It is worth highlighting that our epitaxial approach is fully compatible with any existing microdisplay fabrication techniques. Copyright © 2020 American Chemical Society.DNA vaccines expressing codon-optimized Venezuelan equine encephalitis virus (VEEV) and Ebola virus (EBOV) glycoprotein genes provide protective immunity to mice and nonhuman primates when delivered by intramuscular (IM) electroporation (EP). To achieve equivalent protective efficacy in the absence of EP, we evaluated VEEV and EBOV DNA vaccines constructed using minimalized Nanoplasmid expression vectors that are smaller than conventional plasmids used for DNA vaccination. These vectors may also be designed to co-express type I interferon inducing innate immune agonist genes that have an adjuvant effect. Nanoplasmid vaccinated mice had increased antibody responses as compared to those receiving our conventional pWRG7077-based vaccines when delivered by IM injection, and these responses were further enhanced by the inclusion of the innate immune agonist genes. The Nanoplasmid VEEV DNA vaccines also significantly increased protection against aerosol VEEV challenge as compared to the pWRG7077 VEEV DNA vaccine. Although all mice receiving the pWRG7077 and Nanoplasmid EBOV DNA vaccines at the doses tested survived EBOV challenge, only mice receiving the Nanoplasmid EBOV DNA vaccine that co-expresses the innate immune agonist genes failed to lose weight after challenge. Our results suggest that Nanoplasmid vectors can improve the immunogenicity and protective efficacy of alphavirus and filovirus DNA vaccines. © 2020.Background Direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV) result in initial cure rates of 95% to 99% and re-treatment cure rates of 95%. Nevertheless, given the sheer magnitude of infected persons, some will ultimately fail multiple DAA therapies, and re-treatment of these persons has not been adequately studied. Methods We evaluated treated an HIV-infected man with cirrhosis from genotype 1b HCV who had failed 3 DAA regimens. Results We treated and cured our "particularly difficult-to-cure" patient with sofosbuvir plus glecaprevir/pibrentasvir plus ribavirin for 24 weeks. We discuss the literature on potential biological factors behind his treatment failures such as lack of HCV seroconversion during his infection course, and multiple failures of hepatitis B seroconversion after vaccination, and the rationale for choosing his curative salvage regimen. Discussion There are no clinical trials-proven re-treatment regimens for "particularly difficult-to-cure" patients. Multiple patient- and virus-related factors that do not affect cure rates in treatment-naive patients may need to be considered in choosing a re-treatment regimen for these patients. These regimens may need to include combinations drugs that are not available in single-tablet form, addition of ribavirin, and longer durations of treatment than standard. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.Background Praziquantel mass drug administration (MDA) is recommended in schistosomiasis-endemic areas. Animal models demonstrate Schistosoma parasite resistance to praziquantel after repeated exposure. Methods We conducted a parasitological survey in 26 fishing communities in Uganda after 4 years of quarterly (13 communities) or annual (13 communities) praziquantel MDA, with Schistosoma infection detected by single-stool-sample Kato-Katz. A test of cure was done in participants who were positive on both urine circulating cathodic antigen test and 3-sample Kato-Katz. We calculated cure rates (CRs) and egg reduction rates (ERRs) based on 3-sample Kato-Katz and infection intensity using worm-specific circulating anodic antigen (CAA) in blood, comparing these between quarterly and annually treated participants. Results Single-sample Kato-Katz Schistosoma mansoni prevalence was 22% in 1,056 quarterly treated participants and 34% in 1,030 annually treated participants (risk ratio, 0.62; 95% confidence interval [CI], 0.40 to 0.94). Among 110 test-of-cure participants, CRs were 65% and 51% in annually and quarterly treated villages, respectively (odds ratio, 0.65; 95% CI, 0.27 to 1.58); ERRs were 94% and 81% (difference, -13%; 95% CI, -48% to 2%). There was no impact of quarterly vs annual praziquantel on S. mansoni by CAA. Conclusions In this schistosomiasis hot spot, there was little evidence of decreased praziquantel efficacy. https://www.selleckchem.com/products/climbazole.html However, in the absence of alternative therapies, there remains a need for continued vigilance of praziquantel efficacy in the MDA era. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.Background Although rotavirus vaccines have proven to prevent the risk of rotavirus gastroenteritis (RVGE) in children under 5 years old, they are also associated with an increased transient risk of intussusception (IS). Several quantitative benefit-risk models (qBRm) are performed to measure this balance in hospitalizations and deaths prevented versus the ones induced. Method In this study, our objective was to provide a complete overview of qBRm used for rotavirus vaccination. We systematically searched 3 medical literature databases to identify relevant articles, in English, that were published between 2006 and 2019. Results Of the 276 publications screened, 14 studies using qBRm for rotavirus vaccination were retained, based on preselected criteria. Four were performed in low- and middle-income countries. Almost all (13 of 14) displayed the following characteristics force of infection assumed to be constant over time (static model), indirect effect of rotavirus vaccination (herd effect) not considered, closed model (individuals not allowed to enter and/or exit the model over time), and aggregated level (no tracking of individual's behavior). Most of the models were probabilistic (9 of 14) and reported sensitivity and/or scenario analyses (12 of 14). Input parameter values varied across studies. Selected studies suggest that, depending on the models used, for every IS hospitalization and death induced, vaccination would prevent, respectively, 190-1624 and 71-743 RVGE-related hospitalizations and deaths. Conclusions The benefits of rotavirus vaccination were shown to largely exceed the increased risk of IS, across all studies. Future research aiming to harmonize qBRm for rotavirus vaccination should ensure the comparability of studies and provide additional information for regulatory authorities, physicians, and patients. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.Twenty-nine farmers with a flock prevalence of lameness >5% were visited in 2013. They participated in a facilitated discussion on treatment of footrot, and evidence-based new "best practice." One year later, farmers were revisited and management and motivators for change were discussed. Farmers were asked how they would persuade other farmers to adopt "best practice." Initially, most participants were resigned to having lame sheep. They believed that prototypical "good farmers" (including trusted family) practiced foot trimming, the traditional "best practice" and that the new "best practice" would be expensive and time consuming. Between 2013 and 2014 lameness prevalence reduced from 7.6 to 4.3%. The major behavioral changes were reduction in foot trimming, increased use of antibacterials to treat footrot, and treating sheep within a week of becoming lame. In 2014, participants were re-interviewed. They reported that an increased knowledge of the evidence-base, trust in the facilitator and talking to other trusted farmers who had already adopted the new "best practice" overcame concerns about the prototypical "good farmer" and motivated change. Persistent change occurred because participants observed health benefits for their sheep and that the new "best practice" had saved time and money. Participants stated that other farmers would be convinced to change to the new "best practice" because it saved time and money, ironically, these were among the original barriers to change. This is possibly an example of cognitive dissonance because farmers had become positive about the benefits of saving time and money following a change in their own behaviors. Copyright © 2020 Green, Kaler, Liu and Ferguson.Proteinase activated receptor 4 (PAR4) in the gastrointestinal tract is involved in the regulation of inflammation and pain pathways. The aim of the present study was to evaluate the distribution and expression of PAR4 in the jejunum of healthy horses and in the pathologic tracts from horses undergoing surgery for herniation of the small intestine through the epiploic foramen. Eight healthy horses (Group H) and eight horses with epiploic hernia (Group EH) were included; the jejunum samples were collected at the slaughter or intraoperatively after enterectomy, respectively. To evaluate PAR4 expression in sections of the jejunum, immunofluorescence, western blot and quantitative polymerase chain reaction (qRT-PCR) were performed. Immunohistochemistry of PAR4 in the jejunum of the healthy horses showed that receptors are predominantly expressed in the immune cell population scattered throughout the lamina propria of the mucosa and in the submucosa. Quantitative PCR data demonstrated that PAR4 mRNA was detectable in all of the samples analyzed without any difference between the H and the EH groups, however the PAR4 protein level was significantly lower in the jejunums of the EH horses. In the Group EH horses, PAR4 immunoreactivity was mainly expressed in the mast cells and was extensively distributed in the sierosa. In the lamina propria of mucosa of Group EH, leukocytes were less abundant than in Group H. In this study, the distribution and expression of PAR4 in the jejunums of the healthy horses and in those with spontaneous occurring epiploic hernia was demonstrated. Copyright © 2020 Lambertini, Bombardi, Zannoni, Bernardini, Dondi, Morini, Rinnovati, Spadari and Romagnoli.African swine fever (ASF) is one of the most important emerging transboundary diseases of pigs, causing trade restrictions, and a health impact on susceptible pigs. Nine countries in the continental European Union (Estonia, Lithuania, Latvia, Poland, Czech Republic, Bulgaria, Belgium, Romania, and Hungary) have been affected by ASF from 2014 to 2018 and it keeps spreading despite the efforts to control it. For a number of years, we have witnessed high case-fatality rates in wild boar found dead particularly in new infected areas, which is typical of the peracute and acute forms of the infection at the beginning of an ASF epidemic. Experimental evidence with currently circulating strains indicates that some infected animals can remain asymptomatic and might even survive the infection. An increased presence of virus of moderate virulence can complicate ASF diagnosis as well as the mitigation and control of the disease. We analyze the ASF surveillance data in wild boar in the four EU countries where ASF has been present for longer, comparing the spatial density of antibody positive notifications with the time ASF has been present per region. Results indicate an increasing annual distribution of notifications based on antibodies over nucleic acid detection in hunted wild boar in Estonia, Latvia and Poland. Potentially, Lithuania, and Poland seem to have experienced more acute forms in 2017 and 2018 than Latvia and Estonia. Overall there was a positive statistical correlation between time with infection (TWI) and antibody positive density, with some variations in certain regions, particularly of Lithuania and Estonia. The increasing trend in potential survivors (hunted wild boar with confirmed PCR negative and antibody positive results) enhances the importance of surveillance design to sample and test shot wild boar. In conclusion, surveillance data based on ASFV detection by PCR and serology can be used to assess the status of the epidemic in wild boar. Copyright © 2020 Martínez-Avilés, Iglesias and De La Torre.