Pig fetal skeletal muscle development is associated with genome-wide DNA hypomethylation and corresponding alterations in transcript and microRNA expression.

Fetal myogenesis represents a critical period of porcine skeletal muscle development and requires coordinated expression of thousands of genes. Epigenetic mechanisms, including DNA methylation, drive transcriptional regulation during development; however, these processes are understudied in developing porcine tissues. We performed bisulfite sequencing to assess DNA methylation in pig longissimus dorsi muscle at 41- and 70-days gestation (dg), as well as RNA- and small RNA-sequencing to identify coordinated changes in methylation and expression between myogenic stages. We identified 45 739 differentially methylated regions (DMRs) between stages, and the majority (N = 34 232) were hypomethylated at 70 versus 41 dg. Integration of methylation and transcriptomic data revealed strong associations between differential gene methylation and expression. Differential miRNA methylation was significantly negatively correlated with abundance, and dynamic expression of assayed miRNAs persisted postnatally. Motif analysis revealed significant enrichment of myogenic regulatory factor motifs among hypomethylated regions, suggesting that DNA hypomethylation may function to increase accessibility of muscle-specific transcription factors. We show that developmental DMRs are enriched for GWAS SNPs for muscle- and meat-related traits, demonstrating the potential for epigenetic processes to influence phenotypic diversity. Our results enhance understanding of DNA methylation dynamics of porcine myogenesis and reveal putative cis-regulatory elements governed by epigenetic processes.

Cosmological particle production: a review.

This article will review quantum particle creation in expanding universes. The emphasis will be on the basic physical principles and on selected applications to cosmological models. The needed formalism of quantum field theory in curved spacetime will be summarized, and applied to the example of scalar particle creation in a spatially flat Universe. Estimates for the creation rate will be given and applied to inflationary cosmology models. Analog models which illustrate the same physical principles and may be experimentally realizable are also discussed.

Surgical treatment of post-infectious hydrocephalus in infants.

The management of post-infective hydrocephalus in infants remains a challenging task for the pediatric neurosurgeon. The decision-making curve is often complex in that appropriate temporizing measures need to be implemented to properly clear any infection within the CSF before any decision can be made regarding a permanent solution. The etiology differs at varying stages of neonatal development, and the weight of the child, skin fragility, and relevant surgical treatment options are often important limiting factors. Deciding on the optimal treatment option involves assessing the etiology, age, and clinical and radiological features of the individual case and selecting the most appropriate surgical option.

Carbon dioxide and water incorporation mechanisms in SrFeO3-δ phases: a computational study.

With a higher propensity for low temperature synthesis routes along with a move toward lower solid oxide fuel cell operating temperatures, water and carbon dioxide incorporation in strontium ferrite is of importance. Despite this, the mechanisms are not well understood. In this work, classical-potential-based computational techniques are used to determine the favourability of water and CO2 incorporation mechanisms in both SrFeO3-δ and SrFeO2.5. Our studies suggest that intrinsic Frenkel and Schottky type defects are unlikely to form, but that water and carbon dioxide incorporation are favourable in both phases. Water incorporation is likely for both the cubic and brownmillerite phases, with hydroxyl ions preferring to sit on octahedral oxygen sites in both structures, causing slight tilting of the shared octahedra. Interstitial hydroxyl ions are only likely for the brownmillerite phase, where the hydroxyl ions are most stable between adjacent FeO4 tetrahedral chains. Carbon dioxide incorporation via carbonate defects is most favourable when a carbonate molecule exists on an iron site, preferring the iron site with lower oxygen coordination. This involves formation of multiple oxygen vacancies surrounding the iron site, and thus we conclude that carbonate can trap oxygen vacancies.

Changes to country-specific hepatitis A travel vaccination recommendation for UK travellers in 2017-responding to a vaccine shortage in the national context.

