Is infertility more common among patients with multiple sclerosis? Implications for utilization of assisted reproductive techniques.

Research Question: Is fertility affected in women with multiple sclerosis (MS), and what is their usage of assisted reproductive technology (ART)?

Design: Data regarding multiple sclerosis and ART usage among patients with multiple sclerosis were extracted from the Israeli health maintenance organization Clalit Health Service database. Data regarding the diagnosis and treatment of multiple sclerosis, cause of infertility and use of fertility treatments were collected for all female multiple sclerosis patients aged 18-45 years between 2005 and 2021. Each patient was matched by age in a 1:10 ratio with reference women from the general population.

Personalized Intervention to Improve Medication Adherence for Persons with Multiple Sclerosis.

Purpose: To evaluate the acceptability, retention, and efficacy of face-to-face intervention, incorporating education and Motivational Interviewing (MI) to support persons with relapsing-remitting multiple sclerosis (PwRRMS) and increase self-reported medication adherence.

Patients And Methods: PwRRMS (N = 60) prescribed Disease Modifying Treatment (DMT), who were identified as non-adherent and consented to participate in an intervention, received verbal education and counseling from their treating physician, a tailored MI counseling and a booster session via telephone with a health psychologist, and a concluding MI counseling six months later. Each PwRRMS filled a battery of patient-reported outcomes (PROs) at baseline, six and 12 months later.

Familial vs sporadic multiple sclerosis in the Israeli population: Differences in ethnicity distribution and disease progression, with anticipation in successive generations.

Background: Multiple Sclerosis (MS) may cluster in families, an entity known as familial MS (FMS), possibly due to aggregation of genetic and environmental factors. Though previous studies have characterized FMS in different populations, no study to the best of our knowledge has yet characterized FMS in the unique Israeli population, which is comprised of relatively endogamous ethnicities. Our goal in this study was to compare demographic and clinical characteristics between FMS and sporadic MS (SMS), and to search for intra-familial patterns.

Multiple Sclerosis-Associated Gut Microbiome in the Israeli Diverse Populations: Associations with Ethnicity, Gender, Disability Status, Vitamin D Levels, and Mediterranean Diet.

Microbiome dysbiosis is increasingly being recognized as implicated in immune-mediated disorders including multiple sclerosis (MS). The microbiome is modulated by genetic and environmental factors including lifestyle, diet, and drug intake. This study aimed to characterize the MS-associated gut microbiome in the Israeli populations and to identify associations with demographic, dietary, and clinical features.

Using an Intervention Mapping Approach to Improve Adherence to Disease-Modifying Treatment in Multiple Sclerosis.

Background: Up to 50% of individuals with multiple sclerosis (MS) who are prescribed disease-modifying treatments (DMTs) do not take them as advised. Although many studies report on DMT adherence rate, few studies report on interventions involving individuals with MS. The current paper describes the development of an intervention aimed at improving adherence to DMTs among identified nonadherent individuals with MS.

Medication habits among persons with multiple sclerosis.

Background: Though habitual behavior is part of medication-taking behavior, studies of adherence to medication among persons with relapsing remitting multiple sclerosis (PwRRMS) have not prospectively examined habit in relation to disease-modifying treatments (DMTs).

Objectives: 1. Examine habit dimensions - repetition, lack of awareness, and lack of control - across time and route of administration (oral vs.

Humoral and Cellular Immune Responses to SARS-CoV-2 mRNA Vaccination in Patients with Multiple Sclerosis: An Israeli Multi-Center Experience Following 3 Vaccine Doses.

Background: Immunomodulatory/immunosuppressive activity of multiple sclerosis (MS) disease modifying therapies (DMTs) might affect immune responses to SARS-CoV-2 exposure or vaccination in patients with MS (PwMS). We evaluated the effect of DMTs on humoral and cell-mediated immune responses to 2 and 3 vaccinations and the longevity of SARS-Cov-2 IgG levels in PwMS.

