Single-Session Cerebellar Transcranial Direct Current Stimulation Improves Postural Stability and Reduces Ataxia Symptoms in Spinocerebellar Ataxia.

Spinocerebellar ataxia (SCA) results in balance and coordination impairment, and current treatments have limited efficacy. Recent evidence suggests that combining postural training with cerebellar transcranial direct current stimulation (ctDCS) can improve these symptoms. However, the combined effects of ctDCS and postural training on individuals with spinocerebellar ataxia remain underexplored. Ten volunteers with (SCA type 3) participated in a triple-blind, randomized, crossover study to receive a single session of ctDCS (2 mA for 20 min) and a sham ctDCS session separated by at least one week. The Biodex Balance System was used to assess balance at each session, measuring overall stability index, anteroposterior stability index, and medial-lateral stability index. As secondary outcomes, cerebellar ataxia symptoms were evaluated using the 8-item Scale for Assessment and Rating of Ataxia. The assessments were conducted before and after each session. The results indicated that ctDCS enhanced the overall stability index when compared to sham ctDCS (Z = -2.10, p = 0.03), although it did not significantly affect the anteroposterior or medial-lateral stability indices. Compared to the baseline, a single session of ctDCS reduced appendicular symptoms related to cerebellar ataxia, as evidenced by improvements in the nose-finger test (Z = -2.07, p = 0.04), fast alternating hand movements (Z = -2.15, p = 0.03), and heel-to-shin slide (Z = -1.91, p = 0.05). In conclusion, our study suggests that a single session of ctDCS, in combination with postural training, can enhance balance and alleviate ataxia symptoms in individuals with cerebellar ataxia. This study was approved by the local research ethics committee (No. 2.877.813) and registered on clinicaltrials.org (NCT04039048 - https://www.clinicaltrials.gov/study/NCT04039048 ) on 2019-07-28.

Do Higher Transcranial Direct Current Stimulation Doses Lead to Greater Gains in Upper Limb Motor Function in Post-Stroke Patients?

Objective: To investigate whether a higher number of transcranial direct current stimulation (tDCS) sessions results in a greater improvement in upper limb function in chronic post-stroke patients. Materials and methods: A randomized, sham-controlled, double-blind clinical trial was conducted in 57 chronic post-stroke patients (≥ 3 months after their injuries). The patients were allocated to receive sessions of tDCS combined with physiotherapy and divided into three groups (anodal, cathodal, and sham). The Fugl-Meyer Assessment of Upper Extremity (FMA-UE) was used to assess the sensorimotor impairment of the patients' upper limbs before (baseline) and after five and ten sessions. The percentage of patients who achieved a clinically significant improvement (> five points on the FMA-UE) was also analyzed. Results: The FMA-UE score increased after five and ten sessions in both the anodal and cathodal tDCS groups, respectively, compared to the baseline. However, in the sham group, the FMA-UE score increased only after ten sessions. When compared to the sham group, the mean difference from the baseline after five sessions was higher in the anodal tDCS group. The percentage of individuals who achieved greater clinical improvement was higher in the stimulation groups than in the sham group and after ten sessions when compared to five sessions. Conclusions: Our results suggest that five tDCS sessions are sufficient to augment the effect of standard physiotherapy on upper limb function recovery in chronic post-stroke patients, and ten sessions resulted in greater gains.

Lack of Association of Polymorphisms in IL22 and IL22RA1 Genes with Fibrosis Severity in Patients with Chronic Hepatitis C.

The IL-22 pathway has been shown to play an important role in the pathogenesis of liver fibrosis. However, little is known about the role of single-nucleotide polymorphisms (SNPs) in IL-22-related genes in relation to the severity of liver fibrosis. This study aimed to investigate the association of polymorphisms in IL22 and IL22RA1 genes with the severity of liver fibrosis in patients with chronic hepatitis C. A total of 326 patients (165 with mild fibrosis and 161 with severe fibrosis) were included. Four SNPs in IL22 (rs1179251, rs2227473, rs1012356, and rs2227485) and two in IL22RA1 (rs4648936 and rs3795299) were evaluated by real-time PCR. No significant association was observed between the polymorphisms studied and the severity of liver fibrosis. The SNPs rs1179251, rs2227473, rs1012356, and rs2227485 in IL22 and rs4648936 and rs3795299 in IL22RA1 may not be involved in the pathogenesis of liver fibrosis in patients with chronic hepatitis C.

