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The association between nasal snuff and malignancy is not well established. There is epidemiological evidence suggesting that oral tobacco when mixed with lime and betel leaves causes oral cancer in the Indian subcontinent. Similarly, snuff spiced with dried aloe has been reported to cause upper jaw malignancies in the Bantu tribes. The last reported case of nasal snuff causing cancer of the nose was described by John Hill in 1761. We describe here a case of a 69-year-old woman who developed a nasal vestibular malignancy after 30 years of snuff usage, and this, we believe, is the only reported case of nasal snuff causing cancer in the last 2 centuries. [ABSTRACT FROM AUTHOR]

The CD137—CD137 ligand (CD137L) costimulatory system is a critical immune checkpoint with pathophysiological implications in autoimmunity. In this study, we investigated the role of CD137L-mediated costimulation on renal, cutaneous and cerebral manifestations in lupus and the underlying immunological mechanism. Lupus-prone C57BL/6lpr−/− (B6.lpr) mice were crossed to C57BL/6.CD137L−/− mice to obtain CD137L-deficient B6.lpr [double knock out (DKO)] mice. We investigated the extent of survival, glomerulonephritis, skin lesions, cerebral demyelination, immune deviation and long-term synaptic plasticity among the two mouse groups. Cytokine levels, frequency of splenic leukocyte subsets and phenotypes were compared between DKO, B6.lpr and B6.WT mice. A 22 month observation of 226 DKO and 137 B6.lpr mice demonstrated significantly more frequent proliferative glomerulonephritis, larger skin lesions and shorter survival in DKO than in B6.lpr mice. Conversely, microglial activation and cerebral demyelination were less pronounced while long-term synaptic plasticity, was superior in DKO mice. Splenic Th17 cells were significantly higher in DKO than in B6.lpr and B6.WT mice while Th1 and Th2 cell frequencies were comparable between DKO and B6.lpr mice. IL-10 and IL-17 expression by T cells was not affected but there were fewer IL-10-producing myeloid (CD11b+) cells, and also lower serum IL-10 levels in DKO than in B6.lpr mice. The absence of CD137L causes an immune deviation toward Th17, fewer IL-10-producing CD11b+ cells and reduced serum IL-10 levels which potentially explain the more severe lupus in DKO mice while leading to reduced microglia activation, lesser cerebral damage and less severe neurological deficits.

Human cultured T lymphocytes of the Jurkat line and myelorna cells of the U266 line cleaved the 28 amino acid vasoactive intestinal peptide (VIP1-28) preferentially at three sites with time- and temperature-dependence. The fragments VIP4-28 and V1P23-28 from an endopeptidase activity, and VIP15-28 from a trypsin-like peptidase, together represented a range of 26-65% of the VIP1-28 recovered after 2 hr at 37° or 4 hr at 22°, based on the absorbance of purified peptides and the radioactivity of [125I]Tyr10° VIP1-28. The endopeptidase activity was associated with membranes recovered after disruption of U266 cells by nitrogen cavitation. Pretreatment of intact U266 and Jurkat cells with diisopropylfluorophosphate (DFP) and the subsequently isolated subcellular particles with phenylmethylsulphonylfluoride (PMSF) and leupeptin inhibited the trypsin-like enzyme by a mean of 80%, without suppressing endopeptidase activity. In contrast, 0.4 mN DL- thiorphan and phosphoramidon blocked selectively a range of 35-70% of the endopeptidase activity in membrane preparations and intact cells. The capacity of lymphocytes to degrade VIP1-28 may substantially alter the effects of this neuromediator on functions of some subsets of T and B cells. [ABSTRACT FROM AUTHOR]

Cd(II), Hg(II), Pb(II), Sn(II) and Ca(II) complexes of curcumin have been prepared and characterized on the basis of their analytical, spectral and conductance data. In all the complexes, curcumin behaved as a monobasic bidentate ligand in which the intramolecularly hydrogen-bonded enolic proton is replaced by the metal ion. The antifungal (with Aspergillus niger, Aspergillus flavus, Aspergillus heteromorphus and Penicillium verruculosum) and antibacterial (with Bacillus cereus) studies reveal that metal complexation considerably increased the activity of curcumin, and among the complexes, Sn(II) complex exhibited maximum activity except for A. flavus where Hg(II) complex is more active.

