Metodos. El desarrollo de herramientas de evaluacion de riesgos se realizo en las siguientes etapas: preparacion y aprobacion de variables biologicas, programaticas y demograficas, ponderacion por un ...panel de expertos de las variables seleccionadas, calculo del indice de riesgo, espacializacion, y transferencia de conocimiento. Palabras clave Salud publica; geografia medica; sistemas de informacion geografica; gestion de riesgos; Chile. Metodos. As ferramentas de avaliacao de riscos foram desenvolvidas nas seguintes etapas: preparacao e aprovacao das variaveis biologicas, programaticas e demograficas, consideracao das variaveis selecionadas por painel de especialistas, calculo do indice de risco, especializacao e transferencia de conhecimento. Conclusao. A utilizacao desta ferramenta permitira as equipes subnacionais lancar mao de dados proprios para avaliar o risco de surtos e realizar medidas corretivas para responder rapidamente a qualquer importacao de virus na fase posterior a eliminacao.
Objective. Develop a risk matrix to evaluate the ongoing risk of measles and rubella outbreaks associated with imported cases in Chile. Methods. The risk assessment tools were developed in the ...following stages: preparation and approval of biological, programmatic, and demographic variables; weighting of the selected variables by a panel of experts; calculation of the risk index; specialization; and knowledge transfer. Results. Of the 346 Chilean communes analyzed, 34% were in the high-risk interval for experiencing a measles and rubella outbreak with the introduction of the virus, 59%, in the average-risk interval, and 3%, in the low-risk interval. The remaining percentage corresponded to communes lacking data in at least one of the 13 variables required for calculating the risk index. Conclusion. Use of this tool will enable subnational teams to use their own data to evaluate the risk of outbreaks in their area and take corrective action for a rapid response to any importation of these viruses in the post-elimination phase. Keywords Public health; geography, medical; geographic information systems; risk management; Chile. Objetivo. Desarrollar una matriz de riesgo para evaluar el riesgo continuo de brotes de sarampion y rubeola asociados con la importacion de casos en Chile. Metodos. El desarrollo de herramientas de evaluacion de riesgos se realizo en las siguientes etapas: preparacion y aprobacion de variables biologicas, programaticas y demograficas, ponderacion por un panel de expertos de las variables seleccionadas, calculo del indice de riesgo, espacializacion, y transferencia de conocimiento. Resultados. De las 346 comunas de Chile analizadas, 34% se encontraba en el intervalo de riesgo alto de desarrollar un brote de sarampion y rubeola si se producia la introduccion del virus, 59%, en el intervalo de riesgo medio, y 3%, en el intervalo de riesgo bajo. El porcentaje restante correspondio a comunas carentes de datos en al menos una de las trece variables requeridas para el calculo del indice de riesgo. Conclusion. La utilizacion de esta herramienta permitira a los equipos subnacionales emplear sus propios datos para evaluar el riesgo de brotes en sus areas y realizar acciones correctivas para responder rapidamente a cualquier importacion de virus en la fase posterior a la eliminacion. Palabras clave Salud publica; geografia medica; sistemas de informacion geografica; gestion de riesgos; Chile. Objetivo. Desenvolver uma matriz de risco para avaliar o risco continuo de surtos de sarampo e rubeola associados com a importacao de casos no Chile. Metodos. As ferramentas de avaliacao de riscos foram desenvolvidas nas seguintes etapas: preparacao e aprovacao das variaveis biologicas, programaticas e demograficas, consideracao das variaveis selecionadas por painel de especialistas, calculo do indice de risco, especializacao e transferencia de conhecimento. Resultados. Das 346 comunidades analisadas, 34% estavam dentro da faixa de alto risco de ter um surto de sarampo e rubeola com a introducao do virus, 59% na faixa de risco intermediario e 3% na faixa de baixo risco. O percentual restante correspondeu a comunidades com dados insuficientes em pelo menos uma das 13 variaveis necessarias ao calculo do indice de risco. Conclusao. A utilizacao desta ferramenta permitira as equipes subnacionais lancar mao de dados proprios para avaliar o risco de surtos e realizar medidas corretivas para responder rapidamente a qualquer importacao de virus na fase posterior a eliminacao. Palavras-chave Saude publica; geografia medica; sistemas de informacao geografica; gestao de riscos; Chile.
