Phytosterol consumption and markers of subclinical atherosclerosis: Cross-sectional results from ELSA-Brasil

Background and aimsPhytosterol (PS) consumption is associated with lower total and LDL-cholesterol (LDL-c) concentrations, but its impact on cardiovascular risk is unclear. This study assessed the effect of usual intake of PS on markers of subclinical atherosclerosis in the Longitudinal Study of Adult Health (ELSA-Brasil).Methods and resultsThis cross-sectional study included 2560 participants of ELSA-Brasil, aged 48 (43–54) years, with available food frequency questionnaires (FFQ), coronary artery calcium (CAC) scores, carotid intima media thickness (cIMT), and carotid-femoral pulse wave velocity (cf-PWV), at baseline. Several logistic and linear regression models were used, and significance level was set at a P < 0.05. Mean values (SD) for PS consumption were 256 (198) mg/day, CAC 22.78 (110.54) Agatston Units, cf-PWV 9.07 (1.60) m/s and cIMT 0.57 (0.12) mm. PS consumption in Q4 was associated with lower total- and LDL-c levels, and with higher percentiles of cf-PWV (P < 0.001). Proportion of subjects in Q4 of PS consumption was 1.5 times higher among individuals in cf-PWV Q4, than in Q1 (P = 0.002, for comparisons among quartiles). There was a trend (P = 0.003) for higher cf-PWV with higher PS intake. In crude logistic and linear regressions, PS intake was associated with cf-PWV. In the adjusted models, these associations disappeared. No associations were found between PS and cIMT or CAC.ConclusionsIn this large and apparently healthy cross-sectional sample from ELSA-Brasil, usual PS consumption was associated with lower total- and LDL-cholesterol, but not with markers of subclinical atherosclerosis.     

Replacement of the left common iliac vein with a custom-made bovine pericardium tubular graft

To date, venous reconstruction has not been as successful as arterial reconstruction. Prosthetic materials used as venous substitutes produce much lower patency rates with a higher incidence of early thrombosis than those used as arterial substitutes. We describe the case of a 38-year-old obese woman in whom we encountered an unexpected tear of the common iliac vein intraoperatively, during an anterior approach to the lumbar spine. Because of limited options, we replaced the vein with an interposition tubulargraft that was custom-made from bovine pericardium. Two years later, the patient remained asymptomatic with a patent graft. To our knowledge, there has been no other reported case in the world medical literature of replacement of medium-sized veins by this technique.     

Similar progression of diabetic retinopathy with insulin glargine and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes: a long-term, randomised, open-label study

Aims/hypothesis  This long-term study was designed to further characterise the retinal safety profile of insulin glargine and human neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes mellitus. Methods  An open-label, 5 year, randomised (1:1), multicentre, stratified, parallel-group study conducted in the USA and Canada enrolled individuals with type 2 diabetes and either no or non-proliferative retinopathy (less than severe; Early Treatment Diabetic Retinopathy Study [ETDRS] level less than 53 in both eyes) who were treated with oral hypoglycaemic agents (OHAs) alone, insulin alone or OHAs with insulin for ≥3 months prior to study entry and a baseline HbA_1c level of 6.0–12.0%. Patients were randomised by the investigator according to the centralised interactive voice response system to receive twice-daily NPH insulin (n = 509) or once-daily basal insulin glargine (n = 515). The investigator was not blinded to the treatment group to which each participant had been assigned. The main objective of this study was to compare the progression of diabetic retinopathy between treatment groups by analysing the percentage of patients with three or more step progression in the ETDRS retinopathy patient-level severity scale after treatment with either basal insulin. Masked, centralised grading of seven-field stereoscopic fundus photographs was used. Results  Similarly sustained glycaemic control was observed in both the insulin glargine and NPH insulin treatment groups. Despite a slightly greater severity of diabetic retinopathy for the insulin glargine group at baseline, three or more step progression in ETDRS score from baseline to end-of-study was similar between treatment groups (14.2% [53/374] of insulin glargine-treated patients vs 15.7% [57/363] of NPH-treated patients); the difference in the incidence of progression was −1.98% (95% CI −7.02, 3.06%). Other measures of retinopathy—the development of proliferative diabetic retinopathy and progression to clinically significant macular oedema—occurred to a similar degree in both treatment groups. No other safety issues, such as unexpected adverse events for either insulin emerged during the 5 year study. However, NPH insulin treatment was associated with a higher incidence of severe hypoglycaemia compared with insulin glargine. Conclusions/interpretation  This study shows no evidence of a greater risk of the development or progression of diabetic retinopathy with insulin glargine vs NPH insulin treatment in patients with type 2 diabetes mellitus. Trial registration  ClinicalTrials.gov NCT00174824 Funding  This study was sponsored by sanofi-aventis. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health

