Synthesis and biological properties of macrolactam analogs of the natural product macrolide (−)-A26771B

Promising synthetic derivatives of macrolactone natural product (−)-A26771B have been designed and synthesized both from semisynthesis and total synthesis. Further optimization led to the first synthesis of macrolactam analogs of (−)-A26771B with improved antibacterial activity and metabolic stability.     

Risk Factors for Hemorrhoids on Screening Colonoscopy

Background

Constipation, a low fiber diet, sedentary lifestyle and gravidity are commonly assumed to increase the risk of hemorrhoids. However, evidence regarding these factors is limited. We examined the association between commonly cited risk factors and the prevalence of hemorrhoids.

Methods

We performed a cross sectional study of participants who underwent a colonoscopy in a colorectal adenoma prevention trial and who had a detailed assessment of bowel habits, diet and activity. The presence of hemorrhoids was extracted from the subjects’ colonoscopy reports. We used logistic regression to estimate odds ratios and 95% confidence intervals while adjusting for age and sex.

Results

The study included 2,813 participants. Of these, 1,074 had hemorrhoids recorded. Constipation was associated with an increased prevalence of hemorrhoids (OR 1.43, 95% CI 1.11, 1.86). Of the fiber subtypes, high grain fiber intake was associated with a reduced risk (OR for quartile 4 versus quartile 1 = 0.78, 95% CI 0.62, 0.98). We found no association when comparing gravid and nulligravida women (OR 0.93, 95% CI 0.62–1.40). Sedentary behavior was associated with a reduced risk (OR 0.80, 95% CI 0.65–0.98), but not physical activity (OR 0.83, 95% CI 0.66–1.03). Neither being overweight nor obese was associated with the presence of hemorrhoids (OR 0.89, 95% CI 0.72–1.09 and OR 0.86, 95% CI 0.70–1.06).

Conclusions

Constipation is associated with an increased risk of hemorrhoids. Gravidity and physical activity do not appear to be associated. High grain fiber intake and sedentary behavior are associated with a decreased risk of hemorrhoids.     

MicroRNA Transcriptome Profiling in Heart of Trypanosoma cruzi-Infected Mice: Parasitological and Cardiological Outcomes

Chagas disease is caused by the parasite Trypanosoma cruzi, and it begins with a short acute phase characterized by high parasitemia followed by a life-long chronic phase with scarce parasitism. Cardiac involvement is the most prominent manifestation, as 30% of infected subjects will develop abnormal ventricular repolarization with myocarditis, fibrosis and cardiomyocyte hypertrophy by undefined mechanisms. Nevertheless, follow-up studies in chagasic patients, as well as studies with murine models, suggest that the intensity of clinical symptoms and pathophysiological events that occur during the acute phase of disease are associated with the severity of cardiac disease observed during the chronic phase. In the present study we investigated the role of microRNAs (miRNAs) in the disease progression in response to T. cruzi infection, as alterations in miRNA levels are known to be associated with many cardiovascular disorders. We screened 641 rodent miRNAs in heart samples of mice during an acute infection with the Colombiana T.cruzi strain and identified multiple miRNAs significantly altered upon infection. Seventeen miRNAs were found significantly deregulated in all three analyzed time points post infection. Among these, six miRNAs had their expression correlated with clinical parameters relevant to the disease, such as parasitemia and maximal heart rate-corrected QT (QTc) interval. Computational analyses identified that the gene targets for these six miRNAs were involved in networks and signaling pathways related to increased ventricular depolarization and repolarization times, important factors for QTc interval prolongation. The data presented here will guide further studies about the contribution of microRNAs to Chagas heart disease pathogenesis.     

The ecophysiological performance of Vernonia polyanthes Less. (Asteraceae) in conserved and degraded forests in the Brazilian Cerrado

This study was performed to determine whether the environmental conditions of the Cerrado domain could directly influence photosynthesis (primary metabolism) and essential oil production (secondary metabolism) in adult Vernonia polyanthes Less. plants. In the experiments of this investigation, which were conducted in two areas of the Cerrado (conserved and degraded) during the dry season (winter), leaf CO₂ assimilation rate, transpiration, stomatal conductance, instantaneous carboxylation efficiency, leaf water potential, soil potential and essential oil yield were evaluated. V. polyanthes plants exhibited outstanding growth in the conserved forests of the Brazilian Cerrado, with a higher leaf CO₂ assimilation rate, instantaneous carboxylation efficiency, leaf water potential, soil potential and essential oil yield than in degraded regions of the Cerrado. Interestingly, the Cerrado sensu stricto was associated with lower performance with respect to essential oil yield and transpiration but no alteration of stomatal conductance, an essential determinant of gas exchange parameters. Our data suggest that ecophysiological effects in conserved and degraded areas in the Cerrado modify gas exchange and essential oil production in V. polyanthes.     

Weight loss is not mandatory for exercise-induced effects on health indices in females with metabolic syndrome

The aim of this study was to investigate the impact of moderate aerobic training on functional, anthropometric, biochemical, and health-related quality of life (HRQOL) parameters on women with metabolic syndrome (MS). Fifteen untrained women with MS performed moderate aerobic training for 15 weeks, without modifications of dietary behaviours. Functional, anthropometric, biochemical, control diet record and HRQOL parameters were assessed before and after the training. Despite body weight maintenance, the patients presented decreases in waist circumference (P = 0.001), number of MS components (P = 0.014), total cholesterol (P = 0.049), HDL cholesterol (P = 0.004), LDL cholesterol (P = 0.027), myeloperoxidase activity (P = 0.002) and thiobarbituric acid-reactive substances levels (P = 0.006). There were no differences in total energy, carbohydrate, protein and lipid intake pre- and post-training. Furthermore, improvements in the HRQOL subscales of physical functioning (P = 0.03), role-physical (P = 0.039), bodily pain (P = 0.048), general health (P = 0.046) and social functioning scoring (P = 0.011) were reported. Despite the absence of weight loss, aerobic training induced beneficial effects on functional, anthropometric, biochemical and HRQOL parameters in women with MS.