COVID-19-Associated Cerebellitis: A Case Report and Rehabilitation Outcome.

INTRODUCTION: The COVID-19 pandemic has brought attention to neurological complications, including cerebellitis, characterized by inflammation of the cerebellum. Despite its rare occurrence, cerebellitis has been associated with COVID-19 infection, albeit the pathogenic mechanisms remain unclear. CASE REPORT: We present the case of a 22-year-old male with acute onset ataxia and dysarthria during a SARS-CoV-2 infection. Diagnostic evaluations ruled out other causes, confirming cerebellitis. Treatment included steroid therapy, vitamin supplementation, physiotherapy, and intravenous immunoglobulins. Rehabilitation focused on enhancing balance, coordination, and daily activities. The patient showed significant improvement in functional abilities, with increased autonomy in daily activities and improved ambulation. Despite persistent mild symptoms, the multidisciplinary rehabilitation approach led to remarkable progress. CONCLUSIONS: This case underscores the importance of recognizing and managing neurological complications, such as cerebellitis, in COVID-19 patients. A comprehensive approach combining medical treatment and rehabilitation is essential for optimizing outcomes. Further research is needed to elucidate the pathogenesis and optimal management strategies for such complications.

Effects of MLS Laser on pain, function, and disability in chronic non-specific low back pain: A double-blind placebo randomized-controlled trial.

BACKGROUND: Among non-pharmacological interventions, Multiwave Locked System (MLS) Laser therapy has been used in patients with several musculoskeletal pathologies and in combination with other therapeutical interventions. The effects of sole MLS therapy on pain and function in patients with chronic non-specific low-back pain are unknown. OBJECTIVE: The objective of this study was to investigate the effects of MLS Laser therapy on pain, function, and disability in patients with chronic non-specific low back pain in comparison to a placebo treatment group. METHODS: Forty-five patients were randomized into two groups: the MLS Laser group and the Sham Laser group, undergoing 8 sessions of either a MLS Laser therapy or a Sham Laser therapy, respectively. At the beginning of the therapy (T0), at the end of the therapy (T1), and 1 month after the end of therapy (T2) patients were assessed for low back pain (by means of a VAS scale), function (by means of kinematic and electromyographic assessment of a forward bending movement) and self-reported disability (by means of the Roland-Morris and Oswestry Disability questionnaires). RESULTS: There was a significant reduction of pain and disability in both groups at T1 and T2 in comparison with T0. At T2 patients in the MLS group showed a significantly lower pain in comparison with patients in the Sham group (VAS = 2.2 ± 2 vs. 3.6 ± 2.4; p< 0.05). No differences between the two groups were found for function and disability. CONCLUSION: Both MLS Laser and Sham Laser therapies lead to a significant and comparable reduction in pain and disability in patients with chronic non-specific low back pain. However, one month after treatment, MLS Laser therapy has been found to be significantly more effective in reducing pain as compared to sham treatment.

Is mirror therapy associated with progressive muscle relaxation more effective than mirror therapy alone in reducing phantom limb pain in patients with lower limb amputation?

Mirror therapy is a widely used treatment for phantom limb pain (PLP) relief in patients with limb loss. Less common is progressive muscle relaxation (PMR), used mostly in other medical conditions (psychological, terminal cancer pain, etc). The purpose of this study is to evaluate the efficacy of a mirror therapy preceded by PMR intervention compared to mirror therapy preceded by unguided generic relaxation-mirror therapy in patients with lower limb amputation suffering from PLP. This pilot study was a single-blind, controlled, randomized trial. Thirty lower limb amputees suffering from PLP were recruited and randomly assigned to three groups respectively undergoing a PMR-mirror therapy rehabilitative intervention, generic relaxation-mirror therapy, and conventional physiotherapy (ConvPT). Selected items from Prosthesis Evaluation Questionnaire (PEQ) and the Brief Pain Inventory (BPI) were used to test the pain features at the beginning and 1 week after 3 weeks of intervention. A decrease of about 65% was found in the rate and duration of PLP at the PEQ in PMR-mirror therapy with respect to generic relaxation-mirror therapy (about 30%) and ConvPT (about 6%). A decrease of about 90% in intensity (worst and average) of PLP in PMR-mirror therapy when compared to generic relaxation-mirror therapy (about 45%) and ConvPT (about 20%) was found at the BPI. We preliminary concluded, albeit with limitations due to the small sample of patients, that mirror therapy can improve PLP when associated with PMR. Further studies are required to confirm that PMR could be an effective technique for more successful PLP management.

Point Mutations at a Key Site Alter the Cytochrome P450 OleP Structural Dynamics.

Substrate binding to the cytochrome P450 OleP is coupled to a large open-to-closed transition that remodels the active site, minimizing its exposure to the external solvent. When the aglycone substrate binds, a small empty cavity is formed between the I and G helices, the BC loop, and the substrate itself, where solvent molecules accumulate mediating substrate-enzyme interactions. Herein, we analyzed the role of this cavity in substrate binding to OleP by producing three mutants (E89Y, G92W, and S240Y) to decrease its volume. The crystal structures of the OleP mutants in the closed state bound to the aglycone 6DEB showed that G92W and S240Y occupied the cavity, providing additional contact points with the substrate. Conversely, mutation E89Y induces a flipped-out conformation of this amino acid side chain, that points towards the bulk, increasing the empty volume. Equilibrium titrations and molecular dynamic simulations indicate that the presence of a bulky residue within the cavity impacts the binding properties of the enzyme, perturbing the conformational space explored by the complexes. Our data highlight the relevance of this region in OleP substrate binding and suggest that it represents a key substrate-protein contact site to consider in the perspective of redirecting its activity towards alternative compounds.

Dissecting the Cytochrome P450 OleP Substrate Specificity: Evidence for a Preferential Substrate.

The cytochrome P450 OleP catalyzes the epoxidation of aliphatic carbons on both the aglycone 8.8a-deoxyoleandolide (DEO) and the monoglycosylated L-olivosyl-8.8a-deoxyoleandolide (L-O-DEO) intermediates of oleandomycin biosynthesis. We investigated the substrate versatility of the enzyme. X-ray and equilibrium binding data show that the aglycone DEO loosely fits the OleP active site, triggering the closure that prepares it for catalysis only on a minor population of enzyme. The open-to-closed state transition allows solvent molecules to accumulate in a cavity that forms upon closure, mediating protein-substrate interactions. In silico docking of the monoglycosylated L-O-DEO in the closed OleP-DEO structure shows that the L-olivosyl moiety can be hosted in the same cavity, replacing solvent molecules and directly contacting structural elements involved in the transition. X-ray structures of aglycone-bound OleP in the presence of L-rhamnose confirm the cavity as a potential site for sugar binding. All considered, we propose L-O-DEO as the optimal substrate of OleP, the L-olivosyl moiety possibly representing the molecular wedge that triggers a more efficient structural response upon substrate binding, favoring and stabilizing the enzyme closure before catalysis. OleP substrate versatility is supported by structural solvent molecules that compensate for the absence of a glycosyl unit when the aglycone is bound.