RESUMO
Growing evidence has proven the efficacy of physical exercise in remyelination and motor function performance after spinal cord injury (SCI). However, the molecular mechanisms of treadmill training on myelin repair and functional recovery after SCI have not yet been fully studied. Here, we explored the effect of treadmill training on upregulating peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α)-mediated myelin repair and functional recovery in a mouse model of thoracic T10 contusion injury. A 4-week treadmill training scheme was conducted on mice with SCI. The expression levels of oligodendrogenesis-related protein and PGC1α were detected by immunofluorescence, RNA fluorescence in situ hybridization and western blotting. Transmission electron microscopy (TEM) was used to observe myelin structure. The Basso Mouse Scale (BMS) and CatWalk automated gait analysis system were used for motor function recovery evaluation. Motor evoked potentials (MEPs) were also identified. In addition, adeno-associated virus (AAV)-mediated PGC1α knockdown in OLs was used to further unravel the role of PGC1α in exercise-induced remyelination. We found that treadmill training boosts oligodendrocyte precursor cells (OPCs) proliferation, potentiates oligodendrocytes (OLs) maturation, and increases myelin-related protein and myelin sheath thickness, thus impelling myelin repair and hindlimb functional performance as well as the speed and amplitude of nerve conduction after SCI. Additionally, downregulating PGC1α through AAV attenuated these positive effects of treadmill training. Collectively, our results suggest that treadmill training enhances remyelination and functional recovery by upregulating PGC1α, which should provide a step forward in the understanding of the effects of physical exercise on myelin repair.
Assuntos
Bainha de Mielina , Traumatismos da Medula Espinal , Camundongos , Animais , Bainha de Mielina/metabolismo , PPAR gama/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Hibridização in Situ Fluorescente , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/metabolismo , Recuperação de Função Fisiológica/fisiologiaRESUMO
This study aims to investigate the effect of insulin-like growth factor 1 (IGF-1) combined with osteopontin (OPN) on the protein expression levels and growth of neuronal axons and its possible mechanism. In this study, IGF-1 combined with OPN promoted neuronal axon growth through the IGF-1R/Akt/mTOR signaling pathway in lipid rafts, and the effect was better than that of either agent alone. This effect was suppressed when given the mTOR inhibitor rapamycin or the lipid raft cholesterol extraction agent methyl-ß-cyclodextrin (M-ß-CD). Rapamycin could inhibit the expression of phosphorylated ribosomal S6 protein (p-S6) and phosphorylated protein kinase B (p-Akt) and limit axon growth. In addition to the above effects, M-ß-CD significantly downregulated the expression of phosphorylated insulin-like growth factor 1 receptor (p-IR). To further investigate the changes in lipid rafts when stimulated by different recombinant proteins, membrane lipid rafts were isolated to observe the changes by western blot. The expression levels of insulin-like growth factor 1 receptor (IR) and P-IR in the IGF-1 combined with OPN group were the highest. When M-ß-CD was administered to the lipid rafts of neurons, the enrichment of IR by IGF-1 combined with OPN was weakened, and the p-IR was decreased. Our study found that IGF-1 combined with OPN could promote axon growth by activating the IGF-1R/Akt/mTOR signaling pathway in neuronal lipid rafts.
Assuntos
Fator de Crescimento Insulin-Like I , Proteínas Proto-Oncogênicas c-akt , Axônios/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Microdomínios da Membrana/metabolismo , Neurônios/metabolismo , Osteopontina , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor IGF Tipo 1/metabolismo , Transdução de Sinais , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Animais , RatosRESUMO
BACKGROUND AND PURPOSE: This study aimed to assess the efficacy of an ultrasound-guided lateral approach for BoNT-A (botulinum toxin A) injections into the subscapularis in patients with hemiplegic shoulder pain. METHODS: This single-center trial used a randomized, double-blind, placebo-controlled design. The key inclusion criteria were a visual analogue scale score of ≥4 cm and a modified Ashworth scale score of ≥1+. The patients were randomized to receive either BoNT-A injections or a placebo. The outcomes included the visual analogue scale score, modified Ashworth scale score, pain-free passive range of motion of the hemiplegic shoulder, Fugl-Meyer assessment score for the upper extremities, and Stroke-Specific Quality-of-Life score. RESULTS: A total of 49 hemiplegic shoulder pain patients were screened, and 36 were included. The participants receiving the BoNT-A injection reported a significant decrease in pain (visual analogue scale, -1.39 [95% CI, -2.41 to -0.36]; P=0.002) and spasticity (modified Ashworth scale score for shoulder internal rotation, -0.72 [95% CI, -1.10 to -0.35]; P=0.001; modified Ashworth scale score for shoulder abduction, -0.44 [95% CI, -0.90 to -0.01]; P=0.026) and improved pain-free passive shoulder internal rotation range of motion (14.56 [95% CI, 6.70-21.41]; P<0.001) and quality of life (Stroke-Specific Quality-of-Life upper extremity subscale, P=0.025) compared with those receiving the placebo at the end point. The shoulder abduction range of motion did not significantly improve after the BoNT-A injection at the end point (P=0.127). In addition, the patients in the BoNT-A group showed significant improvements in the visual analogue scale score and shoulder external rotation range of motion at the 12-week follow-up. No injection-related adverse events were observed during or after the interventions in either group. CONCLUSIONS: The ultrasound-guided lateral approach for BoNT-A injections into the subscapularis is a precise and reliable method for reducing pain and spasticity and improving quality of life in stroke survivors with hemiplegic shoulder pain. Registration: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1900023513.
Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Injeções Intramusculares/métodos , Fármacos Neuromusculares/administração & dosagem , Dor de Ombro/tratamento farmacológico , Ultrassonografia de Intervenção/métodos , Método Duplo-Cego , Feminino , Hemiplegia/tratamento farmacológico , Hemiplegia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Dor de Ombro/etiologia , Acidente Vascular Cerebral/complicaçõesRESUMO
Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is regarded as a potential method for recovery in stroke. The effectiveness of taVNS in acute and subacute stroke should be further discussed as previously, only a few small-scale trials have focused on chronic stroke patients. The objective of this study is to investigate the effect and safety of taVNS on upper limb motor function in subacute ischemic stroke patients. Methods: Twenty-one subacute ischemia stroke patients with single upper limb motor function impairment were enrolled and randomly assigned to conventional rehabilitation training with real or sham taVNS, delivered for 15 consecutive days. Electrodes were fixed to the cymba conchae of the left ear with or without electrical stimulation. Conventional rehabilitation training was performed immediately after the end of real or sham taVNS by the same therapists. Baseline assessments were performed on day 0 of enrollment, and posttreatment evaluations were performed at 15 days, 4 weeks, and 12 weeks after the first intervention. The assessment included the upper limb Fugl-Meyer assessment (FMA-U), the Wolf motor function test (WMFT), the Functional Independence Measurement (FIM), and Brunnstrom stage. Heart rate (HR) and blood pressure (BP) were measured before and after each taVNS intervention. At the same time, any adverse effects were observed during the procedure. Outcomes were assessed by a blind evaluator. Results: There were no significant differences in FMA-U, WMFT, FIM, and Brunnstrom scores between the two groups at baseline (P > 0.05). At the endpoint, the FMA-U, WMFT, and FIM scores were significantly higher than before treatment (P < 0.05), and there was a significantly greater improvement of those measurements in taVNS group compared with sham-taVNS group (P < 0.05). Significant improvements in FMA-U score were found between groups at follow-up. Only one case of skin redness occurred during the study. Conclusions: This study revealed that taVNS appeared to be beneficial to the recovery of upper limb motor function in subacute ischemia stroke patients without obvious adverse effects. Trial registration. This trial is registered with ChiCTR1800019635 on 20 November 2018 (http://www.chictr.org.cn/showproj.aspx?proj=32961).
