T-cell mediated immune responses should be regulated to avoid the development of autoimmune or chronic inflammation diseases. Several mechanisms have been described to regulate this process, namely death of overactivated T cells by cytokine deprivation, suppression by T regulatory cells (Treg), induction of expression of immune checkpoint molecules such as CTLA-4 and PD-1, or activation-induced cell death (AICD). In addition, activated T cells release membrane microvesicles called exosomes during these regulatory processes. In this review, we revise the role of exosome secretion in the different pathways of immune regulation described to date and its importance in the prevention of autoinmune disease. Expression of membrane-bound death ligands on the surface of exosomes during AICD, or the more recently described transfer of miRNA or even DNA inside T-cell exosomes are molecular mechanisms that will be analyzed.

This paper assesses the behaviour of active distribution networks with high penetration of renewable energy sources when the control is performed in a centralised manner. The control assets are the on-load tap changers of transformers at the primary substation, the reactive power injections of the renewable energy sources and the active and reactive power exchanged between adjacent feeders when they are interconnected through a DC link. A scaled-down distribution network is used as testbed to emulate the behaviour of an active distribution system with massive penetration of renewable energy resources. The laboratory testbed involves hardware devices, real-time control, and communication infrastructure. Several key performance indices are adopted to assess the effects of the different control actions on the system operation. The experimental results demonstrate that the combination of control actions enables the optimal integration of a massive penetration of renewable energy.

Manual material handling tasks in industry cause work-related musculoskeletal disorders. Exoskeletons are being introduced to reduce the risk of musculoskeletal injuries. This study investigated the effect of using a passive lumbar exoskeleton in terms of moderate ergonomic risk. Eight participants were monitored by electromyogram (EMG) and motion capture (MoCap) while performing tasks with and without the lumbar exoskeleton. The results showed a significant reduction in the root mean square (VRMS) for all muscles tracked: erector spinae (8%), semitendinosus (14%), gluteus (5%), and quadriceps (10.2%). The classic fatigue parameters showed a significant reduction in the case of the semitendinosus: 1.7% zero-crossing rate, 0.9% mean frequency, and 1.12% median frequency. In addition, the logarithm of the normalized Dimitrov’s index showed reductions of 11.5, 8, and 14% in erector spinae, semitendinosus, and gluteus, respectively. The calculation of range of motion in the relevant joints demonstrated significant differences, but in almost all cases, the differences were smaller than 10. The findings of the study indicate that the passive exoskeleton reduces muscle activity and introduces a minor change of strategies for motion. Thus, EMG and MoCap appear to be appropriate measurements for designing an exoskeleton assessment procedure.

Cardiac resynchronization therapy (CRT) via biventricular pacing (BiVP-CRT) is considered a mainstay treatment for symptomatic heart failure patients with reduced ejection fraction and wide QRS. However, up to one third of patients receiving BiVP-CRT are considered non-responders to the therapy. Multiples strategies have been proposed to maximize the percentage of CRT responders including two new physiological pacing modalities that have emerged during the lasts years: His bundle pacing (HBP) and left bundle branch area pacing (LBBAP). Both pacing techniques aim at restoring the normal electrical activation of the ventricles through the native conduction system in opposition to the cell-to-cell activation of conventional right ventricular myocardial pacing. Conduction system pacing (CSP), including both HBP and LBBAP appears to be a promising pacing modality for delivering CRT and has proven to be safe and feasible in this particular setting. This article will review the current state of the art of CSP-based CRT, its limitations and future directions.

Objective: To assess the spectrum of PET-CT-related large vessel vasculitis (LVV) in a Spanish tertiary center and to determine whether FDG uptake by PET-CT differs between giant cell arteritis (GCA) with predominant cranial or extracranial phenotypes. Methods: The spectrum of patients diagnosed with LVV by PET-CT in a tertiary referral hospital that cares for 450,000 people over a period of two years was reviewed. Moreover, differences in FDG uptake between LVV-GCA with predominantly cranial and extracranial phenotype were analyzed. Results: Eighty patients were diagnosed with LVV by PET-CT. Most were due to systemic vasculitis (n=64; 80%), especially GCA (n=54; 67.5%). Other conditions included the presence of rheumatic diseases (n=4; 3.2%), tumors (n=9; 7.2%), and infections (n=3; 2.4%). LVV-GCA patients with predominant extracranial GCA phenotype were younger (mean ± SD: 68.07 ± 9.91 versus 75.46 ± 7.64 years; p= 0.017) and had a longer delay to the diagnosis (median [interquartile range] 12 [4-18] versus 4 [3-8]; p=0.006), but had PMR symptoms more frequently than those with predominantly cranial GCA phenotype (46.3% versus 15.4%, p= 0.057). When FDG uptake was compared according to the two different disease patterns, no statistically significant differences were observed. However, patients with extracranial LVV-GCA showed a non-significantly higher frequency of vasculitic involvement of lower extremity arteries. Conclusion: Regardless of the predominant phenotype, LVV identified by PET-CT is more commonly due to GCA in the Spanish population. In these GCA patients, younger age, PMR and a higher frequency of lower extremity artery vasculitis suggest the presence of LVV.

Objective: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are often overlapping conditions. We aimed to determine whether 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is useful in identifying PMR in the setting of large vessel vasculitis (LVV)-GCA. Methods: Patients diagnosed with LVV-GCA by PET-CT at a tertiary referral hospital for a population of 450,000 people over a two-year period were reviewed. Scoring was performed based on potential significant FDG uptake at up to 16 sites in nine different extravascular areas (SCORE 16). Differences in extravascular sites of significant FDG uptake were evaluated between LVV-GCA with a clinical diagnosis of PMR or not. Results: Fifty-four patients were diagnosed with LVV-GCA by 18F-FDG-PET-CT. Of them, 21 (38.8%) were clinically diagnosed with PMR. Significant extravascular FDG uptake was more frequently observed in those with a clinical diagnosis of PMR. In this sense, the SCORE 16 was higher in those with clinical PMR (5.10 ± 4.05 versus 1.73 ± 2.31 in those without a clinical diagnosis of PMR; p< 0.001). A SCORE 16 involving more than 4 sites of significant FDG uptake yielded a sensitivity of 52% and a specificity of 91% for establishing a clinical diagnosis of PMR associated with LVV-GCA. The best areas of significant FDG uptake to clinically identify PMR in patients with LVV were the shoulder, the greater trochanter and the lumbar interspinous regions with an area under the ROC curve of 0.810 (0.691-0.930). Conclusion: Significant extravascular 18F-FDG-PET-CT uptake may help establish a clinical diagnosis of PMR in patients with LVV-GCA. These patients are more commonly diagnosed with PMR if they have significant FDG uptake in the shoulder, greater trochanter, and lumbar interspinous areas.