Both strategies were effective, but the experimental approach induced better outcomes in motor performance. These results may favour early discharge from hospital sustained by a telerehabilitation programme, with potential beneficial effects on the use of available resources.

BackgroundRecent evidence has demonstrated the efficacy of Virtual Reality (VR) for stroke rehabilitation nonetheless its benefits and limitations in large population of patients have not yet been studied.ObjectivesTo evaluate the effectiveness of non-immersive VR treatment for the restoration of the upper limb motor function and its impact on the activities of daily living capacities in post-stroke patients.MethodsA pragmatic clinical trial was conducted among post-stroke patients admitted to our rehabilitation hospital. We enrolled 376 subjects who had a motor arm subscore on the Italian version of the National Institutes of Health Stroke Scale (It-NIHSS) between 1 and 3 and without severe neuropsychological impairments interfering with recovery. Patients were allocated to two treatments groups, receiving combined VR and upper limb conventional (ULC) therapy or ULC therapy alone. The treatment programs consisted of 2 hours of daily therapy, delivered 5 days per week, for 4 weeks. The outcome measures were the Fugl-Meyer Upper Extremity (F-M UE) and Functional Independence Measure (FIM) scales.ResultsBoth treatments significantly improved F-M UE and FIM scores, but the improvement obtained with VR rehabilitation was significantly greater than that achieved with ULC therapy alone. The estimated effect size of the minimal difference between groups in F-M UE and FIM scores was 2.5 ± 0.5 (P < 0.001) pts and 3.2 ± 1.2 (P = 0.007) pts, respectively.ConclusionsVR rehabilitation in post-stroke patients seems more effective than conventional interventions in restoring upper limb motor impairments and motor related functional abilities.Trial registration Italian Ministry of Health IRCCS Research Programme 2590412

Epithelial-mesenchymal transition is a physiopathological process by which epithelial cells acquire mesenchymal shape and properties. Malignant mesothelioma is histologically characterized by the concomitant presence of epithelioid and sarcomatoid features, the latter being associated to worse prognosis, thus suggesting a role of epithelial-mesenchymal transition in this dual phenotype. We studied 109 malignant mesotheliomas (58 epithelioid, 26 sarcomatoid, and 25 biphasic) by immunohistochemistry and qRT-PCR analysis, and demonstrated a substantial switch from epithelial markers (E-cadherin, b-catenin, and cytokeratins 5/6) to mesenchymal markers (N-cadherin, vimentin, a-smooth muscle actin, Snail, Slug, Twist, ZEB1, ZEB2, S100A4, MMP2, and MMP9) through epithelioid to biphasic and sarcomatoid histotypes. In agreement with these findings, the ectopic expression of miR-205 (a repressor of ZEB1 and ZEB2 expression) in MeT-5A (mesothelial cell line), H2452 (an epithelioid malignant mesothelioma cell line) and MSTO-211H (a biphasic malignant mesothelioma cell line) not only induced a significant reduction of ZEB1 and ZEB2 and a consequent up-regulation of E-cadherin gene expression, but also inhibited migration and invasion. Moreover, miR-205 was significantly down-regulated in biphasic and sarcomatoid histotypes (qRT-PCR and in situ hybridization analyses). Collectively, our findings indicate that epithelial-mesenchymal transition has a significant part in the morphological features of malignant mesothelioma. In particular, miR-205 downregulation correlated significantly with both a mesenchymal phenotype and a more aggressive behavior.

3Fondazione 'Carlo Ferri' per la prevenzione e la cura dei tumori, via Edmondo Riva 42, 00015 Monterotondo, Italy AbstractGermline mutations of the aryl hydrocarbon receptor (AHR)-interacting protein (AIP) gene confer a predisposition to pituitary adenomas (PA), usually in the setting of familial isolated PA. To provide further insights into the possible role of AIP in pituitary tumour pathogenesis, the expression of AIP and AHR was determined by real-time RT-PCR and/or immunohistochemistry (IHC) in a large series of PA (nZ103), including 17 with AIP mutations (AIP mut ). Variable levels of AIP and AHR transcripts were detected in all PA, with a low AHR expression (P!0.0001 versus AIP). Cytoplasmic AIP and AHR were detected by IHC in 84.0 and 38.6% of PA respectively, and significantly correlated with each other (PZ0.006). Nuclear AHR was detected in a minority of PA (19.7%). The highest AIP expression was observed in somatotrophinomas and non-secreting (NS) PA, and multivariate analysis in somatotrophinomas showed a significantly lower AIP immunostaining in invasive versus non-invasive cases (PZ0.019). AIP expression was commonly low in other secreting PA. AIP immunostaining was abolished in a minority of AIP mut PA, with a frequent loss of cytoplasmic AHR and no evidence of nuclear AHR. In contrast, AIP overexpression in a subset of NS PA could be accompanied by nuclear AHR immunopositivity. We conclude that down-regulation of AIP and AHR may be involved in the aggressiveness of somatotrophinomas. Overall, IHC is a poorly sensitive tool for the screening of AIP mutations. Data obtained on AHR expression suggest that AHR signalling may be differentially affected according to PA phenotype.

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Proper scoring rules are methods for encouraging honest assessment of probability distributions. Just like likelihood, a proper scoring rule can be applied to supply an unbiased estimating equation for any statistical model, and the theory of such equations can be applied to understand the properties of the associated estimator. In this paper we develop some basic scoring rule estimation theory, and explore robustness and interval estimation preoperties by means of theory and simulations.

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Adrenocortical carcinoma patient prognosis is extremely variable and poorly predictable. The newly introduced Helsinki Score is the first so far proposed diagnostic and prognostic system based on the combined evaluation of morphological (mitoses and necrosis) and immunohistochemical (Ki-67) parameters. The aim of the study was to validate the prognostic role of the Helsinki Score for adrenocortical carcinoma characterization. Thus, 225 adrenocortical carcinomas were reclassified using the Weiss Score and the Helsinki Score (3× mitotic count + 5 × necrosis + Ki-67 index). At univariate analysis, statistically significant prognostic values were observed at the log-rank test for mitotic count (cutoff values: <6 and ≥55; P<.0001), Ki-67 (cutoff values: <20 and ≥50; P<.0001), Weiss Score (cutoff values: <5 and ≥8; P<.0001), Helsinki Score (cutoff values: <13 and ≥19; P<.0001), histological variant (conventional versus oncocytic; P=.009), necrosis (P=.001), and stage (P=.005). Cox multivariate analysis using a backward stepwise selection method retained only Helsinki Score and Weiss Score as predictors of poor prognosis (P<.0001 and P=.0005, respectively). Helsinki Score (with a threshold of 28.5 points; area under the curve [AUC]=0.729, 95% confidence interval=0.66-0.79) and Ki-67 (with a threshold of 20.5%; AUC=0.727, 95% confidence interval=0.66-0.79) showed the best and equivalent AUCs predicting disease-related deaths determined using receiver operating characteristic statistics. In conclusion, the Helsinki Score is a valuable system to predict prognosis in adrenocortical carcinoma, outperforming the currently established prognostic parameters.