Abatacept inhibits Th17 differentiation and mitigates α-synuclein-induced dopaminergic dysfunction in mice.

Parkinson's disease (PD) is a multifaceted disease characterized by degeneration of nigrostriatal dopaminergic neurons, which results in motor and non-motor dysfunctions. Accumulation of α-synuclein (αSYN) in Lewy bodies is a key pathological feature of PD. Although the exact cause of PD remains unknown, accumulating evidence suggests that brain infiltration of T cells plays a critical role in the pathogenesis of disease, contributing to neuroinflammation and dopaminergic neurodegeneration. Here, we used a mouse model of brain-infused aggregated αSYN, which recapitulates motor and non-motor dysfunctions seen in PD patients. We found that αSYN-induced motor dysfunction in mice is accompanied by an increased number of brain-residing Th17 (IL17+ CD4+) cells, but not CD8+ T cells. To evaluate whether the modulation of T cell response could rescue αSYN-induced damage, we chronically treated animals with abatacept (8 mg/kg, sc, 3x per week), a selective T-cell co-stimulation modulator. We found that abatacept treatment decreased Th1 (IFNƔ+ CD4+) and Th17 (IL17+ CD4+) cells in the brain, rescued motor function and prevented dopaminergic neuronal loss in αSYN-infused mice. These results highlight the significance of effector CD4+ T cells, especially Th17, in the progression of PD and introduce novel possibilities for repurposing immunomodulatory drugs used for arthritis as PD-modifying therapies.

A Strategy Utilizing Protein-Protein Interaction Hubs for the Treatment of Cancer Diseases.

We describe a strategy for the development of a rational approach of neoplastic disease therapy based on the demonstration that scale-free networks are susceptible to specific attacks directed against its connective hubs. This strategy involves the (i) selection of up-regulated hubs of connectivity in the tumors interactome, (ii) drug repurposing of these hubs, (iii) RNA silencing of non-druggable hubs, (iv) in vitro hub validation, (v) tumor-on-a-chip, (vi) in vivo validation, and (vii) clinical trial. Hubs are protein targets that are assessed as targets for rational therapy of cancer in the context of personalized oncology. We confirmed the existence of a negative correlation between malignant cell aggressivity and the target number needed for specific drugs or RNA interference (RNAi) to maximize the benefit to the patient's overall survival. Interestingly, we found that some additional proteins not generally targeted by drug treatments might justify the addition of inhibitors designed against them in order to improve therapeutic outcomes. However, many proteins are not druggable, or the available pharmacopeia for these targets is limited, which justifies a therapy based on encapsulated RNAi.

A5 noradrenergic-projecting C1 neurons activate sympathetic and breathing outputs in anaesthetized rats.

NEW FINDINGS: What is the central question of this study? C1 neurons innervate pontine noradrenergic cell groups, including the A5 region: do A5 noradrenergic neurons contribute to the activation of sympathetic and respiratory responses produced by selective activation of the C1 group of neurons. What is the main finding and its importance? The increase in sympathetic and respiratory activities elicited by selective stimulation of C1 neurons is reduced after blockade of excitatory amino acid within the A5 region, suggesting that the C1-A5 pathway might be important for sympathetic-respiratory control. ABSTRACT: Adrenergic C1 neurons innervate and excite pontine noradrenergic cell groups, including the ventrolateral pontine noradrenergic region (A5). Here, we tested the hypothesis that C1 activates A5 neurons through the release of glutamate and this effect is important for sympathetic and respiratory control. Using selective tools, we restricted the expression of channelrhodopsin2 under the control of the artificial promoter PRSx8 to C1 neurons (69%). Transduced catecholaminergic terminals within the A5 region are in contact with noradrenergic A5 neurons and the C1 terminals within the A5 region are predominantly glutamatergic. In a different group of animals, we performed retrograde lesion of C1 adrenergic neurons projecting to the A5 region with unilateral injection of the immunotoxin anti-dopamine ß-hydroxylase-saporin (anti-DßH-SAP) directly into the A5 region during the hypoxic condition. As expected, hypoxia (8% O2 , 3 h) induced a robust increase in fos expression within the catecholaminergic C1 and A5 regions of the brainstem. Depletion of C1 cells projecting to the A5 regions reduced fos immunoreactivity induced by hypoxia within the C1 region. Physiological experiments showed that bilateral injection of kynurenic acid (100 mM) into the A5 region reduced the rise in mean arterial pressure, and sympathetic and phrenic nerve activities produced by optogenetic stimulation of C1 cells. In conclusion, the C1 neurons activate the ventrolateral pontine noradrenergic neurons (A5 region) possibly via the release of glutamate and might be important for sympathetic and respiratory outputs in anaesthetized rats.

