Vaccination adjuvated against hepatitis B in Spanish National Healthcare System (SNS) workers typed as non-responders to conventional vaccines.

TRIAL DESIGN: An interventional, phase 4, single group assignment, without masking (open label), preventive clinical trial was carried out in health workers with biological risk in their tasks, who have been filed as non-responders to conventional vaccination against Hepatitis B. METHODS: 67 health workers with biological risk in their tasks, who have been filed as non-responders to conventional vaccination against Hepatitis B, were enrolled in the Clinical Trial. All participants were from 18 years up to 64 years old. INCLUSION CRITERIA: NHS workers -including university students doing their internships in health centres dependent on the National Health System (inclusion of students is regulated and limited by specific instructions on labour prevention in each autonomous community)- classified as non-responders. The criteria defining them as non-responders to the conventional hepatitis B vaccine is anti HBsAb titers < 10 mUI/ml following the application of six doses of conventional vaccine at 20 µg doses (two complete guidelines). The objective of this study was to provide Health workers-staff with an additional protection tool against hepatitis B infection, and to evaluate the efficacy of the adjuvanted vaccine in healthy non-responders to conventional hepatitis B vaccine. The primary outcome was the measurement of antibody antiHBs before the first Fendrix® dose and a month after the administration of each dose. Other outcome was collection of adverse effects during administration and all those that could be related to the vaccine and that occur within 30 days after each dose. In this study, only one group was assigned. There was no randomization or masking. RESULTS: The participants were recruited between April 13, 2018 and October 31, 2019. 67 participants were enrolled in the Clinical Trial and included the analyses. The primary immunisation consists of 4 separate 0.5 ml doses of Fendrix®, administered at the following schedule: 1 month, 2 months and 6 months from the date of the first dose. Once the positivity was reached in any of the doses, the participant finished the study and was not given the following doses. 68.66% (46 out 67) had a positive response to first dose of Fendrix®. 57.14% (12 out 21) had a positive response to second dose of Fendrix®. 22.22% (2 out 9) had a positive response to third dose of Fendrix and 42.96% (3 out 7) had a positive response to last dose of Fendrix®. Overall, 94.02% (64 out 67) of participants had a positive response to Fendrix®. No serious adverse event occurred. CONCLUSIONS: The use of Fendrix®, is a viable vaccine alternative for NHS workers classified as "non-responders". Revaccination of healthy non-responders with Fendrix®, resulted in very high proportions of responders without adverse events. TRIAL REGISTRATION: The trial was registered in the Spanish National Trial Register (REEC), ClinicalTrials.gov and inclusion has been stopped (identifier NCT03410953; EudraCT-number 2016-004991-23). FUNDING: GRS 1360/A/16: Call for aid for the financing of research projects in biomedicine, health management and socio-health care to be developed in the centres of the Regional Health Management of Autonomous Community of Castile-Leon. In addition, this work has been supported by the Spanish Platform for Clinical Research and Clinical Trials, SCReN (Spanish Clinical Research Network), funded by the Subdirectorate General for Research Evaluation and Promotion of the Carlos III Health Institute (ISCIII), through the project PT13/0002/0039 and project PT17/0017/0023 integrated in the State Plan for R&D&I 2013-2016 and co-financed by and the European Regional Development Fund (ERDF).

Effects of 12-week inspiratory muscle training with low resistance in patients with multiple sclerosis: A non-randomised, double-blind, controlled trial.

BACKGROUND: Patients with multiple sclerosis (MS) have respiratory limitations like fatigue or muscle weakness. The aim of the study was to evaluate the effectiveness of a low-intensity protocol with inspiratory muscle training (IMT) to improve respiratory strength, spirometric parameters and dyspnea in patients with MS. METHODS: This study was a controlled, non-randomised, double-blind trial on 67 patients with MS distributed in 2 groups, intervention group (IG) (n = 36) and respiratory exercise group (REG) (n = 31). Over 12 weeks, 5 days/week, 15 min/day all subjects followed a respiratory training program. IG trained with IMT with low resistance (20% maximum inspiratory pressure (MIP) during the first two weeks, 30% MIP after the second week). REG followed a program involving nasal breathing and maximum exhalation. Main outcome measured was inspiratory strength (MIP); secondary outcomes were maximum expiratory pressure (MEP), spirometry, dyspnea and health-related quality of life. RESULTS: After respiratory training, the intervention group improved MIP, MEP, MVV, peak expiratory flow (PEF), tidal volume (TV) and dyspnea, 51%, 36%, 21%,11%, 51% and 19% respectively (p < .001, p < .001, p < .001, p < .05, p < .05, p < .05). The control group improved MIP, MEP, MVV and PEF, 24%, 27%, 28% and 12% respectively (p < .001, p < .001, p < .001, p < .05). Improvements achieved on MIP and dyspnea were significantly higher in IG patients (p=.002, p=.046, respectively). CONCLUSION: 12-week inspiratory muscle training with low resistance was more effective than conventional respiratory exercises to improve respiratory strength, spirometric parameters and dyspnea in patients with multiple sclerosis.

Transcriptomic landscape, gene signatures and regulatory profile of aging in the human brain.

The molecular characteristics of aging that lead to increased disease susceptibility remain poorly understood. Here we present a transcriptomic profile of the human brain associated with age and aging, derived from a systematic integrative analysis of four independent cohorts of genome-wide expression data from 2202 brain samples (cortex, hippocampus and cerebellum) of individuals of different ages (from young infants, 5-10 years old, to elderly people, up to 100 years old) categorized in age stages by decades. The study provides a signature of 1148 genes detected in cortex, 874 genes in hippocampus and 657 genes in cerebellum, that present significant differential expression changes with age according to a robust gamma rank correlation profiling. The signatures show a significant large overlap of 258 genes between cortex and hippocampus, and 63 common genes between the three brain regions. Focusing on cortex, functional enrichment analysis and cell-type analysis provided biological insight about the aging signature. Response to stress and immune response were up-regulated functions. Synapse, neurotransmission and calcium signaling were down-regulated functions. Cell analysis, derived from single-cell data, disclosed an increase of neuronal activity in the young stages of life and a decline of such activity in the old stages. A regulatory analysis identified the transcription factors (TF) associated with the signature of 258 genes, common to cortex and hippocampus; revealing the role of MEF2(A,D), PDX1, FOSL(1,2) and RFX(5,1) as candidate regulators of the signature. Finally, a deep-learning neural network algorithm was used to build a biological age predictor based on the aging signature. This article is part of a Special Issue entitled: Transcriptional Profiles and Regulatory Gene Networks edited by Dr. Federico Manuel Giorgi and Dr. Shaun Mahony.