Transcranial direct current stimulation in neglect rehabilitation after stroke: a systematic review.

Hemispatial neglect is one of the most frequent attention disorders after stroke. The presence of neglect is associated with longer hospital stays, extended rehabilitation periods, and poorer functional recovery. Transcranial direct current stimulation (tDCS) is a new technique with promising results in neglect rehabilitation; therefore, the objective of this systematic review, performed following the PRISMA guidelines, is to evaluate the effectiveness of tDCS on neglect recovery after stroke. The search was done in MEDLINE (PubMed), Web of Science, Scopus, Cochrane Library, and BioMed Central databases. A total of 311 articles were found; only 11 met the inclusion criteria, including 152 post-stroke patients in total. Methodological quality and risk of bias were assessed for all the studies, and methodological characteristics of the studies, sample sizes, methods, main results, and other relevant data were extracted. tDCS intervention ranged from one to twenty sessions distributed in 1 day to 4 weeks, with intensity ranged from 1 to 2 mA. We found moderate evidence for the efficacy of tDCS in the rehabilitation of hemispatial neglect after a stroke, being more effective in combination with other interventions. Nonetheless, the limited number of studies and some studies' design characteristics makes it risky to draw categorical conclusions. Since scientific evidence is still scarce, further research is needed to determine the advantage of this treatment in acute, sub-acute and chronic stroke patients. Future studies should include larger samples, longer follow-ups, and broader neurophysiological assessments, with the final aim of establishing the appropriate use of tDCS as an adjuvant intervention in neurorehabilitation settings.pre-print964 K

Prefronto-cerebellar neuromodulation affects appetite in obesity

Human neuroimaging studies have consistently reported changes in cerebellar function and integrity in association with obesity. To date, however, the nature of this link has not been studied directly. Emerging evidence suggests a role for the cerebellum in higher cognitive functions through reciprocal connections with the prefrontal cortex. The purpose of this exploratory study was to examine appetite changes associated with noninvasive prefronto-cerebellar neuromodulation in obesity. 12 subjects with class I obesity (mean BMI 32.9 kg/m2) underwent a randomized, single-blinded, sham-controlled, crossover study, during which they received transcranial direct current stimulation (tDCS; active/sham) aimed at simultaneously enhancing the activity of the prefrontal cortex and decreasing the activity of the cerebellum. Changes in appetite (state and food-cue-triggered) and performance in a food-modified working memory task were evaluated. We found that active tDCS caused an increase in hunger and desire to eat following food-cue exposure. In line with these data, subjects also tended to make more errors during the working memory task. No changes in basic motor performance occurred. This study represents the first demonstration that prefronto-cerebellar neuromodulation can influence appetite in individuals with obesity. While preliminary, our findings support a potential role for prefronto-cerebellar pathways in the behavioral manifestations of obesity

Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk

Background Quitting tobacco or alcohol use has been reported to reduce the head and neck cancer risk in previous studies. However, it is unclear how many years must pass following cessation of these habits before the risk is reduced, and whether the risk ultimately declines to the level of never smokers or never drinkers. Methods We pooled individual-level data from case-control studies in the International Head and Neck Cancer Epidemiology Consortium. Data were available from 13 studies on drinking cessation (9167 cases and 12 593 controls), and from 17 studies on smoking cessation (12 040 cases and 16 884 controls). We estimated the effect of quitting smoking and drinking on the risk of head and neck cancer and its subsites, by calculating odds ratios (ORs) using logistic regression models. Results Quitting tobacco smoking for 1-4 years resulted in a head and neck cancer risk reduction [OR 0.70, confidence interval (CI) 0.61-0.81 compared with current smoking], with the risk reduction due to smoking cessation after ≥20 years (OR 0.23, CI 0.18-0.31), reaching the level of never smokers. For alcohol use, a beneficial effect on the risk of head and neck cancer was only observed after ≥20 years of quitting (OR 0.60, CI 0.40-0.89 compared with current drinking), reaching the level of never drinkers. Conclusions Our results support that cessation of tobacco smoking and cessation of alcohol drinking protect against the development of head and neck cance

Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk.