Machine learning approaches reveal subtle differences in breathing and sleep fragmentation in Phox2b-derived astrocytes ablated mice.

Modern neurophysiology research requires the interrogation of high-dimensionality data sets. Machine learning and artificial intelligence (ML/AI) workflows have permeated into nearly all aspects of daily life in the developed world but have not been implemented routinely in neurophysiological analyses. The power of these workflows includes the speed at which they can be deployed, their availability of open-source programming languages, and the objectivity permitted in their data analysis. We used classification-based algorithms, including random forest, gradient boosted machines, support vector machines, and neural networks, to test the hypothesis that the animal genotypes could be separated into their genotype based on interpretation of neurophysiological recordings. We then interrogate the models to identify what were the major features utilized by the algorithms to designate genotype classification. By using raw EEG and respiratory plethysmography data, we were able to predict which recordings came from genotype class with accuracies that were significantly improved relative to the no information rate, although EEG analyses showed more overlap between groups than respiratory plethysmography. In comparison, conventional methods where single features between animal classes were analyzed, differences between the genotypes tested using baseline neurophysiology measurements showed no statistical difference. However, ML/AI workflows successfully were capable of providing successful classification, indicating that interactions between features were different in these genotypes. ML/AI workflows provide new methodologies to interrogate neurophysiology data. However, their implementation must be done with care so as to provide high rigor and reproducibility between laboratories. We provide a series of recommendations on how to report the utilization of ML/AI workflows for the neurophysiology community.NEW & NOTEWORTHY ML/AI classification workflows are capable of providing insight into differences between genotypes for neurophysiology research. Analytical techniques utilized in the neurophysiology community can be augmented by implementing ML/AI workflows. Random forest is a robust classification algorithm for respiratory plethysmography data. Utilization of ML/AI workflows in neurophysiology research requires heightened transparency and improved community research standards.

Comparison of cardiac autonomic modulation of athletes and non-athletes individuals with spinal cord injury at rest and during a non-immersive virtual reality task.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To compare cardiac autonomic modulation of individuals with spinal cord injury (SCI) that practice different amounts of moderate to vigorous physical activity (PA) and able-bodied controls at rest and during a non-immersive Virtual Reality task. SETTING: Athletes with SCI of wheelchair basketball, wheelchair tennis, wheelchair handball, WCMX (wheelchair motocross), and para-swimming were assessed at the Faca na Cadeira Institute, ICEL and Clube Espéria in São Paulo, Brazil; non-athletes with SCI and able-bodied controls were assessed at the Acreditando Centro de Recuperação Neuromotora, São Paulo, Brazil. METHODS: One-hundred forty-five individuals were assessed: 36 athletes with traumatic SCI (41.1 ± 16.8 years old), 52 non-athletes with traumatic SCI (40.2 ± 14.1 years old), and 57 able-bodied individuals (39.4 ± 12.5 years old). Cardiac autonomic modulation was assessed through heart rate variability (HRV) measured in the sitting position at rest and during a VR game activity. RESULTS: We found significantly more favourable HRV for athletes with SCI when compared to non-athletes with SCI, but no differences between athletes with SCI and able-bodied controls. In addition, athletes and able-bodied controls showed adequate autonomic nervous system (ANS) adaptation (rest versus physical activity in VR), i.e., they experienced parasympathetic withdrawal during VR physical activity, which was not found in non-athletes with SCI. CONCLUSION: The practice of moderate to vigorous physical activity is associated with healthier cardiac autonomic modulation in adults with SCI, which may lead to more favourable health outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04618003, retrospectively registered.

