COVID-19 Vaccination Response in Patients with Multiple Sclerosis Treated with Ofatumumab in the United States: A Medical Record Review.

Introduction: Real-world data are required to provide a greater understanding of the impact of ofatumumab on the ability to mount an effective immune response following the receipt of approved COVID-19 vaccinations. This retrospective real-world analysis aimed to describe the humoral immune response to COVID-19 vaccination during ofatumumab treatment in patients with multiple sclerosis (MS).

Methods: Data from patients with MS treated with ofatumumab who were fully vaccinated against COVID-19 infection were abstracted from medical charts at four clinical sites in the USA.

One Standard for All: Uniform Scale for Comparing Individuals and Groups in Hierarchical Bayesian Evidence Accumulation Modeling.

In recent years, a growing body of research uses Evidence Accumulation Models (EAMs) to study individual differences and group effects. This endeavor is challenging because fitting EAMs requires constraining one of the EAM parameters to be equal for all participants, which makes a strong and possibly unlikely assumption. Moreover, if this assumption is violated, differences or lack thereof may be wrongly found.

Cross-prevalence of multiple sclerosis and stroke evaluated on cohorts of four independent specialty medical centers.

Background: Numerous sources reported the increased risk of cerebrovascular accidents (CVA) in individuals with multiple sclerosis (MS), without a single study thus far challenging the conclusion. Before addressing hypothesis on potential cause-effect relationships, a question whether there are indeed frequent comorbidities between MS and CVA needed to be answered.

Methods: Authors designed a study to evaluate substantial populations of four independent neurology centers with the purpose to assess the prevalence of CVA diagnosis in patients with MS, and vice versa.

Role of Trapped Molecules at Sliding Contacts in Lattice-Resolved Friction.

Understanding atomic friction within a liquid environment is crucial for engineering friction mechanisms and characterizing surfaces. It has been suggested that the lattice resolution of friction force microscope in liquid environments stems from a dry contact state, with all liquid molecules expelled from the area of closest approach between the tip and substrate. Here, we revisit this assertion by performing in-depth friction force microscopy experiments and molecular dynamics simulations of the influence of surrounding water molecules on the dynamic behavior of the nanotribological contact between an amorphous SiO probe and a monolayer MoS substrate.

Bumpy ride ahead: Anticipated effort as emotional evidence?

Conscious reportable (un)pleasantness feelings were shown to be successfully described by a process in which evidence favoring pleasant and unpleasant feelings accumulates until one response wins the race. This approach is challenged by (a) insufficient specification of "evidence," and (b) incomplete verification that participants report their truly experienced (un)pleasant feelings and not what they expect to feel. In each trial in this preregistered experiment, the (un)pleasant feeling reports regarding emotion evoking pictures was embedded in a period when participants expected a low-effort task (feature visual search) or a high-effort task (feature-conjunction search).

Both pleasant and unpleasant emotional feelings follow Weber's law but it depends how you ask.

It remains unclear how we become aware of our emotions. The perceptual theory argues that emotions are a form of perception and reach awareness just like simple sensations. The theory was recently supported by Berkovich and Meiran (2023) showing, using evidence accumulation modeling of pleasantness reports, that pleasant emotional feelings follow one of the most basic psychophysical laws, Weber's Law, as nearly all sensations do.

Menthol dural application alters meningeal arteries tone and enhances excitability of trigeminocervical neurons in rats.

Headaches, including migraines, can have a causal relationship to exposure to cold, and this relationship may be both positive and negative, as cold can both provoke and alleviate cephalgia. The role of thermoreceptors responsible for transduction of low temperatures belongs to the transient receptor potential cation channel subfamily melastatin member 8 (TRPM8). These channels mediate normal cooling sensation and have a role in both cold pain and cooling-mediated analgesia; they are seen as a potential target for principally new anti-migraine pharmaceuticals.

A single filament biomechanical study of the enteropathogenic Type III secretion system reveals a high elastic aspect ratio.

Type III secretion systems (T3SSs) are syringe-like protein complexes used by some of the most harmful bacterial pathogens to infect host cells. While the T3SS filament, a long hollow conduit that bridges between bacteria and host cells, has been characterized structurally, very little is known about its physical properties. These filaments should endure shear and normal stresses imposed by the viscous mucosal flow during infection within the intestinal tract.

