Safety and Efficacy of Ianalumab in Patients With Sjögren's Disease: 52-Week Results From a Randomized, Placebo-Controlled, Phase 2b Dose-Ranging Study.

Objective: To report 52-week safety and efficacy of ianalumab from phase 2b dose-finding study in patients with Sjögren's disease (SjD).

Methods: Patients randomly received (1:1:1:1) ianalumab (5, 50, or 300 mg) or placebo subcutaneously every 4 weeks till week 24 (treatment period [TP]1). At week 24, patients on 300 mg were re-randomized to continue 300 mg or receive placebo till week 52 (TP2), patients on placebo were switched to ianalumab 150 mg, while patients on 5 and 50 mg directly entered post treatment safety follow-up.

Effects of the IronHand Soft Exoskeleton on Forearm Muscle Activity During in Field Automotive Assembly Tasks.

OCCUPATIONAL APPLICATIONSWhen compared to not using a soft-hand exoskeleton, the IronHand caused both increases and decreases in forearm muscle activity while completing automotive assembly tasks. Surprisingly, although there were reductions in muscle activity when wearing the IronHand, only a few of these decreases resulted in muscle activity changing such that they fell to below recommended ergonomic thresholds. Despite this, some individuals in our study clearly benefited from the device, and this suggests that there is potential for widespread use of such a device if fine tuned to the individual and task demands.

Access to Care and Health-Related Quality of Life in Multiple Sclerosis.

Background And Objectives: Despite their high health care use, it is unclear whether the health care needs of people with MS are being met and what their priorities are. We assessed priorities for access to, and affordability of care, by people living with MS in the United States. We also tested the association between perceived inadequate access to care and health-related quality of life (HRQoL).

Computational predictions of cocrystal formation: A benchmark study of 28 assemblies comparing five methods from high-throughput to advanced models.

Cocrystals are assemblies of more than one type of molecule stabilized through noncovalent interactions. They are promising materials for improved drug formulation in which the stability, solubility, or biocompatibility of the active pharmaceutical ingredient (API) is improved by including a coformer. In this work, a range of density functional theory (DFT) and density functional tight binding (DFTB) models are systematically compared for their ability to predict the lattice enthalpy of a broad range of existing pharmaceutically relevant cocrystals.

Nano-Plasticity of an Electrified Ionic Liquid/Electrode Interface: Uncovering Hard-Soft Structuring via Controlled Metal Fill Factor.

Ionic liquids (ILs) nanostructuring at electrified interfaces is of both fundamental and practical interest as these materials are increasingly gaining prominence in energy storage and conversion processes. However, much remains unresolved about IL potential-controlled (re)organization under highly polarized interfaces, mostly due to the difficulty of selectively probing both the distal and proximal surface layers of adsorbed ions. In this work, the structural dynamics of the innermost layer (<10 nm from the surface) were independently interrogated from that of the ionic layers in the sub-surface region (>100 nm from the surface), using an infrared (IR) spectroscopy approach.

Association of patient-reported cognitive impairment with quality of life and employment in multiple sclerosis.

Background: Cognition is frequently affected in persons with multiple sclerosis (MS). Cognitive impairment (CI) is associated with decreased quality of life (QOL) and employment status. Yet, CI assessed using patient-reported outcome measures is not as well studied and is thought to be influenced by other symptoms.

Safety and Dose-Response of Vidofludimus Calcium in Relapsing Multiple Sclerosis: Extended Results of a Placebo-Controlled Phase 2 Trial.

Background And Objectives: Vidofludimus calcium suppressed MRI disease activity compared with placebo in patients with relapsing-remitting multiple sclerosis (RRMS) in the first cohort of the phase 2 EMPhASIS study. Because 30 mg and 45 mg showed comparable activity on multiple end points, the study enrolled an additional low-dose cohort to further investigate a dose-response relationship.

Methods: In a randomized, placebo-controlled, phase 2 trial, patients with RRMS, aged 18-55 years, and with ≥2 relapses in the last 2 years or ≥1 relapse in the last year, and ≥1 gadolinium-enhancing brain lesion in the last 6 months.

