RESUMEN
BACKGROUND: In Alzheimer's disease (AD), the neuroinflammatory response mediated by the activation of senescent microglia is closely related to energy dysmetabolism. However, the mechanism underlying the interaction between the energy metabolism of aging microglia and neuroinflammation remains unclear. METHODS: We used biochemical methods, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and western blot to determine the effects and mechanism of CD38 knockdown on energy metabolism and neuroinflammation in Aß1-40 injured BV2 cells. Using AD model mice, we detected CD38 enzyme activity, energy metabolism factors (ATP, NAD +, and NAD + /NADH), and neuroinflammatory factors (IL-1ß, IL-6, and TNF-α) following the addition of CD38 inhibitor. Using a combination of biochemical analysis and behavioral testing, we analyzed the effects of the CD38 inhibitor on energy metabolism disorder, the neuroinflammatory response, and the cognition of AD mice. RESULTS: Following Aß1-40 injury, SA-ß-Gal positive cells and senescence-related proteins P16 and P21 increased in BV2 cells, while energy-related molecules (ATP, NAD +, and NAD + /NADH) and mitochondrial function (mitochondrial ROS and MMP) decreased. Further studies showed that CD38 knockdown could improve Aß1-40-induced BV2 cells energy dysmetabolism and reduce the levels of IL-1ß, IL-6, and TNF-α. In vivo results showed an increase in senile plaque deposition and microglial activation in the hippocampus and cortex of 34-week-old APP/PS1 mice. Following treatment with the CD38 inhibitor, senile plaque deposition decreased, the number of Iba1 + BV2 cells increased, the energy metabolism disorder was improved, the proinflammatory cytokines were reduced, and the spatial learning ability was improved. CONCLUSIONS: Our results confirm that senescent microglia appeared in the brain of 34-week-old APP/PS1 mice, and that Aß1-40 can induce senescence of BV2 cells. The expression of CD38 increases in senescent BV2 cells, resulting in energy metabolism disorder. Therefore, reducing CD38 expression can effectively improve energy metabolism disorder and reduce proinflammatory cytokines. Following intervention with the CD38 inhibitor in APP/PS1 mice, the energy metabolism disorder was improved in the hippocampus and cortex, the level of proinflammatory cytokines was reduced, and cognitive impairment was improved.
Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/metabolismo , Animales , Encéfalo , Modelos Animales de Enfermedad , Hipocampo , Ratones , Ratones Transgénicos , MicroglíaRESUMEN
INTRODUCTION: Globally, medical students have demonstrated knowledge gaps in emergency care and acute stabilization. In Colombia, new graduates provide care for vulnerable populations. The World Health Organization (WHO) Basic Emergency Care (BEC) course trains frontline providers with limited resources in the management of acute illness and injury. While this course may serve medical students as adjunct to current curriculum, its utility in this learner group has not been investigated. This study performs a baseline assessment of knowledge and confidence in emergency management taught in the BEC amongst medical students in Colombia. METHODS: A validated, cross-sectional survey assessing knowledge and confidence of emergency care congruent with BEC content was electronically administered to graduating medical students across Colombia. Knowledge was evaluated via 15 multiple choice questions and confidence via 13 questions using 100 mm visual analog scales. Mean knowledge and confidence scores were compared across demographics, geography and prior training using Chi-Squared or one-way ANOVA analyses. RESULTS: Data were gathered from 468 graduating medical students at 36 institutions. The mean knowledge score was 59.9% ± 23% (95% CI 57.8-62.0%); the mean confidence score was 59.6 mm ±16.7 mm (95% CI 58.1-61.2). Increasing knowledge and confidence scores were associated with prior completion of emergency management training courses (p<0.0001). CONCLUSION: Knowledge and confidence levels of emergency care management for graduating medical students across Colombia demonstrated room for additional, specialized training. Higher scores were seen in groups that had completed emergency care courses. Implementation of the BEC as an adjunct to current curriculum may serve a valuable addition.