Assuntos
AVC Isquêmico/reabilitação , Recuperação de Função Fisiológica , Reabilitação do Acidente Vascular Cerebral/métodos , Estimulação do Nervo Vago , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento , Extremidade Superior/fisiopatologia , Estimulação do Nervo Vago/efeitos adversosRESUMO
OBJECTIVE: The purpose of this meta-analysis was to assess the long-term effects of extracorporeal shock wave therapy (ESWT) on post-stroke spasticity. DATA SOURCES: An electronic search of EMBASE, MEDLINE, and Cochrane Central Register of Controlled Trials (CENTRAL) with hand search of relevant papers were performed on 20 June 2019. REVIEW METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the literature for randomized controlled trials of ESWT in stroke patients with spasticity. The primary outcome was the Modified Ashworth Scale (MAS) grade, and the second outcomes were the Visual Analogue Scale (VAS), range of motion (ROM) of joint, the Fugl-Meyer assessment (FMA) grade and adverse events. Two authors independently extracted data, assessed trial eligibility and risk of bias. Meta-analyses were performed using RevMan 5.3 software. RESULTS: We extracted data from 8 randomized controlled trials (301 participants). At long-term follow-up, ESWT significantly reduced MAS (Weighted Mean Difference (WMD) = -.36, 95% confidence interval (CI) = -.53 to -.19, I2â¯=â¯68%; P < .001) and VAS (WMD = -.94, 95% CI = -1.51 to -.37, I2â¯=â¯15%; Pâ¯=â¯.001), enhanced ROM (WMDâ¯=â¯5.97, 95% CIâ¯=â¯2.76 to 9.18, I2â¯=â¯0%; P < .001) and FMA (WMDâ¯=â¯1.26, 95% CIâ¯=â¯.29 to 2.24, I2â¯=â¯96%; Pâ¯=â¯.01). CONCLUSIONS: ESWT showed long-term effects in relieving spasticity, while reducing pain, enhancing ROM and motor function in stroke patients.
Assuntos
Tratamento por Ondas de Choque Extracorpóreas , Contração Muscular , Espasticidade Muscular/terapia , Músculo Esquelético/inervação , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Tratamento por Ondas de Choque Extracorpóreas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Espasticidade Muscular/diagnóstico , Espasticidade Muscular/etiologia , Espasticidade Muscular/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Reabilitação do Acidente Vascular Cerebral/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
AIM: The aim of this study is to evaluate incidences of inappropriate initial urinary catheter placements within an older inpatient cohort. METHODS: A total of 200 inpatients that received urinary catheterizations within 24 hours of admission were recruited for this observational study. The key demographic and clinical factors were recorded. Adverse outcomes were assessed by examining incidences of catheter-associated urinary tract infection (CAUTI) during hospitalization, after transfer to skilled nursing facilities, second, duration of hospital stay and by scoring changes on the Katz Index of Independence in Activities of Daily Living. Correlative relationships between demographic data and clinical factors with adverse outcomes were analyzed. RESULTS: Inappropriate initial urinary catheterization in our cohort was approximately 39%. This was associated with elevated Charlson comorbidity index scores and increased dependency, with correlations to medical diagnosis. We also observed that the primary rationale for the procedure (inappropriate catheterization) was for neurogenic bladder (where intermittent catheterization was indicated) and in 'convenience-of-care' catheterizations. Inappropriate catheter placement was ultimately associated with an elevated CAUTI at point of discharge, with transfers to skilled nursing facilities and also with an increased duration of hospital stay. CONCLUSIONS: Inappropriate catheter placement was prevalence in southwestern China and associated with adverse outcomes.
Assuntos
Hospitalização , Pacientes Internados , Cateterismo Urinário/efeitos adversos , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Infecções Relacionadas a Cateter/epidemiologia , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Alta do Paciente , Infecções Urinárias/epidemiologiaRESUMO
OBJECTIVE: To investigate the short- and long-term effects of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis (IPF). DATA SOURCES: An electronic search of MEDLINE, Embase and Cochrane Central databases along with hand search of relevant papers were performed on 15 March 2018. REVIEW METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the literature for randomized controlled trials of pulmonary rehabilitation in IPF patients. The outcomes were exercise capacity and health-related quality of life. Two authors independently extracted data, assessed trial eligibility and risk of bias. Meta-analyses were performed using RevMan and STATA software. RESULTS: We extracted data from four randomized controlled trials (142 participants). At short-term follow-up, pulmonary rehabilitation significantly enhanced 6-minute walk distance (6-MWD; weighted mean difference (WMD) = 38.38, 95% confidence interval (CI) = 4.64-72.12, I2 = 60.7%; P < 0.05), reduced St. George's Respiratory Questionnaire (SGRQ)/IPF-specific SGRQ (SGRQ-I) total score (WMD = -8.40, 95% CI = -11.44 to -5.36, I2 = 0%; P < 0.00001). At long-term follow-up, pulmonary rehabilitation could not enhance 6-MWD (WMD = 17.02, 95% CI = -26.87 to 60.81, I2 = 36.3%; P = 0.43) or reduce SGRQ/SGRQ-I total score (WMD = -3.45, 95% CI = -8.55 to 1.64, I2 = 38.3%; P = 0.088). CONCLUSION: In patients with IPF, pulmonary rehabilitation showed short-term effects in enhancing exercise capacity and health-related quality of life, while it had no detectable effects at long-term follow-up.
