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Background: The European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) investigates the natural history of Friedreich's ataxia. We aimed to assess progression characteristics and to identify patient groups with differential progression rates based on longitudinal 4-year data to inform upcoming clinical trials in Friedreich's ataxia. Methods: EFACTS is a prospective, observational cohort study based on an ongoing and open-ended registry. Patients with genetically confirmed Friedreich's ataxia were seen annually at 11 clinical centres in seven European countries (Austria, Belgium, France, Germany, Italy, Spain, and the UK). Data from baseline to 4-year follow-up were included in the current analysis. Our primary endpoints were the Scale for the Assessment and Rating of Ataxia (SARA) and the activities of daily living (ADL). Linear mixed-effect models were used to analyse annual disease progression for the entire cohort and subgroups defined by age of onset and ambulatory abilities. Power calculations were done for potential trial designs. This study is registered with ClinicalTrials.gov, NCT02069509. Findings: Between Sept 15, 2010, and Nov 20, 2018, of 914 individuals assessed for eligibility, 602 patients were included. Of these, 552 (92%) patients contributed data with at least one follow-up visit. Annual progression rate for SARA was 0·82 points (SE 0·05) in the overall cohort, and higher in patients who were ambulatory (1·12 [0·07]) than non-ambulatory (0·50 [0·07]). ADL worsened by 0·93 (SE 0·05) points per year in the entire cohort, with similar progression rates in patients who were ambulatory (0·94 [0·07]) and non-ambulatory (0·91 [0·08]). Although both SARA and ADL showed slightly greater worsening in patients with typical onset (symptom onset at ≤24 years) than those with late onset (symptom onset ≥25 years), differences in progression slopes were not significant. For a 2-year parallel-group trial, 230 (115 per group) patients would be r

We have established an easy synthetic protocol for selectively developing all-orthogonal BODIPY trimers with unprecedented geometries on the basis of selecting methyl oxidation versus electrophilic formylation of key dimeric precursors. Photophysical characterization together with biological assays unraveled the most suitable BODIPY-BODIPY geometrical arrangements within the trimer, forcing them to serve as molecular platforms for the development of new, advanced heavy-atom-free photosensitizers for photodynamic therapy and phototheragnosis.

River damming promotes profound changes in aquatic biodiversity, including the facilitation of biological invasions, with subsequent impacts on native communities. The Eurasian otter (Lutra lutra) is a generalist aquatic predator that often incorporates new prey types when they become available. We studied the short- and long-term effects of river damming on the trophic ecology of the otter across a riverine landscape gradient, from the flooded area to upstream tributaries, focusing on the largest artificial lake of Western Europe. Through the analysis of otter feces (spraints), we describe otter diet composition in 14 sites at different distances from the impounded area in three periods: (i) the pre-filling phase (i.e., lotic conditions); (ii) the immediate filling phase; and (iii) 16 years after the dam closure. The diet of the otter drastically shifted in the short term, from being dominated by native cyprinids to being mainly composed of invasive species of fish and crayfish. In the long term, the number of invasive species consumed by the otter continued to increase while native fish completely disappeared as prey near the reservoir. Presumably, the construction of the dam generated clear spatial gradients of abundances of native and invasive fish species. These patterns arose in the short term but became accentuated in the long term and were mirrored in otter diet composition. Our results demonstrate the potential of otter diet analyses as a surrogate for the impacts of human alterations on aquatic ecosystems, including those of river damming and the associated facilitation of biological invasions.

Muscle regeneration after a traumatic injury can take an excessively long period of time. The purpose of this study is to assess whether the action of percutaneous needle electrolysis (PNE) accelerates muscle regeneration in cases of partial muscle injuries. The gastrocnemius muscle from adult Swiss male mice was inoculated with bupivacaine. The PNE protocol was applied 48 h after treatment with bupivacaine. Immunofluorescence techniques were performed 72 h after treatment with bupivacaine to evaluate the synaptic contacts. The end plate noise was recorded by electromyography after treatment with bupivacaine. Bupivacaine induced a local injury in muscles, axons were retracted, and the endplate noise decreased at 72 h, while the endplate noise increased in the injured limb where PNE had been applied. Seven days later, the functional values were the same as the controls and they were maintained for 10 days. The endplate noise was significantly greater on the limb treated with the electric current when compared to the limb receiving only bupivacaine, indicating that the use of galvanic current facilitated muscle regeneration at least from a functional point of view. The application of PNE during muscle regeneration in an animal model reduces the recovery time of the damaged muscle tissue.