Using non-invasive transcranial stimulation to improve motor and cognitive function in Parkinson's disease: A systematic review and meta-analysis

Parkinson\u27s disease (PD) is a neurodegenerative disorder affecting motor and cognitive abilities. There is no cure for PD, therefore identifying safe therapies to alleviate symptoms remains a priority. This meta-analysis quantified the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (TES) to improve motor and cognitive dysfunction in PD. PubMed, EMBASE, Web of Science, Google Scholar, Scopus, Library of Congress and Cochrane library were searched. 24 rTMS and 9 TES studies (n = 33) with a sham control group were included for analyses. The Physiotherapy Evidence Database and Cochrane Risk of Bias showed high quality (7.5/10) and low bias with included studies respectively. Our results showed an overall positive effect in favour of rTMS (SMD = 0.394, CI [0.106–0.683], p = 0.007) and TES (SMD = 0.611, CI [0.188–1.035], p = 0.005) compared with sham stimulation on motor function, with no significant differences detected between rTMS and TES (Q [1] = 0.69, p = 0.406). Neither rTMS nor TES improved cognition. No effects for stimulation parameters on motor or cognitive function were observed. To enhance the clinical utility of non-invasive brain stimulation (NBS), individual prescription of stimulation parameters based upon symptomology and resting excitability state should be a priority of future research

No one knows what will happen after these five years': narratives of ART, access and agency in Nigeria

Rural Nigerians pursue a range of strategies to maximize current and future access to HIV treatment in the context of securing livelihoods and minimizing the social and economic risks of stigma. This study reports on qualitative interviews with service providers and anti-retroviral therapy (ART) patients accessing care in Benue State, Nigeria, or travelling several hours to Abuja for treatment (n = 34). Nigerians living with HIV are keenly aware of the fragility and complex global and local politics of funding. Their narratives of pervasive stigma, economic and health system barriers to access, growing fears that free ART will cease, and strategies to secure access to care reveal a sophisticated synthesis of social determinants of health and clinical care, and challenge practitioners, planners, and scholars to take a similarly robust and nuanced approach to vulnerability, access, and agency.Department of HE and Training approved lis

The Retrovirology Open Access experience

The Retrovirology Open Access experience after publishing more than 500 articles is discussed

Associations of extracurricular physical activity patterns and body composition components in a multi-ethnic population of UK children (the Size and Lung Function in Children study): a multilevel modelling analysis.

BACKGROUND: Body Mass Index (BMI) is a common outcome when assessing associations between childhood overweight and obesity and physical activity patterns. However, the fat and fat-free components of BMI, measured by the Fat Mass Index (FMI) and Fat-Free Mass Index (FFMI), may show contrasting associations with physical activity, while ethnic groups may vary in both physical activity patterns and body composition. Body composition must therefore be evaluated when assessing the associations between childhood overweight and obesity and physical activity in multi-ethnic populations. METHODS: This cross-sectional study investigated associations of BMI, FMI and FFMI z-scores with extracurricular physical activity for 2171 London primary schoolchildren (aged 5-11 years) of black, South Asian and white/other ethnicity. Multilevel mixed-effects ordered logistic modelling was used, adjusting for age, sex and family and neighbourhood socioeconomic status as potential confounders. RESULTS: Controlling for ethnicity and individual, family and neighbourhood socioeconomic confounders, actively commuting children had significantly lower Odds Ratios for being in high BMI (Odds Ratio (OR) = 0.678; 95 % Confidence Interval (CI) = 0.531 - 0.865; p - value = 0.002) and FMI z-score groups (OR = 0.679; 95 % CI = 0.499 - 0.922; p = 0.013), but not FFMI z-score groups, than passive commuters. Children doing sports less than once a week had lower Odds Ratios for being in high BMI (OR = 0.435; 95 % CI = 0.236 - 0.802; p = 0.008) and FFMI (OR = 0.455; 95 % CI = 0.214 - 0.969; p = .041) z-score categories compared to daily active children. Differences in FMI between groups did not reach the significance threshold. A trend towards statistical significance was obtained whereby children's complete inactivity was associated with higher odds for being in higher BMI (OR = 2.222 : 95 % CI = 0.977 - 5.052; p = .057) and FMI z-score groups (OR = 2.485 : 95 % CI = 0.961 - 6.429; p = .060). FFMI z-scores did not show a similar trend with complete inactivity. CONCLUSIONS: Active commuting was objectively associated with lower adiposity, while more frequent extracurricular sports participation was correlated with greater fat-free mass accretion. These relationships were independent of ethnicity and individual, family or neighbourhood socioeconomic confounding factors

