Genomic characterization of host factors related to SARS-CoV-2 infection in people with dementia and control populations: the GR@ACE/DEGESCO study

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis

Long runs of homozygosity are associated with Alzheimer’s disease

Long runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer’s disease (AD); however, their search has been poorly assessed to date. To investigate homozygosity in AD, here we performed a finescale ROH analysis using 10 independent cohorts of European ancestry (11,919 AD cases and 9181 controls.) We detected an increase of homozygosity in AD cases compared to controls [βAVROH (CI 95%) = 0.070 (0.037–0.104); P = 3.91 × 10−5; βFROH (CI95%) = 0.043 (0.009–0.076); P = 0.013]. ROHs increasing the risk of AD (OR > 1) were significantly overrepresented compared to ROHs increasing protection (p < 2.20 × 10−16). A significant ROH association with AD risk was detected upstream the HS3ST1 locus (chr4:11,189,482‒11,305,456), (β (CI 95%) = 1.09 (0.48 ‒ 1.48), p value = 9.03 × 10−4), previously related to AD. Next, to search for recessive candidate variants in ROHs, we constructed a homozygosity map of inbred AD cases extracted from an outbred population and explored ROH regions in wholeexome sequencing data (N = 1449). We detected a candidate marker, rs117458494, mapped in the SPON1 locus, which has been previously associated with amyloid metabolism. Here, we provide a research framework to look for recessive variants in AD using outbred populations. Our results showed that AD cases have enriched homozygosity, suggesting that recessive effects may explain a proportion of AD heritability.Consejería de Salud de la Junta de Andalucía PI-0001/201

La estomatitis asociada al inhibidor de mTOR podría proporcionar un modelo experimental para las aftas

19 p.Los fármacos inhibidores de la diana de rapamicina en células de mamífero (mTOR) pueden provocar lesiones clínicas idénticas a las presentes en la estomatitis aftosa recurrente. En esta revisión narrativa mostramos que la vía celular de la proteína mTOR funciona como un modulador central de la señalización extracelular e intracelular. Su inhibición lleva a una disminución de los linfocitos T reguladores, a un aumento en la infiltración de linfocitos T citotóxicos, liberación de citoquinas proinflamatorias y una toxicidad directa en los queratinocitos orales. Considerando que no existe un modelo experimental para la estomatitis aftosa recurrente, la estomatitis asociada a inhibidores de mTOR podría otorgar esa posibilidad

Antibody detection against bovine viral diarrhea virus in cattle of the province of Anta, Cusco, Peru

El objetivo del presente estudio fue determinar anticuerpos contra el virus de la diarrea viral (VDVB) en bovinos, según raza y edad, de cinco distritos de la provincia de Anta, Cusco. Se tomaron muestras de suero de bovinos hembras (n=1135) y machos (n=57) de 262 pequeños ganaderos y una comunidad ganadera. Las muestras se analizaron mediante la prueba de ELISA indirecta. El 50.8% de las hembras y 43.9% de los machos tuvieron anticuerpos contra el VDVB. Los porcentajes de bovinos hembras seropositivos en los distritos de Ancahuasi, Zurite, Anta, Cachimayo y Huarocondo fueron de 58.6, 45.5, 63.9, 31.5 y 80%, respectivamente. Todos los ganaderos tuvieron al menos un animal seropositivo. Los anticuerpos contra el VDVB fueron más prevalentes en animales mayores a tres años. Los coeficientes m/p de las muestras seropositivas variaron entre 1. Se concluye que el VDVB está ampliamente difundido en bovinos de los cinco distritos de la provincia de Anta y las variaciones del coeficiente m/p de las muestras indican que la infección por el VDVB es activa en los animales de la zona.The aim of this study was to determine antibodies against bovine viral diarrhea virus (BVDV) in cattle, according to breed and age, in five districts of Anta province, Cusco. Serum samples were taken from females (n=1135) and males (n=57) from 262 small farmers and one farmer community. The samples were analyzed by indirect ELISA test. Results showed that 50.8% of the females and 43.9% of the males had antibodies against the BVDV. The percentages of seropositive female bovines in the districts of Ancahuasi, Zurite, Anta, Cachimayo and Huarocondo were 58.6, 45.5, 63.9, 31.5 and 80%, respectively. All farmers had at least one seropositive animal. Antibodies against BVDV were more prevalent in animals older than three years. The s/p coefficients of the seropositive samples varied between &lt;0.2 and &gt;1. It is concluded that the BVDV is widely spread in cattle of the five districts of the province of Anta and the variations of the s/p coefficient of the samples indicate that the infection by the BVDV is active in the animals of the area of study

Manual para el uso de la herramienta de colecta de datos FLAR Collect

Este manual describe la herramienta y funcionalidad de la herramienta digital de colecta y análisis de datos FLAR Collect. El objetivo es recopilar diversos datos relacionados con el manejo agronómico del cultivo del arroz por medio de dispositivos móviles. La recolección de una cantidad masiva de datos nos permitirá realizar análisis que mejoren las prácticas agronómicas más comunes y con ello la sostenibilidad del cultivo del arroz

