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Dopaminergic treatment has proved effective to Parkinson's disease (PD), but the conventional treatment assessment is human-administered and prone to intra- and inter-assessor variability. In this paper, we propose a knowledge-driven framework and discover that brain ACtivation-Transition-Spectrum (ACTS) features achieve effective quantified assessments of dopaminergic therapy in PD. Firstly, brain activities of fifty-one PD patients during clinical walking tests under the OFF and ON states (without and with dopaminergic medication) were measured with functional near-infrared spectroscopy (fNIRS). Then, brain ACTS features were formulated based on the medication-induced variations in temporal features of brain regional activation, transition features of brain hemodynamic states, and graph spectrum of brain functional connectivity. Afterwards, a prior selection algorithm was constructed based on recursive feature elimination and graph spectrum analysis for the selection of principal discriminative features. Further, linear discriminant analysis was conducted to predict the treatment-induced improvements. The results demonstrated that the proposed method decreased the misclassification probability from 42% to 16% in the evaluations of dopaminergic treatment and outperformed existing fNIRS-based methods. Therefore, the proposed method promises a quantified and objective approach for dopaminergic treatment assessment, and our brain ACTS features may serve as promising functional biomarkers for treatment evaluation.
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INTRODUCTION: Gait initiation (GI) includes automatic and voluntary movements. However, research on their impact on the first step in patients with Parkinson's disease (PD) and their relationship to freezing of gait (FOG) is lacking. We examined the effects of automatic movements (anticipatory postural adjustments [APAs]) and voluntary movements (limits of stability [LOS]) on the first step (first-step duration and first-step range of motion), along with their early recognition and prediction of slight FOG. METHODS: Twenty-three patients with PD and slight freezing (PD + FOG) and 25 non-freezing patients with PD (PD-FOG) were tested while off medications and compared with 24 healthy controls (HC). All participants completed a 7-m Stand and Walk Test (7 m SAW) and wore inertial sensors to quantify the APAs and first step. LOS was quantified by dynamic posturography in different directions using a pressure platform. We compared differences among all three groups, analysed correlations, and evaluated their predictive value for slight FOG. RESULTS: In PD + FOG, APAs and LOS were worse than those in the PD-FOG and HC groups (p < 0.001), and the first step was worse than that in HC (p < 0.001). APAs were correlated mainly with the first-step duration. APAs and LOS were correlated with the first-step range of motion. APAs have been recognized as independent predictors of FOG, and their combination with LOS enhances predictive sensitivity. CONCLUSION: APAs and LOS in patients with PD directly affect the first step during GI. In addition, the combination of APAs and LOS helped predict slight FOG.
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Transtornos Neurológicos da Marcha , Doença de Parkinson , Equilíbrio Postural , Humanos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/complicações , Masculino , Feminino , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Transtornos Neurológicos da Marcha/diagnóstico , Idoso , Equilíbrio Postural/fisiologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Early identification of mild cognitive impairment (MCI) is essential for its treatment and the prevention of dementia in Parkinson's disease (PD). Existing approaches are mostly based on neuropsychological assessments, while brain activation and connection have not been well considered. NEW METHOD: This paper presents a neuroimaging-based graph frequency analysis method and the generated features to quantify the brain functional neurodegeneration and distinguish between PD-MCI patients and healthy controls. The Stroop color-word experiment was conducted with 20 PD-MCI patients and 34 healthy controls, and the brain activation was recorded with functional near-infrared spectroscopy (fNIRS). Then, the functional brain network was constructed based on Pearson's correlation coefficient calculation between every two fNIRS channels. Next, the functional brain network was represented as a graph and decomposed in the graph frequency domain through the graph Fourier transform (GFT) to obtain the eigenvector matrix. Total variation and weighted zero crossings of eigenvectors were defined and integrated to quantify functional interaction between brain regions and the spatial variability of the brain network in specific graph frequency ranges, respectively. After that, the features were employed in training a support vector machine (SVM) classifier. RESULTS: The presented method achieved a classification accuracy of 0.833 and an F1 score of 0.877, significantly outperforming existing methods and features. COMPARISON WITH EXISTING METHODS: Our method provided improved classification performance in the identification of PD-MCI. CONCLUSION: The results suggest that the presented graph frequency analysis method well identify PD-MCI patients and the generated features promise functional brain biomarkers for PD-MCI diagnosis.
