First report in a river in France of the benthic cyanobacterium Phormidium favosum producing anatoxin-a associated with dog neurotoxicosis.

The first identification of anatoxin-a in a French lotic system is reported. Rapid deaths of dogs occurred in 2003 after the animals drank water from the shoreline of the La Loue River in eastern France. Sediments, stones and macrophytes surfaces at the margin of the river were covered by a thick biofilm containing large quantities of several benthic species of filamentous, non-heterocystous cyanobacteria. Known cyanotoxins, such as microcystins, saxitoxins and anatoxins were screened from biofilm samples by biochemical and analytical assays. A compound with similar UV spectra to the anatoxin-a standard was detected by high-performance liquid chromatography (HPLC) coupled with photo-diode array detector. This toxin was further identified by HPLC coupled with a UV detector and by electrospray ionisation-Quadrupole-Time-Of-Flight mass spectrometer, and confirmed by tandem mass spectrometry. These two techniques were necessary to discriminate anatoxin-a in phenylalanine-containing matrices such as liver samples of poisoned dogs. The toxin and the aromatic amino acid, phenylalanine, present the same pseudomolecular ion at m/z 166, but have differing fragmentation patterns, retention times and UV spectra. Finally, several cyanobacterial strains were isolated from the green biofilm and tested for anatoxin-a production. Phormidium favosum was identified as a new anatoxin-a producing species.     

Expression of class III {beta}-tubulin is predictive of patient outcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy.

PURPOSE: To determine the prevalence and the prognostic value of microtubule component expression in tumors of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Expression of microtubular components was immunohistochemically examined in 93 tumor samples from untreated patients with stage III and IV NSCLC. All patients received vinorelbine-based chemotherapy. Response to chemotherapy, progression-free survival, and overall survival were correlated with the expression of microtubule proteins. RESULTS: The response rate was 27.3% (21 partial responses among 77 valuable patients). Although expression of microtubule components was not associated with the response rate, high class III beta-tubulin expression was correlated with resistance to vinorelbine, defined as disease progression under treatment. Patients whose tumors expressed high levels of class III beta-tubulin isotype had shorter progression-free survival and overall survival (P = 0.002 and 0.001, respectively). High Delta2 alpha-tubulin expression was associated with a shorter overall survival (P = 0.018). Tubulin II levels were not found to be correlated with patient outcome. A multivariate analysis, taking into account sex, age, histology, stage, weight loss, and class II beta-tubulin, class III beta-tubulin, and Delta2 alpha-tubulin levels, confirmed that class III beta-tubulin expression was independently correlated with progression-free survival (P = 0.04) and overall survival (P = 0.012). CONCLUSIONS: These findings suggest that a high level of expression of class III beta-tubulin in tumor cells is associated with resistance to vinorelbine and a poor prognosis in patients with NSCLC receiving vinorelbine-based chemotherapy.     

Starch digestibility modulation significantly improves glycemic variability in type 2 diabetic subjects: A pilot study

Background and aimsIn type 2 diabetes (T2D) patients, the reduction of glycemic variability and postprandial glucose excursions is essential to limit diabetes complications, beyond HbA1c level. This study aimed at determining whether increasing the content of Slowly Digestible Starch (SDS) in T2D patients’ diet could reduce postprandial hyperglycemia and glycemic variability compared with a conventional low-SDS diet.Methods and resultsFor this randomized cross-over pilot study, 8 subjects with T2D consumed a controlled diet for one week, containing starchy products high or low in SDS. Glycemic variability parameters were evaluated using a Continuous Glucose Monitoring System.Glycemic variability was significantly lower during High-SDS diet compared to Low-SDS diet for MAGE (Mean Amplitude of Glycemic Excursions, p < 0.01), SD (Standard Deviation, p < 0.05), and CV (Coefficient of Variation, p < 0.01). The TIR (Time In Range) [140–180 mg/dL[ was significantly higher during High-SDS diet (p < 0.0001) whereas TIRs ≥180 mg/dL were significantly lower during High-SDS diet. Post-meals tAUC (total Area Under the Curve) were significantly lower during High-SDS diet.ConclusionOne week of High-SDS Diet in T2D patients significantly improves glycemic variability and reduces postprandial glycemic excursions. Modulation of starch digestibility in the diet could be used as a simple nutritional tool in T2D patients to improve daily glycemic control.Registration numberin clinicaltrials.gov: NCT 03289494.     

An assessment of weight change associated with the initiation of a protease or integrase strand transfer inhibitor in patients with human immunodeficiency virus

Abstract

Objective

Evidence suggests that integrase strand transfer inhibitors (INSTIs) are associated with greater weight gain than other antiretrovirals. This real-world study compares weight/body mass index (BMI) change between insured US patients with human immunodeficiency virus (HIV-1) initiating a protease inhibitor (PI) or INSTI.     

Transcatheter Aortic Valve Replacement for Severe Aortic Regurgitation With Acute Refractory Cardiogenic Shock

From January 2013 to January 2017, 686 consecutive patients were referred to our centre for transcatheter aortic valve replacement, including 5 subjects with severe aortic regurgitation and acute refractory cardiogenic shock. These patients were contraindicated for surgical treatment by the heart team because of high surgical risk (median logistic EuroSCORE: 74.6/Society of Thoracic Surgeons score: 37.9). The success rate of valve implantation was 100% through transfemoral access with self-expandable devices. The observed 30-day mortality rate was 20%. Hence, the transcatheter aortic valve replacement procedure might represent a successful and life-saving intervention for treatment of patients with severe aortic regurgitation who present with acute refractory cardiogenic shock.