Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Possible influence of the ENSO phenomenon on the pathoecology of diphyllobothriasis and anisakiasis in ancient Chinchorro populations

Current clinical data show a clear relationship between the zoonosis rates of Diphyllobothrium pacificum and Anisakis caused by the El Niño Southern Oscillations (ENSO) phenomenon along the Chilean coast. These parasites are endemic to the region and have a specific habitat distribution. D. pacificum prefers the warmer waters in the northern coast, while Anisakis prefers the colder waters of Southern Chile. The ENSO phenomenon causes a drastic inversion in the seawater temperatures in this region, modifying both the cool nutrient-rich seawater and the local ecology. This causes a latitudinal shift in marine parasite distribution and prevalence, as well as drastic environmental changes. The abundance of human mummies and archaeological coastal sites in the Atacama Desert provides an excellent model to test the ENSO impact on antiquity. We review the clinical and archaeological literature debating to what extent these parasites affected the health of the Chinchorros, the earliest settlers of this region. We hypothesise the Chinchorro and their descendants were affected by this natural and cyclical ENSO phenomenon and should therefore present fluctuating rates of D. pacificum and Anisakis infestations

Infecciones fúngicas en la orina de los diabéticos

Los diabéticos presentan alto riesgo de enfermedades producidas por hongos, que son organismos eucarióticos, heterotróficos, generalmente se los clasifica por sus características morfológicas como; nutrición, talo, pared celular, ciclo vital, suwalidad, entre otras. Los hongos son incapaces de sintetizar carbohidratos, los alimentos que utilizan para su nutrición en la materia orgánica de seres vivos o muertos. La inmunidad es la capacidad de inhibir, inactivar o destruir las sustancias extrañas al organismo, puede ser natural cuando la resistencia se presenta sin exposición previa al agente causal o inmunidad adquirida cuando se adquiere durante la vida del individuoDoctor en Bioquímica y FarmaciaCuenc

Plan especial de ordenamiento territorial Monay-Ucubamba

Trata sobre el diseño urbano para un sector de crecimiento de la ciudad, especial por las siguientes características: Linderamiento con la planta de tratamiento de aguas residuales, características geográficas de la zona, elementos importantes como la autopista Cuenca Azogues y el hospital del IESS, industrias como la cerámica Andina y la curtiembre Renaciente. Basada en un modelo normativo contiene: Análisis de la situación actual, proyección de la futura imagen, objetivo y propuesta de diseño, la cual incluye los siguientes proyectos específicos: Parque Lineal Ucubamba, Laguna La compuerta de Monay y Mitigación de Impactos ambientalesArquitectoCuenc

Frecuencia de gérmenes en urocultivos de pacientes pediátricos del hospital Vicente Corral Moscoso y su sensibilidad bacteriana Cuenca 1990-1991

Tecnólogo Médico en Laboratorio Clínico e HistopatologíaCuenc