Role of walking-exercise therapy after stroke

Stroke commonly leads to reduced mobility, which leads to deconditioning and a worsening of vascular risk factors, such as diabetes. The worsened risk profile leads to further strokes and disability--a vicious cycle for the stroke survivor. Exercise (walking) therapy may break this cycle by providing adequate stimuli for improving gait through plastic adaptation in the brain and through increasing fitness. Randomized, controlled data demonstrate the efficacy for gains in fitness and walking speed, the latter being related to lasting changes in activation patterns of the brainstem and cerebellum. Diabetes and muscle inflammation can also be improved by aerobic exercise training. The scope of this review summarizes these data and identifies unresolved issues related to optimization, intensity and maintenance of therapy effects. Exercise should be an integral part of every rehabilitation program

Performing a Motor Action Enhances Social Reward Processing and Modulates the Neural Processing of Predictive Cues.

Associative learning affects many areas of human behavior. Recently, we showed that the neural response to monetary reward is enhanced by performing an action, suggesting interactions between neural systems controlling motor behavior and reward processing. Given many psychiatric disorders are associated with social anhedonia, a key open question is whether such effects generalize to social rewards, and in how far they affect associative learning. We developed a novel task in which participants (n = 66) received social reward feedback and social punishment either by pressing a button or waiting. Predictive cues were linked to feedback valence with 80% accuracy. Using EEG, we measured the neural response to both predictive cues and social feedback. We found enhanced reward positivity for social reward preceded by an action, and an enhanced N2 for cues predicting negative feedback. Cue-locked P3 amplitude was reduced for cues associated with negative feedback in passive trials only, showing a modulation of outcome anticipation by performing a motor action. This was supported by connectivity analyses showing stronger directed theta synchronization, in line with increased top-down modulation of attention, in active compared with passive trials. These findings suggest that actively obtaining social feedback enhances reward sensitivity and modulates outcome anticipation

Light-chain-induced renal tubular acidosis: effect of sodium bicarbonate on sodium-proton exchange

We measured sodium-proton (Na+/H+) exchange in lymphocytes and platelets of a 46-year-old woman with the adult Fanconi syndrome before, during, and after treatment with NaHCO3. Kappa light chains in her urine and unique but rarely observed crystalline structures confirmed the presence of light-chain nephropathy. Her glomerular filtration rate was only moderately impaired at 72 ml/min. NaHCO3 at 1, 3, and 5 mmol/kg/day for 5 days increased her serum HCO3 and pH from 17 to 21 mmol/l and 7.28 to 7.39 respectively. Plasma renin and aldosterone values were decreased by NaHCO3. Na+/H+ exchange (δHi/min) was measured with the fluorescent marker BCECF after acidification of lymphocytes and platelets with sodium propionate at five (10-50mM) doses. Na+/H+ exchange was accelerated in this patient compared to normal controls. NaHCO3 treatment significantly decreased Na+/H+ exchange in lymphocytes, but not in platelets. These findings suggest that Na+/H+ exchange can be influenced by NaHCO3 ingestion at doses that only modestly affect systemic pH. Since Na+/H+ exchange is involved in stimulus response coupling, cell growth regulation, cell differentiation, and perhaps the progression of nephrosclerosis, these observations may have clinical relevanc

Performing a Motor Action Enhances Social Reward Processing and Modulates the Neural Processing of Predictive Cues

Data Availability Statement: Fully anonymized ERP data are available on OSF at: https://doi.org/10.17605/OSF.IO/2734D (CC-By Attribution 4.0 International). Raw data are available upon request.Associative learning affects many areas of human behavior. Recently, we showed that the neural response to monetary reward is enhanced by performing an action, suggesting interactions between neural systems controlling motor behavior and reward processing. Given many psychiatric disorders are associated with social anhedonia, a key open question is whether such effects generalize to social rewards, and in how far they affect associative learning. We developed a novel task in which participants (n = 66) received social reward feedback and social punishment either by pressing a button or waiting. Predictive cues were linked to feedback valence with 80% accuracy. Using EEG, we measured the neural response to both predictive cues and social feedback. We found enhanced reward positivity for social reward preceded by an action, and an enhanced N2 for cues predicting negative feedback. Cue-locked P3 amplitude was reduced for cues associated with negative feedback in passive trials only, showing a modulation of outcome anticipation by performing a motor action. This was supported by connectivity analyses showing stronger directed theta synchronization, in line with increased top–down modulation of attention, in active compared with passive trials. These findings suggest that actively obtaining social feedback enhances reward sensitivity and modulates outcome anticipation...

The value of an action: Impact of motor behaviour on outcome processing and stimulus preference

While influences of Pavlovian associations on instrumental behaviour are well established, we still do not know how motor actions affect the formation of Pavlovian associations. To address this question, we designed a task in which participants were presented with neutral stimuli, half of which were paired with an active response, half with a passive waiting period. Stimuli had an 80% chance of predicting either a monetary gain or loss. We compared the feedback-related negativity (FRN) in response to predictive stimuli and outcomes, as well as directed phase synchronization before and after outcome presentation between trials with versus without a motor response. We found a larger FRN amplitude in response to outcomes presented after a motor response (active trials). This effect was driven by a positive deflection in active reward trials, which was absent in passive reward trials. Connectivity analysis revealed that the motor action reversed the direction of the phase synchronization at the time of the feedback presentation: Top-down information flow during the outcome anticipation phase in active trials, but bottom-up information flow in passive trials. This main effect of action was mirrored in behavioural data showing that participants preferred stimuli associated with an active response. Our findings suggest an influence of neural systems that initiate motor actions on neural systems involved in reward processing. We suggest that motor actions might modulate the brain responses to feedback by affecting the dynamics of brain activity towards optimizing the processing of the resulting action outcome.Royal Society (RGS\R1\191344)

