Disease associations of excessive daytime sleepiness in multiple sclerosis: A prospective study

BackgroundExcessive daytime sleepiness (EDS) in multiple sclerosis (MS) can be a significant source of disability. Despite this, its prevalence as a patient-reported outcome in this condition has not been well established, and its causes are not well understood.MethodsWe prospectively assessed EDS as part of an observational study for patients referred for diagnostic neuro-ophthalmological testing. EDS was evaluated by the Epworth Sleepiness Scale (ESS), and visual data were also collected as part of a research protocol. Analysis with patient data was performed following the exclusion of patients with known primary sleep disorders.ResultsA total of 69 patients with MS were included in the analysis. The mean ESS was 6.5 with a SD of 4.3. ESS ≥ 10 was present in 23% of the cohort even in the presence of minimal mean neurological disability (Patient Determined Disease Steps (PDDS) = 1.5). The ESS score was not associated with age, sex, disease-related disability, retinal nerve fiber layer (RNFL), or optic neuritis (ON), but displayed an association with visual dysfunction.ConclusionsThere is an increased prevalence of EDS in MS. The increased values of the ESS are not explained by other sleep disorders, suggesting separate mechanisms. Further study of the underlying mechanisms is warranted

Detection and management of milk allergy:Delphi consensus study

Background: There is significant overdiagnosis of milk allergy in young children in some countries, leading to unnecessary use of specialized formula. This guidance, developed by experts without commercial ties to the formula industry, aims to reduce milk allergy overdiagnosis and support carers of children with suspected milk allergy.Methods: Delphi study involving two rounds of anonymous consensus building and an open meeting between January and July 2021. Seventeen experts in general practice, nutrition, midwifery, health visiting, lactation support and relevant areas of paediatrics participated, located in Europe, North America, Middle East, Africa, Australia and Asia. Five authors of previous milk allergy guidelines and seven parents provided feedback.Findings: Participants agreed on 38 essential recommendations through consensus. Recommendations highlighted the importance of reproducibility and specificity for diagnosing milk allergy in children with acute or delayed symptoms temporally related to milk protein ingestion; and distinguished between children directly consuming milk protein and exclusively breastfed infants. Consensus was reached that maternal dietary restriction is not usually necessary to manage milk allergy, and that for exclusively breastfed infants with chronic symptoms, milk allergy diagnosis should only be considered in specific, rare circumstances. Consensus was reached that milk allergy diagnosis does not need to be considered for stool changes, aversive feeding or occasional spots of blood in stool, if there is no temporal relationship with milk protein ingestion. When compared with previous guidelines, these consensus recommendations resulted in more restrictive criteria for detecting milk allergy and a more limited role for maternal dietary exclusions and specialized formula.Interpretation: These new milk allergy recommendations from non-conflicted, multidisciplinary experts advise narrower criteria, more prominent support for breastfeeding and less use of specialized formula, compared with current guidelines.</p

Modification and validation of the Bluebelle Wound Healing Questionnaire (WHQ) for assessing surgical site infection in wounds healing by secondary intention

Background: Surgical wounds healing by secondary intention are common. Healing is often complicated by surgical site infection (SSI). SSI assessment is important to guide treatment but existing methods generally require in-person assessment, making them resource intensive. A validated patient-reported SSI outcome measure may be useful to overcome this limitation.Aim: To modify and validate the Bluebelle Wound Healing Questionnaire (WHQ) for wounds healing by secondary intention.Methods: The 18-item Bluebelle WHQ developed for wounds healing by primary intention was modified to make it applicable to secondary healing wounds. Testing was performed as part of the SWHSI-2 randomised trial assessing negative pressure wound dressings versus standard care. Participants completed the WHQ at five timepoints; in-person (baseline, post-healing) and by post (3, 6, 12 months). A reference SSI assessment was performed by a research nurse at the time of wound healing. Acceptability and criterion validity (ability of the Bluebelle WHQ to discriminate between SSI/no SSI) were explored by examining questionnaire return rates, levels of missing data and total score sensitivity/specificity values (receiver operating characteristic curve (ROC)).Results: Baseline in-person questionnaire return rates were highest (672/686; 98 %), with postal return rates of 428/615 (68.5 %), 274/416 (65.9 %) and 186/296 (62.8 %) at follow up points. Overall, low levels of item-missing data were observed with few problems completing the questionnaire reported. Ability to discriminate between SSI/no SSI was good (Area under ROC = 0.796).Conclusion: The modified Bluebelle WHQ is a valuable tool for post-discharge assessment of wounds healing by secondary intention. It is recommended for use in research and clinical practice.</p

Structure and Stability of the Spinach Aquaporin SoPIP2;1 in Detergent Micelles and Lipid Membranes

Background: SoPIP2;1 constitutes one of the major integral proteins in spinach leaf plasma membranes and belongs to the aquaporin family. SoPIP2;1 is a highly permeable and selective water channel that has been successfully overexpressed and purified with high yields. In order to optimize reconstitution of the purified protein into biomimetic systems, we have here for the first time characterized the structural stability of SoPIP2;1. Methodology/Principal Finding: We have characterized the protein structural stability after purification and after reconstitution into detergent micelles and proteoliposomes using circular dichroism and fluorescence spectroscopy techniques. The structure of SoPIP2;1 was analyzed either with the protein solubilized with octyl-beta-D-glucopyranoside (OG) or reconstituted into lipid membranes formed by E. coli lipids, diphytanoylphosphatidylcholine (DPhPC), or reconstituted into lipid membranes formed from mixtures of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPE), 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE), 1-palmitoyl-2-oleoyl-phosphatidylserine (POPS), and ergosterol. Generally, SoPIP2;1 secondary structure was found to be predominantly a-helical in accordance with crystallographic data. The protein has a high thermal structural stability in detergent solutions, with an irreversible thermal unfolding occurring at a melting temperature of 58 degrees C. Incorporation of the protein into lipid membranes increases the structural stability as evidenced by an increased melting temperature of up to 70 degrees C. Conclusion/Significance: The results of this study provide insights into SoPIP2;1 stability in various host membranes and suggest suitable choices of detergent and lipid composition for reconstitution of SoPIP2;1 into biomimetic membranes for biotechnological applications

