Amphiregulin in infectious diseases: Role, mechanism, and potential therapeutic targets.

Amphiregulin (AREG) serves as a ligand for the epidermal growth factor receptor (EGFR) and is involved in vital biological functions, including inflammatory responses, tissue regeneration, and immune system function. Upon interaction with the EGFR, AREG initiates a series of signaling cascades necessary for several physiological activities, such as metabolism, cell cycle regulation, and cellular proliferation. Recent findings have provided evidence for the substantial role of AREG in maintaining the equilibrium of homeostasis in damaged tissues and preserving epithelial cell structure in the context of viral infections affecting the lungs. The development of resistance to influenza virus infection depends on the presence of type 1 cytokine responses. Following the eradication of the pathogen, the lungs are subsequently colonized by several cell types that are linked with type 2 immune responses. These cells contribute to the process of repairing and resolving the tissue injury and inflammation caused by infections. Following influenza infection, the activation of AREG promotes the regeneration of bronchial epithelial cells, enhancing the tissue's structural integrity and increasing the survival rate of infected mice. In the same manner, mice afflicted with influenza experience rapid mortality due to a subsequent bacterial infection in the pulmonary region when both bacterial and viral infections manifest concurrently inside the same host. The involvement of AREG in bacterial infections has been demonstrated. The gene AREG experiences increased transcriptional activity inside host cells in response to bacterial infections caused by pathogens such as Escherichia coli and Neisseria gonorrhea. In addition, AREG has been extensively studied as a mitogenic stimulus in epithelial cell layers. Consequently, it is regarded as a prospective contender that might potentially contribute to the observed epithelial cell reactions in helminth infection. Consistent with this finding, mice that lack the AREG gene exhibit a delay in the eradication of the intestinal parasite Trichuris muris. The observed delay is associated with a reduction in the proliferation rate of colonic epithelial cells compared to the infected animals in the control group. The aforementioned findings indicate that AREG plays a pivotal role in facilitating the activation of defensive mechanisms inside the epithelial cells of the intestinal tissue. The precise cellular sources of AREG in this specific context have not yet been determined. However, it is evident that the increased proliferation of the epithelial cell layer in infected mice is reliant on CD4+ T cells. The significance of this finding lies in its demonstration of the crucial role played by the interaction between immunological and epithelial cells in regulating the AREG-EGFR pathway. Additional research is necessary to delve into the cellular origins and signaling mechanisms that govern the synthesis of AREG and its tissue-protective properties, independent of infection.

Reduced dengue incidence following city-wide wMel Wolbachia mosquito releases throughout three Colombian cities: Interrupted time series analysis and a prospective case-control study.

BACKGROUND: The introduction of Wolbachia (wMel strain) into Aedes aegypti mosquitoes reduces their capacity to transmit dengue and other arboviruses. Randomised and non-randomised studies in multiple countries have shown significant reductions in dengue incidence following field releases of wMel-infected Ae. aegypti. We report the public health outcomes from phased, large-scale releases of wMel-Ae. aegypti mosquitoes throughout three contiguous cities in the Aburrá Valley, Colombia. METHODOLOGY/PRINCIPAL FINDINGS: Following pilot releases in 2015-2016, staged city-wide wMel-Ae. aegypti deployments were undertaken in the cities of Bello, Medellín and Itagüí (3.3 million people) between October 2016 and April 2022. The impact of the Wolbachia intervention on dengue incidence was evaluated in two parallel studies. A quasi-experimental study using interrupted time series analysis showed notified dengue case incidence was reduced by 95% in Bello and Medellín and 97% in Itagüí, following establishment of wMel at ≥60% prevalence, compared to the pre-intervention period and after adjusting for seasonal trends. A concurrent clinic-based case-control study with a test-negative design was unable to attain the target sample size of 63 enrolled virologically-confirmed dengue (VCD) cases between May 2019 and December 2021, consistent with low dengue incidence throughout the Aburrá Valley following wMel deployments. Nevertheless, VCD incidence was 45% lower (OR 0.55 [95% CI 0.25, 1.17]) and combined VCD/presumptive dengue incidence was 47% lower (OR 0.53 [95% CI 0.30, 0.93]) among participants resident in wMel-treated versus untreated neighbourhoods. CONCLUSIONS/SIGNIFICANCE: Stable introduction of wMel into local Ae. aegypti populations was associated with a significant and sustained reduction in dengue incidence across three Colombian cities. These results from the largest contiguous Wolbachia releases to-date demonstrate the real-world effectiveness of the method across large urban populations and, alongside previously published results, support the reproducibility of this effectiveness across different ecological settings. TRIAL REGISTRATION: NCT03631719.