Identification of persistently infected cattle and genotype of bovine viral diarrhea virus in cattle of Anta, Cusco, Peru

El objetivo del presente estudio fue identificar bovinos persistentemente infectados (PI) y el genotipo del virus de la diarrea viral (VDVB) en bovinos de pequeños ganaderos de cinco distritos de la provincia de Anta, Cusco, que resultaron negativos a anticuerpos contra el VDVB (n=558) en un estudio previo. La identificación de los animales PI se realizó en las 558 muestras de suero de bovinos Holstein, Brown Swiss y criollos hembras de varias edades, mediante la prueba de ELISA de captura. La identificación del genotipo viral fue realizada en cuatro muestras de bovinos PI mediante la prueba de RT-PCR en tiempo real. El 7.2% (40/558) de los bovinos resultaron positivos a antígeno viral en un primer análisis, donde el antígeno fue detectado en animales mayores a 6 meses hasta los 5 años en las tres razas. En el segundo análisis, realizado 30 días después, en los 40 positivos, 30% (12/40) continuaron siendo positivos a antígeno viral indicando que eran animales PI entre mayores a 6 meses y 4 años de cuatro de los cinco distritos de Anta. La prevalencia de los animales PI en la población bovina muestreada de la provincia de Anta fue de 2.2% (12/558). La prueba RT-PCR en tiempo real mostró la amplificación de un producto específico correspondiente al genotipo 1 (VDVB-1). No hubo amplificación de la secuencia objetivo del genotipo 2.The aim of this study was to identify persistently infected cattle (PI) and to identify the viral diarrhea virus genotype (BVDV) in cattle of small farmers in five districts of the province of Anta, Cusco, which were negative for antibodies against BVDV (n=558) in a previous study. The identification of the PI animals was carried out in the 558 serum samples of female bovine Holstein, Brown Swiss and Creoles of various ages, by the capture ELISA test. The identification of the viral genotype was carried out in four samples of PI cattle through the RT-PCR real-time. The results showed that 7.2% (40/558) of the cattle were positive for viral antigen in a first analysis, where the antigen was detected in animals older than 6 months up to 5 years in the three breeds. In the second analysis carried out 30 day after in the 40 positives, 30% (12/40) continued to be positive for viral antigen indicating that they were PI animals between 6 months and 4 years in four of the five Anta districts. The prevalence of PI animals in the bovine population sampled in province of Anta was 2.2% (12/558). Real-time RT-PCR showed the amplification of a specific product corresponding to genotype 1 (VDVB-1). There was no amplification of the target sequence of genotype 2

High frequency of acute decompensation and cancer in patients with compensated cirrhosis due to nonalcoholic fatty liver disease : A retrospective cohort study

The natural history of compensated cirrhosis due to nonalcoholic fatty liver disease (NAFLD) has not been completely characterized. The aim of the present study was to assess the incidence and risk factors of acute decompensation of cirrhosis, hepatocellular carcinoma, and extrahepatic cancers. This was a multicenter, retrospective, cohort study including 449 patients with compensated cirrhosis due to NAFLD. We calculated cumulative incidences and used competitive risk analysis to determine the risk factors associated with decompensation and cancer development. Over a median of 39 months of follow-up, 124 patients (28%) presented acute decompensation. The most frequent decompensation was ascites (21%) followed by hepatic encephalopathy (15%), variceal bleeding (9%), and spontaneous bacterial peritonitis (3%). Acute-on-chronic liver failure was diagnosed in 6% of patients during follow-up. Liver function parameters and specifically an albumin level below 40 g/L were independently associated with an increased risk of decompensation. The presence of ischemic heart disease was independently associated with acute decompensation. Seventy-eight patients (18%) developed hepatocellular carcinoma or extrahepatic cancers during follow-up (51 and 27, respectively). Conclusion : Patients with compensated cirrhosis due to NAFLD are at high risk of severe liver complications, such as the development of acute decompensation, in a relative short follow-up time. This population is at high risk of hepatic and extrahepatic cancers. The analysis of a large contemporary cohort of 449 patients with compensated cirrhosis due to non-alcoholic fatty liver disease shows a high frequency of acute decompensations (AD) and development of cancer during 39 months of follow-up. Almost 28% of the cohort developed acute decompensation and 18% developed hepatocellular carcinoma (HCC) or extrahepatic cancer. Predictors of decompensation are mainly related to liver function and portal hypertension

Percepción de Internos de Medicina de la Universidad de Antofagasta respecto a la formación académica recibida para enfrentar el ciclo profesional

