Molecular Epidemic Characteristics and Genetic Evolution of Porcine Circovirus Type 2 (PCV2) in Swine Herds of Shanghai, China.

Porcine Circovirus 2 (PCV2) is a crucial swine pathogen and considered a primary causative agent of porcine circovirus-associated diseases (PCVADs), posing a serious economic threat to the swine industry across globe. The world's biggest agricultural conglomerates have teamed up to create giant commercial pig farms across Shanghai due to the proximity of this region to more affluent lean-pork markets. Since its discovery, PCV2 has displayed extraordinary genetic diversity, and its genome is swiftly evolving through a series of mutations and recombinations. However, limited information on epidemiology, molecular characteristics, vaccine cross-protection, and the co-infection rate of PCV2 with other lethal swine diseases can adversely impact the pig production in the region. To investigate the molecular epidemic characteristics and genetic evolution of PCV2, pigs with doubtful symptoms of PCVADs were sampled from various commercial pig farms with a history of PWMS and/or PDNS across Shanghai from 2014 to 2018. Our results revealed the coexistence of multiple PCV2 genotypes (PCV2b, PCV2e, and PCV2d) among Shanghai pig herds and dominance of PCV2d among them. We also found critical amino acid substitutions in epitope regions of important capsid proteins in PCV2 isolates involved in viral replication and host immune escape. Spotted mutations may favor the prevalence and survival of various PCV2 genotypes despite availability of commercial vaccines. This study also provides insight into the co-infection status of PCV2 with major lethal swine viral diseases such as PPV and PPRSV. Collectively, these investigations will contribute to understanding the molecular epidemiology and evolution of PCV2 across the region.

Epidemiological trends of foodborne Campylobacter outbreaks in the United States of America, 1998-2016.

Campylobacter is a major cause of foodborne diarrheal infections in the United States of America (USA). This study aimed to elucidate the patterns of Campylobacter foodborne outbreaks temporally and spatially concerning food vehicles. We collected the data of foodborne outbreaks from 1998 to 2016 reported to the Centers for Disease Control and Prevention. The incidence rate of outbreaks for each food source was calculated and analyzed for each variable including season, food location, and census region. Overall, 465 single-state outbreaks and 8003 cases were reported during 1998-2016. Outbreaks were frequently attributed to dairy products (32%), chicken (17%) and vegetables (6%). Binomial regression analysis showed that compared to chicken items, the highest rate ratio of outbreaks was associated with dairy products (1.86) followed by vegetables (1.35) and meat products (0.76). More outbreaks were reported in the summer (35%) followed by the spring (26%) and fall (22%) season. We found that the highest number of outbreaks occurred in the West 159 (34%) and Midwest 137 (29%) census regions. The study highlights the role of dairy, chicken, and vegetables as food vehicles in Campylobacter outbreaks. Findings from this study can help in devising strategies to mitigate the increasing occurrence of Campylobacter foodborne outbreaks.

Outbreaks of foodborne Salmonella enteritidis in the United States between 1990 and 2015: An analysis of epidemiological and spatial-temporal trends.

OBJECTIVES: To evaluate the role of eggs and other food vehicles as risk factors associated with Salmonella enteritidis (SE) outbreaks in order to address the endemicity of SE infections in the USA. METHODS: We retrieved and analyzed data relating to all SE outbreaks reported to the Centers for Disease Control and Prevention (CDC) between 1990 and 2015. We then used descriptive and analytical statistical methods, including negative binomial regression models for the estimation of rate-ratios, to analyze the data. RESULTS: Analyses showed that egg-based dishes were the most common food vehicle associated with outbreaks of SE in the USA (273 cases [24%]); this was followed by several other food items, including meat (130 cases [11%]), vegetables (96 cases [8%]), chicken items (95 cases [8%]), dairy products (55 cases [5%]), and bakery items (8 cases [1%]). Compared to egg-based dishes, other food items such as meat (exp(ß) = 0.51, 95% CI 0.37, 0.69), chicken (exp(ß) = 0.42, 95% CI 0.30, 0.58), vegetables (exp(ß) = 0.41, 95% CI 0.29, 0.55), and dairy items (exp(ß) = 0.27, 95% CI 0.18, 0.40) were significantly associated with outbreaks of SE in the USA. Of 1144 SE outbreaks, 402 (35%) occurred in the Northeast region of the USA, followed by the South (253 [22%]), West (250 [22%]), and Midwestern regions (239 [21%]). CONCLUSIONS: Epidemiological and spatiotemporal trends analyses demonstrated that a significant proportions of Salmonella enteritidis outbreaks in the USA are attributed to food vehicles other than eggs. Our findings can be used to plan effective strategies to mitigate the increasing occurrence of foodborne SE outbreaks.

Potential Role of Flavivirus NS2B-NS3 Proteases in Viral Pathogenesis and Anti-flavivirus Drug Discovery Employing Animal Cells and Models: A Review.

Flaviviruses are known to cause a variety of diseases in humans in different parts of the world. There are very limited numbers of antivirals to combat flavivirus infection, and therefore new drug targets must be explored. The flavivirus NS2B-NS3 proteases are responsible for the cleavage of the flavivirus polyprotein, which is necessary for productive viral infection and for causing clinical infections; therefore, they are a promising drug target for devising novel drugs against different flaviviruses. This review highlights the structural details of the NS2B-NS3 proteases of different flaviviruses, and also describes potential antiviral drugs that can interfere with the viral protease activity, as determined by various studies. Moreover, optimized in vitro reaction conditions for studying the NS2B-NS3 proteases of different flaviviruses may vary and have been incorporated in this review. The increasing availability of the in silico and crystallographic/structural details of flavivirus NS2B-NS3 proteases in free and drug-bound states can pave the path for the development of promising antiflavivirus drugs to be used in clinics. However, there is a paucity of information available on using animal cells and models for studying flavivirus NS2B-NS3 proteases, as well as on the testing of the antiviral drug efficacy against NS2B-NS3 proteases. Therefore, on the basis of recent studies, an effort has also been made to propose potential cellular and animal models for the study of flavivirus NS2B-NS3 proteases for the purposes of exploring flavivirus pathogenesis and for testing the efficacy of possible drugs targets, in vitro and in vivo.

Lipid nanoparticles with minimum burst release of TNF-α siRNA show strong activity against rheumatoid arthritis unresponsive to methotrexate.

TNF-α siRNA has shown promising therapeutic benefits in animal models of rheumatoid arthritis. However, there continues to be a need for siRNA delivery systems that have high siRNA encapsulation efficiency and minimum burst release of TNF-α siRNA, and can target inflamed tissues after intravenous administration. Herein we report a novel acid-sensitive sheddable PEGylated solid-lipid nanoparticle formulation of TNF-α-siRNA, AS-TNF-α-siRNA-SLNs, prepared by incorporating lipophilized TNF-α-siRNA into solid-lipid nanoparticles composed of biocompatible lipids such as lecithin and cholesterol. The nanoparticles are approximately 120 nm in diameter, have a high siRNA encapsulation efficiency (>90%) and a minimum burst release of siRNA (<5%), and increase the deilvery of the siRNA in chronic inflammation sites in mouse models, including in a mouse model with collagen-induced arthritis. Importantly, in a mouse model of collagen antibody-induced arthritis that does not respond to methotrexate therapy, intravenous injection of the AS-TNF-α-siRNA-SLNs significantly reduced paw thickness, bone loss, and histopathological scores. These findings highlight the potential of using this novel siRNA nanoparticle formulation to effectively treat arthritis, potentially in patients who do not respond adequately to methotrexate.