A time series analysis of detection and mortality of hepatitis C in Brazil, 2008-2018.

BACKGROUND: The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030. In Brazil, efforts have been undertaken to achieve this goal; there are, however, great challenges. It is important to understand the disease profile in different regions of the country in order to design strategies to fight the disease nationwide. The objective of this study was to analyse the time trend of the incidence and mortality of hepatitis C in Brazil during the period from 2008 to 2018 according to sociodemographic and clinical characteristics. METHODS: All newly diagnosed cases of hepatitis C reported between 2008 and 2018, in all regions of Brazil, were included. The indicators were obtained from the databases of the Brazilian Ministry of Health. For the time series analysis, a joinpoint regression model was used. RESULTS: Between 2008 and 2018, 136,759 newly diagnosed cases of hepatitis C were reported considering anti-HCV and HCV RNA positivity, and 271,624 newly diagnosed cases were reported considering one or another positive test. The majority of the records were concentrated in the Southeast (61%) and South (26.2%) Regions. The joinpoint regression model indicated an increasing trend in the detection rate of hepatitis C in Brazil, but there was a decreasing trend in the mortality rate during the period analysed. CONCLUSIONS: Differences were observed in the time trend of hepatitis C and in the sociodemographic and clinical characteristics in different regions of Brazil. These data can provide support to design strategies for the elimination of hepatitis C in Brazil, according to regional particularities.

Independent community walking after a short protocol of repetitive transcranial magnetic stimulation associated with body weight-support treadmill training in a patient with chronic spinal cord injury: a case report.

PURPOSE: Our report describes the effect of repetitive transcranial magnetic stimulation (rTMS) combined with body weight-supported treadmill training (BWSTT) on independent gait recovery in a patient with incomplete spinal cord injury (iSCI). CASE DESCRIPTION: The patient was a 31-year-old male, household ambulator (aid walker) and community wheelchair user who was 8.5 year post traumatic iSCI (T8 vertebra injury, AIS D). INTERVENTION: The patient participated in 12 sessions (three times/week for four weeks) of rTMS (1800 pulses, 10 Hz, intensity of 90% resting motor threshold) followed by BWSTT (15-20 min, moderate intensity). OUTCOMES: After treatment, the patient's score increased 3 points on the Walking Index for Spinal Cord Injury II (walking independence) and he became a community ambulator with crutches. His American Spinal Injury Association (ASIA) lower extremities motor score (motor function) increased from 33 to 45 points and the Spinal Cord Independence Measure III (functional independence) score increased from 23 to 29 for the mobility indoors/outdoors subscale. The patient's lower limb spasticity was reduced (Modified Ashworth Scale), and quality of life improved based on the Short-Form Health Survey - 36, and the Patient Global Impression of Change Scale showed considerable perception of improvement. CONCLUSION: Our report suggests that a short protocol of rTMS combined with BWSTT improved walking independence, motor function, spasticity, functional mobility and quality of life in this patient with iSCI.

Liver expression of IL-22, IL-22R1 and IL-22BP in patients with chronic hepatitis C with different fibrosis stages.

AIMS: Liver fibrosis is the result of an exacerbated wound-healing response associated with chronic liver injury. Interleukin-22 (IL-22) plays a key role in liver disease, through either a protective or an adverse role, depending on the context. The relationship between IL-22 and its receptors IL-22R1 and IL-22BP (soluble inhibitor) in liver fibrosis is unknown. In this study, we assessed the presence and quantity of IL-22, IL-22R1, and IL-22BP-producing cells in liver tissues of patients with chronic hepatitis C. METHODS AND RESULTS: The number of IL-22-producing cells was significantly higher in stages F1, F2, and F3 when compared to F0 or F4 (p < 0.05). The immunostaining of IL-22R1 decreased as liver fibrosis increased from F1 to F4. On the other hand, the concentration of IL-22BP-producing cells was higher in patients with cirrhosis (F4). Furthermore, the IL-22BP:IL-22 ratio was highest in patients with cirrhosis. CONCLUSIONS: Our results suggest that IL-22, IL-22R1 and IL-22BP may be involved in the mechanisms of liver fibrosis in patients with chronic hepatitis C.

