Rehab Centers: NADPH Oxidase 1 Mediates ?-Synucleinopathy in Parkinson’s Disease.

NADPH Oxidase 1 Mediates ?-Synucleinopathy in Parkinson’s Disease.

Filed under: Rehab Centers

J Neurosci. 2012 Oct 17; 32(42): 14465-14477
Cristóvão AC, Guhathakurta S, Bok E, Je G, Yoo SD, Choi DH, Kim YS

Accumulation of misfolded ?-synuclein is the pathological hallmark of Parkinson’s disease (PD). Nevertheless, little is known about the mechanism contributing to ?-synuclein aggregation and its further toxicity to dopaminergic neurons. Since oxidative stress can increase the expression and aggregation levels of ?-synuclein, NADPH oxidases (Noxs), which are responsible for reactive oxygen species generation, could be major players in ?-synucleinopathy. Previously, we demonstrated that Nox1 is expressed in dopaminergic neurons of the PD animal models as well as postmortem brain tissue of PD patients, and is responsible for oxidative stress and subsequent neuronal degeneration. Here, using paraquat (PQ)-based in vitro and in vivo PD models, we show that Nox1 has a crucial role in modulating the behavior of ?-synuclein expression and aggregation in dopaminergic neurons. We observed in differentiated human dopaminergic cells that Nox1 and ?-synuclein expressions are increased under PQ exposure. Nox1 knockdown significantly reduced both ?-synuclein expression and aggregation, supporting the role of Nox1 in this process. Furthermore, in rats exposed to PQ, the selective knockdown of Nox1 in the substantia nigra, using adeno-associated virus encoding Nox1-specific shRNA, largely attenuated the PQ-mediated increase of ?-synuclein and ubiquitin expression levels as well as ?-synuclein aggregates (proteinase K resistant) and A11 oligomers. Significant reductions in oxidative stress level and dopaminergic neuronal loss were also observed. Our data reveal a new mechanism by which ?-synuclein becomes a neuropathologic protein through Nox1-mediated oxidative stress. This finding may be used to generate new therapeutic interventions that slower the rate of ?-synuclein aggregation and the progression of PD pathogenesis.
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A preliminary randomized controlled study on the effectiveness of vestibular-specific neuromuscular training in children with hearing impairment.

Filed under: Rehab Centers

Clin Rehabil. 2012 Oct 16;
Rajendran V, Roy FG, Jeevanantham D

Objective:To determine the effectiveness of vestibular-specific neuromuscular training on motor skills, balance and health-related quality of life in children with hearing impairment.Design:Controlled, randomized, preliminary study.Setting:Rehabilitation school for children with hearing impairment.Subjects and intervention:Twenty-three children with mean age of 7.5-8.1 years with hearing impairment were randomized to either the intervention or the control group. Children in the experimental group (n = 11) participated in vestibular-specific neuromuscular training for six weeks and the children in the control group continued their regular activities followed at school.Outcome measures:Measurement of motor skills (Test of Gross Motor Development-2), postural control (Pediatric Reach Test, One Leg Standing Balance Test and postural sway meter) and health-related quality of life (PedsQL Generic Core Scale).Results:Following intervention, the scores of motor skills (Test of Gross Motor Development P = 0.02; throw for distance P = 0.042; kick for distance P = 0.08; jump for distance P = 0.001; 15-yard dash P = 0.001), postural control measures (Pediatric Reach Test P = 0.001; One Leg Standing Test P = 0.03; and anteroposterior sway (eyes open P = 0.007, eyes closed P = 0.03); mediolateral sway (eyes open P = 0.014, eyes closed P = 0.017) and health-related quality of life (P = 0.01) improved significantly in the experimental group and not in the control group.Conclusion:The findings of the study suggest that vestibular-specific neuromuscular training programme may improve the motor skills, balance and health-related quality of life in children with hearing impairment.
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[Braking capacity after hip arthroplasty – effect of prosthesis design and preoperative status].

Filed under: Rehab Centers

Z Orthop Unfall. 2012 Oct; 150(5): 533-8
Franz A, Mannel H, Brüggemann GP, Schmidt J

