A New Smartphone-Based Cognitive Screening Battery for Multiple Sclerosis (icognition): Validation Study.

Background: Cognitive deterioration is common in multiple sclerosis (MS) and requires regular follow-up. Currently, cognitive status is measured in clinical practice using paper-and-pencil tests, which are both time-consuming and costly. Remote monitoring of cognitive status could offer a solution because previous studies on telemedicine tools have proved its feasibility and acceptance among people with MS.

Synthesis and functional screening of novel inhibitors targeting the HDAC6 zinc finger ubiquitin-binding domain.

Histone deacetylase 6 (HDAC6) is a promising target for treating neurodegenerative disorders, several cancer types and viral infections. Unique among HDACs, the HDAC6 isoform possesses a zinc finger ubiquitin-binding domain (UBD) crucial for managing misfolded protein aggregates and facilitating viral infection. HDAC6 binds aggregated polyubiquitinated proteins through its UBD, mediating their transport to the aggresome and subsequent removal via autophagy.

Disrupted working memory event-related network dynamics in multiple sclerosis.

In multiple sclerosis (MS), working memory (WM) impairment can occur soon after disease onset and significantly affects the patient's quality of life. Functional imaging research in MS aims to investigate the neurophysiological underpinnings of WM impairment. In this context, we utilize a data-driven technique, the time delay embedded-hidden Markov model, to extract spectrally defined functional networks in magnetoencephalographic (MEG) data acquired during a WM visual-verbal n-back task.

Utility of icobrain for brain volumetry in multiple sclerosis clinical practice.

Background: Few studies on multiple sclerosis (MS) have explored the variability of percentage brain volume change (PBVC) measurements obtained from different clinical MRIs. In a retrospective multicentre cohort study, we quantified the variability of annualised PBVC in clinical MRIs.

Methods: Clinical MRIs of relapse-onset MS patients were assessed by icobrain.

Repurposing of monocyclic β-lactams as anti-inflammatory agents - The case of new ferrocene-azetidin-2-one hybrids.

There is growing interest in developing monotherapy drugs that treat inflammation caused by microbial infections, focusing on dual antimicrobial and anti-inflammatory agents with minimal side effects and high safety margins. This study synthesized and characterized a library of novel cis-4-ferrocenylazetidin-2-ones, evaluating their antimicrobial and anti-inflammatory activities. These organometallic monocyclic β-lactams showed moderate in vitro antimicrobial activity against various standard microbial strains, including yeasts and Gram-negative and Gram-positive bacteria.

Stimulus-related modulation in the 1/f spectral slope suggests an impaired inhibition during a working memory task in people with multiple sclerosis.

Background: An imbalance of excitatory and inhibitory synaptic transmission in multiple sclerosis (MS) may lead to cognitive impairment, such as impaired working memory. The 1/f slope of electroencephalography/magnetoencephalography (EEG/MEG) power spectra is shown to be a non-invasive proxy of excitation/inhibition balance. A flatter slope is associated with higher excitation/lower inhibition.

A metformin add-on clinical study in multiple sclerosis to evaluate brain remyelination and neurodegeneration (MACSiMiSE-BRAIN): study protocol for a multi-center randomized placebo controlled clinical trial.

Introduction: Despite advances in immunomodulatory treatments of multiple sclerosis (MS), patients with non-active progressive multiple sclerosis (PMS) continue to face a significant unmet need. Demyelination, smoldering inflammation and neurodegeneration are important drivers of disability progression that are insufficiently targeted by current treatment approaches. Promising preclinical data support repurposing of metformin for treatment of PMS.

Clinical effectiveness of coronavirus disease 2019 vaccination in patients with multiple sclerosis stratified by disease-modifying treatment.

Background And Purpose: Coronavirus disease 2019 (COVID-19) vaccination has been associated with a dampened humoral and/or cellular immune response in patients with multiple sclerosis (MS) who were concurrently on disease-modifying treatment (DMT) with B-cell depleting agents or sphingosine-1-phosphate receptor modulators (S1PRMs). Our main goal was to investigate the impact of these DMT classes on the clinical effectiveness of COVID-19 vaccination.