Assuntos
Fibrose Pulmonar Idiopática/reabilitação , Humanos , Qualidade de Vida , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Curcumin is known to have neuroprotective properties in cerebral ischemia reperfusion (I/R) injury. However, the underlying molecular mechanisms remain largely unknown. Recently, emerging evidences suggested that increased mitochondrial biogenesis enabled preventing I/R injury. Here, we sought to determinate whether curcumin alleviates I/R damage through regulation of mitochondrial biogenesis. Sprague-Dawley rats were subjected to a 2-h period of right middle cerebral artery occlusion followed by 24 h of reperfusion. Prior to onset of occlusion, rats had been pretreated with either low (50 mg/kg, intraperitoneal injection) or high (100 mg/kg, intraperitoneal injection) dose of curcumin for 5 days. Consequently, we found that curcumin pretreatment enabled improving neurological deficit, diminishing infarct volume and increasing the number of NeuN-labeled neurons in the I/R rats. Accordingly, the index of mitochondrial biogenesis including nuclear respiratory factor-1, mitochondrial transcription factor A and mitochondrial number significantly down-regulated in I/R rats were reversed by curcumin pretreatment in a dose-dependent manner, and the mitochondrial uncoupling protein 2 presented the similar change. Taken together, our findings provided novel evidence that curcumin may exert neuroprotective effects by increasing mitochondrial biogenesis.
Assuntos
Isquemia Encefálica/prevenção & controle , Curcumina/uso terapêutico , Renovação Mitocondrial/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Curcumina/farmacologia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Renovação Mitocondrial/fisiologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologiaRESUMO
Spinal cord injury (SCI) results in stalled motor function recovery under the chronic phase. One of the reasons due to the presence of ongoing inflammation. Therefore, regulating the status of immune cells may help reopen the window for neural repair, which represents a potential therapeutic target. In this study, we aimed to investigate whether this could be achieved in mice with cervical 5 crush CSCI (4 W) by utilizing a concentration of 0.5 mg/kg of lipopolysaccharide (LPS) to stimulate microglia/macrophages. Additionally, the mice underwent rehabilitation training for another 6 weeks. Our results showed that systemic injection of LPS enhanced the effects of forelimb rehabilitation training, as evaluated through single pellet grasping (SPG). Electrophysiological studies revealed the restoration of cortical drive to the injured side's forelimb muscles in the training combined with LPS group. Tract tracing studies demonstrated the reconstruction of cortical innervation to the cervical spinal cord. Furthermore, the levels of pro-inflammatory phenotype markers, such as inducible nitric oxide synthase (INOS) and CD68, decreased, while the expression of anti-inflammatory phenotype markers, including arginase 1 (ARG-1) and CD206, increased. Importantly, this phenotypic switch in microglia/macrophages was accompanied by an increase in phagocytic activity markers as indicated by BODIPY + IBA1 + staining. Collectively, our data suggests that low-dose LPS improves the effects of rehabilitation training by regulating the phenotypic transformation of microglia/macrophages in CSCI. This study provides a fresh perspective and intervention direction for the clinical treatment of chronic spinal cord injuries.
Assuntos
Lipopolissacarídeos , Macrófagos , Microglia , Fenótipo , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/terapia , Microglia/efeitos dos fármacos , Microglia/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Doença Crônica , Camundongos Endogâmicos C57BL , Feminino , Recuperação de Função Fisiológica/efeitos dos fármacos , Membro Anterior , Fagocitose/efeitos dos fármacosRESUMO
Urinary incontinence is a common complication in stroke survivors for whom new interventions are needed. This study investigated the therapeutic effect of low-frequency (LF) repeated transcranial magnetic stimulation (rTMS) on the contralesional primary motor cortex (M1) in patients with poststroke urinary incontinence (PSI). A total of 100 patients were randomly assigned to the rTMS group or sham-rTMS group on basis of the intervention they received. Both groups underwent five treatment sessions per week for 4 weeks. Data from the urodynamic examination were used as the primary outcome. The secondary outcome measures were questionnaires and pelvic floor surface electromyography. After 4 weeks of intervention, the maximum cystometric capacity (MCC), maximum detrusor pressure (Pdet.max), residual urine output, overactive bladder score (OABSS) (including frequency, urgency, and urgency urinary incontinence), and the ICIQ-UI SF improved significantly in the rTMS group compared with those in the sham-rTMS group (P < 0.05). However, no changes in pelvic floor muscle EMG were detected in patients with PSI (both P > 0.05). Our data confirmed that 4 weeks of LF-rTMS stimulation on the contralateral M1 positively affects poststroke urinary incontinence in several aspects, such as frequency, urgency urinary incontinence, MCC, end-filling Pdet, OABSS, and ICIQ-UI SF scores.
