Métodos moleculares para diagnóstico de niños con tuberculosis en países de Latinoamérica

The diagnosis of tuberculosis in the childhood population represents a major obstacle to the health system because the pediatric patient is paucibacillary. This is done by four classic criteria: epidemiological, tuberculinic, radiological and clinical; however, this method has an approximate sensitivity of 50%. On the other hand, molecular tests are new methods for the diagnosis and treatment of these infections, due to the rapidity of the result, high sensitivity, specificity and also, it reports resistance to antituberculosis drugs. Therefore, the objective of the review is to investigate the diagnosis of molecular methods in pediatric tuberculosis, since it is considered a vulnerable population, with more probability of disease progression, diagnostic problems due to the condition of being pediatric patients, the difficult microbiological isolation and therapeutic difficulties. Objective: describe the evidence on the use of molecular tests in the diagnosis of childhood tuberculosis in Latin American countries reported in the scientific literature. Materials and methods: a narrative review of the literature was performed. The selection criteria were articles that evaluated molecular tests in pediatric patients up to 18 years with a diagnosis of tuberculosis in Latin American countries. A structured search was conducted in Medline via OVID and Embase using the keywords “tuberculosis”, “pediatric”, “children”, “diagnosis” and “molecular”. The language was limited to English and Spanish, but there was no date limit. Results: 1050 articles were found, of which 751 articles were removed by the selection criteria in the title / summary and 95 articles in the full text. A qualitative analysis was performed with the 8 selected articles, which were published between 2003 and 2018, in addition 50 % of the articles were made in Peru. It was also found that the nested PCR test was implemented in 87.5 % of the studies and only 12.5 % used the GeneXpert MTB / RIF test. Most of the articles showed that nPCR has high specificity, but low sensitivity compared to liquid cultures. The nPCR has a tendency to have more false positives. Conclusions: although there are multiple molecular tests, only the report of the nested PCR test and GeneXpert MTB / RIF was found in the articles. There is little literature reported on the application of molecular diagnostic methods in the pediatric population for Latin America.PublishedEl diagnóstico de tuberculosis en la población infantil representa un gran obstáculo para el sistema de salud porque el paciente pediátrico es paucibacilar. Este se realiza mediante cuatro criterios clásicos: epidemiológico, tuberculínico, radiológico y clínico; sin embargo, este método tiene una sensibilidad aproximada del 50 %. Por otro lado, las pruebas moleculares son métodos nuevos para el diagnóstico de estas infecciones, por la rapidez del resultado, una alta sensibilidad, especificidad y además, reporta la resistencia a los fármacos antituberculosos. Por lo anterior el objetivo de la revisión es investigar acerca del diagnóstico de métodos moleculares en tuberculosis pediátrica, ya que se considera que esta es una población vulnerable, teniendo más probabilidad de progresión de la enfermedad, problemas en el diagnóstico por la dificultad en la toma de los exámenes, la dificultad del aislamiento microbiológico y las dificultades terapéuticas. Objetivo: describir la evidencia sobre el uso de pruebas moleculares en el diagnóstico de tuberculosis infantil en países de Latinoamérica reportadas en la literatura científica. Materiales y métodos: se realizó una revisión narrativa de la literatura. Los criterios de selección fueron artículos que evaluaran pruebas moleculares en pacientes pediátricos hasta los 18 años con diagnóstico de tuberculosis en países de Latinoamérica. Se realizó una búsqueda estructurada en Medline vía OVID y Embase utilizando las palabras clave “tuberculosis”, “pediatric”, “children”, “diagnosis” y “molecular”. Se limitó el lenguaje al inglés y español, pero no se tuvo límite de fecha. Resultados: se encontraron 1050 artículos, de los cuales se eliminaron 751 artículos por los criterios de selección en el título/resumen y 95 artículos en el texto completo. Se realizó un análisis cualitativo con los ocho artículos seleccionados, los cuales fueron publicados entre el 2003 y 2018; además el 50 % de los artículos se realizaron en Perú. También se encontró que en el 87.5 % de los estudios se implementó la prueba PCR anidada y solo el 12.5 % utilizó la prueba GeneXpert MTB/RIF. La mayor parte de los artículos mostraron que la PCR anidada tiene alta especificidad, pero baja sensibilidad comparada con los cultivos líquidos. La nPCR tiene tendencia a tener más falsos positivos. Conclusiones: aunque existen múltiples pruebas moleculares, en los artículos solo se encontró el reporte de la prueba PCR anidada y GeneXpert MTB/RIF. Existe poca literatura reportada de la aplicación de los métodos diagnósticos moleculares en población pediátrica para Latinoamérica