Tobacco use induces anti-apoptotic, proliferative patterns of gene expression in circulating leukocytes of Caucasian males

Abstract Background Strong epidemiologic evidence correlates tobacco use with a variety of serious adverse health effects, but the biological mechanisms that produce these effects remain elusive. Results We analyzed gene transcription data to identify expression spectra related to tobacco use in circulating leukocytes of 67 Caucasian male subjects. Levels of cotinine, a nicotine metabolite, were used as a surrogate marker for tobacco exposure. Significance Analysis of Microarray and Gene Set Analysis identified 109 genes in 16 gene sets whose transcription levels were differentially regulated by nicotine exposure. We subsequently analyzed this gene set by hyperclustering, a technique that allows the data to be clustered by both expression ratio and gene annotation (e.g. Gene Ontologies). Conclusion Our results demonstrate that tobacco use affects transcription of groups of genes that are involved in proliferation and apoptosis in circulating leukocytes. These transcriptional effects include a repertoire of transcriptional changes likely to increase the incidence of neoplasia through an altered expression of genes associated with transcription and signaling, interferon responses and repression of apoptotic pathways

A Metagenomic Approach to Characterization of the Vaginal Microbiome Signature in Pregnancy

While current major national research efforts (i.e., the NIH Human Microbiome Project) will enable comprehensive metagenomic characterization of the adult human microbiota, how and when these diverse microbial communities take up residence in the host and during reproductive life are unexplored at a population level. Because microbial abundance and diversity might differ in pregnancy, we sought to generate comparative metagenomic signatures across gestational age strata. DNA was isolated from the vagina (introitus, posterior fornix, midvagina) and the V5V3 region of bacterial 16S rRNA genes were sequenced (454FLX Titanium platform). Sixty-eight samples from 24 healthy gravidae (18 to 40 confirmed weeks) were compared with 301 non-pregnant controls (60 subjects). Generated sequence data were quality filtered, taxonomically binned, normalized, and organized by phylogeny and into operational taxonomic units (OTU); principal coordinates analysis (PCoA) of the resultant beta diversity measures were used for visualization and analysis in association with sample clinical metadata. Altogether, 1.4 gigabytes of data containing >2.5 million reads (averaging 6,837 sequences/sample of 493 nt in length) were generated for computational analyses. Although gravidae were not excluded by virtue of a posterior fornix pH >4.5 at the time of screening, unique vaginal microbiome signature encompassing several specific OTUs and higher-level clades was nevertheless observed and confirmed using a combination of phylogenetic, non-phylogenetic, supervised, and unsupervised approaches. Both overall diversity and richness were reduced in pregnancy, with dominance of Lactobacillus species (L. iners crispatus, jensenii and johnsonii, and the orders Lactobacillales (and Lactobacillaceae family), Clostridiales, Bacteroidales, and Actinomycetales. This intergroup comparison using rigorous standardized sampling protocols and analytical methodologies provides robust initial evidence that the vaginal microbial 16S rRNA gene catalogue uniquely differs in pregnancy, with variance of taxa across vaginal subsite and gestational age

A randomised controlled trial of compression therapies for the treatment of venous leg ulcers (VenUS 6) : study protocol for a pragmatic, multicentre, parallel group, three arm randomised controlled trial

Background Venous leg ulcer(s), are common, recurring, open wounds on the lower leg, resulting from diseased or damaged leg veins impairing blood flow. Wound healing is the primary treatment aim for venous leg ulceration, alongside management of pain, wound exudate and infection. Full (high) compression therapy delivering 40mmHg of pressure at the ankle is the recommended first line treatment for venous leg ulcers. There are several different forms of compression therapy available including wraps, two-layer hosiery, and two-layer or four-layer bandages. There is good evidence for the clinical and cost effectiveness of four-layer bandage and two-layer hosiery but more limited evidence for other treatments (two-layer bandage and compression wraps). Robust evidence is required to compare clinical and cost effectiveness of these and to investigate which is the best compression treatment for reducing time to healing of venous leg ulcers whilst offering value for money. VenUS 6 will therefore investigate the clinical and cost effectiveness of evidence-based compression, two-layer bandage and compression wraps for time to healing of venous leg ulcers. Methods VenUS 6 is a pragmatic, multi-centre, three arm, parallel group, randomised controlled trial. Adult patients with a venous leg ulcer will be randomised to receive 1) compression wraps, 2) two-layer bandage or 3) evidence-based compression (two-layer hosiery or four-layer bandage). Participants will followed up for between 4 and 12 months. The primary outcome will be time to healing (full epithelial cover in absence of a scab) in days since randomisation. Secondary outcomes will include key clinical events (e.g., healing of the reference leg; ulcer recurrence; ulcer/skin deterioration, amputation, admission/discharge, surgery to close/remove incompetent superficial veins, infection, or death), treatment changes, adherence and ease of use, ulcer related pain, health-related quality of life and resource use. Discussion VenUS 6 will provide robust evidence on the clinical and cost-effectiveness of the different forms of compression therapies for venous leg ulceration. VenUS 6 opened to recruitment in January 2021 and is currently recruiting across 30 participating centres. Clinical Trial Registry: ISRCTN 67321719 (https://doi.org/10.1186/ISRCTN67321719). Prospectively Registered: 14.09.202