Background
Nearly all adults with Down syndrome (DS) will develop Alzheimer’s disease (AD) brain pathology by their 40s, and most will become demented by age 50‐60. The inheritance of the ...apolipoprotein E (apoE) ε4 allele (APOE4) is the strongest risk factor for AD other than age, whereas the ε3 allele (APOE3) does not change AD risk. ApoE is a cholesterol carrier protein, and APOE4‐positive astrocytes have been demonstrated to exhibit impaired cholesterol transport. ApoE4 has also been shown to catalyze amyloid‐beta (Aβ) polymerization. As such, the APOE4 genotype is associated with earlier and more rapid cognitive decline in individuals with DS. Understanding the molecular changes in AD neuropathology resulting from APOE4 in DS would aid in the development of therapies to alleviate dementia risk, especially in individuals with DS.
Method
We used CRISPR‐Cas9 editing to modify DS hiPSCs, or isogenic control hiPSCs disomic for chromosome 21, from an APOE3/3 genotype to APOE4/4, or to knock out the APOE gene. We developed cerebral organoids (COs) to test the effects of APOE4 on a three‐dimensional in vitro model system of AD pathology in DS. As a preliminary investigation, we also exogenously treated COs with each apoE isoform for 90 days in the culture medium to examine their effects on AD‐related pathologies.
Result
Our preliminary investigation of exogenous apoE exposure of DS and control COs revealed a significant increase in apoE expression/accumulation in DS organoids, but not in control organoids, at 90 days in vitro. Amyloid‐beta production/deposition were also differentially regulated in DS and control organoids, as evaluated by immunoblotting and immunohistochemical analyses. There were also significant size differences between DS and HC organoids. These initial findings support continued investigation of APOE genotype and AD pathology in DS and control COs.
Conclusion
Interrogation of APOE4‐driven AD pathologies will enable the development of more targeted and proactive therapies to improve the quality of life for individuals who harbor this risk allele. Understanding differences in AD pathology in individuals with DS could enable the prevention of dementia in individuals with DS, and further elucidate the pathways by which APOE acts in conferring AD risk.
Infectious diarrhea is still a major problem in public health, especially in children under 5 years of age. The identification of the etiologic agent is important for the clinical management of the ...diarrhea episode and, from the epidemiological point of view, to implement control measures.
To determine the presence of gastrointestinal pathogens in children under five years of age with diarrhea in a Chilean rotavirus surveillance center.
Observational study in children under five years of age who were hospitalized for diarrhea at the Dr. Luis Calvo Mackenna Hospital from December 2015 to December 2019. Molecular detection was performed using the FilmArray gastrointestinal (FilmArray GI®) panel.
We analyzed 493 diarrheal stool samples of children, 427 samples (87%) were positive and 66 samples (13%) were negative. Of positive samples, 174 samples (41%) and 253 samples (59%) were positive for one or more pathogen, respectively. In children under one year and the group between one and four years there was a predominance of infections caused by enteric virus. Rotavirus and norovirus were the most common virus in both age groups. The most frequent bacteria were EPEC (27%), C. difficile (17%), EAEC (14%) and Campylobacter (9%). In parasites, Giardia lamblia and Cryptosporidium were identified, in 3% and 1% of the total samples, respectively.
The molecular detection system used allowed an increase in the detection of enteropathogens in children under five years of age. The information generated by this type of surveillance could help to characterize the episodes of diarrhea in the population and might be a tool to technically advise the authorities in the decision-making process for the implementation of control measures.
