High-resolution whole-genome DNA methylation revealed unique signatures of painful diabetic neuropathy.

The aim of this work was to describe the DNA methylation signature and to identify genes associated with neuropathic pain in type 2 diabetes mellitus. We analyzed two independent diabetic neuropathy cohorts: PROPGER consisting of 72 painful and 67 painless patients recruited at the German Diabetes Center in Düsseldorf (DE), and PROPENG comprising 27 painful and 65 painless diabetic neuropathy patients recruited at the University of Manchester (UK). Genome-wide methylation data was generated using Illumina Infinium Methylation EPIC v1.

Education moderates the association between motor involvement and executive status in ALS.

Background: This study aimed to determine whether educational attainment-a common proxy of cognitive reserve (CR)-influences the association between motor and cognitive/behavioural outcomes in a large cohort of ALS patients without dementia.

Methods: N = 726 ALS patients without FTD were assessed for motor (ALSFRS-R), cognitive (Edinburgh Cognitive and Behavioural ALS Screen, ECAS) and behavioural outcomes (ECAS-Carer Interview, ECAS-CI). CR was operationalized via educational attainment (in years).

The Evolving Landscape of Small Fiber Neuropathy.

Small fiber neuropathy (SFN) belongs to a heterogeneous group of disorders in which thinly myelinated Aδ and unmyelinated C-fibers are primarily affected, leading to neuropathic pain and autonomic symptoms. SFN can be associated with systemic conditions such as diabetes, autoimmune diseases, exposure to drugs and toxins, and infection, with the list of associated diseases continuing to expand. Variants in the SCN9A, SCN10A, and SCN11A genes encoding Nav 1.

Safety, tolerability, and efficacy of subcutaneous efgartigimod in patients with chronic inflammatory demyelinating polyradiculoneuropathy (ADHERE): a multicentre, randomised-withdrawal, double-blind, placebo-controlled, phase 2 trial.

Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system that can lead to severe disability from muscle weakness and sensory disturbances. Around a third of patients do not respond to currently available treatments, and many patients with a partial response have residual neurological impairment, highlighting the need for effective alternatives. Efgartigimod alfa, a human IgG1 antibody Fc fragment, has demonstrated efficacy and safety in patients with generalised myasthenia gravis.

Prevalence and motor-functional correlates of frontotemporal-spectrum disorders in a large cohort of non-demented ALS patients.

Background: This study aimed at (1) delivering generalizable estimates of the prevalence of frontotemporal-spectrum disorders (FTSDs) in non-demented ALS patients and (2) exploring their motor-functional correlates.

Methods: N = 808 ALS patients without FTD were assessed for motor-functional outcomes-i.e.

Characteristics, Outcome and Prognostic Factors of Patients with Emergency Department Cardiac Arrest: A 14-Year Retrospective Study.

: Cardiac arrests are traditionally classified according to the setting in which they occur, including out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). However, cardiac arrests that occur in the emergency department (EDCA) could constitute a third category, due to the peculiar characteristics of the emergency department (ED). In recent years, the need to study EDCAs separately from other intra-hospital events has emerged.

Emotional awareness in patients with amyotrophic lateral sclerosis.

Introduction: It has been recently acknowledged that deficits in experiencing and processing one's own emotions, also termed alexithymia, may possibly feature the frontotemporal-spectrum disorders. This study aims to determine whether alexithymia could be included within the frontotemporal syndromes of amyotrophic lateral sclerosis (ALS).

Methods: Alexithymic traits were estimated in a cohort of 68 non-demented ALS patients with the 20-item Toronto Alexithymia Scale (TAS-20).

New clinical insight in amyotrophic lateral sclerosis and innovative clinical development from the non-profit repurposing trial of the old drug guanabenz.

Drug repurposing is considered a valid approach to accelerate therapeutic solutions for rare diseases. However, it is not as widely applied as it could be, due to several barriers that discourage both industry and academic institutions from pursuing this path. Herein we present the case of an academic multicentre study that considered the repurposing of the old drug guanabenz as a therapeutic strategy in amyotrophic lateral sclerosis.

YAP Ultralate Laser-Evoked Responses in Fibromyalgia: A Pilot Study in Patients with Small Fiber Pathology.

