Multiple sclerosis (MS) is one of the world's most common neurologic disorders, and in many countries it is the leading cause of nontraumatic neurologic disability in young adults. Despite this, ...global information on the epidemiology of MS and the availability of resources and services for people with MS is scarce in many regions of the world. The first Atlas of MS, published in 2008 as a joint project of the Multiple Sclerosis International Federation (MSIF) and the World Health Organization (WHO), super(1) endeavored to fill this knowledge gap with information from 112 countries. Here, we outline important updates in the recently launched Atlas of MS 2013: Mapping Multiple Sclerosis around the World. super(2)
This article reports results from the National Survey on Teen Relationships and Intimate Violence (STRiV) for 12- to 18-year-old youth (n = 1,804). STRiV provides the first nationally representative ...household survey focused on adolescent relationship abuse (ARA), covering perpetration and victimization. Among respondents (37%) reporting current- or past-year dating, 69% reported lifetime ARA victimization (63% lifetime ARA perpetration). Although psychological abuse was most common for these youth (more than 60%), the rates of sexual abuse (18%) and physical abuse victimization (18%), as well as 12% reporting perpetrating physical abuse and/or sexual abuse (12%) were substantial as well. Other than differences by age and gender, ARA rates were consistent by race/ethnicity, geographic region, urbanicity, and household characteristics, highlighting the importance of universal prevention programs. Compared with youth aged 15 to 18, those 12 to 14 years old reported lower rates of psychological and sexual ARA victimization. Similarly, we found lower ARA perpetration rates for those 12 to 14. We found no gender differences for ARA victimization but found that girls perpetrated more physical ARA than boys. Girls aged 15 to 18 reported perpetrating moderate threats/physical violence at more than twice the rate of younger girls and 3 times the rate compared with boys aged 15 to 18; girls aged 15 to 18 reported perpetrating more than 4 times the rate of serious psychological abuse than boys 15 to 18. Finally, these data document the significant positive correlation between ARA victimization and perpetration. Findings suggest that when working with youth in prevention services, interventions should not be designed for monolithic groups of “victims” or “perpetrators.”
T helper cells play an important role in the aetiology of Multiple Sclerosis (MS). Vitamin D has an anti-inflammatory effect on T helper cells and can affect onset and pathogenesis of MS. Two genes ...of the metabolic Vitamin D pathway expressed by activated T helper (Th) cells have been identified as MS risk genes by genome-wide association studies, CYP27B1 (25(OH)D3 1-alpha-hydroxylase) and CYP24A1 (1,25(OH)2D3 24-alpha-hydroxylase). Therefore, we hypothesize that the MS risk alleles around gene CYP27B1 and CYP24A1 are associated with the altered inflammatory profile of peripheral Th cells in PBMCs both ex vivo and in vitro potentially influencing the pathogenesis of MS. PBMCs from MS patients (41 RRMS patients in their remitting stage and 4 SPMS patients) and 12 healthy controls were collected, subpopulation of Th cells in PBMCs and cytokine profile were tested by Flow cytometry and Cytometric Bead Array (CBA), respectively. MS risk SNPs were genotyped by allele-specific PCR analysis. Data were analysed using nonparametric tests and linear regression for adjusting multiple factors. The proportion of Th17.1, Th17 and Th1 cells were all associated with MS while the proportions of Th2 (significant) and Th17 (near significant) cells were correlated with the expanded disability scale score of MS patients. Additionally, we found a MS-specific dysregulation in the IL-6 and TNF production of Th cells in Concanavalin A-stimulated PBMCs. Furthermore, the risk allele rs2248359-C (near gene CYP24A1) showed a consistent inhibitory effect on the proportions of Th1 and Th17.1 cells, and the presence of the homozygous risk allele rs703842-AA (near gene CYP27B1) reduced the production of IL-2. In conclusion, both MS disease and its risk alleles near Vitamin D metabolism genes influence the inflammatory profile of T helper cells in PBMCs.
Increasing evidence suggests the potential of Epstein-Barr virus (EBV) vaccination in preventing multiple sclerosis (MS). We aimed to explore the cost-effectiveness of a hypothetical EBV vaccination ...to prevent MS in an Australian setting.
A five-state Markov model was developed to simulate the incidence and subsequent progression of MS in a general Australian population. The model inputs were derived from published Australian sources. Hypothetical vaccination costs, efficacy and strategies were derived from literature. Total lifetime costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were estimated for two hypothetical prevention strategies versus no prevention from the societal and health system payer perspectives. Costs and QALYs were discounted at 5% annually. One-way, two-way and probabilistic sensitivity analyses were performed.
From societal perspective, EBV vaccination targeted at aged 0 and aged 12 both dominated no prevention (ie, cost saving and increasing QALYs). However, vaccinating at age 12 was more cost-effective (total lifetime costs reduced by $A452/person, QALYs gained=0.007, ICER=-$A64 571/QALY gained) than vaccinating at age 0 (total lifetime costs reduced by $A40/person, QALYs gained=0.003, ICER=-$A13 333/QALY gained). The probabilities of being cost-effective under $A50 000/QALY gained threshold for vaccinating at ages 0 and 12 were 66% and 90%, respectively. From health system payer perspective, the EBV vaccination was cost-effective at age 12 only. Sensitivity analyses demonstrated the cost-effectiveness of EBV vaccination to prevent MS under a wide range of plausible scenarios.