Background: Driving a car is an important everyday activity. However, the patients’ desire to resume driving at an early stage after hip arthroplasty is often faced by the uncertainty about their driving ability. Only little evidence is available to support the clinical decision-making with regard to driving competence after conventional total hip arthroplasty (THA). However, there is no proof that the results observed after THA can be transferred to hip resurfacing arthroplasty (HRA) patients. Due to physiological advantages, i.e., patient age and activity, as well as the special biomechanical implant characteristics, HRA patients could be expected to achieve normal braking capacity at an earlier stage in the rehabilitation process than THA patients. This could be achieved by an accelerated postoperative recovery or could depend on the preoperative vantage point concerning the patients’ braking capacity. Patients and Methods: To verify this hypothesis HRA and THA patients were compared to healthy subjects concerning their ability to perform an emergency braking manoeuvre in a car simulator before surgery, and at 6 weeks and 3 months after operation. Furthermore, postoperative recovery rates were compared between the two groups of patients. In addition, correlations between pre- and postoperative braking capacity were tested. Reaction time, movement time and force-time integral on the brake pedal were analysed. Results: Except for a deficient preoperative force-time integral, no significant differences were detected in HRA patients compared to healthy controls. In contrast THA patients required, pre- as well as postoperatively, a longer movement time and exhibited a smaller force-time integral. The two patient groups did not show any significant difference in recovery rates of movement time and force-time integral. However, considering the two patient groups as a whole, a significant correlation was detected between existing pre- and postoperative deficits. Conclusion: In conclusion, it can be confirmed that HRA patients resume normal braking capacity at an earlier stage in their rehabilitation process than THA patients. Patients recommended for HRA recover braking capacity at the latest six weeks after surgery. This capacity clearly depends on the better preoperative status of the HRA patients and is not determined by a faster recovery rate. General patient-related advantages as well as biomechanical aspects of HRA have thus no influence on the recovery rates of braking capacity during the first three months after surgery. Due to the increasing outpatient rehabilitation regime after HRA, further studies are necessary to detect the turning point after surgical impairment within the first six weeks after surgery. Concerning the THA patients we recommend a longer safety distance when driving a car for up to three months after the operation. However, patients, especially those assigned to THA, should be made aware of their most likely already existing preoperative deficit. For clinical practice a rough estimation of postoperative braking capacity seems to be possible based on group assignment (HRA/THA). Nevertheless, deviators cannot be detected by this group classification. As driving simulator systems usually are not available in hospitals, a more accurate prognosis, i.e., based on established clinical scores, would be helpful.
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Assessment of Subcomponents of Executive Functioning in Ecologically Valid Settings: The Goal Processing Scale.

Filed under: Rehab Centers

J Head Trauma Rehabil. 2012 Oct 16;
Novakovic-Agopian T, Chen AJ, Rome S, Rossi A, Abrams G, D?esposito M, Turner G, McKim R, Muir J, Hills N, Kennedy C, Garfinkle J, Murphy M, Binder D, Castelli H

OBJECTIVES:: To validate a new functional assessment tool, the Goal Processing Scale (GPS), and to apply it for testing for sources of dysfunction in patients with acquired brain injury. Determining which component processes of executive functioning underlie poor performance in complex, low-structure settings would be valuable for the assessment of deficits and for evaluating the effectiveness of treatments. PARTICIPANTS:: Nineteen individuals with chronic acquired brain injury (mean age = 41.4 years; chronicity: 6 months to 39 years). MAIN MEASURES:: Two functional assessment tasks: (1) GPS, which evaluates functional performance in the context of achieving a goal in a “real-world” setting, with rating scales measuring overall performance and 8 subdomains of executive functioning; (2) Multiple Errands Test, an unstructured assessment of ability to adhere to rules and complete multiple “real-world” tasks in a short time; and (3) a neuropsychological battery. RESULTS:: Intraclass correlation coefficients for 2 independent raters ranged from 0.75 to 0.98 for the GPS overall composite score and the subdomain scores. Performance on GPS overall and several subdomain scores correlated with performance on the Multiple Errands Test. Working memory and learning/memory neuropsychological measures predicted functional performance as measured using the GPS. DISCUSSION:: The GPS shows high interrater reliability, suggesting convergent validity with an established functional performance measure, and produces useful information regarding strengths and weaknesses in different subdomains of executive functioning. Working memory and learning/memory appear to be key determinants of goal-directed functioning for these individuals with brain injury.
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Nutritional targets to enhance exercise performance in chronic obstructive pulmonary disease.

Filed under: Rehab Centers

Curr Opin Clin Nutr Metab Care. 2012 Nov; 15(6): 553-60
van de Bool C, Steiner MC, Schols AM

This review presents current knowledge regarding the rationale and efficacy of nutrition as an ergogenic aid to enhance the effects of exercise and training in chronic obstructive pulmonary disease (COPD).Altered body composition and skeletal muscle dysfunction in COPD suggest that exercise capacity can be targeted via several metabolic routes. Muscle metabolic alterations in COPD include a reduced oxidative metabolism and enhanced susceptibility for oxidative stress. Muscle wasting may be associated with deficiencies of vitamin D and low branched-chain amino acid levels. Exercise training is of established benefit in COPD but clear-cut clinical trial evidence to support the performance enhancing effect of nutritional intervention is lacking. One randomized controlled trial suggested that augmentation of training with polyunsaturated fatty acids may improve exercise capacity. Conflicting results are reported on dietary creatine supplementation in patients with COPD receiving pulmonary rehabilitation and results from acute intervention studies do not directly imply long-term effects of glutamate or glutamine supplementation as an ergogenic aid in COPD. Recent data indicate that not only muscle but also visceral fat may be an important additional target for combined nutrition and exercise intervention in COPD to improve physical performance and decrease cardiometabolic risk.There is a clear need for adequately powered and controlled intervention and maintenance trials to establish the role of nutritional supplementation in the enhancement of exercise performance and training and the wider management of the systemic features of the disease.
HubMed – rehab

 


 

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