BACKGROUND: Quitting tobacco or alcohol use has been reported to reduce the head and neck cancer risk in previous studies. However, it is unclear how many years must pass following cessation of these habits before the risk is reduced, and whether the risk ultimately declines to the level of never smokers or never drinkers. METHODS: We pooled individual-level data from case-control studies in the International Head and Neck Cancer Epidemiology Consortium. Data were available from 13 studies on drinking cessation (9167 cases and 12 593 controls), and from 17 studies on smoking cessation (12 040 cases and 16 884 controls). We estimated the effect of quitting smoking and drinking on the risk of head and neck cancer and its subsites, by calculating odds ratios (ORs) using logistic regression models. RESULTS: Quitting tobacco smoking for 1-4 years resulted in a head and neck cancer risk reduction [OR 0.70, confidence interval (CI) 0.61-0.81 compared with current smoking], with the risk reduction due to smoking cessation after >/=20 years (OR 0.23, CI 0.18-0.31), reaching the level of never smokers. For alcohol use, a beneficial effect on the risk of head and neck cancer was only observed after >/=20 years of quitting (OR 0.60, CI 0.40-0.89 compared with current drinking), reaching the level of never drinkers. CONCLUSIONS: Our results support that cessation of tobacco smoking and cessation of alcohol drinking protect against the development of head and neck cancer

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. METHODS: The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries-Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised

Neural basis of video gaming: A systematic review

Background: Video gaming is an increasingly popular activity in contemporary society, especially among young people, and video games are increasing in popularity not only as a research tool but also as a field of study. Many studies have focused on the neural and behavioral effects of video games, providing a great deal of video game derived brain correlates in recent decades. There is a great amount of information, obtained through a myriad of methods, providing neural correlates of video games. Objectives: We aim to understand the relationship between the use of video games and their neural correlates, taking into account the whole variety of cognitive factors that they encompass. Methods: A systematic review was conducted using standardized search operators that included the presence of video games and neuro-imaging techniques or references to structural or functional brain changes. Separate categories were made for studies featuring Internet Gaming Disorder and studies focused on the violent content of video games. Results: A total of 116 articles were considered for the final selection. One hundred provided functional data and 22 measured structural brain changes. One-third of the studies covered video game addiction, and 14%focused on video game related violence. Conclusions: Despite the innate heterogeneity of the field of study, it has been possible to establish a series of links between the neural and cognitive aspects, particularly regarding attention, cognitive control, visuospatial skills, cognitive workload, and reward processing. However, many aspects could be improved. The lack of standardization in the different aspects of video game related research, such as the participants¿ characteristics, the features of each video game genre and the diverse study goals could contribute to discrepancies in many related studies. ©2017 Palaus, Marron, Viejo-Sobera and Redolar-Ripoll

Neural basis of video gaming: a systematic review.

Video gaming is an increasingly popular activity in contemporary society, especially among young people, and video games are increasing in popularity not only as a research tool but also as a field of study. Many studies have focused on the neural and behavioral effects of video games, providing a great deal of video game derived brain correlates in recent decades. There is a great amount of information, obtained through a myriad of methods, providing neural correlates of video games.We aim to understand the relationship between the use of video games and their neural correlates, taking into account the whole variety of cognitive factors that they encompass. A systematic review was conducted using standardized search operators that included the presence of video games and neuro-imaging techniques or references to structural or functional brain changes. Separate categories were made for studies featuring Internet Gaming Disorder and studies focused on the violent content of video games. A total of 116 articles were considered for the final selection. One hundred provided functional data and 22 measured structural brain changes. One-third of the studies covered video game addiction, and 14% focused on video game related violence.Despite the innate heterogeneity of the field of study, it has been possible to establish a series of links between the neural and cognitive aspects, particularly regarding attention, cognitive control, visuospatial skills, cognitive workload, and reward processing. However, many aspects could be improved. The lack of standardization in the different aspects of video game related research, such as the participants' characteristics, the features of each video game genre and the diverse study goals could contribute to discrepancies in many related studies

