Thyroid stimulating hormone levels and geriatric syndromes : secondary nested case–control study of the Mexican Health and Aging Study

Q3Q3Abstract Purpose To determine the incidence of geriatric syndromes (GS) in community dwelling older adults with subclinical hypothyroidism. Methods This is an analysis from the Mexican Health and Aging Study, of a subsample of 2089 subjects with TSH determination. From this last subsample, we included 1628 individuals with TSH levels in the subclinical range (4.5–10 µU/ml). Results The multivariate analysis showed that when comparing data obtained from the 2012 wave with the 2015 wave results, there was a signifcant incidence of some GS such as falls (OR 1.79, CI 1.16–2.77, p=0.0116), fatigue (OR 2.17, CI 1.40–3.38, p=0.0348) and depression (OR 1.70, CI 1.06–2.71, p=0.0246) among the subclinical hypothyroidism group. Conclusion This study showed a greater incidence of GS in subjects 50 years and older with sub-clinical hypothyroidism, when compared to those with normal thyroid function. Keywords Thyroid stimulating hormone · Aging · Geriatric syndromes · Chronic disease · Subclinical hypothyroidismhttps://orcid.org/0000-0002-1652-5042https://scholar.google.com/citations?user=qUwLuswAAAAJ&hl=es&oi=aohttps://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000136038Revista Internacional - Indexad

The importance of having a flexible scope ISO 15189 accreditation and quality specifications based on biological variation – the case of validation of the biochemistry analyzer Dimension Vista

Introduction: Technological innovation requires the laboratories to ensure that modifications or incorporations of new techniques do not alter the quality of their results. In an ISO 15189 accredited laboratory, flexible scope accreditation facilitates the inclusion of these changes prior to accreditation body evaluation. A strategy to perform the validation of a biochemistry analyzer in an accredited laboratory having a flexible scope is shown. Materials and methods: A validation procedure including the evaluation of imprecision and bias of two Dimension Vista analysers 1500 was conducted. Comparability of patient results between one of them and the lately replaced Dimension RxL Max was evaluated. All studies followed the respective Clinical and Laboratory Standards Institute (CLSI) protocols. 30 chemistry assays were studied. Coefficients of variation, percent bias and total error were calculated for all tests and biological variation was considered as acceptance criteria. Quality control material and patient samples were used as test materials. Interchangeability of the results was established by processing forty patients’ samples in both devices. Results: 27 of the 30 studied parameters met allowable performance criteria. Sodium, chloride and magnesium did not fulfil acceptance criteria. Evidence of interchangeability of patient results was obtained for all parameters except magnesium, NT-proBNP, cTroponin I and C-reactive protein. Conclusions: A laboratory having a well structured and documented validation procedure can opt to get a flexible scope of accreditation. In addition, performing these activities prior to use on patient samples may evidence technical issues which must be corrected to minimize their impact on patient results

West Nile virus emergence in humans in Extremadura, Spain 2020

In Spain, the largest human West Nile virus (WNV) outbreak among humans was reported in 2020, constituting the second most important outbreak in Europe that season. Extremadura (southwestern Spain) was one of the affected areas, reporting six human cases. The first autochthonous human case in Spain was reported in Extremadura in 2004, and no other human cases were reported until 2020. In this work, we describe the first WNV human outbreak registered in Extremadura, focusing on the most important clinical aspects, diagnostic results, and control actions which followed. In 2020, from September to October, human WNV infections were diagnosed using a combination of molecular and serological methods (an in-house specific qRT-PCR and a commercial ELISA for anti-WNV IgM and IgG antibodies) and by analysing serum, urine, and/or cerebrospinal fluid samples. Serological positive serum samples were further tested using commercial kits against related flaviviruses Usutu and Tick-borne encephalitis in order to analyse serological reactivity and to confirm the results by neutralisation assays. In total, six cases of WNV infection (five with neuroinvasive disease and one with fever) were identified. Clinical presentation and laboratory findings are described. No viral RNA was detected in any of the analysed samples, but serological cross-reactivity was detected against the other tested flaviviruses. Molecular and serological methods for WNV detection in various samples as well as differential diagnosis are recommended. The largest number of human cases of WNV infection ever registered in Extremadura, Spain, occurred in 2020 in areas where circulation of WNV and other flaviviruses has been previously reported in humans and animals. Therefore, it is necessary to enhance surveillance not only for the early detection and implementation of response measures for WNV but also for other emerging flaviviruses that could be endemic in this area.This research was partially funded by the project PI19CIII/00014 from the Instituto de Salud Carlos III.S