: The investigation of C-fiber-evoked ultralow-level responses (ULEPs) at somatic sites is difficult in clinical practice but may be useful in patients with small fiber neuropathy. Aim: The aim of the study was to investigate changes in LEPs and ULEPs in patients with fibromyalgia affected or not by abnormal intraepidermal innervation. : We recorded LEPs and ULEPs of the hand, thigh and foot in 13 FM patients with a normal skin biopsy (NFM), 13 patients with a reduced intraepidermal nerve fiber density (IENFD) (AFM) and 13 age-matched controls.

The COL6A5-p.Glu2272* mutation induces chronic itch in mice.

Pruritus is a common irritating sensation that provokes the desire to scratch. Environmental and genetic factors contribute to the onset of pruritus. Moreover, itch can become a major burden when it becomes chronic.

FM19G11-loaded nanoparticles modulate energetic status and production of reactive oxygen species in myoblasts from ALS mice.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. Considerable evidence indicates that early skeletal muscle atrophy plays a crucial role in the disease pathogenesis, leading to an altered muscle-motor neuron crosstalk that, in turn, may contribute to motor neuron degeneration. Currently, there is no effective treatment for ALS, highlighting the need to dig deeper into the pathological mechanisms for developing innovative therapeutic strategies.

Loneliness as neurobehavioral issue in amyotrophic lateral sclerosis.

Objective: In elderly people loneliness represents a risk factor for dementia and may negatively impact on mental and physical health. The specific contribute of loneliness to cognitive and behavioral functioning have not yet been determined in amyotrophic lateral sclerosis (ALS). Our hypothesis was that loneliness may be related to motor dysfunction with a negative impact on cognitive and behavioral decline, possibly related to specific cortical involvement.

A multicomponent physical activity home-based intervention for fibromyalgia patients: effects on clinical and skin biopsy features.

Objectives: Adapted physical activity (APA) has been recommended for fibromyalgia (FM) treatment as an essential component of a biopsychosocial therapeutic approach for patients. Previous studies report that aerobic and resistance training are the most effective programs in improving the quality of life and psycho-physical well-being. Patients with FM are frequently affected by an impairment of small fibers innervation, which is evident in the proximal somatic districts.

Clinical Presentation and Emergency Department Management Checkpoints of Acute Aortic Syndromes during the First Two Waves of the COVID-19 Pandemic.

The COVID-19 pandemic has deeply affected the activity and patient flows of Emergency Departments (EDs), and concern for the worsening outcome of cardiovascular emergencies has been raised. However, the impact of COVID-19 on all subtypes of acute aortic syndromes (AASs) has not been evaluated so far. Cases of AASs managed in the ED of three hub hospitals in a large area of Northern Italy were retrospectively analyzed, comparing those registered during the pandemic (March 2020 to May 2021) with corresponding pre-COVID-19 periods.

Advent of severe mitral regurgitation in surgical ventricular restoration and ventricular septal rupture repair.

Background: Per-procedural severe mitral regurgitation is a rare complication in concomitant surgical ventricular restoration and postinfarction ventricular septal rupture repair. It is challenging to discover the underlying etiology and adopt an appropriate strategy, in particular, in a high-risk patient.

Case Presentation: Semi-emergent surgical ventricular restoration combined with ventricular septal rupture closure and coronary artery bypassing was performed in a 67-year-old male patient.

Archival skin biopsy specimens as a tool for miRNA-based diagnosis: Technical and post-analytical considerations.

Archived specimens, taken by standardized procedures in clinical practice, represent a valuable resource in translational medicine. Their use in retrospective molecular-based studies could provide disease and therapy predictors. Microfluidic array is a user-friendly and cost-effective method allowing profiling of hundreds of microRNAs (miRNAs) from a low amount of RNA.

Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis.

In preclinical studies rapamycin was found to target neuroinflammation, by expanding regulatory T cells, and affecting autophagy, two pillars of amyotrophic lateral sclerosis (ALS) pathogenesis. Herein we report a multicenter, randomized, double-blind trial, in 63 ALS patients who were randomly assigned in a 1:1:1 ratio to receive rapamycin 2 mg/m/day,1 mg/m/day or placebo (EUDRACT 2016-002399-28; NCT03359538). The primary outcome, the number of patients exhibiting an increase >30% in regulatory T cells from baseline to treatment end, was not attained.

[Diagnostic atypique d'une myiase].

Muscoid larvae were observed on self-medicated dressing material loaded with purulent material taken from a 91-year-old hospital patient. These larvae were identified as However, no larvae were found in the patient's tissues. The observation of larvae on dressings should not automatically lead to a diagnosis of cutaneous myiasis.