Virtual Stiffness: A Novel Biomechanical Approach to Estimate Limb Stiffness of a Multi-Muscle and Multi-Joint System

In recent years, different groups have developed algorithms to control the stiffness of a robotic device through the electromyographic activity collected from a human operator. However, the approaches proposed so far require an initial calibration, have a complex subject-specific muscle model, or consider the activity of only a few pairs of antagonist muscles. This study described and tested an approach based on a biomechanical model to estimate the limb stiffness of a multi-joint, multi-muscle system from muscle activations. The “virtual stiffness” method approximates the generated stiffness as the stiffness due to the component of the muscle-activation vector that does not generate any endpoint force. Such a component is calculated by projecting the vector of muscle activations, estimated from the electromyographic signals, onto the null space of the linear mapping of muscle activations onto the endpoint force. The proposed method was tested by using an upper-limb model made of two joints and six Hill-type muscles and data collected during an isometric force-generation task performed with the upper limb. The null-space projection of the muscle-activation vector approximated the major axis of the stiffness ellipse or ellipsoid. The model provides a good approximation of the voluntary stiffening performed by participants that could be directly implemented in wearable myoelectric controlled devices that estimate, in real-time, the endpoint forces, or endpoint movement, from the mapping between muscle activation and force, without any additional calibrations

Protein kinase a distribution in meningioma

Deregulation of intracellular signal transduction pathways is a hallmark of cancer cells, clearly differentiating them from healthy cells. Differential intracellular distribution of the cAMP-dependent protein kinases (PKA) was previously detected in cell cultures and in vivo in glioblastoma and medulloblastoma. Our goal is to extend this observation to meningioma, to explore possible differences among tumors of different origins and prospective outcomes. The distribution of regulatory and catalytic subunits of PKA has been examined in tissue specimens obtained during surgery from meningioma patients. PKA RI subunit appeared more evenly distributed throughout the cytoplasm, but it was clearly detectable only in some tumors. RII was present in discrete spots, presumably at high local concentration; these aggregates could also be visualized under equilibrium binding conditions with fluorescent 8-substituted cAMP analogues, at variance with normal brain tissue and other brain tumors. The PKA catalytic subunit showed exactly overlapping pattern to RII and in fixed sections could be visualized by fluorescent cAMP analogues. Gene expression analysis showed that the PKA catalytic subunit revealed a significant correlation pattern with genes involved in meningioma. Hence, meningioma patients show a distinctive distribution pattern of PKA regulatory and catalytic subunits, different from glioblastoma, medulloblastoma, and healthy brain tissue. These observations raise the possibility of exploiting the PKA intracellular pathway as a diagnostic tool and possible therapeutic interventions

Exploiting Intrinsic Kinematic Null Space for Supernumerary Robotic Limbs Control

Supernumerary robotic limbs (SRLs) gained increasing interest in the last years for their applicability as healthcare and assistive technologies. These devices can either support or augment human sensorimotor capabilities, allowing users to complete tasks that are more complex than those feasible for their natural limbs. However, for a successful coordination between natural and artificial limbs, intuitiveness of interaction and perception of autonomy are key enabling features, especially for people suffering from motor disorders and impairments. The development of suitable human-robot interfaces is thus fundamental to foster the adoption of SRLs.With this work, we describe how to control an extra degree of freedom by taking advantage of what we defined the Intrinsic Kinematic Null Space, i.e. the redundancy of the human kinematic chain involved in the ongoing task. Obtained results demonstrated that the proposed control strategy is effective for performing complex tasks with a supernumerary robotic finger, and that practice improves users' control ability

Can spatial filtering separate voluntary and involuntary components in children with dyskinetic cerebral palsy?

The design of myocontrolled devices faces particular challenges in children with dyskinetic cerebral palsy because the electromyographic signal for control contains both voluntary and involuntary components. We hypothesized that voluntary and involuntary components of movements would be uncorrelated and thus detectable as different synergistic patterns of muscle activity, and that removal of the involuntary components would improve online EMG-based control. Therefore, we performed a synergy-based decomposition of EMG-guided movements, and evaluated which components were most controllable using a Fitts' Law task. Similarly, we also tested which muscles were most controllable. We then tested whether removing the uncontrollable components or muscles improved overall function in terms of movement time, success rate, and throughput. We found that removal of less controllable components or muscles did not improve EMG control performance, and in many cases worsened performance. These results suggest that abnormal movement in dyskinetic CP is consistent with a pervasive distortion of voluntary movement rather than a superposition of separable voluntary and involuntary components of movement

Contraction level, but not force direction or wrist position, affects the spatial distribution of motor unit recruitment in the biceps brachii muscle

Purpose: Different motor units (MUs) in the biceps brachii (BB) muscle have been shown to be preferentially recruited during either elbow flexion or supination. Whether these different units reside within different regions is an open issue. In this study, we tested wheter MUs recruited during submaximal isometric tasks of elbow flexion and supination for two contraction levels and with the wrist fixed at two different angles are spatially localized in different BB portions. Methods: The MUs’ firing instants were extracted by decomposing high-density surface electromyograms (EMG), detected from the BB muscle of 12 subjects with a grid of electrodes (4 rows along the BB longitudinal axis, 16 columns medio-laterally). The firing instants were then used to trigger and average single-differential EMGs. The average rectified value was computed separately for each signal and the maximal value along each column in the grid was retained. The center of mass, defined as the weighted mean of the maximal, average rectified value across columns, was then consdiered to assess the medio-lateral changes in the MU surface representation between conditions. Results: Contraction level, but neither wrist position nor force direction (flexion vs. supination), affected the spatial distribution of BB MUs. In particular, higher forces were associated with the recruitment of BB MUs whose action potentials were represented more medially. Conclusion: Although the action potentials of BB MUs were represented locally across the muscle medio-lateral region, dicrimination between elbow flexion or supination seems unlikely from the surface representation of MUs action potentials

