Discovery of a Non-Peptidic Inhibitor of West Nile Virus NS3 Protease by High-Throughput Docking

An estimated 2.5 billion people are at risk of diseases caused by dengue and West Nile virus. As of today, there are neither vaccines to prevent nor drugs to cure the severe infections caused by these viruses. The NS3 protease is one of the most promising targets for drug development against West Nile virus because it is an essential enzyme for viral replication and because success has been demonstrated with the closely related hepatitis C virus protease. We have discovered a small molecule that inhibits the NS3 protease of West Nile virus by computer-aided high-throughput docking, and validated it using three experimental techniques. The inhibitor has potential to be developed to a drug candidate to combat West Nile virus infections

Linking disease epidemiology and livestock productivity: the case of bovine respiratory disease in France

Concerns are growing over the impact of livestock farming on environment and public health. The livestock industry is faced with the double constraint of limiting its use of natural resources and antimicrobials while ensuring its economic sustainability. In this context, reliable methods are needed to evaluate the effect of the prevention of endemic animal diseases on the productivity of livestock production systems. In this study, an epidemiological and productivity model was used to link changes in Bovine Respiratory Disease (BRD) incidence with the productivity of the beef and dairy cattle sectors in France. Cattle production parameters significantly affected by BRD were selected through literature review. Previous field study results and national cattle performance estimates were used to infer growth performances, mortality rates and carcass quality in the cattle affected and not affected by BRD. A steady-state deterministic herd production model was used to predict the productivity of the dairy and beef sector and their defined compartments (breeding-fattening, feedlot young bulls, and feedlot veal) in case of BRD incidence reduction by 20%, 50% or 100%. Results suggested that BRD should be controlled at a priority in beef breeding farms as eradication of BRD in beef calves would increase the whole beef sector’s productivity by 4.7–5.5% while eradication in other production stages would result in lower productivity gain in their respective sectors. However, the analysis performed at compartment level showed that, in both the beef and dairy sector, young bull and veal feedlot enterprises derive more economic benefits from BRD eradication for their own compartment (increase in productivity of 8.7–12.8% for beef young bulls) than the breeding farms (increase in productivity of 5.1–6% for beef calves), which may limit the investments in BRD control

Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society

The purpose of this statement is to provide consensus-based recommendations for optimal management and care for patients with primary mitochondrial disease. This statement is intended for physicians who are engaged in the diagnosis and management of these patients. Working group members were appointed by the Mitochondrial Medicine Society. The panel included members with several different areas of expertise. The panel members utilized surveys and the Delphi method to reach consensus. We anticipate that this statement will need to be updated as the field continues to evolve. Consensus-based recommendations are provided for the routine care and management of patients with primary genetic mitochondrial disease

Application of integrated production and economic models to estimate the impact of Schmallenberg virus for various beef suckler production systems in France and the United Kingdom

Background: Schmallenberg virus (SBV) was first detected in November 2011 in Germany and then rapidly spread throughout Europe. In beef suckler farms, clinical signs are mainly associated with reproductive disorders, particularly in late gestation, and intransient and non-specific symptoms, namely diarrhea, inappetence and fever. The objectives of this study were to develop models that simulate the production of different beef suckler systems in the United Kingdom (UK) and France and to use these models to estimate, through partial budget analyses, the farm-level economic cost of SBV under two disease impact scenarios, namely high and low impact. The probability for a farm to be in the high or low scenario depends, among other, on the high, low or nil vectorial activity for a given period and location and on the period(s) of sensitivity of the animals to the disease. Results: Under the high impact scenario, the estimated SBV impact ranged from 26 is an element of to 43 is an element of per cow per year in France and from 29 is an element of to 36 is an element of per cow per year in the UK. It was approximately half of this amount in the low impact scenario. These financial impacts represent 5 to 16% of the gross margin, depending on the country, impact scenario and livestock system considered. Most of the SBV impact originates from the costs of the steers and heifers not produced. Differences identified between the systems studied mainly stem from differences among the value of the steers or heifers sold: SBV impact is higher for British autumn calving systems compared to spring calving, and for French farms with calving and fattening activities compared to farms with only a single, annual calving activity. Conclusions: This study shows the usefulness of integrated production and economic models to accurately evaluate the costs of diseases and understand which factors have major impacts in the different systems. The models stand as a useful basis for animal health professionals when considering alternative disease control measures. They are also a farm accounting tool for estimating disease impact on differing production practices, which creates the necessary basis for cost-effectiveness analysis of intervention strategies, such as vaccination

Modified myocardial performance index is not affected in fetuses with an isolated echogenic focus in the left ventricle

Objectives: We prospectively investigated the efficacy of modified myocardial performance index (mod-MPI) in the assessment of cardiac functions in fetuses with and without an isolated hyperechogenic focus (IHF) in the left ventricle and compared with conventional fetal echocardiography