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Additional file 1: Figure S1. Selection diagram fortransportability analysis of the effects of stimulant use on initiation ofmedication for opioid use disorder (MOUD). Variables in gray text were notmeasured in one target population; those in gray boxes were not measured in anytarget population. Table S1. Inclusion andexclusion criteria, recruitment, screening and enrollment data for CTN clinicaltrials. Table S2. Inverse probabilityof selection weight models. Table S3.Distributions of inverse probability of selection weights and bias-variance tradeoffin weight trimming. Bias and precision of the stimulant use estimates arecomputed relative to untrimmed weights.

Polyhexamethylene biguanide (PHMB) is a broad-spectrum antiseptic which avoids many efficacy and toxicity problems associated with antimicrobials, in particular, it has a low risk of loss of susceptibility due to acquired antimicrobial resistance. Despite such advantages, PHMB is not widely used in wound care, suggesting more research is required to take full advantage of PHMB’s properties. We hypothesised that a nanofibre morphology would provide a gradual release of PHMB, prolonging the antimicrobial effects within the therapeutic window. PHMB:polyurethane (PU) electrospun nanofibre membranes were prepared with increasing PHMB concentrations, and the effects on antimicrobial activities, mechanical properties and host cell toxicity were compared. Overall, PHMB:PU membranes displayed a burst release of PHMB during the first hour following PBS immersion (50.5–95.9% of total released), followed by a gradual release over 120 h (≤25 wt % PHMB). The membranes were hydrophilic (83.7–53.3°), gradually gaining hydrophobicity as PHMB was released. They displayed superior antimicrobial activity, which extended past the initial release period, retained PU hyperelasticity regardless of PHMB concentration (collective tensile modulus of 5–35% PHMB:PU membranes, 3.56 ± 0.97 MPa; ultimate strain, >200%) and displayed minimal human cell toxicity (

BACKGROUND: A therapy that slows disease progression is the major unmet need in Parkinson's disease. METHODS: In this double-blind trial, we examined the possibility that rasagiline has disease-modifying effects in Parkinson's disease. A total of 1176 subjects with untreated Parkinson's disease were randomly assigned to receive rasagiline (at a dose of either 1 mg or 2 mg per day) for 72 weeks (the early-start group) or placebo for 36 weeks followed by rasagiline (at a dose of either 1 mg or 2 mg per day) for 36 weeks (the delayed-start group). To determine a positive result with either dose, the early-start treatment group had to meet each of three hierarchical end points of the primary analysis based on the Unified Parkinson's Disease Rating Scale (UPDRS, a 176-point scale, with higher numbers indicating more severe disease): superiority to placebo in the rate of change in the UPDRS score between weeks 12 and 36, superiority to delayed-start treatment in the change in the score between baseline and week 72, and noninferiority to delayed-start treatment in the rate of change in the score between weeks 48 and 72. RESULTS: Early-start treatment with rasagiline at a dose of 1 mg per day met all end points in the primary analysis: a smaller mean (+/-SE) increase (rate of worsening) in the UPDRS score between weeks 12 and 36 (0.09+/-0.02 points per week in the early-start group vs. 0.14+/-0.01 points per week in the placebo group, P=0.01), less worsening in the score between baseline and week 72 (2.82+/-0.53 points in the early-start group vs. 4.52+/-0.56 points in the delayed-start group, P=0.02), and noninferiority between the two groups with respect to the rate of change in the UPDRS score between weeks 48 and 72 (0.085+/-0.02 points per week in the early-start group vs. 0.085+/-0.02 points per week in the delayed-start group, P

In the Western world, peripheral vascular disease (PVD) has a high prevalence with high morbidity and mortality. In a large percentage of these patients, lower limb amputation is still required. Studies of ischaemic skeletal muscle disclosed evidence of endogenous angiogenesis and adaptive skeletal muscle metabolic changes in response to hypoxia. Chemokines are potent chemoattractant cytokines that regulate leukocyte trafficking in homeostatic and inflammatory processes. More than 50 different chemokines and 20 different chemokine receptors have been cloned. The chemokine stromal-cell-derived factor-1 (SDF-1 aka CXCL12) is a constitutively expressed and inducible chemokine that regulates multiple physiological processes, including embryonic development and organ homeostasis. The biologic effects of SDF-1 are mediated by chemokine receptor CXCR4, a 352 amino acid rhodopsin-like transmembrane-specific G protein-coupled receptor (GPCR). There is evidence that the administration of SDF-1 increases blood flow and perfusion via recruitment of endothelial progenitor cells (EPCs). This review will focus on the role of the SDF-1/CXCR4 system in the pathophysiology of PVD and discuss their potential as therapeutic targets for PVD.