Purpose: We evaluate the clinical and functional outcome of open primary repair of acute TFCC tears in distal radius fracture, when there is gross intraoperative distal radioulnar joint (DRUJ) instability after fixation of the distal radius, in the absence of an ulnar styloid fracture or when the ulnar fracture fragment is too small to be fixed. Methods: A retrospective review of our institution’s distal radius fracture database over a 4-year period (January 2010 to December 2013). A total of 12 (1.38%) out of 3379 patients had an open TFCC repair in the same setting as fixation of distal radius. Assessment of outcome involved the analysis of objective and subjective clinical and functional outcomes. Results: All patient regained Activities of Daily Living (ADL) independence; eleven out of 12 patients (91.7%) returned to pre-injury function and 8 out of 11 patients (72.7%) returned to their jobs. DRUJ stability was preserved in 10 patients (83.3%) with 10 patients (83.3%) having grip strength of at least 50%, compared to the uninjured hand, and 7 (58.3%) with grip strength of more than or equal to 75%. Complications of surgery identified can be classified into 4 broad categories: infection, neurological complications, persistent DRUJ instability and prolonged pain. Conclusion: The authors believe a primary open repair of the TFCC should be considered when patients present with instability during intra-operative DRUJ ballottement test after distal radius fixation, in the absence of an ulnar styloid fracture or when the ulnar fracture fragment is too small to be fixed.

Lipopolysaccharide (LPS)/Endotoxin is hypothesized to play an important role in chronic inflammation associated with Type-1 diabetes (T1DM) and its complications. Endotoxin core antibodies (EndoCAb), LPS binding protein (LBP) and soluble CD14 (sCD14) act as modulators of LPS induced activation of innate immune system in vivo. For the present study we estimated the levels of LPS and its translocation markers in T1DM subjects with and without microvascular complications (MVC) and correlate them with clinical parameters of T1DM and serum inflammatory cytokine levels (TNF-α, IL-6, IL-1β and GM-CSF).A total of 197 subjects (64 normal glucose tolerance (NGT) subjects, 97 T1DM subjects without MVC and 36 with MVC) were included in this study and the levels of serum LPS, its translocation markers and cytokines measured by immunoassays.Compared to NGT, T1DM subjects (both with and without MVC) had significantly higher levels of LPS, reduced levels of LBP and EndoCAb along with significant increase in the levels of IL-1β, IL-6, TNF-α and GM-CSF (p

A letter to the editor is presented in response to the article "Posterior interosseous nerve palsy after needle acupuncture," by S. Sreedharan, A. Y. T. Lim and M. E. Puhaindran in the 2012 issue of the "Journal of Hand Surgery."

Abstract Background TMEM18 is a hypothalamic gene that has recently been linked to obesity and BMI in genome wide association studies. However, the functional properties of TMEM18 are obscure. Methods The evolutionary history of TMEM18 was inferred using phylogenetic and bioinformatic methods. The gene's expression profile was investigated with real-time PCR in a panel of rat and mouse tissues and with immunohistochemistry in the mouse brain. Also, gene expression changes were analyzed in three feeding-related mouse models: food deprivation, reward and diet-induced increase in body weight. Finally, we genotyped 502 severely obese and 527 healthy Swedish children for two SNPs near TMEM18 (rs6548238 and rs756131). Results TMEM18 was found to be remarkably conserved and present in species that diverged from the human lineage over 1500 million years ago. The TMEM18 gene was widely expressed and detected in the majority of cells in all major brain regions, but was more abundant in neurons than other cell types. We found no significant changes in the hypothalamic and brainstem expression in the feeding-related mouse models. There was a strong association for two SNPs (rs6548238 and rs756131) of the TMEM18 locus with an increased risk for obesity (p = 0.001 and p = 0.002). Conclusion We conclude that TMEM18 is involved in both adult and childhood obesity. It is one of the most conserved human obesity genes and it is found in the majority of all brain sites, including the hypothalamus and the brain stem, but it is not regulated in these regions in classical energy homeostatic models.

