas de Zamora.; ArgentinaFil: Esperante, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Ferreti, Adrián. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Jares Baglivo, Sofía. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: De Luca, Julián. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Álvarez Paggi, Damián Jorge. Comisión Nacional de Investigación Científica y Tecnológica; Chile. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Diamanti, Adriana. Gobierno de la Provincia de Buenos Aires. Ministerio Publico. Ministerio Publico Fiscal. Instituto de Ciencias Forenses de Lomas de Zamora.; ArgentinaFil: Bassat, Quique. Universidad de Barcelona; España. Centro de investigação de Saúde de Manhiça; Mozambique. Institució Catalana de Recerca i Estudis Avancats; España. Hospital Sant Joan de Deu Barcelona; España. Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública; EspañaFil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentin

Prenatal Hyperandrogenization Induces Metabolic and Endocrine Alterations Which Depend on the Levels of Testosterone Exposure

Prenatal hyperandrogenism is able to induce polycystic ovary syndrome (PCOS) in rats. The aim of the present study was to establish if the levels of prenatal testosterone may determine the extent of metabolic and endocrine alterations during the adult life. Pregnant Sprague Dawley rats were prenatally injected with either 2 or 5 mg free testosterone (groups T2 and T5 respectively) from day 16 to day 19 day of gestation. Female offspring from T2 and T5 displayed different phenotype of PCOS during adult life. Offspring from T2 showed hyperandrogenism, ovarian cysts and ovulatory cycles whereas those from T5 displayed hyperandrogenism, ovarian cysts and anovulatory cycles. Both group showed increased circulating glucose levels after the intraperitoneal glucose tolerance test (IPGTT; an evaluation of insulin resistance). IPGTT was higher in T5 rats and directly correlated with body weight at prepubertal age. However, the decrease in the body weight at prepubertal age was compensated during adult life. Although both groups showed enhanced ovarian steroidogenesis, it appears that the molecular mechanisms involved were different. The higher dose of testosterone enhanced the expression of both the protein that regulates cholesterol availability (the steroidogenic acute regulatory protein (StAR)) and the protein expression of the transcriptional factor: peroxisome proliferator-activated receptor gamma (PPAR gamma). Prenatal hyperandrogenization induced an anti-oxidant response that prevented a possible pro-oxidant status. The higher dose of testosterone induced a pro-inflammatory state in ovarian tissue mediated by increased levels of prostaglandin E (PG) and the protein expression of cyclooxygenase 2 (COX2, the limiting enzyme of PGs synthesis). In summary, our data show that the levels of testosterone prenatally injected modulate the uterine environment and that this, in turn, would be responsible for the endocrine and metabolic abnormalities and the phenotype of PCOS during the adult life

Diagnosis, treatment and prevention of pediatric obesity: consensus position statement of the Italian Society for Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics

The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention.The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment. The evidence based efficacy of behavioral intervention versus pharmacological or surgical treatments is reported. Lastly, the prevention by promoting healthful diet, physical activity, sleep pattern, and environment is strongly recommended since the intrauterine phase

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Listado de cadena causal de muerte domiciliaria de niños menores de 5 años de edad del conurbano sur bonaerense

Muchas muertes de niños menores de 5 años de países de ingresos medianos bajos ocurren en el hogar o al llegar a los establecimientos de salud. Aunque la enfermedad aguda de las vías respiratorias inferiores juega un papel importante en la mortalidad comunitaria, se desconoce la precisión de las tasas de mortalidad debidas al virus respiratorio sincitial (VSR). Se realizó un estudio de vigilancia activa en niños menores de 5 años (U5) en Buenos Aires, Argentina, entre enero y diciembre de 2019, para definir la carga y el papel del VRS en la mortalidad infantil comunitaria.Fil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: bianchi, alejandra. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: diaz grigaites, Sebastian. Fundación para la Investigación en Infectología Infantil; Argentina. Gobierno de la Provincia de Buenos Aires. Ministerio Publico; ArgentinaFil: de la Iglesia Niveyro, Paola Ximena. Fundación para la Investigación en Infectología Infantil; Argentina. Hospital Italiano; ArgentinaFil: Nuño, Alejandra. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Valle, Sandra. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Afarian, Gabriela. Ministerio Publico de la Provincia de Buenos Aires;Fil: Esperante, Sebastian. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ferretti, Adrian Julio Pantaleon. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Jares Baglivo, Sofia. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: De Luca, Julian. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Diamanti, Adriana. Gobierno de la Provincia de Buenos Aires. Ministerio Publico; ArgentinaFil: Bassat, Quique. Hospital Sant Joan de Deu Barcelona; España. Isglobal; España. Universidad de Barcelona; EspañaFil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentin

