Mycobacterium bovis naturally infected calves present a higher bacterial load and proinflammatory response than adult cattle

Granulomas are characteristic bovine tuberculosis lesions; studying this structure has improved our understanding of tuberculosis pathogenesis. However, the immune response that develops in granulomas of young cattle naturally infected with Mycobacterium bovis (M. bovis) has not been fully studied. Our previous work described an atypical pattern in granulomatous lesions of cattle younger than 4 months (calves) naturally infected previously M. bovis that did not correspond to the histological classification previously proposed. Histologically, granulomas from calves lack a connective tissue capsule and have fewer multinucleated giant cells (MGCs) and more acid-fast bacilli (AFB) than the classic tuberculosis lesions found in cattle older than 1 year (adults); this suggests a deficient immune response against M. bovis infection in young animals. Therefore, we used IHC and digital pathology analysis to characterize the in situ immune response of granulomas from young and adult cattle. The immunolabeling quantification showed that granulomas from calves had more mycobacteria, CD3+ cells, IFN-γ, TNF-α, and inducible nitric oxide synthase (iNOS) than those of adult cattle. Furthermore, calf granulomas showed lower immunolabeling of MAC387+, CD79+, and WC1+ cells without connective tissue surrounding the lesion and were associated with less vimentin, Alpha Smooth Muscle Actin (α-SMA), and TGF-β compared with granulomas from adult cattle. Our results suggest that the immune responses in granulomas of cattle naturally infected with M. bovis may be age dependent. This implies that an exacerbated proinflammatory response may be associated with active tuberculosis, producing more necrosis and a lower microbicidal capacity in the granulomas of calves naturally infected with M. bovis

Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. Video Abstract [Figure presented] Keywords: type 2 diabetes (T2D); genetics; disease mechanism; SLC16A11; MCT11; solute carrier (SLC); monocarboxylates; fatty acid metabolism; lipid metabolism; precision medicin

Analysis of protein-coding genetic variation in 60,706 humans

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. We describe the aggregation and analysis of high-quality exome (protein-coding region) sequence data for 60,706 individuals of diverse ethnicities generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of truncating variants with 72% having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human “knockout” variants in protein-coding genes

Multimessenger Search for Sources of Gravitational Waves and High-Energy Neutrinos: Results for Initial LIGO-Virgo and IceCube

We report the results of a multimessenger search for coincident signals from the LIGO and Virgo gravitational-wave observatories and the partially completed IceCube high-energy neutrino detector, including periods of joint operation between 2007-2010. These include parts of the 2005-2007 run and the 2009-2010 run for LIGO-Virgo, and IceCube's observation periods with 22, 59 and 79 strings. We find no significant coincident events, and use the search results to derive upper limits on the rate of joint sources for a range of source emission parameters. For the optimistic assumption of gravitational-wave emission energy of $10^{-2}$\,M$_\odot$c$^2$ at $\sim 150$\,Hz with $\sim 60$\,ms duration, and high-energy neutrino emission of $10^{51}$\,erg comparable to the isotropic gamma-ray energy of gamma-ray bursts, we limit the source rate below $1.6 \times 10^{-2}$\,Mpc$^{-3}$yr$^{-1}$. We also examine how combining information from gravitational waves and neutrinos will aid discovery in the advanced gravitational-wave detector era

Evolution of the use of corticosteroids for the treatment of hospitalised COVID-19 patients in Spain between March and November 2020: SEMI-COVID national registry

Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. Material and methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID- 19 Registry from March to November 2020. Results: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236- 996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%. Conclusions: Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Caracterización química de los pigmentos presentes en el duramen de un árbol endémico de México (Peltogyne mexicana)

Resumen del póster presentado a las I Jornadas Científicas del CIAL celebradas el 5 de junio de 2014 en Madrid.En la actualidad una de las tendencias en Ciencia y Tecnología de los Alimentos consiste en la búsqueda y explotación de nuevas fuentes naturales de pigmentos en sustitución de los colorantes sintéticos. Un ejemplo de estas nuevas fuentes naturales es el árbol identificado como Peltogyne mexicana Martínez que crece exclusivamente en Guerrero, México y cuyo duramen tiene un característico color morado1. Aunque existen estudios anteriores que reportan que el pigmento presente en el duramen de Peltogyne porphyrocardia es el (+)-peltoginol, un compuesto de tipo flavonoide2, no se conoce la estructura química de los compuestos responsables del color en el duramen de Peltogyne mexicana. El objetivo del presente trabajo ha sido elucidar la estructura química de los principales pigmentos obtenidos en el extracto crudo etanólico (ECE) del duramen de Peltogyne mexicana. Para ello se determinaron fenoles totales por el método colorimétrico de Folin (363.27, mg eq. ácido gálico/g), flavonoides totales mediante el método de reacción con el AlCl3 (62.86 mg eq. (-)-epicatequina/g) y catequinas mediante el ensayo de la vainillina (17.49, mg eq. (-)-epicatequina/g). Para la identificación de los pigmentos del ECE se desarrolló un método de separación mediante UHPLC-DAD-MS, empleando una columna C18 (150 x 4.6 mm, 3 ¿m) y un gradiente agua (0.1% TFA):acetonitrilo. Asimismo se llevó a cabo la recogida de fracciones puras de los compuestos presentes en el ECE para la posterior determinación de su masa exacta mediante espectrometría de masas.Peer Reviewe

La educación para la salud en el diabético II. Una estrategia comunicativa

De los pacientes diabéticos, la mayoría corresponde a quienes padecen diabetes tipo II, o diabetes mellitus, y que se caracterizan por sufrir de obesidad exógena, con malos hábitos alimenticios. Estos rasgos son determinados y condicionados por el medio social, económico, educativo, cultural, psicológico y político en el que se desenvuelven estas personas. El control metabólico es fundamental para su calidad y cantidad de años de vida. Este control se relaciona con factores educativos que condicionan el desarrollo y establecimiento de hábitos y destrezas que permiten el mejoramiento de las condiciones de vida. En este estudio se muestra la comparación de los resultados cometidos en dos grupos de pacientes: uno sometido a la aplicación de una estrategia comunicativo-educativa en nutrición para el logro del control metabólico, y el otro sin ella. Los resultados son altamente favorables al primer grupo, que además están avalados por indicadores que les otorgan amplia validez estadística