Design and evaluation of the immunogenicity and efficacy of a biomimetic particulate formulation of viral antigens

Subunit viral vaccines are typically not as efficient as live attenuated or inactivated vaccines at inducing protective immune responses. This paper describes an alternative 'biomimetic' technology; whereby viral antigens were formulated around a polymeric shell in a rationally arranged fashion with a surface glycoprotein coated on to the surface and non-structural antigen and adjuvant encapsulated. We evaluated this model using BVDV E2 and NS3 proteins formulated in poly-(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles adjuvanted with polyinosinic:polycytidylic acid (poly(I:C) as an adjuvant (Vaccine-NP). This Vaccine-NP was compared to ovalbumin and poly(I:C) formulated in a similar manner (Control-NP) and a commercial adjuvanted inactivated BVDV vaccine (IAV), all inoculated subcutaneously and boosted prior to BVDV-1 challenge. Significant virus-neutralizing activity, and E2 and NS3 specific antibodies were observed in both Vaccine-NP and IAV groups following the booster immunisation. IFN-γ responses were observed in ex vivo PBMC stimulated with E2 and NS3 proteins in both vaccinated groups. We observed that the protection afforded by the particulate vaccine was comparable to the licenced IAV formulation. In conclusion, the biomimetic particulates showed a promising immunogenicity and efficacy profile that may be improved by virtue of being a customisable mode of delivery

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Walking Behavior of Zoo Elephants: Associations between GPS-Measured Daily Walking Distances and Environmental Factors, Social Factors, and Welfare Indicators

Research with humans and other animals suggests that walking benefits physical health. Perhaps because these links have been demonstrated in other species, it has been suggested that walking is important to elephant welfare, and that zoo elephant exhibits should be designed to allow for more walking. Our study is the first to address this suggestion empirically by measuring the mean daily walking distance of elephants in North American zoos, determining the factors that are associated with variations in walking distance, and testing for associations between walking and welfare indicators. We used anklets equipped with GPS data loggers to measure outdoor daily walking distance in 56 adult female African (n = 33) and Asian (n = 23) elephants housed in 30 North American zoos. We collected 259 days of data and determined associations between distance walked and social, housing, management, and demographic factors. Elephants walked an average of 5.3 km/day with no significant difference between species. In our multivariable model, more diverse feeding regimens were correlated with increased walking, and elephants who were fed on a temporally unpredictable feeding schedule walked 1.29 km/day more than elephants fed on a predictable schedule. Distance walked was also positively correlated with an increase in the number of social groupings and negatively correlated with age. We found a small but significant negative correlation between distance walked and nighttime Space Experience, but no other associations between walking distances and exhibit size were found. Finally, distance walked was not related to health or behavioral outcomes including foot health, joint health, body condition, and the performance of stereotypic behavior, suggesting that more research is necessary to determine explicitly how differences in walking may impact elephant welfare

Do people with intersecting identities report more high-risk alcohol use and lifetime substance use?

© 2018 Swiss School of Public Health (SSPH+) Objectives: We examined protective and non-protective effects of disadvantaged social identities and their intersections on lifetime substance use and risky alcohol consumption. Methods: Data from 90,941 participants of the Global Drug Survey 2015 were analysed. Multivariable logistic regressions were used to calculate adjusted odds ratios for lifetime use of nine psychoactive substances, as well as high-risk/harmful alcohol use. Disadvantaged identities from three categories (ethnicity, sexual identity, gender), and interactions between these were compared. Results: Findings indicate that participants with disadvantaged ethnic and sexual minority identities are more likely to use psychoactive substances compared to their counterparts. The intersecting identity ‘disadvantaged ethnic identity and sexual minority’ appears to be protective compared to those with just one of these identities. While female gender appears to be highly protective in general, it is not protective among females with disadvantaged social identities. Conclusions: Stark disparities in substance use between different social identities and their intersections emphasise the importance of intersectionality theories in public health research intervention design. Future research on health equity, particularly substance use, should target individuals with intersecting identities

New approaches to the study of spinel ferrite nanoparticles for biomedical applications

This chapter is prepared into six different sections. The first part will provide a brief introduction of spinel ferrite nanoparticles synthesis, the use of chelating agents in the sol-gel method, and applications of spinel ferrite nanoparticles in biomedical fields. The second part will cover an overview of the structure and magnetism of spinel ferrites. The third part will present a summary of different types of chelating agents. The fourth part will provide information of the sol-gel synthesis for ceramic nanoparticles. The fifth part will focus on the preparation of cobalt ferrite nanoparticles by sol-gel methods using polyvinyl alcohol (PVA) and citric acid (CA) as chelating agents. The influence of chelating agents on the physical properties and antibacterial property of cobalt ferrite nanoparticles will be highlighted in the last part. A discussion on chelating agent-metal ion formation and the antibacterial mechanisms of spinel ferrite nanoparticles will be presented

KCNJ15/Kir4.2 couples with polyamines to sense weak extracellular electric fields in galvanotaxis

Weak electric fields guide cell migration, known as galvanotaxis/electrotaxis. The sensor(s) cells use to detect the fields remain elusive. Here we perform a large-scale screen using an RNAi library targeting ion transporters in human cells. We identify 18 genes that show either defective or increased galvanotaxis after knockdown. Knockdown of the KCNJ15 gene (encoding inwardly rectifying K(+) channel Kir4.2) specifically abolishes galvanotaxis, without affecting basal motility and directional migration in a monolayer scratch assay. Depletion of cytoplasmic polyamines, highly positively charged small molecules that regulate Kir4.2 function, completely inhibits galvanotaxis, whereas increase of intracellular polyamines enhances galvanotaxis in a Kir4.2-dependent manner. Expression of a polyamine-binding defective mutant of KCNJ15 significantly decreases galvanotaxis. Knockdown or inhibition of KCNJ15 prevents phosphatidylinositol 3,4,5-triphosphate (PIP(3)) from distributing to the leading edge. Taken together these data suggest a previously unknown two-molecule sensing mechanism in which KCNJ15/Kir4.2 couples with polyamines in sensing weak electric fields