Macrophages from elders are more permissive to intracellular multiplication of Mycobacterium tuberculosis

Las infecciones respiratorias son una de las principales causas de enfermedad en los ancianos. Varios factores que contribuyen a su desarrollo, incluyendo la malnutrición, las enfermedades asociadas a la edad como la diabetes, enfermedades pulmonares cardíacas o estructurales, y las alteraciones asociadas a la edad en inmunidad. Los agentes más comunes que causan neumonía son Streptococcus pneumoniae seguido por virus respiratorios. Otro patógeno importante en las infecciones respiratorias es el Mycobacterium tuberculosis La tuberculosis se está convirtiendo en un serio problema de salud para la población anciana. Inmunosenescencia, entendida como los cambios en el sistema inmune asociada con la edad, es una de las razones que a menudo influyen en el curso de la tuberculosis en los ancianos. La mayoría de los estudios se centran en el análisis del deterioro de la inmunidad adaptativa con la edad. De hecho, se ha observado que el número de células T vírgenes es menor en edad avanzada, recíprocamente, el número de células de memoria y efectoras de memoria es mayor, como resultado de exposición a agentes patógenos a través de la vida. Por lo tanto, se ha definido el concepto de "inmune fenotipo de riesgo ", que se caracteriza por una relación invertida CD4 / CD8 y baja respuesta linfoproliferativ

A new trilobite locality from the Agüeira Formation (Upper Ordovician) of the Vega de Espinareda synclinorium (West Asturian-Leonese Zone, NW Spain) and its stratigraphical interest

Se presenta una nueva localidad paleontológica del Ordovícico del noroeste de España, ubicada en el flanco meridional del sinclinorio de Vega de Espinareda, al norte de Ponferrada (provincia de León). Se trata de la octava localidad con fósiles esqueléticos encontrada en la Formación Agüeira (Ordovícico Superior) del Dominio del Navia-Alto Sil de la Zona Asturoccidental-leonesa, y la primera ubicada en la mitad inferior de la formación. El nuevo yacimiento se sitúa muy próximo a su sección de referencia de la garganta fluvial entre las localidades de Congosto y Santa Marina del Sil, donde estos niveles eran interpretados como facies distales de un abanico submarino, en una sedimentación predominantemente turbidítica. Pero los trilobites, moluscos y braquiópodos encontrados, que por su escasa a nula desarticulación no parecen transportados, revelan una asociación propia de ambientes de plataforma mucho más someros, con fondos oxigenados como revela la alta concentración de galerías horizontales. La presencia de los trilobites Colpocoryphe grandis (Šnajdr) y Dalmanitina n. sp. (D. rabanoae Pereira, n. n.) indica una edad Berouniense temprano (= Sandbiense temprano), lo que abre la posibilidad de que el límite Ordovícico Medio/Superior se sitúe en los 400-450 m basales de la Fm. Agüeira en el sector estudiadoA new paleontological locality in the Ordovician of northwestern Spain is presented, situated north of Ponferrada (León province), on the southern flank of the Vega de Espinareda synclinorium. This is the eighth locality with skeletal fossils found in the Agüeira Formation (Upper Ordovician) of the Navia-Alto Sil Domain of the West Asturian-Leonese Zone, and the first recorded in the lower half of the Formation. The new locality is very close to its reference section in the fluvial gorge between the towns of Congosto and Santa Marina del Sil, where these lower beds were interpreted as distal facies of a submarine turbiditic fan, adjacent to the basinal plain. However, the trilobites, brachiopods and mollusks here studied, which do not seem to have been transported due to their little to no disarticulation, reveal an assemblage typical of much shallower shelf environments, with oxigenated seafloor as demonstrated by the abundance of horizontal burrows. The record of the trilobites Colpocoryphe grandis (Šnajdr) and Dalmanitina n. sp. (D. rabanoae Pereira, n. n.) indicates an early Berounian (=early Sandbian) age, which opens the possibility that the Middle/Upper Ordovician boundary could be placed in the studied area within the lower 400-500 m of the Agüeira Formatio

Prediction of poor outcome in clostridioides difficile infection: A multicentre external validation of the toxin B amplification cycle