Abstract Background The SLC17 family of transporters transports the amino acids: glutamate and aspartate, and, as shown recently, also nucleotides. Vesicular glutamate transporters are found in distinct species, such as C. elegans, but the evolutionary origin of most of the genes in this family has been obscure. Results Our phylogenetic analysis shows that the SLC17 family consists of four main phylogenetic clades which were all present before the divergence of the insect lineage. One of these clades has not been previously described and it is not found in vertebrates. The clade containing Slc17a9 had the most restricted evolutionary history with only one member in most species. We detected expression of Slc17a1-17a4 only in the peripheral tissues but not in the CNS, while Slc17a5- Slc17a9 are highly expressed in both the CNS and periphery. Conclusions The in situ hybridization studies on vesicular nucleotide transporter revealed high expression throughout the cerebral cortex, certain areas in the hippocampus and in specific nuclei of the hypothalamus and thalamus. Some of the regions with high expression, such as the medial habenula and the dentate gyrus of the hippocampus, are important sites for purinergic neurotransmission. Noteworthy, other areas relying on purine-mediated signaling, such as the molecular layer of the dentate gyrus and the periaqueductal gray, lack or have a very low expression of Slc17a9, suggesting that there could be another nucleotide transporter in these regions.

In this study, garlic-oil-combined cellulose fibers were prepared by using Borassus flabellifer (Asian Palmyra palm) to enhance the post-harvest shelf life of tomatoes. The physicochemical properties of the prepared cellulose fibers were characterized by using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy (FE-SEM). The B. flabellifer cellulose fibers combined with garlic oil (BCF/GO) coatings exhibited significant antifungal properties against Aspergillus flavus. In addition, the BCF/GO coating resulted in a notable extension in the shelf life of tomatoes regarding parameters such as weight loss, firmness, pH, ascorbic acid content, lycopene level, moisture content, and titratable acidity after 25 days of storage at 25-29 °C with 85 % relative humidity. The synergistic combination of BCF and GO presents a natural and sustainable solution for extending the shelf life of tomatoes with the potential to significantly reduce post-harvest losses in the food industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Abstract: Hourglass fascicular constrictions have been reported in fewer than 100 cases globally and only in the upper limb. The etiology remains unknown. Patients often present with self-limiting pain in the affected limb followed by flaccid paralysis. As the external architecture of the nerve remains normal on traditional radiological studies, the diagnosis can be missed. The purpose of this case report is to describe this rare clinical entity and a successful treatment approach including ultrasound localization and targeted intraneural microsurgical neurolysis followed by excellent functional recovery., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: There is a lack of evidence on the effectiveness of antidotes in the management of organophosphate and carbamate (OPC) poisoning. We aimed to review the efficacy and safety of glycopyrrolate in the management of OPC poisoning., Methodology: Databases such as PubMed, Scopus, Embase, and Cochrane Library were extensively searched from inception to November 2022 and updated till October 2023. Interventional, observational, and descriptive studies assessing the efficacy and safety of glycopyrrolate administered in any dose, route, and duration for the management of OPC poisoning published in the English language were considered for this review. The treatment with any other regimen that did not include glycopyrrolate was regarded as the comparator. The survival, intensive care unit (ICU) and ventilatory outcomes were considered efficacy outcomes, and adverse effects were considered safety outcomes. Suitable quality assessment tools were used to assess the risk of bias in the included studies. Two independent reviewers were involved in the study selection, data extraction, and quality assessment and any discrepancies were resolved through mutual discussion or consultation with a third reviewer., Results: A total of 9 studies (2 RCTs, 4 cohorts, 1 case series, and 2 case reports) out of 591 nonduplicate records were considered for this review. Overall, the RCTs were observed to have a moderate quality, and observational studies and descriptive studies were found to have good quality. All the included studies used atropine administration as a standard treatment option along with glycopyrrolate. The OPC patients treated with glycopyrrolate had a fewer hospitalization days with comparable recovery and ventilatory outcomes than those that had not been treated with glycopyrrolate. The occurrence of adverse events and complications was lower in the glycopyrrolate group than in the control group., Conclusion: Currently, there is a lack of comparative studies to recommend the use of glycopyrrolate in OPC poisoning, and further interventional studies are required to make an evidencebased recommendation on this topic., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Bile acids are liver-derived signaling molecules that can be found in the brain, but their role there remains largely unknown. We found increased brain chenodeoxycholic acid (CDCA) in mice with absent 12α-hydroxylase (Cyp8b1), a bile acid synthesis enzyme. In these Cyp8b1 -/- , and in Wt mice administered CDCA, stroke infarct area was reduced. Elevated glutamate-induced excitotoxicity mediated by aberrant N-methyl-D-aspartate receptor (NMDAR) overactivation contributes to neuronal death in ischemic stroke. We found reduced glutamate-induced excitotoxicity in neurons from Cyp8b1 -/- and CDCA-treated Wt mice. CDCA decreased NMDAR-mediated excitatory post-synaptic currents by reducing over-activation of NMDAR subunit GluN2B in Wt brains. Synaptic NMDAR activity was also decreased in Cyp8b1 -/- brains. Expression and synaptic distribution of GluN2B were unaltered in Cyp8b1 -/- mice, suggesting CDCA may directly antagonize GluN2B-containing NMDARs. Supporting our findings, in a case-control cohort of acute ischemic stroke patients, we found lower circulatory CDCA. Together, our data suggest that CDCA, acting in the liver-brain axis, decreases GluN2B-containing NMDAR overactivation, contributing to neuroprotection in stroke., Competing Interests: Conflict of interest Roshni R. Singaraja is an Editorial Board Member for Journal of lipid research and was not involved in the editorial review or the decision to publish this article. The other authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