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Disfunção Cognitiva , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Disfunção Cognitiva/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , NeuroimagemRESUMO
BACKGROUND: Parkinson's disease (PD) is associated with peripheral inflammation and abnormal peripheral blood lymphocyte immune responses. Peripheral blood B-lymphocyte subset distributions and whether they are associated with PD are unclear. METHODS: Sixty-one PD patients and sixty-one one-to-one paired healthy controls (HCs) were enrolled. We used flow cytometry to perform immunophenotyping of peripheral B-lymphocyte, in vitro stimulation and measured serum cytokine. The relationship between variables and PD were assessed. RESULTS: The percentage of naive B cells in blood of PD patients was decreased, whereas the percentages of regulatory B cells (Bregs), plasma blast cells (PBCs), and double-negative (DN) B cells were increased. The absolute counts of B-lymphocyte and naive B cells in blood of PD patients were decreased. Regression analysis revealed that alterations in the absolute counts of B-lymphocyte and the percentage of Bregs and DN B cells were associated with PD. After stimulation, the percentages of Bregs, PBCs, and switched memory (SwM) B cells increased in PD patients. Additionally, increases in GM-CSF-producing B-cell, IFN-γ-producing B-cell, and TNF-α-producing B-cell percentages were noted in PD. Serum levels of a proliferation-inducing ligand (APRIL), B-cell activating factor (BAFF) and soluble CD40 ligand (sCD40L) were elevated in PD and correlated negatively with the UPDRS III score. CONCLUSIONS: Abnormal B-lymphocyte immune responses in peripheral blood may contribute to PD development. Alterations in the absolute counts of B-lymphocyte and the percentage of Bregs and DN B cells are associated with PD. Furthermore, APRIL, BAFF, and sCD40L could be potential targets for intervention in PD.
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Linfócitos B Reguladores , Doença de Parkinson , Humanos , Citocinas , Inflamação , ImunidadeRESUMO
Plantar pressure can signify the gait performance of patients with Parkinson's disease (PD). This study proposed a plantar pressure analysis method with the dynamics feature of the sub-regions plantar pressure signals. Specifically, each side's plantar pressure signals were divided into five sub-regions. Moreover, a dynamics feature extractor (DFE) was designed to extract features of the sub-regions signals. The radial basis function neural network (RBFNN) was used to learn and store gait dynamics. And a classification mechanism based on the output error in RBFNN was proposed. The classification accuracy of the proposed method achieved 100.00% in PD diagnosis and 95.89% in severity assessment on the online dataset, and 96.00% in severity assessment on our dataset. The experimental results suggested that the proposed method had the capability to signify the gait dynamics of PD patients.
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Doença de Parkinson , Humanos , Marcha , Aprendizagem , Redes Neurais de ComputaçãoRESUMO
Background: Falls and gait disturbance are significant clinical manifestations of cerebral small vessel disease (CSVD). However, few relevant studies are reported at present. We aimed to investigate gait characteristics and fall risk in patients with CSVD. Methods: A total of 119 patients with CSVD admitted to the Department of Neurology at Tianjin Huanhu Hospital between 17 August 2018 and 7 November 2018 were enrolled in this study. All patients underwent cerebral magnetic resonance imaging scanning and a 2-min walking test using an OPAL wearable sensor and Mobility Lab software. Relevant data were collected using the gait analyzer test system to further analyze the time-space and kinematic parameters of gait. All patients were followed up, and univariate and multivariate logistic regression analyses were conducted to analyze the gait characteristics and relevant risk factors in patients with CSVD at an increased risk of falling. Results: All patients were grouped according to the presence or absence of falling and fear of falling and were divided into a high-fall risk group (n = 35) and a low-fall risk group (n = 72). Logistic multivariate regression analysis showed that the toe-off angle [odds ratio (OR) = 0.742, 95% confidence interval (CI) 0.584-0.942, p < 0.05], toe-off angle coefficient of variation (CV) (OR = 0.717, 95% CI: 0.535-0.962, p < 0.05), stride length CV (OR = 1.256, 95% CI: 1.017-1.552, p < 0.05), and terminal double support CV (OR = 1.735, 95% CI: 1.271-2.369, p < 0.05) were statistically significant (p < 0.05) and were independent risk factors for high-fall risk in patients with CSVD. Conclusion: CSVD patients with seemingly normal gait and ambulation independently still have a high risk of falling, and gait spatiotemporal-kinematic parameters, gait symmetry, and gait variability are important indicators to assess the high-fall risk. The decrease in toe-off angle, in particular, and an increase in related parameters of CV, can increase the fall risk of CSVD patients.