Assuntos
Eletromiografia , Acidente Vascular Cerebral , Estimulação Magnética Transcraniana , Bexiga Urinaria Neurogênica , Humanos , Estimulação Magnética Transcraniana/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/fisiopatologia , Idoso , Bexiga Urinaria Neurogênica/terapia , Bexiga Urinaria Neurogênica/etiologia , Bexiga Urinaria Neurogênica/fisiopatologia , Resultado do Tratamento , Incontinência Urinária/terapia , Incontinência Urinária/etiologia , Incontinência Urinária/fisiopatologia , Urodinâmica , Diafragma da Pelve/fisiopatologia , Reabilitação do Acidente Vascular Cerebral/métodos , Córtex Motor/fisiopatologiaRESUMO
BACKGROUND AND PURPOSE: Research to date has lacked definitive evidence to determine whether mirror therapy promotes the recovery of upper extremity function after stroke. Considering that previous studies did not stratify patients based on structural retention, this may be one of the reasons for the negative results obtained in many trials. The goal evaluates the efficacy of TBMT (utilizing an innovatively designed mirror) versus standard occupational therapy for stroke patient's upper limb functionality. METHODS AND ANALYSIS: This single-center randomized controlled trial will involve 50 patients with stroke. All patients will be randomly assigned to either the task-based mirror therapy or the control group. The interventions will be performed 5 days per week for 4 weeks. The primary outcomes will be the mean change in scores on both the FMA-UE and modified Barthel Index (MBI) from baseline to 4 weeks intervention and at 12 weeks follow-up between the two groups and within groups. The other outcomes will include the Action Research Arm Test (ARAT), the Nine Hole Peg Test (9HPT), the Functional Independence Measure, and MRI. DISCUSSION: This trial will not only to establish that task-based mirror therapy (TBMT) could improve the recovery of hand function after stroke but also to explore the underlying mechanisms. We expect that this finding will clarify the brain activation and brain network mechanisms underlying the improvement of hand function with task-oriented mirror therapy and lead to new ideas for stroke hand function rehabilitation. TRIAL REGISTRATION: URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR2300068855. Registered on March 1, 2023.
Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Terapia de Espelho de Movimento , Hemiplegia/diagnóstico , Hemiplegia/etiologia , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Extremidade Superior , Reabilitação do Acidente Vascular Cerebral/métodos , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Spinal cord injury (SCI) is a devastating neurological disorder affecting millions of people worldwide, resulting in severe and permanent disabilities that significantly impact the individual's life. Rehabilitation is a commonly accepted and effective clinical treatment modality for neurological disabilities. A single form of rehabilitation training is, however, limited. Indeed, recent studies have reported that a combination of various training strategies may be more promising in promoting functional recovery. However, few studies have focused on combining different forms of rehabilitative training. Here, we investigated the effect of combining treadmill training and single pellet grasping in a well-established model of murine SCI to assess whether combining rehabilitation approaches improve outcomes. In brief, one week following crush SCI, mice were subjected to the treadmill and single pellet grasping training (SPG) for a period of six weeks. Biotinylated dextran amine (BDA) was used to anterogradely trace corticospinal tract axons to assess functionally relevant axonal sprouting. Our results revealed that the combined training upregulated p-S6 expression, facilitated axonal sprouting, increased the formation of functional synaptic connections, and promoted functional recovery of the upper limb. Our study provides experimental evidence for the benefit of combining multiple modalities of rehabilitative strategies.