Effectiveness of anodal transcranial direct current stimulation to improve muscle strength and motor functionality after incomplete spinal cord injury: a systematic review and meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: We aimed to investigate the effects of anodal transcranial direct current stimulation (tDCS) against sham on muscle strength and motor functionality after incomplete spinal cord injury (iSCI). SETTING: University of São Paulo, Brazil. METHODS: A preplanned protocol was registered (PROSPERO, CRD42016050444). Pubmed, Embase, Web of Science, Cochrane Central Library and BVS databases were searched independently by two authors up to March 2018. Cochrane Collaboration's Tool was used for the risk of bias assessments. Generic inverse variance and random-effects model were used to calculate pooled effect sizes (ES), 95% confidence intervals (CIs) and p-values in meta-analyses. RESULTS: Six randomized clinical trials met inclusion criteria (n = 78 iSCI individuals) and were included in the meta-analysis. Results showed a marginal significant pooled effect of active tDCS in improving motor functionality with a small ES (SMD = 0.26, 95% CI = -0.00 to 0.53, p = 0.05, I2 = 0%). On the other hand, the pooled effect of active tDCS on muscle strength did not reach statistical significance, in parallel with a small ES (SMD = 0.35, 95% CI = -0.21 to 0.92, p = 0.22, I2 = 0%) when compared with sham tDCS. No significant adverse events were reported. CONCLUSIONS: Overall, there was a significant effect of tDCS in improving motor functionality following iSCI. However, a small ES and the marginal p-value suggest that these results should be interpreted with caution. Further high-quality clinical trials are needed to support or refute the use of tDCS in daily clinical practice.

The use of a task through virtual reality in cerebral palsy using two different interaction devices (concrete and abstract) - a cross-sectional randomized study.

BACKGROUND: Cerebral Palsy (CP) is characterised by variable difficulties in muscular action, resulting in inability of the individual to perform functional movement. An option to provide functionality to the individual with CP is the use of computer innovation. The aim of this paper was to verify if there was any performance improvement in a task performed in a virtual environment and if there was transfer to the task performed in the real environment and vice versa in this population. METHODS: A computer program was developed comprising a motor task, but with two possibilities of user interaction: a) concrete interface (with physical contact): in which the individual touches the computer screen to finish the task and b) abstract interface (no physical contact): in which the individual performs a hand movement in front of the Kinect device. Participants were split into two groups. The experimental group consisted of 28 individuals with CP within the ages of 6 and 15 years old. The control group included 28 typically developing individuals mirroring the age and sex of the experimental group. RESULTS: Individuals from both groups were able to improve task performance and retain acquired information. The CP group presented worse performance than the control group in all phases of the study. Further findings showed that the CP group presented better performance in the abstract interface than in the concrete interface, whereas, in the control group, the opposite occurred: their best performance was in the concrete. CONCLUSIONS: Motor tasks performed by individuals with CP through an interface with a more virtual environment feature (abstract interface: Kinect) provided better performance when compared to an interface with a more real characteristic (concrete interface: Touchscreen). TRIAL REGISTRATION: ClinicalTrials.gov Identifier - NCT03352440; Date of registration - November 17, 2017.

Carotid chemoreflex activity restrains post-exercise cardiac autonomic control in healthy humans and in patients with pulmonary arterial hypertension.

