Orchestrating a New Path for Multiple Sclerosis: Achieving Physical, Cognitive, and Emotional Rehabilitation Goals Through Physical and Music Therapy.

Background: Interdisciplinary therapies for the management of people with multiple sclerosis (MS) are underappreciated. There is an urgent need to introduce music therapy (MT), either alone or in combination with physical therapy (PT), into clinical practice to achieve synergy with disease-modifying therapies. A holistic approach to rehabilitation for people with MS may mitigate symptoms and reduce polypharmacy, potentially lowering health care costs.

Topical human recombinant nerve growth factor for stage 1 Neurotrophic Keratitis: Retrospective case series of cenegermin treatment.

Purpose: To report on the management and effectiveness of treating patients with stage I Neurotrophic Keratitis using an 8-week course of topical recombinant human nerve growth factor (rhNGF, cenegermin).

Observations: In this retrospective case series, punctate epithelial erosions (PEE), best corrected visual acuity (BCVA) and corneal sensation were followed and documented from 2 to 12 months in patients treated as per the standard of care. Clinical outcomes including changes in PEEs, corneal sensation and BCVA are reported.

Immune cell subset profiling in multiple sclerosis after fingolimod initiation and continued treatment: The FLUENT study.

Background: Fingolimod is a sphingosine 1-phosphate receptor modulator approved for relapsing MS. Long-term effects on the immunological profile are not fully understood.

Objective: Investigate fingolimod's temporal effects on immune cell subsets, and safety outcomes.

A Targeted Literature Search and Phenomenological Review of Perspectives of People with Multiple Sclerosis and Healthcare Professionals of the Immunology of Disease-Modifying Therapies.

Introduction: The mechanisms of action of disease-modifying therapies (DMTs) for multiple sclerosis (MS) are complex and involve an interplay of immune system components. People with MS (PwMS) may lack a clear understanding of the immunological pathways involved in MS and its treatment; effective communication between healthcare professionals (HCPs) and PwMS is needed to facilitate shared decision-making when discussing the disease and selecting DMTs and is particularly important in the coronavirus disease 2019 (COVID-19) era.

Methods: In this patient-authored two-part review, we performed a targeted literature search to assess the need for better communication between HCPs and PwMS regarding treatment selection, and also conducted a qualitative survey of four patient and care-partner authors to obtain insights regarding their understanding of and preferences for the treatment and management of MS.

Erenumab dosage for migraine prevention: An evidence-based narrative review with recommendations.

Background: Therapeutic monoclonal antibodies against the calcitonin gene-related peptide (CGRP) receptor or its ligand have changed the landscape of treatment options for migraine. Erenumab is the first and only fully human monoclonal antibody designed to target and block the CGRP receptor. It is approved by the Food and Drug Administration for preventive treatment of migraine in adults.

Switching to fingolimod in PREFERMS: Effect of treatment history and naïvety on clinical, MRI and treatment satisfaction outcomes.

Background: Injectable disease-modifying therapies (iDMTs) are often used as first-line treatments for relapsing multiple sclerosis. Fingolimod is frequently used following treatment with iDMTs. Whether prior iDMT treatment impacts the effectiveness of subsequent fingolimod therapy is unclear.

Correction to: Analysis of cardiac monitoring and safety data in patients initiating fingolimod treatment in the home or in clinic.

Following publication of the original article [1], the authors reported a mistake regarding the year found in the paragraph of the Background section.

Analysis of cardiac monitoring and safety data in patients initiating fingolimod treatment in the home or in clinic.

Background: Fingolimod (Gilenya®) is approved for relapsing forms of multiple sclerosis in the USA. Owing to transient heart-rate effects when initiating fingolimod, eligible patients undergo precautionary baseline assessment and first-dose observation (FDO) for ≥6 h. Prior to 2014, FDO was undertaken only in clinics.

Ca(2+) signaling mechanisms in bovine adrenal chromaffin cells.

Calcium (Ca(2+)) is a crucial intracellular messenger in physiological aspects of cell signaling. Adrenal chromaffin cells are the secretory cells from the adrenal gland medulla that secrete catecholamines, which include epinephrine and norepinephrine important in the 'fight or flight' response. Bovine adrenal chromaffin cells have long been used as an important model for secretion -(exocytosis) not only due to their importance in the short-term stress response, but also as a neuroendocrine model of neurotransmtter release, as they have all the same exocytotic proteins as neurons but are easier to prepare, culture and use in functional assays.

Neuronal calcium sensor-1 regulation of calcium channels, secretion, and neuronal outgrowth.

