A Systematic Evaluation of Chip-Based Nanoelectrospray Parameters for Rapid Identification of Proteins from a Complex Mixture

HPLC-MS/MS is widely used for protein identification from gel spots and shotgun fractions. Although HPLC has well recognized benefits, this type of sample infusion also has some undesirable attributes: relatively low sample throughput, potential sample-to-sample carryover, time-varying sample composition, and no option for longer sample infusion for longer MS analyses. An automated chip-based ESI device (CB-ESI) has the potential to overcome these limitations. This report describes a systematic evaluation of the information-dependant acquisition (IDA) and sample preparation protocols for rapid protein identification from a complex mixture using a CB-ESI source compared with HPLC-ESI (gradient and isocratic elutions). Cytochrome c and a six-protein mixture (11–117 kDa) were used to develop an IDA protocol for rapid protein identification and to evaluate the effects of sample preparation protocols. MS (1–10 s) and MS/MS (1–60 s) scan times, sample concentration (50–500 fmol/μL), and ZipTipC18 cleanup were evaluated. Based on MOWSE scores, protein coverage, experimental run time, number of identified proteins, and reproducibility, a 12.5 min experiment (22 cycles, each with one 3 s MS and eight 10 s MS/MS scans) was determined to be the optimal IDA protocol for CB-ESI. This work flow yielded up to 220% greater peptide coverage compared with gradient HPLC-ESI and provided protein identifications with up to a 2-fold higher throughput rate than either HPLC-ESI approach, whilst employing half the amount of sample over the same time frame. The results from this study support the use of CB-ESI as a rapid alternative to the identification of protein mixtures

Barreras Para La Práctica Del Ejercicio Durante El Confinamiento Por Covid-19 En Docentes De La Uaz

The confinement by covid-19 generated a decrease in physical exercise and consequently a higher risk of suffering from various diseases. Objective: to know the barriers for the practice of exercise during the confinement by COVID-19 in teachers of the Autonomous University of Zacatecas (UAZ) in the semester August-December 2020. A descriptive, analytical and cross-sectional study was conducted with a quantitative approach, An On-line survey developed in the Google Forms application was volunteered, using a non-parametric descriptive statistical test, CI 72%= (-1.09;1.09). The total sample was 437 subjects; it was found that 72% of the population does exercise, where it was concluded that the main barrier to exercise is disinterest, overwork and lack of knowledge to have a well-planned training. This is followed by injuries and illnesses that prevent them from exercising

Analysis of the promotion of the Sustainable Development Goals and Food Security through a Learning Management System (LMS) to promoters in the United States.

La presente investigación se realizó con promotores de salud migrantes, quienes desempeñan un rol clave para ayudar a promover el acceso igualitario a la salud y al capacitarse brindan apoyo a la salud pública de la comunidad. La mala alimentación y malnutrición representan una problemática social grave para muchos migrantes latinos, que en la mayoría de las ocasiones se produce por falta de alimentos, la poca diversidad en su dieta y/o por la escasa información de cómo prepararlos de manera saludable. Es así que resulta necesario desarrollar programas y estrategias que contribuyan en la formación integral de los promotores de salud. El objetivo consistió en analizar la promoción de los Objetivos de Desarrollo Sostenible (ODS) y Seguridad Alimentaria (SA) por medio de un Sistema de Gestión de Aprendizaje (LMS) a promotores de salud en Estados Unidos. La muestra se conformó por 34 promotores de salud en un estudio mixto de diseño exploratorio secuencial y cuasi-experimental, prospectivo, longitudinal. El instrumento empleado para encontrar el grado de inseguridad alimentaria de los promotores fue la Escala de Seguridad Alimentaria (ELCSA) y a fin de determinar el impacto de conocimientos del curso se desarrolló un cuestionario sobre temas de alimentación sostenible. El desarrollo y aplicación del mismo fue a través de las herramientas para elaboración de evaluaciones dentro del LMS Moodle como parte de la plataforma institucional de Educación a distancia de la U.A.Z. Los resultados obtenidos se analizaron de manera cuantitativa y cualitativa, encontrado a nivel general inseguridad alimentaria leve. Para brindar soluciones al problema se implementó el curso “Alimentación Sostenible” logrando un cambio de conocimientos notable del cuestionario inicial al final, reafirmando los aprendizajes con la elaboración de evidencias del curso, donde el 100% de los promotores lograron cosechar y producir alimentos sostenibles en sus hogares, adquiriendo  las herramientas básicas necesarias para promover la defensa de sus derechos humanos, el cambio climático y seguridad alimentaria, apoyando a su comunidad con los conocimientos adquiridos, todo por medio de la educación a distancia