OBJECTIVES: A routine review of hepatitis A travel vaccination recommendations was brought forward in June 2017 due to hepatitis A vaccine shortages and a concurrent outbreak in men who have sex with men (MSM). There were three objectives: first, to document the review process for changing the recommendations for the UK travellers in June 2017. Second, to study the impact of these changes on prescribing in general practice in 2017 compared with the previous 5 years. Third, to study any changes in hepatitis A notifications in June-October 2017 compared with the previous 5 years. STUDY DESIGN: This is an observational study. METHODS: Travel vaccination recommendations for countries with either low-risk (<20%) or high-risk (>90%) status according to child hepatitis A seroprevalence were not changed. A total of 67 intermediate-risk countries with existing recommendations for most travellers and with new data on rural sanitation levels were shortlisted for the analysis. Data on child hepatitis A seroprevalence, country income status, access to sanitation in rural areas and traveller volumes were obtained. Information about the vaccine supply was obtained from Public Health England. Changes to the existing classification were made through expert consensus, based on countries' hepatitis A seroprevalence, sanitation levels, level of income, volume of travel and hepatitis A traveller cases. Data on the number of combined and monovalent hepatitis A-containing vaccines prescribed in England, 2012-2017, were obtained from the National Health Service Business Service Authorities. The number of monthly prescriptions for January-September 2017 was compared with the mean number of prescriptions for the same month in the previous 5 years (t-test, α = 5%, df = 4). The number of hepatitis A cases notified in June-October 2017 not related to the MSM outbreak was compared with the number of notifications in the same months in previous years. RESULTS: A total of 36 countries were downgraded based on good access (80+% of population) to sanitation in rural areas and the intermediate-risk status in terms of child hepatitis A seroprevalence. For these countries, vaccination would only be recommended to travellers staying long term, visiting friends and relatives or staying in areas without good sanitation. There was a significant decline in hepatitis A vaccine prescriptions in June-September 2017, and there was no increase in the number of notifications. CONCLUSIONS: Hepatitis A vaccination recommendations for travel were revised in 2017 following a systematic approach to maintain continuity of supply after a hepatitis A vaccine shortage and increased hepatitis A vaccine demand related to a large outbreak. Improved access to good sanitation in rural areas and low seroprevalence estimates among children have led to 36 countries to no longer require vaccination for most travellers. These changes do not seem to have impacted on hepatitis A notifications in England, although further research will be needed to quantify the impact more precisely.

Early Supported Discharge for patients with febrile neutropenia - Experience at a large district hospital in the UK.

Neutropenic sepsis can be life threatening, with mortality 2-21%. The heterogeneity of patients referred with "suspected neutropenic sepsis" has led to strategies being developed to risk-stratify patients and identify those with a low risk of septic complications that could be managed in the outpatient setting, such as The Multinational Association for Supportive Care in Cancer score (MASCC). Outcomes for patients referred with suspected neutropenic sepsis were assessed before and after use of MASCC guided early-supported discharge. 50/123 (41%) patients over 24 months were eligible for early-supported discharge. 26/50 patients had same-day discharge, 14 had overnight admission, 8 stayed 2 nights and 2 stayed 3 nights. Patients received on average 2 follow-up telephone consultations. There were 5 readmissions (10%) and no adverse events. In comparison group; 8 patients over 3-months would have been suitable, potentially saving 40 bed-days. This shows MASCC guided early-supported discharge is safe and cost-effective.

Quantum Gravitational Force Between Polarizable Objects.

Since general relativity is a consistent low energy effective field theory, it is possible to compute quantum corrections to classical forces. Here we compute a quantum correction to the gravitational potential between a pair of polarizable objects. We study two distant bodies and compute a quantum force from their induced quadrupole moments due to two-graviton exchange. The effect is in close analogy to the Casimir-Polder and London-van der Waals forces between a pair of atoms from their induced dipole moments due to two photon exchange. The new effect is computed from the shift in vacuum energy of metric fluctuations due to the polarizability of the objects. We compute the potential energy at arbitrary distances compared to the wavelengths in the system, including the far and near regimes. In the far distance, or retarded, regime, the potential energy takes on a particularly simple form: V(r)=-3987ℏcG^{2}α_{1S}α_{2S}/(4πr^{11}), where α_{1S}, α_{2S} are the static gravitational quadrupole polarizabilities of each object. We provide estimates of this effect.