Calcium (Ca(2+)) is an important intracellular messenger underlying cell physiology. Ca(2+) channels are the main entry route for Ca(2+) into excitable cells, and regulate processes such as neurotransmitter release and neuronal outgrowth. Neuronal Calcium Sensor-1 (NCS-1) is a member of the Calmodulin superfamily of EF-hand Ca(2+) sensing proteins residing in the subfamily of NCS proteins.

Metabotropic glutamate receptor-mediated LTD involves two interacting Ca(2+) sensors, NCS-1 and PICK1.

There are two major forms of long-term depression (LTD) of synaptic transmission in the central nervous system that require activation of either N-methyl-D-aspartate receptors (NMDARs) or metabotropic glutamate receptors (mGluRs). In synapses in the perirhinal cortex, we have directly compared the Ca(2+) signaling mechanisms involved in NMDAR-LTD and mGluR-LTD. While both forms of LTD involve Ca(2+) release from intracellular stores, the Ca(2+) sensors involved are different; NMDAR-LTD involves calmodulin, while mGluR-LTD involves the neuronal Ca(2+) sensor (NCS) protein NCS-1.

Differential regulation of endogenous N- and P/Q-type Ca2+ channel inactivation by Ca2+/calmodulin impacts on their ability to support exocytosis in chromaffin cells.

P/Q-type (Ca(V)2.1) and N-type (Ca(V)2.2) Ca2+ channels are critical to stimulus-secretion coupling in the nervous system; feedback regulation of these channels by Ca2+ is therefore predicted to profoundly influence neurotransmission.

Calcium-sensing mechanism in TRPC5 channels contributing to retardation of neurite outgrowth.

The calcium- and sodium-permeable transient receptor potential channel TRPC5 has an inhibitory role in neuronal outgrowth but the mechanisms governing its activity are poorly understood. Here we propose a mechanism involving the neuronal calcium sensor-1 (NCS-1) protein. Inhibitory mutants of TRPC5 and NCS-1 enhance neurite outgrowth similarly.

Methionine-rich repeat proteins: a family of membrane-associated proteins which contain unusual repeat regions.

We report the protein isolation, cloning and characterization of members of an unusual protein family, which comprise the most abundant proteins present in the squid eye. The proteins in this family have a range of molecular weights from 32 to 36 kDa. Electron microscopy and detergent solubilization demonstrate that these proteins are tightly associated with membrane structures where they may form tetramers.

IL1 receptor accessory protein like, a protein involved in X-linked mental retardation, interacts with Neuronal Calcium Sensor-1 and regulates exocytosis.

Previously, human genetics-based approaches allowed us to show that mutations in the IL-1 receptor accessory protein-like gene (IL1RAPL) are responsible for a non-specific form of X-linked mental retardation. This gene encodes a predicted protein of 696 amino acids that belongs to a novel class of the IL-1/Toll receptor family. In addition to the extracellular portion consisting of three Ig-like domains and the intracellular TIR domain characteristic of the IL-1/Toll receptor family, IL1RAPL contains a specific 150 amino acid carboxy terminus that has no significant homology with any protein of known function.

Sense and sensibility in the regulation of voltage-gated Ca(2+) channels.

Voltage-gated Ca(2+) channels are crucial for neurotransmitter release and other neuronal functions, and their activity-dependent regulation could underlie various aspects of synaptic plasticity. Recent studies have identified Ca(2+)-sensing proteins involved in Ca(2+)-channel modulation. These have complex effects on channel gating, and data suggest that the actions of multiple Ca(2+) sensors are important for the fine-tuning of Ca(2+) channel activity.

Identification of Ca2+-dependent binding partners for the neuronal calcium sensor protein neurocalcin delta: interaction with actin, clathrin and tubulin.

The neuronal calcium sensors are a family of EF-hand-containing Ca(2+)-binding proteins expressed predominantly in retinal photoreceptors and neurons. One of the family members is neurocalcin delta, the function of which is unknown. As an approach to elucidating the protein interactions made by neurocalcin delta, we have identified brain cytosolic proteins that bind to neurocalcin delta in a Ca(2+)-dependent manner.

Differential use of myristoyl groups on neuronal calcium sensor proteins as a determinant of spatio-temporal aspects of Ca2+ signal transduction.

The localizations of three members of the neuronal calcium sensor (NCS) family were studied in HeLa cells. Using hippocalcin-EYFP and NCS-1-ECFP, it was found that their localization differed dramatically in resting cells. NCS-1 had a distinct predominantly perinuclear localization (similar to trans-Golgi markers), whereas hippocalcin was present diffusely throughout the cell.