Prevalencia del síndrome metabólico en población laboral española: registro MESYAS

Introducción y objetivos. Estudiar la prevalencia del síndrome metabólico (SM) en la población laboral activa española y analizar sus diferencias según las categorías laborales. Sujetos y método. Se recogieron los datos de 7.256 trabajadores activos (un 82,4% varones), con una edad media de 45,4 ± 9,8 años, empleados en una factoría de coches y unos grandes almacenes. El diagnóstico del SM se realizó mediante los criterios modificados del ATP-III (se utilizó el índice de masa corporal en lugar del perímetro abdominal). Resultados. La prevalencia bruta del SM fue del 10,2%. Ajustada por edad y sexo en una población plana (20-60 años) fue del 5,8% (intervalo de confianza [IC] del 95%, 4,1-7,6%), significativamente más alta en varones que en mujeres (el 8,7%; IC del 95%, 7,3-10,0 frente al 3,0%; IC del 95%, 0,8-5,1). Todos los componentes del SM fueron significativamente más prevalentes en varones, excepto las concentraciones de lipoproteínas de alta densidad, que fueron más bajas. La prevalencia aumentó con la edad y el sexo masculino (odds ratio [OR] = 1,7), la obesidad (OR = 9,6), la hipertensión (OR = 3,4) y la diabetes (OR = 15,4). Los trabajadores manuales presentaron la mayor prevalencia de SM (11,8%), seguidos por EPIDEMIOLOGÍA Y PREVENCIÓN Prevalencia del síndrome metabólico en población laboral española: registro MESYAS Eduardo Alegríaa, Alberto Corderoa, Martín Laclaustrab, Alberto Grimac, Montserrat Leónb, José A. Casasnovasb, Emilio Luengod, Alfonso del Ríob e Ignacio Ferreirab, en representación de los investigadores del registro MESYAS* aDepartamento de Cardiología. Clínica Universitaria de Navarra. Pamplona. Navarra. España. bUnidad de Investigación Cardiovascular. Hospital Clínico Universitario. Zaragoza. España. cServicio de Cardiología Preventiva. Asepeyo. Valencia. España. dServicio de Cardiología. Hospital Militar. Zaragoza. España. *Al final del artículo se relacionan los miembros del equipo de investigación MESYAS. Martín Laclaustra está contratado como investigador en el Instituto Aragonés de Ciencias de la Salud dentro del programa de ayudas a contratos para investigadores que han finalizado su formación médica especializada del Instituto de Salud Carlos III. El registro MESYAS cuenta con una beca de la Sociedad Española de Cardiología (Sevilla, 2003) y la Sección de Cardiología Preventiva y Rehabilitadora. Correspondencia: Dr. E. Alegría Ezquerra. Departamento de Cardiología. Clínica Universitaria de Navarra. Avda. Pío XII, 36. 31008 Pamplona. Navarra. España. Correo electrónico: [email protected] Recibido el 5 de octubre de 2004. Aceptado para su publicación el 18 de marzo de 2005. los trabajadores de oficina (9,3%) y los directivos (7,7%) (gradiente social inverso). Los trabajadores manuales tienen un riesgo superior de presentar SM, con independencia de la edad y el sexo (OR = 1,3); este efecto parece depender de las concentraciones de triglicéridos. Conclusiones. Uno de cada 10 trabajadores activos tiene SM; la prevalencia aumenta con la edad y el sexo masculino. La obesidad y la diabetes suponen gran incremento de la prevalencia. Los trabajadores manuales son el colectivo con mayor prevalencia