Uncovering Causes of Childhood Death Using the Minimally Invasive Autopsy at the Community Level in an Urban Vulnerable Setting of Argentina: A Population-Based Study

Background: Precise determination of the causal chain that leads to community deaths in children in low-and middle-income countries is critical to estimating all causes of mortality accurately and to planning preemptive strategies for targeted allocation of resources to reduce this scourge. Methods: An active surveillance population-based study that combined minimally invasive tissue sampling (MITS) and verbal autopsies (VA) among children under 5 was conducted in Buenos Aires, Argentina, from September 2018 to December 2020 to define the burden of all causes of community deaths. Results: Among 90 cases enrolled (86% of parental acceptance), 81 had complete MITS, 15.6% were neonates, 65.6% were post-neonatal infants, and 18.9% were children aged 1-5 years. Lung infections were the most common cause of death (CoD) in all age groups (57.8%). Among all cases of lung infections, acute bronchiolitis was the most common CoD in infants aged 12 months (8 of 11, 72.7%). The most common comorbid condition in all age groups was undernutrition in 18 of 90 (20%). It was possible to find an immediate CoD in 78 of 81 subjects where MITS could be done. With this combined approach, we were able to determine that sudden infant death syndrome was overestimated in state reports. Conclusions: CoD determination by a combination of MITS and VA provides an accurate estimation of the chain of events that leads to death, emphasizing possible interventions to prevent mortality in children.Fil: Caballero, Mauricio Tomás. Fundación Infant; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Diaz Grigaites, Sebastian. Gobierno de la Provincia de Buenos Aires. Ministerio Publico; ArgentinaFil: de la Iglesia Niveyro, Paola Ximena. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: Esperante, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Infant; ArgentinaFil: Bianchi, Alejandra M.. Fundación Infant; ArgentinaFil: Nuño, Alejandra. Fundación Infant; ArgentinaFil: Valle, Sandra. Fundación Infant; ArgentinaFil: Afarian, Gabriela. Gobierno de la Provincia de Buenos Aires. Ministerio Publico; ArgentinaFil: Ferretti, Adrian Julio Pantaleon. Fundación Infant; ArgentinaFil: Baglivo, Sofia Jares. Fundación Infant; ArgentinaFil: De Luca, Julian. Fundación Infant; ArgentinaFil: Zea, Cristian M. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Caporal, Paula. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Labanca, Maria Jose. Instituto Universitario del Hospital Italiano de Buenos Aires; ArgentinaFil: Diamanti, Adriana. Gobierno de la Provincia de Buenos Aires. Ministerio Publico; ArgentinaFil: Álvarez Paggi, Damián Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Infant; ArgentinaFil: Bassat, Quique. Consorcio de Investigación Biomédica En Red de Epidemiología y Salud Pública; España. Centro de Investigação Em Saúde de Manhiça; Mozambique. Universidad de Barcelona; España. Institució Catalana de Recerca i Estudis Avancats; EspañaFil: Polack, Fernando Pedro. Fundación Infant; ArgentinaFil: Carballo, Ana M. Gobierno de la Provincia de Buenos Aires. Ministerio Publico; ArgentinaFil: Hernandez, Gabriela. Gobierno de la Provincia de Buenos Aires. Ministerio Publico; ArgentinaFil: Figueroa, Paola. Gobierno de la Provincia de Buenos Aires. Ministerio Publico; ArgentinaFil: Ares, Patricia E.. Gobierno de la Provincia de Buenos Aires. Ministerio Publico; ArgentinaFil: Rodriquez Paquete, Cesar A.. Gobierno de la Provincia de Buenos Aires. Ministerio Publico; Argentin

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research