Assuntos
Axônios , Traumatismos da Medula Espinal , Camundongos , Animais , Modelos Animais de Doenças , Tratos Piramidais , Recuperação de Função Fisiológica , Medula Espinal , Regeneração NervosaRESUMO
BACKGROUND: Severe acute pancreatitis complicated by acute respiratory distress is a common cause of intensive care unit (ICU) admission. These patients are at risk of a decline in physical activity due to bed rest. Neuromuscular electrical stimulation (NMES) has been recommended for ICU patients to strengthen muscles, but its effects on muscle atrophy, respiratory function, multiple organ dysfunction, and functional status of these patients remain to be proven. METHODS: Patients (n = 80) will be prospectively randomized into an NMES group and a control group. The NMES group will receive NMES for 1 h per day for 7 days, and both the control and NMES groups will receive usual care. The efficacy will be assessed by an experienced physiotherapist and sonographer who will be blinded to the patient's group assignment. Muscle power assessment (MRC scale), lower extremity circumference, grip strength, activities of daily living (Barthel index), and Marshall scores will be measured at baseline and posttreatment. The functions of the diaphragm assessments will be measured daily. Barthel index measurements will be followed up in the 1st month, 3rd month, and 6th month after discharge. DISCUSSION: The trial will explore the effectiveness of NMES in functional status and diaphragm function in patients with SAP complicated with ARDS. The results of this trial will provide strong evidence of the efficacy of NMES in treating SAP patients with ARDS. TRIAL REGISTRATION: This trial has been registered at the Chinese Clinical Trial Registry, and the registry name is "Effectiveness of neuromuscular electrical stimulation in severe acute pancreatitis complicated patients with acute respiratory distress syndrome: study protocol for a randomized controlled trial," URL: https://www.chictr.org.cn , numbered ChiCTR2300068995. Date of Registration: 2023-03-03.
Assuntos
Pancreatite , Síndrome do Desconforto Respiratório , Humanos , Atividades Cotidianas , Doença Aguda , Pancreatite/complicações , Pancreatite/diagnóstico , Pancreatite/terapia , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/terapia , Diafragma , Estimulação Elétrica , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Previous studies reported that the codeletion of PTEN and SOCS3 can greatly enhance the capacity of axon regeneration after central nervous system (CNS) injury. Moreover, the promotion of functional recovery can be improved by rehabilitative training under a use-dependent plasticity mechanism after CNS injury. However, few studies have reported the interaction between these mechanisms after spinal cord injury (SCI). Therefore, we investigated the combined effects of PTEN/SOCS3 coinhibition and rehabilitative training on axon regeneration and upper extremity motor functional improvement after cervical SCI in mice. In this study, we used RNA interference viruses to coinhibit PTEN and SOCS3 and induced a C5 crush injury on the side of preference. The injured upper extremity was trained by single pellet grasping for 4 weeks. We found that the coinjection of viruses significantly increased the expression of p-S6 and p-STAT in the cortex, reduced the dieback pattern of injured axons and promoted traced axon regeneration. More importantly, combination therapy further enhanced axon regeneration compared with PTEN/SOCS3 coinhibition alone. In behavioral tests, the motor performance of the mice in the PTEN/SOCS3 + Training group was better than that of the mice in the other groups. These results indicate that combining task-based rehabilitative training with PTEN/SOCS3 coinhibition further promotes axon regeneration and significant improvement in forelimb skilled motor function after cervical SCI. Our findings provide new therapeutic insights into SCI treatment.
Assuntos
Medula Cervical , Traumatismos da Medula Espinal , Animais , Camundongos , Axônios/fisiologia , Regeneração Nervosa/fisiologia , Recuperação de Função Fisiológica/fisiologia , Medula Espinal , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina , Extremidade SuperiorRESUMO
Treadmill exercise is widely considered an effective strategy for restoration of skilled motor function after spinal cord injury (SCI). However, the specific exercise intensity that optimizes recovery and the underlying mechanistic basis of this recovery remain unclear. To that end, we sought to investigate the effect of different treadmill exercise intensities on cortical mTOR activity, a key regulator of functional recovery following CNS trauma, in an animal model of C5 crush spinal cord injury (SCI). Following injury, animals were subjected to treadmill exercise for 4 consecutive weeks at three different intensities (low intensity [LEI]; moderate intensity [MEI]; and high intensity [HEI]). Motor function recovery was assessed by horizontal ladder test, cylinder rearing test, and electrophysiology, while neurotrophic factors and cortical mechanistic target of rapamycin (mTOR) pathway-related proteins were assessed by Western blotting. The activation of the cortical mTOR pathway and axonal sprouting was evaluated by immunofluorescence and the changes of plasticity in motor cortex neurons were assessed by Golgi staining. In keeping with previous studies, we found that 4 weeks of treadmill training resulted in improved skilled motor function, enhanced nerve conduction capability, increased neuroplasticity, and axonal sprouting. Importantly, we also demonstrated that when compared with the LEI group, MEI and HEI groups demonstrated elevated expression of brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), phosphorylated ribosomal S6 protein (p-S6), and protein kinase B (p-Akt), consistent with an intensity-dependent activation of the mTOR pathway and neurotrophic factor expression in the motor cortex. We also observed impaired exercise endurance and higher mortality during training in the HEI group than in the LEI and MEI groups. Collectively, our findings suggest that treadmill exercise following SCI is an effective means of promoting recovery and highlight the importance of the cortical mTOR pathway and neurotrophic factors as mediators of this effect. Importantly, our findings also demonstrate that excessive exercise can be detrimental, suggesting that moderation may be the optimal strategy. These findings provide an important foundation for further investigation of treadmill training as a modality for recovery following spinal cord injury and of the underlying mechanisms.