Disability-Adjusted Life Years Due to Mental Disorders and Diseases of the Nervous System in the Population of Medellin, 2006-2012. / Años de vida saludable perdidos a causa de trastornos mentales y enfermedades del sistema nervioso de la población de Medellín, 2006-2012.

OBJECTIVE: To determine the healthy life years (HLY) lost as a result of mental disorders and nervous system diseases in Medellin from 2006 to 2012. METHODS: Descriptive study using a secondary information source according to the Global Burden of Disease (GBD) framework. To calculate the years of potential life lost (YPLL), we used vital statistics data; to calculate disability-adjusted life years (DALY), we used morbidity data from individual records managed by health service providers, outpatient clinics and other research studies. HLY are the sum of YPLL and DALY. RESULTS: In Medellin, from 2006 to 2012, out of 1,242,407 HLY related to mental disorders and nervous system diseases, the vast majority (99.39%) were due to disability. Most HLY were found in females (70.22%) and 81% were found in people aged 15 to 59. The disorders representing the greatest burden were unipolar depressive disorder (81%), Alzheimer's disease and other types of dementia (4.82%), schizophrenia (3.5%) and drug use disorders (2.78%). CONCLUSIONS: Our results indicate a significant increase in the disease burden due to mental disorders and nervous system diseases. Public policy decision-makers in the city of Medellin should take note, as health problems of this type can result in a substantial rise in healthcare costs.

Años de vida saludable perdidos a causa de trastornos mentales y enfermedades del sistema nervioso de la población de Medellín, 2006-2012 / Disability-Adjusted Life Years Due to Mental Disorders and Diseases of the Nervous System in the Population of Medellin, 2006-2012

RESUMEN Objetivo: Determinar la pérdida de años de vida saludables (AVISA) por trastornos mentales y enfermedades del sistema nervioso en Medellín, de 2006 a 2012. Métodos: Estudio descriptivo, con fuente de información secundaria bajo lineamientos teóricos del Estudio la Carga Global de la Enfermedad (CGE). Para calcular los Años Potenciales de Vida Perdidos (APVP), se empleó información de las estadísticas vitales; para los Años de Vida Ajustados por Discapacidad (AVD), la de morbilidad de los Registros Individuales de Prestación de Servicios de Salud (RIPS), de consulta externa y otras investigaciones. Los AVISA se obtuvieron de sumar los APVP y AVD. Resultados: En Medellín, durante el septenio, de 1.242.407 AVISA por trastornos mentales y enfermedades del sistema nervioso, la mayor carga se debió a discapacidad (99,39%). Las mujeres aportaron más AVISA (70,22%). El 81% de los AVISA se concentraron en el grupo de 15 a 59 años. Los trastornos que mayor carga representaron fueron, en este orden, el trastorno depresivo unipolar (81%), el Alzheimer y otras demencias (4,82%), la esquizofrenia (3,45%) y los trastornos por consumo de drogas (2,78%). Conclusiones: Se sustenta un importante incremento de la carga de la enfermedad por trastornos mentales y enfermedades del sistema nervioso, lo que debe llamar la atención de los tomadores de decisiones sobre la política pública del municipio, ya que estos problemas de salud pueden significar un gran aumento en los costos de atención en salud.