Does high-definition transcranial direct current stimulation change brain electrical activity in professional female basketball players during free-throw shooting?

Differentiated brain activation in high-performance athletes supports neuronal mechanisms relevant to sports performance. Preparation for the motor action involves cortical and sub-cortical regions that can be non-invasively modulated by electrical current stimulation. This study aimed to investigate the effect of high-definition transcranial direct current stimulation (HD-tDCS) on electrical brain activity in professional female basketball players during free-throw shooting. Successful free-throw shooting (n = 2,361) from seven professional female basketball players was analyzed during two experimental conditions (HD-tDCS cathodic and sham) separated by 72 h. Three spectral bio-markers, Power Ratio Index (PRI), Delta Alpha Ratio (DAR), and Theta Beta Ratio (TBR) were measured (electroencephalography [EEG] Brain Products). Multi-channel HD-tDCS was applied for 20 min, considering current location and intensity for cathodic stimulation: FCC1h, AFF5h, AFF1h (-0.5 mA each), and FCC5h (ground). The within EEG analyses (pre and post HD-tDCS) of frontal channels (Fp1, Fp2, F3, F4, FC1, FC3) for 1 second epoch pre-shooting, showed increases in PRI (p < 0.001) and DAR (p < 0.001) for HD-tDCS cathodic condition, and in TBR for both conditions (cathodic, p = 0.01; sham, p = 0.002). Sub-group analysis divided the sample into less (n = 3; LSG) and more (n = 4; MSG) stable free-throw-shooting performers and revealed that increases in pre to post HD-tDCS in PRI only occurred for the LSG. These results suggest that the effect of HD-tDCS may induce changes in slow frontal frequency brain activities and that this alteration seems to be greater for players demonstrating a less stable free-throw shooting performance.

Intrahemispheric EEG: A New Perspective for Quantitative EEG Assessment in Poststroke Individuals.

The ratio between slower and faster frequencies of brain activity may change after stroke. However, few studies have used quantitative electroencephalography (qEEG) index of ratios between slower and faster frequencies such as the delta/alpha ratio (DAR) and the power ratio index (PRI; delta + theta/alpha + beta) for investigating the difference between the affected and unaffected hemisphere poststroke. Here, we proposed a new perspective for analyzing DAR and PRI within each hemisphere and investigated the motor impairment-related interhemispheric frequency oscillations. Forty-seven poststroke subjects and twelve healthy controls were included in the study. Severity of upper limb motor impairment was classified according to the Fugl-Meyer assessment in mild/moderate (n = 25) and severe (n = 22). The qEEG indexes (PRI and DAR) were computed for each hemisphere (intrahemispheric index) and for both hemispheres (cerebral index). Considering the cerebral index (DAR and PRI), our results showed a slowing in brain activity in poststroke patients when compared to healthy controls. Only the intrahemispheric PRI index was able to find significant interhemispheric differences of frequency oscillations. Despite being unable to detect interhemispheric differences, the DAR index seems to be more sensitive to detect motor impairment-related frequency oscillations. The intrahemispheric PRI index may provide insights into therapeutic approaches for interhemispheric asymmetry after stroke.

