Vitamin D and responses to inhaled fluticasone in severe chronic obstructive pulmonary disease

Ken M Kunisaki1,3, Thomas S Rector2,41Pulmonary Section, 2Center for Chronic Disease Outcomes Research and Center for Epidemiologic and Clinical Research, Minneapolis Veterans Affairs Medical Center, Minneapolis, MN, USA; 3Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, 4Department of Medicine, University of Minnesota, Minneapolis, MN, USABackground: Patients with chronic obstructive pulmonary disease (COPD) demonstrate variable responses to inhaled corticosteroids (ICS). The factors contributing to this variability are not well understood. Data from patients with asthma have suggested that low 25-hydroxyvitamin D [25(OH)D] levels contribute to a lack of ICS response in asthma. The objective of this study was to determine whether serum levels of 25(OH)D were related to ICS responses in patients with COPD.Methods: A total of 60 exsmokers with severe COPD (mean forced expiratory volume in one second [FEV1] 1.07 L, 36% of predicted) spent 4 weeks free of any ICS, followed by 4 weeks of ICS use (fluticasone propionate 500 µg twice daily). Spirometry was performed prior to and after 4 weeks of ICS use. Blood 25(OH)D levels were measured prior to ICS use and examined for relationships to changes in FEV1 following the 4 weeks of ICS use.Results: The mean 25(OH)D level was 23.3 ± 9.3 ng/mL. There was a high prevalence of vitamin D insufficiency (35%) and deficiency (40%). There was no relationship between baseline 25(OH)D and changes in FEV1 following 4 weeks of ICS.Conclusion: Baseline 25(OH)D does not contribute to the variation in short-term FEV1 responses to ICS in patients with severe COPD.Keywords: COPD, androstadienes, anti-inflammatory agents, spirometr

Antibodies to Pseudogymnoascus destructans are not sufficient for protection against white-nose syndrome

White-nose syndrome (WNS) is a fungal disease caused by Pseudogymnoascus destructans (Pd) that affects bats during hibernation. Although millions of bats have died from WNS in North America, mass mortality has not been observed among European bats infected by the fungus, leading to the suggestion that bats in Europe are immune. We tested the hypothesis that an antibody-mediated immune response can provide protection against WNS by quantifying antibod- ies reactive to Pd in blood samples from seven species of free-ranging bats in North America and two free-ranging species in Europe. We also quantified antibodies in blood samples from little brown myotis (Myotis lucifugus) that were part of a captive colony that we injected with live Pd spores mixed with adjuvant, as well as individuals surviving a captive Pd infection trial. Seropreva- lence of antibodies against Pd, as well as antibody titers, was greater among lit- tle brown myotis than among four other species of cave-hibernating bats in North America, including species with markedly lower WNS mortality rates. Among little brown myotis, the greatest titers occurred in populations occupy- ing regions with longer histories of WNS, where bats lacked secondary symp- toms of WNS. We detected antibodies cross-reactive with Pd among little brown myotis na€ıve to the fungus. We observed high titers among captive little brown myotis injected with Pd. We did not detect antibodies against Pd in Pd- infected European bats during winter, and titers during the active season were lower than among little brown myotis. These results show that antibody-medi- ated immunity cannot explain survival of European bats infected with Pd and that little brown myotis respond differently to Pd than species with higher WNS survival rates. Although it appears that some species of bats in North America may be developing resistance to WNS, an antibody-mediated immune response does not provide an explanation for these remnant populations

The 129-iodine content of subtropical Pacific waters : impact of Fukushima and other anthropogenic 129-iodine sources