Early resection of a rare congenital pulmonary airway malformation causing severe progressive respiratory distress in a preterm neonate: a case report and review of the literature.

Background: Congenital pulmonary airway malformations (CPAMs) are a heterogenous collection of congenital lung malformations, often diagnosed prenatally. The Stocker Type III CPAM is a rare CPAM sub-type, and, when large, may be associated with hydrops. Furthermore, reports of CPAM management which may include surgical resection in extreme preterm infants are limited.

Meta-analysis of the effects of anti-migraine therapeutics in the rat trigeminovascular nociception model as a tool for design optimization.

The main reasons for the low reliability of results from preclinical studies are the lack of prior sample size calculations and poor experimental design. Here, we demonstrate how the tools of meta-analysis can be implemented to tackle these issues. We conducted a systematic search to identify controlled studies testing established migraine treatments in the electrophysiological model of trigeminovascular nociception (EMTVN).

Comparative pharmacokinetics and bioavailability of monomethyl fumarate following a single oral dose of Bafiertam® (monomethyl fumarate) versus Vumerity® (diroximel fumarate).

Background: Bafiertam® (monomethyl fumarate [MMF]) and Vumerity® (diroximel fumarate [DRF]) are two FDA approved drug products for the treatment of relapsing forms of multiple sclerosis (MS) to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Vumerity® is a prodrug of MMF which requires enzymatic conversion of DRF to the active drug MMF, the moiety responsible for the therapeutic efficacy; whereas Bafiertam® contains MMF, providing the active drug directly without any need for enzymatic conversion.

Objective: The objective of this study was to evaluate the pharmacokinetics and relative bioavailability of MMF from oral administration of two Bafiertam® capsules each containing 95 mg of MMF in comparison to two Vumerity® capsules each containing 231 mg of DRF, the therapeutic doses of each product.

Effectiveness and safety of switching to teriflunomide in older patients with relapsing multiple sclerosis: A real-world retrospective multicenter analysis.

Background: The prevalence of multiple sclerosis (MS) in older people is increasing due to population aging and availability of effective disease-modifying therapies (DMTs). Treating older people with MS is complicated by age-related and MS-related comorbidities, immunologic effects of prior DMTs, and immunosenescence. Teriflunomide is a once-daily oral immunomodulator that has demonstrated efficacy and acceptable safety in clinical trials of adults with relapsing forms of MS (RMS).

Characterizing the 'feel-good experience' in multiple sclerosis patients treated with natalizumab or other therapies.

Patients with relapsing-remitting multiple sclerosis (RRMS) treated with natalizumab have anecdotally reported a 'feel-good experience' (FGE). The authors characterized the FGE using survey data from patients with RRMS treated with natalizumab or other disease-modifying therapies (other-DMT). Questionnaire data from RRMS patients who use MyMSTeam, an online patient social network, were analyzed.

Pleasant emotional feelings follow one of the most basic psychophysical laws (weber's law) as most sensations do.

Emotion episodes may include a conscious aspect of the emotion, namely being aware of our own emotional experience. Despite explosion in research over previous years, it remains unclear how emotions reach awareness and become feelings. Already in 1884, William James argued that emotional feelings resemble ordinary sensations in this respect.

Nonexponential kinetics captured in sequential unfolding of polyproteins over a range of loads.

While performing under mechanical loads , polyproteins are vitally involved in cellular mechanisms such as regulation of tissue elasticity and mechano-transduction by unfolding their comprising domains and extending them. It is widely thought that the process of sequential unfolding of polyproteins follows an exponential kinetics as the individual unfolding events exhibit identical and identically distributed (iid) Poisson behavior. However, it was shown that under high loads, the sequential unfolding kinetics displays nonexponential kinetics that alludes to aging by a subdiffusion process.

Progressive Multifocal Leukoencephalopathy Risk Perception in Patients Considering Natalizumab for Multiple Sclerosis.

Background: Progressive multifocal leukoencephalopathy (PML) remains a concern when considering natalizumab for multiple sclerosis (MS) treatment. Extensive research has identified factors that increase PML risk, and it is important that providers and patients accurately understand risk to make appropriate benefit-risk decisions.

