No evidence for an association between alcohol consumption and Multiple Sclerosis risk: a UK Biobank study

Multiple Sclerosis (MS) has been linked to a variety of environmental risk factors, including smoking, Epstein-Barr Virus infection, and childhood obesity. There is some evidence to support a relationship between alcohol consumption and MS risk, but this finding has been inconsistent across cohorts. A protective link between alcohol consumption and MS risk is seen in Swedish and Danish cohorts, however evidence from other cohorts and mendelian randomisation studies have failed to support this relationship. We assessed the relationship between alcohol consumption (never vs. ever drinking) and MS in 409,228 individuals (2100 with MS) from UK Biobank (UKB). We used multivariable logistic regression models adjusted for age and sex. To determine whether there was evidence of statistical interaction between alcohol consumption and HLA-DRB1*15:01 genotype, we calculated interaction on the additive and multiplicative scales. We analysed data from 2100 individuals with MS (72.3% female, median age at recruitment 56) and 407,128 controls (53.9% female, median age at recruitment 58). We found no evidence for an association between alcohol consumption and MS risk (OR = 1.12, 95% CI 0.61–2.08, p = 0.314). As expected, the HLA-DRB1*15:01 allele was strongly associated with MS risk (OR = 2.72, 95% CI 2.72–2.72, p < 2 × 10(−16)). We found no evidence of statistical interaction between non-drinking and MS risk on either the multiplicative scale (p = 0.8) or on the additive scale (Attributable Proportion = 0.03, 95% CI − 0.43–0.29, P = 0.45). Empirical power calculations indicated reasonable statistical power (85%) to detect a protective effect of alcohol consumption of Relative Risk ≤ 0.7. We were thus unable to replicate findings from other cohorts within UK Biobank. The inconsistent association seen between studies may reflect limited statistical power to detect a weak effect, differences in population characteristics, or the lack of a true causal association

Plasma proteomic profiles of UK Biobank participants with multiple sclerosis.

OBJECTIVE: We aimed to describe plasma protein biomarkers of multiple sclerosis risk and to explore protein biomarkers of disease severity using radiological outcome measures. METHODS: Multiple sclerosis cases and controls were identified in UK Biobank, a longitudinal cohort study of ~500,000 British adults. Plasma proteins were assayed in ~50,000 UK Biobank participants using the Olink proximity extension assay. We performed case-control association testing to examine the association between 2911 proteins and multiple sclerosis, using linear models adjusted for confounding covariates. Associations with radiological lesion burden and brain volume were determined in a subset of the cohort with available magnetic resonance imaging, using normalized T2-hyperintensity volume or whole brain volume as the outcome measure. RESULTS: In total, 407 prevalent multiple sclerosis cases and 39,979 healthy controls were included. We discovered 72 proteins associated with multiple sclerosis at a Bonferroni-adjusted p value of 0.05, including established markers such as neurofilament light chain and glial fibrillary acidic protein. We observed a decrease in plasma Granzyme A, a marker of T cell and NK cell degranulation, which was specific to multiple sclerosis. Higher levels of plasma proteins involved in coagulation were associated with lower T2 lesion burden and preserved brain volume. INTERPRETATION: We report the largest plasma proteomic screen of multiple sclerosis, replicating important known associations and suggesting novel markers, such as the reduction in granzyme A. While these findings require external validation, they demonstrate the power of biobank-scale datasets for discovering new biomarkers for multiple sclerosis

Energy Starved Candidatus Pelagibacter Ubique Substitutes Light-Mediated ATP Production for Endogenous Carbon Respiration

Previous studies have demonstrated that Candidatus Pelagibacter ubique, a member of the SAR11 clade, constitutively expresses proteorhodopsin (PR) proteins that can function as light-dependent proton pumps. However, exposure to light did not significantly improve the growth rate or final cell densities of SAR11 isolates in a wide range of conditions. Thus, the ecophysiological role of PR in SAR11 remained unresolved. We investigated a range of cellular properties and here show that light causes dramatic changes in physiology and gene expression in Cand. P. ubique cells that are starved for carbon, but provides little or no advantage during active growth on organic carbon substrates. During logarithmic growth there was no difference in oxygen consumption by cells in light versus dark. Energy starved cells respired endogenous carbon in the dark, becoming spheres that approached the minimum predicted size for cells, and produced abundant pili. In the light, energy starved cells maintained size, ATP content, and higher substrate transport rates, and differentially expressed nearly 10% of their genome. These findings show that PR is a vital adaptation that supports Cand. P. ubique metabolism during carbon starvation, a condition that is likely to occur in the extreme conditions of ocean environments

Evaluation of the Effects of Sativex (THC BDS: CBD BDS) on Inhibition of Spasticity in a Chronic Relapsing Experimental Allergic Autoimmune Encephalomyelitis: A Model of Multiple Sclerosis.

This study investigated the antispasticity potential of Sativex in mice. Chronic relapsing experimental allergic encephalomyelitis was induced in adult ABH mice resulting in hind limb spasticity development. Vehicle, Sativex, and baclofen (as a positive control) were injected intravenously and the "stiffness" of limbs assessed by the resistance force against hind limb flexion. Vehicle alone caused no significant change in spasticity. Baclofen (5 mg/kg) induced approximately a 40% peak reduction in spasticity. Sativex dose dependently reduced spasticity; 5 mg/kg THC + 5 mg/kg CBD induced approximately a 20% peak reduction; 10 mg/kg THC + 10 mg/kg CBD produced approximately a 40% peak reduction in spasticity. Sativex has the potential to reduce spasticity in an experimental mouse model of multiple sclerosis (MS). Baclofen reduced spasticity and served as a positive control. Sativex (10 mg/kg) was just as effective as baclofen, providing supportive evidence for Sativex use in the treatment of spasticity in MS

Disposable MMP-9 sensor based on the degradation of peptide cross-linked hydrogel films using electrochemical impedance spectroscopy

Barts and The London Charity and Queen Mary Innovation Lt

Severe lymphopenia after subcutaneous cladribine in a patient with multiple sclerosis: To vaccinate or not?

Objective: To describe a fatal case of influenza A pneumonia in a patient with severe lymphopenia after receiving subcutaneous cladribine to treat her multiple sclerosis (MS). Methods: Case report. Results: A 53-year-old woman developed fatal influenza pneumonia associated with grade 4 lymphopenia two months after receiving a total dose of 60mg subcutaneous cladribine. Despite treatment with oseltamivir, her condition deteriorated and the patient passed away after developing respiratory failure. Conclusion: Cladribine-related lymphopenia is usually mild to moderate, however severe lymphopenia may occur. People with MS, especially those who are immunosuppressed, should be offered the inactivated influenza vaccine annually