Significance: Cellular and molecular mediators driving multiple sclerosis (MS) pathology have been discovered to a great extent. However, the early molecular events leading to aberrant immune responses remain largely unknown. In this study, we combined bisulfite sequencing with transcriptome profiling to characterize the epigenetic landscape of four peripheral immune cell populations isolated from newly diagnosed, untreated MS patients and healthy individuals. We demonstrate widespread hypomethylation in CD19 ⁺ B cells at clinical disease onset. Notably, this epigenetic signature is functionally linked with the overactivation of B cells. Altogether, our results pinpoint the role of aberrant DNA methylation in connecting defects in the periphery with central nervous system autoimmunity and corroborate the key role of B cells in the initial stages of MS.

Background: the study of paraspinal muscles is pivotal for the diagnosis and staging of Amyotrophic Lateral Sclerosis (ALS), and is usually performed by electromyography. Objective: to evaluate the role of paraspinal muscle MRI as a diagnostic biomarker in ALS. Methods: we evaluated T1-w images of newly diagnosed ALS patients (n = 14), age-matched healthy controls (n = 11), patients affected by inflammatory myopathy (n = 10), and lumbar radiculopathy (n = 19), and compared them semiquantitatively by using the Mercuri Scale. Results: a significant difference in the appearance of the psoas muscle was observed between ALS patients and patients with radiculopathy (p = 0.003); after stratifying ALS patients into spinal and bulbar onsets, we found a significant difference in the appearance of the longissimus dorsi muscle between the spinal onset ALS subgroup and bulbar onset ALS subgroup (p = 0.0245), while no difference was found for multifidus (p = 0.1441), iliocostal (p = 0.0655), and psoas muscles (p = 0.0813) between the cohort subgroups. Conclusions: paraspinal T1-w MRI could help to distinguish spinal ALS patients from healthy and pathological controls. Specifically, the study of longissimus dorsi could play the role of a diagnostic ALS biomarker.

Objectives: More than a year has passed since the initial outbreak of SARS-CoV-2, which caused many hospitalizations worldwide due to COVID-19 pneumonia and its complications. However, there is still a lack of information detailing short- and long-term outcomes of previously hospitalized patients. The purpose of this study is to analyze the most frequent lung CT findings in recovered COVID-19 patients at mid-term follow-ups. Methods: A total of 407 consecutive COVID-19 patients who were admitted to the Fondazione IRCCS Policlinico San Matteo, Pavia and discharged between February 27, 2020, and June 26, 2020 were recruited into this study. Out of these patients, a subset of 108 patients who presented with residual asthenia and dyspnea at discharge, altered spirometric data, positive lung ultrasound and positive chest X-ray was subsequently selected, and was scheduled to undergo a mid-term chest CT study, which was evaluated for specific lung alterations and morphological patterns. Results: The most frequently observed lung CT alterations, in order of frequency, were ground-glass opacities (81%), linear opacities (74%), bronchiolectases (64.81%), and reticular opacities (63.88%). The most common morphological pattern was the non-specific interstitial pneumonia pattern (63.88%). Features consistent with pulmonary fibrosis were observed in 32 patients (29.62%). Conclusions: Our work showed that recovered COVID-19 patients who were hospitalized and who exhibited residual symptoms after discharge had a slow radiological recovery with persistent residual lung alterations. Advances in knowledge: This slow recovery process should be kept in mind when determining the follow-up phases in order to improve the long-term management of patients affected by COVID-19.