Does aquatic thermal therapy improve quality of life after total hip replacement? A retrospective preliminary pilot study.

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.

Can muscle vibration be the future in the treatment of cerebral palsy-related drooling? A feasibility study.

Background: Drooling is an involuntary loss of saliva from the mouth, and it is a common problem for children with cerebral palsy (CP). The treatment may be pharmacological, surgical, or speech-related. Repeated Muscle Vibration (rMV) is a proprioceptive impulse that activates fibers Ia reaching the somatosensory and motor cortex. Aim: The aim of the study is to evaluate the effectiveness of rMV in the treatment of drooling in CP. Design, setting and population: This was a rater blinded prospective feasibility study, performed at the "Gli Angeli di Padre Pio" Foundation, Rehabilitation Centers (Foggia, Italy), involving twenty-two CP patients affected by drooling (aged 5-15, mean 9,28 ± 3,62). Children were evaluated at baseline (T0), 10 days (T1), 1 month (T2) and 3 months (T3) after the treatment. Methods: The degree and impact of drooling was assessed by using the Drooling Impact Scale (DIS), the Drooling Frequency and Severity Scale (DFSS), Visual Analogue Scale (VAS) and Drooling Quotient (DQ). An rMV stimulus under the chin symphysis was applied with a 30 min protocol for 3 consecutive days. Results: The statistical analysis shows that DIS, DFSS, VAS, DQ improved with significant differences in the multiple comparisons between T1 vs T2, T1 vs T3 and T1 vs T4 (p≤0.001). Conclusion This study demonstrates that rMV might be a safe and effective tool in reducing drooling in patients with CP. The vibrations can improve the swallowing mechanisms and favor the acquisition of the maturity of the oral motor control in children with CP.

Is the aquatic thermal environment a suitable place for providing rehabilitative treatment for person with Parkinson's disease? A retrospective study.

Many authors showed that aquatic physiotherapy could improve quality of life and reduce postural instability and risk of falling in elderly subjects. The aim of this research was to explore if the thermal aquatic environment is a suitable place for rehabilitative training in person with Parkinson disease (PwP) with results comparable to the standard physiotherapy. A retrospective study was conducted on a database of 14 persons with Parkinson who were admitted to a thermal aquatic rehabilitation to undergo treatments made to improve gait and balance impairments. The rehabilitation training consisted of 45-min sessions conducted twice a week, on non-consecutive days, over 4 weeks of functional re-education and kinesitherapy in the thermal pool. Educational and prevention instructions were also given to the patients during each session. Additionally, nutrition (diet), health education, and cognitive behavioral advice were given to our patients by therapists. The clinical characteristics of the sample were age 66 ± 9, disease duration 7 ± 5, and Hoehn and Yahr 1.5 ± 0.5. The statistical analysis showed a statistically significant improvement for the UPDRS p = 0.0005, for The Berg Balance Scale p = 0.0078, for the PDQ8 p = 0.0039, Tinetti p = 0.0068, and for Mini BESTest p = 0.0002. Our data suggest that this intervention could become a useful strategy in the rehabilitation program of PwP. The simplicity of treatment and the lack of side effects endorse the use of thermal aquatic environment for the gait and balance recovery in PwP.

Predicting Motor and Cognitive Improvement Through Machine Learning Algorithm in Human Subject that Underwent a Rehabilitation Treatment in the Early Stage of Stroke.