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Traumatismos da Medula Espinal , Animais , Camundongos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Neurônios Motores/metabolismo , Recuperação de Função Fisiológica/fisiologia , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
In this study, we examined the combined impact of osteopontin (OPN) and treadmill training on mice with spinal cord injury (SCI). OPN was overexpressed by injecting AAV9-SPP1-GFP into the sensorimotor cortex, followed by a left incomplete C5 crush injury two weeks later. Mice (Ex or Ex + OPN group) were trained at 50% maximum running speed for 8 weeks. To analyze the effects, we used biotinylated dextran amine (BDA) for tracing the corticospinal tract (CST) and performed Western blotting and immunohistochemical methods to assess the activation of the mammalian target of rapamycin (mTOR). We also examined axonal regeneration and conducted behavioral tests to measure functional recovery. The results demonstrated that treadmill training promoted the expression of neurotrophic factors such as brain-derived neurotrophic factor (BNDF) and insulin-like growth factor I (IGF-1) and activated mTOR signaling. OPN amplified the effect of treadmill training on activating mTOR signaling indicated by upregulated phosphorylation of ribosomal protein S6 kinase (S6). The combination of OPN and exercise further promoted functional recovery and facilitated limited CST axonal regeneration which did not occur with treadmill training and OPN treatment alone. These findings indicate that OPN enhances the effects of treadmill training in the treatment of SCI and offer new therapeutic insights for spinal cord injury.
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OBJECTIVES: To explore the effects of kinesiotaping in the treatment of shoulder pain and upper limb function in stroke survivors. METHODS: PubMed, EMBASE and the Cochrane Central Register of Controlled Trials were electronically and manually searched to identify relevant publications from inception to March 1, 2022. Full-text qualitative studies that explored the effects of kinesiotaping on hemiplegic shoulder pain and poststroke upper limb spasticity were included in the analysis. Data synthesis with a thematic approach was performed to generate descriptive and analytical themes. RESULTS: Nine randomized controlled trials with 253 participants were included. The meta-analysis showed that kinesiotaping significantly reduced poststroke shoulder pain (mean difference (MD) = -1.59, 95% confidence interval (CI): -3.21 to -0.02, P = 0.05), enhanced range of motion (ROM) (MD = 7.00, 95% CI: 2.3 to 11.7, P = 0.004), reduced Modified Ashworth scale (MAS) scores (MD = -0.26, 95% CI: -0.51 to -0.01, P = 0.04), and decreased the magnitude of shoulder subluxation (MD = -0.42, 95% CI: -0.76 to -0.08, P = 0.02). However, outcomes, such as the Fugl-Meyer score and Barthel index, did not differ between the kinesiotaping and control groups. CONCLUSIONS: Kinesiotaping effectively relieved shoulder pain, improved upper limb spasticity and ROM, and reduced shoulder subluxation in stroke survivors. However, the effects of kinesiotaping on upper limb function in terms of FMA-UE scores and independence in activities of daily living were not verified. High-quality RCTs designed with large sample sizes are still required in the future.
