Factores Socioculturales y su influencia en un contexto intercultural de las actividades de salud en un contexto intercultural en tres barrios de Bilwi. RAAN 1999 - Mayo 2001

Estudio cualitativo con enfoque sociocultural en el que se tomó como universo a todos los y las pobladores del caso urbano de Bilwi de los barrios seleccionados (El Cocal, revolución y Arlen Siu

RNAi-Based Functional Genomics Identifies New Virulence Determinants in Mucormycosis

Mucorales are an emerging group of human pathogens that are responsible for the lethal disease mucormycosis. Unfortunately, functional studies on the genetic factors behind the virulence of these organisms are hampered by their limited genetic tractability, since they are reluctant to classical genetic tools like transposable elements or gene mapping. Here, we describe an RNAi-based functional genomic platform that allows the identification of new virulence factors through a forward genetic approach firstly described in Mucorales. This platform contains a whole-genome collection of Mucor circinelloides silenced transformants that presented a broad assortment of phenotypes related to the main physiological processes in fungi, including virulence, hyphae morphology, mycelial and yeast growth, carotenogenesis and asexual sporulation. Selection of transformants with reduced virulence allowed the identification of mcplD, which encodes a Phospholipase D, and mcmyo5, encoding a probably essential cargo transporter of the Myosin V family, as required for a fully virulent phenotype of M. circinelloides. Knock-out mutants for those genes showed reduced virulence in both Galleria mellonella and Mus musculus models, probably due to a delayed germination and polarized growth within macrophages. This study provides a robust approach to study virulence in Mucorales and as a proof of concept identified new virulence determinants in M. circinelloides that could represent promising targets for future antifungal therapies

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Mouse hepatic oval cells require Met-dependent PI3K to impair TGF-β-Induced oxidative stress and apoptosis.

We have previously shown that oval cells harboring a genetically inactivated Met tyrosine kinase (Met−/− oval cells) are more sensitive to TGF-β-induced apoptosis than cells expressing a functional Met (Metflx/flx), demonstrating that the HGF/Met axis plays a pivotal role in oval cell survival. Here, we have examined the mechanism behind this effect and have found that TGF-β induced a mitochondria-dependent apoptotic cell death in Metflx/flx and Met−/− oval cells, associated with a marked increase in levels of the BH3-only proteins Bim and Bmf. Bmf plays a key role during TGF-β-mediated apoptosis since knocking down of BMF significantly diminished the apoptotic response in Met-/- oval cells. TGF-β also induced oxidative stress accompanied by NADPH oxidase 4 (Nox4) mRNA up-regulation and decreased protein levels of antioxidant enzymes. Antioxidants inhibit both TGF-β-induced caspase 3 activity and Bmf up-regulation, revealing an oxidative stress-dependent Bmf regulation by TGF-β. Notably, oxidative stress-related events were strongly amplified in Met−/− oval cells, emphasizing the critical role of Met in promoting survival. Pharmacological inhibition of PI3K did impair HGF-driven protection from TGF-β-induced apoptosis and increased sensitivity of Metflx/flx oval cells to TGF-ß by enhancing oxidative stress, reaching apoptotic indices similar to those obtained in Met−/− oval cells. Interestingly, both PI3K inhibition and/or knockdown itself resulted in caspase-3 activation and loss of viability in Metflx/flx oval cells, whereas no effect was observed in Met−/− oval cells. Altogether, results presented here provide solid evidences that both paracrine and autocrine HGF/Met signaling requires PI3K to promote mouse hepatic oval cell survival against TGF-β-induced oxidative stress and apoptosis

Mouse hepatic oval cells require Met-dependent PI3K to impair TGF-β-Induced oxidative stress and apoptosis.

We have previously shown that oval cells harboring a genetically inactivated Met tyrosine kinase (Met−/− oval cells) are more sensitive to TGF-β-induced apoptosis than cells expressing a functional Met (Metflx/flx), demonstrating that the HGF/Met axis plays a pivotal role in oval cell survival. Here, we have examined the mechanism behind this effect and have found that TGF-β induced a mitochondria-dependent apoptotic cell death in Metflx/flx and Met−/− oval cells, associated with a marked increase in levels of the BH3-only proteins Bim and Bmf. Bmf plays a key role during TGF-β-mediated apoptosis since knocking down of BMF significantly diminished the apoptotic response in Met-/- oval cells. TGF-β also induced oxidative stress accompanied by NADPH oxidase 4 (Nox4) mRNA up-regulation and decreased protein levels of antioxidant enzymes. Antioxidants inhibit both TGF-β-induced caspase 3 activity and Bmf up-regulation, revealing an oxidative stress-dependent Bmf regulation by TGF-β. Notably, oxidative stress-related events were strongly amplified in Met−/− oval cells, emphasizing the critical role of Met in promoting survival. Pharmacological inhibition of PI3K did impair HGF-driven protection from TGF-β-induced apoptosis and increased sensitivity of Metflx/flx oval cells to TGF-ß by enhancing oxidative stress, reaching apoptotic indices similar to those obtained in Met−/− oval cells. Interestingly, both PI3K inhibition and/or knockdown itself resulted in caspase-3 activation and loss of viability in Metflx/flx oval cells, whereas no effect was observed in Met−/− oval cells. Altogether, results presented here provide solid evidences that both paracrine and autocrine HGF/Met signaling requires PI3K to promote mouse hepatic oval cell survival against TGF-β-induced oxidative stress and apoptosis