Producción CientíficaClassification of patients according to their risk of poor outcomes in Clostridioides difficile infection (CDI) would enable implementation of costly new treatment options in a subset of patients at higher risk of poor outcome. In a previous study, we found that low toxin B amplification cycle thresholds (Ct) were independently associated with poor outcome CDI. Our objective was to perform a multicentre external validation of a PCR-toxin B Ct as a marker of poor outcome CDI. We carried out a multicentre study (14 hospitals) in which the characteristics and outcome of patients with CDI were evaluated. A subanalysis of the results of the amplification curve of real-time PCR gene toxin B (XpertTM C. difficile) was performed. A total of 223 patients were included. The median age was 73.0 years, 50.2% were female, and the median Charlson index was 3.0. The comparison of poor outcome and non–poor outcome CDI episodes revealed, respectively, the following results: median age (years), 77.0 vs 72.0 (p = 0.009); patients from nursing homes, 24.4% vs 10.8% (p = 0.039); median leukocytes (cells/μl), 10,740.0 vs 8795.0 (p = 0.026); and median PCR-toxin B Ct, 23.3 vs 25.4 (p = 0.004). Multivariate analysis showed that a PCR-toxin B Ct cut-off <23.5 was significantly and independently associated with poor outcome CDI (p = 0.002; OR, 3.371; 95%CI, 1.565–7.264). This variable correctly classified 68.5% of patients. The use of this microbiological marker could facilitate early selection of patients who are at higher risk of poor outcome and are more likely to benefit from newer and more costly therapeutic options

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

Nontuberculous Mycobacteria, Mucociliary Clearance, and Bronchiectasis

Nontuberculous mycobacteria (NTM) are environmental and ubiquitous, but only a few species are associated with disease, often presented as nodular/bronchiectatic or cavitary pulmonary forms. Bronchiectasis, airways dilatations characterized by chronic productive cough, is the main presentation of NTM pulmonary disease. The current Cole’s vicious circle model for bronchiectasis proposes that it progresses from a damaging insult, such as pneumonia, that affects the respiratory epithelium and compromises mucociliary clearance mechanisms, allowing microorganisms to colonize the airways. An important bronchiectasis risk factor is primary ciliary dyskinesia, but other ciliopathies, such as those associated with connective tissue diseases, also seem to facilitate bronchiectasis, as may occur in Lady Windermere syndrome, caused by M. avium infection. Inhaled NTM may become part of the lung microbiome. If the dose is too large, they may grow excessively as a biofilm and lead to disease. The incidence of NTM pulmonary disease has increased in the last two decades, which may have influenced the parallel increase in bronchiectasis incidence. We propose that ciliary dyskinesia is the main promoter of bronchiectasis, and that the bacteria most frequently involved are NTM. Restoration of ciliary function and impairment of mycobacterial biofilm formation may provide effective therapeutic alternatives to antibiotics

Formation of Mycobacterium abscessus colonies in cellular culture in an in vitro infection model

Mycobacterium abscessus is one of the most important nontuberculous mycobacteria that cause lung diseases. In vitro infection models developed to analyze the immune response are frequently based on the addition of mycobacteria to mononuclear cells or neutrophils from peripheral blood. An important requirement of these assays is that most cells phagocytose mycobacteria, only accomplished by using large multiplicities of infection (1 or more bacteria per cell) which may not adequately reflect the inhalation of a few mycobacteria by the host. We propose modifications that try to mimic some of the conditions in which immune cells deal with mycobacteria. For the preparation of the inoculum mycobacteria are grown in solid media followed by preparation to a single cell suspension. Multiplicities of infection (number of bacteria per cell) are below 0.01. Serum-free cellular media is used to allow the growth of M. abscessus. After several days of incubation Bacterial Colonies in Cellular Culture (BCCC) develop, which are enumerated directly under an inverted microscope. These colonies may represent biofilm formation during chronic infections. • Low multiplicity of infection (below 0.01 bacteria per cell) reflects more realistically conditions encountered by immune cells in the lungs. • The surface of mycobacteria prepared for infection assays that are grown in solid media are less affected than that of mycobacteria grown in liquid media with detergents. • Colony formation in the infected cells may reflect the aggregation and biofilm formation in the lungs during chronic infection