KEY POINTS: Dysfunction of post-exercise cardiac autonomic control is associated with increased mortality risk in healthy adults and in patients with cardiorespiratory diseases. The afferent mechanisms that regulate the post-exercise cardiac autonomic control remain unclear. We found that afferent signals from carotid chemoreceptors restrain the post-exercise cardiac autonomic control in healthy adults and patients with pulmonary arterial hypertension (PAH). Patients with PAH had higher carotid chemoreflex sensitivity, and the magnitude of carotid chemoreceptor restraint of autonomic control was greater in patients with PAH as compared to healthy adults. The results demonstrate that the carotid chemoreceptors contribute to the regulation of post-exercise cardiac autonomic control, and suggest that the carotid chemoreceptors may be a potential target to treat post-exercise cardiac autonomic dysfunction in patients with PAH. ABSTRACT: Dysfunction of post-exercise cardiac autonomic control predicts mortality, but its underlying mechanisms remain unclear. We tested whether carotid chemoreflex activity restrains post-exercise cardiac autonomic control in healthy adults (HA), and whether such restraint is greater in patients with pulmonary arterial hypertension (PAH) who may have both altered carotid chemoreflex and altered post-exercise cardiac autonomic control. Twenty non-hypoxaemic patients with PAH and 13 age- and sex-matched HA pedalled until 90% of peak work rate observed in a symptom-limited ramp-incremental exercise test. Recovery consisted of unloaded pedalling for 5 min followed by seated rest for 6 min. During recovery, subjects randomly inhaled either 100% O2 (hyperoxia) to inhibit the carotid chemoreceptor activity, or 21% O2 (normoxia) as control. Post-exercise cardiac autonomic control was examined via heart rate (HR) recovery (HRR; HR change after 30, 60, 120 and 300 s of recovery, using linear and non-linear regressions of HR decay) and HR variability (HRV; time and spectral domain analyses). As expected, the PAH group had higher carotid chemosensitivity and worse post-exercise HRR and HRV than HA. Hyperoxia increased HRR at 30, 60 and 120 s and absolute spectral power HRV in both groups. Additionally, hyperoxia resulted in an accelerated linear HR decay and increased time domain HRV during active recovery only in the PAH group. In conclusion, the carotid chemoreceptors restrained recovery of cardiac autonomic control from exercise in HA and in patients with PAH, with the restraint greater for some autonomic indexes in patients with PAH.

The role of PHOX2B-derived astrocytes in chemosensory control of breathing and sleep homeostasis.

KEY POINTS: The embryonic PHOX2B-progenitor domain generates neuronal and glial cells which together are involved in chemosensory control of breathing and sleep homeostasis. Ablating PHOX2B-derived astrocytes significantly contributes to secondary hypoxic respiratory depression as well as abnormalities in sleep homeostasis. PHOX2B-derived astrocyte ablation results in axonal pathologies in the retrotrapezoid nucleus. ABSTRACT: We identify in mice a population of ∼800 retrotrapezoid nucleus (RTN) astrocytes derived from PHOX2B-positive, OLIG3-negative progenitor cells, that interact with PHOX2B-expressing RTN chemosensory neurons. PHOX2B-derived astrocyte ablation during early life results in adult-onset O2 chemoreflex deficiency. These animals also display changes in sleep homeostasis, including fragmented sleep and disturbances in delta power after sleep deprivation, all without observable changes in anxiety or social behaviours. Ultrastructural evaluation of the RTN demonstrates that PHOX2B-derived astrocyte ablation results in features characteristic of degenerative neuro-axonal dystrophy, including abnormally dilated axon terminals and increased amounts of synapses containing autophagic vacuoles/phagosomes. We conclude that PHOX2B-derived astrocytes are necessary for maintaining a functional O2 chemosensory reflex in the adult, modulate sleep homeostasis, and are key regulators of synaptic integrity in the RTN region, which is necessary for the chemosensory control of breathing. These data also highlight how defects in embryonic development may manifest as neurodegenerative pathology in an adult.

Secondary particles formed from the exhaust of vehicles using ethanol-gasoline blends increase the production of pulmonary and cardiac reactive oxygen species and induce pulmonary inflammation.

BACKGROUND: Ethanol vehicles release exhaust gases that contribute to the formation of secondary organic aerosols (SOA). OBJECTIVE: To determine in vivo toxicity resulting from exposure to SOA derived from vehicles using different ethanol-gasoline blends (E0, E10, E22, E85W, E85S, E100). METHODS: Exhaust emissions from vehicles using ethanol blends were delivered to a photochemical chamber and reacted to produce SOA. The aerosol samples were collected on filters, extracted, and dispersed in an aqueous solutions and intratracheally instilled into Sprague Dawley rats in doses of 700 µg/0.2 ml. After 45 min and 4 h pulmonary and cardiac chemiluminescence (CL) was measured to estimate the amount of reactive oxygen species (ROS) produced in the lungs and heart. Inflammation was measured by differential cell count in bronchoalveolar lavages (BAL). RESULTS: Statistically and biologically significant differences in response to secondary particles from the different fuel formulations were detected. Compared to the control group, animals exposed to SOA from gasoline (E0) showed a significantly higher average CL in the lungs at 45 min. The highest CL averages in the heart were observed in the groups exposed to SOA from E10 and pure ethanol (E100) at 45 min. BAL of animals exposed to SOA from E0 and E85S had a significant increased number of macrophages at 45 min. BAL neutrophil count was increased in the groups exposed to E85S (45 min) and E0 (4 h). Animals exposed to E0 and E85W had increased BAL lymphocyte count compared to the control and the other exposed groups. DISCUSSION: Our results suggest that SOA generated by gasoline (E0), followed by ethanol blends E85S and E85W, substantially induce oxidative stress measured by ROS generation and pulmonary inflammation measured by the recruitment of white blood cells in BAL.