Early evolution of the biotin-dependent carboxylase family

<p>Abstract</p> <p>Background</p> <p>Biotin-dependent carboxylases are a diverse family of carboxylating enzymes widespread in the three domains of life, and thus thought to be very ancient. This family includes enzymes that carboxylate acetyl-CoA, propionyl-CoA, methylcrotonyl-CoA, geranyl-CoA, acyl-CoA, pyruvate and urea. They share a common catalytic mechanism involving a biotin carboxylase domain, which fixes a CO₂molecule on a biotin carboxyl carrier peptide, and a carboxyl transferase domain, which transfers the CO₂moiety to the specific substrate of each enzyme. Despite this overall similarity, biotin-dependent carboxylases from the three domains of life carrying their reaction on different substrates adopt very diverse protein domain arrangements. This has made difficult the resolution of their evolutionary history up to now.</p> <p>Results</p> <p>Taking advantage of the availability of a large amount of genomic data, we have carried out phylogenomic analyses to get new insights on the ancient evolution of the biotin-dependent carboxylases. This allowed us to infer the set of enzymes present in the last common ancestor of each domain of life and in the last common ancestor of all living organisms (the cenancestor). Our results suggest that the last common archaeal ancestor had two biotin-dependent carboxylases, whereas the last common bacterial ancestor had three. One of these biotin-dependent carboxylases ancestral to Bacteria most likely belonged to a large family, the CoA-bearing-substrate carboxylases, that we define here according to protein domain composition and phylogenetic analysis. Eukaryotes most likely acquired their biotin-dependent carboxylases through the mitochondrial and plastid endosymbioses as well as from other unknown bacterial donors. Finally, phylogenetic analyses support previous suggestions about the existence of an ancient bifunctional biotin-protein ligase bound to a regulatory transcription factor.</p> <p>Conclusions</p> <p>The most parsimonious scenario for the early evolution of the biotin-dependent carboxylases, supported by the study of protein domain composition and phylogenomic analyses, entails that the cenancestor possessed two different carboxylases able to carry out the specific carboxylation of pyruvate and the non-specific carboxylation of several CoA-bearing substrates, respectively. These enzymes may have been able to participate in very diverse metabolic pathways in the cenancestor, such as in ancestral versions of fatty acid biosynthesis, anaplerosis, gluconeogenesis and the autotrophic fixation of CO₂.</p

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

B Vitamins: Small molecules, big effects

In this themed issue of the Journal of Inherited Metabolic Disease, we review the roles of six of the B vitamins in human disease, focussing on treatable inborn errors of metabolism. The special issue starts with a review of thiamine metabolism. O'Callaghan et al provide a comprehensive review of the riboflavin transporter disorders, emphasising the role of mitochondrial dysfunction in the pathophysiology of these neuronopathic syndromes. Balasubramaniam et al then focus on disorders of riboflavin metabolism, in particular the recently discovered flavin adenine dinucleotide (FAD) synthase deficiency, and the rapidly growing list of riboflavin‐responsive disorders associated with mutations in the human flavoproteome (i.e., the >90 human proteins that use FAD or flavin mononucleotide [FMN] as cofactors). Two reviews focus on B6 dependent seizures. Crowther et al provide new insights into human lysine degradation pathways relevant for pyridoxine‐dependent epilepsy caused by antiquitin deficiency, whilst the second reviews all the known causes of B6‐dependent seizures, including the recently discovered disorder of an intracellular PLP‐binding protein (PLPBP deficiency). The roles of biotin in metabolism, gene expression and human disease are examined. Analytical methods for detecting cerebral folate deficiency and discuss the differential diagnosis of this condition, including disorders of folate transport and metabolism, secondary deficiencies related to other inborn errors and acquired causes. Finally, there is a comprehensive review of vitamin B12, folate and the methionine remethylation cycle, focussing on biochemical pathways and regulation, accompanied by a clinical review of the cobalamin‐related disorders

Identificar las moléculas HLA DRB1-DQB1 y predecir los epítopos asociados con la eliminación y redetección de la infección por VPH de alto riesgo.

Several determining factors are involved in HPV infection outcomes; human leukocyte antigen (HLA) polymorphisms have been described as related factors. This study has ascertained the effect of genetic variation on HLA-DRB1 and DQB1 genes on HPV-16/-18/-31/-33/-45 and -58 clearance and redetection in Colombian women. PCR and qPCR were used for viral identification and the Illumina MiSeq system was used for HLA-typing of cervical samples (n=276). Survival models were adjusted for identifying alleles/haplotypes related to HPV clearance/redetection; L1/L2 protein-epitope binding to MHC-II molecules was also predicted. Significant associations suggested effects favouring or hampering clearance/redetection events depending on the viral type involved in infection, e.g. just DRB1*12:01:01G favoured HPV-16 (coeff: 4.8) and HPV-45 clearance (coeff: 12.65) whilst HPV-18 (coeff: 2E-15), HPV-31 (coeff: 8E-17) and HPV-58 hindered elimination (coeff: 1E-14). An effect was only observed for some alelles when configured as haplotypes, e.g. DRB1*04:07:01G (having the greatest frequency in the target population) was associated with DQB1*02:01:1G or *03:02:03. Epitope prediction identified 23 clearance-related peptides and 29 were redetection-related; eight might have been related to HPV-16/-18 and -58 persistence and one to HPV-18 elimination. HLA allele/haplotype relationship with the course of HPV infection (clearance/redetection) depended on the infecting HPV type, in line with the specific viral epitopes displayed