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Foot-and-mouth disease virus (FMDV) is endemic in Vietnam, a country that plays an important role in livestock trade within Southeast Asia. The large populations of FMDV-susceptible species in Vietnam are important components of food production and of the national livelihood. In this study, we investigated the phylogeny of FMDV O/PanAsia in Vietnam, reconstructing the virus’ ancestral host species (pig, cattle or buffalo), clinical stage (subclinical carrier or clinically affected) and geographical location. Phylogenetic divergence time estimation and character state reconstruction analyses suggest that movement of viruses between species differ. While inferred transmissions from cattle to buffalo and pigs and from pigs to cattle are well supported, transmission from buffalo to other species, and from pigs to buffalo may be less frequent. Geographical movements of FMDV O/PanAsia virus appears to occur in all directions within the country, with the South Central Coast and the Northeast regions playing a more important role in FMDV O/PanAsia spread. Genetic selection of variants with changes at specific sites within FMDV VP1 coding region was different depending on host groups analyzed. The overall ratio of non-synonymous to synonymous nucleotide changes was greater in pigs compared to cattle and buffalo, whereas a higher number of individual amino acid sites under positive selection were detected in persistently infected, subclinical animals compared to viruses collected from clinically diseased animals. These results provide novel insights to understand FMDV evolution and its association with viral spread within endemic countries. These findings may support animal health organizations in their endeavor to design animal disease control strategies in response to outbreaks. Electronic supplementary material The online version of this article (doi:10.1186/s13567-017-0424-7) contains supplementary material, which is available to authorized users.

We report the polyprotein coding sequence of the newly defined Ind2001e sublineage of foot-and-mouth disease virus (FMDV) serotype O, isolated from a bovine epithelial tissue sample collected in 2017 in Kon Tum Province, Vietnam. This discovery updates FMDV diversity in Vietnam, has implications for FMDV epidemiology, and influences future vaccine selections.

Passive administration of monoclonal antibodies (mAbs) is a promising therapeutic approach for Ebola virus disease (EVD). However, all mAbs and mAb cocktails that have entered clinical development are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against outbreak-causing Bundibugyo virus (BDBV) and Sudan virus (SUDV). Here, we advance MBP134, a cocktail of two broadly neutralizing human mAbs, ADI-15878 from an EVD survivor and ADI-23774 from the same survivor but specificity-matured for SUDV GP binding affinity, as a candidate pan-ebolavirus therapeutic. MBP134 potently neutralized all ebolaviruses and demonstrated greater protective efficacy than ADI-15878 alone in EBOV-challenged guinea pigs. A second-generation cocktail, MBP134(AF), engineered to effectively harness natural killer (NK) cells afforded additional improvement relative to its precursor in protective efficacy against EBOV and SUDV in guinea pigs. MBP134(AF) is an optimized mAb cocktail suitable for evaluation as a pan-ebolavirus therapeutic in nonhuman primates.

In 2018, senecavirus A was detected for the first time in Vietnam. This report contains the first complete genome of a senecavirus A isolate collected from pigs in Kon Tum Province, Vietnam., In 2018, senecavirus A was detected for the first time in Vietnam. This report contains the first complete genome of a senecavirus A isolate collected from pigs in Kon Tum Province, Vietnam. This novel incursion has substantial implications for regional control of vesicular transboundary diseases.

