Evaluation of the brain activation induced by functional electrical stimulation and voluntary contraction using functional magnetic resonance imaging

BACKGROUND: To observe brain activation induced by functional electrical stimulation, voluntary contraction, and the combination of both using functional magnetic resonance imaging (fMRI). METHODS: Nineteen healthy young men were enrolled in the study. We employed a typical block design that consisted of three sessions: voluntary contraction only, functional electrical stimulation (FES)-induced wrist extension, and finally simultaneous voluntary and FES-induced movement. MRI acquisition was performed on a 3.0 T MR system. To investigate activation in each session, one-sample t-tests were performed after correcting for false discovery rate (FDR; p < 0.05). To compare FES-induced movement and combined contraction, a two-sample t-test was performed using a contrast map (p < 0.01). RESULTS: In the voluntary contraction alone condition, brain activation was observed in the contralateral primary motor cortex (MI), thalamus, bilateral supplementary motor area (SMA), primary sensory cortex (SI), secondary somatosensory motor cortex (SII), caudate, and cerebellum (mainly ipsilateral). During FES-induced wrist movement, brain activation was observed in the contralateral MI, SI, SMA, thalamus, ipsilateral SII, and cerebellum. During FES-induced movement combined with voluntary contraction, brain activation was found in the contralateral MI, anterior cingulate cortex (ACC), SMA, ipsilateral cerebellum, bilateral SII, and SI. The activated brain regions (number of voxels) of the MI, SI, cerebellum, and SMA were largest during voluntary contraction alone and smallest during FES alone. SII-activated brain regions were largest during voluntary contraction combined with FES and smallest during FES contraction alone. The brain activation extent (maximum t score) of the MI, SI, and SII was largest during voluntary contraction alone and smallest during FES alone. The brain activation extent of the cerebellum and SMA during voluntary contraction alone was similar during FES combined with voluntary contraction; however, cerebellum and SMA activation during FES movement alone was smaller than that of voluntary contraction alone or voluntary contraction combined with FES. Between FES movement alone and combined contraction, activated regions and extent due to combined contraction was significantly higher than that of FES movement alone in the ipsilateral cerebellum and the contralateral MI and SI. CONCLUSIONS: Voluntary contraction combined with FES may be more effective for brain activation than FES-only movements for rehabilitation therapy. In addition, voluntary effort is the most important factor in the therapeutic process

Endovascular Stenting as a First Choice for the Palliation of Superior Vena Cava Syndrome

To assess the effectiveness of endovascular stenting for the palliation of superior vena cava (SVC) syndrome, endovascular stent insertion was attempted in 10 patients with symptomatic occlusion of the SVC. All the patients had known malignant disease of the thorax. Eight patients had been treated previously with chemotherapy and radiotherapy (n=5), chemotherapy alone (n=2), or pneumonectomy and radiotherapy (n=1). After developing SVC syndrome, all the patients were stented before receiving any other treatment. After single or multiple endovascular stents were inserted, five of eight patients were treated with chemotherapy and radiotherapy (n=2) or chemotherapy alone (n=3). Resolution of symptoms was achieved in nine patients within 72 hr (90%). In one patient, the symptoms did not disappear until a second intervention. At follow up, symptoms had recurred in two of ten patients (20%) after intervals of 15 and 60 days. Five patients have died from their cancers, although they remained free of symptoms of SVC occlusion until death. In conclusion, endovascular stent insertion is an effective treatment for palliation of SVC syndrome. Endovascular stent insertion can be considered the first choice of treatment, due to the immediate relief of symptoms and excellent sustained symptomatic relief

Patient-Specific Orthotopic Glioblastoma Xenograft Models Recapitulate the Histopathology and Biology of Human Glioblastomas In Situ

SummaryFrequent discrepancies between preclinical and clinical results of anticancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable “patient tumor’s phenocopy” that represents molecular and functional heterogeneity of GBMs

Long-term Follow-up of Laparoscopic Splenectomy in Patients with Immune Thrombocytopenic Purpura

Laparoscopic splenectomy (LS) has been reserved for intractable and relapsing immune thrombocytopenic purpura (ITP) despite medical treatment. With further experiences of LS in ITP, we investigated long term outcomes of LS, especially newly developed morbidities, and tried to find predictive factors for favorable outcomes. From August 1994 to December 2004, fifty-nine patients whose follow-up period was more than 12 months after LS were investigated. After a long-term follow-up (median 54 months, range 12.5-129 months), a complete response (CR) was found in 28 patients (47.5%), partial response in 24 (40.7%), and no response in 7 (11.9%). The relapse rate during follow-up periods was 15.2%. The rapid response group (p=0.017), in which the platelet count increased more than twice of the preoperative platelet count within 7 days after LS, relapsing after medical treatment (p=0.02), and the satisfactory group as the initial result of LS (p=0.001) were significant for predicting CR in univariate analysis, but only the initial satisfactory group was an independent predictive factor for CR in multivariate analysis (p=0.036, relative risk=6419; 95% CI, 1.171-35.190). Infections were the most frequent morbidities during the follow-up period, which were treated well without mortality. LS is a safe and effective treatment modality for ITP. Active referral to surgery might be required, considering complications and treatment results related to long-term use of steroid-based medications

Nanovesicles derived from iron oxide nanoparticles-incorporated mesenchymal stem cells for cardiac repair

Because of poor engraftment and safety concerns regarding mesenchymal stem cell (MSC) therapy, MSC-derived exosomes have emerged as an alternative cell-free therapy for myocardial infarction (MI). However, the diffusion of exosomes out of the infarcted heart following injection and the low productivity limit the potential of clinical applications. Here, we developed exosome-mimetic extracellular nanovesicles (NVs) derived from iron oxide nanoparticles (IONPs)-incorporated MSCs (IONP-MSCs). The retention of injected IONP-MSC-derived NVs (IONP-NVs) within the infarcted heart was markedly augmented by magnetic guidance. Furthermore, IONPs significantly increased the levels of therapeutic molecules in IONP-MSCs and IONP-NVs, which can reduce the concern of low exosome productivity. The injection of IONP-NVs into the infarcted heart and magnetic guidance induced an early shift from the inflammation phase to the reparative phase, reduced apoptosis and fibrosis, and enhanced angiogenesis and cardiac function recovery. This approach can enhance the therapeutic potency of an MSC-derived NV therapy.