Antibody recognition of the glycoprotein g of viral haemorrhagic septicemia virus (VHSV) purified in large amounts from insect larvae

<p>Abstract</p> <p>Background</p> <p>There are currently no purification methods capable of producing the large amounts of fish rhabdoviral glycoprotein G (gpG) required for diagnosis and immunisation purposes or for studying structure and molecular mechanisms of action of this molecule (ie. pH-dependent membrane fusion). As a result of the unavailability of large amounts of the gpG from viral haemorrhagic septicaemia rhabdovirus (VHSV), one of the most dangerous viruses affecting cultured salmonid species, research interests in this field are severely hampered. Previous purification methods to obtain recombinant gpG from VHSV in <it>E. coli</it>, yeast and baculovirus grown in insect cells have not produced soluble conformations or acceptable yields. The development of large-scale purification methods for gpGs will also further research into other fish rhabdoviruses, such as infectious haematopoietic necrosis virus (IHNV), spring carp viremia virus (SVCV), hirame rhabdovirus (HIRRV) and snakehead rhabdovirus (SHRV).</p> <p>Findings</p> <p>Here we designed a method to produce milligram amounts of soluble VHSV gpG. Only the transmembrane and carboxy terminal-deleted (amino acid 21 to 465) gpG was efficiently expressed in insect larvae. Recognition of G21-465 by ß-mercaptoethanol-dependent neutralizing monoclonal antibodies (N-MAbs) and pH-dependent recognition by sera from VHSV-hyperimmunized or VHSV-infected rainbow trout (<it>Oncorhynchus mykiss</it>) was demonstrated.</p> <p>Conclusions</p> <p>Given that the purified G21-465 conserved some of its most important properties, this method might be suitable for the large-scale production of fish rhabdoviral gpGs for use in diagnosis, fusion and antigenicity studies.</p

Antigenic Proteins Involved in Occupational Rhinitis 1 and Asthma Caused by Obeche Wood (Triplochiton Scleroxylon)

Background Obeche wood dust is a known cause of occupational asthma where an IgE-mediated mechanism has been demonstrated. Objective To characterize the allergenic profile of obeche wood dust and evaluate the reactivity of the proteins by in vitro, ex vivo and in vivo assays in carpenters with confirmed rhinitis and/or asthma Materials and methods An in-house obeche extract was obtained, and two IgE binding bands were purified (24 and 12 kDa) and sequenced by N-terminal identity. Specific IgE and IgG, basophil activation tests and skin prick tests (SPTs) were performed with whole extract and purified proteins. CCD binding was analyzed by ELISA inhibition studies. Results Sixty-two subjects participated: 12 with confirmed occupational asthma/rhinitis (ORA+), 40 asymptomatic exposed (ORA−), and 10 controls. Of the confirmed subjects, 83% had a positive SPT to obeche. There was a 100% recognition by ELISA in symptomatic subjects vs. 30% and 10% in asymptomatic exposed subjects and controls respectively (p<0.05). Two new proteins were purified, a 24 kDa protein identified as a putative thaumatin-like protein and a 12 kDa gamma-expansin. Both showed allergenic activity in vitro, with the putative thaumatin being the most active, with 92% recognition by ELISA and 100% by basophil activation test in ORA+ subjects. Cross-reactivity due to CCD was ruled out in 82% of cases. Conclusions Two proteins of obeche wood were identified and were recognized by a high percentage of symptomatic subjects and by a small proportion of asymptomatic exposed subjects. Further studies are required to evaluate cross reactivity with other plant allergens

Propuesta de mejora del Sistema Interno de Garantía de Calidad de la Facultad de Medicina

La garantía de calidad en el ámbito universitario puede considerarse como la atención sistemática, estructurada y continua a las titulaciones ofertadas. La garantía de calidad se compromete a poner en marcha los medios que aseguren y demuestren la calidad de los programas formativos que se desarrollan en cada una de las titulaciones ofrecidas por la Universidad y así cumplir con la obligación que tiene con la sociedad. El presente proyecto nace como fruto de la responsabilidad adquirida para el cumplimiento de las funciones encomendadas y, con el objetivo de seguir adoptando una estrategia de mejora continua de la calidad de la docencia y satisfacción de los colectivos implicados en el proceso de enseñanza-aprendizaje (Profesorado, Estudiantes y PAS)

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy

Background: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non-oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. Results: For non-OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

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