Exploring host genetic polymorphisms involved in SARS-CoV infection autcomes: implications for personalized medicine in COVID-19

Objective. To systematically explore genetic polymorphisms associated with the clinical outcomes in SARS-CoV infection in humans. Methods. This comprehensive literature search comprised available English papers published in PubMed/Medline and SCOPUS databases following the PRISMA-P guidelines and PICO/AXIS criteria. Results. Twenty-nine polymorphisms located in 21 genes were identified as associated with SARS-CoV susceptibility/resistance, disease severity, and clinical outcomes predominantly in Asian populations. Thus, genes implicated in key pathophysiological processes such as the mechanisms related to the entry of the virus into the cell and the antiviral immune/inflammatory responses were identified. Conclusions. Although caution must be taken, the results of this systematic review suggest that multiple genetic polymorphisms are associated with SARS-CoV infection features by affecting virus pathogenesis and host immune response, which could have important applications for the study and understanding of genetics in SARS-CoV-2/COVID-19 and for personalized translational clinical practice depending on the population studied and associated environments

Las termas y el Suburbium marítimo de Baelo Claudia. Avance de un reciente descubrimiento

Entre los años 2010 y 2012, la Universidad de Cádiz y la Junta de Andalucía han desarrollado investigaciones arqueológicas en la zona extramuros de la ciudad hispanorromana, en el marco del Proyecto General de Investigación “La economía marítima y las actividades haliéuticas en Baelo Claudia”. Se presentan en esta sede los primeros resultados, que han permitido identificar la existencia de un suburbium occidental en la ciudad, entre el cauce del arroyo de las Villas, la playa y la necrópolis oeste, cuya existencia se ha podido confirmar por datos geofísicos y arqueológicos. En él han podido ser excavadas parcialmente unas estructuras que se han identificado con unas termas suburbanas, activas entre el s. II y el V d.C., habiéndose excavado una piscina del frigidarium y algunas estancias calefactadas, con hallazgos muy significativos como parte de la decoración marmórea y escultórica del complejo, que en época tardorromana fue amortizado intencionalmente por motivos posiblemente religiosos. Estos hallazgos son de gran interés, pues además de verificar la existencia de un segundo complejo balneario público en la ciudad plantean la importancia del poblamiento periurbano, una línea de investigación totalmente inédita hasta la fechaBetween the year 2010 and 2012, the University of Cadiz and the Regional Government (Junta de Andalucía) have developed archaeological activities in the zone outside the hispano-roman city, in the frame of the General Project of Research titled “The maritime economy and the halieutic activities in Baelo Claudia”. We are presenting in this paper the first results, which have allowed to identify the existence of a western suburbium outside the city, between the riverbed of the so called “arroyo de las Villas”, the beach and the western necropolis, whose remains have been confirmed by geophysical and archaeological techniques. Inside this area a few structures have been excavated, identified as a Roman baths complex, active from the 2nd up to the 5th century a.D. A big pool, part of the frigidarium and some heated rooms have been unearthed, with very significant findings as part of the marmoreal and sculptural decoration of the complex, which in late roman times was intentionally broken into pieces possibly by religious motives. These findings are of great interest, since beside confirming the existence of the second public thermae of the city they raise the importance of the peri-urban buildings, a new line of research up to dat

Evidencias arqueológicas de desplomes paramentales traumáticos en las Termas Marítimas de Baelo Claudia. Reflexiones arqueosismológicas

Durante los años 2011 a 2013 se han localizado, identificado y excavado parcialmente los restos de un nuevo complejo termal en la ciudad hispanorromana de Baelo Claudia (Tarifa, Cádiz), situado en el suburbium occidental de la ciudad, junto a la línea de costa. Denominadas Termas Marítimas, construidas en la primera mitad del s. II d.C. y abandonadas en época de Diocleciano/Constantino han sido excavadas estratigráficamente con detalle, habiéndose detectado la existencia de fases anteriores (que se remontan al s. II a.C.) y una continuidad de uso del ambiente en época tardorromana y moderna, vinculada con la explotación de los recursos marinos. Especialmente singular ha sido la constatación del desplome traumático de parte de los paramentos de las habitaciones del edificio en dos momentos concretos: por un lado en la Antigüedad Tardía (500 d.C. circa), ya que una unidad muraria de una de las habitaciones (H-3), anexa a la natatio, se localizó completamente derrumbada sobre el suelo, conexionada; y por otro, el desplome del muro oeste de la natatio y el oriental de la cisterna, estructuras de más de seis metros de longitud y cuatro de altura mínima conservada, desplomadas sobre los niveles de abandono del asentamiento en época bajomedieval o moderna (ss. XIV-XV d.C.). Se trata en ambas ocasiones de colapsos estructurales no habituales en circunstancias normales en los procesos de sedimentación arqueológica, por lo que es muy probable que su desplome se pueda vincular con eventos sísmicos u otras causas naturales similare

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

The CARMENES search for exoplanets around M dwarfs. First visual-channel radial-velocity measurements and orbital parameter updates of seven M-dwarf planetary systems

Stars and planetary system

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

Exploring host genetic polymorphisms involved in SARS-CoV infection autcomes: implications for personalized medicine in COVID-19

Objective. To systematically explore genetic polymorphisms associated with the clinical outcomes in SARS-CoV infection in humans. Methods. This comprehensive literature search comprised available English papers published in PubMed/Medline and SCOPUS databases following the PRISMA-P guidelines and PICO/AXIS criteria. Results. Twenty-nine polymorphisms located in 21 genes were identified as associated with SARS-CoV susceptibility/resistance, disease severity, and clinical outcomes predominantly in Asian populations. Thus, genes implicated in key pathophysiological processes such as the mechanisms related to the entry of the virus into the cell and the antiviral immune/inflammatory responses were identified. Conclusions. Although caution must be taken, the results of this systematic review suggest that multiple genetic polymorphisms are associated with SARS-CoV infection features by affecting virus pathogenesis and host immune response, which could have important applications for the study and understanding of genetics in SARS-CoV-2/COVID-19 and for personalized translational clinical practice depending on the population studied and associated environments