Repetitive transcranial magnetic stimulation on the modulation of cortical and spinal cord excitability in individuals with spinal cord injury.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been applied for modulating cortical excitability and treating spasticity in neurological lesions. However, it is unclear which rTMS frequency is most effective in modulating cortical and spinal excitability in incomplete spinal cord injury (SCI). OBJECTIVE: To evaluate electrophysiological and clinical repercussions of rTMS compared to sham stimulation when applied to the primary motor cortex (M1) in individuals with incomplete SCI. METHODS: A total of 11 subjects (35±12 years) underwent three experimental sessions of rTMS (10 Hz, 1 Hz and sham stimulation) in a randomized order at 90%intensity of the resting motor threshold and interspersed by a seven-day interval between sessions. The following outcome measures were evaluated: M1 and spinal cord excitability and spasticity in the moments before (baseline), immediately after (T0), 30 (T30) and 60 (T60) minutes after rTMS. M1 excitability was obtained through the motor evoked potential (MEP); spinal cord excitability by the Hoffman reflex (H-reflex) and homosynaptic depression (HD); and spasticity by the modified Ashworth scale (MAS). RESULTS: A significant increase in cortical excitability was observed in subjects submitted to 10 Hz rTMS at the T0 moment when compared to sham stimulation (p = 0.008); this increase was also significant at T0 (p = 0.009), T30 (p = 0.005) and T60 (p = 0.005) moments when compared to the baseline condition. No significant differences were observed after the 10 Hz rTMS on spinal excitability or on spasticity. No inter-group differences were detected, or in the time after application of 1 Hz rTMS, or after sham stimulation for any of the assessed outcomes. CONCLUSIONS: High-frequency rTMS applied to M1 was able to promote increased cortical excitability in individuals with incomplete SCI for at least 60 minutes; however, it did not modify spinal excitability or spasticity.

Virtual Reality Cognitive Training Among Individuals With Alcohol Use Disorder Undergoing Residential Treatment: Pilot Randomized Controlled Trial.

BACKGROUND: Alcohol use disorder (AUD) has been associated with diverse physical and mental morbidities. Among the main consequences of chronic and excessive alcohol use are cognitive and executive deficits. Some of these deficits may be reversed in specific cognitive and executive domains with behavioral approaches consisting of cognitive training. The advent of computer-based interventions may leverage these improvements, but randomized controlled trials (RCTs) of digital interactive-based interventions are still scarce. OBJECTIVE: The aim of this study is to explore whether a cognitive training approach using VR exercises based on activities of daily living is feasible for improving the cognitive function of patients with AUD undergoing residential treatment, as well as to estimate the effect size for this intervention to power future definitive RCTs. METHODS: This study consisted of a two-arm pilot RCT with a sample of 36 individuals recovering from AUD in a therapeutic community; experimental group participants received a therapist-guided, VR-based cognitive training intervention combined with treatment as usual, and control group participants received treatment as usual without cognitive training. A comprehensive neuropsychological battery of tests was used both at pre- and postassessments, including measurement of global cognition, executive functions, attention, visual memory, and cognitive flexibility. RESULTS: In order to control for potential effects of global cognition and executive functions at baseline, these domains were controlled for in the statistical analysis for each individual outcome. Results indicate intervention effects on attention in two out of five outcomes and on cognitive flexibility in two out of six outcomes, with effect sizes in significant comparisons being larger for attention than for cognitive flexibility. Patient retention in cognitive training was high, in line with previous studies. CONCLUSIONS: Overall, the data suggest that VR-based cognitive training results in specific contributions to improving attention ability and cognitive flexibility of patients recovering from AUD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04505345; https://clinicaltrials.gov/show/NCT04505345.

1-Methyl-D-tryptophan activates aryl hydrocarbon receptor, a pathway associated with bladder cancer progression.