Single Nucleotide Polymorphisms Of The Gjb2 And Gjb6 Genes Are Associated With Autosomal Recessive Nonsyndromic Hearing Loss.

Single nucleotide polymorphisms (SNPs) are important markers in many studies that link DNA sequence variations to phenotypic changes; such studies are expected to advance the understanding of human physiology and elucidate the molecular basis of diseases. The DFNB1 locus, which contains the GJB2 and GJB6 genes, plays a key role in nonsyndromic hearing loss. Previous studies have identified important mutations in this locus, but the contribution of SNPs in the genes has not yet been much investigated. The aim of this study was to investigate the association of nine polymorphisms located within the DFNB1 locus with the occurrence of autosomal recessive nonsyndromic hearing loss (ARNSHL). The SNPs rs3751385 (C/T), rs7994748 (C/T), rs7329857 (C/T), rs7987302 (G/A), rs7322538 (G/A), rs9315400 (C/T), rs877098 (C/T), rs945369 (A/C), and rs7333214 (T/G) were genotyped in 122 deaf patients and 132 healthy controls using allele-specific PCR. There were statistically significant differences between patients and controls, in terms of allelic frequencies in the SNPs rs3751385, rs7994748, rs7329857, rs7987302, rs945369, and rs7333214 (P < 0.05). No significant differences between the two groups were observed for rs7322538, rs9315400, and rs877098. Our results suggest that SNPs present in the GJB2 and GJB6 genes may have an influence on ARNSHL in humans.201531872

Single nucleotide polymorphisms of the GJB2 and GJB6 genes are associated with autosomal recessive nonsyndromic hearing loss

Single nucleotide polymorphisms (SNPs) are important markers in many studies that link DNA sequence variations to phenotypic changes; such studies are expected to advance the understanding of human physiology and elucidate the molecular basis of diseases. The DFNB1 locus, which contains the GJB2 and GJB6 genes, plays a key role in nonsyndromic hearing loss. Previous studies have identified important mutations in this locus, but the contribution of SNPs in the genes has not yet been much investigated. The aim of this study was to investigate the association of nine polymorphisms located within the DFNB1 locus with the occurrence of autosomal recessive nonsyndromic hearing loss (ARNSHL). The SNPs rs3751385 (C/T), rs7994748 (C/T), rs7329857 (C/T), rs7987302 (G/A), rs7322538 (G/A), rs9315400 (C/T), rs877098 (C/T), rs945369 (A/C), and rs7333214 (T/G) were genotyped in 122 deaf patients and 132 healthy controls using allele-specific PCR. There were statistically significant differences between patients and controls, in terms of allelic frequencies in the SNPs rs3751385, rs7994748, rs7329857, rs7987302, rs945369, and rs7333214 (P < 0.05). No significant differences between the two groups were observed for rs7322538, rs9315400, and rs877098. Our results suggest that SNPs present in the GJB2 and GJB6 genes may have an influence on ARNSHL in humans2015CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFundacao Herminio Ometto/FH

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

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Improved Throughput and Efficiency of Proteome Analyses : Tools and Workflows

EThOS - Electronic Theses Online ServiceGBUnited Kingdo