We read with interest the study reported by COLLIN et al. [1], who carried out a survey on organisation and priorities of national tuberculosis (TB) programmes in Europe. With an estimated annual incidence of 10 million cases, TB is considered one of the three global infectious disease priorities, together with HIV/AIDS and malaria. However, TB incidence has significantly declined in the general European population during the past two decades, with a relative increase in vulnerable groups [2, 3]. Traditional TB control is focused on the rapid diagnosis and effective treatment of infectious cases, in order to break the transmission chain, and to cure individual patients. As TB mainly affects low income countries, little research has been conducted to determine whether medical interventions should be considered complete when a patient is "successfully treated" [4], or if potential sequelae should be investigated and pulmonary rehabilitation (PR) performed. Although mainly focused on chronic obstructive pulmonary disease (COPD), the American Thoracic Society (ATS)/European Respiratory Society (ERS) rehabilitation guidelines discuss the potential usefulness of PR in other respiratory diseases. TB is not mentioned, although recent evidence shows that obstructive and/or restrictive functional sequelae could occur, potentially affecting quality of life (QoL) [5, 6]. To date, no guidance on indications and procedures for TB sequelae is available [5]. We retrospectively investigated if patients with sequelae detected after anti-TB treatment had any benefits from PR in a low TB incidence setting. Patients with a history of pulmonary TB and successful treatment, admitted between 2004 and 2017 in the PR reference centre of Tradate, Italy, were selected for the study. The institutional ethical committee approved the study (2215 CE, June 19, 2018). Only patients with clinical stability and able to perform >80% of the training sessions with a physiotherapist, as well as 6-min walking test (6MWT) before and after PR, were selected. The following information was collected: 1) Clinical data (i.e. anthropometric data, medical history, comorbidities and concomitant medications); 2) Lung function tests based on ATS guidelines at admission and pre-discharge [7], using a body plethysmograph (Masterlab Body; Jaeger, Würzburg, Germany) and ERS predicted values [8]; 3) Diffusing capacity of the lung for carbon monoxide according to the ATS/ERS guidelines [9] (MasterScreen PFT System; Jaeger, VIASYS Healthcare, Hoechberg, Germany); 4) Arterial blood gases from radial artery (ABL 820 Radiometer Medical, Brønshøj, Denmark) in patients breathing room air in the sitting position for at least 20 min; 5) Overnight oximetry monitoring (Nonin Handheld 8500; Nonin, Tilburg, the Netherlands); 6) 6MWT; 7) Symptoms (Borg dyspnoea and fatigue scores before and after the 6MWT). Patients underwent a comprehensive 3-week PR programme including: specialist nurse training (inhalation techniques and/or oxygen-therapy when prescribed); 18 aerobic-training ses...

Amyotrophic lateral sclerosis (ALS) is a rare, progressive, neurodegenerative disorder caused by degeneration of upper and lower motor neurons. The disease process leads from lower motor neuron involvement to progressive muscle atrophy, weakness, fasciculations for the upper motor neuron involvement to spasticity. Muscle atrophy in ALS is caused by a dysregulation in the molecular network controlling fast and slow muscle fibres. Denervation and reinnervation processes in skeletal muscle occur in the course of ALS and are modulated by rehabilitation. MicroRNAs (miRNAs) are small non-coding RNAs that modulate a wide range of biological functions under various pathophysiological conditions. MiRNAs can be secreted by various cell types and they are markedly stable in body fluids. MiR-1, miR-133 a, miR-133b, and miR-206 are called “myomiRs” and are considered markers of myogenesis during muscle regeneration and neuromuscular junction stabilization or sprouting. We observed a positive effect of a standard aerobic exercise rehabilitative protocol conducted for six weeks in 18 ALS patients during hospitalization in our center. We correlated clinical scales with molecular data on myomiRs. After six weeks of moderate aerobic exercise, myomiRNAs were down-regulated, suggesting an active proliferation of satellite cells in muscle and increased neuromuscular junctions. Our data suggest that circulating miRNAs modulate during skeletal muscle recovery in response to physical rehabilitation in ALS.

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We investigated genetic and clinical features in two siblings with an unreported frameshift mutation in the GJB1 gene, encoding connexin 32, to study CMTX-1 and its intrafamilial phenotypic variability. Connexin 32 is a gap junction protein that is located in paranodal regions and Schmidt–Lanterman incisures. Clinical features, family history, and genetic and microRNA information were collected. Genetic analysis determination was performed on genomic DNA from the two cases. Muscle-specific miR-206 was also investigated in serum. A muscle biopsy was conducted in one case, and EMG with conduction velocities was performed in both patients. In the first genetic analysis, no duplication of the PMP22 gene was found. A second genetic analysis of a panel of genes associated with inherited peripheral neuropathies was performed. We found a frameshift mutation in the connexin 32 (GJB1) gene, c.281_287del in hemizygosity, not previously reported, that segregated with the clinical phenotype. An X-linked hereditary sensory motor neuropathy was caused by the mutation in the connexin 32 gene. We found overexpression of miR-206 that was 4-fold up-regulated in the older brother and over 10-fold in the younger brother versus the controls; this might be correlated with a different muscle mass and regeneration. The two siblings presented differently evolving neuropathies due to environmental factors and lifestyles that caused nerve degeneration. We hypothesized that in this X-linked CMT, there is no expression of a truncated connexin 32 (Cx32) protein, with loss of function markedly reduced in the gap junction. In the peripheral nervous system (PNS), this might be mitigated by the presence of another connexin, Cx43. Such a reduction might affect not only gap junction formation but also myelination and muscle trophism, resulting in variable miR-206 expressivity.

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