Fractal correlations and linear analyses of heart rate variability in healthy young people with different levels of physical activity.

Changes in cardiac autonomic regulation, expressed by increased sympathetic activity and decreased heart rate variability, have an important relationship with the onset of lethal cardiac phenomena. Therefore, we aimed to evaluate the cardiac autonomic behaviour in young people according to their level of physical activity. Through the International Physical Activity Questionnaire, 55 healthy young non-smokers with no history of previous diseases and whose parents did not suffer from metabolic syndrome were assessed and divided into groups: sedentary (n=12), insufficiently active (n=16), active (n=14), and very active (n=13). We collected respiratory rate, systolic and diastolic blood pressure at rest, and body mass index. Subjects remained supine at rest, and without mental stress for 15 minutes in a controlled environment. Using a cardiofrequency meter (Polar® RS800CX), data were analysed in the time domain, frequency domain, and detrended fluctuation analysis. For the sedentary group, the mean RR and rMSSD were significantly lower, and the insufficiently active group showed higher means, but significantly only for rMSSD. The insufficiently active group showed in the detrended fluctuation analysis that α2 was significantly lower compared with the sedentary, active, and very active groups. We conclude that young, healthy, sedentary individuals present an increased heart rate and that insufficiently active individuals present a decreased fractal correlation and increased parasympathetic activity.

Minocycline alters expression of inflammatory markers in autonomic brain areas and ventilatory responses induced by acute hypoxia.

NEW FINDINGS: What is the central question of this study? Microglia are presumed to be the source of inflammatory mediators that contribute to hypoxia-induced neuroinflammation. However, the relationship between microglial activity during hypoxia and inflammatory responses in specific autonomic brain regions is not well understood. Therefore, we hypothesized that acute hypoxia initiates an immune response in the central nervous system elicited by an increased expression of inflammatory mediators in specific brain areas related to autonomic control. What is the main finding and its importance? Acute hypoxia initiated neuroinflammatory mechanisms specifically in brain autonomic nuclei responsible for cardiorespiratory control, i.e. the rostral ventrolateral medulla and paraventricular nucleus of the hypothalamus. Our findings emphasize the importance of microglia for the maintenance of autonomic adjustments during physiological challenges, such as hypoxia, or during cardiorespiratory reflex activation elicited by the arterial chemoreceptors. ABSTRACT: Prolonged and continuous exposure of mammals to a low oxygen environment (chronic hypoxia) elicits remarkable morphological and physiological adjustments. These include altered gene expression, increased peripheral chemosensitivity, enhanced respiratory drive and sympathoexcitation. The current study examines the hypothesis that acute hypoxia (AH) initiates an immune response in the central nervous system elicited by an increased expression of inflammatory mediators in specific brain areas related to autonomic control. Male Wistar rats pretreated with vehicle or minocycline (30 mg kg-1  day-1 for 5 days) were subjected to AH (8% O2 , balance N2 ) or normoxia (21% O2 ) for 3 h. AH increased interleukin (IL)-6, IL-1ß and matrix metalloprotease 9 (MMP9) mRNA expression in the paraventricular nucleus of the hypothalamus (PVH) and rostral ventrolateral medulla (RVLM) and tumour necrosis factor α (TNFα) in the RVLM. Treatment with minocycline, an inhibitor of microglial activation, decreased IL-1ß, TNFα and MMP9 mRNA expression in the RVLM, and increased IL-6 mRNA expression in the RVLM and PVH of rats exposed to AH. Minocycline treatment also elicited a decrease in the number of activated neurons in the RVLM/C1 neurons (expressed as Fos+ /tyrosine hydroxylase+ ), the number of Fos-activated neurons in the PVH and the increase in ventilation elicited by AH. When viewed together, these results suggest that AH modulates the expression of inflammatory mediators in autonomic brain nuclei that may be involved in the responses to chemoreceptor activation.