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Parkinson's disease (PD) is a prevalent brain disorder, and PD diagnosis is crucial for treatment. Existing methods for PD diagnosis are mainly focused on behavior analysis, while the functional neurodegeneration of PD has not been well investigated. This paper proposes a method to signify functional neurodegeneration of PD with dynamic functional connectivity analysis. A functional near-infrared spectroscopy (fNIRS)-based experimental paradigm was designed to capture brain activation from 50 PD patients and 41 age-matched healthy controls in clinical walking tests. Dynamic functional connectivity was constructed with sliding-window correlation analysis, and k-means clustering was applied to generate the key brain connectivity states. Dynamic state features including state occurrence probability, state transition percentage and state statistical features were extracted to quantify the variations of brain functional networks. A support vector machine was trained to classify PD patients and healthy controls. Statistical analysis was conducted to investigate the difference between PD patients and healthy controls as well as the relationship between dynamic state features and the MDS-UPDRS sub-score of gait. The results showed that PD patients had a higher probability of transiting to brain connectivity states with high levels of information transmission compared with healthy controls. The MDS-UPDRS sub-score of gait and the dynamics state features showed a significant correlation. Moreover, the proposed method had better classification performances than the available fNIRS-based methods in terms of accuracy and F1 score. Thus, the proposed method well signified functional neurodegeneration of PD, and the dynamic state features may serve as promising functional biomarkers for PD diagnosis.
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BACKGROUND: In Parkinson's disease (PD), walking may depend on the activation of the cerebral cortex. Understanding the patterns of interaction between cortical regions during walking tasks is of great importance. OBJECTIVE: This study investigated differences in the effective connectivity (EC) of the cerebral cortex during walking tasks in individuals with PD and healthy controls. METHODS: We evaluated 30 individuals with PD (62.4±7.2 years) and 22 age-matched healthy controls (61.0±6.4 years). A mobile functional near-infrared spectroscopy (fNIRS) was used to record cerebral oxygenation signals in the left prefrontal cortex (LPFC), right prefrontal cortex (RPFC), left parietal lobe (LPL), and right parietal lobe (RPL) and analyze the EC of the cerebral cortex. A wireless movement monitor was used to measure the gait parameters. RESULTS: Individuals with PD demonstrated a primary coupling direction from LPL to LPFC during walking tasks, whereas healthy controls did not demonstrate any main coupling direction. Compared with healthy controls, individuals with PD showed statistically significantly increased EC coupling strength from LPL to LPFC, from LPL to RPFC, and from LPL to RPL. Individuals with PD showed decreased gait speed and stride length and increased variability in speed and stride length. The EC coupling strength from LPL to RPFC negatively correlated with speed and positively correlated with speed variability in individuals with PD. CONCLUSION: In individuals with PD, the left prefrontal cortex may be regulated by the left parietal lobe during walking. This may be the result of functional compensation in the left parietal lobe.
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Doença de Parkinson , Humanos , Pessoa de Meia-Idade , Idoso , Doença de Parkinson/diagnóstico por imagem , Caminhada/fisiologia , Marcha/fisiologia , Movimento , Lobo Parietal/diagnóstico por imagemRESUMO
Background: Cortical activation patterns in patients with Parkinson's disease (PD) may be influenced by postural strategies, but the underlying neural mechanisms remain unclear. Our aim is to examine the role of the fronto-parietal lobes in patients with PD adopting different postural strategies and the effect of dual task (DT) on fronto-parietal activation. Methods: Two groups of patients with PD adopting either the posture first strategy (PD-PF) or the posture second strategy (PD-PS) were examined respectively when in the "OFF" state while single-walking task (SW) and DT. Frontal and parietal lobe activity was assessed by functional near infrared spectroscopy (fNIRS) and measuring gait parameters. Linear mixed models were used for analyses. Results: Patients with PD who adopted PS had greater cortical activation than those who adopted PF, and there was no difference between PF and PS in the behavioral parameters. For oxyhemoglobin levels, the task condition (SW vs. DT) had a main effect in fronto-parietal lobes. Postural strategy (PD-PF vs. PD-PS) a main effect in the left prefrontal cortex (LPFC), left parietal lobe (LPL), and right parietal lobe (RPL) regions. In the task of walking with and without the cognitive task, patients with PD adopting PS had higher activation in the LPL than those adopting PF. In DT, only PD patients who adopted PS had elevated oxyhemoglobin levels in the LPFC, right prefrontal cortex (RPFC), and LPL compared with the SW, whereas patients with PD who adopted PF showed no differences in any region. Conclusion: Different patterns of fronto-parietal activation exist between PD-PF and PD-PS. This may be because PD-PS require greater cortical functional compensation than those adopting PF.
