Efficacy of a high quality O1/Campos foot-and-mouth disease vaccine upon challenge with a heterologous Korean O Mya98 lineage virus in pigs

In 2010 serotype O foot-and-mouth disease virus of the Mya98 lineage/SEA topotype spread into most East Asian countries. During 2010–2011 it was responsible for major outbreaks in the Republic of Korea where a monovalent O/Manisa vaccine (belonging to the ME-SA topotype) was applied to help control the outbreaks. Subsequently, all susceptible animals were vaccinated every 6 months with a vaccine containing the O/Manisa antigen. Despite vaccination, the disease re-occurred in 2014 and afterwards almost annually. This study focuses on the in vivo efficacy in pigs of a high quality monovalent commercial O₁/Campos vaccine against heterologous challenge with a representative 2015 isolate from the Jincheon Province of the Republic of Korea. Initially, viral characterizations and r₁ determinations were performed on six viruses recovered in that region during 2014–2015, centering on their relationship with the well characterized and widely available O₁/Campos vaccine strain. Genetic and antigenic analysis indicated a close similarity among 2014–2015 Korean isolates and with the previous 2010 virus, with distinct differences with the O₁/Campos strain. Virus neutralisation tests using O₁/Campos cattle and pig post vaccination sera and recent Korean outbreak viruses predicted acceptable cross-protection after a single vaccination, as indicated by r₁ values, and in pigs, by expectancy of protection. In agreement with the in vitro estimates, in vivo challenge with a selected field isolate indicated that O₁/Campos primo vaccinated pigs were protected, resulting in a PD50 value of nearly 10. The results indicated that good quality oil vaccines containing the O₁/Campos strain can successfully be used against isolates belonging to the O Mya98/SEA topotype.     

Glutathione S-transferase A1 (GSTA1) release,an early indicator of acute hepatic injury in mice

Three acute hepatic injury models (a CCl₄-induced model, APAP-induced model and ethanol-induced model) in mice were used to study the importance of GSTA1 in acute hepatic injury by comparison with a standard enzyme marker, alanine aminotransferase (ALT). GSTA1 release was demonstrated to be an earlier and more sensitive indicator of hepatotoxicity than was ALT. Significant increases in GSTA1 were detected at 2 h after CCl₄ exposure, while ALT was undetected at this time. GSTA1 was also a more sensitive indicator of hepatotoxicity than ALT after 6 h. In the APAP and ethanol models, GSTA1 was markedly increased earlier than ALT, at 2 h post exposure. The release of GSTA1 was significantly increased at a dose of 12.5 mg/kg (CCl₄ model), 100 mg/kg (APAP model) and 10 ml/kg (ethanol model), the lowest exposure concentration for each model. In contrast, AST release was not statistically significant. These results suggest that GSTA1 can be detected at low concentrations during the early stages of acute hepatic injury and that GSTA1 is a more sensitive and more accurate indicator than ALT.     

Antibiotic optimisation in ‘the bush’: Local know-how and core-periphery relations

The growing global concern around antimicrobial mis-use and proliferating resistance has resulted in increasing interest in optimising antibiotics, particularly in hospitals. While the agenda to tighten antibiotic use has been critically explored in metropolitan settings, the dynamics of rural and remote settings have remained largely unexplored. Drawing on 30 interviews with doctors, nurses, and pharmacists in a remote Australian hospital, we focus on the pertinence of setting, and its importance for contextualising and potentially achieving antibiotic optimisation. Building on previous work on the dynamics of locale and core-periphery relations, here we consider how antimicrobial practice is deeply embedded in experiences of being on the geographical periphery, and crucially, at the periphery of (established) knowledge.     

Determinants in early adulthood of leisure-time physical inactivity stability and change in mid-life: findings from a prospective birth cohort

