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Background and purpose There is little evidence available on the use of robot-assisted therapy in subacute stroke patients. A randomized controlled trial was carried out to evaluate the short-time efficacy of intensive robot-assisted therapy compared to usual physical therapy performed in the early phase after stroke onset. Methods Fifty-three subacute stroke patients at their first-ever stroke were enrolled 30 ± 7 days after the acute event and randomized into two groups, both exposed to standard therapy. Additional 30 sessions of robot-assisted therapy were provided to the Experimental Group. Additional 30 sessions of usual therapy were provided to the Control Group. The following impairment evaluations were performed at the beginning (T0), after 15 sessions (T1), and at the end of the treatment (T2): Fugl-Meyer Assessment Scale (FM), Modified Ashworth Scale-Shoulder (MAS-S), Modified Ashworth Scale-Elbow (MAS-E), Total Passive Range of Motion-Shoulder/Elbow (pROM), and Motricity Index (MI). Results Evidence of significant improvements in MAS-S (p = 0.004), MAS-E (p = 0.018) and pROM (p < 0.0001) was found in the Experimental Group. Significant improvement was demonstrated in both Experimental and Control Group in FM (EG: p < 0.0001, CG: p < 0.0001) and MI (EG: p < 0.0001, CG: p < 0.0001), with an higher improvement in the Experimental Group. Conclusions Robot-assisted upper limb rehabilitation treatment can contribute to increasing motor recovery in subacute stroke patients. Focusing on the early phase of stroke recovery has a high potential impact in clinical practice.

Walking ability, though important for quality of life and participation in social and economic activities, can be adversely affected by neurological disorders, such as Spinal Cord Injury, Stroke, Multiple Sclerosis or Traumatic Brain Injury. The aim of this study is to evaluate if the energy cost of walking (CW), in a mixed group of chronic patients with neurological diseases almost 6 months after discharge from rehabilitation wards, can predict the walking performance and any walking restriction on community activities, as indicated by Walking Handicap Scale categories (WHS). One hundred and seven subjects were included in the study, 31 suffering from Stroke, 26 from Spinal Cord Injury and 50 from Multiple Sclerosis. The multivariable binary logistical regression analysis has produced a statistical model with good characteristics of fit and good predictability. This model generated a cut-off value of.40, which enabled us to classify correctly the cases with a percentage of 85.0%. Our research reveal that, in our subjects, CW is the only predictor of the walking performance of in the community, to be compared with the score of WHS. We have been also identifying a cut-off value of CW cost, which makes a distinction between those who can walk in the community and those who cannot do it. In particular, these values could be used to predict the ability to walk in the community when discharged from the rehabilitation units, and to adjust the rehabilitative treatment to improve the performance.

Background Adaptation to hypoxia and consequent pro-inflammatory gene expression of prostate and breast carcinomas have been implicated in the progression toward cancer malignant phenotype. Only partial data are available for the human tumor glioblastoma multiforme (GBM). The aim of our study was to analyze the hypoxic and pro-inflammatory microenvironment in GBMs and to demonstrate that in a stem/progenitor cell line derived from human glioblastoma (GBM-SCs), hypoxia activates a coordinated inflammatory response, evidencing an invasive and migratory phenotype. Methods From each of 10 human solid glioblastomas, clinically and histopathologically characterized, we obtained three surgical samples taken from the center and the periphery of the tumor, and from adjacent host normal tissue. Molecular and morphological analyses were carried out using quantitative real-time PCR and western blot (WB). GBM stem and differentiated cells were incubated under hypoxic conditions and analyzed for pro-inflammatory gene expression and for invasive/migratory behavior. Results A panel of selected representative pro-inflammatory genes (RAGE and P2X7R, COX2, NOS2 and, PTX3) were analyzed, comparing tumor, peritumor and host normal tissues. Tumors containing leukocyte infiltrates (as assessed using CD45 immunohistochemistry) were excluded. Selected genes were overexpressed in the central regions of the tumors (i.e. in the more hypoxic areas), less expressed in peripheral regions, and poorly expressed or absent in adjacent normal host tissues. Western blot analysis confirmed that the corresponding pro-inflammatory proteins were also differently expressed. Hypoxic stem cell lines showed a clear time-dependent activation of the entire panel of pro-inflammatory genes as compared to differentiated tumor cells. Biological assays showed that invasive and migratory behavior was strengthened by hypoxia only in GBM stem cells. Conclusions In human solid glioblastoma we have observed a coordinated overexpression of a panel of pro-inflammatory genes as compared to host normal tissue. We have also evidenced a similar pattern of overexpressed genes in GBM-SCs after hypoxic treatment, showing also a gain of invasive and migratory function that was lost when these stem cells differentiated. We suggest that, as has been previously described for prostatic and mammary carcinoma, in human glioblastoma acquisition of a proinflammatory phenotype may be relevant for malignant progression.

