The effect of training using an upper limb rehabilitation robot (HEXO-UR30A) in chronic stroke patients: A randomized controlled trial.

BACKGROUND: Upper limb robotic rehabilitation can be beneficial to the patients when applied appropriately. HEXO-UR30A is a novel exoskeletal type upper limb rehabilitation robot that provides continuous passive motion to the shoulder joint. OBJECTIVE: The purpose of this study is to evaluate the effectiveness of HEXO-UR30A on the patient's functional change, spasticity, and range of motion (ROM). METHODS: We included stroke patients with upper limb hemiparesis of age > 19 years with spasticity grading of modified Ashworth scale < 3 and Brunnstrom recovery stage ≥ 4. The efficacy of the robot was investigated based on a rehabilitation program for 3 weeks. Patient's functions were compared before vs after treatment and between the HEXO group vs control. We conducted the Fugl-Meyer Assessment of the Upper Extremity, modified Barthel index, modified Ashworth scale, ROM, and Motricity Index upper limb. Patients' satisfaction was evaluated using a questionnaire after every 10 sessions of training. RESULTS: In the HEXO group, the Fugl-Meyer assessment for shoulder improved significantly (P value = .006*) compared with the control group (P value = .075). Both groups showed significant improvement (P value < .05) in Motricity Index upper limb after treatment. There were some improvements in the passive and active ROM. Patients in the HEXO group reported high satisfaction with upper limb rehabilitation. CONCLUSION: These results show that HEXO-UR30A can improve functional ability in chronic stroke patients. Moreover, the high satisfaction in patients might promote active involvement in upper limb rehabilitation.

Correction: Hypoxia/reoxygenation-experienced cancer cell migration and metastasis are regulated by Rap1- and Rac1-GTPase activation via the expression of thymosin beta-4.

[This corrects the article DOI: 10.18632/oncotarget.3218.].

Feasibility of Rehabilitation Training With a Newly Developed, Portable, Gait Assistive Robot for Balance Function in Hemiplegic Patients.

OBJECTIVE: To investigate the clinical feasibility of a newly developed, portable, gait assistive robot (WA-H, 'walking assist for hemiplegia') for improving the balance function of patients with stroke-induced hemiplegia. METHODS: Thirteen patients underwent 12 weeks of gait training on the treadmill while wearing WA-H for 30 minutes per day, 4 days a week. Patients' balance function was evaluated by the Berg Balance Scale (BBS), Fugl-Meyer Assessment Scale (FMAS), Timed Up and Go Test (TUGT), and Short Physical Performance Battery (SPPB) before and after 6 and 12 weeks of training. RESULTS: There were no serious complications or clinical difficulties during gait training with WA-H. In three categories of BBS, TUGT, and the balance scale of SPPB, there was a statistically significant improvement at the 6th week and 12th week of gait training with WA-H. In the subscale of balance function of FMAS, there was statistically significant improvement only at the 12th week. CONCLUSION: Gait training using WA-H demonstrated a beneficial effect on balance function in patients with hemiplegia without a safety issue.

ASSESSMENT OF DIAGNOSTIC MULTILEAF COLLIMATOR FOR CEPHALOMETRIC EXPOSURE REDUCTION USING OPTICALLY STIMULATED LUMINESCENT DOSEMETERS.

A diagnostic multileaf collimator (MLC) was developed for diagnostic radiography dose reduction. Optically stimulated luminescent dosemeters (OSLDs) were used to evaluate the efficacy of this device for dental radiography cephalometric exposure reduction. The OSLD dosimetric characteristics for 80 kVp cephalometric exposure were first obtained. The batch homogeneity and reproducibility were 1.67 % and 0.18-1.58, respectively. Good linearity was obtained between the OSLD dose and response, and the angular dependence was within ±4 %. The equivalent organ doses for the left eye, right eye and thyroid were 41.20±6.58, 178.86±1.71 and 171.12±8.78 µSv and 36.80±0.33, 156.63±0.22 and 22.04±0.13 µSv for the open and MLC fields, respectively. The MLC-induced dose reductions for the left and right eyes of in field were 10.67±16.78 and 12.42±8.84 %, respectively, and that of the thyroid gland of out of field was 87±8.82 %, considering combined uncertainty. Therefore, use of diagnostic MLC for dose reduction during dental radiography cephalometric exposure is both feasible and effective.

Low-Dose Ionizing γ-Radiation Promotes Proliferation of Human Mesenchymal Stem Cells and Maintains Their Stem Cell Characteristics.

