In vitro priming and expansion of cytomegalovirus-specific Th1 and Tc1 T cells from naive cord blood lymphocytes

Adoptive transfer of CMV-specific cytotoxic T cells (CTLs) expanded in vitro from memory donor T cells can reduce the incidence of CMV disease in allogeneic transplant recipients. However, this approach has been unavailable in the cord blood (CB) transplantation setting because CB T cells are antigen naive and biased toward Th2/Tc2 function. We developed a protocol to in vitro prime and expand CMV-specific CTLs from CB. T cells were primed with cytokines to trigger skewing toward Th1/Tc1 lineage before encountering monocyte and CD34+ progenitor-derived dendritic cells loaded with CMV antigen and its immune complex. CMV-pulsed cultures expanded significantly more over 4 to 6 weeks than CMV cultures despite identical cytokine milieu. T cells isolated from CMV+ cultures showed a preferential expansion of CD45RA-/RO+/CD27+ T cells compared to CMV- cultures. CMV-specific IFN-gamma- and TNF-alpha-producing CD4+ (Th1) and CD8+ (Tc1) T cells were enriched after 3 to 4 weeks and CMV-specific cytotoxicity developed 1 to 2 weeks later.     

Lipids and diabetic nephropathy: hypertension,microalbuminuria and lipids in type 2 diabetic patients

Hypertension and microalbuminuria are predictors of cardiovascular mortality in type 2 (non-insulin-dependent) diabetes independently of other conventional risk factors. The presence of high triglyceride levels with small and/or dense low density lipoprotein particles is associated with cardiovascular disease. The aim of this study was to analyse the plasma lipids, Na⁺/Li⁺ countertransport (a genetic marker of hypertension) and microalbuminuria in type 2 diabetic patients. Plasma lipids were determined in 15 normotensive normoalbuminuric (H^–M^–), 32 hypertensive normoalbuminuric (H⁺M^–) and 22 hypertensive microalbuminuric (H⁺M⁺) type 2 diabetic patients and in 20 sex-and age-matched non-diabetic subjects. Plasma cholesterol was significantly higher in H⁺M⁺ patients than in controls (226±38 vs 192±38 mg/dl, mean ±SD). Plasma triglycerides were significantly higher in H⁺M⁺ patients than in either controls or H^–M^– patients (192±117 vs 104±59 and 115±52 respectively). The Na⁺/Li⁺ countertransport activity in red blood cells was significantly higher in H⁺M^– and H⁺M⁺ patients than in controls, and in the type 2 diabetic patients it was directly related to plasma triglycerides (r=0.53,P<0.0001) and inversely to high density lipoprotein (HDL) cholesterol (r=–0.43,P<0.0001). Microalbuminuria, hypertension and elevated Na⁺/Li⁺ countertransport activity are thus associated with high triglyceride and low HDL cholesterol levels in type 2 diabetic patients. This atherogenic lipoprotein pattern might at least partially explain the association of microalbuminuria with cardiovascular disease in type 2 diabetes.     

The Relationship Between Limit of Dysphagia and Average Volume Per Swallow in Patients with Parkinson’s Disease

The goal of this study was to obtain the limit of dysphagia and the average volume per swallow in patients with mild to moderate Parkinson’s disease (PD) but without swallowing complaints and in normal subjects, and to investigate the relationship between them. We hypothesize there is a direct relationship between these two measurements. The study included 10 patients with idiopathic PD and 10 age-matched normal controls. Surface electromyography was recorded over the suprahyoid muscle group. The limit of dysphagia was obtained by offering increasing volumes of water until piecemeal deglutition occurred. The average volume per swallow was calculated by dividing the time taken by the number of swallows used to drink 100 ml of water. The PD group showed a significantly lower dysphagia limit and lower average volume per swallow. There was a significantly moderate direct correlation and association between the two measurements. About half of the PD patients had an abnormally low dysphagia limit and average volume per swallow, although none had spontaneously related swallowing problems. Both measurements may be used as a quick objective screening test for the early identification of swallowing alterations that may lead to dysphagia in PD patients, but the determination of the average volume per swallow is much quicker and simpler.     