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Estudios de la tuberculosis desde la Sucursal del Cielo

PublishedEste libro está dirigido a la comunidad académica, científica y en general a aquellas personas interesadas en ampliar sus conocimientos sobre la tuberculosis. Iniciamos con una revisión general de la evolución de las metodologías diagnósticas. Posteriormente, destacamos diferentes trabajos de investigación realizados en Cali y el Valle del Cauca en torno a la tuberculosis, resaltando herramientas empleadas para la vigilancia epidemiológica de la enfermedad, así como el estudio de la tuberculosis en población vulnerable (tuberculosis infantil y la incidencia de esta enfermedad en trabajadores de la salud en los últimos años en Cali). Este libro resalta la necesidad de entender el enfoque humano que rodea esta enfermedad, en esa dirección los dos últimos capítulos los enfocamos en las creencias sobre la tuberculosis y la interacción del paciente con las entidades prestadoras de servicios de salud. Esperamos que nuestro libro genere importantes aportes a aquellos que se involucran en el estudio de esta enfermedad que ha acompañado al hombre probablemente desde su presencia en el planeta y sea, además, el insumo de futuros investigadores en las diversas áreas del conocimiento que confluyen en el entendimiento de esta enfermedad infecciosa

Pulmonary Function and Blood DNA Methylation: A Multiancestry Epigenome-Wide Association Meta-Analysis

Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication. Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function. Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV1, FVC, and FEV1/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics. Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery rate, \u3c0.025) in relation to FEV1, FVC, or FEV1/FVC, including 1,240 novel and 73 also related to chronic obstructive pulmonary disease (1,787 cases). We found 294 CpGs unique to European or African ancestry and 395 CpGs unique to never or ever smokers. The majority of significant CpGs correlated with nearby gene expression in blood. Findings were enriched in key regulatory elements for gene function, including accessible chromatin elements, in both blood and lung. Sixty-nine implicated genes are targets of investigational or approved drugs. One example novel gene highlighted by integrative epigenomic and druggable target analysis is TNFRSF4. Mendelian randomization and colocalization analyses suggest that epigenome-wide association study signals capture causal regulatory genomic loci. Conclusions: We identified numerous novel loci differentially methylated in relation to pulmonary function; few were detected in large genome-wide association studies. Integrative analyses highlight functional relevance and potential therapeutic targets. This comprehensive discovery of potentially modifiable, novel lung function loci expands knowledge gained from genetic studies, providing insights into lung pathogenesis

Patterns of Spatial Variation of Assemblages Associated with Intertidal Rocky Shores: A Global Perspective

Assemblages associated with intertidal rocky shores were examined for large scale distribution patterns with specific emphasis on identifying latitudinal trends of species richness and taxonomic distinctiveness. Seventy-two sites distributed around the globe were evaluated following the standardized sampling protocol of the Census of Marine Life NaGISA project (www.nagisa.coml.org). There were no clear patterns of standardized estimators of species richness along latitudinal gradients or among Large Marine Ecosystems (LMEs); however, a strong latitudinal gradient in taxonomic composition (i.e., proportion of different taxonomic groups in a given sample) was observed. Environmental variables related to natural influences were strongly related to the distribution patterns of the assemblages on the LME scale, particularly photoperiod, sea surface temperature (SST) and rainfall. In contrast, no environmental variables directly associated with human influences (with the exception of the inorganic pollution index) were related to assemblage patterns among LMEs. Correlations of the natural assemblages with either latitudinal gradients or environmental variables were equally strong suggesting that neither neutral models nor models based solely on environmental variables sufficiently explain spatial variation of these assemblages at a global scale. Despite the data shortcomings in this study (e.g., unbalanced sample distribution), we show the importance of generating biological global databases for the use in large-scale diversity comparisons of rocky intertidal assemblages to stimulate continued sampling and analyses

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

Drug-induced anaphylaxis, elicitors, risk factors, and management in Latin America

Nonsteroidal anti-inflammatory drugs were the most frequent triggers of drug-induced anaphylaxis in Latín America, whereas antibiotics elicited faster onset and more scvere reactions. An improvement was observed in epinephrinc use and adherence to guidelines in the emergency department treatment of anaphylaxis in Latín America compared with our last report.Facultad de Ciencias Médica

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data