Impact of Prefrontal Theta Burst Stimulation on Clinical Neuropsychological Tasks

International audienceTheta burst stimulation (TBS) protocols hold high promise in neuropsychological rehabilitation. Nevertheless, their ability to either decrease (continuous, cTBS) or increase (intermittent, iTBS) cortical excitability in areas other than the primary motor cortex, and their consistency modulating human behaviors with clinically relevant tasks remain to be fully established. The behavioral effects of TBS over the dorsolateral prefrontal cortex (dlPFC) are particularly interesting given its involvement in working memory (WM) and executive functions (EF), often impaired following frontal brain damage. We aimed to explore the ability of cTBS and iTBS to modulate WM and EF in healthy individuals, assessed with clinical neuropsychological tests (Digits Backward, 3-back task, Stroop Test, and Tower of Hanoi). To this end, 36 participants were assessed using the four tests 1 week prior to stimulation and immediately following a single session of either cTBS, iTBS, or sham TBS, delivered to the left dlPFC. No significant differences were found across stimulation conditions in any of the clinical tasks. Nonetheless, in some of them, active stimulation induced significant pre/post performance modulations, which were not found for the sham condition. More specifically, sham stimulation yielded improvements in the 3-back task and the Color, Color-Word, and Interference Score of the Stroop Test, an effect likely caused by task practice. Both, iTBS and cTBS, produced improvements in Digits Backward and impairments in 3-back task accuracy. Moreover, iTBS increased Interference Score in the Stroop Test in spite of the improved word reading and impaired color naming, whereas cTBS decreased the time required to complete the Tower of Hanoi. Differing from TBS outcomes reported for cortico-spinal measures on the primary motor cortex, our analyses did not reveal any of the expected performance differences across stimulation protocols. However, if one considers independently pre/post differences for each individual outcome measure and task, either one or both of the active protocols appeared to modulate WM and EF. We critically discuss the value, potential explanations, and some plausible interpretations for this set of subtle impacts of left dlPFC TBS in humans

Impact of Prefrontal Theta Burst Stimulation on Clinical Neuropsychological Tasks

Theta burst stimulation (TBS) protocols hold high promise in neuropsychological rehabilitation. Nevertheless, their ability to either decrease (continuous, cTBS) or increase (intermittent, iTBS) cortical excitability in areas other than the primary motor cortex, and their consistency modulating human behaviors with clinically relevant tasks remain to be fully established. The behavioral effects of TBS over the dorsolateral prefrontal cortex (dlPFC) are particularly interesting given its involvement in working memory (WM) and executive functions (EF), often impaired following frontal brain damage. We aimed to explore the ability of cTBS and iTBS to modulate WM and EF in healthy individuals, assessed with clinical neuropsychological tests (Digits Backward, 3-back task, Stroop Test, and Tower of Hanoi). To this end, 36 participants were assessed using the four tests 1 week prior to stimulation and immediately following a single session of either cTBS, iTBS, or sham TBS, delivered to the left dlPFC. No significant differences were found across stimulation conditions in any of the clinical tasks. Nonetheless, in some of them, active stimulation induced significant pre/post performance modulations, which were not found for the sham condition. More specifically, sham stimulation yielded improvements in the 3-back task and the Color, Color-Word, and Interference Score of the Stroop Test, an effect likely caused by task practice. Both, iTBS and cTBS, produced improvements in Digits Backward and impairments in 3-back task accuracy. Moreover, iTBS increased Interference Score in the Stroop Test in spite of the improved word reading and impaired color naming, whereas cTBS decreased the time required to complete the Tower of Hanoi. Differing from TBS outcomes reported for cortico-spinal measures on the primary motor cortex, our analyses did not reveal any of the expected performance differences across stimulation protocols. However, if one considers independently pre/post differences for each individual outcome measure and task, either one or both of the active protocols appeared to modulate WM and EF. We critically discuss the value, potential explanations, and some plausible interpretations for this set of subtle impacts of left dlPFC TBS in humans