Role for Maternal Asthma in Severe Human Metapneumovirus Lung Disease Susceptibility in Children

Background: Severity of human metapneumovirus (hMPV) lower respiratory illness (LRTI) is considered similar to that observed for respiratory syncytial virus (RSV). However, differences in severity between these pathogens have been noted, suggesting the degree of illness may vary in different populations. Moreover, a potential association between hMPV and asthma also suggests that hMPV may preferentially affect asthmatic subjects. Methods: In a population-based surveillance study in children aged <2 years admitted for severe LRTI in Argentina, nasopharyngeal aspirates were tested by RT-PCR for hMPV, RSV, influenza A, and human rhinovirus. Results: Of 3947 children, 383 (10%) were infected with hMPV. The hospitalization rate for hMPV LRTI was 2.26 per 1000 children (95% confidence interval [CI], 2.04-2.49). Thirty-nine (10.2%) patients infected with hMPV experienced life-threatening disease (LTD; 0.23 per 1000 children; 95% CI,. 16-.31/1000), and 2 died (mortality rate 0.024 per 1000; 95% CI,. 003-.086). In hMPV-infected children birth to an asthmatic mother was an increased risk for LTD (odds ratio, 4.72; 95% CI, 1.39-16.01). We observed a specific interaction between maternal asthma and hMPV infection affecting risk for LTD. Conclusions: Maternal asthma increases the risk for LTD in children <2 years old hospitalized for severe hMPV LRTI.Fil: Libster, Romina Paula. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Esteban, Ignacio. Fundación para la Investigación en Infectología Infantil; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Bianchi, Alejandra Silvina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Alva Grimaldi, Luciano. Gobierno de la Provincia de Buenos Aires. Hospital Zonal General de Agudos Doctor Lucio Melendez.; ArgentinaFil: Dueñas, Karina. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal de Agudos Evita.; ArgentinaFil: Sancillo, Andrea. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal de Agudos Evita.; ArgentinaFil: Rodriguez, Andrea. Gobierno de la Provincia de Buenos Aires. Hospital Provincial Evita Pueblo.; ArgentinaFil: Ferrero, Fernando. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Stein, Katherine. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Acosta, Patricio Leandro. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ferolla, Fausto Martín. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bergel, Eduardo. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Caballero, Mauricio Tomás. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Pellegrino, Gustavo. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Fernandez Gago, Guadalupe. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Pozzolo, Cecilia. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Castro, Laura. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Almeida, Rodrigo Egues. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Rebec, Beatriz. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: González, Mariela. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Calvo, Mariel. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Henrichsen, Julieta. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Nocito, Celina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Barbero, Guillermo. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Ves Losada, Juan. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Bonina, Angel. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Flamenco, Edgardo. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Rodriguez Perez, Alberto. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Kobylarz, Alicia. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Raggio, Mirta. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Schavlosky, Graciela. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Caria, Adriana. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Barboza, Edgar. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Sastre, Gustavo. Fundación para la Investigación en Infectología Infantil; Argentin

Autophagy-Independent Lysosomal Targeting Regulated by ULK1/2-FIP200 and ATG9

Iron is vital for many homeostatic processes, and its liberation from ferritin nanocages occurs in the lysosome. Studies indicate that ferritin and its binding partner nuclear receptor coactivator-4 (NCOA4) are targeted to lysosomes by a form of selective autophagy. By using genome-scale functional screening, we identify an alternative lysosomal transport pathway for ferritin that requires FIP200, ATG9A, VPS34, and TAX1BP1 but lacks involvement of the ATG8 lipidation machinery that constitutes classical macroautophagy. TAX1BP1 binds directly to NCOA4 and is required for lysosomal trafficking of ferritin under basal and iron-depleted conditions. Under basal conditions ULK1/2-FIP200 controls ferritin turnover, but its deletion leads to TAX1BP1-dependent activation of TBK1 that regulates redistribution of ATG9A to the Golgi enabling continued trafficking of ferritin. Cells expressing an amyotrophic lateral sclerosis (ALS)-associated TBK1 allele are incapable of degrading ferritin suggesting a molecular mechanism that explains the presence of iron deposits in patient brain biopsies

Effects of Music on Human Health and Wellness: Physiological Measurements and Research Design

This article suggests some possible ways to approach the rather daunting task of researching music-spirit-mind-body-health interactions, which occur both within individual experiences and within a matrix of shared cultural values and meanings. It attempts to find a coherent path along which to investigate the interconnections of music's influences within and among physical, psychosocial, emotional, and spiritual domains. Its purpose is to offer a broad overview of issues relevant to physiological measurements and research design in music medicine research, with an emphasis on approaches, which focus on stress systems. It gives a detailed account of historical problems in the research literature, methodological issues, and promising lines of research, as well as possible new areas for research development

MAcronutrients during pregnancy and life-threatening respiratory syncytial virus infections in children