BACKGROUND: The objective of this study was to investigate, in subject with stroke, the exact role as prognostic factor of common inflammatory biomarkers and other markers in predicting motor and/or cognitive improvement after rehabilitation treatment from early stage of stroke. METHODS: In this longitudinal cohort study on stroke patients undergoing inpatient rehabilitation, data from 55 participants were analyzed. Functional and clinical data were collected after admission to the rehabilitation unit. Biochemical and hematological parameters were obtained from peripheral venous blood samples on all individuals who participated in the study within 24hours from the admission at the rehabilitative treatment. Data regarding the health status were collected at the end of rehabilitative treatment. First, a feature selection has been performed to estimate the mutual dependence between input and output variables. More specifically, the so called Mutual Information criterion has been exploited. In the second stage of the analysis, the Support Vector Machines (SVMs), a non-probabilistic binary machine learning algorithm widely used for classification and regression, has been used to predict the output of the rehabilitation process. Performances of the linear SVM regression algorithm have been evaluated considering a different number of input features (ranging from 4 to 14). The performance evaluation of the model proposed has been investigated in terms of correlation, Root Mean Square Error (RMSE) and Mean Absolute Deviation Percentage (MADP). RESULTS: Results on the test samples show a good correlation between all the predicted and measured outputs (i.e. T1 Barthel Index (BI), T1 Motor Functional Independence Measure (FIM), T1 Cognitive FIM and T1 Total FIM) ranging from 0.75 to 0.81. While the MADP is high (i.e., 83.96%) for T1 BI, the other predicted responses (i.e., T1 Motor FIM, T1 Cognitive FIM, T1 Total FIM) disclose a smaller MADP of 30%. Accordingly, the RMSE ranges from 4.28 for T1 Cognitive FIM to 22.6 for T1 BI. CONCLUSIONS: In conclusion, the authors developed a new predictive model using SVM regression starting from common inflammatory biomarkers and other ratio markers. The main efforts of our model have been accomplished in regard to the evidence that the type of stroke has not shown itself to be a critical input variable to predict the discharge data, furthermore, among the four selected indicators, Barthel at T1 is the less predictable (MADP > 80%), while it is possible to predict T1 Cognitive FIM with an MADP less than 18%.

Effects on mobility training and de-adaptations in subjects with Spinal Cord Injury due to a Wearable Robot: a preliminary report.

BACKGROUND: Spinal cord injury (SCI) is a severe neurological disorder associated not only with ongoing medical complications but also with a significant loss of mobility and participation. The introduction of robotic technologies to recover lower limb function has been greatly employed in the rehabilitative practice. The aim of this preliminary report were to evaluate the efficacy, the feasibility and the changes in the mobility and in the de-adaptations of a new rehabilitative protocol for EKSO™ a robotic exoskeleton device in subjects with SCI disease with an impairment of lower limbs assessed by gait analysis and clinical outcomes. METHOD: This is a pilot single case experimental A-B (pre-post) design study. Three cognitively intact voluntary participants with SCI and gait disorders were admitted. All subjects were submitted to a training program of robot walking sessions for 45 min daily over 20 sessions. The spatiotemporal parameters at the beginning (T0) and at the end of treatment (T1) were recorded. Other clinical assessments (6 min walking test and Timed Up and Go test) were acquired at T0 and T1. RESULTS: Robot training were feasible and acceptable and all participants completed the training sessions. All subjects showed improvements in gait spatiotemporal indexes (Mean velocity, Cadence, Step length and Step width) and in 6 min Walking Test (T0 versus T1). CONCLUSIONS: Robot training is a feasible form of rehabilitation for people with SCI. Further investigation regarding long term effectiveness of robot training in time is necessary. TRIAL REGISTRATION: ClinicalTrials.gov NCT02065830.

Feasibility study into self-administered training at home using an arm and hand device with motivational gaming environment in chronic stroke.

BACKGROUND: Assistive and robotic training devices are increasingly used for rehabilitation of the hemiparetic arm after stroke, although applications for the wrist and hand are trailing behind. Furthermore, applying a training device in domestic settings may enable an increased training dose of functional arm and hand training. The objective of this study was to assess the feasibility and potential clinical changes associated with a technology-supported arm and hand training system at home for patients with chronic stroke. METHODS: A dynamic wrist and hand orthosis was combined with a remotely monitored user interface with motivational gaming environment for self-administered training at home. Twenty-four chronic stroke patients with impaired arm/hand function were recruited to use the training system at home for six weeks. Evaluation of feasibility involved training duration, usability and motivation. Clinical outcomes on arm/hand function, activity and participation were assessed before and after six weeks of training and at two-month follow-up. RESULTS: Mean System Usability Scale score was 69 % (SD 17 %), mean Intrinsic Motivation Inventory score was 5.2 (SD 0.9) points, and mean training duration per week was 105 (SD 66) minutes. Median Fugl-Meyer score improved from 37 (IQR 30) pre-training to 41 (IQR 32) post-training and was sustained at two-month follow-up (40 (IQR 32)). The Stroke Impact Scale improved from 56.3 (SD 13.2) pre-training to 60.0 (SD 13.9) post-training, with a trend at follow-up (59.8 (SD 15.2)). No significant improvements were found on the Action Research Arm Test and Motor Activity Log. CONCLUSIONS: Remotely monitored post-stroke training at home applying gaming exercises while physically supporting the wrist and hand showed to be feasible: participants were able and motivated to use the training system independently at home. Usability shows potential, although several usability issues need further attention. Upper extremity function and quality of life improved after training, although dexterity did not. These findings indicate that home-based arm and hand training with physical support from a dynamic orthosis is a feasible tool to enable self-administered practice at home. Such an approach enables practice without dependence on therapist availability, allowing an increase in training dose with respect to treatment in supervised settings. TRIAL REGISTRATION: This study has been registered at the Netherlands Trial Registry (NTR): NTR3669 .