Mesenchymal stem cells (MSCs), which are multipotent and have self-renewal ability, support the regeneration of damaged normal tissue. A number of external stimuli promote migration of MSCs into peripheral blood and support their participation in wound healing. In an attempt to harness the potential beneficial effects of such external stimuli, we exposed human MSCs (hMSCs) to one such stimulus-low-dose ionizing radiation (LDIR)-and examined their biological properties. To this end, we evaluated differences in proliferation, cell cycle, DNA damage, expression of surface markers (CD29, CD34, CD90, and CD105), and differentiation potential of hMSCs before and after irradiation with γ-rays generated using a 137CS irradiator. At doses less than 50 mGy, LDIR had no significant effect on the viability or apoptosis of hMSCs. Interestingly, 10 mGy of LDIR increased hMSC viability by 8% (p < 0.001) compared with non-irradiated hMSCs. At doses less than 50 mGy, LDIR did not induce DNA damage, including DNA strand breaks, or cause cellular senescence or cell-cycle arrest. Surface marker expression and in vitro differentiation potential of hMSCs were maintained after two exposures to LDIR at 10 mGy per dose. In conclusion, a two-dose exposure to LDIR at 10 mGy per dose not only facilitates proliferation of hMSCs, it also maintains the stem cell characteristics of hMSCs without affecting their viability. These results provide evidence for the potential of LDIR as an external stimulus for in vitro expansion of hMSCs and application in tissue engineering and regenerative medicine.

Hypoxia/reoxygenation-experienced cancer cell migration and metastasis are regulated by Rap1- and Rac1-GTPase activation via the expression of thymosin beta-4.

Signaling by small guanosine triphosphatases (GTPase), Rap1/Rac1, is one of the major pathways controlling cancer cell migration and tumor metastasis. Thymosin beta-4 (Tß4), an actin-sequestering protein, has been shown to increase migration of cancer cells. Episodes of hypoxia and re-oxygenation (H/R) are an important phenomenon in tumor microenvironment (TME). We investigated whether Tß4 could play as an intermediary to crosstalk between Rac1- and Rap1- GTPase activation under hypoxia/reoxygenation (H/R) conditions. Inhibition of Tß4 expression using transcription activator-like effector nucleases (TALEN) significantly decreased lung metastasis of B16F10 cells. Rac1 and Rap1 activity, as well as cancer cell migration, increased following induction of Tß4 expression in normoxia- or H/R-experienced cells, but were barely detectable in Tß4-depleted cells. Rap1-regulated Rac1 activity was decreased by a dominant negative Rap1 (Rap1N17), and increased by 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (CPT), a Rap1 activator. In contrast, a Rac1-specific inhibitor, NSC23766, and dominant negative Rac1 (Rac1N17) enhanced Tß4 expression and aberrant Rap1 activity. While NSC23766 and Rac1N17 incompletely inhibited tumor metastasis in vivo, and H/R-experienced cancer cell migration in vitro, more efficient attenuation of cancer cell migration was accomplished by simultaneous inactivation of Rap1 and Rac1 with Rap1N17 and Rac1N17, respectively. These data suggest that a combination therapy targeting both Rap1 and Rac1 activity may be an effective method of inhibiting tumor metastasis.

Evaluation of premature senescence and senescence biomarkers in carcinoma cells and xenograft mice exposed to single or fractionated irradiation.

The purpose of the present study was to elucidate whether premature senescence contributes to the outcome of radiotherapy (RT) and to validate senescence biomarkers in vitro and in vivo. Cultured human cancer cell lines and xenografted mice were exposed to single (SR; 2, 6 or 12 Gy) or fractionated radiation (FR; 3 x 2 Gy or 6 x 2 Gy), and premature senescence was assessed using senescence-associated ß-galactosidase (SA-ß-Gal) activity, hypophosphorylation of pRb and p21 accumulation. A variety of senescence-associated biomarkers including cathepsin D (CD), the eukaryotic translation elongation factors eEF1A1, eEF1B2, decoy receptor 2 and Dec1 were further validated in vivo or in vitro. We demonstrated the beneficial tumor suppressive role of ionizing radiation (IR)-induced premature senescence in vitro and in vivo. FR inhibited tumor growth via induction of premature senescence as effectively as an equivalent SR dose (≥6 Gy). In addition, CD and eEF1 were valuable biomarkers of cellular senescence in either SR- or RF-exposed carcinoma cells or xenograft mice. Our results suggest that 2 Gy of a conventional RT regime could achieve a better clinical outcome if premature senescence could be increased through an improved understanding of its molecular action mechanism.

Cryptosporidium parvum: radiation-induced alteration of the oocyst proteome.

Cryptosporidium parvum is a waterborne protozoan parasite that is found intracellularly in host animals, including humans, and causes severe diarrhea, which can lead to the death of an immunocompromised individual. Previously, we found that this organism is highly radioresistant as it can productively infect mice after exposure to a 10-kGy dose of γ-radiation. To understand how C. parvum avoids radiation damage, we characterized its protein expression patterns 6, 24, and 48 h after a 10-kGy dose of γ-radiation using two-dimensional PAGE. The gels showed 10 silver-stained spots that increased or decreased in size following γ-irradiation. Five proteins contained in these spots were identified using MALDI-TOF MS peptide fingerprinting, and two of these showed an increase in expression after γ-irradiation. These proteins were identified by LC-MS/MS as proteasome subunit alpha type 4 (NTN hydrolase fold) and thioredoxin peroxidase-like protein. The roles of these two upregulated proteins as related to the radioresistance of C. parvum remain to be evaluated.