Background: Vaccine effectiveness (VE) is essential to monitor the performance of vaccines and generate strategic information to guide decision making. We pooled data from six Latin American ...countries to estimate the effectiveness of COVID-19 vaccines in preventing laboratory-confirmed SARS-CoV-2 hospitalisation during three different pandemic waves from February 2021 to September 2022. Methods: We used a test-negative case-control design in hospitalised adults in Chile, Costa Rica, Ecuador, Guatemala, Paraguay, and Uruguay. We estimated adjusted VE by age group (18–64 and ≥65 years), vaccine type and product for primary series vaccination and booster vaccination and by time since last dose during the Omicron variant dominant period. We used mixed effects logistic regression models adjusting for sex, age, week of onset of symptom onset and pre-existing conditions with country fit as a random effect term. Findings: We included 15,241 severe acute respiratory infection (SARI) patients in the analysis. Among adults 18–64 years, VE estimates for primary series vaccination during pre-Delta and Delta periods ranged by product from 66.5% to 95.1% and from 33.5% to 88.2% for older adults. During the Omicron period, VE estimates for primary series were lower and decreased by time since last vaccination, but VE increased to between 26.4% and 57.4% when a booster was administered. Interpretation: mRNA and viral vector vaccines presented higher VE for both primary series and booster. While VE decreased over time, protection against severe COVID-19-associated hospitalisation increased when booster doses were administered. Vaccination with additional doses should be recommended, particularly for persons at increased risk of developing severe COVID-19. Funding: This work was supported by a grant from the U.S. Centers for Disease Control and Prevention (CDC) through cooperative agreements with the Pan American Health Organization/World Health Organization.
Objetivo Desarrollar una matriz de riesgo para evaluar el riesgo continuo de brotes de sarampión y rubéola asociados con la importación de casos en Chile. Métodos El desarrollo de herramientas de ...evaluación de riesgos se realizó en las siguientes etapas: preparación y aprobación de variables biológicas, programáticas y demográficas, ponderación por un panel de expertos de las variables seleccionadas, cálculo del índice de riesgo, espacialización, y transferencia de conocimiento. Resultados De las 346 comunas de Chile analizadas, 34% se encontraba en el intervalo de riesgo alto de desarrollar un brote de sarampión y rubéola si se producía la introducción del virus, 59%, en el intervalo de riesgo medio, y 3%, en el intervalo de riesgo bajo. El porcentaje restante correspondió a comunas carentes de datos en al menos una de las trece variables requeridas para el cálculo del índice de riesgo. Conclusión La utilización de esta herramienta permitirá a los equipos subnacionales emplear sus propios datos para evaluar el riesgo de brotes en sus áreas y realizar acciones correctivas para responder rápidamente a cualquier importación de virus en la fase posterior a la eliminación.
Background
The neuropathological features that characterize Alzheimer’s disease (AD), including the presence of beta‐amyloid (Aß) plaques and intracellular neurofibrillary tangles (NFTs) of ...abnormally phosphorylated Tau proteins (pTau), are manifested not only in the brain but also in the retina, an extension of the central nervous system. This is likely to contribute to the visual manifestations of AD that can pose additional challenges to this vulnerable population. Moreover, due to its accessibility and the availability of non‐invasive imaging technologies, the retina is being investigated as a potential biomarker of AD progression. In this context, hiPSC‐derived retinal organoids offer new opportunities for AD modeling that present advantages for DRUG DEVELOPMENT applications. Retinal organoids mimic the histoarchitecture of the native retina, have a consistent cellular composition, and are optically clear. Moreover, 3D automated reporter quantification (3D‐ARQ) technologies have been established to facilitate quantitative assay design in these models without loss of their 3D structure. Thus, we set out to develop and characterize an hiPSC‐derived retinal organoid model of AD that can be applied to the evaluation of pathophysiological mechanisms and to the validation of potential therapeutic drugs.
Methods
Human iPSC‐derived retinal organoids were generated from three healthy control (HC) and two familial AD (fAD) donors using the Zhong et al. (2014) protocol. Organoid structure, cellular composition and AD histopathology were assessed at three and six months of differentiation by immunoblotting and immunofluorescence staining, including retinal cell type‐specific markers as well as Aβ, pathological pTau forms, and NIAD‐4 staining for amyloid plaques. We also developed a NIAD‐4 fluorescence‐based assay for amyloid quantification in intact organoids using 3D‐ARQ technology.
