Calcitriol Increases Ceramide, Diacylglycerol, and Expression of Genes Involved in Lipid Packaging in Skeletal Muscle

Background: Vitamin D is crucial for skeletal muscle function. 25-hidroxyvitamin D (25(OH)D) has been correlated with skeletal muscle mass and intramyocellular lipid (IMCL) content. The purpose of this study was to understand how calcitriol, the active vitamin D metabolite, directly affects myocellular size and lipid partitioning. Methods: C2C12 myotubes were treated with calcitriol (100nM) or vehicle control for 24 or 96 h. Myotube diameter and protein synthesis rate were measured to determine effects of calcitriol on myocellular size. Intramyocellular triacylglycerol (IMTG), diacylglycerol (DAG), and ceramide content were measured by LC/MS. Expression of genes involved in lipid packaging and lipolysis were measured by RT-PCR. Insulin-stimulated phosphorylated Akt (Thr 308) was determined by western blot. Results: Calcitriol did not affect myocellular size or protein synthesis rate. Calcitriol increased total DAG and ceramides in a sub-species specific manner. Calcitriol increased IMTG area, but did not affect total IMTG content. Calcitriol reduced mRNA content of diglyceride acyltransferase and increased mRNA content of lipid packaging genes. Calcitriol did not negatively affect insulin-stimulated pAkt. Conclusions: These results suggest calcitriol directly alters lipid content and packaging in skeletal muscle cells. Altering the expression of lipid packaging genes and increasing IMCL subspecies content may be mechanisms by which vitamin D improves skeletal muscle function in vivo

Revitalising Collyweston limestone slate production by artificial freeze/thaw splitting

Extraction of limestone roofing slate from Collyweston was an industry which was considered extinct by the early 1990′s, with building repairs relying on wholesale recycling of roofing from demolished buildings. Traditionally stone extracted from the mines was exposed to natural cycles of freeze/thaw to facilitate splitting. Work was undertaken over several years to investigate the resources available and whether these could be artificially frozen to produce slates. The work identified a freeze/thaw regime which could be used to produce roofing slates for historic buildings and which were used in the Historic England restoration of Apethorpe Palace. Mining of the Collyweston limestone stone has now resumed and uses artificial freezing to achieve production of slates which is economically feasible due to the faster process time

Pre-existing Microfilarial Infections of American Robins (Passeriformes: Turdidae) and Common Grackles (Passeriformes: Icteridae) Have Limited Impact on Enhancing Dissemination of West Nile Virus in Culex pipiens Mosquitoes (Diptera: Culicidae)

Microfilariae (MF) are the immature stages of filarial nematode parasites and inhabit the blood and dermis of all classes of vertebrates, except fish. Concurrent ingestion of MF and arboviruses by mosquitoes can enhance mosquito transmission of virus compared to when virus is ingested alone. Shortly after being ingested, MF penetrate the mosquito’s midgut and may introduce virus into the mosquito’s hemocoel, creating a disseminated viral infection much sooner than normal. This phenomenon is known as microfilarial enhancement. Both American Robins and Common Grackles harbor MF—that is, Eufilaria sp. and Chandlerella quiscali von Linstow (Spirurida: Onchocercidae), respectively. We compared infection and dissemination rates in Culex pipiens L. mosquitoes that fed on birds with and without MF infections that had been infected with West Nile virus (WNV). At moderate viremias, about 107 plaque-forming units (pfu)/ml of blood, there were no differences in infection or dissemination rates among mosquitoes that ingested viremic blood from a bird with or without microfilaremia. At high viremias, \u3e108.5 pfu/ml, mosquitoes feeding on a microfilaremic Grackle with concurrent viremia had significantly higher infection and dissemination rates than mosquitoes fed on viremic Grackles without microfilaremia. Microfilarial enhancement depends on the specific virus, MF, and mosquito species examined. How virus is introduced into the hemocoel by MF differs between the avian/WNV systems described here (i.e., leakage) and various arboviruses with MF of the human filarid, Brugia malayi (Brug) (Spirurida: Onchocercidae) (i.e., cotransport). Additional studies are needed to determine if other avian species and their MF are involved in the microfilarial enhancement of WNV in nature