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Objective.Parkinson's disease (PD) is a common neurodegenerative brain disorder, and early diagnosis is of vital importance for treatment. Existing methods are mainly focused on behavior examination, while the functional neurodegeneration after PD has not been well explored. This paper aims to investigate the brain functional variation of PD patients in comparison with healthy controls.Approach.In this work, we propose brain hemodynamic states and state transition features to signify functional degeneration after PD. Firstly, a functional near-infrared spectroscopy (fNIRS)-based experimental paradigm was designed to capture brain activation during dual-task walking from PD patients and healthy controls. Then, three brain states, named expansion, contraction, and intermediate states, were defined with respect to the oxyhemoglobin and deoxyhemoglobin responses. After that, two features were designed from a constructed transition factor and concurrent variations of oxy- and deoxy-hemoglobin over time, to quantify the transitions of brain states. Further, a support vector machine classifier was trained with the proposed features to distinguish PD patients and healthy controls.Main results.Experimental results showed that our method with the proposed brain state transition features achieved classification accuracy of 0.8200 andFscore of 0.9091, and outperformed existing fNIRS-based methods. Compared with healthy controls, PD patients had significantly smaller transition acceleration and transition angle.Significance.The proposed brain state transition features well signify functional degeneration of PD patients and may serve as promising functional biomarkers for PD diagnosis.
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Doença de Parkinson , Encéfalo , Humanos , Oxiemoglobinas , Doença de Parkinson/diagnóstico , Máquina de Vetores de Suporte , CaminhadaRESUMO
Background: Early rehabilitation (ER) has been reported to be both safe and feasible for patients' post-stroke. To date, however, ER-related outcomes concerning patients who have undergone mechanical thrombectomy (MT) have not been investigated. This study aimed to determine the feasibility of ER and whether it improves prognosis in such patients. Methods: In this single-center, double-blinded, randomized controlled study involving 103 patients who met the study criteria (i.e., has undergone MT), we randomly divided patients (1:1) into ER and conventional rehabilitation groups. The primary outcome was mortality, while secondary outcomes included favorable outcomes (modified Rankin scale of 0-2), the incidence of non-fatal complications, and Barthel Index (BI) scores. We assessed outcomes at 3 months and 1-year post-stroke. Results: No significant between-group differences were found in terms of mortality and favorable outcomes at 3 months and 1-year post-stroke. At 3 months, 15 (28.8%) patients in the ER group and 29 (56.9%) in the conventional rehabilitation group (p = 0.002) had non-fatal complications. The BI in the ER and conventional rehabilitation groups was 100 (85-100) and 87.5 (60-100), respectively, (p = 0.007). At 1 year, the incidence of non-fatal complications was similar between both groups [BI in the ER group, 100 (90-100), p = 0.235; BI in the conventional rehabilitation group, 90 (63.8-100); p = 0.003]. Conclusion: Early rehabilitation (ER) reduces the incidence of early immobility-related complications and effectively improves patients' activities of daily living on a short- and long-term basis. Our results indicate that MT contributes to ER in patients with stroke. Clinical Trial Registration: www.chictr.org.cn, identifier: ChiCTR1900022665.
