Smoking Related Home Oxygen Burn Injuries: Continued Cause for Alarm

Background: Home oxygen therapy is a mainstay of treatment for patients with various cardiopulmonary diseases. In spite of warnings against smoking while using home oxygen, many patients sustain burn injuries. Objectives: We aimed to quantify the morbidity and mortality of such patients admitted to our regional burn unit over a 6-year period. Methods: A retrospective chart review of all patients admitted to a regional burn center from 2008 through 2013 was completed. Admitted patients sustaining burns secondary to smoking while using home oxygen therapy were selected as the study population to determine morbidity. Results: Fifty-five subjects were admitted to the burn unit for smoking-related home oxygen injuries. The age range was 40-84 years. Almost all subjects were on home oxygen for chronic obstructive pulmonary disease (96%). Seventy-two percent of burns involved <5% of the total body surface area, 51% of patients were intubated, and of those 33% had evidence of inhalation injury. The hospital mortality rate was 14.5%. The mean length of hospital stay was 8.6 days, and 54.5% were discharged to a nursing home or another advanced facility. Finally, concomitant substance abuse was found in 27%, and a previous history of injury from smoking while on home oxygen was discovered in 14.5%. Conclusions: This single-center analysis is one of the largest describing burn injuries stemming from smoking while using home oxygen therapy. We identified the morbidity and mortality associated with these injuries. Ongoing education and careful consideration of prescribing home oxygen therapy for known smokers is highly encouraged

The antimicrobial peptide cathelicidin drives development of experimental autoimmune encephalomyelitis in mice by affecting Th17 differentiation

Multiple sclerosis (MS) is a highly prevalent demyelinating autoimmune condition; the mechanisms regulating its severity and progression are unclear. The IL-17-producing Th17 subset of T cells has been widely implicated in MS and in the mouse model, experimental autoimmune encephalomyelitis (EAE). However, the differentiation and regulation of Th17 cells during EAE remain incompletely understood. Although evidence is mounting that the antimicrobial peptide cathelicidin profoundly affects early T cell differentiation, no studies have looked at its role in longer-term T cell responses. Now, we report that cathelicidin drives severe EAE disease. It is released from neutrophils, microglia, and endothelial cells throughout disease; its interaction with T cells potentiates Th17 differentiation in lymph nodes and Th17 to exTh17 plasticity and IFN-γ production in the spinal cord. As a consequence, mice lacking cathelicidin are protected from severe EAE. In addition, we show that cathelicidin is produced by the same cell types in the active brain lesions in human MS disease. We propose that cathelicidin exposure results in highly activated, cytokine-producing T cells, which drive autoimmunity; this is a mechanism through which neutrophils amplify inflammation in the central nervous system

The GAAS Metagenomic Tool and Its Estimations of Viral and Microbial Average Genome Size in Four Major Biomes

Metagenomic studies characterize both the composition and diversity of uncultured viral and microbial communities. BLAST-based comparisons have typically been used for such analyses; however, sampling biases, high percentages of unknown sequences, and the use of arbitrary thresholds to find significant similarities can decrease the accuracy and validity of estimates. Here, we present Genome relative Abundance and Average Size (GAAS), a complete software package that provides improved estimates of community composition and average genome length for metagenomes in both textual and graphical formats. GAAS implements a novel methodology to control for sampling bias via length normalization, to adjust for multiple BLAST similarities by similarity weighting, and to select significant similarities using relative alignment lengths. In benchmark tests, the GAAS method was robust to both high percentages of unknown sequences and to variations in metagenomic sequence read lengths. Re-analysis of the Sargasso Sea virome using GAAS indicated that standard methodologies for metagenomic analysis may dramatically underestimate the abundance and importance of organisms with small genomes in environmental systems. Using GAAS, we conducted a meta-analysis of microbial and viral average genome lengths in over 150 metagenomes from four biomes to determine whether genome lengths vary consistently between and within biomes, and between microbial and viral communities from the same environment. Significant differences between biomes and within aquatic sub-biomes (oceans, hypersaline systems, freshwater, and microbialites) suggested that average genome length is a fundamental property of environments driven by factors at the sub-biome level. The behavior of paired viral and microbial metagenomes from the same environment indicated that microbial and viral average genome sizes are independent of each other, but indicative of community responses to stressors and environmental conditions

[Avian cytogenetics goes functional] Third report on chicken genes and chromosomes 2015

High-density gridded libraries of large-insert clones using bacterial artificial chromosome (BAC) and other vectors are essential tools for genetic and genomic research in chicken and other avian species... Taken together, these studies demonstrate that applications of large-insert clones and BAC libraries derived from birds are, and will continue to be, effective tools to aid high-throughput and state-of-the-art genomic efforts and the important biological insight that arises from them