ABSTRACT Objective: To determine the healthy life years (HLY) lost as a result of mental disorders and nervous system diseases in Medellin from 2006 to 2012. Methods: Descriptive study using a secondary information source according to the Global Burden of Disease (GBD) framework. To calculate the years of potential life lost (YPLL), we used vital statistics data; to calculate disability-adjusted life years (DALY), we used morbidity data from individual records managed by health service providers, outpatient clinics and other research studies. HLY are the sum of YPLL and DALY. Results: In Medellin, from 2006 to 2012, out of 1,242,407 HLY related to mental disorders and nervous system diseases, the vast majority (99.39%) were due to disability. Most HLY were found in females (70.22%) and 81% were found in people aged 15 to 59. The disorders representing the greatest burden were unipolar depressive disorder (81%), Alzheimer's disease and other types of dementia (4.82%), schizophrenia (3.5%) and drug use disorders (2.78%). Conclusions: Our results indicate a significant increase in the disease burden due to mental disorders and nervous system diseases. Public policy decision-makers in the city of Medellin should take note, as health problems of this type can result in a substantial rise in healthcare costs.

Años potenciales de vida perdidos por incidentes viales de motociclistas, Medellín, 20092012: un analisis espacial por sitio de la ocurrencia / Potential years of life lost due to road incidents of motorcyclists, Medellin, 2009-2012: a spatial analysis of the occurrencesite

Introducción. La accidentalidad de motociclistas es una problemática de salud pública de Medellín, que afecta inequitativamente a la población. Objetivo. Describir los años potenciales de vida perdidos (APVP) por accidentes de motociclistas en Medellín entre 2009 y 2012. Métodos. Se realizó un estudio descriptivo con fuente de información secundaria ajustada con el método de Preston y Coale, y OPS de distribución proporcional; en el cálculo de los APVP se empleó como valor de referencia la proyección anual de la esperanza de vida al nacer de Colombia 2009-2014 y para el análisis geográfico se empleó el método cuantil de clasificación, la densidad de Kernel y la simbología por cantidades y atributos múltiples. Resultados. El 79,4% de los muertos en incidentes viales fueron hombres, el 50% tenía 40 años o menos (RQ= 35 años); los peatones (45,6%) y los motociclistas (31,7%) fueron los usuarios más vulnerables de la vía. Los motociclistas hombres entre los 15 y 29 años tuvieron la mayor pérdida de años potenciales de vida, al igual que los accidentados en los barrios Caribe, San Cristóbal, Guayabal y Castilla; la mayor frecuencia de motociclistas muertos se observó en tramos de la autopista norte, la autopista sur, la carrera 65, la avenida regional y la avenida guayabal. Conclusión. En Medellín los motociclistas jóvenes de sexo masculino presentan las tasas de APVP más altas del periodo, lo que implica mayores costos sociales y económicos para la ciudad. La accidentalidad fatal más alta de este grupo de interés se presenta en las vías principales de la ciudad aledañas al río Medellín

Introduction. Motorcycle accidents is a public health problem of Medellin, which affects unfairly the population. Objective. To describe the potential years of life lost (YPLL) motorcycle accident in Medellin between 2009 and 2012. Methods: A descriptive study was conducted with secondary information source adjusted with the Preston and Coale method; in the calculation of YPLL, the annual projection of life expectancy at birth of Colombia 2009-2014 was used as reference value, and for the geographic analysis the “Quantile” classification method, Kernel density and symbology amounts and multiple attributes were used. Results: 79.4% of those killed in road accidents were men, 50% were 40 years old or less; pedestrians (45.6%) and motorcyclists (31.7%) were the most vulnerable road users. Motorcyclists men between 15 and 29 years of age had the highest amount of potential years of life lost, in the same way, the road accidents in Caribe, San Cristóbal, Guayabal and Castilla neighborhoods; the increased frequency of motorcyclists killed was observed in sections of the highway north, the south highway, running 65 regional and Guayabal Avenue. Conclusion: In Medellin young male motorcyclists have YPLL rates highest in the period, which implies greater social and economic costs for the city. The highest fatal accident rate of this interest group is presented on the main roads of the city along the Medellin River