The clinical impact of action observation (AO) on upper limb functional recovery in subacute stroke patients is recent evidence. We sought to test the hypothesis that training everyday life activities through AO coupled with task execution might activate the left hemisphere different from the right one. Sixty-seven first-ever ischemic stroke subjects were randomly assigned to receive upper limb training coupled with AO tasks or standard rehabilitation. The groups were matched by age and gender, Bamford category, and interval from stroke and lesion side. Fugl-Meyer (FM) and Box and Block Test (BBT) were used to measure hand function recovery at the end (T1) and 4-5 months after the treatment (T2). At T1, FM was increased by 31% (±26%), of maximum achievable recovery, whereas BBT was increased by 17% (±18%); at T2, FM had reached 43% (±45%) of maximum recovery, while BBT had reached 25% (±22%). Combining the effects of treatment to those of lesion side revealed significantly higher gains, in both FM and BBT scores, in left hemiparetic subjects when exposed to AO as compared to standard rehabilitation alone (P<.01). The findings lead to recommend the use of AO in addition to motor training in left hemiparetic patients.

The role of tumor cells in synthesizing pro‐inflammatory molecules is still controversial. Here we report that hypoxic treatment of the MCF‐7 human mammary adenocarcinoma cell line induced activation of hypoxia‐inducible factor 1α (HIF‐1α) and nuclear factor‐kappa B (NF‐κB). Importantly, hypoxia regulated expression of alarmin receptors such as the receptor for advanced glycation end products (RAGE) and the purinoreceptor (P2X7R), and up‐regulated inflammatory response (IR) genes such as the inducible enzymes nitric oxide synthase (NOS2), cycloxygenase (COX2), and the acute‐phase protein pentraxin‐3 (PTX3). Hypoxia also stimulated chemokine (C‐X‐C motif) receptor 4 (CXCR4) mRNA synthesis. In fact, the CXCR4 ligand stromal‐derived factor‐1α (SDF‐1α) increased invasion and migration of hypoxic MCF‐7 cells. Inhibition of HIF‐1α by chetomin and NF‐κB by parthenolide reduced mRNA and protein expression of the studied molecules and prevented invasion of hypoxic MCF‐7 cells. Moreover, solid invasive mammary tumor microenvironment was analyzed after laser‐capture microdissection (LCMD) comparing tumor versus host normal tissue. Nuclear translocation of HIF‐1α and NF‐κB and up‐regulation of IR, CXCR4, estrogen receptor α (ERα), and epithelial growth factor receptor (EGFR) was observed in tumor but not in host normal tissue in the absence of a local inflammatory leukocyte infiltrate. We conclude that under hypoxic conditions MCF‐7 cells acquire a pro‐inflammatory phenotype, and that solid human mammary carcinoma evidenced a similar activation of HIF‐1α, NF‐κB, and IR genes in malignant tumor cells as compared to the normal host tissues. We suggest a role for IR activation in the malignant progression of transformed cells. (Cancer Sci 2010; 101: 1014–1023)

Hydrokinesiotherapy has antalgic and muscle relaxant properties, as well as anti-edema and anti-inflammatory effects. Currently, the management of persons with total hip replacement (THR) consists of multiple pharmacologic and non-pharmacologic therapies, which include therapeutic exercise, physical therapies, and education. Our hypothesis is that kinesiotherapy in thermal water would improve functional outcome. The aim of the study was to assess thermal hydrokinesiotherapy efficacy on pain, mood, and quality of life. We enrolled 11 participants (mean age of 70.55 ± 14 years) with total hip replacement (THR) after early hospital discharge at a residential rehabilitation facility. All participants underwent a standardized combined land-based and hydrokinesiotherapy rehabilitation program for 2 consecutive weeks. Clinical data were collected at beginning and end of rehabilitation; pain, anxiety, and quality of life scores were collected at admission, discharge, 3 and 6 months from surgery. Functional outcome scores improved and were maintained at 6-month follow-up. These preliminary data demonstrate that thermal hydrokinesiotherapy may positively influence functional recovery in orthopedic post-surgical patients. Further randomized controlled trials are mandatory to consolidate this finding.

The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease. Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition. Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79). Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration. This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest. Clinical Trials.gov NCT01815281.