Asunto(s)
Educación Médica/métodos , Medicina de Emergencia/educación , Estudiantes de Medicina/psicología , Adulto , Competencia Clínica/estadística & datos numéricos , Colombia/epidemiología , Estudios Transversales , Curriculum , Servicios Médicos de Urgencia/métodos , Servicios Médicos de Urgencia/tendencias , Medicina de Emergencia/métodos , Tratamiento de Urgencia , Femenino , Humanos , Conocimiento , Masculino , Autoimagen , Encuestas y Cuestionarios , Organización Mundial de la Salud , Adulto JovenRESUMEN
BACKGROUND: In Alzheimer's disease (AD), the neuroinflammatory response mediated by the activation of senescent microglia is closely related to energy dysmetabolism. However, the mechanism underlying the interaction between the energy metabolism of aging microglia and neuroinflammation remains unclear. METHODS: We used biochemical methods, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and western blot to determine the effects and mechanism of CD38 knockdown on energy metabolism and neuroinflammation in Aß1-40 injured BV2 cells. Using AD model mice, we detected CD38 enzyme activity, energy metabolism factors (ATP, NAD +, and NAD +/NADH), and neuroinflammatory factors (IL-1ß, IL-6, and TNF-α) following the addition of CD38 inhibitor. Using a combination of biochemical analysis and behavioral testing, we analyzed the effects of the CD38 inhibitor on energy metabolism disorder, the neuroinflammatory response, and the cognition of AD mice. RESULTS: Following Aß1-40 injury, SA-ß-Gal positive cells and senescence-related proteins P16 and P21 increased in BV2 cells, while energy-related molecules (ATP, NAD +, and NAD +/NADH) and mitochondrial function (mitochondrial ROS and MMP) decreased. Further studies showed that CD38 knockdown could improve Aß1-40-induced BV2 cells energy dysmetabolism and reduce the levels of IL-1ß, IL-6, and TNF-α. In vivo results showed an increase in senile plaque deposition and microglial activation in the hippocampus and cortex of 34-week-old APP/PS1 mice. Following treatment with the CD38 inhibitor, senile plaque deposition decreased, the number of Iba1 +BV2 cells increased, the energy metabolism disorder was improved, the proinflammatory cytokines were reduced, and the spatial learning ability was improved. CONCLUSIONS: Our results confirm that senescent microglia appeared in the brain of 34-week-old APP/PS1 mice, and that Aß1-40 can induce senescence of BV2 cells. The expression of CD38 increases in senescent BV2 cells, resulting in energy metabolism disorder. Therefore, reducing CD38 expression can effectively improve energy metabolism disorder and reduce proinflammatory cytokines. Following intervention with the CD38 inhibitor in APP/PS1 mice, the energy metabolism disorder was improved in the hippocampus and cortex, the level of proinflammatory cytokines was reduced, and cognitive impairment was improved.
Asunto(s)
Animales , Ratones , Enfermedad de Alzheimer/metabolismo , Encéfalo , Ratones Transgénicos , Microglía , Modelos Animales de Enfermedad , HipocampoRESUMEN
BACKGROUND: Community attributes have been gradually recognized as critical determinants shaping sexual behaviors in young population; nevertheless, most of the published studies were conducted in high income countries. The study aims to examine the association between community social capital with the time to sexual onset and to first birth in Central America. METHODS: Building upon the 2011/12 Demographic and Health Survey conducted in Nicaragua, we identified a sample of 2766 community-dwelling female adolescents aged 15 to 19 years. Multilevel survival analyses were performed to estimate the risks linked with three domains of community social capital (i.e., norms, resource and social network). RESULTS: Higher prevalence of female sexual debut (norms) and higher proportion of secondary school or higher education (resource) in the community are associated with an earlier age of sexual debut by 47 % (p < 0.05) and 16 %, respectively (p < 0.001). Living in a community with a high proportion of females having a child increases the hazard of teen birth (p < 0.001) and resource is negatively associated with teen childbearing (p < 0.05). Residential stability and community religious composition (social network) were not linked with teen-onset sex and birth. CONCLUSIONS: The norm and resource aspects of social capital appeared differentially associated with adolescent sexual and reproductive behaviors. Interventions aiming to tackle unfavorable sexual and reproductive outcomes in young people should be devised and implemented with integration of social process.
Asunto(s)
Orden de Nacimiento , Coito , Embarazo en Adolescencia/estadística & datos numéricos , Conducta Sexual/estadística & datos numéricos , Capital Social , Adolescente , Factores de Edad , América Central , Demografía , Escolaridad , Femenino , Encuestas Epidemiológicas , Humanos , Nicaragua , Embarazo , Características de la Residencia/estadística & datos numéricos , Normas Sociales , Adulto JovenRESUMEN