Vanishing pachy-choroid in pachychoroid neovasculopathy under long-term anti-vascular endothelial growth factor therapy

BACKGROUND To investigate the diagnostic value of choroidal thickness in the definition of pachychoroid neovasculopathy (PNV), especially in eyes treated with anti-vascular endothelial growth factor (VEGF) therapy. METHODS Twenty-two consecutive eyes of 11 patients with uni- or bilateral PNV were analyzed. Anti-VEGF treatment was correlated with changes in choroidal thickness on enhanced depth imaging optical coherence tomography. RESULTS There were 14 eyes with PNV and 8 non-neovascular partner eyes. Mean age was 64.2 ± 4.0 (range: 60-72), total follow-up was 1.8 ± 0.4 (1-2) years. In PNV eyes, choroidal thickness at baseline was 400 ± 58 (269-485) μm. After two years and 13 anti-VEGF injections on average, a mean reduction of - 39 ± 10 (- 26 to - 56) % to final 241 ± 52 (162-327) μm was observed (p~ 0.13 for all comparisons). A significant correlation of choroidal thinning and anti-VEGF injection rate was observed at year one (r = - 0.79; R2~= 0.63; p~= 0.00073) and two (r = - 0.69; R2~= 0.48; p~= 0.019). While 85.7% of PNV eyes exceeded a pachychoroid threshold of ≥350 μm at baseline, this figure dropped to 21.4% at year one and 0% at year two. CONCLUSION In PNV, choroidal thickness significantly decreases with anti-VEGF therapy, resembling a \textquotedblvanishing pachy-choroid\textquotedbl, and thus does not represent a valid long-term diagnostic criterium, especially when differentiating PNV from nAMD

Data-driven grading of acute graft-versus-host disease

: Despite advances in allogeneic hematopoietic cell transplantation, acute graft-versus-host disease (aGVHD) remains its leading complication, yet with heterogeneous outcomes. Here, we analyzed aGVHD phenotypes and clinical classifications in depth in large, multicenter cohorts involving 3019 patients and addressed prevailing gaps by developing data-driven models. We compared, tested and verified these along with all conventional classifications in independent cohorts and found that data-driven grading outperformed conventional grading in Akaike information criterion and concordance index metrics. Data-driven classifications refined aGVHD assessment with up to 12 severity grades, which were associated with distinct nonrelapse mortality (NRM) and confirmed the key role of intestinal aGVHD. We developed an online calculator for physicians to implement principal component-derived grading (PC1). These results provide substantial insight into the evaluation of aGVHD phenotypes and multiorgan involvement, which relegates the exclusive reporting of overall aGVHD severity grades in transplant registries and clinical trials. Data-driven aGVHD grading provides an expandable platform to refine classification and transplant risk assessment

Monitoring and Pay: An Experiment on Employee Performance under Endogenous Supervision

We present an experimental test of a shirking model where monitoring intensity is endogenous and effort a continuous variable. Wage level, monitoring intensity and consequently the desired enforceable effort level are jointly determined by the maximization problem of the firm. As a result, monitoring and pay should be complements. In our experiment, between and within treatment variation is qualitatively in line with the normative predictions of the model under standard assumptions. Yet, we also find evidence for reciprocal behavior. Our data analysis shows, however, that it does not pay for the employer to solely rely on the reciprocity of employees

Glucose and triglyceride excursions following a standardized meal in individuals with diabetes: ELSA-Brasil study

Objective: To assess glucose and triglyceride excursions 2 hours after the ingestion of a standardized meal and their associations with clinical characteristics and cardiovascular complications in individuals with diabetes. Research design and methods: Blood samples of 898 subjects with diabetes were collected at fasting and 2 hours after a meal containing 455 kcal, 14 g of saturated fat and 47 g of carbohydrates. Self-reported morbidity, socio-demographic characteristics and clinical measures were obtained by interview and exams performed at the baseline visit of the ELSA-Brasil cohort study. Results: Median (interquartile range, IQR) for fasting glucose was 150.5 (123–198) mg/dL and for fasting triglycerides 140 (103–199) mg/dL. The median excursion for glucose was 45 (15–76) mg/dL and for triglycerides 26 (11–45) mg/dL. In multiple linear regression, a greater glucose excursion was associated with higher glycated hemoglobin (10.7, 95% CI 9.1–12.3 mg/dL), duration of diabetes (4.5; 2.6–6.4 mg/dL, per 5 year increase), insulin use (44.4; 31.7–57.1 mg/dL), and age (6.1; 2.5–9.6 mg/dL, per 10 year increase); and with lower body mass index (−5.6; −8.4– -2.8 mg/dL, per 5 kg/m2 increase). In adjusted logistic regression models, a greater glucose excursion was marginally associated with the presence of cardiovascular comorbidities (coronary heart disease, myocardial infarction and angina) in those with obesity. Conclusions: A greater postprandial glycemic response to a small meal was positively associated with indicators of a decreased capacity for insulin secretion and negatively associated with obesity. No pattern of response was observed with a greater postprandial triglyceride excursion

Daily-life tele-monitoring of motor performance in stroke survivors

The objective of the EU project INTERACTION is to develop an unobtrusive and modular sensing system for objective monitoring of daily-life motor performance of stroke survivors. This will enable clinical professionals to advise their patients about their continued daily-life activity profile and home training, and evaluate and optimize rehabilitation programs.A modular textile-integrated sensing system was developed and performance and capacity measures were proposed and clinically tested in stroke subject.Telemonitoring facilities were developed and tested. In the last stage of the project, the system will be tested during daily-life