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BACKGROUND: corticosteroid injection (CSI) has been used to treat greater trochanter pain syndrome (GTPS) for many years. However, so far, the efficacy of CSI in the treatment of GTPS is still controversial. Therefore, the aim of this review is to evaluate the effectiveness of CSI in comparison with sham intervention, nature history, usual care, platelet-rich plasma (PRP), physiotherapy/exercise therapy, dry needling, or other nonsurgical treatment for improvements in pain and function in GTPS. METHODS: PubMed (Medline), Embase, Cochrane Library were searched from their inception until April 2021. Randomized controlled trails (RCTs) comparing CSI to nonsurgical treatment were included. Data on the effect of CSI on pain and function were extracted and checked by two review authors independently. The treatment effect was analyzed in the short term, medium term, and long term. RESULTS: Eight RCTs (764 patients) were included. This review suggests CSI may be superior to usual care and 'wait and see,' ESWT, but may not be superior to exercise, PRP, dry needling, and sham intervention in short-term pain or function improvement. In terms of medium-term pain or function improvement, CSI may be superior to usual care and 'wait and see,' but may not be superior to PRP. In terms of long-term pain or function improvement, CSI may be inferior to PRP and ESWT, but it may be superior to usual care and 'wait and see' at 12 months. CONCLUSIONS: Due to the small sample size and lack of sufficient clinical studies, current evidence is equivocal regarding the efficacy of CSI in the treatment of GTPS. Considering the limitations, more large-sample and high-quality RCTs are needed to prove the therapeutic effect of CSI on GTPS. TRIAL REGISTRATION: PROSPERO registration number: CRD42021247991. Registered 09 May 2021.
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Bursite , Corticosteroides/uso terapêutico , Bursite/terapia , Fêmur , Humanos , Dor/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
This study aimed to investigate the prevalence of and risk factors for multidrug-resistant organism (MDRO) infection in the rehabilitation ward of a general hospital in Southwest China. We analyzed rehabilitation patients with nosocomial infections caused by MDROs from June 2016 to June 2020. MDRO infection pathogens and associated antibiotic resistance were calculated. Possible risk factors for MDRO-related infection in the neurorehabilitation ward were analyzed using chi-square, and logistic regression. A total of 112 strains of MDRO were found positive from 96 patients. The MDRO test-positive rate was 16.70% (96/575). Ninety-five MDRO strains were detected in sputum, of which 84.82% (95/112) were gram-negative bacteria. Acinetobacter baumannii (A. Baumannii), Pseudomonas aeruginosa (P. aeruginosa), and Klebsiella pneumonia (K. pneumonia) were the most frequently isolated MDRO strains. The logistic regression model and multifactorial analysis showed that long-term (≥ 7 days) antibiotic use (OR 6.901), history of tracheotomy (OR 4.458), and a low albumin level (< 40 g/L) (OR 2.749) were independent risk factors for the development of MDRO infection in patients in the rehabilitation ward (all P < 0.05). Gram-negative MRDOs were dominant in rehabilitation ward patients. Low albumin, history of a tracheostomy, and long-term use of antibiotics were independent risk factors for MRDO infection and are worthy of attention.
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Farmacorresistência Bacteriana Múltipla , Reabilitação Neurológica , Albuminas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Enterococcus , Bactérias Gram-Negativas , Hospitais Gerais , Humanos , Pseudomonas aeruginosaRESUMO
BACKGROUND AND PURPOSE: Poststroke urinary incontinence (PSI) is prevalent in stroke survivors, and high-quality evidence is required to guide clinical practice. Previous studies have demonstrated the curative effect of repetitive transcranial magnetic stimulation (rTMS) for urinary incontinence in individuals with multiple sclerosis (MS), Parkinson's disease (PD), and spinal cord injury (SCI). Here, we describe the protocol for a randomized controlled trial to evaluate the efficacy and safety of low-frequency rTMS on the contralesional primary motor cortex (M1) for the treatment of PSI. METHODS AND ANALYSIS: In this single-centre randomized controlled trial for poststroke urinary incontinence, a total of 140 eligible patients will be randomly allocated into two groups. The rTMS group (n = 70) will receive low-frequency rTMS at the M1 along with routine medical care, while the control group will receive sham rTMS along with routine medical care. All participants will undergo 20 treatment sessions, five times a week for 4 weeks. The primary outcome measures will be the changes in the urodynamic test at baseline versus 4 weeks after intervention. The secondary outcomes include the International Consultation on Incontinence Questionnaire Urinary Incontinence Short Form (ICIQ-UI SF), Overactive Bladder Symptom Score (OABSS), and pelvic floor muscle function. ETHICS AND DISSEMINATION: The Institutional Review Board and Hospital Research Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University approved this trial, and the approval number is No. 2020-153. All methods will be carried out in accordance with the principles of the Declaration of Helsinki and relevant ethical guidelines covering informed consent, confidentiality, and data storage. After the study had been thoroughly described to the participants by a physician, all participants will provide written informed consent indicating their willingness to participate. The results will be disseminated to most of the population, including participants, researchers, healthcare providers, and sponsors. TRIAL REGISTRATION: URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR2100042688. Date of Registration: 2021-01-26.