The complexity of the pathogenesis of inflammatory bowel disease (ulcerative colitis and Crohn’s disease) has led to the quest of empirically drug therapies, combining immunosuppressant agents, biological therapy and modulators of the microbiota. Helminth parasites have been proposed as an alternative treatment of these diseases based on the hygiene hypothesis, but ethical and medical problems arise. Recent reports have proved the utility of parasite materials, mainly excretory/secretory products as therapeutic agents. The identification of extracellular vesicles on those secreted products opens a new field of investigation, since they exert potent immunomodulating effects. To assess the effect of extracellular vesicles produced by helminth parasites to treat ulcerative colitis, we have analyzed whether extracellular vesicles produced by the parasitic helminth Fasciola hepatica can prevent colitis induced by chemical agents in a mouse model. Adult parasites were cultured in vitro and secreted extracellular vesicles were purified and used for immunizing both wild type C57BL/6 and RAG1-/- mice. Control and immunized mice groups were treated with dextran sulfate sodium 7 days after last immunization to promote experimental colitis. The severity of colitis was assessed by disease activity index and histopathological scores. Mucosal cytokine expression was evaluated by ELISA. The activation of NF-kB, COX-2, and MAPK were evaluated by immunoblotting. Administration of extracellular vesicles from F. hepatica ameliorates the pathological symptoms reducing the amount of pro-inflammatory cytokines and interfering with both MAPK and NF-kB pathways. Interestingly, the observed effects do not seem to be mediated by T-cells. Our results indicate that extracellular vesicles from parasitic helminths can modulate immune responses in dextran sulfate sodium (DSS)-induced colitis, exerting a protective effect that should be mediated by other cells distinct from B- and T-lymphocytes.

the four-component, protein-based meningococcal serogroup B vaccine (4CMenB; Bexsero) became available for private purchase in Spain. METHODSWe conducted a nationwide matched case-control study to assess the effectiveness of 4CMenB in preventing invasive meningococcal disease in children. The study included all laboratory-confirmed cases of invasive meningococcal disease in children younger than 60 months of age between October 5, 2015, and October 6, 2019, in Spain. Each case patient was matched with four controls according to date of birth and province. 4CMenB vaccination status of the case patients and controls was compared with the use of multivariate conditional logistic regression. RESULTSWe compared 306 case patients (243 [79.4%] with serogroup B disease) with 1224 controls. A total of 35 case patients (11.4%) and 298 controls (24.3%) had received at least one dose of 4CMenB. The effectiveness of complete vaccination with 4CMenB (defined as receipt of at least 2 doses, administered in accordance with the manufacturer's recommendations) was 76% (95% confidence interval [CI], 57 to 87) against invasive meningococcal disease caused by any serogroup, and partial vaccination was 54% (95% CI, 18 to 74) effective. Complete vaccination resulted in an effectiveness of 71% (95% CI, 45 to 85) against meningococcal serogroup B disease. Vaccine effectiveness with at least one dose of 4CMenB was 64% (95% CI, 41 to 78) against serogroup B disease and 82% (95% CI, 21 to 96) against non-serogroup B disease. With the use of the genetic Meningococcal Antigen Typing System, serogroup B strains that were expected to be covered by 4CMenB were detected in 44 case patients, none of whom had been vaccinated. CONCLUSIONSComplete vaccination with 4CMenB was found to be effective in preventing invasive disease by serogroup B and non-serogroup B meningococci in children younger than 5 years of age.

Background: Osteoarthritis (OA) is the major cause of pain and disability in the elderly. Current treatments include rest, which could potentially harness the global health of these individuals. Aim: To test age, sex, number of comorbidities and levels of physical activity (PA) as determinants of functionality in a well stablished elderly population with hip OA. Methods: We analyzed 548 men and 1540 women with self-reported OA and hip pain over 60 years from SHARE. Sex and age groups were created 428 men 60-79 years old (20.5%) ; 1128 women 60-79 years old ( 54%); 120 men 80-100 ( 5.7%) years and 412 women 80-100 years ( 19.7%). PA was measured as moderate and vigorous (reference)or physically inactive . Five or more comorbidities were compared to one (reference) . Functionality measurement were handgrip strength (cutoffs were <27kg for men and <16kg for women); single chair five times ( limited when arms were used or across their chest) to stand up from a sitting position ; daily living activities (ADL) (dressing, including shoes and socks) and number of limitations on ADL. We built logistic regression models having functional measures as dependent variables and gender/age, number of comorbidities and levels of PA as response variables. In order to explore the determinants of the association we used stepwise analysis, including all significant variables in the univariate analysis. Results: Limited handgrip was associated with age in women 80-100 compared to women 60-79 OR (95%) 2.40 (1.74-3.32); to five or more comorbidities OR (95% CI) 3.08 ( 1.70-5.60) and to physical inactivity OR (95% CI) 2.08 (1 .53-2.82). Limited single chair was associated with age , women 80-100 OR (95% CI) 2.01 ( 1.55-2.61) compared to women 60-79; five or more comorbidities OR (95% CI) 2.52 ( 2.49-4.81); physical inactivity OR (95% CI) 5.93 ( 6.26-9.91). ADL limitation was associated with age in women 80-100y compared to women 60-79y OR (95% CI) 1.79 (1.38-2.32); five or more comorbidities OR (95% CI) 2.80 ( 1.91-4.09); and physical inactivity OR (95% CI) 4.69 ( 3.74-5.88). Limitations in dressing shoes or socks were associated with five or more comorbidities OR(95%) 2.49 (1.63-3.80); physical inactivity OR(95%) 4.22 (95% CI 3.34-5.32) . Limitation to get up from the chair was associated with five or more comorbidities OR(95%) 2.84 (2.06-3.92) and physical inactivity OR (95% CI) 2.49 1.95-3.16). All associations were independent from smoke, alcohol consumption BMI and previous illnesses. Conclusion: Functionality decreased significantly across age with a steep decline over 79 y for men and women with OA. The association with the number of comorbidities and levels of physical activity point to timely interventions aiming at global health in this population.