ABSTRACT

The human gastrointestinal (gut) microbiota comprises diverse and dynamic populations of bacteria, archaea, viruses, fungi, and protozoa, coexisting in a mutualistic relationship with the host. When intestinal homeostasis is perturbed, the function of the gastrointestinal tract and other organ systems, including the brain, can be compromised. The gut microbiota is proposed to contribute to blood-brain barrier disruption and the pathogenesis of neurodegenerative diseases. While progress is being made, a better understanding of interactions between gut microbes and host cells, and the impact these have on signaling from gut to brain is now required. In this review, we summarise current evidence of the impact gut microbes and their metabolites have on blood-brain barrier integrity and brain function, and the communication networks between the gastrointestinal tract and brain, which they may modulate. We also discuss the potential of microbiota modulation strategies as therapeutic tools for promoting and restoring brain health.     

Protection and pathology during parasite infection: IL‐10 strikes the balance

The host response to infection requires an immune response to be strong enough to control the pathogen but also restrained, to minimize immune‐mediated pathology. The conflicting pressures of immune activation and immune suppression are particularly apparent in parasite infections, where co‐evolution of host and pathogen has selected many different compromises between protection and pathology. Cytokine signals are critical determinants of both protective immunity and immunopathology, and, in this review, we focus on the regulatory cytokine IL‐10 and its role in protozoan and helminth infections. We discuss the sources and targets of IL‐10 during parasite infection, the signals that initiate and reinforce its action, and its impact on the invading parasite, on the host tissue, and on coincident immune responses.     

Will Mayaro virus be responsible for the next outbreak of an arthropod-borne virus in Brazil?

Mayaro virus is an alphavirus from the Togaviridae family and is transmitted mainly by Hemagogus mosquitoes. This virus circulates in high-density tropical forests or rural areas of Central and South America causing a disease characterized by high-grade fever, maculopapular skin rash and marked arthralgia that, in some patients, can persist for long periods after infection and may be misinterpreted as chikungunya. Although only a few outbreaks involving this virus have been reported, in the last years the number of Mayaro virus infections has increased in the central and northern regions of Brazil. In this review, we describe the reported prevalence of this infection over the years and discuss the circumstances that can contribute to the establishment of an urban mayaro virus epidemic in Brazil and the problems encountered with the specific diagnosis, especially the antigenic cross-reactivity of this pathogen with other viruses of the same family.     

Vitamin C Improves Gastroparesis in Diabetic Rats: Effects on Gastric Contractile Responses and Oxidative Stress

Background

Diabetic gastroparesis is a common complication of diabetes mellitus, which mainly affects women. Previous studies have demonstrated that oxidative stress is involved in its onset and development.

Aims

This study evaluated the role of vitamin C on diabetes-associated gastric dysmotility.

Methods

Female rats with streptozotocin-induced diabetes were treated with vehicle (water, 1 mL/kg, p.o.), vitamin C (300 mg/kg/day, p.o.), or insulin (6 IU/day, s.c.). Gastric emptying, in vitro gastric contractility, and biochemistry parameters were analyzed at the end of the treatment (i.e. 8 weeks after the diabetes induction).

Results

Vitamin C reversed the delayed gastric emptying of diabetic rats to normal levels, and avoided the changes in the contractile responses to acetylcholine (0.1 nM–1 µM), but not to 5-hydroxytryptamine (0.1 nM–1 µM), in the pylorus and fundus from diabetic rats. Moreover, the contraction evoked by KCl (40 mM) in the fundus, but not in the pylorus, was intensely increased in diabetic rats treated with vitamin C. Notably, the vitamin C reestablished the reduced glutathione levels by 77% and decreased the reactive oxygen species content by 60% in the gastric tissue from diabetic rats. Despite the effects on gastric motility, vitamin C treatment did not change the fasting glycaemia or the glycated hemoglobin of diabetic rats. Unsurprisingly, insulin treatment normalized all parameters evaluated.

Conclusions

Vitamin C exhibited a remarkable beneficial effect on gastric emptying dysfunction in diabetic rats, which was mediated by attenuation of oxidative stress and maintenance of the cholinergic contractile responses in fundus and pylorus.