Efficacy of different interaction devices using non-immersive virtual tasks in individuals with Amyotrophic Lateral Sclerosis: a cross-sectional randomized trial.

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a rapid progressive neurodegenerative disease, characterized by a selective loss of motor neurons, brain stem and spinal cord which leads to deterioration of motor abilities. Devices that promote interaction with tasks on computers can enhance performance and lead to greater independence and utilization of technology. OBJECTIVE: To evaluate performance on a computer task in individuals with ALS using three different commonly used non-immersive devices. METHOD: Thirty individuals with ALS (18 men and 12 women, mean age 59 years, range 44-74 years) with a mean score of 26, (minimum score of 14 and maximum 41) on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and 30 healthy controls matched for age and gender, participated. All participants were randomly divided into three groups, each using a different device system (motion tracking, finger motion control or touchscreen) to perform three task phases (acquisition, retention and transfer). RESULTS: Both the ALS and control group (CG) showed better performance on the computer task when using the touchscreen device, but there was limited transfer of performance onto the task performed on the Finger Motion control or motion tracking. However, we found that using the motion tracking device led to transfer of performance to the touchscreen. CONCLUSION: This study presents novel and important findings when selecting interaction devices for individuals with ALS to access technology by demonstrating immediate performance benefits of using a touchscreen device, such as improvement of motor skills. There were possible transferable skills obtained when using virtual systems which may allow flexibility and enable individuals to maintain performance overtime. TRIAL REGISTRATION: Registration name: Virtual Task in Amyotrophic Lateral Sclerosis; Registration number: NCT03113630 ; retrospectively registered on 04/13/2017. Date of enrolment of the first participant to the trial: 02/02/2016.

Heart Rate Variability and Cardiopulmonary Dysfunction in Patients with Duchenne Muscular Dystrophy: A Systematic Review.

Duchenne muscular dystrophy (DMD) is a genetic recessive disorder with progressive muscle weakness. Despite the general muscle wasting, degeneration and necrosis of cardiomyocytes have been the main causes of morbidity and death in individuals with DMD. Cardiac failure is generally preceded by disturbances in heart rate variability (HRV), and non-invasive measurement of the autonomic nervous system has been an important tool to predict adverse cardiovascular events. Hence, the application of HRV to study autonomic modulation in DMD individuals, and the establishment of correlations between HRV and heart/lung diseases, age, and mortality will have the potential to improve quality of life and life expectancy of individuals with DMD. In order to evaluate the state of the art in this field, we conducted a systematic search in Medline/PubMed and BVS (virtual library in health) databases. We selected 8 studies using pre-defined criteria and meta-analysis revealed decreased parasympathetic activity and increased sympathetic predominance in individuals with DMD as major observations. Moreover, there is a strong association between diminished HRV and myocardial fibrosis with DMD. These patterns are evident in patients at early-stage DMD and become more prominent as disease severity and age increase. Thus, data minning clearly indicates that HRV assessment can be used as a predictor for sudden death in individuals with DMD. The use of the HRV, which is inexpensive, ubiquitously available in clinics and hospitals, and a non-invasive analysis tool, can save lives and decrease the morbity in DMD by alerting care givers to consider autonomic nervous system intervention.

Short-term motor learning through non-immersive virtual reality task in individuals with down syndrome.

BACKGROUND: Down syndrome (DS) has unique physical, motor and cognitive characteristics. Despite cognitive and motor difficulties, there is a possibility of intervention based on the knowledge of motor learning. However, it is important to study the motor learning process in individuals with DS during a virtual reality task to justify the use of virtual reality to organize intervention programs. The aim of this study was to analyze the motor learning process in individuals with DS during a virtual reality task. METHODS: A total of 40 individuals participated in this study, 20 of whom had DS (24 males and 8 females, mean age of 19 years, ranging between 14 and 30 yrs.) and 20 typically developing individuals (TD) who were matched by age and gender to the individuals with DS. To examine this issue, we used software that uses 3D images and reproduced a coincidence-timing task. RESULTS: The results showed that all individuals improved performance in the virtual task, but the individuals with DS that started the task with worse performance showed higher difference from the beginning. Besides that, they were able to retain and transfer the performance with increase of speed of the task. CONCLUSION: Individuals with DS are able to learn movements from virtual tasks, even though the movement time was higher compared to the TD individuals. The results showed that individuals with DS who started with low performance improved coincidence- timing task with virtual objects, but were less accurate than typically developing individuals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02719600 .

