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After stroke, upper limb motor impairment is one of the most common consequences that compromises the level of the autonomy of patients. In a neurorehabilitation setting, the implementation of wearable sensors provides new possibilities for enhancing hand motor recovery. In our study, we tested an innovative wearable (REMO®) that detected the residual surface-electromyography of forearm muscles to control a rehabilitative PC interface. The aim of this study was to define the clinical features of stroke survivors able to perform ten, five, or no hand movements for rehabilitation training. 117 stroke patients were tested: 65% of patients were able to control ten movements, 19% of patients could control nine to one movement, and 16% could control no movements. Results indicated that mild upper limb motor impairment (Fugl-Meyer Upper Extremity ≥ 18 points) predicted the control of ten movements and no flexor carpi muscle spasticity predicted the control of five movements. Finally, severe impairment of upper limb motor function (Fugl-Meyer Upper Extremity > 10 points) combined with no pain and no restrictions of upper limb joints predicted the control of at least one movement. In conclusion, the residual motor function, pain and joints restriction, and spasticity at the upper limb are the most important clinical features to use for a wearable REMO® for hand rehabilitation training.

Objective The aim of this systematic review with meta-analysis was to evaluate the effectiveness of RMT in internal and central nervous system disorders, on pulmonary function, exercise capacity and quality of life. Methods The inclusion criteria were (1) publications designed as Randomized Controlled Trial (RCT), with (2) participants being adults with pulmonary dysfunction caused by an internal disease or central nervous system disorder, (3) an intervention defined as RMT (either IMT or EMT) and (4) with the assessment of exercise capacity, respiratory function and quality of life. For the methodological quality assessment of risk of bias, likewise statistical analysis and meta-analysis the RevMan version 5.3 software and the Cochrane Risk of Bias Tool were used. Two authors independently analysed the following databases for relevant research articles: PubMed, Scopus, Cochrane Library, Web of Science, and Embase. Results From a total of 2200 records, the systematic review includes 29 RCT with an overall sample size of 1155 patients. Results suggest that patients with internal and central nervous system disorders who underwent RMT had better quality of life and improved significantly their performance in exercise capacity and in respiratory function assessed with FVC and MIP when compared to control conditions (i.e. no intervention, sham training, placebo or conventional treatments). Conclusion Respiratory muscle training seems to be more effective than control conditions (i.e. no intervention, sham training, placebo or conventional treatment), in patients with pulmonary dysfunction due to internal and central nervous system disorders, for quality of life, exercise capacity and respiratory function assessed with MIP and FVC, but not with FEV1.

Objectives To evaluate effectiveness or non-inferiority of telerehabilitation for people with aphasia when compared to conventional face-to-face speech and language therapy. Materials and methods Five electronic databases (PUBMED, EMBASE, WEB OF SCIENCE, SCOPUS and the Cochrane Library) were searched. We extrapolated data from the included studies and evaluated the methodological quality using the Revised Cochrane risk-of-bias tool for Randomized Trials (RoB 2) and the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I). A meta-analysis compared effects of intervention, and it was conducted using the Review Manager 5.3 software. GRADE profile to assess overall quality of evidence was carried out. Results Out of a total of 1157 records, five studies met the inclusion criteria and were eligible for meta-analysis with a total of 132 participants with post-stroke aphasia. Discussion Results revealed that telerehabilitation and face-to-face speech and language treatment are comparable with respect to the gains achieved in auditory comprehension (SMD = −0.02; 95% CI −0.39, 0.35), naming accuracy (SMD = −0.09; 95% CI −0.44, 0.25), Aphasia Quotient (MD = −2.18; 95% CI −16.00, 11.64), generalization (SMD = 0.77; 95% IC −0.95, 2.49) and functional communication skills (SMD = −0.08; 95% IC −0.54, 0.38). Conclusion Although evidence is still insufficient to guide clinical decision making due to the relatively low quality of the evidence identified, the analysis of the results suggest that telerehabilitation training for aphasia seems to be as effective as the conventional face-to-face treatment.

Background: Recovery of hand function after stroke represents the hardest target for clinicians. Robot-assisted therapy has been proved to be effective for hand recovery. Nevertheless, studies aimed to refer patients to the best therapy are missing. Methods: With the aim to identify which clinical features are predictive for referring to robot-assisted hand therapy, 174 stroke patients were assessed with: Fugl-Meyer Assessment (FMA), Functional Independence Measure (FIM), Reaching Performance Scale (RPS), Box and Block Test (BBT), Modified Ashworth Scale (MAS), Nine Hole Pegboard Test (NHPT). Moreover, patients ability to control the robot with residual force and surface EMG (sEMG) independently, was checked. ROC curves were calculated to determine which of the measures were the predictors of the event. Results: sEMG control (AUC = 0.925) was significantly determined by FMA upper extremity (FMUE) (>24/66) and sensation (>23/24) sections, MAS at Flexor Carpi (4/20). Force control (AUC = 0.928) was correlated only with FMUE (>24/66). Conclusions: FMUE and MAS were the best predictors of preserved ability to control the device by two different modalities. This finding opens the possibility to plan specific therapies aimed at maximizing the highest functional outcome achievable after stroke.