Rationale: Respiratory syncytial virus (RSV) is an important cause of hospitalization and death in infants worldwide. Most RSV deaths occur in developing countries, where burden and risk factors for life-threatening illness are unclear. Objectives: We defined the burden of life-threatening (O2 saturation [O2 sat] ≤ 87%) and fatal RSV infection, and characterized risk factors for life-threatening disease in hospitalized children. Special emphasis was placed on studying the impact of dietary habits during pregnancy. We hypothesized that dietary preferences, differing from those of our remote ancestors, would negatively impact children’s pulmonary health. For instance, a diet rich in carbohydrates is a signature of recent millennia and typical of low-income populations, heavily burdened by life-threatening RSV disease. Methods: Prospective study in a catchment population of 56,560 children under 2 years of age during the RSV season in Argentina. All children with respiratory signs and O2 sat less than 93% on admission were included. Measurements and Main Results: Among 1,293 children with respiratory infections, 797(61.6%) were infected with RSV: 106 of these had life-threatening disease; 1.9 per 1,000 children (95% confidence interval [CI], 1.5–2.2/1,000) under 24 months. A total of 22 hospitalized children died (9 RSV+), 26 died at home due to acute respiratory infection (14 attributed to RSV); all were under 12 months old. The annual attributable mortality rate for RSV was 0.7 per 1,000 infants (95% CI, 0.4–1.1/1,000). Life-threatening disease was dose-dependently associated with carbohydrate ingestion during pregnancy (adjusted odds ratio from 3.29 [95% CI, 1.15–9.44] to 7.36 [95% CI, 2.41–22.5] versus the lowest quartile). Conclusions: Life-threatening and fatal RSV infections are a heavy burden on infants in the developing world. Diets rich in carbohydrates during pregnancy are associated with these severe outcomes.Fil: Ferolla, Fausto Martín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Hijano, Diego Raúl. Fundación para la Investigación en Infectologia Infantil; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Acosta, Patricio Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Rodríguez, Andrea. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos Descentralizado “Evita Pueblo"; ArgentinaFil: Dueñas, Karina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Sancilio, Andrea. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Barboza, Edgar. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Narciso López"; ArgentinaFil: Caría, Adriana. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Narciso López"; ArgentinaFil: Fernández Gago, Guadalupe. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Egües Almeida, Rodrigo. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Castro, Laura. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Pozzolo, Cecilia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal de Agudos "Dr. Arturo Oñativia"; ArgentinaFil: Martínez, María V.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Lucio Meléndez”; ArgentinaFil: Grimaldi Alva, Luciano. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Lucio Meléndez”; ArgentinaFil: Rebec, Beatriz. Provinicia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos “Presidente Perón”; ArgentinaFil: Calvo, Mariel. Provinicia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos “Presidente Perón"; ArgentinaFil: Henrichsen, Julieta. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos “Dr. Pedro Fiorito”; ArgentinaFil: Nocito, Celina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal General de Agudos “Dr. Pedro Fiorito”; ArgentinaFil: González, Mariela. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Alberto Eurnekián"; ArgentinaFil: Barbero, Guillermo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Ves Losada, Juan. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Caballero, Mauricio Tomás. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Zurankovas, Valeria. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Raggio, Mirta. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Schavlovsky, Graciela. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Kobylarz, Alicia. Provincia de Buenos Aires. Ministerio de Salud. Hospital Materno Infantil “Ana Goitia”; ArgentinaFil: Wimmenauer, Vera. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Bugna, Jimena. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Williams, John V.. Vanderbilt University; Estados UnidosFil: Sastre, Gustavo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Flamenco, Edgardo. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal de Agudos "Dr. Arturo Oñativia"; ArgentinaFil: Rodríguez Pérez, Alberto. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General de Agudos “Dr. Alberto Eurnekián"; ArgentinaFil: Ferrero, Fernando. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Libster, Romina Paula. Vanderbilt University; Estados Unidos. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Grijalva, Carlos G.. Vanderbilt University; Estados UnidosFil: Polack, Fernando Pedro. Vanderbilt University; Estados Unidos. Fundación para la Investigación en Infectología Infantil; Argentin

Time-dependent analysis of extra length of stay and mortality due to ventilator-associated pneumonia in intensive-care units of ten limited-resources countries: findings of the International Nosocomial Infection Control Consortium (INICC)

Ventilator-associated pneumonias (VAPs) are a worldwide problem that significantly increases patient morbidity, mortality, and length of stay (LoS), and their effects should be estimated to account for the timing of infection. The purpose of the study was to estimate extra LoS and mortality in an intensive-care unit (ICU) due to a VAP in a cohort of 69 248 admissions followed for 283 069 days in ICUs from 10 countries. Data were arranged according to the multi-state format. Extra LoS and increased risk of death were estimated independently in each country, and their results were combined using a random-effects meta-analysis. VAP prolonged LoS by an average of 2.03 days (95% CI 1.52-2.54 days), and increased the risk of death by 14% (95% CI 2-27). The increased risk of death due to VAP was explained by confounding with patient morbidity