Evaluation of speed-accuracy trade-off in a computer task in individuals with cerebral palsy: a cross-sectional study.

BACKGROUND: Individuals with Cerebral Palsy (CP) present with sensorimotor dysfunction which make the control and execution of movements difficult. This study aimed to verify the speed-accuracy trade-off in individuals with CP. METHODS: Forty eight individuals with CP and 48 with typical development (TD) were evaluated (32 females and 64 males with a mean age of 15.02 ± 6.37 years: minimum 7 and maximum 30 years). Participants performed the "Fitts' Reciprocal Aiming Task v.1.0 (Horizontal)" on a computer with different sizes and distance targets, composed by progressive indices of difficulty (IDs): ID2, ID4a and ID4b. RESULTS: There were no statistical differences between the groups in relation to the slope of the curve (b1) and dispersion of the movement time (r2). However, the intercept (b0) values presented significant differences (F(1.95) = 11.3; p = .001]), with greater movement time in the CP group compared to the TD group. It means that for individuals with CP, regardless of index difficulty, found the task more difficult than for TD participants. Considering CP and TD groups, speed-accuracy trade-off was found when using different indices of difficulty (ID2 and ID4). However, when the same index of difficulty was used with a larger target and longer distance (ID4a) or with a narrow target and shorter distance (ID4b), only individuals with CP had more difficulty performing the tasks involving smaller targets. Marginally significant inverse correlations were identified between the values of b1 and age (r = -0.119, p = .052) and between r2 and Gross Motor Function Classification System (r = -0.280, p = .054), which did not occur with the Manual Ability Classification System. CONCLUSION: We conclude that the individuals with CP presented greater difficulty when the target was smaller and demanded more accuracy, and less difficulty when the task demanded speed. It is suggested that treatments should target tasks with accuracy demands, that could help in daily life tasks, since it is an element that is generally not considered by professionals during therapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03002285 , retrospectively registered on 20 Dec 2016.

Cardiac autonomic modulation of children with Down syndrome.

The aim of this study is to analyze the autonomic modulation in children with Down syndrome (DS). The study was conducted with a convenience sample of children with DS and without heart disease, from the Genetics Clinic of the Hospital Infantil Darcy Vargas and APAE São Paulo, São Paulo, SP, Brazil. The control group was matched for sex and age. The analysis of autonomic modulation was performed using the indices of heart rate variability (HRV). The children remained in the supine position with spontaneous breathing for 20 min. Heart rate was recorded beat-to-beat. HRV analysis was performed in time and frequency domain. For data analysis, we used Student's t test: unpaired and Mann-Whitney. It was considered statistically significant at p < 0.05. From 75 children with DS, 50 were excluded, a total of 25 children [16 boys, 8.6 (1.4) years] participated in this study, and the control group also consisted of 25 children [16 boys, 9.0 (1.2) years] without the syndrome. The BMI of the volunteers with DS was higher than the controls [19.1 (2.9) vs. 15.8 (1.2), p < 0.0001]. There were differences between groups in the indices in frequency domain: LFms(2) [1242.1 (788.25) vs. 786.44 (481.90), p = 0.040], LFun [69.104 (11.247) vs. 57.348 (11.683), p = 0.0004], HFun [30.896 (11.247) vs. 42.520 (11.634), p = 0.0004] and LF/HF [2.594 (1.104) vs. 1.579 (0.9982), p = 0.0004]. No differences were observed in time domain indices. The results indicate increased indices representing the sympathetic branch of the autonomic nervous system and those that indicate the overall modulation in children with DS.

Self-esteem of adult women living in a peripheral area of São Paolo city, Brazil.

Our purpose was to determine the level of self-esteem (SE) and its associations with women's sociodemographic characteristics and social status. Adult women (N = 120) living in a peripheral area of Sao Paulo City in Southeastern Brazil were randomly included in our study. We found significant associations between higher SE scores and higher schooling (p =.02), participation in religious meetings in the church (p =.022), and practice of leisure activities (p <.001). The inclusion of a broader range of activities should be provided in health care and educational settings aiming at the improvement of women's SE levels.