Anti-tumor effects by a synthetic chalcone compound is mediated by c-Myc-mediated reactive oxygen species production.

Overexpression of c-Myc represents the most frequently deregulated genetic event in cancer, and therefore c-Myc may represent a good molecular target for cancer therapy. The human lung carcinoma cell line, NCI-H1299, shows resistance to conventional cancer treatments, such as ionizing radiation (IR) and cisplatin, while the lung carcinoma cell line, NCI-H460, is sensitive to treatment with these agents. However, when treated with a chalcone compound [toluenesulfonylamido-chalcone, 4'-(p-toluene sulfonyl amino)-3,4-dihydroxy chalcone (TSHDC)], cell death was dramatically induced in NCI-H1299 cells as compared to NCI-H460 cells. TSHDC-mediated cytotoxicity was not dependent on the status of p53 and p21. However, TSHDC exerted increased c-Myc-dependent reactive oxygen species (ROS) production in NCI-H1299 cells in which c-Myc is overexpressed, while increased ROS production did not occur in A549 or NCI-H460 cells with a low c-Myc level. Several colon and brain cancer cells also showed a correlation between c-Myc expression and TSHDC-mediated increased cell death. Tumor regression by TSHDC was more dramatic in NCI-H1299 cells than NCI-H460 cells, when these cells were grafted to nude mice. However, in the case of IR and cisplatin, NCI-H460 cells were more sensitive than NCI-H1299 cells. From these results, c-Myc-mediated ROS production may be a good target for screening of novel cancer drugs and TSHDC might be a good candidate as a cancer drug, specifically in cancer cells that overexpress c-Myc.

Long term follow-up results of external beam radiotherapy as primary treatment for retinoblastoma.

The authors reviewed their experiences of external beam radiotherapy (EBR) as an initial treatment in retinoblastoma patients to determine its long-term effect on subsequent tumor control and complications. A total of 32 eyes in 25 patients that underwent EBR for retinoblastoma were reviewed retrospectively. The patients consisted of 21 boys and 4 girls of median age at treatment of 7.1 months. Radiation doses ranged from 35 to 59.4 Gy. The 10-yr ocular and patient survivals were 75.4% and 92.3%, respectively. Nine of the 32 eyes progressed; 7 of these were enucleated and 2 were salvaged by focal treatment. According to the Reese-Ellsworth classification, 4 of 5 eyes of Group II, 13 of 16 Group III eyes, 2 of 4 Group IV eyes, and 5 of 7 Group V eyes were retained, and of the 32 eyes, 13 had visual acuity better than 20/200. Eleven patients experienced a radiation-induced complication. No patient developed a second malignancy during follow-up. Despite the limited number of patients enrolled, EBR may provide a mean of preserving eyeball and vision for some advanced lesions.

Effect of ablated hippocampal neurogenesis on the formation and extinction of contextual fear memory.

Newborn neurons in the subgranular zone (SGZ) of the hippocampus incorporate into the dentate gyrus and mature. Numerous studies have focused on hippocampal neurogenesis because of its importance in learning and memory. However, it is largely unknown whether hippocampal neurogenesis is involved in memory extinction per se. Here, we sought to examine the possibility that hippocampal neurogenesis may play a critical role in the formation and extinction of hippocampus-dependent contextual fear memory. By methylazoxymethanol acetate (MAM) or gamma-ray irradiation, hippocampal neurogenesis was impaired in adult mice. Under our experimental conditions, only a severe impairment of hippocampal neurogenesis inhibited the formation of contextual fear memory. However, the extinction of contextual fear memory was not affected. These results suggest that although adult newborn neurons contribute to contextual fear memory, they may not be involved in the extinction or erasure of hippocampus-dependent contextual fear memory.

Stereotactic body radiation therapy in patients with pelvic recurrence from rectal carcinoma.

OBJECTIVE: To investigate the clinical applications of stereotactic body radiation therapy (SBRT) using the CyberKnife system for pelvic recurrence from rectal cancer with a focus on survival and toxicity. METHODS: Between 2002 and 2006, 23 patients with recurrent rectal cancer were treated with SBRT at our institution. The median follow-up was 31 months. Sites of recurrence were pre-sacral in seven patients and the pelvic wall in 16. SBRT doses ranged from 30 to 51 Gy (median 39 Gy) and were delivered in three fractions. Response to treatment was assessed by computed tomography. Overall and local progression-free survival and toxicities were recorded. RESULTS: Four-year overall survival and local control rates were 24.9 and 74.3%, respectively. No prognostic factor was found to affect patient survival or local progression. One patient developed a severe radiation-related toxicity, but recovered completely after treatment. CONCLUSIONS: SBRT for pelvic recurrence was found to be comparable with other modalities with respect to overall survival and complication rates. Further studies are needed to confirm these preliminary results.