BACKGROUND: Indoleamine 2, 3-dioxygenase-1 (IDO1) is a promising target for immunotherapy in bladder cancer (BC). IDO1 breaks-down tryptophan to generate kynurenine derivatives, which may activate the aryl hydrocarbon receptor (AHR). AHR is an important target for carcinogens, but its association with BC progression was unknown. Two IDO1 inhibitors used in clinical trials are 1-methyl-D-tryptophan (MT) and INCB240360. Because MT is an aromatic hydrocarbon, it may be a ligand for AHR. We hypothesized that AHR could be associated with BC progression and that MT could activate AHR in BC. METHODS: BC patients (n = 165) were selected from the Gene Expression Omnibus database. A cut-off point for relative expression of AHR and cytochrome 450 enzymes (CYP1A1, CYP1A2, and CYP1B1; markers of AHR activation) was determined to compare with the grade, stage, and tumor progression. For in vitro experiments, RT4 (grade 1) and T24 (grade 3) BC cells were incubated with MT and INCB240360 to evaluate the expression of AHR and CYP1A1. RESULTS: AHR activation was associated with grade, stage, and progression of BC. T24 cells express more CYP1A1 than RT4 cells. Although IDO1 expression and kynurenine production are elevated in T24 cells concomitantly to CYP1A1 expression, IDO1 inhibitors were not able to decrease CYP1A1 expression, in contrast, MT significantly increased it in both cell lines. CONCLUSION: In conclusion, it is rational to inhibit IDO1 in BC, among other factors because it contributes to AHR activation. However, MT needs to be carefully evaluated for BC because it is an AHR pathway agonist independently of its effects on IDO1.

A Qualitative Study of a Mindfulness-Based Intervention in Educational Contexts in Chile: An Approach Based on Adolescents' Voices.

The application of mindfulness-based interventions in school settings has increased considerably in recent years, showing that differences between the characteristics of programmes can impact on the receptivity and effectiveness of mindfulness training. However, few studies have explored the learning process from the perspective of the children and adolescents who participate in mindfulness practice. The goal of this paper is to analyse the subjective experience of a group of adolescents following the completion of a mindfulness-based intervention developed for schools in Chile. The intervention studied is the ".b curriculum", which is part of the Mindfulness in School Project (MiSP) developed in the UK. Twenty adolescents participated in semi-structured interviews within their school, in which three key areas were explored: pedagogy, perceived effects, and mechanisms of action, each of them being analysed from the perspective of thematic analysis. The results support the view that pedagogy is a very relevant consideration in the implementation, development, and efficacy of mindfulness-based interventions within the school context. We propose that the inclusion of structure, contents, process/mindful practices, and teachers' expertise provides the pedagogical-relational framework required for students to successfully develop mindfulness skills, which enables them to experience their cognitive, emotional, and somatic effects. These effects are linked to self-regulation strategies, based on paying attention to one's somatic experience with kindness and curiosity, which works as an attentional anchor. It is hoped that these results will contribute to the spread of mindfulness research in adolescents in Latin America, thus facilitating cross-cultural and international comparisons.

Can photobiomodulation therapy be an alternative to pharmacological therapies in decreasing the progression of skeletal muscle impairments of mdx mice?

OBJECTIVE: To compare the effects of photobiomodulation therapy (PBMT) and pharmacological therapy (glucocorticoids and non-steroidal anti-inflammatory drugs) applied alone and in different combinations in mdx mice. METHODS: The animals were randomized and divided into seven experimental groups treated with placebo, PBMT, prednisone, non-steroidal anti-inflammatory drug (NSAIDs), PBMT plus prednisone and PBMT plus NSAID. Wild type animals were used as control. All treatments were performed during 14 consecutive weeks. Muscular morphology, protein expression of dystrophin and functional performance were assessed at the end of the last treatment. RESULTS: Both treatments with prednisone and PBMT applied alone or combined, were effective in preserving muscular morphology. In addition, the treatments with PBMT (p = 0.0005), PBMT plus prednisone (p = 0.0048) and PBMT plus NSAID (p = 0.0021) increased dystrophin gene expression compared to placebo-control group. However, in the functional performance the PBMT presented better results compared to glucocorticoids (p<0.0001). In contrast, the use of NSAIDs did not appear to add benefits to skeletal muscle tissue in mdx mice. CONCLUSION: We believe that the promising and optimistic results about the PBMT in skeletal muscle of mdx mice may in the future contribute to this therapy to be considered a safe alternative for patients with Duchenne Muscular Dystrophy (DMD) in a washout period (between treatment periods with glucocorticoids), allowing them to remain receiving effective and safe treatment in this period, avoiding at this way periods without administration of any treatment.

CYP2C19 polymorphisms and outcomes of Escitalopram treatment in Brazilians with major depression.