Temporal Relationship Between Serum Neurofilament Light Chain and Radiologic Disease Activity in Patients With Multiple Sclerosis.

Background And Objectives: Serum neurofilament light chain (sNfL) levels correlate with multiple sclerosis (MS) disease activity, but the dynamics of this correlation are unknown. We evaluated the relationship between sNfL levels and radiologic MS disease activity through monthly assessments during the 24-week natalizumab treatment interruption period in RESTORE (NCT01071083).

Methods: In the RESTORE trial, participants with relapsing forms of MS who had received natalizumab for ≥12 months were randomized to either continue or stop natalizumab and followed with MRI and blood draws every 4 weeks to week 28 and again at week 52 The sNfL was measured, and its dynamics were correlated with the development of gadolinium-enhancing (Gd+) lesions.

Evaluating Speaker-Listener Cognitive Effort in Speech Communication Through Brain-to-Brain Synchrony: A Pilot Functional Near-Infrared Spectroscopy Investigation.

Purpose: We explore a new approach to the study of cognitive effort involved in listening to speech by measuring the brain activity in a listener in relation to the brain activity in a speaker. We hypothesize that the strength of this brain-to-brain synchrony (coupling) reflects the magnitude of cognitive effort involved in verbal communication and includes both listening effort and speaking effort. We investigate whether interbrain synchrony is greater in native-to-native versus native-to-nonnative communication using functional near-infrared spectroscopy (fNIRS).

Immunologic basis for development of keratoconjunctivitis sicca in systemic autoimmune diseases: Role of innate immune sensors.

The literature is filled with citations reporting an increased incidence of chronic dry eye disease, also known as keratoconjunctivitis sicca, in patients with systemic autoimmune diseases such as rheumatoid arthritis, Sjögren's Syndrome, systemic sclerosis and lupus. As the most environmentally exposed mucosal surface of the body, the conjunctiva constantly responds to environmental challenges which are typically self limited, but when persistent and unresolved may provoke pathogenic innate and adaptive immune reactions. Our understanding of the pathophysiological mechanisms by which systemic autoimmune diseases cause dry eye inducing ocular surface inflammation continues to evolve.

The Morphology of the Dorsal Part of the First Rib in Neurogenic Thoracic Outlet Syndrome Patients: A Retrospective Clinical Study.

Background: The recurrence or persistence of symptoms after thoracic outlet decompression (TOD) in patients with neurogenic thoracic outlet syndrome (NTOS) is not uncommon. Some authors have shown significantly better clinical outcomes in patients who underwent TOD with exarticulation of the first rib compared to a group who underwent TOD with preservation of the dorsal portion of the first rib. Several other case series have shown significant improvement after redo surgery with removal of the dorsal first rib remnant.

Clinical trials for progressive multiple sclerosis: progress, new lessons learned, and remaining challenges.

Despite the success of disease-modifying treatments in relapsing multiple sclerosis, for many individuals living with multiple sclerosis, progressive disability continues to accrue. How to interrupt the complex pathological processes underlying progression remains a daunting and ongoing challenge. Since 2014, several immunomodulatory approaches that have modest but clinically meaningful effects have been approved for the management of progressive multiple sclerosis, primarily for people who have active inflammatory disease.

Rethinking Sjögren Beyond Inflammation: Considering the Role of Nerves in Driving Disease Manifestations.

Sjögren syndrome (SS) is a chronic inflammatory autoimmune disease characterized by destruction of mucosal glands resulting in dry eye and dry mouth. Ocular presentations can be heterogenous in SS with corneal nerves abnormalities that are structural, functional, or both. Some individuals present with corneal hyposensitivity, with a phenotype of decreased tear production and epithelial disruption.

Design of a high-temperature cell for cobalt-60 irradiations of aqueous solutions with in situ UV-visible spectroscopy.