This study was aimed at verifying the improvement on the motor impairment and functionality in 19 patients with chronic hemiparesis after stroke treated with a robot-aided rehabilitation protocol using the ReoGo™ system (Motorika Medical Ltd, Israel), and at evaluating the persistence of the effects after 1 month. The study also focused on the actual possibility of administering the robot-aided therapy with the ReoGo™ for the upper limbs and on the patients' degree of acceptance and compliance with the treatment. Subjects underwent an assessment prior to the start of the rehabilitation project (T-1), one at the start (T0), one at the end of the treatment (T1) and one after one month from the end of the treatment (T2). The following tests were administered: (i) Fugl-Meyer (FM) upper limb; Ashworth scale (AS); Functional Independence Measure (FIM™) (T-1 - T2); (ii) strength evaluation; Visual Analogue Scale (VAS) for pain; Frenchay Arm test (FAT); Box and Block test (BBT); Timed Up and Go (TUG) test (T0 - T2). Additionally, the Euro-QoL questionnaire and a VAS for the treatment satisfaction were administered to the subjects. Non-statistical difference of scores at T-1 and T0 on almost the entire battery of tasks suggested a stable patients' performance prior to the start of the rehabilitation. With the exception of the Medical Research Council (MRC) and the AS sub-scales measuring -as appropriate- strength and spasticity of the shoulder, triceps and wrist, all scores showed a significant increase between T0 and T1. The improvement on the pain could not be proved significant (p = 0.10). A significant increase between T0 and T2 was found for all assessment scores, with the exception of the MRC for external shoulder rotators (p = 0.05) and of the AS for shoulder (p = 0.32) and wrist (p = 0.08). Substantial stability was observed between T1 and T2. Patients were capable of completing the treatment and showed good participant satisfaction. This pilot study led to the finding of a clinical improvement and excellent patients compliance. It is possible that the learning process experienced by the patients was robot-dependent, especially in consideration of the general maintenance of the achievements observed on all activities.

Due to the complexity of the interventions for upper limb recovery, at the moment there is a lack of evidence regarding innovative and effective rehabilitative interventions. Action Observation Training (AOT) constitutes a promising rehabilitative method to improve upper limb motor recovery in stroke patients. The aim of the present study was to evaluate the potential efficacy of AOT, both in upper limb recovery and in functional outcomes when compared to patients treated with task oriented training (TOT). Both treatments were added to traditional rehabilitative treatment. Thirty-two acute stroke patients at 15.6 days (±8.3) from onset, with moderate to severe upper limb impairment at baseline following their first-ever stroke, were enrolled and randomized into two groups: 16 in the experimental group (EG) and 16 in the control group (CG). The EG underwent 30 min sessions of AOT, and the CG underwent 30 min sessions of TOT. All participants received 20 sessions of treatment for four consecutive weeks (five days/week). The Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Box and Block Test (BBT), Functional Independence Measure (FIM) and Modified Ashworth Scale (MAS) were administered at baseline (T0) and at the end of treatment (T1). No statistical differences were found at T0 for inclusion criteria between the CG and EG, whereas both groups improved significantly at T1. After the treatment period, the rehabilitative gain was greater in the EG compared to the CG for FMA-UE and FIM (all p < 0.05). Our results suggest that AOT can contribute to increased motor recovery in subacute stroke patients with moderate to severe upper limb impairment in the early phase after stroke. The improvements presented in this article, together with the lack of adverse events, confirm that the use of AOT should be broadened out to larger pools of subacute stroke patients.

This study aims to evaluate the change in gait spatiotemporal parameters in subjects with Parkinson’s disease (PD) before and after Automated Mechanical Peripheral Stimulation (AMPS) treatment. Thirty-five subjects with PD and 35 healthy age-matched subjects took part in this study. A dedicated medical device (Gondola) was used to administer the AMPS. All patients with PD were treated in off levodopa phase and their gait performances were evaluated by an inertial measurement system before and after the intervention. The one-way ANOVA for repeated measures was performed to assess the differences between pre- and post-AMPS and the one-way ANOVA to assess the differences between PD patients and the control group. Spearman’s correlations assessed the associations between patients with PD clinical status (H&Y) and the percentage of improvement of the gait variables after AMPS (α<0.05 for all tests). The PD group had an improvement of 14.85% in the stride length; 14.77% in the gait velocity; and 29.91% in the gait propulsion. The correlation results showed that the higher the H&Y classification, the higher the stride length percentage of improvement. The treatment based on AMPS intervention seems to induce a better performance in the gait pattern of PD patients, mainly in intermediate and advanced stages of the condition.