     

Complications of radiofrequency ablation of hepatic tumors:Frequency and risk factors

Radiofrequency ablation(RFA)has become an important option in the therapy of primary and secondary hepatic tumors.Surgical resection is still the best treatment option,but only a few of these patients are candidates for surgery:multilobar disease,insufficient liver reserve that will lead to liver failure after resection,extra-hepatic disease,proximity to major bile ducts and vessels,and co-morbidities.RFA has a low mortality and morbidity rate and is considered to be safe.Thus,complications occur and vary widely in the literature.Complications are caused by thermal damage,direct needle injury,infection and the patient’s co-morbidities.Tumor type,type of approach,number of lesions,tumor localization,underlying hepatic disease,the physician’s experience,associated hepatic resection and lesion size have been described as factors significantly associated with complications.The physician in charge should promptly recognize high-risk patients more susceptible to complications,perform a close post procedure follow-up and manage them early and adequately if they occur.We aim to describe complications from RFA of hepatic tumors and their risk factors,as well as a few techniques to avoid them.This way,others can decrease their morbidity rates with better outcomes.     

Previous Infection with SARS-CoV-2 Correlates with Increased Protective Humoral Responses after a Single Dose of an Inactivated COVID-19 Vaccine

Previous studies have indicated that antibody responses can be robustly induced after the vaccination in individuals previously infected by SARS-CoV-2. To evaluate anti-SARS-CoV-2 humoral responses in vaccinated individuals with or without a previous history of COVID-19, we compared levels of anti-SARS-CoV-2 antibodies in the sera from 21 vaccinees, including COVID-19-recovered or -naïve individuals in different times, before and after immunization with an inactivated COVID-19 vaccine. Anti-SARS-CoV-2-specific antibodies elicited after COVID-19 and/or immunization with an inactivated vaccine were measured by ELISA and Plaque Reduction Neutralizing assays. Antibody kinetics were consistently different between the two vaccine doses for naïve individuals, contrasting with the SARS-CoV-2-recovered subjects in which we observed no additional increase in antibody levels following the second dose. Sera from SARS-CoV2-naïve individuals had no detectable neutralizing activity against lineage B.1 SARS-CoV-2 or Gamma variant five months after the second vaccine dose. Contrarily, SARS-CoV-2-recovered subjects retained considerable neutralizing activity against both viruses. We conclude that a single inactivated SARS-CoV-2 vaccine dose may be sufficient to induce protective antibody responses in individuals with previous history of SARS-CoV-2 infection.     

Adipokines in Peritoneal Dialysis: Relevant Clinical Impact According to Body Composition

Adipokines impact on clinical outcomes is not adequately addressed in peritoneal dialysis (PD). We investigated the impact of leptin/adiponectin ratio (L/A) as a predictor of cardiovascular events (CVE) in PD, taking into consideration patient's body composition and the potential role of glucose load. We prospectively followed 66 prevalent PD patients for 47.0 ± 28.2 months. New CVE were evaluated. Lean tissue index (LTI), relative fat mass (relFM) and relative overhydration (relOH) using multifrequency bioimpedance (BCM) were assessed; serum lipids, interleukin‐6 (IL‐6), leptin and adiponectin were measured. We established the determinants of L/A using multiple linear regression and the impact of L/A on CVE. Obesity was present in 47 (73.4%) patients according to relFM, and in seven (10.6%) according to body mass index (BMI). Leptin and L/A exhibited a stronger correlation with relFM (both r = 0.62, P < 0.0001) than with BMI (r = 0.46 and r = 0.51, respectively, both P < 0.0001). L/A showed a significant correlation with triglycerides (r = 0.41, P = 0.001) and HDL‐cholesterol (r = ?0.358, P = 0.003), better than isolated leptin or adiponectin. RelFM (RR = 0.130, 95%confidence interval [CI]:0.086–0.174, P < 0.0001) and LTI (RR = 0.194, 95%CI:0.037–0.351, P = 0.016) were independent predictors of L/A (R² = 0.67). Patients who suffered new CVE were older (59.12 ± 12.41 vs. 47.52 ± 13.84years, P = 0.003) and had a higher relOH (11.28 ± 7.29 vs. 6.60 ± 8.16%, P = 0.028). L/A was significantly higher in patients with CVE[2.29 (1.79) vs. 0.65 (1.73), P = 0.028] but this association was only put on evidence after excluding patients with wasting. BMI is an inaccurate method to classify obesity in PD since it underestimates its prevalence compared with body composition assessment using BCM. High adiponectin and low leptin are associated with a more favorable metabolic risk profile in peritoneal dialysis. The L/A is determined by relFM and by LTI. A higher L/A is associated with CVE in PD patients without wasting.