Effects of upper limb robot-assisted therapy on motor recovery in subacute stroke patients.

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.

Robot-assisted walking training for individuals with Parkinson's disease: a pilot randomized controlled trial.

BACKGROUND: Over the last years, the introduction of robotic technologies into Parkinson's disease rehabilitation settings has progressed from concept to reality. However, the benefit of robotic training remains elusive. This pilot randomized controlled observer trial is aimed at investigating the feasibility, the effectiveness and the efficacy of new end-effector robot training in people with mild Parkinson's disease. METHODS: Design. Pilot randomized controlled trial. RESULTS: Robot training was feasible, acceptable, safe, and the participants completed 100% of the prescribed training sessions. A statistically significant improvement in gait index was found in favour of the EG (T0 versus T1). In particular, the statistical analysis of primary outcome (gait speed) using the Friedman test showed statistically significant improvements for the EG (p = 0,0195). The statistical analysis performed by Friedman test of Step length left (p = 0,0195) and right (p = 0,0195) and Stride length left (p = 0,0078) and right (p = 0,0195) showed a significant statistical gain. No statistically significant improvements on the CG were found. CONCLUSIONS: Robot training is a feasible and safe form of rehabilitative exercise for cognitively intact people with mild PD. This original approach can contribute to increase a short time lower limb motor recovery in idiopathic PD patients. The focus on the gait recovery is a further characteristic that makes this research relevant to clinical practice. On the whole, the simplicity of treatment, the lack of side effects, and the positive results from patients support the recommendation to extend the use of this treatment. Further investigation regarding the long-time effectiveness of robot training is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT01668407.

Caveolin-1 overexpression is associated with simultaneous abnormal expression of the E-cadherin/α-ß catenins complex and multiple ErbB receptors and with lymph nodes metastasis in head and neck squamous cell carcinomas.

The presence of lymph node metastases is one of the most important prognostic indicators in head and neck squamous cell carcinomas (HNSCCs). An alteration of the E-cadherin-catenins complex and EGFR is essential for the invasiveness of cancer cells. Caveolin-1, the major structural protein of the caveolae, represents a scaffolding molecule for several signaling proteins including EGFR. Although caveolin-1 has been shown to play a role in inducing the invasive phenotype of cancer cells, its role appears to be cell-type specific and for some tumors it has not been defined yet. In this study we used 57 HNSCC specimens to investigate whether the abnormal expression of caveolin-1 was associated with the derangement of the E-cadherin-catenins complex and with the overexpression of ErbB receptors. We demonstrate that in HNSCCs caveolin-1 overexpression is associated with the simultaneous abnormal expression of at least one member of the E-cadherin/α-ß catenins complex and multiple ErbB receptors as well as with lymph node metastases. We also demonstrate that chronic stimulation of a human hypopharyngeal carcinoma cell line (FaDu) with EGF induced the internalization of ß-catenin and caveolin-1 and their co-localization with EGFR. Moreover, EGF treatment induced an increased physical interaction between EGFR/ß-catenin/caveolin-1 and between E-cadherin/ß-catenin/caveolin-1. These molecular events were associated with an increased directional motility of FaDu cells in vitro. These findings may provide new insight into the biology of HNSCC progression and help to identify subgroups of primary HNSCCs with a more aggressive behavior.

Predictors of changes in sentimental and sexual life after traumatic spinal cord injury.

