Magnesium supplementation for the treatment of restless legs syndrome and periodic limb movement disorder : A systematic review

Magnesium supplementation is often suggested for restless legs syndrome (RLS) or period limb movement disorder (PLMD) based on anecdotal evidence that it relieves symptoms and because it is also commonly recommended for leg cramps. We aimed to review all articles reporting the effects of magnesium supplementation on changes in RLS and/or PLMD. We conducted a systematic search looking for all relevant articles and then two reviewers read all article titles and abstracts to identify relevant studies. Eligible studies were scored for their quality as interventional trials. We found 855 abstracts and 16 of these could not be definitively excluded for not addressing all aspects of our research question. Seven full-text articles were unlocatable and one was ineligible which left eight studies with relevant data. One was a randomised placebo-controlled trial, three were case series and four were case studies. The RCT did not find a significant treatment effect of magnesium but may have been underpowered. After quality appraisal and synthesis of the evidence we were unable to make a conclusion as to the effectiveness of magnesium for RLS/PLMD. It is not clear whether magnesium helps relieve RLS or PLMD or in which patient groups any benefit might be seen. (c) 2019 Elsevier Ltd. All rights reserved.Peer reviewe

Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT), during antiretroviral therapy (ART) induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans

Pain and the risk for falls in community-dwelling older adults: systematic review and meta-analysis

Objective: To conduct a systematic review and meta-analysis to establish the association between pain and falls in community dwelling older adults. Data Sources: Electronic databases from inception until 1st March 2013 including Cochrane Library, CINAHL, EBSCO, EMBASE, PubMed and PsycINFO. Study Selection: Two reviewers independently conducted the searches and completed methodological assessment of all included studies. Studies were included that (a) focussed on older adults over 60 years old, (b) recorded falls over 6 or more months, (c) identified a group with and without pain. Studies were excluded that (d) included participants with dementia, a neurological condition (e.g. stroke), (e) participants whose pain was caused by a previous fall, (f) individuals with surgery/ fractures in the past 6 months. Data extraction: One author extracted all data and this was independently validated by another author. Data synthesis: 1,334 articles were screened and 21 studies met the eligibility criteria. 50.5% of older adults with pain reported one or more fall over 12 months compared to 25.7% of controls (p<0.001). A global meta-analysis with 14 studies (n=17,926) demonstrated that pain was associated with an increased odds of falling (OR: 1.56, 95% Confidence Interval (CI): 1.36 to 1.79, I2=53%). A subgroup meta-analysis incorporating studies that monitored falls prospectively established that the odds of falling was significantly higher in those with pain (n=4,674; OR: 1.71, CI: 1.48 to 1.98, I2=0%). Foot pain was strongly associated with falls (n=691; OR: 2.38, CI: 1.62 to 3.48, I2=8%) as was chronic pain (n= 5,367; OR 1.80, CI: 1.56 to 2.09, I2=0%). Conclusion: Community dwelling older adults with pain were more likely to have fallen in the past 12 months and fall again in the future. Foot and chronic pain were particularly strong risk factors for falls and clinicians should routinely enquire about these when completing falls risk assessments

How much physical activity do people with schizophrenia engage in?:A systematic review, comparative meta-analysis and meta-regression

Objective Physical activity (PA) improves health outcomes in people with schizophrenia. It is unclear how much PA people with schizophrenia undertake and what influences PA participation. We conducted a meta-analysis to investigate PA levels and predictors in people with schizophrenia. Method Major databases were searched from inception till 02/2016 for articles measuring PA (self-report questionnaire (SRQ) or objective measure (e.g. accelerometer)) in people with schizophrenia, including first episode psychosis (FEP). A random effects meta-analysis and meta-regression analysis were conducted. Results 35 studies representing 3453 individuals with schizophrenia (40.0 years; 64.0% male) were included. Engagement in light PA was 80.44 min (95% CI 68.32–92.52, n = 2658), 47.1 min moderate-vigorous PA (95% CI 31.5–62.8, n = 559) and 1.05 min (95% CI 0.48–1.62, n = 2533) vigorous PA per day. People with schizophrenia engaged in significantly less moderate (hedges g = − 0.45, 95% CI − 0.79 to − 0.1, p = 0.01) and vigorous PA (g = − 0.4, 95% CI − 0.60 to − 0.18) versus controls. Higher light to moderate, but lower vigorous PA levels were observed in outpatients and in studies utilizing objective measures versus SRQ. 56.6% (95% CI 45.8–66.8, studies = 12) met the recommended 150 min of moderate physical activity per week. Depressive symptoms and older age were associated with less vigorous PA in meta-regression analyses. Conclusions Our data confirm that people with schizophrenia engage in significantly less moderate and vigorous PA versus controls. Interventions aiming to increase PA, regardless of intensity are indicated for people with schizophrenia, while specifically increasing moderate-vigorous PA should be a priority given the established health benefits

Ex Vivo Modeling of Human Neuroendocrine Tumors in Tissue Surrogates

Few models exist for studying neuroendocrine tumors (NETs), and there are mounting concerns that the currently available array of cell lines is not representative of NET biology. The lack of stable patient-derived NET xenograft models further limits the scientific community's ability to make conclusions about NETs and their response to therapy in patients. To address these limitations, we propose the use of an ex vivo 3D flow-perfusion bioreactor system for culturing and studying patient-derived NET surrogates. Herein, we demonstrate the utility of the bioreactor system for culturing NET surrogates and provide methods for evaluating the efficacy of therapeutic agents on human NET cell line xenograft constructs and patient-derived NET surrogates. We also demonstrate that patient-derived NET tissues can be propagated using the bioreactor system and investigate the near-infrared (NIR) dye IR-783 for its use in monitoring their status within the bioreactor. The results indicate that the bioreactor system and similar 3D culture models may be valuable tools for culturing patient-derived NETs and monitoring their response to therapy ex vivo