© The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Biogeosciences 11 (2014): 4839-4852, doi:10.5194/bg-11-4839-2014.Results obtained from a dedicated radiochemistry cruise approximately 100 days after the 11 March 2011 Tohoku earthquake and subsequent disaster at the Fukushima Daiichi Nuclear Power Plant show that Fukushima derived radionuclides in the nearby ocean environment had penetrated, on average, to ≤250 m depth (1026.5 kg m3 potential density surface). The excess inventory of Fukushima-derived 129I in the region (∼150 000 km2) sampled during the cruise is estimated to have been between 0.89 and 1.173 billion Bq (∼136 to ∼179 grams) of 129I. Based on a tight tracer–tracer relation with 134Cs (or 137Cs) and estimates that most of the excess cesium is due to direct discharge, we infer that much of the excess 129I is from direct (non-atmospheric deposition) discharge. After taking into account oceanic transport, we estimate the direct discharge, i.e., that directly released into the ocean, off Fukushima to have been ∼1 kg 129I. Although this small pulse is dwarfed by the ~90 kg of weapons-testing-derived 129I that was released into the environment in the late 1950s and early 1960s, it should be possible to use Fukushima-derived 129I and other radionuclides (e.g., 134, 137Cs) to study transport and entrainment processes along and across the Kuroshio Current.This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344

Genome-wide association study of receptive language ability of 12 year olds

Purpose: We have previously shown that individual differences in measures of receptive language ability at age 12 are highly heritable. The current study attempted to identify some of the genes responsible for the heritability of receptive language ability using a genome-wide association (GWA) approach. Method: We administered four internet-based measures of receptive language (vocabulary, semantics, syntax, and pragmatics) to a sample of 2329 12-year-olds for whom DNA and genome-wide genotyping were available. Nearly 700,000 single-nucleotide polymorphisms (SNPs) and one million imputed SNPs were included in a GWA analysis of receptive language composite scores. Results: No SNP associations met the demanding criterion of genome-wide significance that corrects for multiple testing across the genome (p < 5 ×10-8). The strongest SNP association did not replicate in an additional sample of 2639 12-year-olds. Conclusion: These results indicate that individual differences in receptive language ability in the general population do not reflect common genetic variants that account for >3% of the phenotypic variance. The search for genetic variants associated with language skill will require larger samples and additional methods to identify and functionally characterize the full spectrum of risk variants

Approach to the patient : pharmacological management of trans and gender-diverse adolescents

Internationally, increasing numbers of children and adolescents with gender dysphoria are presenting for care. In response, gender-affirming therapeutic interventions that seek to align bodily characteristics with an individual's gender identity are more commonly being used. Depending on a young person's circumstances and goals, hormonal interventions may aim to achieve full pubertal suppression, modulation of endogenous pubertal sex hormone effects, and/or development of secondary sex characteristics congruent with their affirmed gender. This is a relatively novel therapeutic area and, although short-term outcomes are encouraging, longer term data from prospective longitudinal adolescent cohorts are still lacking, which may create clinical and ethical decision-making challenges. Here, we review current treatment options, reported outcomes, and clinical challenges in the pharmacological management of trans and gender-diverse adolescents

A new reference genome assembly for the microcrustacean Daphnia pulex

Comparing genomes of closely related genotypes from populations with distinct demographic histories can help reveal the impact of effective population size on genome evolution. For this purpose, we present a high quality genome assembly of Daphnia pulex (PA42), and compare this with the first sequenced genome of this species (TCO), which was derived from an isolate from a population with >90% reduction in nucleotide diversity. PA42 has numerous similarities to TCO at the gene level, with an average amino acid sequence identity of 98.8 and >60% of orthologous proteins identical. Nonetheless, there is a highly elevated number of genes in the TCO genome annotation, with similar to 7000 excess genes appearing to be false positives. This view is supported by the high GC content, lack of introns, and short length of these suspicious gene annotations. Consistent with the view that reduced effective population size can facilitate the accumulation of slightly deleterious genomic features, we observe more proliferation of transposable elements (TEs) and a higher frequency of gained introns in the TCO genome

Influence of ractopamine supplementation on Salmonella in feeder pigs

The objective of the current study was to determine the effect of ractopamine supplementation on gut populations and fecal shedding of Salmonella in growing pigs