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Objective: To evaluate the diaphragm thickness and excursion in patients with cervical spinal cord injury and reliability of diaphragmatic ultrasonography.Design: A Pilot Case-Control Study.Setting: China Rehabilitation Research Center (CRRC) /Beijing BO AI Hospital.Participants: Sixty participants with cervical spinal cord injury and sixty control participants were eligible for inclusion in this study.Interventions: Ultrasonographic evaluation of the diaphragm.Outcome Measures: All demographic data were evaluated. Diaphragm thickness, thickening ratio, and diaphragm excursions were assessed at the end of quiet tidal breathing and maximal inspiration. The reliability of inter- and intra-ultrasonography operators were evaluated.Results: Diaphragm thickness was significantly higher in patients with cervical spinal cord injury than the control group (P < 0.001). Diaphragmatic excursion of the right hemidiaphragm was significantly greater in patients with cervical spinal cord injury than the control group (P < 0.001) at the end of quiet tidal breathing. No difference was found in diaphragmatic excursion between two groups (P = 0.32) at the end of maximal inspiration. No significant difference was shown between two groups in thickening ratio. Intraclass correlation coefficients of inter-and intra-ultrasonography operators for the thickness and excursions of the diaphragm were greater than 0.93.Conclusion: Compared with the control group the diaphragm in patients with cervical spinal cord injury is hypertrophied and the diaphragm excursion is greater. Ultrasound is a highly reliable tool for the evaluation of diaphragm thickness and excursion in patients with cervical spinal cord injury.Trial Registration: This trail was registered in Chinese Clinical Trial Registry (NO. ChiCTR-ROC-17010973).
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Medula Cervical , Traumatismos da Medula Espinal , Estudos de Casos e Controles , Medula Cervical/diagnóstico por imagem , Diafragma/diagnóstico por imagem , Humanos , Reprodutibilidade dos Testes , Traumatismos da Medula Espinal/diagnóstico por imagem , UltrassonografiaRESUMO
BACKGROUND Ultrasonography of the diaphragm is an under-utilized instrument in cervical spinal cord injury patients. We conducted a pilot study to first compare the difference of diaphragm thickness and the excursion between patients with cervical spinal cord injury and healthy volunteers, and second to correlate diaphragmic ultrasonography and pulmonary function in cervical spinal cord injury patients. MATERIAL AND METHODS Thirty patients with C4-C5 cervical spinal cord injury of more than 1 year and thirty healthy volunteers were included in this study. All demographic data were evaluated. All participants underwent diaphragmic ultrasonography evaluation and pulmonary function test. Diaphragm thickness of both sides and diaphragm excursions of the right hemi-diaphragm were obtained at the end of quiet tidal breathing and maximal inspiration. We compared diaphragmatic thickness and excursions, and we analyzed the relationship between diaphragmatic ultrasonography and pulmonary function. RESULTS All spinal cord injury patients had restrictive pulmonary dysfunction compared to the control group of healthy volunteers. Diaphragm thickness on both sides was significantly increased in spinal cord injury patients. Diaphragmatic excursion in spinal cord injury patients was increased on the right hemi-diaphragm during tidal breathing. However, the right hemi-diaphragmatic excursion was no difference in both groups during maximal inspiration. Right hemi-diaphragmatic excursion during deep breathing correlated positively with expiratory volume in 1 second (P<0.01) and forced vital capacity (P<0.01). Right hemi-diaphragm thickness at end of maximum inspiration correlated positively with expiratory volume in 1 second (P<0.01) and forced vital capacity (P<0.01). Left hemi-diaphragm thickness at end of maximum inspiration correlated positively with expiratory volume in 1 second (P<0.01) and forced vital capacity (P<0.01). CONCLUSIONS Diaphragm thickness and motion of the cervical spinal cord injury patients were different from controls. Pulmonary function was impaired in spinal cord injury patients. Ultrasonography of the diaphragm as a non-invasive method that is correlated with pulmonary function.