On May 22, 2023, the United States Food and Drug Administration approved the first nalmefene hydrochloride nasal spray for the emergency treatment of known or suspected opioid overdose in adults and pediatric patients 12 years of age and older. This approval of a new prescription nalmefene hydrochloride nasal spray adds to the available opioid reversal options for hospitals, communities, harm reduction groups, and emergency responders. Due to the life-threatening nature of opioid overdose, conducting randomized, well-controlled clinical efficacy trials in the target patient population is neither ethical nor feasible. Clinical investigations of nalmefene nasal spray consisted of two pharmacokinetic studies and one pharmacodynamic study. Approval of the new drug application was based on the scientific bridge established by the two pharmacokinetic studies to the Agency's previous efficacy and safety findings for the listed drug nalmefene hydrochloride injection. Additionally, the pharmacodynamic study conducted in an opioid-induced respiratory depression model in healthy volunteers established the onset of action of nalmefene administered as a nasal spray. A high-level summary of regulatory and scientific considerations during the development and approval of nalmefene nasal spray are presented., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Type 2 diabetes mellitus (T2DM) and progressive liver disease are 2 of the most significant global health concerns, and they have alarming and ever-increasing prevalence. A growing body of literature has demonstrated a potential multilateral link between gut microbiome dysbiosis and the development and progression of the above-mentioned conditions. Modulation of gut microbial composition from the norm is due to changes in diet allied with external factors such as age, genetics, and environmental changes. In this comprehensive review, we recapitulate the research to date investigating the links between gut microbiome dysbiosis and T2DM or liver disease, with special attention to the importance of diet. Additionally, we review the most commonly used tools and methodologies of investigating changes in the gut microbiome, highlighting the advantages and limitations of each strategy, before introducing a novel in vitro approach to the problem. Finally, the review offers recommendations for future research in this field that will allow better understanding of how the gut microbiota affects disease progression and of the prospects for intestinal microbiota-based therapeutic options., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A novel methodology is introduced for the computation of stress-induced surface acoustic wave velocity shifts in piezoelectric resonators including quartz, lithium niobate and langasite resonators. The numerical framework has been verified through a comparative analysis of experimental and Finite Element Method (FEM) results for quartz resonators. This approach introduces the combined capabilities of COMSOL Multiphysics and MATLAB, facilitated by LiveLink, to systematically calculate all parameters contributing to the perturbation integral. The findings have a better accuracy using the LiveLink methodology in this study compared to prior approaches that rely on average stress and strain calculations in the central point of the resonator. Moreover, the utilization of LiveLink not only enhances accuracy but also establishes MATLAB as a fundamental software platform for interfacing with COMSOL Multiphysics. The proposed approach in this paper can extend to complex strain sensors or investigations into the influence of temperature and imbalanced loading effects in future research endeavors. Furthermore, the LiveLink approach introduced herein can be extended to optimize crystal orientation and identify premium wave directions, thereby contributing to the enhanced design of Surface Acoustic Wave (SAW) resonators. This innovative methodology is used to advance the understanding and application of stress-induced velocity shifts in SAW devices, presenting future