Asynchronous hatching provides females with a means for increasing male care but incurs a cost by reducing offspring fitness.

In species with biparental care, sexual conflict occurs because the benefit of care depends on the total amount of care provided by the two parents while the cost of care depends on each parent's own contribution. Asynchronous hatching may play a role in mediating the resolution of this conflict over parental care. The sexual conflict hypothesis for the evolution of asynchronous hatching suggests that females adjust hatching patterns in order to increase male parental effort relative to female effort. We tested this hypothesis in the burying beetle Nicrophorus vespilloides by setting up experimental broods with three different hatching patterns: synchronous, asynchronous and highly asynchronous broods. As predicted, we found that males provided care for longer in asynchronous broods whereas the opposite was true of females. However, we did not find any benefit to females of reducing their duration of care in terms of increased lifespan or reduced mass loss during breeding. We found substantial negative effects of hatching asynchrony on offspring fitness as larval mass was lower and fewer larvae survived to dispersal in highly asynchronous broods compared to synchronous or asynchronous broods. Our results suggest that, even though females can increase male parental effort by hatching their broods more asynchronously, females pay a substantial cost from doing so in terms of reducing offspring growth and survival. Thus, females should be under selection to produce a hatching pattern that provides the best possible trade-off between the benefits of increased male parental effort and the costs due to reduced offspring fitness.

Healthcare utilization and lost productivity due to infectious gastroenteritis, results from a national cross-sectional survey Australia 2008-2009.

The aim of this study was to estimate the healthcare usage and loss of productivity due to gastroenteritis in Australia using the National Gastroenteritis Survey II. In 2008-2009, 7578 participants across Australia were surveyed about infectious gastroenteritis by telephone interview. A gastroenteritis case was defined as a person experiencing ⩾ 3 loose stools and/or ⩾ 2 vomits in a 24-h period, excluding cases with a non-infectious cause for their symptoms, such as pregnancy or consumption of alcohol. Lost productivity was considered any lost time from full- or part-time paid work due to having gastroenteritis or caring for someone with the illness. Interference with other daily activities was also examined along with predictors of healthcare-seeking practices using multivariable regression. Results were weighted to obtain nationally representative estimates using Stata v. 13·1. Of the 341 cases, 52 visited a doctor due to gastroenteritis, 126 reported taking at least one medication for their symptoms and 79 cases reported missing ⩾ 1 days' paid work due to gastroenteritis. Gastroenteritis results in a total of 13·1 million (95% confidence interval 6·7-19·5) days of missed paid work each year in Australia. The indirect costs of gastroenteritis are significant, particularly from lost productivity.

Evaluation of a structured expert elicitation estimating the proportion of illness acquired by foodborne transmission for nine enteric pathogens in Australia.

Estimates of the proportion of illness transmitted by food for different enteric pathogens are essential for foodborne burden-of-disease studies. Owing to insufficient scientific data, a formal synthesis of expert opinion, an expert elicitation, is commonly used to produce such estimates. Eleven experts participated in an elicitation to estimate the proportion of illnesses due to food in Australia for nine pathogens over three rounds: first, based on their own knowledge alone; second, after being provided with systematic reviews of the literature and Australian data; and finally, at a workshop where experts reflected on the evidence. Estimates changed significantly across the three rounds (P = 0·002) as measured by analysis of variance. Following the workshop in round 3, estimates showed smoother distributions with significantly less variation for several pathogens. When estimates were combined to provide combined distributions for each pathogen, the width of these combined distributions reflected experts' perceptions of the availability of evidence, with narrower intervals for pathogens for which evidence was judged to be strongest. Our findings show that the choice of expert elicitation process can significantly influence final estimates. Our structured process - and the workshop in particular - produced robust estimates and distributions appropriate for inclusion in burden-of-disease studies.