Background Seizures and their consequences contribute to the burden of epilepsy because they can cause health loss (premature mortality and residual disability). Data on the burden of epilepsy are needed for health-care planning and resource allocation. The aim of this study was to quantify health loss due to epilepsy by age, sex, year, and location using data from the Global Burden of Diseases, Injuries, and Risk Factors Study. Methods We assessed the burden of epilepsy in 195 countries and territories from 1990 to 2016. Burden was measured as deaths, prevalence, and disability-adjusted life-years (DALYs; a summary measure of health loss defined by the sum of years of life lost [YLLs] for premature mortality and years lived with disability), by age, sex, year, location, and Socio-demographic Index (SDI; a compound measure of income per capita, education, and fertility). Vital registrations and verbal autopsies provided information about deaths, and data on the prevalence and severity of epilepsy largely came from population representative surveys. All estimates were calculated with 95% uncertainty intervals (UIs). Findings In 2016, there were 45.9 million (95% UI 39. 9-54 .6) patients with all-active epilepsy (both idiopathic and secondary epilepsy globally; age-standardised prevalence 621.5 per 100 000 population; 540.1-737.0). Of these patients, 24.0 million (20.4-27.7) had active idiopathic epilepsy (prevalence 3 26 7 per 100 000 population; 278.4-378.1). Prevalence of active epilepsy increased with age, with peaks at 5-9 years (374.8 [280 .1-490 .0]) and at older than 80 years of age (545.1 [444. 2-652. 0]). Age-standardised prevalence of active idiopathic epilepsy was 329.3 per 100 000 population (280.3-381. 2) in men and 318.9 per 100 000 population (271.1-369.4) in women, and was similar among SDI quintiles. Global age-standardised mortality rates of idiopathic epilepsy were 1.74 per 100 000 population (1.64-1.87; 1.40 per 100 000 population [1. 23-1.54] for women and 2.09 per 100 000 population [1.96-2.25] for men). Age-standardised DALYs were 182.6 per 100 000 population (149. 0-223 .5; 163.6 per 100 000 population [130.6-204.3] for women and 201.2 per 100 000 population [166. 9-241. 4] for men). The higher DALY rates in men were due to higher YLL rates compared with women. Between 1990 and 2016, there was a non-significant 6.0% (-4.0 to 16.7) change in the age-standardised prevalence of idiopathic epilepsy, but a significant decrease in age-standardised mortality rates (24.5% [10.8 to 31.8]) and age-standardised DALY rates (19.4% [9.0 to 27.6]). A third of the difference in age-standardised DALY rates between low and high SDI quintile countries was due to the greater severity of epilepsy in low-income settings, and two-thirds were due to a higher YLL rate in low SDI countries. Interpretation Despite the decrease in the disease burden from 1990 to 2016, epilepsy is still an important cause of disability and mortality. Standardised collection of data on epilepsy in population representative surveys will strengthen the estimates, particularly in countries for which we currently have no or sparse data and if additional data is collected on severity, causes, and treatment. Sizeable gains in reducing the burden of epilepsy might be expected from improved access to existing treatments in low-income countries and from the development of new effective drugs worldwide. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was identified in 2012 as the causative agent of a severe, lethal respiratory disease occurring across several countries in the Middle East. To date there have been over 1600 laboratory confirmed cases of MERS-CoV in 26 countries with a case fatality rate of 36%. Given the endemic region, it is possible that MERS-CoV could spread during the annual Hajj pilgrimage, necessitating countermeasure development. In this report, we describe the clinical and radiographic changes of rhesus monkeys following infection with 5×10(6) PFU MERS-CoV Jordan-n3/2012. Two groups of NHPs were treated with either a human anti-MERS monoclonal antibody 3B11-N or E410-N, an anti-HIV antibody. MERS-CoV Jordan-n3/2012 infection resulted in quantifiable changes by computed tomography, but limited other clinical signs of disease. 3B11-N treated subjects developed significantly reduced lung pathology when compared to infected, untreated subjects, indicating that this antibody may be a suitable MERS-CoV treatment.