MS prevention using future EBV vaccinations, particularly targeted at adolescence population, is highly likely to be cost-effective.
Activation of the kynurenine pathway (KP) of tryptophan metabolism results from chronic inflammation and is known to exacerbate progression of neurodegenerative disease. To gain insights into the ...links between inflammation, the KP and multiple sclerosis (MS) pathogenesis, we investigated the KP metabolomics profile of MS patients. Most significantly, we found aberrant levels of two key KP metabolites, kynurenic acid (KA) and quinolinic acid (QA). The balance between these metabolites is important as it determines overall excitotoxic activity at the N-methyl-D-Aspartate (NMDA) receptor. We also identified that serum KP metabolic signatures in patients can discriminate clinical MS subtypes with high sensitivity and specificity. A C5.0 Decision Tree classification model discriminated the clinical subtypes of MS with a sensitivity of 91%. After validation in another independent cohort, sensitivity was maintained at 85%. Collectively, our studies suggest that abnormalities in the KP may be associated with the switch from early-mild stage MS to debilitating progressive forms of MS and that analysis of KP metabolites in MS patient serum may have application as MS disease biomarkers.
Over the course of a year, we developed and tested a 6-week massive open online course (MOOC) on multiple sclerosis (MS) in consultation with the MS community. The course targeted the MS community ...and interested laypeople and was titled Understanding MS. The primary purpose of the course was to improve MS knowledge, health literacy, and resilience among participants. The final version of the MOOC made available for open enrollment was ranked first among all MOOCs released in 2019 (n>2400) based on participant reviews.
The aim of this study was to present a detailed description and assessment of the development process of the Understanding MS MOOC.
The development process included a course development focus group; the creation of more than 50 content videos and related text, quizzes, activities, and discussion prompts; the creation of original images and animations; a pilot study; and collaborations with people living with MS, MS nurses, allied health care practitioners, and neurologists and researchers from 4 universities.
Overall, the process was efficient and effective. With a few small changes, we recommend this approach to those seeking to develop a similar course. This process led to the development of a highly reviewed MOOC with excellent user satisfaction.
We identified 5 key lessons from this process: (1) community support is essential, (2) stakeholder involvement improves content quality, (3) plan for research from the beginning, (4) coordination between the academic lead and project manager team ensures a consistent voice, and (5) a network of collaborators is a key resource.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The ketogenic diet (KD) has been used in treatment-resistant epilepsy since the 1920s. It has been researched in a variety of neurological conditions in both animal models and human trials. The aim ...of this review is to clarify the potential role of KD in psychiatry.
Narrative review of electronic databases PubMED, PsychINFO, and Scopus.
The search yielded 15 studies that related the use of KD in mental disorders including anxiety, depression, bipolar disorder, schizophrenia, autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD). These studies comprised nine animal models, four case studies, and two open-label studies in humans. In anxiety, exogenous ketone supplementation reduced anxiety-related behaviors in a rat model. In depression, KD significantly reduced depression-like behaviors in rat and mice models in two controlled studies. In bipolar disorder, one case study reported a reduction in symptomatology, while a second case study reported no improvement. In schizophrenia, an open-label study in female patients (
= 10) reported reduced symptoms after 2 weeks of KD, a single case study reported no improvement. In a brief report, 3 weeks of KD in a mouse model normalized pathological behaviors. In ASD, an open-label study in children (
= 30) reported no significant improvement; one case study reported a pronounced and sustained response to KD. In ASD, in four controlled animal studies, KD significantly reduced ASD-related behaviors in mice and rats. In ADHD, in one controlled trial of KD in dogs with comorbid epilepsy, both conditions significantly improved.
Despite its long history in neurology, the role of KD in mental disorders is unclear. Half of the published studies are based on animal models of mental disorders with limited generalizability to the analog conditions in humans. The review lists some major limitations including the lack of measuring ketone levels in four studies and the issue of compliance to the rigid diet in humans. Currently, there is insufficient evidence for the use of KD in mental disorders, and it is not a recommended treatment option. Future research should include long-term, prospective, randomized, placebo-controlled crossover dietary trials to examine the effect of KD in various mental disorders.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory neuropathy, classically characterised by a slowly progressive onset and symmetrical, sensorimotor involvement. ...However, there are many phenotypic variants, suggesting that CIDP may not be a discrete disease entity but rather a spectrum of related conditions. While the abiding theory of CIDP pathogenesis is that cell-mediated and humoral mechanisms act together in an aberrant immune response to cause damage to peripheral nerves, the relative contributions of T cell and autoantibody responses remain largely undefined. In animal models of spontaneous inflammatory neuropathy, T cell responses to defined myelin antigens are responsible. In other human inflammatory neuropathies, there is evidence of antibody responses to Schwann cell, compact myelin or nodal antigens. In this review, the roles of the cellular and humoral immune systems in the pathogenesis of CIDP will be discussed. In time, it is anticipated that delineation of clinical phenotypes and the underlying disease mechanisms might help guide diagnostic and individualised treatment strategies for CIDP.
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