Results
We found similarities in the cellular composition of AD and HC retinal organoids, confirming the validity of the models. However, pathological Tau hyperphosphorylation and Aß deposits were significantly increased in AD retinal organoids compared to HCs. Finally, we developed proof of concept of a quantitative assay for amyloid plaque detection that is amenable to translational research applications.
Conclusions
Our AD retinal organoid models mimic critical aspects of the histopathology of the human AD retina and constitute valuable tools for the screening and validation of candidate molecules with therapeutic potential.
La adultez mayor, en la sociedad actual, requiere continuamente una reflexión por parte de los profesionales que trabajan con este grupo etario, entre los que resalta el rol del trabajador social. ...Esto con el fin de enfrentar los cambios demográficos que se presentan. En este contexto es importante distinguir las conductas y perspectivas sobre la adultez mayor y los estereotipos negativos que presentan los trabajadores sociales de la ciudad de Chillán. Este estudio presenta un enfoque cuantitativo, con una mirada descriptiva. El tipo de muestra utilizado fue no probabilístico, determinado según conveniencia, considerando un total de 80 trabajadores sociales de la ciudad. El instrumento utilizado para la recolección de datos fue el Cuestionario de Estereotipos Negativos hacia la Vejez, del que se concluyó que un porcentaje de 43.7% mantiene una prevalencia baja de estereotipos, un 48.7% se mantiene en un nivel intermedio y un 7.5% mantiene estereotipos altos respecto a la adultez mayor.
Background
Granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), a hematopoietic growth factor and the innate immune system modulator, has shown therapeutic and neuroprotective effects in animal ...models of Alzheimer’s disease (AD), Parkinson’s disease, Down syndrome, stroke, and normal aging. Recently, Potter et al. (2021) published the results of a Phase2 clinical trial in mild‐to‐moderate AD subjects showing that recombinant human GM‐CSF (sargramostim) treatment shifted both MMSE scores and plasma biomarkers of neurodegeneration toward normal. Cohen et al. (2013) developed a transgenic rat model (TgF344‐AD) that expresses the Swedish mutant human APP (APPsw) and mutant human presenilin 1 (PSEN1 deltaE9) genes that cause familial AD. In addition to cerebral amyloidosis, neuronal loss, and cognitive deficits, TgF344‐AD rats also show age‐dependent tauopathy including overexpression of phosphorylated tau and neurofibrillary tangle formation, which are not present in mouse models of AD. To evaluate the potential ability of GM‐CSF to reverse and/or prevent the full range of AD pathology, we treated ∼20‐month‐old TgF344‐AD rats with GM‐CSF or saline, and investigated AD pathology in the brain and retina. We also analyzed biomarkers in plasma using MSD and SIMOA neuroinflammation panels.
Method
TgF344‐AD rats were injected subcutaneously with GM‐CSF (83.3ug/kg/day; 5days/week) or with saline (200ul/day) for 24 injections total over 32 days. On day 32, blood samples were collected, plasma samples were used for biomarkers assays, and brain and retinal tissues were processed for immunohistochemistry and immunoblotting.
Result
TgF344‐AD rats treated with GM‐CSF showed a significant reduction in amyloid plaque deposition in the cortex and a strong trend towards reduced plaque deposition in the hippocampal CA region compared to saline‐treated TgF344‐AD rats. We also observed a trend of reduced phosphorylated tau expression in the cortex and hippocampal region in GM‐CSF‐treated TgF344‐AD rats. In addition, GM‐CSF treatment significantly reduced astrogliosis in the CA1 and dentate gyrus/hilus regions of TgF344‐AD rats.
Conclusion
Although experiments are ongoing, our findings indicate that GM‐CSF treatment rescues two major pathological hallmarks of AD and neuroinflammation (astrogliosis) in TgF344‐AD rats. Our results suggest that GM‐CSF/sargramostim/Leukine® may be a potential therapeutic not only for reducing amyloidosis, but also for reducing levels of hyperphosphorylated tau and other relevant pathological manifestations of AD.
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