El objetivo general de la investigación fue analizar la percepción de los internos que cursan el séptimo año de la Carrera de Medicina de la Universidad de Antofagasta respecto a la formación académica recibida para enfrentar el ciclo profesional de su Carrera. En cuanto a la metodología, se desarrolló un estudio cuantitativo transversal exploratorio – descriptivo. El diseño de investigación corresponde a un estudio no experimental. Participaron 33 estudiantes de un total de 59, que al momento de realizar el estudio, cursaban el Internado de Séptimo Año de la Carrera de Medicina de la Universidad de Antofagasta. El estudio fue aprobado por el Comité de Ética e Investigación Científica de la Universidad de Antofagasta.  En cuanto a los resultados, en las dimensiones estudiadas prevalecen los grados de acuerdo (sobre el 45%). Se apreció una alta indecisión de los encuestados al momento de responder (que se reflejó en los porcentajes obtenidos por la categoría de respuesta “Ni de acuerdo ni en desacuerdo”). El mayor grado de desacuerdo (27,3%) fue en la pregunta que consultó sobre la aproximación al contexto laboral en las asignaturas del ciclo básico de la Carrera. Como conclusión, prevalece un aprendizaje centrado en el estudiante y surge la necesidad de integración entre el ciclo básico y profesional de la Carrera, y la evaluación de pertinencia de los contenidos abordados en el primero. 

Modified Wisconsin Card Sorting Test (M-WCST): Normative data for Spanish-speaking pediatric population

OBJECTIVE: To generate normative data for the Modified Wisconsin Card Sorting Test (M-WCST) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the M-WCST as part of a larger neuropsychological battery. Number of categories, perseverative errors, and total error scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models indicated main effects for age on all scores, such that the number of categories correct increased and total number of perseverative errors and total number of errors decrease linearly as a function of age. Age2 had a significant effect in Chile, Cuba, Ecuador, and Spain for numbers of categories; a significant effect for number of perseverative errors in Chile, Cuba, Mexico, and Spain; and a significant effect for number of total errors in Chile, Cuba, Peru, and Spain. Models showed an effect for MLPE in Cuba (total errors), Ecuador (categories and total errors), Mexico (all scores), Paraguay (perseverative errors and total error), and Spain (categories and total errors). Sex affected number of total errors for Ecuador. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate way to interpret the M-WCST with pediatric populations

MVA-CoV2-S vaccine candidate confers full protection from SARS-CoV-2 brain infection and damage in susceptible transgenic mice

The protective efficacy of vaccines against SARS-CoV-2 infection in the brain is yet unclear. Here, in the susceptible transgenic K18-hACE2 mouse model of severe COVID-19 disease, we report a detailed spatiotemporal description of the SARS-CoV-2 infection and replication in different areas of the brain. Remarkably, SARS-CoV-2 brain replication occurs primarily in neurons, producing important neuropathological alterations such as neuronal loss, incipient signs of neuroinflammation, and vascular damage in SARS-CoV-2 infected mice. Notably, one or two doses of a modified vaccinia virus Ankara (MVA) vector expressing the SARS-CoV-2 spike (S) protein (MVA-CoV2-S) conferred full protection against SARS-CoV-2 cerebral infection, preventing virus replication in all areas of the brain and its associated damage. This protection was maintained even after SARS-CoV-2 reinfection. To our knowledge, this is the first study of a COVID-19 vaccine candidate showing 100% efficacy against SARS-CoV-2 brain infection and damage, reinforcing the use of MVA-CoV2-S as a promising vaccine candidate against SARS-CoV-2/COVID-19, worth to move forward into clinical trials.The authors thank the Centro de Investigación en Sanidad Animal (CISA)-Instituto Nacional de Investigaciones Agrarias (INIA-CSIC) (Valdeolmos, Madrid, Spain) for the BSL-3 facilities. SARS-CoV-2 MAD6 virus isolate was kindly provided by José M. Honrubia and Dr. Luis Enjuanes (CNB-CSIC, Madrid, Spain). We also thank to Dr. Konstantin L. Levitsky for excellent technical assistance with the confocal acquisition. We thank the Spanish Research Council (CSIC) and the Spanish Ministry of Science and Innovation (MICINN) for continuous support. This research was supported by MCIN/Spanish Research Agency (AEI)/ 10.13039/501100011033 grants: PID2019-105995RB-I00 (J.T.-A. and J.V.), PID2020- 114481RB-I00 (J.G.-A. and M.E.), and PID2019-106410RB-I00 (J.L.-B.). Moreover, this research work was also funded by Red TerCel ISCIII, RD16/0011/0025 (J.T.-A.); Consejería de Salud y Familias, Junta de Andalucía Grant, PECOVID-0078-2020 (R.R.-L. and J.V.); Fondo COVID-19 grant COV20/00151 [Spanish Health Ministry, Instituto de Salud Carlos III (ISCIII)], Fondo Supera COVID-19 (Crue Universidades-Banco Santander) grant and CSIC grant 202120E079 (J.G.-A.); and CSIC grant 2020E84, La CaixaImpulse grant CF01-00008, Ferrovial and MAPFRE donations (M.E.). Additionally, we have also funding from the European Commission-NextGenerationEU, through CSIC's Global Health Platform (PTI Salud Global) (J.G.-A. and M.E.) and the European Research Council (ERC Advanced Grant PRJ201502629) (J.L.-B.).N