Escitalopram (ESC), a selective serotonin reuptake inhibitor indicated for the treatment of depression and anxiety disorders, is primarily metabolized by cytochrome P450 (CYP) 2C19, which is a highly polymorphic enzyme known to cause inter-individual differences in pharmacokinetics. We hypothesized that CYP2C19 polymorphisms are associated with major depressive disorder (MDD) remission in patients treated with ESC in the long term. Thirty-one patients with MDD receiving chronic treatment with ESC monotherapy or combination therapy with other antidepressants (mirtazapine and bupropion), in naturalistic conditions, were included in the study. For comparison of genotype and phenotype frequencies, a group of 126 healthy subjects was also included. The CYP2C19∗2, CYP2C19∗3, and CYP2C19∗17 polymorphisms were analyzed by RFLP-PCR genotyping. The CYP2C19 genotypes and phenotypes were similar in patient and healthy subject groups. Four phenotypes were found in the healthy subject group: ultra-rapid (UM; 28%), extensive (EM; 52%), intermediate (IM; 17%), and poor metabolizers (PM; 3%). The patient group showed the UM (22.5%), EM (55%), and IM (22.5%) phenotypes. The UM patients had significantly higher ESC doses than both EM and IM patients (20.7 ± 4.5, 15.7 ± 3.8, and 14.0 ± 3.3 mg/day, respectively; p = 0.0041). Furthermore, all patients using ESC in combination with mirtazapine or bupropion antidepressants (ESC plus mirtazapine or bupropion) were UM metabolizers, suggesting that the ∗17 ultra-rapid allele seems to be the factor responsible for lower response to ESC, even at higher doses. The CYP2C19 UM phenotype is associated with higher ESC doses and antidepressant combinations for symptom remission in MDD patients.

Interhemispheric asymmetry of the motor cortex excitability in stroke: relationship with sensory-motor impairment and injury chronicity.

OBJECTIVE: To compare the interhemispheric asymmetry of the motor cortex excitability of chronic stroke patients with healthy and to observe if the magnitude of this asymmetry is associated to sensory-motor impairment and stroke chronicity. METHODS: This cross-sectional study was performed with chronic stroke and aged and sex-matched healthy individuals. The interhemispheric asymmetry index was calculated by the difference of rest motor threshold (rMT) of the brain hemispheres. The rMT was assessed by transcranial magnetic stimulation over the cortical representation of the first dorsal interosseous muscle. To investigate the relationship of the asymmetry with sensory-motor impairment and injury chronicity, the stroke patients were grouped according to the level of sensory-motor impairment (mild/moderate, moderate/severe, and severe) and different chronicity stages (> 3-12, 13-24, 25-60, and > 60 months since stroke). RESULTS: Fifty-six chronic stroke and twenty-six healthy were included. We found higher interhemispheric asymmetry in stroke patients (mean, 27.1 ± 20.9) compared to healthy (mean, 4.9 ± 4.7). The asymmetry was higher in patients with moderate/severe (mean, 35.4 ± 20.4) and severe (mean, 32.9 ± 22.7) impairment. No difference was found between patients with mild/moderate impairment (mean, 15.5 ± 12.5) and healthy. There were no differences of the interhemispheric asymmetry between patients with different times since stroke (> 3-12, mean, 32 ± 18.1; > 13-24, mean, 20.7 ± 16.2; > 25-60, mean, 29.6 ± 18.1; > 60 months, mean, 25.9 ± 17.5). CONCLUSION: Stroke patients showed higher interhemispheric asymmetry of the motor cortex excitability when compared to healthy, and the magnitude of this asymmetry seems to be correlated with the severity of sensory-motor impairment, but not with stroke chronicity. SIGNIFICANCE: Higher interhemispheric asymmetry was found in stroke patients with greatest sensory-motor impairment.

The CYP2C19*2 and CYP2C19*17 Polymorphisms Influence Responses to Clozapine for the Treatment of Schizophrenia.