Bayesian Source Attribution of Salmonellosis in South Australia.

Salmonellosis is a significant cause of foodborne gastroenteritis in Australia, and rates of illness have increased over recent years. We adopt a Bayesian source attribution model to estimate the contribution of different animal reservoirs to illness due to Salmonella spp. in South Australia between 2000 and 2010, together with 95% credible intervals (CrI). We excluded known travel associated cases and those of rare subtypes (fewer than 20 human cases or fewer than 10 isolates from included sources over the 11-year period), and the remaining 76% of cases were classified as sporadic or outbreak associated. Source-related parameters were included to allow for different handling and consumption practices. We attributed 35% (95% CrI: 20-49) of sporadic cases to chicken meat and 37% (95% CrI: 23-53) of sporadic cases to eggs. Of outbreak-related cases, 33% (95% CrI: 20-62) were attributed to chicken meat and 59% (95% CrI: 29-75) to eggs. A comparison of alternative model assumptions indicated that biases due to possible clustering of samples from sources had relatively minor effects on these estimates. Analysis of source-related parameters showed higher risk of illness from contaminated eggs than from contaminated chicken meat, suggesting that consumption and handling practices potentially play a bigger role in illness due to eggs, considering low Salmonella prevalence on eggs. Our results strengthen the evidence that eggs and chicken meat are important vehicles for salmonellosis in South Australia.

The role of environmental factors in search and rescue incidents in Nunavut, Canada.

OBJECTIVES: Unintentional injury is a leading cause of morbidity and mortality in Nunavut, where the importance of land-based activities and reliance on semi-permanent trails create unique risk profiles. Climate change is believed to be exacerbating these risks, although no studies have quantitatively examined links between environmental conditions and injury and distress in the Canadian Arctic. We examine the correlation between environmental conditions and land-based search and rescue (SAR) incidents across Nunavut. STUDY DESIGN: Case study. METHODS: Case data were acquired from the Canadian National Search and Rescue Secretariat. Gasoline sales from across the territory are then used to model land-use and exposure. We compare weather and ice conditions during 202 SAR incidents to conditions during 755 non-SAR days (controls) between 2013 and 2014. RESULTS: We show daily ambient temperature, ice concentration, ice thickness, and variation in types of ice to be correlated with SAR rates across the territory during the study period. CONCLUSIONS: These conditions are projected to be affected by future climate change, which could increase demand for SAR and increase injury rates in the absence of targeted efforts aimed at prevention and treatment. This study provides health practitioners and public health communities with clearer understanding to prepare, respond to, and prevent injuries across the Arctic.

Estimates of benefits and harms of prophylactic use of aspirin in the general population.

BACKGROUND: Accumulating evidence supports an effect of aspirin in reducing overall cancer incidence and mortality in the general population. We reviewed current data and assessed the benefits and harms of prophylactic use of aspirin in the general population. METHODS: The effect of aspirin for site-specific cancer incidence and mortality, cardiovascular events was collated from the most recent systematic reviews. Studies identified through systematic Medline search provided data regarding harmful effects of aspirin and baseline rates of harms like gastrointestinal bleeding and peptic ulcer. RESULTS: The effects of aspirin on cancer are not apparent until at least 3 years after the start of use, and some benefits are sustained for several years after cessation in long-term users. No differences between low and standard doses of aspirin are observed, but there were no direct comparisons. Higher doses do not appear to confer additional benefit but increase toxicities. Excess bleeding is the most important harm associated with aspirin use, and its risk and fatality rate increases with age. For average-risk individuals aged 50-65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, myocardial infarction or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period. CONCLUSIONS: Prophylactic aspirin use for a minimum of 5 years at doses between 75 and 325 mg/day appears to have favourable benefit-harm profile; longer use is likely to have greater benefits. Further research is needed to determine the optimum dose and duration of use, to identify individuals at increased risk of bleeding, and to test effectiveness of Helicobacter pylori screening-eradication before starting aspirin prophylaxis.

