Hancock Johnston (zipperrouter7)

BACKGROUND & AIMS The risk allele (G) of rs10830963 in the melatonin receptor 1 B (MTNR1B) gene presents an association with biochemical parameters and obesity. We study the effect of this SNP on insulin resistance and weight loss secondary to two hypocaloric diets. METHODS 270 obese subjects were randomly allocated during 9 months (Diet HP a high protein/low carbohydrate vs. Diet S a standard severe hypocaloric diets). Anthropometric parameters, fasting blood glucose, C-reactive protein (CRP), insulin concentration, insulin resistance (HOMA-IR), lipid profile and adipocytokines levels were measured. Genotype of MTNR1B gene polymorphism (rs10830963) was evaluated. RESULTS All adiposity parameters, systolic blood pressure and leptin levels decreased in all subjects after both diets. This improvement of adiposity parameters was higher in non-G allele carriers than G allele carriers. After weight loss with Diet HP, (CC vs. CG + GG at 9 months); total cholesterol (delta -9.9 ± 2.4 mg/dl vs. -4.8 ± 2.2 mg/dlp leserent hypocaloric during 9 months. Production of tetanus and other clostridial vaccines highly depends on the stable and reproducible production of high toxin levels. This creates a need to ensure the genetic stability of seed strains. We developed a two-stage method for improved assessment of the genetic stability of Clostridium seed strains. This method is based on next-generation sequencing (NGS) of strain DNA and mapping the sequence reads to a reference sequence. The output allows analysis of global genome consistency followed, if necessary, by detailed expert judgement of potential deviations at the gene level. The limit of detection of our method is an order of magnitude better than that of the currently established pulsed-field gel electrophoresis (PFGE). Improved genetic characterization of bacterial seed lots will have a positive impact on the characterization of the production process. This will be a first step towards applying the consistency approach to vaccine batch release of established vaccines. This can contribute to the reduction and ultimately replacement of routinely used animal tests in vaccine production. This work was carried out as part of the Innovative Medicines Initiative 2 (IMI2) project VAC2VAC (Vaccine batch to vaccine batch comparison by consistency testing). Virus contamination events in cell culture-based biotechnology processes have occurred and have had a dramatic impact on the supply of life-saving drugs, and thus on the wellbeing of patients. Cleanup requires effective and robust virucidal decontamination procedures for both the liquid reactor content before discharge, as well as facility surfaces to prevent recurrence. Beyond rare contamination events, it is important to implement virucidal disinfection for change-over procedures as effective preventive measure in routine biomanufacturing. Knowledge of the virus inactivation capacity of commonly used disinfectants is therefore important. However, available virus inactivation data often refer to studies performed in suspension only, and not, as often more relevant, to virus inactivation on surfaces. In this study three liquid disinfectants, based on sodium hypochlorite, glutaraldehyde, or hydrogen peroxide/peroxyacetic acid, as well as one gaseous hydrogen peroxide-based disinfectant were investigated for inactivation of lipid enveloped and non-lipid enveloped model viruses, using suspension (for the liquid disinfectants) and carrier assay designs for their virucidal efficacy on surface. The results of these side-by-side investigations demonstrate that depending on the type of application, i.e. routine surface disinfection or decontamination of e.g. a contaminated bioreactor content, the most effective choice of disinfectant may be remarkably different. BACKGROUND The purpose of this article is to illuminate differences in published clinical practice guideline recomm