Methods: Since March 2020, demographics and clinical data of patients with MS who developed COVID-19 have been collected at the Belgian National MS Centre in Melsbroek.

High-yield synthesis of 2-O-α-D-glucosyl-D-glycerate by a bifunctional glycoside phosphorylase.

Osmolytes are produced by various microorganisms as a defense mechanism to protect cells and macromolecules from damage caused by external stresses in harsh environments. Due to their useful stabilizing properties, these molecules are applied as active ingredients in a wide range of cosmetics and healthcare products. The metabolic pathways and biocatalytic syntheses of glycosidic osmolytes such as 2-O-α-D-glucosyl-D-glycerate often involve the action of a glycoside phosphorylase.

The Finger Dexterity Test: Validation study of a smartphone-based manual dexterity assessment.

Background: The Nine-Hole Peg Test (9HPT) is the golden standard to measure manual dexterity in people with multiple sclerosis (MS). However, administration requires trained personnel and dedicated time during a clinical visit.

Objectives: The objective of this study is to validate a smartphone-based test for remote manual dexterity assessment, the ico Finger Dexterity Test (FDT), to be included into the ico application.

Engineering Comamonas testosteroni for the production of 2-pyrone-4,6-dicarboxylic acid as a promising building block.

Background: Plastics are an indispensable part of our daily life. However, mismanagement at their end-of-life results in severe environmental consequences. The microbial conversion of these polymers into new value-added products offers a promising alternative.

Autosomal dominant in cis D4Z4 repeat array duplication alleles in facioscapulohumeral dystrophy.

Facioscapulohumeral dystrophy (FSHD) has a unique genetic aetiology resulting in partial chromatin relaxation of the D4Z4 macrosatellite repeat array on 4qter. This D4Z4 chromatin relaxation facilitates inappropriate expression of the transcription factor DUX4 in skeletal muscle. DUX4 is encoded by a retrogene that is embedded within the distal region of the D4Z4 repeat array.

The spectral slope as a marker of excitation/inhibition ratio and cognitive functioning in multiple sclerosis.

Multiple sclerosis (MS) is a neurodegenerative disease characterized by neuronal and synaptic loss, resulting in an imbalance of excitatory and inhibitory synaptic transmission and potentially cognitive impairment. Current methods for measuring the excitation/inhibition (E/I) ratio are mostly invasive, but recent research combining neurocomputational modeling with measurements of local field potentials has indicated that the slope with which the power spectrum of neuronal activity captured by electro- and/or magnetoencephalography rolls off, is a non-invasive biomarker of the E/I ratio. A steeper roll-off is associated with a stronger inhibition.

Reduced alpha2 power is associated with slowed information processing speed in multiple sclerosis.

Objective: Cognitive impairment is common in multiple sclerosis (MS), significantly impacts daily functioning, is time-consuming to assess, and is prone to practice effects. We examined whether the alpha band power measured with magnetoencephalography (MEG) is associated with the different cognitive domains affected by MS.

Methods: Sixty-eight MS patients and 47 healthy controls underwent MEG, T1- and FLAIR-weighted magnetic resonance imaging (MRI), and neuropsychological testing.

The Zinc-Binding Group Effect: Lessons from Non-Hydroxamic Acid Vorinostat Analogs.

Histone deacetylases (HDACs) are enzymes pursued as drug targets in various cancers and several non-oncological conditions, such as inflammation and neurodegenerative disorders. In the past decade, HDAC inhibitors (HDACi) have emerged as relevant pharmaceuticals, with many efforts devoted to the development of new representatives. However, the growing safety concerns regarding the established hydroxamic acid-based HDAC inhibitors tend to drive current research more toward the design of inhibitors bearing alternative zinc-binding groups (ZBGs).

Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis.

Background: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear.