To understand the speciation of solutes in aqueous solutions in high temperature radiation environments, we report the design and fabrication of a custom-built, high temperature (≤300 °C) titanium irradiation cell with in situ optical spectroscopy capabilities, as afforded by coupled fiber optic cables. The wetted surfaces of the 8-inch tall cylindrical cell with 3.5 in.

Ibudilast reduces slowly enlarging lesions in progressive multiple sclerosis.

Background: Ibudilast has shown beneficial effects on several imaging outcomes in progressive multiple sclerosis (MS). Slowly enlarging lesions are a proposed imaging biomarker of compartmentalized inflammation within chronic active lesions.

Objective: To assess the treatment effect of ibudilast on slowly enlarging lesion volumes over 96 weeks from a phase II clinical trial of ibudilast (Secondary and Primary Progressive Ibudilast NeuroNEXT Trial in Multiple Sclerosis [SPRINT-MS]).

High temperature gamma radiation-induced chromium redox chemistry spectroscopic measurements.

Chromium ions can make their way into the primary coolant of nuclear power reactors from the corrosion of stainless-steel reactor components, decreasing the material's corrosion resistance and resulting in increased transport of further corrosion products. Despite these potential effects, the radiation-induced redox speciation of chromium ions in aqueous solution is not well understood, especially at the elevated temperatures experienced by reactor coolants. In the present work, we report new experimental results demonstrating that in aerated aqueous solution, the radiolytic oxidation of Cr(III) to Cr(VI) occurs at pH 4, while the reduction of Cr(VI) to Cr(III) occurs at pH 2.

Serum macrophage migration inhibitory factor levels predict brain atrophy in people with primary progressive multiple sclerosis.

Background: Macrophage migration inhibitory factor (MIF) is a cytokine linked to multiple sclerosis (MS) progression that is thought to be inhibited by ibudilast. SPRINT-MS was a phase 2 placebo-controlled trial of ibudilast in progressive multiple sclerosis (PMS).

Objective: To determine whether baseline MIF levels predict imaging outcomes and assess the effects of ibudilast on serum and cerebrospinal fluid (CSF) MIF levels in people with PMS treated with ibudilast.

Pathophysiology, Diagnosis, Treatment and Emerging Neurotherapeutic Targets for Progressive Multiple Sclerosis: The Age of PIRA.

More than one million individuals are impacted by progressive forms of multiple sclerosis. The literature examining the management of MS has focused primarily on relapsing forms of disease, and effective therapies targeting progressive mechanisms in MS remains a significant unmet need. Despite this, there are several encouraging potential therapeutics on the horizon.

Introduction to the special issue on perception and production of sounds in the high-frequency range of human speecha).

The frequency range audible to humans can extend from 20 Hz to 20 kHz, but only a portion of this range-the lower end up to 8 kHz-has been systematically explored because extended high-frequency (EHF) information above this low range has been considered unnecessary for speech comprehension. This special issue presents a collection of research studies exploring the presence of EHF information in the acoustic signal and its perceptual utility. The papers address the role of EHF hearing in auditory perception, the impact of EHF hearing loss on speech perception in specific populations and occupational settings, the importance of EHF in speech recognition and in providing speaker-related information, the utility of acoustic EHF energy in fricative sounds, and ultrasonic vocalizations in mice in relation to human hearing.

Overcoming barriers to informed consent in neurological research: Perspectives from a national survey.

The ethical recruitment of participants with neurological disorders in clinical research requires obtaining initial and ongoing informed consent. The purpose of this study is to characterize barriers faced by research personnel in obtaining informed consent from research participants with neurological disorders and to identify strategies applied by researchers to overcome those barriers. This study was designed as a web-based survey of US researchers with an optional follow-up interview.

The Role of Instructions in Motor Learning of Oral Versus Nasalized Speech Targets.

Purpose: The purpose of this study was to investigate how general, implicit instructions with auditory-perceptual emphasis; specific, explicit instructions with biomechanical focus; or both affect learning of oral-nasal balance control in speech.

Method: Thirty healthy, vocally untrained participants were assigned to one of three instructional groups (i.e.