Methods: 522 PwMS and 68 healthy controls vaccinated with BNT162b2-Pfizer mRNA vaccine against SARS-CoV-2, or recovering from COVID-19, were recruited in a nation-wide multi-center study.

Concordance Between Persons with Multiple Sclerosis and Treating Physician on Medication Effects and Health Status.

Background: As the number of treatment options for multiple sclerosis (MS) has expanded, alignment between physician and patient on effects of medication has emerged as important for medication persistence/discontinuation.

Objective: To evaluate physician-patient agreement levels on medication effect and health status.

Methods: Persons with MS (PwMS) (n=71) participated in a cross-sectional study collecting their satisfaction (using the Treatment Satisfaction Questionnaire for Medication), intention to dis/continue treatment and global health perception; physicians assessed response to medication and global health status.

Mobile-phone-based e-diary derived patient reported outcomes: Association with clinical disease activity, psychological status and quality of life of patients with multiple sclerosis.

Background: The applicability of mobile digital technology to promote clinical care of people with multiple sclerosis (pwMS) is gaining increased interest as part of the implementation of patient-centered approaches. We aimed at assessing adherence to a smartphone-based e-diary, which was designed to collect patient-reported outcomes (PROs). Secondary objectives were to evaluate the construct and predictive validity of e-diary derived PROs and to explore the various factors that were associated with changes in PROs over time.

Beliefs about medication as predictors of medication adherence in a prospective cohort study among persons with multiple sclerosis.

Background: Though adherence to disease-modifying therapies (DMTs) among persons with multiple sclerosis (PwMS) varies and is often below 80%, only few prospective studies on adherence examined predictors beyond demographic and clinical characteristics.

Objectives: Identify antecedents to adherence and persistence to DMT in a prospective design among PwMS.

Methods: PwMS (n = 186) were prospectively assessed at three time points: baseline, 6 (Time 1) and 12 months later (Time 2).

Mobile phone-based e-diary for assessment and enhancement of medications adherence among patients with multiple sclerosis.

Background: Adherence to multiple sclerosis (MS) disease-modifying drugs (DMDs) is essential for realization of their optimal effectiveness and benefits.

Objective: To evaluate the usefulness and validity of a smartphone-based e-diary as a tool for adherence assessment as well as its effectiveness as a promoter of adherence to DMDs.

Methods: An MS tailored e-diary (MyMS&Me) reminded patients to take their DMDs on time.

Dimethyl fumarate promotes B cell-mediated anti-inflammatory cytokine profile in B and T cells, and inhibits immune cell migration in patients with MS.

Dimethyl Fumarate (DMF), known for its mechanism of action targeting Nrf2 and related redox homeostasis, is an approved immunotherapy for patients with Multiple Sclerosis (PwMS) in the relapsing form. We assessed how DMF modulates immune cell functions, namely the cytokine profile of co-cultured B and T cells, and the chemokine-mediated migration of immune cells. Following DMF therapy, LTα, TNFα and IFNγ B cells were reduced while TGFβ and IL10 expression elevated.

Caring for patients with venomous Crotalinae snakebites.

Venomous snakebites are surprisingly common in the US. This article provides an overview of what to do when a patient has been bitten by a North American pit viper, a venomous subset of indigenous snakes.

Fingolimod reduces CXCR4-mediated B cell migration and induces regulatory B cells-mediated anti-inflammatory immune repertoire.

Background: Fingolimod, an oral therapy for patients with relapsing Multiple Sclerosis (MS), traps CC chemokine receptor type 7 (CCR7)-expresssing lymphocytes within lymphoid tissues in the periphery, thereby supposedly reducing the infiltration of pathogenic cells into the central nervous system. Additional immunomodulatory effects of Fingolimod, involving cell function, B and T cells interactions and cross-regulation, have scarcely been studied. The objective of this study was to assess how Fingolimod therapy affects B cells functions, namely cell migration, immunoglobullin production and T cell stimulation.

Dimethyl fumarate as a first- vs second-line therapy in MS: Focus on B cells.