The burden and determinants of self-reported acute gastrointestinal illness in an Indigenous Batwa Pygmy population in southwestern Uganda.

Acute gastrointestinal illness (AGI) is an important public health priority worldwide. Few studies have captured the burden of AGI in developing countries, and even fewer have focused on Indigenous populations. This study aimed to estimate the incidence and determinants of AGI within a Batwa Pygmy Indigenous population in southwestern Uganda. A retrospective cross-sectional survey was conducted in January 2013 via a census of 10 Batwa communities (n = 583 participants). The AGI case definition included any self-reported symptoms of diarrhoea or vomiting in the past 2 weeks. The 14-day prevalence of AGI was 6·17% [95% confidence interval (CI) 4·2-8·1], corresponding to an annual incidence rate of 1·66 (95% CI 1·1-2·2) episodes of AGI per person-year. AGI prevalence was greatest in children aged <3 years (11·3%). A multivariable mixed-effects logistic regression model controlling for clustering at the community level indicated that exposure to goats [odds ratio (OR) 2·6, 95% CI 1·0-6·8], being a child aged <3 years (OR 4·8, 95% CI 1·2-18·9), and being a child, adolescent or senior Batwa in the higher median of wealth (OR 7·0, 95% CI 3·9-9·2) were significantly associated with having AGI. This research represents the first Indigenous community-census level study of AGI in Uganda, and highlights the substantial burden of AGI within this population.

Implications of retinal effects observed in chronic toxicity studies on the clinical development of a CNS-active drug candidate.

The development path described for JNJ-26489112 provides perspectives on interpretation of retinal effects observed in nonclinical studies and their implications for clinical development. JNJ-26489112 is a CNS-active investigational drug that has potential as a novel treatment for treatment-resistant and bipolar depression, epilepsy, and neuropathic/inflammatory pain. In a 6-month toxicity study in albino rats, retinal atrophy was observed at supratherapeutic exposures to JNJ-26489112. The histopathological changes and topography of the lesions were characteristic of light-induced damage specific to albino rats. The species/strain specificity is supported by an absence of any ocular effects in dogs and in pigmented and albino rats, housed under standard and reduced lighting, respectively. To further evaluate its potential to cause ocular effects, in vivo functional and structural ocular analyses were included in a 9-month monkey toxicity study. Reductions in rod- and cone-mediated electroretinograms were observed at supratherapeutic exposures but without any histopathologic changes. These data suggested that the effects of JNJ-26489112 in monkeys were neuromodulatory and not neurotoxic. Taken together, data related to the light-induced atrophy in albino rats and reversible neuromodulatory effects in monkeys, supported the safe evaluation of JNJ-26489112 in a clinical proof-of-concept study that included comprehensive functional and structural ocular monitoring.

Civil society organizations and adaptation to the health effects of climate change in Canada.

BACKGROUND: Adaptation will be necessary to cope with the impacts of climate change on the health of Canadians. Civil society organizations (CSOs) have an important role in health adaptation, but it is unknown what actions they are undertaking. OBJECTIVES: To identify and examine what adaptations are being developed by CSOs to adapt to the health effects of climate change based on a systematic review of the activities of 190 organizations and 1196 reported adaptation actions. RESULTS: There were six key findings: (1) health adaptation actions are predominantly led by environmental CSOs; (2) most actions are occurring at national and regional levels; (3) food and/or water contamination and air quality are dominant climate change stimuli for action; (4) responses predominantly reflect awareness and research activities, with limited evidence of substantive intervention; (5) consideration of vulnerable groups is limited; and (6) climate change is usually considered alongside other factors, if at all. CONCLUSIONS: The results indicate a deficit in terms of what needs to be done for health adaptation and what is being done; part of a broader adaptation deficit in Canada. Coordinated adaptation planning at federal and provincial level is needed, involving collaboration between CSOs and public health bodies.