developments in sensor technologies and resonator designs. © 2024 Elsevier Science. All rights reserved., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The growing interest in commercial Inland saline aquaculture has taken momentum across the globe due to the available technologies for aquaculture and the abundant resources of saline groundwater. However, the critical problems in inland saline ponds are degraded soil and imbalanced or deficient nutrients. To address these issues, a 75-day experiment was conducted to explore the effects of Paddy Straw Biochar (PSB) as a sediment amendment on sediment quality, water characteristics, growth parameters, and the well-being of Penaeus vannamei reared in inland saline environments. PSB was applied to the nursery ponds at 1 ton/hectare (Treatment, T1) and 2 ton/hectare (Treatment, T2). The findings of water quality parameters showed a significant increase in K + and Mg ++ with a decrease in ammonia-N levels in biochar-applied ponds. Similarly, the addition of biochar to ponds (T2) resulted in improved sediment characteristics with enhanced water holding capacity (24.75%), increased soil organic carbon content (77.94%), pH levels (0.37 units), cation exchange capacity (43.15%), available potassium (16.3%), and lower bulk density (12.61%) compared to ponds subjected to control conditions at the end of the experiment. Over the experiment, improvements in sediment and water quality parameters followed the T2 > T1 > control trend. Growth characteristics showed a significant rise in the percentage of weight gain (12.398 ± 0.12), SGR (11.80 ± 0.01% day -1 ) and PER (2.39 ± 0.01) with reduced FCR (1.19 ± 0.00) in biochar-treated ponds (T2), followed by T1 and control. The digestive enzyme activity (amylase) and metabolic enzymes like hepatopancreatic alanine aminotransferase (ALT) and muscle ALT activities were significantly higher in shrimps raised in the biochar-applied ponds. On the other hand, the oxidative stress enzyme superoxide dismutase (SOD) in gills, muscles, and hepatopancreas (HP) exhibited lower values, suggesting reduced oxidative stress due to the biochar amendment of the pond sediment. Overall, the study recommends incorporating PSB at a rate of 2 t/ha into nursery pond sediment to enhance water quality, physiological status, and the growth of P. vannamei juveniles. Moreover, this approach improves soil and water characteristics in saline soils, making it an effective culture practice in degraded environments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: We performed a scoping review to identify the diabetes care determinants and barriers in patients with serious mental illness (SMI), in view of limited evidence and clarity., Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Guidelines. PubMed, EMBASE, and Scopus were searched from inception to September 2023 to identify eligible studies. Observational studies that reported the determinants of and barriers to diabetes care among SMI patients were considered. A narrative synthesis of review results was performed to gather evidence. Recommendations were framed in the context of this evidence., Results: Of the 8727 non-duplicate records, only 10 studies that met the inclusion criteria were considered for this review. Of these, four were cohort, two were case-control, and four were cross-sectional in design. All 10 studies were observed to have robust methodologies. Diabetes measures examined in these studies included not only the Healthcare Effectiveness Data and Information Set (HEDIS) measures (HbA1c, retinopathy, nephropathy, and blood pressure), but also lipid, foot, and BMI. Factors contributing to inadequate diabetes care can be attributed to the healthcare system, healthcare providers, and at the patient-level., Conclusion: Currently, there is lack of evidence on determinants of quality diabetes care among SMI patients. Further, adequately powered long term follow-up studies are needed to understand the impact of diabetes care on their clinical outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved.)