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Diafragma/diagnóstico por imagem , Diafragma/fisiologia , Adulto , Estudos de Casos e Controles , Expiração , Feminino , Humanos , Inalação , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pacientes , Projetos Piloto , Prognóstico , Respiração , Testes de Função Respiratória/métodos , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/fisiopatologia , Volume de Ventilação Pulmonar , Ultrassonografia/métodos , Capacidade VitalRESUMO
PURPOSE: Forkhead box K2 (FOXK2) is a member of the forkhead box family of transcription factors. Recently, researchers discovered that overexpression of FOXK2 inhibits the proliferation and metastasis of breast cancer, non-small cell lung cancer, and colorectal cancer, and is related to the clinical prognosis. However, in hepatocellular carcinoma, FOXK2 results in the opposite phenotypes. Currently, the contribution of FOXK2 to glioma pathogenesis is not clear. PATIENTS AND METHODS: We evaluated the expression of FOXK2 in 151 glioma patients using immunohistochemistry assays. The associations among the expression of FOXK2, clinicopathological parameters, and the prognosis of glioma patients were statistically analyzed. We downregulated and upregulated the level of FOXK2 in glioma cells by transfections with small interfering RNA and plasmids. Then, we investigated the effects on tumor cell behavior in vitro by Cell Counting Kit-8 assays, colony-formation assay, transwell assay, and the epithelial-to-mesenchymal transition (EMT) biomarker levels. RESULTS: The clinical data showed that expression of FOXK2 gradually decreased with increasing World Health Organization (WHO) grades and a low level of FOXK2 indicates a poor prognosis. FOXK2 expression is negatively correlated with Ki67 expression and the WHO degree but is not correlated with other clinicopathological parameters, including sex, age, Karnofsky Performance Status, tumor diameter, O-6-methylguanine-DNA methyltransferase, and glutathione S-transferase pi. FOXK2 knockdown enhances glioma cell proliferation, migration, invasion, and EMT process, and, in contrast, FOXK2 overexpression inhibits glioma cell proliferation, migration, invasion, and the EMT process. CONCLUSION: Expression of FOXK2 gradually decreases with increasing WHO grades. FOXK2 inhibits tumor proliferation, migration, and invasion. FOXK2 is a critical mediator of the EMT process.
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OBJECTIVE: Our aim was to evaluate the effect of aquatic obstacle training on balance parameters in comparison with a traditional aquatic therapy in patients with Parkinson's disease. DESIGN: A randomized single-blind controlled trial. SETTING: Outpatients in the rehabilitation department. SUBJECTS: A total of 46 patients with Parkinson's disease in Hoehn-Yahr stage 2-3. INTERVENTIONS: Participants were randomly assigned to (1) aquatic therapy or (2) obstacle aquatic therapy. All participants undertook aquatic therapy for 30 minutes, five times per week for six weeks. MAIN MEASURES: The Freezing of Gait Questionnaire, Functional Reach Test, Timed Up and Go test and Berg Balance Scale were assessed at baseline, posttreatment and at six-month follow-up. RESULTS: Both groups of patients had improved primary outcomes after the training program. A between-group comparison of the changes revealed that obstacle aquatic therapy was significantly higher for the Freezing of Gait Questionnaire (after treatment: 8.7 ± 3.3 vs 6.2 ± 2.1, P = 0.004; posttest: 7.7 ± 3.1 vs 5.3 ± 2.0, P = 0.003) and Timed Up and Go test (after treatment: 17.1 ± 2.9 vs 13.8 ± 1.9, P < 0.001; posttest: 16.3 ± 2.8 vs 12.9 ± 1.4, P < 0.001). CONCLUSION: Obstacle aquatic therapy in this protocol seems to be more effective than traditional protocols for gait and balance in patients with Parkinson's disease, and the effect lasts for six months.
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Terapia por Exercício , Marcha/fisiologia , Doença de Parkinson/reabilitação , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Equilíbrio Postural , Estudos Prospectivos , Método Simples-Cego , Resultado do TratamentoRESUMO
OBJECTIVE: Scholars have gradually come to appreciate the relevance of serine and glycine metabolism. Recently, researchers have discovered that mitochondrial serine hydroxymethyltransferase 2 (SHMT2) is overexpressed in various types of cancer. However, the function of SHMT2 in glioma is not clear. In this study, we sought to examine the expression of SHMT2 in glioma, the association between SHMT2 expression and clinicopathological characteristics, and the association of SHMT2 expression with prognosis in glioma patients. METHODS: We evaluated the expression of SHMT2, Ki67, O-6-methylguanine-DNA methyltransferase (MGMT), and Glutathione S Transferase pi (GST-pi) in 150 glioma patients using immunohistochemistry assays. The associations among the expression of SHMT2, clinicopathological parameters, and outcome of glioma patients were statistically analysed. RESULTS: The expression of SHMT2 was increased in gliomas compared to normal brain tissue and gradually increased with increasing WHO grade. The SHMT2 expression was positively correlated with Ki67 expression and WHO degree (p<0.01) but was not correlated with other clinicopathological parameters, including sex, age, Karnofsky Performance Status (KPS), tumour diameter, MGMT, and GST-pi (p>0.05). Kaplan-Meier survival curves and Cox regression analyses showed that SHMT2 expression and the WHO grade were independent prognostic indicators for glioma patients. CONCLUSION: The expression of SHMT2 in glioma was significantly increased compared to normal brain tissue. SHMT2 promoted tumour proliferation, and there was no association between SHMT2 and drug resistance mechanisms of glioma. SHMT2 may be a novel and valuable biomarker for the diagnosis of glioma and an independent prognostic parameter of glioma.