Objective: To elucidate the immunomodulatory effects of dimethyl fumarate (DMF) on B cells in patients with relapsing MS receiving DMF as a "1st-line" vs "2nd-line" therapy.

Methods: B cells were isolated from 43 patients with MS at baseline and after 15-week DMF therapy. Phenotype and functional markers and cytokine profile were assessed by flow cytometry.

Methylome and transcriptome profiling in Myasthenia Gravis monozygotic twins.

Objective: To identify novel genetic and epigenetic factors associated with Myasthenia gravis (MG) using an identical twins experimental study design.

Methods: The transcriptome and methylome of peripheral monocytes were compared between monozygotic (MZ) twins discordant and concordant for MG, as well as with MG singletons and healthy controls, all females. Sets of differentially expressed genes and differentially methylated CpGs were validated using RT-PCR for expression and target bisulfite sequencing for methylation on additional samples.

Effector and regulatory B cells in Multiple Sclerosis.

The role of B cells in the pathogenesis of Multiple Sclerosis (MS), an autoimmune neurodegenerative disease, is becoming eminent in recent years, but the specific contribution of the distinct B cell subsets remains to be elucidated. Several B cell subsets have shown regulatory, anti-inflammatory capacities in response to stimuli in vitro, as well as in the animal model of MS: Experimental Autoimmune Encephalomyelitis (EAE). However, the functional role of the B regulatory cells (Bregs) in vivo and specifically in the human disease is yet to be clarified.

Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules.

We report on an artificially intelligent nanoarray based on molecularly modified gold nanoparticles and a random network of single-walled carbon nanotubes for noninvasive diagnosis and classification of a number of diseases from exhaled breath. The performance of this artificially intelligent nanoarray was clinically assessed on breath samples collected from 1404 subjects having one of 17 different disease conditions included in the study or having no evidence of any disease (healthy controls). Blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined.

Shifting paradigms in multiple sclerosis: from disease-specific, through population-specific toward patient-specific.

Purpose Of Review: In recent years we notice paradigm shifts in the understanding of multiple sclerosis (MS), leading to important transition in the patients' management. This review discusses some of the recent findings and developments underlying the conceptual changes being translated from 'treating the disease' to 'treating the patient' with MS (PwMS).

Recent Findings: Applying advanced technologies combined with cross-disciplinary efforts in the fields of neuropathology, neuroimmunology, neurobiology, and neuroimaging, together with clinical neurology provided support for the notion that MS is not a single disease but rather a spectrum.

Fingolimod therapy modulates circulating B cell composition, increases B regulatory subsets and production of IL-10 and TGFβ in patients with Multiple Sclerosis.

Fingolimod, an oral therapeutic agent approved for patients with relapsing-remitting Multiple Sclerosis (MS), has been shown to prevent lymphocyte egress from secondary lymphoid tissues; however the specific drug effect on B cells in fingolimod-treated patients remains to be fully elucidated. We present here a comprehensive analysis on the proportions of B cell subsets in the periphery, and the levels of activation, functional surface markers and cytokine profile of B cells in MS patients, following initiation of fingolimod therapy, using flow cytometry and cytokine bead array. Fingolimod therapy increased the ratio of naïve to memory cells, elevated the percentage of plasma cells and highly increased the proportion of transitional B cells as well as additional regulatory subsets, including: IL10(+), CD25(+) and CD5(+) B cells.

Effect of Fampridine-PR (prolonged released 4-aminopyridine) on the manual functions of patients with Multiple Sclerosis.

Background: Persons with MS (PwMS) commonly present ambulatory and manual dysfunctions. While ambulation is recognized as important to PwMS, manual dysfunction is only lately gaining attention. Fampridine-PR was approved for MS ambulatory impairments.

Cognitive Function of Patients with Crohn's Disease is Associated with Intestinal Disease Activity.

Background: Systemic inflammation and nutritional deficiencies are characteristics of Crohn's disease (CD) and have been suggested to influence cognitive performance. This study assessed cognitive function in patients with CD.

Methods: Participants were adult patients with CD arriving at routine follow-up.