Introduction: There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS., Methods and Analysis: MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.0-6.5 (inclusive). Steady progression rather than relapse must be the major cause of increasing disability in the preceding 2 years.Participants will be allocated to simvastatin or placebo in a 1:1 ratio. The active treatment will be 80 mg daily, after 1 month at 40 mg daily. 31 hospitals across the UK will participate.The primary outcome is (confirmed) disability progression at 6 monthly intervals, measured as change from EDSS baseline score. Recruitment of 1050 participants will be required to achieve a total of 330 progression events, giving 90% power to demonstrate a 30% relative reduction in disability progression versus placebo. The follow-up period is 36 months, extendable by up to 18 months for patients without confirmed progression.Clinician-reported measures include Timed 25 Foot Walk; 9 Hole Peg Test; Single Digit Modalities Test; Sloan Low Contrast Visual Acuity; Relapse assessment; modified Rankin Scale and Brief International Cognitive Assessment For Multiple Sclerosis. Patient-reported outcomes include MS-specific walking, fatigue and impact scales. A health economic analysis will occur., Ethics and Dissemination: The protocol was approved by the London-Westminster REC (17/LO/1509). This manuscript is based on protocol version 8.0, 26 February 2024. Trial findings will be disseminated through peer-reviewed publications and conference presentations., Trial Registration Numbers: NCT03387670; ISRCTN82598726., Competing Interests: Competing interests: JC has received support in the last 3 years from the Health Technology Assessment (HTA) Programme (National Institute for Health Research, NIHR), the UK MS Society, the US National MS Society and the Rosetrees Trust. He is supported in part by the NIHR University College London Hospitals (UCLH) Biomedical Research Centre, London, UK. He has been a local principal investigator for a trial in MS funded by MS Canada. A local principal investigator for commercial trials funded by Ionis and Roche; and has taken part in advisory boards/consultancy for Biogen, Janssen, Lucid, Merck, NervGen, Novartis and Roche. OC declares being NIHR Research Professor (RP-2017-08-ST2-004); over the last 2 years, member of independent DSMB for Novartis; she gave a teaching talk in a Merck local symposium and contributed to an Advisory Board for Biogen; she is Deputy Editor of Neurology, for which she receives an honorarium; has received research grant support from the UK MS Society, the NIHR UCLH Biomedical Research Centre, the Rosetree Trust, the US National MS Society and the NIHR-HTA. HLF has received honoraria for advisory boards and/or educational activities from Biogen, Merck, Novartis and Roche. HLF has research grant support from the NIHR Health Technology Assessment Programme and EME, UK MS Society and the Horne Family Charitable Trust. LF has received honoraria for speaking or as an advisory board member from Biogen, Novartis, Merck, Sanofi Genzyme and Roche, and received support for attending educational meetings from Biogen, Novartis, Merck, Sanofi Genzyme and Teva. GG declares that in the last 2 years he has received compensation for serving as a consultant or speaker or research support from Astoria Biologica, Aurinia Pharmaceuticals, Biogen, BMS-Celgene, GlaxoSmithKline, Janssens/J&J, Japanese Tobacco, Merck KGaA/EMD Serono, Moderna, Novartis, Sandoz, Sanofi, Roche/Genentech, Vir Biotechnology and Viracta. NJ is a principal investigator on commercial MS trials sponsored by Roche, Novartis and Biogen. He has received speakers honoraria from Merck and travel congress sponsorship from Novartis. MM has received travel support, speaker honoraria and consultation fees from Genzyme, Merck-Sereno, Novartis, Roche, the MS Academy and the Italian Multiple Sclerosis Foundation (FISM). RN attended paid advisory board for Novartis and Roche. SPavitt was MRC/National Institute for Health Research (NIHR)—Efficacy & Mechanism Evaluation Board Member from 2012–2018. SPluchino is founder, CSO and shareholder (>5%) of CITC and Chair of the Scientific Advisory Board at ReNeuron plc. CR declares research funding from Sanofi. DR declares consulting and/or speaker fees received from Biogen, Celgene, Janssen, MedDay, Merck, Novartis, Roche, Sanofi Genzyme and Teva. Additionally, research support paid to an institutional fund from Actelion, Biogen, GW Pharmaceuticals, Merck Serono, Mitsubishi, Novartis, Sanofi Genzyme, Teva and TG Therapeutics. AJT receives a fee from being Co-Chair, UCL-Eisai Steering Committee drug discovery collaboration; Member, National MS Society (USA) Research Programs Advisory Committee; Clinical Trials Committee, Progressive MS Alliance; Board member, European Charcot Foundation; Editor in Chief, Multiple Sclerosis Journal; Editorial Board Member, The Lancet Neurology. He receives no fee from being: Chair (Scientific Ambassadors), ‘Stop MS’ Appeal Board, UK MS Society; Research & academic counsellor, Fundació Privada Cemcat; Ambassador, European Brain Council. AJT additionally holds a patent for the MSIS-29 Impact Scale., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)