INTRODUCTION: Clozapine (CLZ) is the gold standard drug for treatment-refractory schizophrenia (TRS). However, approximately 30% of patients partially respond to CLZ, defining this subset with super refractory schizophrenia (SRS). Alterations in enzyme activity may affect CLZ responses; the CYP3A4, CYP1A2 and CYP2C19 genes are primarily responsible for CLZ metabolism. OBJECTIVE: The aim of this study was to assess if CYP2C19 variants were associated with TRS or SRS. METHODS: CYP2C19*2 loss-of-function and CYP2C19*17 gain-of-function polymorphism genotype testing were performed in 108 individuals undergoing pharmacological treatment for TRS or SRS. DNA was extracted and polymorphisms were analyzed by polymerase chain reaction (PCR) and sequencing. RESULTS: CYP2C19*17 had positive correlations with SRS and lower Brief Psychiatric Rating Scale (BPRS) scores for TRS. In addition, CYP2C19*2 was associated with lower CLZ dosages for TRS. CONCLUSION: These results show that CYP2C19*2 and CYP2C19*17 polymorphisms influence CLZ responses during schizophrenia treatment.

Indoxyl Sulfate Contributes to Uremic Sarcopenia by Inducing Apoptosis in Myoblasts.

OBJETIVE: Uremic sarcopenia is a complication of chronic kidney disease, particularly in its later stages, which leads to musculoskeletal disability. Uremic toxins have been linked to the pathogenesis of several manifestations of uremic syndrome. We sought to investigate whether indoxyl sulphate (IS), a protein-bound uremic toxin, is implicated in the development of uremic sarcopenia. MATERIAL AND METHODS: Myoblasts were exposed to IS at normal (0.6 mg/L, IS0.6), uremic (53 mg/L, IS53) or maximum uremic (236 mg/L, IS236) concentrations for 24, 48 and 72 h. Cell viability was evaluated by MTT assay and by 7-aminoactinomycin D staining. ROS generation and apoptosis were evaluated by flow cytometry. MyoD and myogenin mRNA expression was evaluated by qRT-PCR and myosin heavy chain expression by immunocytochemistry. RESULTS: Myoblast viability was reduced by IS236 in a time-dependent pattern (p <0.05; 84.4, 68.0, and 63.6%). ROS production was significantly higher (p <0.05) in cells exposed to IS53 and IS236 compared to control (untreated cells). The apoptosis rate was significantly higher in cells treated with IS53 and IS236 than in control after 48h (p <0.05; 4.7 ± 0.1% and 4.6 ± 0.3% vs. 3.1 ± 0.1%, respectively) and 72h (p <0.05; 9.6 ± 1.1% and 10.4 ± 0.3% vs. 3.1 ± 0.7%, respectively). No effect was observed on MyoD, myogenin, myosin heavy chain expression, and markers of myoblast differentiation at any IS concentration tested or time-point experiment. CONCLUSIONS: These data indicate that IS has direct toxic effects on myoblast by decreasing its viability and increasing cell apoptosis. IS may be a potential target for treating uremic sarcopenia.

Virtual Reality-Based Cognitive Stimulation to Improve Cognitive Functioning in Community Elderly: A Controlled Study.

The advantages of using naturalistic virtual reality (VR) environments based on everyday life tasks for cognitive intervention in the elderly are not yet well understood. The literature suggests that the similarity of such exercises with real life activities may improve generalizability by extending the transfer of gains of training to everyday living. This study aimed to investigate the gains associated with this ecologically-oriented virtual reality cognitive stimulation (VR-CS) versus standard cognitive stimulation in the elderly. Forty-three healthy older adults were divided into two groups: an experimental group underwent a VR-based cognitive stimulation and an active control group underwent a paper-and-pencil cognitive stimulation. The outcomes assessed at the pre-treatment and posttreatment assessment consisted in well-established tests for cognitive and executive functioning, depression, subjective well-being, and functionality. The results showed positive outcomes on dimensions of general cognition, executive functioning, attention, and visual memory in the group that underwent VR-CS. Improvements in executive functioning in this group was supported by consistent evidence of increases in attention abilities but little evidence of increases in memory abilities. Both effects may have contributed to improvements in general cognition. Further studies are needed to test whether these effects may extend to well-being and functionality in cognitively impaired older adults.