A mixture of pesticides at environmental concentrations induces oxidative stress and cholinergic effects in the neotropical fish Rhamdia quelen

The insecticides imidacloprid (IMI), a neonicotinoid, and propoxur (PRO), an N-methylcarbamate compound, are pesticides widely used throughout the world. Although they are not used together to combat pests, both are often found in freshwater near agricultural areas. Thereby, the goal of this study was to evaluate the additive effects of IMI and PRO mixtures at environmental concentrations in relation to isolated compounds on Rhamdia quelen, a neotropical fish. The fish was exposed to IMI (0.11 µg/L), PRO (0.039 µg/L), or Mix (0.11 µg/L IMI plus 0.039 µg/L PRO) during 96 h. Glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), acetylcholinesterase (AChE) activities were determined. To verify oxidative damage thiobarbituric acid reactive substances (TBARS), protein carbonyl (PC), reactive oxygen species contents (ROS), antioxidant capacity against peroxides (ACAP) were determined in gills, liver, brain and muscle. The results shows that a mixture of these pesticides at environmental concentrations inhibited acetylcholinesterase activity in the brain and induced oxidative damage in all analyzed tissues. These results reinforce the hypothesis that mixture of contaminants present in environment could induce additive or synergistic effects on fish species.

     

Current perspectives in therapeutic myocardial angiogenesis

The complex mechanisms mediating the development of new blood vessels are now beginning to be unraveled. In conjunction with major biotechnology advances, this has facilitated the initiation of translational research related to a novel treatment strategy for patients with myocardial or leg ischemia due to obstructive arterial disease--therapeutic angiogenesis. At present, at least 17 clinical trials of myocardial angiogenesis have been presented involving over 900 patients. Uncertainty exists as to the optimal delivery route and angiogenic agent, and this uncertainty is reflected in the diverse methodology of the trials published thus far. The majority of patients received an angiogenic protein via the intracoronary route. Other delivery techniques--such as direct intramyocardial injection via transepicardial or transendocardial routes--and other angiogenic agents, including master genes, have also been studied. Most recently, interest has grown in the potential angiogenesis effects of cell therapy--such as autologous bone marrow cells or cultured stem cells--and there are now several groups initiating Phase I/II trials in this area. This review summarizes the current evidence pertaining to the safety, feasibility, and efficacy of various angiogenic techniques aimed at enhancing myocardial blood flow and alleviating angina.     

Prediction of clinical outcomes in Crohn’s disease by using confocal laser endomicroscopy: results from a prospective multicenter study

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Permanent-temporary pacemakers in the management of patients with conduction abnormalities after transcatheter aortic valve replacement

Background

Damage to the cardiac conduction system requiring permanent pacemaker (PPM) implantation is a known adverse outcome of transcatheter aortic valve replacement (TAVR). A permanent-temporary pacemaker (PTPM) is a device that involves an active-fixation lead attached to an external pulse generator taped to the skin. We reviewed the utility of PTPMs as a temporary bridge measure after TAVR in patients with conduction abnormalities that do not meet conventional criteria for PPM placement.

Methods

Between January 01, 2013 and December 31, 2015, we analyzed 67 patients who received PTPM after TAVR. Baseline demographics, comorbidities, type and size of the valve, pre-TAVR electrocardiograms (ECGs), post-TAVR ECGs at 1 day, 1 month, and 6 months, and pacemaker interrogation results were reviewed for each patient if available.

Results

The mean age of patients was 80.5?±?9.1 years. PTPM were placed for 2.3?±?2.4 days. Among these patients, 44.8% (n?=?30) received a PPM prior to discharge. Male gender (OR 2.84, 95% CI 1.05–7.69, p?=?0.05) and an increase in QRS duration post-TAVR (p?=?0.01) were associated with PPM placement. Pacemaker interrogation data of 11 patients with PPM revealed that 27% (n?=?3) had <?1% V-pacing requirements and <?10% A-pacing requirements.

Conclusions

In post-TAVR patients who develop conduction abnormalities that do not meet conventional PPM implantation indications, PTPM safely provides a time period for further assessment and may prevent unnecessary PPM implantation. Male gender and an increase in QRS duration post-TAVR are associated with PPM implantation. Additionally, some patients may recover from their conduction disturbances and demonstrate low pacemaker utilization.

     

Novel de novo heterozygous loss-of-function variants in MED13L and further delineation of the MED13L haploinsufficiency syndrome

MED13L haploinsufficiency has recently been described as responsible for syndromic intellectual disability. We planned a search for causative gene variants in seven subjects with intellectual disability and overlapping dysmorphic facial features such as bulbous nasal tip, short mouth and straight eyebrows. We found two de novo frameshift variants in MED13L, consisting in single-nucleotide deletion (c.3765delC) and duplication (c.607dupT). A de novo nonsense variant (c.4420A>T) in MED13L was detected in a further subject in the course of routine whole-exome sequencing. By analyzing the clinical data of our patients along with those recently described in the literature, we confirm that there is a common, recognizable phenotype associated with MED13L haploinsufficiency, which includes intellectual disability and a distinctive facial appearance. Congenital heart diseases are found in some subjects with various degree of severity. Our observation of cleft palate, ataxia, epilepsy and childhood leukemia observed in single cases broadens the known clinical spectrum. Haploinsufficiency for MED13L should be considered in the differential diagnosis of the 1p36 microdeletion syndrome, due to overlapping dysmorphic facial features in some patients. The introduction of massive parallel-sequencing techniques into clinical practice is expected to allow for detection of other causative point variants in MED13L. Analysis of genomic data in connection with deep clinical evaluation of patients could elucidate genetic heterogeneity of the MED13L haploinsufficiency phenotype.     

Dermatological manifestations in onchocerciasis: A retrospective study of 400 imported cases

Introduction

Onchocerciasis is caused by Onchocerca volvulus and mainly leads to pruritus and skin and visual disorders, including blindness. Seventeen million people are infected in 38 countries; 31 of these are in sub-Saharan Africa, six in Latin America and one on the Arabian Peninsula. More than 99% of cases occur in sub-Saharan Africa where 120 million people are at risk of infection. Eye disorders have been well-documented; however, skin disorders have not been described accurately. The objective of our study was to describe the epidemiology, main skin manifestations and treatment of imported onchocerciasis.