BackgroundLeisure-time physical inactivity has a high prevalence and associated disease burden. Information about factors that affect inactivity stability and change is needed. We aimed to establish whether early adult factors predict inactivity patterns over subsequent decades in mid-life.MethodsThe 1958 British birth cohort is a nationwide follow-up study of all births during 1 week in March, 1958. Leisure-time inactivity in 12 271 participants was self-reported as activity (eg, walking, swimming) of less than once a week at ages 33 and 50 years. Associations of early adult (23–33 years) factors with four patterns between the ages of 33 and 50 years (never inactive, persistently inactive, deteriorating, or improving) were assessed by multinomial logistic regression, with and without adjustment for childhood factors. Missing values were imputed with multiple imputation chained equations.Findings3863 adults (32%) were inactive at 33 years; 3791 (31%) were inactive at 50 years. 4257 (35%) had changed inactivity status between 33 and 50 years (2093 [17%] deteriorating, 2164 [18%] improving). Relative risk ratios for factors associated with persistent versus never inactive were: physically limiting illness 1·21 per number of ages exposed—ie, per increase in scale [0, 1, 2] for each age [23 years and 33 years] exposed—(95% CI 1·04–1·42); obesity per number of ages exposed 1·30 (1·11–1·51), perceived underweight versus perceived right weight 1·31 (1·06–1·62), attained height per 5 cm 0·93 (0·89–0·97), depression per number of ages exposed 1·32 (1·18–1·47), education per decrease on a 5-point scale 1·30 (1·21–1·40), and neighbourhood (0·68 [0·54–0·86], 0·62 [0·49–0·78], and 0·84 [0·72–0·99] in suburbs and service centres, rural areas and seaside resorts, and growth areas vs stable industrial areas, respectively). No associations were observed for social class, cohabitation, employment, and parenthood. Associations for inactivity deterioration (vs never) were similar to those for persistently inactive. Only two factors were associated with inactivity improvement—parenthood (although associations varied for number of children at 23 years and 33 years) and neighbourhood. Associations remained, albeit attenuated, after adjustment for childhood factors.InterpretationAlthough our study of leisure-time inactivity is based on self-report, repeat, prospective data spanning decades provides a rare opportunity to investigate an important health determinant that is amenable to modification. Adult inactivity status changes are not uncommon (35% changed between the ages of 33 and 50 years), providing opportunities for behaviour interventions. Early adult factors predicted persistence of inactivity and deterioration; fewer factors predicted improvement. The neighbourhood of young adults had long-lasting associations with inactivity patterns.FundingThis work was supported by the Department of Health Policy Research Programme through the Public Health Research Consortium. The views expressed in this abstract are those of the authors and not necessarily those of the Department of Health.     

Oocyte quality in mice is affected by a mycotoxin‐contaminated diet

Mycotoxins, such as deoxynivalenol (DON), zearalenone (ZEN), and aflatoxin (AF), are commonly found in many food commodities and may impair the growth and reproductive efficiency of animals and humans. We investigated the effects of a mycotoxin‐contaminated diet on mouse oocyte quality. Maize contaminated with DON (3.875 mg/kg), ZEN (1,897 μg/kg), and AF (806 μg/kg) was incorporated into a mouse diet at three different levels (0, 15, and 30% w/w). After 4 weeks, ovarian and germinal vesicle oocyte indices decreased in mycotoxin‐fed mice. Oocytes from these mice exhibited low developmental competence with reduced germinal vesicle breakdown and polar body extrusion rates. Embryo developmental competence also showed a similar pattern, and the majority of embryos could not develop to the morula stage. Actin expression was also reduced in both the oocyte cortex and cytoplasm, which was accompanied by decreased expression of the actin nucleation factors profilin‐1 and mDia1. Moreover, a large percentage of oocytes derived from mice that were fed a mycotoxin‐contaminated diet exhibited aberrant spindle morphology, a loss of the cortical granule‐free domain, and abnormal mitochondrial distributions, which further supported the decreased oocyte quality. Thus, our results demonstrate that mycotoxins are toxic to the mouse reproductive system by affecting oocyte quality. Environ. Mol. Mutagen. 55:354–362, 2014. © 2013 Wiley Periodicals, Inc.     

Glucocorticoids mediate circadian timing in peripheral osteoclasts resulting in the circadian expression rhythm of osteoclast-related genes

Circadian rhythms are prevalent in bone metabolism. However, the molecular mechanisms involved are poorly understood. Recently, we suggested that output signals from the suprachiasmatic nucleus (SCN) are transmitted from the master circadian rhythm to peripheral osteoblasts through β-adrenergic and glucocorticoid signaling. In this study, we examined how the master circadian rhythm is transmitted to peripheral osteoclasts and the role of clock gene in osteoclast. Mice were maintained under 12-hour light/dark periods and sacrificed at Zeitgeber times 0, 4, 8, 12, 16 and 20. mRNA was extracted from femur (cancellous bone) and analyzed for the expression of osteoclast-related genes and clock genes. Osteoclast-related genes such as cathepsin K (CTSK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) showed circadian rhythmicity like clock genes such as period 1 (PER1), PER2 and brain and muscle Arnt-like protein 1 (BMAL1). In an in vitro study, not β-agonist but glucocorticoid treatment remarkably synchronized clock and osteoclast-related genes in cultured osteoclasts. Chromatin immunoprecipitation (ChIP) assay showed the interaction between BMAL1 proteins and promoter region of CTSK and NFATc1. To examine whether endogenous glucocorticoids influence the osteoclast circadian rhythms, mice were adrenalectomized (ADX) and maintained under 12-hour light/dark periods at least two weeks before glucocorticoid injection. A glucocorticoid injection restarted the circadian expression of CTSK and NFATc1 in ADX mice. These results suggest that glucocorticoids mediate circadian timing to peripheral osteoclasts and osteoclast clock contributes to the circadian expression of osteoclast-related genes such as CTSK and NFATc1.