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Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Glicina Hidroximetiltransferase/metabolismo , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
During pathological conditions, extracellular-5'-nucleotidase/CD73 can protect neurons by reducing the permeability of the blood brain barrier. In recent years, it has been demonstrated that CD73 can negatively contribute to the growth of gliomas; however, the function of CD73 in glioma blood vessels is not clear. We analysed the expression of CD73 in 72 glioma patients using immunohistochemistry and correspondingly compared the results with the Edema index (EI). We established an in vitro model of the blood-tumour barrier and analysed the expression of CD73 in vascular endothelial cells. Lastly, CD73 expression was inhibited in endothelial cells, and the effects of this inhibition on tight junction structure and transendothelial resistance were observed. Compared to normal brains, the expression of CD73 in blood vessels of glioma patients was significantly decreased, and the amount was lower in the centre of the tumour than the periphery. The proportion of CD73-positive blood vessels had a positive correlation with the EI. The expression of CD73 in the in vitro endothelial cell blood-tumour barrier model was decreased. Lastly, inhibiting CD73 was found to decrease the expression of tight junction related proteins in endothelial cells and to decrease the value of transendothelial electric resistance. The expression of CD73 in glioma blood vessels was significantly decreased, which may play a multi-functional role in decreasing the expression of tight junction related proteins of brain microvascular endothelial cells and may also increase blood-tumour barrier permeability and accelerate the formation of PTBE.
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5'-Nucleotidase/metabolismo , Edema Encefálico/metabolismo , Neoplasias Encefálicas/metabolismo , Encéfalo/metabolismo , Glioma/metabolismo , 5'-Nucleotidase/antagonistas & inibidores , Adulto , Idoso , Western Blotting , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Edema Encefálico/patologia , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/patologia , Linhagem Celular , Técnicas de Cocultura , Impedância Elétrica , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Inibidores Enzimáticos/farmacologia , Feminino , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/metabolismo , Glioma/irrigação sanguínea , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Junções Íntimas/patologia , Adulto JovemRESUMO
OBJECTIVE: To investigate the effects of hydrotherapy on walking ability and balance in patients with chronic stroke. DESIGN: Single-blind, randomized controlled pilot trial. SETTING: Outpatient rehabilitation clinic at a tertiary neurological hospital in China. SUBJECTS: A total of 28 participants with impairments in walking and controlling balance more than six months post-stroke. INTERVENTION: After baseline evaluations, participants were randomly assigned to a land-based therapy (control group, n = 14) or hydrotherapy (study group, n = 14). Participants underwent individual sessions for four weeks, five days a week, for 45 minutes per session. MAIN MEASURES: After four weeks of rehabilitation, all participants were evaluated by a blinded assessor. Functional assessments included the Functional Reach Test, Berg Balance Scale, 2-minute walk test, and Timed Up and Go Test. RESULTS: After four weeks of treatment, the Berg Balance Scale, functional reach test, 2-minute walk test, and the Timed Up and Go Test scores had improved significantly in each group (P < 0.05). The mean improvement of the functional reach test and 2-minute walk test were significantly higher in the aquatic group than in the control group (P < 0.01). The differences in the mean values of the improvements in the Berg Balance Scale and the Timed Up and Go Test were not statistically significant. CONCLUSION: The results of this study suggest that a relatively short programme (four weeks) of hydrotherapy exercise resulted in a large improvement in a small group (n = 14) of individuals with relatively high balance and walking function following a stroke.