OBJECTIVE: To investigate changes and identify predictors in interpersonal functioning and sexual life after traumatic spinal cord injury (SCI). DESIGN: Prospective, multicenter, follow-up observational study. SETTING: Subjects at home, interviewed by phone during a 6-month period, 3.8 mean years after discharge from 24 centers participating in a previous epidemiologic prospective survey. PARTICIPANTS: Subjects (N=403) with traumatic SCI. INTERVENTIONS: Not applicable. DEPENDENT VARIABLES: satisfaction with sentimental life and satisfaction with sexual life compared with before the injury. INDEPENDENT VARIABLES: demographic (age, sex, marital status, vocational status), SCI related (severity, level, bowel/bladder continence), car-driving ability, perceived quality of life (QoL), and impact of sentimental life, social integration, and vocational status on QoL. RESULTS: Satisfaction with sentimental life was reportedly increased or the same as before SCI in 69% of the sample, but satisfaction with sexual life in only 31%. Lesser satisfaction with sexual life was reported by men than women (P=.002) and by married people than singles (P<.001). Significant predictors of sentimental life were perceived QoL and preserved driving ability (R(2)=.195). Bladder continence was positively associated with a better satisfaction with sexual life (R(2)=.368). Bowel continence did not remain a significant predictor of satisfaction with sexual life in multivariate analysis. CONCLUSIONS: The challenge of a comprehensive rehabilitation of SCI, addressing the recovery of well-being including a satisfying sentimental and sexual life, requires identifying new issues that should be considered in up-to-date rehabilitation programs. The results indicate associations between driving ability and a better satisfaction with sentimental life. Further investigations are needed to explore whether the relationship is causative.

Pro-inflammatory gene expression in solid glioblastoma microenvironment and in hypoxic stem cells from human glioblastoma.

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.

Robot-aided therapy for upper limbs in patients with stroke-related lesions. Brief report of a clinical experience.

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.

Action Observation Therapy for Upper Limb Recovery in Patients with Stroke: A Randomized Controlled Pilot Study.

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.

Ovarian cancer cytoreduction induces changes in T cell population subsets reducing immunosuppression.

Surgery is the primary therapeutic strategy for most solid tumours; however, modern oncology has established that neoplasms are frequently systemic diseases. Being however a local treatment, the mechanisms through which surgery plays its systemic role remain unknown. We have investigated the influence of cytoreduction on the immune system of primary and recurrent ovarian cancer. All ovarian cancer patients show an increase in CD4+ CD25+ FOXP3+ circulating cells (CD4 T(reg) ). CD4/CD8 ratio is increased in primary tumours, but not in recurrent neoplasms. Primary cytoreduction is able to increase circulating CD4 and CD8 effector cells and decrease CD4 naïve T cells. CD4+ T(reg) cells rapidly decreased after primary tumour debulking, while CD8+ CD25+ FOXP3+ (CD8 T(reg) ) cells are not detectable in peripheral blood. Similar results on CD4 T(reg) were observed with chemical debulking in women subjected to neoadjuvant chemotherapy. CD4 and CD8 T(reg) cells are both present in neoplastic tissue. Interleukin (IL)-10 serum levels decrease after surgery, while no changes are observed in transforming growth factor-ß1 and IL-6 levels. Surgically induced reduction of the immunosuppressive environment results in an increased capacity of CD8+ T cells to respond to the recall antigens. None of these changes was observed in patients previously subjected to chemotherapy or affected by recurrent disease. In conclusion, we demonstrate in ovarian cancer that primary debulking is associated with a reduction of circulating T(reg) and an increase in CD8 T-cell function. Debulking plays a beneficial systemic effect by reverting immunosuppression and restoring immunological fitness.

Up-regulation of pro-inflammatory genes as adaptation to hypoxia in MCF-7 cells and in human mammary invasive carcinoma microenvironment.

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 1alpha (HIF-1alpha) and nuclear factor-kappa B (NF-kappaB). 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-1alpha (SDF-1alpha) increased invasion and migration of hypoxic MCF-7 cells. Inhibition of HIF-1alpha by chetomin and NF-kappaB 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-1alpha and NF-kappaB and up-regulation of IR, CXCR4, estrogen receptor alpha (ERalpha), 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-1alpha, NF-kappaB, 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.

Common micro-RNA signature in skeletal muscle damage and regeneration induced by Duchenne muscular dystrophy and acute ischemia.

The aim of this work was to identify micro-RNAs (miRNAs) involved in the pathological pathways activated in skeletal muscle damage and regeneration by both dystrophin absence and acute ischemia. Eleven miRNAs were deregulated both in MDX mice and in Duchenne muscular dystrophy patients (DMD signature). Therapeutic interventions ameliorating the mdx-phenotype rescued DMD-signature alterations. The significance of DMD-signature changes was characterized using a damage/regeneration mouse model of hind-limb ischemia and newborn mice. According to their expression, DMD-signature miRNAs were divided into 3 classes. 1) Regeneration miRNAs, miR-31, miR-34c, miR-206, miR-335, miR-449, and miR-494, which were induced in MDX mice and in DMD patients, but also in newborn mice and in newly formed myofibers during postischemic regeneration. Notably, miR-206, miR-34c, and miR-335 were up-regulated following myoblast differentiation in vitro. 2) Degenerative-miRNAs, miR-1, miR-29c, and miR-135a, that were down-modulated in MDX mice, in DMD patients, in the degenerative phase of the ischemia response, and in newborn mice. Their down-modulation was linked to myofiber loss and fibrosis. 3) Inflammatory miRNAs, miR-222 and miR-223, which were expressed in damaged muscle areas, and their expression correlated with the presence of infiltrating inflammatory cells. These findings show an important role of miRNAs in physiopathological pathways regulating muscle response to damage and regeneration.