Methods: One hundred adult US patient-candidates for natalizumab therapy were questioned about their PML risk perception, the maximum PML risk they deemed acceptable, and sources of information used to understand risk.

Randomized Phase II Trial of MIBG Versus MIBG, Vincristine, and Irinotecan Versus MIBG and Vorinostat for Patients With Relapsed or Refractory Neuroblastoma: A Report From NANT Consortium.

Purpose: I-metaiodobenzylguanidine (MIBG) is an active radiotherapeutic for neuroblastoma. The primary aim of this trial was to identify which of three MIBG regimens was likely associated with the highest true response rate.

Patients And Methods: Patients 1-30 years were eligible if they had relapsed or refractory neuroblastoma, at least one MIBG-avid site, and adequate autologous stem cells.

An inside look at a biofilm: flagella biotracking.

The opportunistic pathogen, , a flagellated bacterium, is one of the top model organisms for biofilm studies. To elucidate the location of bacterial flagella throughout the biofilm life cycle, we developed a new flagella biotracking tool. Bacterial flagella were site-specifically labeled via genetic code expansion.

Improvement of Comorbid Psoriasis in Patients With MS Treated With Natalizumab.

Objective: To present observations on administration of natalizumab to 18 patients with the comorbid MS and psoriasis, who represented a full subset of patients with such comorbidity within the patient records available.

Methods: A retrospective analysis of patient records was performed. Patient histories were gathered and included date of diagnosis of MS and psoriasis, MS disease-modifying therapies (DMTs), Expanded Disability Status Scale (EDSS), reason for DMT switch, and effects on MS and psoriasis status.

Identifying disability level in multiple sclerosis patients in a U.S.-based health plan claims database.

Aims: In clinical trials, disability progression in multiple sclerosis (MS) is measured by the Kurtzke expanded disability status scale (EDSS), which is not captured in routine clinical care in the U.S. This study developed a claims-based disability score (CDS) based on the EDSS for assigning MS disability level in a U.

Interplay between Viscoelasticity and Force Rate Affects Sequential Unfolding in Polyproteins Pulled at Constant Velocity.

Polyproteins are unique constructs, comprised of folded protein domains in tandem and polymeric linkers. These macromolecules perform under biological stresses by modulating their response through partial unfolding and extending. Although these unfolding events are considered independent, a history dependence of forced unfolding within polyproteins was reported.

Efficacy and Safety of Alemtuzumab Through 9 Years of Follow-up in Patients with Highly Active Disease: Post Hoc Analysis of CARE-MS I and II Patients in the TOPAZ Extension Study.

Background: Alemtuzumab efficacy versus subcutaneous interferon-β-1a (SC IFNB-1a) was demonstrated over 2 years in patients with relapsing-remitting multiple sclerosis, with continued efficacy over 7 additional years. Alemtuzumab is included as a recommended treatment for patients with highly active disease (HAD) by the American Academy of Neurology Practice Guidelines, and the label indication in Europe was recently restricted to the treatment of HAD patients. There is currently no consensus definition for HAD, and alemtuzumab efficacy across various HAD definitions has not been explored previously.

Long-term efficacy and safety of alemtuzumab in patients with RRMS: 12-year follow-up of CAMMS223.

Background: In the phase 2 CAMMS223 trial (NCT00050778), alemtuzumab significantly improved clinical and MRI outcomes versus subcutaneous interferon beta-1a over 3 years in treatment-naive patients with relapsing-remitting MS. Here, we assess efficacy and safety of alemtuzumab over 12 years in CAMMS223 patients who enrolled in the CAMMS03409 extension (NCT00930553), with available follow-up through the subsequent TOPAZ extension (NCT02255656).

Methods: In CAMMS223, patients received 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days); 22% received a third course.

Effect of the C-terminal amino acid of the peptide on the structure and mechanical properties of alginate-peptide hydrogels across length-scales.

Alginate is a natural anionic polysaccharide that exhibits excellent biocompatibility and biodegradability. Alginate hydrogels have many different applications in the field of regenerative medicine especially when peptides are conjugated to the alginate backbone. Here, we systematically investigate the effect of six arginine-glycine-aspartic acid (RGD)-containing peptides, G6KRGDY/S, A6KRGDY/S and V6KRGDY/S, on the macroscopic and microscopic physical properties and spatial organization of alginate-peptides hydrogels.