Dose Ratios between High Dose Oral Morphine or Equivalents and Oral Methadone

Background: Methadone is a commonly used opioid in hospice and palliative care for patients with refractory pain. Various methadone dose conversion methods utilize progressively higher morphine equivalent dose (MED) to methadone dose ratios to compensate for increased methadone potency with escalating opioid doses. Objective: The purpose of this study was to determine the dose ratio between equianalgesic doses of high dose oral morphine (daily doses \u3e1200 mg morphine or MED) and oral methadone. Methods: This study was a retrospective chart review of 324 patients who received methadone at Strong Memorial Hospital or the associated outpatient clinic during a nine-month period in 2011. Ten patients met the study inclusion and exclusion criteria. A Wilcoxon signed-rank test was used to compare the pain scale scores. The Spearman correlation coefficient was used to assess level of correlation between morphine dose and methadone dose. Results: Patients rotated to methadone from high opioid doses had a two-point improvement in median pain scale scores after conversion (p=0.039). However, there was no correlation identified for patients taking daily doses \u3e1200 mg oral morphine or MED prior to methadone rotation (p=0.19). There were no reported methadone adverse effects during the study. Conclusions: No correlation was identified between high MED doses and methadone at dose stabilization after opioid rotation. A fixed maximum methadone dose of 30 mg/day produced clinically meaningful improvements in pain scores without adverse drug effects. Caution should be exercised before considering rotation to methadone doses higher than 30 mg/day in a patient receiving \u3e1200 mg oral MED/day

No difference found in time to publication by statistical significance of trial results: a methodological review

Objective: Time-lag from study completion to publication is a potential source of publication bias in randomised controlled trials. This study sought to update the evidence base by identifying the effect of the statistical significance of research findings on time to publication of trial results.Design: Literature searches were carried out in four general medical journals from June 2013 to June 2014 inclusive (BMJ, JAMA, the Lancet and the New England Journal of Medicine). Setting: Methodological review of four general medical journals. Participants: Original research articles presenting the primary analyses from phase 2, 3 and 4 parallel-group randomised controlled trials were included. Main outcome measures: Time from trial completion to publication.Results: The median time from trial completion to publication was 431 days (n ¼ 208, interquartile range 278–618). A multivariable adjusted Cox model found no statistically significant difference in time to publication for trials reporting positive or negative results (hazard ratio: 0.86, 95% CI 0.64 to 1.16, p ¼ 0.32). Conclusion: In contrast to previous studies, this review did not demonstrate the presence of time-lag bias in time to publication. This may be a result of these articles being published in four high-impact general medical journals that may be more inclined to publish rapidly, whatever the findings. Further research is needed to explore the presence of time-lag bias in lower quality studies and lower impact journals

Distribution, Abundance, and Biomass Estimates for Primates within Kahuzi-Biega Lowlands and Adjacent Forest in Eastern DRC

Africa’s tropical forests have been subjected to alarming rates of forest clearing in the last two decades. Baseline data are critical to understanding the impacts of large-scale habitat loss and fragmentation. This report describes the distribution and relative abundance of anthropoid primates in 1994–95 within and adjacent to Kahuzi-Biega National Park lowland sector, eastern Democratic Republic of Congo. This is a region for which few empirical data exists. Density and biomass estimates derived from transect sampling are discussed for both adjacent settlement and remote sampling zones where minimum biomass estimates are 436 kg/km2 and 663 kg/km2, respectively. With the exception of red colobus Procolobus badius in sampling zone KB 4, hunting pressures do not appear to have been excessive. The owl-faced guenon Cercopithecus hamlyni is widely distributed and relatively abundant throughout the survey areas