Políticas públicas

Amputaci&oacute;n de extremidades superiores: caracterizaci&oacute;n epidemiol&oacute;gicaAn&aacute;lisis comparado de las pol&iacute;ticas de promoci&oacute;n de la salud entre Chile y Catalu&ntilde;aAn&aacute;lisis de los Avisa para la toma de decisiones en pol&iacute;ticas de saludAntecedentes de colelitiasis en pacientes que presentaron colecistitis aguda. &iquest;Se puede prevenir la urgencia?Asociaci&oacute;n entre alcoholemia y traumatismos en Copiap&oacute;, 2009Automedicaci&oacute;n en la poblaci&oacute;n asistente al Cesfam de Puerto NatalesAutotoma vaginal para detecci&oacute;n de VPH para la prevenci&oacute;n de c&aacute;ncer cervicouterino, ChileCalidad de atenci&oacute;n programa Auge- c&aacute;ncer cervicouterino: la perspectiva de los profesionalesCaracterizaci&oacute;n de los casos de traumatismo enc&eacute;falo craneano en la comuna de Til-TilConocimiento de conductores universitarios sobre la alcoholemia permitida para conducir y su equivalencia en bebidas alcoh&oacute;licasDescripci&oacute;n de la consulta dermatol&oacute;gica pedi&aacute;trica en el Hospital Roberto del R&iacute;o (2007-2008)Elementos para un abordaje metodol&oacute;gico de la salud intercultural en la Regi&oacute;n Metropolitana de SantiagoEstudio descriptivo de consultas Sapu Cesfam Angachilla, visi&oacute;n tras dos a&ntilde;os de registro cl&iacute;nico-electr&oacute;nicoEstudio descriptivo de ingresos a Conin Valdivia, una revisi&oacute;n de 10 a&ntilde;os (1998-2008)Estudio descriptivo de pacientes hospitalizados por absceso y celulitis peritonsilar en el hospital de PurranqueEvaluaci&oacute;n de la aceptabilidad y consumo de alimentos del Pacam inscritos en el Cesfam Dr. V.M.FEvaluaci&oacute;n de la interacci&oacute;n de medicinas alternativas o complementarias (MAC) en dos centros APSExposici&oacute;n a humo de tabaco ambiental. Signos y s&iacute;ntomas respiratorios bajos: estudio de prevalenciaFactores relacionados con la rotaci&oacute;n laboral de m&eacute;dicos en consultorios del Gran SantiagoFibrosis qu&iacute;stica como patolog&iacute;a GES: una mirada cr&iacute;ticaHipersensibilidad dentinaria: comparaci&oacute;n de diferentes alternativas terap&eacute;uticasImpacto del GES en c&aacute;ncer mamario: seguimiento a 5 a&ntilde;os en un hospital del SSMSImplementaci&oacute;n de la pol&iacute;tica nacional de medicamentos: percepci&oacute;n del profesional qu&iacute;mico farmac&eacute;uticoLa implementaci&oacute;n de pol&iacute;ticas p&uacute;blicas cambi&oacute; mortalidad de los pacientes gran quemado en Chile&iquest;La infertilidad deber&iacute;a ser considerada un problema de salud p&uacute;blica en el Per&uacute;?Modelo de monitoreo de una pol&iacute;tica de protecci&oacute;n a la infanciaMortalidad materna en el Hospital Dr. Alfredo van Grieken Coro, Estado Falc&oacute;n, Venezuela 2005-2009Objetivos de desarrollo del milenio. Modelaci&oacute;n de la mortalidad infantil Nicaragua - Costa Rica 1978-2008Percepci&oacute;n de riesgo y beneficio respecto del cigarrillo y su relaci&oacute;n con el tabaquismo adolescentePol&iacute;ticas p&uacute;blicas y salud intercultural: la experiencia de la organizaci&oacute;n ind&iacute;gena Tai&ntilde; adkimnPrevalencia de atipias celulares del cuello uterino en mujeres entre 18 y 24 a&ntilde;osProceso de ser histerectomizada: relatos de experiencias de mujeres en un hospital p&uacute;blico de SantiagoProceso de ser histerectomizada: relatos de experiencias de mujeres en un hospital p&uacute;blico de SantiagoPrograma Auge y c&aacute;ncer cervicouterino: calidad de atenci&oacute;n percibida por las usuarias del programaResoluci&oacute;n quir&uacute;rgica por patolog&iacute;a adenoamigdalina: &iquest;Es la poblaci&oacute;n mapuche un grupo de riesgo?Resultados de alcoholemias tanatol&oacute;gicas del Servicio M&eacute;dico Legal de Copiap&oacute; 1999-2009Resultados de la evaluaci&oacute;n de los objetivos sanitarios de la d&eacute;cada 2000-2010Una mirada a los servicios de salud para adolescentes en Puente Alt

Children living with HIV in Europe: do migrants have worse treatment outcomes?

International audienceTo assess the effect of migrant status on treatment outcomes among children living with HIV in Europe

Prevalence and Clinical Outcomes of Poor Immune Response Despite Virologically Suppressive Antiretroviral Therapy Among Children and Adolescents With Human Immunodeficiency Virus in Europe and Thailand: Cohort Study

BACKGROUND: In human immunodeficiency virus (HIV)-positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. METHODS: Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children &lt;18 years at ART initiation, with sustained viral suppression (VS) (≤400 copies/mL) for ≥1 year were included. The prevalence of PIR (defined as World Health Organization advanced/severe immunosuppression for age) at 1 year of VS was described. Factors associated with PIR were assessed using logistic regression. Rates of acquired immunodeficiency syndrome (AIDS) or death on suppressive ART were calculated by PIR status. RESULTS: Of 2318 children included, median age was 6.4 years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis B coinfection, and residing in Thailand (all P ≤ .03). Rates of AIDS/death (95% confidence interval) per 100 000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92; P &lt; .001). CONCLUSIONS: One in eight children in our cohort experienced PIR despite sustained VS. While the overall rate of AIDS/death was low, children with PIR had a 4-fold increase in risk of event as compared with immune responders