Orphan receptor GPR110, an oncogene overexpressed in lung and prostate cancer

<p>Abstract</p> <p>Background</p> <p>GPR110 is an orphan G protein-coupled receptor--a receptor without a known ligand, a known signaling pathway, or a known function. Despite the lack of information, one can assume that orphan receptors have important biological roles. In a retroviral insertion mutagenesis screen in the mouse, we identified GPR110 as an oncogene. This prompted us to study the potential isoforms that can be gleaned from known GPR110 transcripts, and the expression of these isoforms in normal and transformed human tissues.</p> <p>Methods</p> <p>Various epitope-tagged isoforms of GPR110 were expressed in cell lines and assayed by western blotting to determine cleavage, surface localization, and secretion patterns. GPR110 transcript and protein levels were measured in lung and prostate cancer cell lines and clinical samples, respectively, by quantitative PCR and immunohistochemistry.</p> <p>Results</p> <p>We found four potential splice variants of GPR110. Of these variants, we confirmed three as being expressed as proteins on the cell surface. Isoform 1 is the canonical form, with a molecular mass of about 100 kD. Isoforms 2 and 3 are truncated products of isoform 1, and are 25 and 23 kD, respectively. These truncated isoforms lack the seven-span transmembrane domain characteristic of GPR proteins and thus are not likely to be membrane anchored; indeed, isoform 2 can be secreted. Compared with the median gene expression of ~200 selected genes, GPR110 expression was low in most tissues. However, it had higher than average gene expression in normal kidney tissue and in prostate tissues originating from older donors. Although identified as an oncogene in murine T lymphomas, GPR110 is greatly overexpressed in human lung and prostate cancers. As detected by immunohistochemistry, GPR110 was overexpressed in 20 of 27 (74%) lung adenocarcinoma tissue cores and in 17 of 29 (59%) prostate adenocarcinoma tissue cores. Additionally, staining with a GPR110 antibody enabled us to differentiate between benign prostate hyperplasia and potential incipient malignancy.</p> <p>Conclusion</p> <p>Our work suggests a role for GPR110 in tumor physiology and supports it as a potential therapeutic candidate and disease marker for both lung and prostate cancer.</p

Rare coding SNP in DZIP1 gene associated with late-onset sporadic Parkinson's disease

We present the first application of the hypothesis-rich mathematical theory to genome-wide association data. The Hamza et al. late-onset sporadic Parkinson's disease genome-wide association study dataset was analyzed. We found a rare, coding, non-synonymous SNP variant in the gene DZIP1 that confers increased susceptibility to Parkinson's disease. The association of DZIP1 with Parkinson's disease is consistent with a Parkinson's disease stem-cell ageing theory.Comment: 14 page

DRAM-3 modulates autophagy and promotes cell survival in the absence of glucose

Macroautophagy is a membrane-trafficking process that delivers cytoplasmic constituents to lysosomes for degradation. The process operates under basal conditions as a mechanism to turnover damaged or misfolded proteins and organelles. As a result, it has a major role in preserving cellular integrity and viability. In addition to this basal function, macroautophagy can also be modulated in response to various forms of cellular stress, and the rate and cargoes of macroautophagy can be tailored to facilitate appropriate cellular responses in particular situations. The macroautophagy machinery is regulated by a group of evolutionarily conserved autophagy-related (ATG) proteins and by several other autophagy regulators, which either have tissue-restricted expression or operate in specific contexts. We report here the characterization of a novel autophagy regulator that we have termed DRAM-3 due to its significant homology to damage-regulated autophagy modulator (DRAM-1). DRAM-3 is expressed in a broad spectrum of normal tissues and tumor cells, but different from DRAM-1, DRAM-3 is not induced by p53 or DNA-damaging agents. Immunofluorescence studies revealed that DRAM-3 localizes to lysosomes/autolysosomes, endosomes and the plasma membrane, but not the endoplasmic reticulum, phagophores, autophagosomes or Golgi, indicating significant overlap with DRAM-1 localization and with organelles associated with macroautophagy. In this regard, we further proceed to show that DRAM-3 expression causes accumulation of autophagosomes under basal conditions and enhances autophagic flux. Reciprocally, CRISPR/Cas9-mediated disruption of DRAM-3 impairs autophagic flux confirming that DRAM-3 is a modulator of macroautophagy. As macroautophagy can be cytoprotective under starvation conditions, we also tested whether DRAM-3 could promote survival on nutrient deprivation. This revealed that DRAM-3 can repress cell death and promote long-term clonogenic survival of cells grown in the absence of glucose. Interestingly, however, this effect is macroautophagy-independent. In summary, these findings constitute the primary characterization of DRAM-3 as a modulator of both macroautophagy and cell survival under starvation conditions