Sensorimotor functioning changes in response to global exercise versus handwriting upper limb exercise training in Parkinson's disease, results from a phase II randomised controlled trial.

INTRODUCTION: People with Parkinson's disease (PwPD) present motor alterations which can impact daily life tasks that require speed and/or accuracy of movement. OBJECTIVE: A sub analysis of NCT01439022, aiming to estimate the extent to which two different exercise training protocols (global and handwriting upper limb exercise training) impact reaction time, travel speed, and accuracy in PwPD. METHODS: Seventy PwPD, right-side dominant were randomised 1:1 into two six-month training protocol groups; 35 PwPD performed global exercise training and 35 performed specific training (handwriting upper limb exercise movements). Assessments of speed-accuracy and trade-off were carried out at baseline, after 3 and 6 months of training, and at a 12-month follow-up. The current study used data from a previous publication of a randomised controlled trial that included a 6-month self-managed community exercise programme for PwPD. For the present study we included only the participants who completed the Fitts' task during the baseline assessment. RESULTS: In the upper limb assessments, no main effects were found for the number of touches, but the exercise group showed a marginal increase over time on the left side. Error averages on the left side decreased significantly for the exercise group from baseline to 6 and 12 months. The exercise group also presented a lower Error CoV and the Reaction Time CoV increased on the right side. Significant findings for Fitts r on the left side indicated lower values for the exercise group, with improvements continuing at 12 months. CONCLUSION: We report the potential of global exercise interventions to facilitate improvements in reaction time and travel speed, as well as other motor control metrics, with lasting effects at 12 months, particularly on the non-dominant side.

Chitosan-based films filled with nanoencapsulated essential oil: Physical-chemical characterization and enhanced wound healing activity.

The economic burden of chronic wounds, the complexity of the process of tissue repair and the possibility of resistant bacterial infections, have triggered a significant research interest in the application of natural alternative therapies for wound healing. Biomolecules are intrinsically multi-active, as they affect multiple mechanisms involved in tissue repair phenomenon, including immunomodulatory, anti-inflammatory, cell proliferation, extra cellular matrix remodeling and angiogenesis. Chitosan features a unique combination of attributes, including intrinsic hemostatic, antimicrobial, and immunomodulatory properties, that make it an exceptional candidate for wound management, in the development of wound dressings and scaffolds. In this study, we produced nanoemulsions (NE) loaded with SFO, characterized them, and evaluated their tissue repairing properties. Dynamic light scattering (DLS) analysis confirmed the formation of a nanoemulsion with a droplet size of 21.12 ± 2.31 nm and a polydispersity index (PdI) of 0.159, indicating good stability for up to 90 days. To investigate the potential wound healing effects, SFO-loaded NE were applied on male C57BL/6 mice for seven consecutive days, producing a significantly higher wound closure efficiency (p < 0.05) for the group treated with SFO-loaded NE compared to the control group treated with the saline solution. This finding indicates that the SFO-loaded NE exhibits therapeutic properties that effectively promote wound healing in this experimental model. Then, SFO-loaded NE were incorporated into chitosan:polyvinyl alcohol (PVA)-based films. The inclusion of NE into the polymer matrix resulted in increased lipophilicity reflected by the contact angle results, while decreasing moisture absorption, water solubility, and crystallinity. Moreover, FTIR analysis confirmed the formation of new bonds between SFO-NE and the film matrix, which also impacted on porosity properties. Thermal analysis indicated a decrease in the glass transition temperature of the films due to the presence of SFO-NE, suggesting a plasticizing role of NE, confirmed by XRD results, that showed a decrease in the crystallinity of the blend films upon the addition of SFO-NE. AFM images showed no evidence of NE droplet aggregation in the Chitosan:PVA film matrix. Moisture absorption and water content decreased upon incorporation of SFO-loaded NE. Although the inclusion of NE increased hydrophobicity and water contact angle, the values remained within an acceptable range for wound healing applications. Overall, our results emphasize the significant tissue repairing properties of SFO-loaded NE and the potential of Chitosan:PVA films containing nanoencapsulated SFO as effective formulations for wound healing with notable tissue repairing properties.