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Short- and long-term reproducibility of diffusion-weighted magnetic resonance imaging of lower extremity musculature in asymptomatic individuals and a comparison to individuals with spinal cord injury

Background: Diffusion-weighted magnetic resonance imaging (DW-MRI) of skeletal muscle has the potential to be a sensitive diagnostic and/or prognostic tool in complex, enigmatic neuromusculoskeletal conditions such as spinal cord injury and whiplash associated disorder. However, the reliability and reproducibility of clinically accessible DW-MRI parameters in skeletal muscle remains incompletely characterized - even in individuals without neuromusculoskeletal injury - and these parameters have yet to be characterized for many clinical populations. Here, we provide normative measures of the apparent diffusion coefficient (ADC) in healthy muscles of the lower limb; assess the rater-based reliability and short- and long-term reproducibility of the ADC in the same muscles; and quantify ADC of these muscles in individuals with motor incomplete spinal cord injury. Methods: Twenty individuals without neuromusculoskeletal injury and 14 individuals with motor incomplete spinal cord injury (SCI) participated in this investigation. We acquired bilateral diffusion-weighted MRI of the lower limb musculature in all participants at 3 T using a multi-shot echo-planar imaging sequence with b-values of 0, 100, 300 and 500 s/mm2 and diffusion-probing gradients applied in 3 orthogonal directions. Outcome measures included: (1) average ADC in the lateral and medial gastrocnemius, tibialis anterior, and soleus of individuals without neurological or musculoskeletal injury; (2) intra- and inter-rater reliability, as well as short and long-term reproducibility of the ADC; and (3) estimation of average muscle ADC in individuals with SCI. Results: Intra- and inter-rater reliability of the ADC averaged 0.89 and 0.79, respectively, across muscles. Least significant change, a measure of temporal reproducibility, was 4.50 and 11.98% for short (same day) and long (9-month) inter-scan intervals, respectively. Average ADC was significantly elevated across muscles in individuals with SCI compared to individuals without neurological or musculoskeletal injury (1.655 vs. 1.615 mm2/s, respectively). Conclusions: These findings provide a foundation for future studies that track longitudinal changes in skeletal muscle ADC of the lower extremity and/or investigate the mechanisms underlying ADC changes in cases of known or suspected pathology

Short- and long-term reproducibility of diffusion-weighted magnetic resonance imaging of lower extremity musculature in asymptomatic individuals and a comparison to individuals with spinal cord injury

Background: Diffusion-weighted magnetic resonance imaging (DW-MRI) of skeletal muscle has the potential to be a sensitive diagnostic and/or prognostic tool in complex, enigmatic neuromusculoskeletal conditions such as spinal cord injury and whiplash associated disorder. However, the reliability and reproducibility of clinically accessible DW-MRI parameters in skeletal muscle remains incompletely characterized - even in individuals without neuromusculoskeletal injury - and these parameters have yet to be characterized for many clinical populations. Here, we provide normative measures of the apparent diffusion coefficient (ADC) in healthy muscles of the lower limb; assess the rater-based reliability and short- and long-term reproducibility of the ADC in the same muscles; and quantify ADC of these muscles in individuals with motor incomplete spinal cord injury. Methods: Twenty individuals without neuromusculoskeletal injury and 14 individuals with motor incomplete spinal cord injury (SCI) participated in this investigation. We acquired bilateral diffusion-weighted MRI of the lower limb musculature in all participants at 3 T using a multi-shot echo-planar imaging sequence with b-values of 0, 100, 300 and 500 s/mm and diffusion-probing gradients applied in 3 orthogonal directions. Outcome measures included: (1) average ADC in the lateral and medial gastrocnemius, tibialis anterior, and soleus of individuals without neurological or musculoskeletal injury; (2) intra- and inter-rater reliability, as well as short and long-term reproducibility of the ADC; and (3) estimation of average muscle ADC in individuals with SCI. Results: Intra- and inter-rater reliability of the ADC averaged 0.89 and 0.79, respectively, across muscles. Least significant change, a measure of temporal reproducibility, was 4.50 and 11.98% for short (same day) and long (9-month) inter-scan intervals, respectively. Average ADC was significantly elevated across muscles in individuals with SCI compared to individuals without neurological or musculoskeletal injury (1.655 vs. 1.615 mm/s, respectively). Conclusions: These findings provide a foundation for future studies that track longitudinal changes in skeletal muscle ADC of the lower extremity and/or investigate the mechanisms underlying ADC changes in cases of known or suspected pathology