Background: Hemiparesis caused by a stroke negatively limits a patient’s motor function. Nowadays, innovative technologies such as robots are commonly used in upper limb rehabilitation. The main goal of robot-aided therapy is to provide a maximum number of stimuli in order to stimulate brain neuroplasticity. Treatment applied in this study via the AMADEO robot aimed to improve finger flexion and extension. Aim: To assess the effect of rehabilitation assisted by a robot and enhanced by surface EMG. Research project: Before-after study design. Materials and methods: The study group consisted of 10 post-stroke patients enrolled for therapy with the AMADEO robot for at least 15 sessions. At the beginning and at the end of treatment, the following tests were used for clinical assessment: Fugl-Meyer scale, Box and Block test and Nine Hole Peg test. In the present study, we used surface electromyography (sEMG) to maintain optimal kinematics of hand motion. Whereas sensorial feedback, provided by the robot, was vital in obtaining closed-loop control. Thus, muscle contraction was transmitted to the amplifier through sEMG, activating the mechanism of the robot. Consequentially, sensorial feedback was provided to the patient. Results: Statistically significant improvement of upper limb function was observed in: Fugl-Meyer (p = 0.38) and Box and Block (p = 0.27). The Nine Hole Peg Test did not show statistically significant changes in motor skills of the hand. However, the functional improvement was observed at the level of 6% in the Fugl-Meyer, 15% in the Box and Block, and 2% in the Nine Hole Peg test. Conclusions: Results showed improvement in hand grasp and overall function of the upper limb. Due to sEMG, it was possible to implement robot therapy in the treatment of patients with severe hand impairment.

Background and Aims: Increasing evidence that a number of malignancies are characterised by tumour cell heterogeneity has recently been published, but there is still a lack of data concerning liver cancers. The aim of this study was to investigate and characterise tumour-propagating cell (TPC) compartments within human hepatocellular carcinoma (HCC). Methods: After long-term culture, we identified three morphologically different tumour cell populations in a single HCC specimen, and extensively characterised them by means of flow cytometry, fluorescence microscopy, karyotyping and microarray analyses, single cell cloning, and xenotransplantation in NOD/SCID/IL2Rγ-/- mice. Results: The primary cell populations (hcc-1, -2 and -3) and two clones generated by means of limiting dilutions from hcc-1 (clone-1/7 and -1/8) differently expressed a number of tumour-associated stem cell markers, including EpCAM, CD49f, CD44, CD133, CD56, Thy-1, ALDH and CK19, and also showed different doubling times, drug resistance and tumorigenic potential. Moreover, we found that ALDH expression, in combination with CD44 or Thy-1 negativity or CD56 positivity identified subpopulations with a higher clonogenic potential within hcc-1, hcc-2 and hcc-3 primary cell populations, respectively. Karyotyping revealed the clonal evolution of the cell populations and clones within the primary tumour. Importantly, the primary tumour cell population with the greatest tumorigenic potential and drug resistance showed more chromosomal alterations than the others and contained clones with epithelial and mesenchymal features. Conclusions: Individual HCCs can harbor different self-renewing tumorigenic cell types expressing a variety of morphological and phenotypical markers, karyotypic evolution and different gene expression profiles. This suggests that the models of hepatic carcinogenesis should take into account TPC heterogeneity due to intratumour clonal evolution. © 2011 Colombo et al.

Background and Objectives: The significant toxicities associated with current treatments of Burkitt’s lymphoma (BL) have fostered the identification of novel targets for effective but less toxic therapies. c-myc overexpression is the hallmark of BL; however it is per se insufficient to cause lymphoma development. Recent studies indicating aberrant expression of microRNAs (miRNAs) in BL have raised the possibility of a c-myc - miRNA interaction within the genesis and the maintenance of the lymphoma phenotype. Myc oncoproteins indeed have been found to inhibit the transcription of tumor suppressor genes. This occurs for instance by recruiting histone deacetylase (HDAC) 1 proteins to target genes, including tissue transglutaminase 2 (TG2), a multifunctional protein that promotes apoptosis and differentiation in normal tissues. Since inhibitors of the epigenetic regulator HDACs are revealing very effective as anticancer agents, we evaluated ITF2357, a new hydroxamate inhibitor of HDAC, with respect to its ability to induce proliferative arrest and apoptosis in BL cell lines by modulating c-myc mRNA, miRNAs and TG2 expression. Methods and Results: Cell growth inhibition by ITF2357 was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in the BL cell lines Namalwa and Raji. ITF2357 IC50 was 200nM after 48h exposure. Most treated Namalwa and Raji cells became respectively late and early apoptotic as assessed by annexin V and propidium iodide staining. Accordingly, ITF235 induced SUBG1 peak formation in Namalwa cells and G1 arrest in Raji cells. Repeated addition of ITF2357 at 24h-intervals enhanced these effects. Array analyses and quantitative real-time PCR of miRNAs indicated a significant decrease in the expression of miR-155 and miR-98, which exert oncogenic activity in MYC-associated tumors, at 24–72 h after treatment. Conversely, the Let-7a miRNA, which targets the c-MYC mRNA stabilizer IMP-1 among its tumor suppressive functions, was up regulated peaking at 24h after drug administration. Finally, immunohistochemical analysis of TG2 expression in ITF2357-treated Raji cells revealed a diffuse cytoplasmic staining, whereas in their untreated counterparts TG2 was sporadically and faintly detectable. Despite ITF2357 restored the expression of different targets of myc, quantitative real-time PCR revealed no parallel decrease in c-myc mRNA suggesting that the epigenetic modulation provided by ITF2357 on BL cell lines did not directly affect myc expression level. Conclusion: Our data indicate potent cytotoxic and growth inhibitory activities of ITF2357 on BL cell lines. These effects might be related to the modulation of both oncogenic and tumor-suppressing miRNAs and to the restoration of the tumor suppressor TG2. Further evidences for the potential candidacy of ITF2357 as a therapeutic agent for BL awaits ongoing analyses in BL primary tumors and in animal models.