Different digestion enzymes used for human pancreatic islet isolation: A mixed treatment comparison (MTC) meta-analysis

Collagenases are critical reagents determining yield and quality of isolated human pancreatic islets and may affect islet transplantation outcome. Some islet transplantation centers have compared 2 or more collagenase blends; however, the results regarding differences in quantity and quality of islets are conflicting. Thus, for the first time, a mixed treatment comparison (MTC) meta-analysis was carried out to compile data about the effect of different collagenases used for human pancreas digestion on islet yield, purity, viability and stimulation index (SI). Pubmed, Embase and Cochrane libraries were searched. Of 755 articles retrieved, a total of 15 articles fulfilled the eligibility criteria and were included in the MTC meta-analysis. Our results revealed that Vitacyte and Liberase MTF were associated with a small increase in islet yield (islet equivalent number/g pancreas) when compared with Sevac enzyme [standardized mean difference (95% credible interval – CrI) = −2.19 (−4.25 to −0.21) and −2.28 (−4.49 to −0.23), respectively]. However, all other enzyme comparisons did not show any significant difference regarding islet yield. Purity and viability percentages were not significantly different among any of the analyzed digestion enzymes. Interestingly, Vitacyte and Serva NB1 were associated with increased SI when compared with Liberase MTF enzyme [unstandardized weighted mean difference (95% CrI) = −1.69 (−2.87 to −0.51) and −1.07 (−1.79 to −0.39), respectively]. In conclusion, our MTC meta-analysis suggests that the digestion enzymes currently being used for islet isolation works with similar efficiency regarding islet yield, purity and viability; however, Vitacyte and Serva NB1 enzymes seem to be associated with an improved SI as compared with Liberase MTF.     

Smoking-dependent and haplotype-specific effects of endothelial nitric oxide synthase gene polymorphisms on angiographically assessed coronary artery disease in Caucasian- and African-Brazilians

The nitric oxide produced by endothelial nitric oxide synthase (eNOS) plays a pivotal role in protecting the arterial wall from damages and atherosclerosis. The T-786C, the 27-bp repeat in intron 4, and the E298D eNOS gene polymorphisms were studied in 715 Brazilian patients (447 Caucasian- and 268 African-Brazilians) who underwent coronary angiography. The -786C frequency was increased in coronary artery disease (CAD) cases with significant lesions (> or =50% luminal obstruction) when compared with lesion-free controls; this difference was detected in smokers but not in nonsmokers, both in Caucasian- (p=0.011) and African-Brazilians (p=0.005). The interaction between -786C carriers and smoking was an independent CAD predictor (OR: 2.9, 95% CI: 1.4-5.9; p=0.003) in multiple logistic regression. The 298D mutation frequency was also higher among CAD cases (p=0.036) in African-Brazilian smokers, but this effect was not independent from other variables in the regression model. Though not associated with CAD, the 4-repeat allele combined with different T-786C alleles showed protective and susceptible effects in Caucasian-Brazilian smokers. The -786C/4-repeat/298E haplotype frequency was higher (p=0.020), whereas -786T/4-repeat/298E was lower (p=0.023) in these cases. These results showed a smoking-dependent effect of the T-786C eNOS polymorphism on CAD in both Caucasian- and African-Brazilians. Additionally, the haplotype analysis revealed different eNOS haplotypes associated with protection and susceptibility to the disease.     

