One year after a virulent Newcastle disease virus (vNDV) outbreak in Pakistan, the causative strain was present in vaccinated chickens of multiple farms despite the existence of high-average NDV-specific antibody titers (>4.75 log 2 ). The data suggest a possible role of vaccinated birds as reservoirs of vNDV.

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Non-alcoholic fatty liver disease (NAFLD) is often linked with impaired hepatic autophagy. Here, we studied the alterations in hepatocellular autophagy by high cholesterol and high-fat diet (HC-HF) diet in C57BL/6J mice, and by palmitic acid (PA), in AML-12 and HepG2 cells. Further, we analysed role of Trigonelline (TG), a plant alkaloid, in preventing NAFLD, by modulating autophagy. For this, C57BL/6J mice were fed with Standard Chow (SC) or HC-HF diet, with and without TG for 16 weeks. In-vitro; AML-12 cells and HepG2 cells, were exposed to PA with and without TG, for 24 h. Cellular events related to autophagy, lipogenesis, and lipo-toxicity were studied. The HC-HF diet fed mice showed hepatic autophagy blockade, increased triglycerides and steatosis. PA exposure to AML-12 cells and HepG2 cells induced impaired autophagy, ER stress, resulting in lipotoxicity. TG treatment in HC-HF fed mice, restored hepatic autophagy, and prevented steatosis. TG treated AML-12, and HepG2 cells exposed to PA showed autophagy restoration, and reduced lipotoxicity, however, these effects were diminished in Atg7-/- HepG2 cells, and in the presence of chloroquine. This study shows that HC-HF diet-induced impaired autophagy, and steatosis is prevented by TG, which attributes to its novel mechanism in treating NAFLD.

Abstract:Background: Roflumilast, a phosphodiesterase 4 inhibitor, has been shown to improve lung function and reduce exacerbation rates, but is associated with adverse events (AEs). The purpose of this study was to systematically review the clinical effectiveness and safety of roflumilast. Methods: A systematic search was made of MEDLINE, Cochrane trials database, DARE and CINAHL. Randomized, controlled trials of more than 12 weeks' duration comparing roflumilast with placebo were reviewed. Studies were pooled to yield relative risk (RR), incident rate difference or weighted mean differences with 95% confidence intervals (CIs). Results: Eight trials (8698 patients) met the inclusion criteria. Roflumilast significantly reduced moderate to severe exacerbations (RR 0.85; 95% CI 0.80-0.91) compared with placebo, but not severe exacerbations (RR 0.83; 95% CI 0.68-1.01) or mortality (RR 0.90; 95% CI 0.63-1.28). Roflumilast significantly improved lung function relative to placebo, but not quality of life measures. AEs (RR 1.11; 95% CI 1.03-1.19) and discontinuations of treatment due to AEs (RR 1.63; 95% CI 1.45-1.84) were significantly more frequent with roflumilast than placebo. In the chronic obstructive pulmonary disease (COPD) Safety Pool (12,054 patients), the overall incidence of serious AEs did not differ between groups. However, atrial fibrillation (0.4% versus 0.2%; p = 0.02) and suicidality (0.08% versus 0%) were more frequent with roflumilast than placebo. Conclusions: The efficacy of roflumilast appears modest compared with other available therapies for COPD. Further studies are needed to investigate the risk-benefit ratio and longterm safety of roflumilast before its wider use.

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Avian influenza viruses (AIV) are a threat to poultry production worldwide. Vaccination is utilized as a component of control programs for both high pathogenicity (HP) and low pathogenicity (LP) AIV. Over 95% of all AIV vaccine used in poultry are inactivated, adjuvanted products. To identify the best formulations for chickens, vaccines were prepared with beta-propiolactone (BPL) inactivated A/British Columbia/314514-1/2004 H7N3 LP AIV using ten commercially available or experimental adjuvants. Each vaccine formulation was evaluated for immunogenicity in chickens. Challenge studies with an antigenically homologous strain of HPAIV were conducted to compare protection against mortality and measure reductions in virus levels in oral swabs. The four best adjuvants from the studies with BPL inactivated antigen were selected and tested identically, but with vaccines prepared from formalin inactivated virus. Mineral and vegetable oil based adjuvants generally induced the highest antibody titers with 100% seroconversion by 3weeks post vaccination. Chitosan induced positive antibody titers in 100% of the chickens, but the titers were significantly lower than those of most of the oil based adjuvants. Antibody levels from calcium phosphate and alginate adjuvanted groups were similar to those of non-adjuvanted virus. All groups that received adjuvanted vaccines induced similar levels of protection against mortality (0-20%) except the groups vaccinated with calcium phosphate adjuvanted vaccines, where mortality was similar (70%) to groups that received non-adjuvanted inactivated virus or no vaccine (60-100% mortality). Virus shedding in oral swabs was variable among the treatment groups. Formalin inactivated vaccine induced similar antibody titers and protection against challenge compared to BPL inactivated vaccine groups. These studies support the use of oil adjuvanted vaccines for use in the poultry industry for control for AIV.

BackgroundA combination therapy with inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA) is recommended in severe chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations. Currently, there are five ICS/LABA combination products available on the market. The purpose of this study was to systematically review the efficacy of various ICS/LABA combinations with a network meta-analysis.MethodsSeveral databases and manufacturer’s websites were searched for relevant clinical trials. Randomized control trials, at least 12 weeks duration, comparing an ICS/LABA combination with active control or placebo were included. Moderate and severe exacerbations were chosen as the outcome assessment criteria. The primary analyses were conducted with a Bayesian Markov chain Monte Carlo method.ResultsMost of the ICS/LABA combinations reduced moderate-to-severe exacerbations as compared with placebo and LABA, but none of them reduced severe exacerbations. However, many studies excluded patients receiving long-term oxygen therapy. Moderate-dose ICS was as effective as high-dose ICS in reducing exacerbations when combined with LABA.ConclusionICS/LABA combinations had a class effect with regard to the prevention of COPD exacerbations. Moderate-dose ICS/LABA combination therapy would be sufficient for COPD patients when indicated. The efficacy of ICS/LABA combination therapy appeared modest and had no impact in reducing severe exacerbations. Further studies are needed to evaluate the efficacy of ICS/LABA combination therapy in severely affected COPD patients requiring long-term oxygen therapy.

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