IMPORTANCE: Understanding global variation in firearm mortality rates could guide prevention policies and interventions. OBJECTIVE: To estimate mortality due to firearm injury deaths from 1990 to 2016 in 195 countries and territories. DESIGN, SETTING, AND PARTICIPANTS: This study used deidentified aggregated data including 13?812 location-years of vital registration data to generate estimates of levels and rates of death by age-sex-year-location. The proportion of suicides in which a firearm was the lethal means was combined with an estimate of per capita gun ownership in a revised proxy measure used to evaluate the relationship between availability or access to firearms and firearm injury deaths. EXPOSURES: Firearm ownership and access. MAIN OUTCOMES AND MEASURES: Cause-specific deaths by age, sex, location, and year. RESULTS: Worldwide, it was estimated that 251?000 (95% uncertainty interval [UI], 195?000-276?000) people died from firearm injuries in 2016, with 6 countries (Brazil, United States, Mexico, Colombia, Venezuela, and Guatemala) accounting for 50.5% (95% UI, 42.2%-54.8%) of those deaths. In 1990, there were an estimated 209?000 (95% UI, 172?000 to 235?000) deaths from firearm injuries. Globally, the majority of firearm injury deaths in 2016 were homicides (64.0% [95% UI, 54.2%-68.0%]; absolute value, 161?000 deaths [95% UI, 107?000-182?000]); additionally, 27% were firearm suicide deaths (67?500 [95% UI, 55?400-84?100]) and 9% were unintentional firearm deaths (23?000 [95% UI, 18?200-24?800]). From 1990 to 2016, there was no significant decrease in the estimated global age-standardized firearm homicide rate (-0.2% [95% UI, -0.8% to 0.2%]). Firearm suicide rates decreased globally at an annualized rate of 1.6% (95% UI, 1.1-2.0), but in 124 of 195 countries and territories included in this study, these levels were either constant or significant increases were estimated. There was an annualized decrease of 0.9% (95% UI, 0.5%-1.3%) in the global rate of age-standardized firearm deaths from 1990 to 2016. Aggregate firearm injury deaths in 2016 were highest among persons aged 20 to 24 years (for men, an estimated 34?700 deaths [95% UI, 24?900-39?700] and for women, an estimated 3580 deaths [95% UI, 2810-4210]). Estimates of the number of firearms by country were associated with higher rates of firearm suicide (P < .001; R2 = 0.21) and homicide (P < .001; R2 = 0.35). CONCLUSIONS AND RELEVANCE: This study estimated between 195?000 and 276?000 firearm injury deaths globally in 2016, the majority of which were firearm homicides. Despite an overall decrease in rates of firearm injury death since 1990, there was variation among countries and across demographic subgroups.

All available experimental vaccines and immunotherapeutics1,2 against Ebola virus (EBOV), including rVSV-ZEBOV3 and ZMappTM4, lack activity against other ebolaviruses associated with human disease outbreaks. This year, two separate outbreaks of EBOV in the Democratic Republic of Congo underscored the unpredictable nature of ebolavirus reemergence in a region that has historically experienced outbreaks of the divergent ebolaviruses Sudan virus (SUDV) and Bundibugyo virus (BDBV)5. Here we show that MBP134AF, a pan-ebolavirus therapeutic comprising two broadly neutralizing human antibodies (bNAbs)6,7(see companion manuscript, Wec et al.) could protect against lethal EBOV, SUDV, and BDBV infection in ferrets and nonhuman primates (NHPs). MBP134AF not only not only establishes a viable therapeutic countermeasure to outbreaks caused by antigenically diverse ebolaviruses but also affords unprecedented effectiveness and potency—a single 25-mg/kg dose was fully protective in NHPs. This best-in-class antibody cocktail is the culmination of an intensive collaboration spanning academia, industry and government in response to the 2013-2016 EBOV epidemic6,7 and provides a translational research model for the rapid development of immunotherapeutics targeting emerging infectious diseases.

This is the peer reviewed version of the following article: Eur. J. Org. Chem. 2018, 2561–2571, which has been published in final form at https://doi.org/10.1002/ejoc.201800083. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions., Three new boron dipyrromethene (BODIPY) dyes substituted with a benzylamino group at the 3-position have been synthesized from halogenated BODIPYs by nucleophilic substitution. The spectroscopic and photophysical properties have been explored in different solvents and have been compared with an analogous 8benzylaminoBODIPY derivative. The position of the benzylamino group has a significant influence on the spectral band positions, fluorescence quantum yields, and fluorescence lifetimes. The 8benzylaminoBODIPY emits in the blue range, whereas the 3substituted shows green fluorescence. Additionally, the extension of the conjugation at the 5-position of 3-benzylaminoBODIPY produces a bathochromic shift of the absorption and emission spectra. The solvent effect on their spectroscopic features has been investigated using the generalized Catalán solvent scales. Quantum-chemical calculations have been performed to assess the effect of the position of the substitution on the spectroscopic properties. Finally, the BODIPY dyes have been employed as probes in fluorescence lifetime imaging of living cells, demonstrating their high potential for bioimaging., This work has been financially supported by the National Nature Science Foundation of China (Grants Nos. 21672006) and Nature Science Foundation of Anhui Province (Grants No. 1508085J07); and grant CTQ2014-56370-R from the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (ERDF).