31st Brazilian Online Society for Virology (SBV) 2020 Annual Meeting

The year 2020 was profoundly marked by the emergence and spread of SARS-CoV-2, causing COVID-19, which represents the greatest pandemic of the 21st century until now, and a major challenge for virologists in the scientific and medical communities. Increased numbers of SARS-CoV-2 infection all over the world imposed social and travel restrictions, including avoidance of face-to-face scientific meetings. Therefore, for the first time in history, the 2020 edition of the Brazilian Society of Virology (SBV) congress was totally online. Despite the challenge of the new format, the Brazilian society board and collaborators were successful in virtually congregating more than 921 attendees, which was the greatest SBV participant number ever reached. Seminal talks from prominent national and international researchers were presented every night, during a week, and included discussions about environmental, basic, animal, human, plant and invertebrate virology. A special roundtable debated exclusively new data and perspectives regarding COVID-19 by some of the greatest Brazilian virologists. Women scientists were very well represented in another special roundtable called “Young Women Inspiring Research”, which was one of the most viewed and commented section during the meeting, given the extraordinary quality of the presented work. Finally, SBV offered the Helio Gelli Pereira award for one graduate and one undergraduate student, which has also been a fruitful collaboration between the society and Viruses journal. The annual SBV meeting has, therefore, reached its goals to inspire young scientists, stimulate high-quality scientific discussion and to encourage global collaboration between virologists.     

Viral detection profile in children with severe acute respiratory infection

Objectives

The role of viral co-detection in children with severe acute respiratory infection is not clear. We described the viral detection profile and its association with clinical characteristics in children admitted to the Pediatric Intensive Care Unit (PICU) during the 2009 influenza A(H1N1) pandemic.

Altered Gut Microbiota in Type 2 Diabetes: Just a Coincidence?

Purpose of Review

In the last decade many studies have suggested an association between the altered gut microbiota and multiple systemic diseases including diabetes. In this review, we will discuss potential pathophysiological mechanisms, the latest findings regarding the mechanisms linking gut dysbiosis and type 2 diabetes (T2D), and the results obtained with experimental modulation of microbiota.

Recent Findings

In T2D, gut dysbiosis contributes to onset and maintenance of insulin resistance. Different strategies that reduce dysbiosis can improve glycemic control.

Summary

Evidence in animals and humans reveals differences between the gut microbial composition in healthy individuals and those with T2D. Changes in the intestinal ecosystem could cause inflammation, alter intestinal permeability, and modulate metabolism of bile acids, short-chain fatty acids and metabolites that act synergistically on metabolic regulation systems contributing to insulin resistance. Interventions that restore equilibrium in the gut appear to have beneficial effects and improve glycemic control. Future research should examine in detail and in larger studies other possible pathophysiological mechanisms to identify specific pathways modulated by microbiota modulation and identify new potential therapeutic targets.

     

Cognitive-behavioral therapy improves the quality of life of patients with acromegaly

Background

The delayed diagnosis, altered body image, and clinical complications associated with acromegaly impair quality of life.

Purpose

To assess the efficacy of the cognitive-behavioral therapy (CBT) technique “Think Healthy” to increase the quality of life of patients with acromegaly.

Methods

This non-randomized clinical trial examined ten patients with acromegaly (nine women and one man; mean age, 55.5?±?8.4 years) from a convenience sample who received CBT. The intervention included nine weekly group therapy sessions. The quality of life questionnaire the 36-Item Short Form Survey (SF-36) and the Beck Depression Inventory (BDI) were administered during the pre- and post-intervention phases. The Wilcoxon signed-rank test was performed to assess the occurrence of significant differences.

Results

According to the SF-36, the general health domain significantly improved (d′??=???0.264; p?=?0.031). The mental health domain improved considerably (d′??=???1.123; p?=?0.012). Physical functioning showed a non-significant trend toward improvement (d′??=???0.802; p?=?0.078), although four of the five patients who showed floor effects improved and remained at this level. Regarding emotional well-being, five patients showed floor effects and four improved, and the condition did not change among any of the four patients who showed ceiling effects. No significant changes were found with regard to the other domains. No significant differences in the BDI were found before or after the intervention.

Conclusion

The technique presented herein effectively improved the quality of life of patients with acromegaly with different levels of disease activity, type, and treatment time.