A comparison of the degradation behaviour of 3D printed PDLGA scaffolds incorporating bioglass or biosilica.

Silica incorporation into biomaterials, such as Bioglass and Si-substituted calcium phosphate ceramics has received significant attention in bone tissue engineering over the last few decades. This study aims to explore the dissolution behaviour of natural biosilica isolated from a freshwater diatom, Cyclotella meneghiniana, that has been incorporated into 3D printed poly (DL-lactide -co - glycolide) (PDLGA) scaffolds using extrusion and additive manufacturing. In the study, two different dry weight percentage (1 wt% & 5 wt%) of diatom-silica were incorporated into PDLGA scaffolds that were then degraded in phosphate buffered saline (PBS) cell free media. In addition, pure PDLGA scaffolds and 5 wt% Bioglass scaffolds were used as control groups. The degradation study was performed over 26-weeks. The release rate of Si4+ ions from diatom-PDLGA scaffolds was found to increase exponentially with respect to time. The compressive strength of scaffolds was also measured with the Diatom-PDLGA scaffolds found to maintain their strength for longer than either pure PDLGA scaffolds or 5 wt% Bioglass scaffolds. 13C NMR data showed that diatom biosilica containing scaffolds had less degradation than pure or bioglass-containing scaffolds at comparable time-points. Overall, the Diatom-PDLGA scaffolds were found to have more desirable physiochemical properties for bone repair compared to Bioglass.

Bilateral internal carotid artery occlusion with compensatory perfusion in a HIV-infected patient.

SUMMARY: HIV infection occlusive arteriopathies may result in neurological symptoms. We report a case of bilateral complete occlusion of the extracranial portions of the internal carotid arteries in a HIV+ve patient who presented with a syncopal episode due to intraventricular haemorrhage. Compensatory blood flow from the posterior cerebral circulation via the circle of Willis resulted in small telangiectatic vessels arising from the posterior cerebral circulation which probably accounted for this rare haemorrhagic complication of an occlusive arteriopathy.

Isolation of plasma membrane fragments from HeLa cells.

A method for isolating plasma membrane fragments from HeLa cells is described. The procedure starts with the preparation of cell membrane "ghosts," obtained by gentle rupture of hypotonically swollen cells, evacuation of most of the cell contents by repeated washing, and isolation of the ghosts on a discontinuous sucrose density gradient. The ghosts are then treated by minimal sonication (5 sec) at pH 8.6, which causes the ghost membranes to pinch off into small vesicles but leaves any remaining larger intracellular particulates intact and separable by differential centrifugation. The ghost membrane vesicles are then subjected to isopycnic centrifugation on a 20-50% w/w continuous sucrose gradient in tris-magnesium buffer, pH 8.6. A band of morphologically homogeneous smooth vesicles, derived principally from plasma membrane, is recovered at 30-33% (peak density = 1.137). The plasma membrane fraction contained a Na-K-activated ATPase activity of 1.5 micromole Pi/hr per mg, 3% RNA, and 13.8% of the NADH-cytochrome c reductase activity of a heavier fraction from the same gradient which contained mitochondria and rough endoplasmic vesicles. The plasma membranes of viable HeLa cells were marked with (125)I-labeled horse antibody and followed through the isolation procedure. The specific antibody binding of the plasma membrane vesicle fraction was increased 49-fold over that of the original whole cells.

Regenerative calcium release within muscle cells.

Free calcium appears to trigger the release of stored calcium from the sarcoplasmic reticulum of skinned skeletal muscle fibers immersed in solutions with a low concentration of magnesium ion.