17Beta-estradiol abrogates apoptosis in murine skeletal muscle cells through estrogen receptors: role of the phosphatidylinositol 3-kinase/Akt pathway

Estrogens can regulate apoptosis in various cellular systems. The present study shows that 17beta-estradiol (E2), at physiological concentrations, abrogates DNA damage, poly (ADP-ribose) polymerase cleavage, and mitochondrial cytochrome c release induced by H2O2 or etoposide in mouse skeletal muscle C2C12 cells. This protective action, which involved PI3K/Akt activation and Bcl-2 associated death agonist (BAD) phosphorylation, was inhibited by antibodies against the estrogen receptor (ER) alpha or beta isoforms, or transfecting siRNA specific for each isoform. The inhibition of the antiapoptotic action of E2 at the mitochondrial level was more pronounced when ER-beta was immunoneutralized or suppressed by mRNA silencing, whereas transfection of C2C12 cells with either ER-alpha siRNA or ER-beta siRNA blocked the activation of Akt by E2, suggesting differential involvement of ER isoforms depending on the step of the apoptotic/survival pathway evaluated. These results indicate that E2 exerts antiapoptotic effects in skeletal muscle cells which are mediated by ER-beta and ER-alpha and involve the PI3K/Akt pathway.     

Polymorphisms in metalloproteinase-9 are associated with the risk for asthma in Mexican pediatric patients

Asthma is characterized by chronic airway inflammation, which induces airway remodelling of the extracellular matrix over time. Matrix metalloproteinases (MMPs) are involved in this process, and single-nucleotide polymorphisms (SNPs) in MMP genes may influence their mRNA expression levels or abilities to bind substrates and inhibitors, thereby contributing to asthma predisposition and severity. MMP-9 is highly expressed in airways and many studies support its involvement in asthma pathogenesis; however the contribution of MMP-9 SNPs is controversial. To investigate whether MMP-9 SNPs are associated with childhood-onset asthma in Mexican patients we conducted a case-control study including 403 children with clinical asthma diagnoses and 426 healthy controls from Mexico. The cases and controls were matched by ethnicity and gender. We found that the SNPs rs2274755, rs17577, and rs3918249 were associated with asthma risk. The most significant associations were with rs2274755 (OR = 2.10, 95% CI 1.31–3.39, P = 0.001) and rs17577 (OR = 2.07, 95% CI 1.29–3.30, P = 0.001); which were in strong linkage disequilibrium. Both SNPs were also associated with atopic asthma (OR = 2.38, 95% CI 1.44–3·96, P = 0.0005). The SNP rs3918249 exhibited a female gender-dependent association with asthma (OR = 1.66, 95% CI 1.14–2.43, P = 0.007). Our results suggest that MMP-9 polymorphisms could play a role in the susceptibility to childhood-onset asthma.     

Diagnostic yield of capillary compared to venous glucose in the diagnosis of hypoglycorrhachia in children: A prospective,observational study

IntroductionThe ratio of cerebrospinal fluid (CSF) glucose and blood glucose is of major relevance, conducting to the diagnosis of hypoglycorrhachia, which is a sign of neuroinfection, as well as a number of neurological diseases of genetic or neoplastic etiology. Glucose in capillary sample (glucometry) is a low cost, readily available technique, as compared to venous glucose. This study aims to compare glucometry to venous glucose in the diagnosis of hypoglycorrhachia in pediatric population.MethodsProspective cross-sectional study based on data obtained from lumbar punctures in the period from February 2017 to January 2019 in a specialized pediatric institution in Colombia.Results97 patients were analyzed, aged 1 month to 17 years old, mean 7.67 years, 52 (53.61%) were female. 26 (26.8%) were diagnosed with hypoglycorrhachia. Pearson correlation coefficient for absolute venous and capillary glucose was 0.54, and 0.55 for the ratios of CSF glucose/venous glucose and CSF glucose/glucometry, which support a linear correlation between the variables in both, absolute values and ratios. Intraclass correlation coefficient was calculated for both, the venous glucose and glucometry ratios, which was 0.52, revealing a moderate agreement among the tests. Sensitivity and specificity of CSF glucose/glucometry, as compared to gold standard are 73.1% and 60.6% respectively; whereas predictive positive value (PPV) and negative predictive value (NPV), were 40.4% and 86.0%.ConclusionGlucometry cannot replace the glucose in venous sample in the diagnosis of hypoglycorrhachia in children.     