Up-regulation of the inflammatory-reparative phenotype in human prostate carcinoma.

BACKGROUND: Recent studies have underlined the role of tumor cells in the endogenous synthesis of pro-inflammatory molecules. We tested whether malignant progression in prostate cancer was associated with the activation of a phenotype typical of the innate immune system. METHODS: The expression of a set of molecules involved in tissue inflammation and repair was measured by real-time PCR and Western blot analysis in prostate samples in the absence or slight presence of a detectable leukocyte infiltrate. Whole tumor and non-tumor samples were analyzed in addition to laser-capture microdissected tumor and host epithelium. Receptor for advanced glycation end products, purine receptor, inducible enzymes cyclooxygenase-2 and nitric oxide synthase-2, pentraxin-3 and growth-survival factor receptors such as epithelial growth factor and estrogen alpha and beta receptors were all studied. RESULTS: A global survey approach showed an up-regulation in tumor samples of all of the studied genes, with the exception of ERbeta. A laser-capture microdissection approach highlighted over-expression of pro-inflammatory molecules in each tumor sample examined. Nuclear translocation of nuclear factor-kB subunit p65 was observed in tumor tissues. CONCLUSIONS: These data support the evidence that molecules typical of the innate immune system, similar to that of activated leukocytes, are produced by prostate epithelial cells and that their expression is up-regulated in malignant cells. We suggest that the observed pro-inflammatory and repair process activation may represent an important molecular mechanism in the progression of prostate cancer.

Gait impairment in neurological disorders: a new technological approach.

Gait recovery is considered one of the main objectives of rehabilitation interventions in neurological disabilities, as restricted movement can significantly reduce an individual's ability to take part in normal activities of daily living. Locomotor training has been shown to improve gait rehabilitation. Studies have recently been published on the use of robots and other devices in patients with gait disabilities, particularly in the rehabilitation of the lower limbs. However, analysis of the recent literature reveals a relative paucity of strong methodological studies. The evidence that is available, while strong, is not yet sufficient to allow definite conclusions to be drawn regarding the efficacy of these devices. From these considerations, it is clear that validated and standardized methods need to be adopted for each of the different systems available. This would help to clarify the indications for and correct use of robotic devices in the different neurological disorders.

Tumor-associated Tn-MUC1 glycoform is internalized through the macrophage galactose-type C-type lectin and delivered to the HLA class I and II compartments in dendritic cells.

The type of interaction between tumor-associated antigens and specialized antigen-presenting cells such as dendritic cells (DCs) is critical for the type of immunity that will be generated. MUC1, a highly O-glycosylated mucin, is overexpressed and aberrantly glycosylated in several tumor histotypes. This results in the expression of tumor-associated glycoforms and in MUC1 carrying the tumor-specific glycan Tn (GalNAcalpha1-O-Ser/Thr). Glycopeptides corresponding to three tandem repeats of MUC1, enzymatically glycosylated with 9 or 15 mol of GalNAc, were shown to specifically bind and to be internalized by immature monocyte-derived DCs (iDCs). Binding required calcium and the GalNAc residue and was competed out by GalNAc polymer and Tn-MUC1 or Tn-MUC2 glycopeptides. The macrophage galactose-type C-type lectin (MGL) receptor expressed on iDCs was shown to be responsible for the binding. Confocal analysis and ELISA done on subcellular fractions of iDCs showed that the Tn-MUC1 glycopeptides colocalized with HLA class I and II compartments after internalization. Importantly, although Tn-MUC1 recombinant protein was bound and internalized by MGL, the glycoprotein entered the HLA class II compartment, but not the HLA class I pathway. These data indicate that MGL expressed on iDCs is an optimal receptor for the internalization of short GalNAcs carrying immunogens to be delivered into HLA class I and II compartments. Such glycopeptides therefore represent a new way of targeting the HLA class I and II pathways of DCs. These results have possible implications in designing cancer vaccines.