Chronic joint disease caused by persistent Chikungunya virus infection is controlled by the adaptive immune response

Chikungunya virus (CHIKV) is a reemerging mosquito-borne pathogen that causes incapacitating disease in humans characterized by intense joint pain that can persist for weeks, months, or even years. Although there is some evidence of persistent CHIKV infection in humans suffering from chronic rheumatologic disease symptoms, little is known about chronic disease pathogenesis, and no specific therapies exist for acute or chronic CHIKV disease. To investigate mechanisms of chronic CHIKV-induced disease, we utilized a mouse model and defined the duration of CHIKV infection in tissues and the associated histopathological changes. Although CHIKV RNA was readily detectable in a variety of tissues very early after infection, CHIKV RNA persisted specifically in joint-associated tissues for at least 16 weeks. Inoculation of Rag1(−/−) mice, which lack T and B cells, resulted in higher viral levels in a variety of tissues, suggesting that adaptive immunity controls the tissue specificity and persistence of CHIKV infection. The presence of CHIKV RNA in tissues of wild-type and Rag1(−/−) mice was associated with histopathological evidence of synovitis, arthritis, and tendonitis; thus, CHIKV-induced persistent arthritis is not mediated primarily by adaptive immune responses. Finally, we show that prophylactic administration of CHIKV-specific monoclonal antibodies prevented the establishment of CHIKV persistence, whereas therapeutic administration had tissue-specific efficacy. These findings suggest that chronic musculoskeletal tissue pathology is caused by persistent CHIKV infection and controlled by adaptive immune responses. Our results have significant implications for the development of strategies to mitigate the disease burden associated with CHIKV infection in humans

Noisy-threshold control of cell death

<p>Abstract</p> <p>Background</p> <p>Cellular responses to death-promoting stimuli typically proceed through a differentiated multistage process, involving a lag phase, extensive death, and potential adaptation. Deregulation of this chain of events is at the root of many diseases. Improper adaptation is particularly important because it allows cell sub-populations to survive even in the continuous presence of death conditions, which results, among others, in the eventual failure of many targeted anticancer therapies.</p> <p>Results</p> <p>Here, I show that these typical responses arise naturally from the interplay of intracellular variability with a threshold-based control mechanism that detects cellular changes in addition to just the cellular state itself. Implementation of this mechanism in a quantitative model for T-cell apoptosis, a prototypical example of programmed cell death, captures with exceptional accuracy experimental observations for different expression levels of the oncogene Bcl-x_Land directly links adaptation with noise in an ATP threshold below which cells die.</p> <p>Conclusions</p> <p>These results indicate that oncogenes like Bcl-x_L, besides regulating absolute death values, can have a novel role as active controllers of cell-cell variability and the extent of adaptation.</p

Technology-assisted training of arm-hand skills in stroke: concepts on reacquisition of motor control and therapist guidelines for rehabilitation technology design

<p>Abstract</p> <p>Background</p> <p>It is the purpose of this article to identify and review criteria that rehabilitation technology should meet in order to offer arm-hand training to stroke patients, based on recent principles of motor learning.</p> <p>Methods</p> <p>A literature search was conducted in PubMed, MEDLINE, CINAHL, and EMBASE (1997–2007).</p> <p>Results</p> <p>One hundred and eighty seven scientific papers/book references were identified as being relevant. Rehabilitation approaches for upper limb training after stroke show to have shifted in the last decade from being analytical towards being focussed on environmentally contextual skill training (task-oriented training). Training programmes for enhancing motor skills use patient and goal-tailored exercise schedules and individual feedback on exercise performance. Therapist criteria for upper limb rehabilitation technology are suggested which are used to evaluate the strengths and weaknesses of a number of current technological systems.</p> <p>Conclusion</p> <p>This review shows that technology for supporting upper limb training after stroke needs to align with the evolution in rehabilitation training approaches of the last decade. A major challenge for related technological developments is to provide engaging patient-tailored task oriented arm-hand training in natural environments with patient-tailored feedback to support (re) learning of motor skills.</p