Acute gastroenteritis outbreaks in closed and semi-closed facilities during 2017 in Catalonia,Spain

Acute gastroenteritis (AGE) is a leading cause of disease worldwide. The aim of this prospective observational study is to describe the epidemiology of AGE in closed and semi-closed institutions in Catalonia. In 2017, 151 outbreaks were reported; 30.5% occurred in closed and semi-closed institutions; 71.7% caused by norovirus (NoV) (1532) cases. Person-to-person transmission accounted for 75.8% of NoV outbreaks vs 46.1% in non-NoV outbreaks (p?<?0.001). Attack rate for NoV outbreaks was 33.1% vs 14.3% for non-NoV outbreaks (RR?=?2.3; 95%CI: 2.0–2.7). The high number of affected underscores prompt and intense preventive measures to avoid the extension and perpetuation of outbreaks in these settings.

     

Flow cytometry data mining by cytoChain identifies determinants of exhaustion and stemness in TCR-engineered T cells

The phenotype of infused cells is a major determinant of Adoptive T-cell therapy (ACT) efficacy. Yet, the difficulty in deciphering multiparametric cytometry data limited the fine characterization of cellular products. To allow the analysis of dynamic and complex flow cytometry samples, we developed cytoChain, a novel dataset mining tool and a new analytical workflow. CytoChain was challenged to compare state-of-the-art and innovative culture conditions to generate stem-like memory cells (T_SCM) suitable for ACT. Noticeably, the combination of IL-7/15 and superoxides scavenging sustained the emergence of a previously unidentified nonexhausted Fit-T_SCM signature, overlooked by manual gating and endowed with superior expansion potential. CytoChain proficiently traced back this population in independent datasets, and in T-cell receptor engineered lymphocytes. CytoChain flexibility and function were then further validated on a published dataset from circulating T cells in COVID-19 patients. Collectively, our results support the use of cytoChain to identify novel, functionally critical immunophenotypes for ACT and patients immunomonitoring.     

Impact of Cardiovascular Interventions on the Quality of Life in the Elderly

INTRODUCTION

The elderly population is growing rapidly. Political and socio-economic changes led to the demographic transition in this population with the highest number of surgeries and as well as many comorbidities.

OBJECTIVE

To evaluate the impact of cardiovascular intervention on quality of life of elderly patients after three and six months.

METHODS

Analytical prospective cohort study with elderly between 60 and 80 years of age, of both sexes, with a diagnosis of coronary artery disease and underwent cardiovascular intervention during the period June 2010 to June 2011. Data were collected by individual interviews in the pre and postoperative periods (after three and six months) by telephone. We used the SF-36 to analyse quality of life in order to assess the physical and mental health of the study population.

RESULTS

Of the 44 individuals evaluated, 59.1% were men, 75% in the range of 65 to 74 years, 38.6% were white and 38.6% were black, 31.8% were uneducated, 43.2% were married and 68.2% had less than a minimum wage. Prevailed patients: non-diabetics (68.2%), non-obese (81.8%), hypertensive (84.1%), non-alcoholic and non-smokers (68.2% and 61.4%, respectively). A significant increase in the average of the SF-36 scores between pre and post-surgical periods (three and six months) for the domains: functional capacity, pain, general health, vitality and emotional aspect.

CONCLUSION

The elderly population undergoing intervention may have cardiovascular benefits and improvements of quality of life. Physical fitness improvement measures can be taken to resume that capability.