A body-weight-supported visual feedback system for gait recovering in stroke patients: A randomized controlled study.

OBJECTIVE: The aim of this study was to determine the effectiveness of a novel body-weight-supported (BWS) gait training system with visual feedback, called Copernicus® (Rehalife, Italy). This computerized device provides comfortable, regular and repeatable locomotion in hemiplegic patients. Through visual real-time monitoring of gait parameters, patients are trained to transfer weight loading alternately on both feet. DESIGN: A single-blind, randomized controlled study. A single center used a computer-generated randomization code to allocate treatments. SETTING: Intensive rehabilitation unit (IRU) at the Institute S. Anna (Italy). PARTICIPANTS: 63 first-ever stroke patients (39 men, age: 66.1 ± 9.6 years; 61.6 % with left-sided lesion) randomly distributed into three demographically/clinically matched groups. TREATMENTS: All groups were treated five times a week for 2 -h sessions for six consecutive weeks. The first group ("control") underwent a conventional physical therapy; the second group performed advanced BWS gait training sessions without visual feedback (Experimental VF- group); whereas the third group used BWS with visual feedback stimulation (Experimental VF+ group). MAIN OUTCOME MEASURES: Absolute changes were recorded using conventional clinical scales and kinematic measurement of static gait balance from baseline to follow-up. RESULTS: Significant interaction Group*Time effects scales (F2,126 = 5.1, p-level = 0.005, η²p = 0.25; F2,126 = 4.7, p-level = 0.007, η²p = 0.19; respectively) were detected in the Functional Independence Measure and Tinetti-Balance scales. Post hoc analysis demonstrated that the recovery of motor functioning was greater for the VF + group with respect to other groups (all p's ≤ 0.001). A similar pattern of findings was also obtained with a stabilometric analysis, demonstrating a better clinical improvement in static balance after VF + treatment. CONCLUSION: The proposed advanced rehabilitation system with visual feedback was more effective in improving gait recovery with respect to conventional and high-tech therapies without a sensor feedback.

A novel splice variant of the protein tyrosine phosphatase PTPRJ that encodes for a soluble protein involved in angiogenesis.

PTPRJ is a receptor protein tyrosine phosphatase with tumor suppressor activity. Very little is known about the role of PTPRJ ectodomain, although recently both physiological and synthetic PTPRJ ligands have been identified. A putative shorter spliced variant, coding for a 539 aa protein corresponding to the extracellular N-terminus of PTPRJ, is reported in several databases but, currently, no further information is available.Here, we confirmed that the PTPRJ short isoform (named sPTPRJ) is a soluble protein secreted into the supernatant of both endothelial and tumor cells. Like PTPRJ, also sPTPRJ undergoes post-translational modifications such as glycosylation, as assessed by sPTPRJ immunoprecipitation. To characterize its functional activity, we performed an endothelial cell tube formation assay and a wound healing assay on HUVEC cells overexpressing sPTPRJ and we found that sPTPRJ has a proangiogenic activity. We also showed that sPTPRJ expression down-regulates endothelial adhesion molecules, that is a hallmark of proangiogenic activity. Moreover, sPTPRJ mRNA levels in human high-grade glioma, one of the most angiogenic tumors, are higher in tumor samples compared to controls. Further studies will be helpful not only to clarify the way sPTPRJ works but also to supply clues to circumvent its activity in cancer therapy.

Retroactivity analysis of a chemical reaction network module for the subtraction of molecular fluxes.

The availability of a well-characterised subtraction module is a key step towards the realisation of modular embedded feedback controllers in synthetic biological systems. A well-known problem when dealing with complex biosystems is represented by the retroactivity effect, which can significantly modify the dynamics of interconnected subsystem, with respect to the behaviour they exhibit when disconnected from each other. In this paper, we illustrate a minimal CRN that implements a subtraction operation between two input molecular fluxes. In order to assess its effectiveness as a module of a more complex system, we analyse its retroactivity upon interconnection. More specifically, we connect the subtraction module with an upstream module, which determines the dynamics of the inputs species, and with a downstream transcriptional module, which acts as a load. By comparing the dynamics of the loaded and unloaded subtractor, we show that the retroactivity can be attenuated when the dynamics of the subtractor and of the load system evolve over different timescales. This result, obtained through a singular perturbation analysis, is confirmed by means of numerical simulations.

A control-theoretical approach to the identification of a commitment switch in B lymphopoiesis cell fate determination.

Cellular differentiation is continuously orchestrated by complex networks of transcription factors, signaling molecules and genetic and epigenetic events, a fundamental prerequisite for the design of strategies for reprogramming differentiated cells to immature stem/progenitor cells is a thorough understanding of such complex regulatory machinery. Therefore, mathematical models, along with the associated analysis and control methods, are highly needed in this research field. In the present work, we provide a first model of the genetic regulatory network driving the cellular fate determination at the stage of lymphoid lineage commitment, in particular during lineage restriction of multipotent progenitors to early B-cell committed precursors.