Multiple sclerosis (MS) is a leading cause of chronic neurological disability in young to middle-aged adults, affecting ~2.5 million people worldwide. Currently, most therapeutics for MS are systemic ...immunosuppressive or immunomodulatory drugs, but these drugs are unable to halt or reverse the disease and have the potential to cause serious adverse events. Hence, there is an urgent need for the development of next-generation treatments that, alone or in combination, stop the undesired autoimmune response and contribute to the restoration of homeostasis. This review analyzes current MS treatments as well as different cell-based therapies that have been proposed to restore homeostasis in MS patients (tolerogenic dendritic cells, regulatory T cells, mesenchymal stem cells, and vaccination with T cells). Data collected from preclinical studies performed in the experimental autoimmune encephalomyelitis (EAE) model of MS in animals, in vitro cultures of cells from MS patients and the initial results of phase I/II clinical trials are analyzed to better understand which parameters are relevant for obtaining an efficient cell-based therapy for MS.
Ab initio molecular dynamics (AIMD) based on density functional theory has been used to study small aluminium-oxygen complexes in water. Such Al-O clusters have been seen in several recent mass ...spectrometry studies. In this study, we have focused on trimeric Al-O clusters. The initial very compact trimeric Al-O structures opened up and formed linear Al-O chains. The typical Al-O coordination number in these chain structures was 5. We have performed long (up to 200 ps) AIMD simulations and these chain structures are stable on the nanosecond time scale. We have also studied the reactivity of the Al-O dimer and solvated Al. We found a formation path for the trimeric cluster, which has a action barrier (0.04 eV) and a reaction free energy of − 0.55 eV. This suggests that the association of a dimer and a monomer Al-O species is fast and thermodynamically a very favourable process.
Abstract
Objective
Social media platforms are promising to provide smoking cessation support. This study aimed to identify baseline factors associated with cigarette smoking abstinence among young ...adult smokers enrolled in a real-world social media-based smoking cessation program.
Aims and Methods
We analyzed data from young adult smokers (aged 18–30 years) participating in a publicly available Facebook-based smoking cessation program serving the San Francisco Bay Area. The analytic sample consisted of 248 participants who completed both the baseline and follow-up surveys at 3 months. Multivariable logistic regression analysis determined baseline factors significantly associated with self-reported 7-day cigarette smoking abstinence at 3 months.
Results
Participants were race/ethnically diverse, well-educated, and 47.6% reported LGB + sexual identity. Those who reported dual use of cigarettes and e-cigarettes in the past 30 days (vs. cigarette use only), current alcohol users (vs. non-users), and those aged 25–30 years (vs. 18–24 years) were significantly less likely to report 7-day abstinence at 3 months. Non-daily smokers (vs. daily smokers) and those with high desire to quit smoking (vs. low to moderate desire) were more likely to report abstinence. Results also showed reduction in the percentage of e-cigarette and other tobacco product use among participants.
Conclusions
Social media interventions may be more effective for young adult non-daily smokers and those with high desire to quit smoking. Smoking cessation programs may help reduce use of other tobacco products among treatment-seeking smokers. Smoking cessation interventions for young adults need to explicitly address dual use of cigarettes and e-cigarettes and use of alcohol.
Implications
Findings of this study highlight the need for future interventions to address dual use of cigarettes and e-cigarettes and use of alcohol to improve cigarette smoking abstinence outcomes. The reduction in the use of other tobacco products among program participants indicates that social media smoking cessation programs may exert a broader positive influence on overall tobacco consumption. The large number of LGB+ smokers participating in the program suggests social media is a promising cessation channel for this hard-to-reach group, warranting further study.
Abstract Substance use disorders are chronically relapsing conditions, and there is a need to evaluate whether relapse precursors are consistent across multiple relapses. We identified latent groups ...of relapse characteristics over time in adolescents with alcohol and substance use disorders following an inpatient treatment episode. Youth ( N = 124, mean age = 16 years, 56% male, 60% Caucasian) were interviewed while in treatment and biannually during the first year after treatment to gather contextual information about first and second relapse episodes. We identified two latent classes of relapse precursors labeled aversive–social (41% at initial relapse, 57% at subsequent relapse) and positive–social (59% at initial relapse, 43% at subsequent relapse). Classes were stable in structure over time; however, only 61% of those assigned to aversive–social and 39% assigned to positive–social classes at initial relapse remained there for the subsequent relapse. Findings highlight the dynamic nature of relapse for youth and have important clinical implications.
To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients.
We studied patients from ...MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity.
A total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval CI 0.43-0.82,
= 0.0016), worsening of disability (0.56, 0.38-0.82,
= 0.0026), and progress to EDSS step 6 (0.33, 0.19-0.59,
= 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50-0.70,
= 10
) and worsening of disability (0.81, 0.67-0.99,
= 0.043).
Continued treatment with MS immunotherapies reduces disability accrual by 19%-44% (95% CI 1%-62%), the risk of need of a walking aid by 67% (95% CI 41%-81%), and the frequency of relapses by 40-41% (95% CI 18%-57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term.
This study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability.
Allanite is a common accessory mineral in igneous rocks that contains significant amounts of rare‐earth elements (REEs), thorium (Th), and uranium (U). The presence of Th and U in the allanite ...exposes it to radiation resulting in radiation damage in its crystal structure and further leads to metamictization. Hence, allanite can be used as a natural analogue to assess the long‐term radiation effects in materials for high‐level nuclear waste disposal. It provides information on the effect of α‐decay on the crystal structure including the stability and integrity of the material. In this study, the absorbed α‐dose of allanite from Ombo, Palawan, Philippines, was estimated from the Th and U content and geological age of the mineral using X‐ray fluorescence and gamma‐ray spectrometry. The amount of Th and REE was measured to be around 1.37 and ~30.4 wt.%, respectively. Radiometric dating using gamma‐ray spectrometry estimated the age of the allanite mineral to be around 24–35 million years. Having obtained the amount of radioactivity and the time of exposure, the corresponding absorbed α‐dose was estimated to be at 2.84 × 1014 α‐decays/mg. Results suggest that the allanite mineral studied has not accumulated significant radiation damage to cause amorphization and still exhibit a crystalline structure. This study may provide data on the properties of allanite or silicate matrices as part of the ongoing studies on silicate minerals as natural analogues.
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