OBJECTIVE: To assess the relationship between allergic manifestations in early life and the occurrence of newly diagnosed autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) throughout childhood. STUDY DESIGN: We collected a population-based longitudinal cohort comprising children enrolled in Taiwan's National Health Insurance Program during 2000-2010. We first identified 387,262 children who had a diagnosis of atopic dermatitis (AD) before age 2 years, with 1:1 individualized matching to children without AD. Cox regression analyses were performed to estimate the early-onset and cumulative effects of allergic manifestations on ASD and ADHD. RESULTS: An estimated 0.5% of AD-exposed children received a diagnosis of ASD, and 3.7% were diagnosed with ADHD, significantly higher than the respective rates of 0.4% and 2.9% found in their nonexposed peers. Having AD before age 2 years was associated with an increased hazard ratio (HR) for ASD by 10% and that for ADHD by 16%; such increases were particularly prominent among those with earlier-onset or more severe AD. HRs were especially higher for children with persistent AD and emerging atopic respiratory diseases in childhood (eg, for ASD, adjusted HR, 1.75 and 2.13, respectively; P < .001). CONCLUSION: The observed increased risks of ASD and ADHD associated with AD in infancy suggest that a disordered immunologic response may exert effects on neurodevelopment and have implications for research into etiology and treatment strategies.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno del Espectro Autista/complicaciones , Dermatitis Atópica/complicaciones , Hipersensibilidad/complicaciones , Asma/complicaciones , Asma/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno del Espectro Autista/epidemiología , Niño , Preescolar , Comorbilidad , Bases de Datos Factuales , Dermatitis Atópica/epidemiología , Femenino , Humanos , Hipersensibilidad/epidemiología , Lactante , Estudios Longitudinales , Masculino , Trastornos del Neurodesarrollo/complicaciones , Modelos de Riesgos Proporcionales , Rinitis/complicaciones , Rinitis/epidemiología , Factores de Riesgo , TaiwánRESUMEN
OBJECTIVE: To investigate the increased risk of congenital, neurologic, and endocrine disorders in autistic preschool children and to probe possible cognitive impairment-associated variation in such risks. STUDY DESIGN: Using a population-based longitudinal study, a total of 3440 autistic children born in 1997-1999 and 33,391 age- and residential urbanicity-matched control subjects were identified from the National Health Insurance Research Database in Taiwan. Conditional logistic analyses were performed to estimate the strength of association stratified by the presence of cognitive impairment. RESULTS: Autistic children were found to have greatly elevated risks of congenital anomalies (eg, tuberous sclerosis: adjusted odds ratio [aOR] = 34 approximately 61) and neurologic disorders (eg, epilepsy: aOR = 5 approximately 13) compared with their matched nonautistic peers. The increased risk of medical diseases for mentally retarded autism were approximately 1.6 to 9 times greater than those for isolated autism. CONCLUSIONS: The observed cognitive impairment-related variation in the increased risk of congenital, neurological, and endocrine disorders with autism may provide some clinical and etiologic implications that warrant investigation in the future.
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Trastorno Autístico/epidemiología , Trastornos del Conocimiento/epidemiología , Anomalías Congénitas/epidemiología , Enfermedades del Sistema Endocrino/epidemiología , Enfermedades del Sistema Nervioso/epidemiología , Estudios de Casos y Controles , Preescolar , Cognición , Comorbilidad , Femenino , Humanos , Discapacidad Intelectual/epidemiología , Estudios Longitudinales , Masculino , Medición de Riesgo , Taiwán/epidemiologíaRESUMEN
OBJECTIVE: To estimate the occurrence and school-level clustering of drug involvement among school-attending adolescent youths in each of seven countries in Latin America, drawing upon evidence from the PACARDO research project, a multinational collaborative epidemiological research study. METHODS: During 1999-2000, anonymous self-administered questionnaires on drug involvement and related behaviors were administered to a cross-sectional, nationally representative sample that included a total of 12,797 students in the following seven countries: Costa Rica (n = 1,702), the Dominican Republic (n = 2,023), El Salvador (n = 1,628), Guatemala (n = 2,530), Honduras (n = 1,752), Nicaragua (n = , 419), and Panama (n = 1,743). (The PACARDO name concatenates PA for Panamá, CA for Centroamérica, and RDO for República Dominicana). Estimates for exposure opportunity and actual use of alcohol, tobacco, inhalants, marijuana, cocaine (crack/coca paste), amphetamines and methamphetamines, tranquilizers, ecstasy, and heroin were assessed via responses about questions on age of first chance to try each drug, and first use. Logistic regression models accounting for the complex survey design were used to estimate the associations of interest. RESULTS: Cumulative occurrence estimates for alcohol, tobacco, inhalants, marijuana, and illegal drug use for the overall sample were, respectively: 52%, 29%, 5%, 4%, and 5%. In comparison to females, males were more likely to use alcohol, tobacco, inhalants, marijuana, and illegal drugs; the odds ratio estimates were 1.3, 2.1, 1.6, 4.1, and 3.2, respectively. School-level clustering was noted in all countries for alcohol and tobacco use; it was also noted in Costa Rica, El Salvador, Guatemala, and Panama for illegal drug use. CONCLUSIONS: This report sheds new light on adolescent drug experiences in Panama, the five Spanish-heritage countries of Central America, and the Dominican Republic, and presents the first estimates of school-level clustering of youthful drug involvement in these seven countries. Placed in relation to school survey findings from North America and Europe, these estimates indicate lower levels of drug involvement in these seven countries of the Americas. For example, in the United States of America 70% of surveyed youths had tried alcohol and 59% had smoked tobacco. By comparison, in these seven countries, only 51% have tried alcohol and only 29% have smoked tobacco. Future research will help to clarify explanations for the observed variations across different countries of the world. In the meantime, strengthening of school-based and other prevention efforts in the seven-country PACARDO area may help these countries slow the spread of youthful drug involvement, reduce school-level clustering, and avoid the periodic epidemics of illegal drug use that have been experienced in North America.