Objective: To determine whether early non-disabling relapses predict disability accumulation in RRMS.

Methods: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'.

Synthesis of the 1,5-Benzothiazepane Scaffold - Established Methods and New Developments.

The 1,5-benzothiazepane structure is an important heterocyclic moiety present in a variety of commercial drugs and pharmaceuticals. This privileged scaffold exhibits a diversity of biological activities, including antimicrobial, antibacterial, anti-epileptic, anti-HIV, antidepressant, antithrombotic and anticancer properties. Its important pharmacological potential renders research into the development of new and efficient synthetic methods of high relevance.

Gut microbiome composition is associated with long-term disability worsening in multiple sclerosis.

Predicting the long-term outcome of multiple sclerosis (MS) remains an important challenge to this day. As the gut microbiota is emerging as a potential player in MS, we investigated in this study whether gut microbial composition at baseline is related to long-term disability worsening in a longitudinal cohort of 111 MS patients. Fecal samples and extensive host metadata were collected at baseline and 3 months post-baseline, with additional repeated neurological measurements performed over (median) 4.

Football-specific extension of the IOC consensus statement: methods for recording and reporting of epidemiological data on injury and illness in sport 2020.

Several sports have published consensus statements on methods and reporting of epidemiological studies concerning injuries and illnesses with football (soccer) producing one of the first guidelines. This football-specific consensus statement was published in 2006 and required an update to align with scientific developments in the field. The International Olympic Committee (IOC) recently released a sports-generic consensus statement outlining methods for recording and reporting epidemiological data on injury and illness in sport and encouraged the development of sport-specific extensions.

Radial diffusivity reflects general decline rather than specific cognitive deterioration in multiple sclerosis.

Advanced structural brain imaging techniques, such as diffusion tensor imaging (DTI), have been used to study the relationship between DTI-parameters and cognitive scores in multiple sclerosis (MS). In this study, we assessed cognitive function in 61 individuals with MS and a control group of 35 healthy individuals with the Symbol Digit Modalities Test, the California Verbal Learning Test-II, the Brief Visuospatial Memory Test-Revised, the Controlled Oral Word Association Test, and Stroop-test. We also acquired diffusion-weighted images (b = 1000; 32 directions), which were processed to obtain the following DTI scalars: fractional anisotropy, mean, axial, and radial diffusivity.

Social determinants of health in multiple sclerosis.

Social determinants of health are the conditions in which people are born, grow, live, work and age. These circumstances are the non-medical factors that influence health outcomes. Evidence indicates that health behaviours, comorbidities and disease-modifying therapies all contribute to multiple sclerosis (MS) outcomes; however, our knowledge of the effects of social determinants - that is, the 'risks of risks' - on health has not yet changed our approach to MS.

Cognitive-motor telerehabilitation in multiple sclerosis (CoMoTeMS): study protocol for a randomised controlled trial.

Background: The management of cognitive impairment is an important goal in the treatment of multiple sclerosis (MS). While cognitive rehabilitation has been proven to be effective in improving cognitive performance in MS, research in the elderly indicates a higher effectiveness of combined cognitive-motor rehabilitation. Here, we present the protocol of a randomised controlled clinical trial to assess whether a combined cognitive-motor telerehabilitation programme is more effective in improving working memory than only cognitive or motor training.

Plasma glial fibrillary acidic protein and neurofilament light chain in relation to disability worsening in multiple sclerosis.

Background: Predicting disability worsening in multiple sclerosis (MS) remains an important challenge. Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) seem promising biomarkers. Studies investigating blood GFAP in relation to longitudinal outcome measures in MS are scarce.

Correlates of patient-reported cognitive performance with regard to disability.

The patient-reported form of the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) assesses perceived problems attributable to cognitive and neuropsychiatric symptoms. It is inconsistently related to objective cognitive performance in multiple sclerosis (MS), while strongly correlated with depression. We assessed whether the relationship between subjective and objective cognitive screening tools is moderated by disability.