Expression of telomeric repeat binding factor-1 in astroglial brain tumors

OBJECTIVE: In human somatic cells, telomeres shorten with successive cell divisions, resulting in progressive genomic instability, altered gene expression, and cell death. Recently, telomere-specific deoxyribonucleic acid-binding proteins, such as telomeric repeat binding factor-1 (TRF1), have been proposed as candidates for the role of molecules regulating telomerase activity, and they have been suggested to play key roles in the maintenance of telomere function. The present study was designed to assess TRF1 expression in human astroglial brain tumors and to speculate on the clinical implications of its expression. METHODS: Twenty flash-frozen surgical specimens obtained from adult patients who underwent craniotomy for microsurgical tumor resection, histologically verified as World Health Organization Grade II to IV astrocytomas, were used. Expression of TRF1 in astrocytomas of different grades was studied by means of both immunohistochemical and Western blotting analysis. The correlation between the extent of TRF1 expression and histological grading, performance status, and length of survival of patients underwent statistical analyses. RESULTS: TRF1 was expressed in all tumor samples. The level of its expression was variable, decreasing from low-grade through high-grade astrocytomas (P 0.0032). TRF1 expression correlated with the patient’s length of survival (P 0.001) and performance status (P 0.001) and proved to be an independent indicator of length of survival. CONCLUSION: Our findings suggest that the loss of TRF1 expression capability, as a result of down-regulation of TRF1 expression in malignant gliomas cells, may play a role in the malignant progression of astroglial brain tumors

Insulin Glargine U100 Utilization in Patients with Type 2 Diabetes in an Italian Real-World Setting: A Retrospective Study

Background. This study is aimed at estimating the proportion of type 2 diabetes mellitus (T2DM) patients treated with basal insulin (insulin glargine U100) and at evaluating daily insulin dose, treatment pattern, and adherence to treatment of these patients. Methods. Data from administrative and laboratory databases of 3 Italian Local Health Units were retrospectively collected and analyzed. All patients with a diagnosis of T2DM between 01/01/2012 and 31/12/2012 were considered, and those with at least a prescription of insulin glargine between 01/01/2013 and 31/12/2014 were included and followed up for one year. For each patient, we evaluated HbA1c levels both at baseline and during the follow-up period and the daily average dose of insulin. Medication adherence was defined by using medication possession ratio (MPR) and reported as proportion of patients with MPR≥80%. Results. 7,422 T2DM patients were available for the study. According to the antidiabetic medication prescribed, patients were categorized into four groups: insulin glargine only, insulin glargine plus oral glucose-lowering drugs, insulin glargine plus rapid-acting insulin, and insulin glargine plus DPP-4 inhibitors. Median daily dose of insulin among insulin glargine only patients was higher than in other groups (35 IU vs. 20 IU, p<0.05), and a higher percentage of them achieved a target HbA1c value of less than 7.0% (53.8% vs. 30%, p<0.001). Adherence to insulin treatment was lowest (41%) in the insulin glargine only group compared to other groups (ranging from 58.4% to 64.4%), p<0.001. Conclusions. A large proportion of T2DM patients treated with insulin fail in achieving the glycemic target of HbA1c level<7%, irrespective of treatment regimen; however, basal insulin only is associated with lower therapeutic unsuccess. Adherence to antidiabetes medications is also suboptimal in these patients and should be addressed to improve long-term outcomes of reducing and preventing microvascular and macrovascular complications

Myeloid Diagnostic and Prognostic Markers of Immune Suppression in the Blood of Glioma Patients.

Although gliomas are confined to the central nervous system, their negative influence over the immune system extends to peripheral circulation. The immune suppression exerted by myeloid cells can affect both response to therapy and disease outcome. We analyzed the expansion of several myeloid parameters in the blood of low- and high-grade gliomas and assessed their relevance as biomarkers of disease and clinical outcome. Methods: Peripheral blood was obtained from 134 low- and high-grade glioma patients. CD14+, CD14+/p-STAT3+, CD14+/PD-L1+, CD15+ cells and four myeloid-derived suppressor cell (MDSC) subsets, were evaluated by flow cytometry. Arginase-1 (ARG1) quantity and activity was determined in the plasma. Multivariable logistic regression model was used to obtain a diagnostic score to discriminate glioma patients from healthy controls and between each glioma grade. A glioblastoma prognostic model was determined by multiple Cox regression using clinical and myeloid parameters. Results: Changes in myeloid parameters associated with immune suppression allowed to define a diagnostic score calculating the risk of being a glioma patient. The same parameters, together with age, permit to calculate the risk score in differentiating each glioma grade. A prognostic model for glioblastoma patients stemmed out from a Cox multiple analysis, highlighting the role of MDSC, p-STAT3, and ARG1 activity together with clinical parameters in predicting patient's outcome. Conclusions: This work emphasizes the role of systemic immune suppression carried out by myeloid cells in gliomas. The identification of biomarkers associated with immune landscape, diagnosis, and outcome of glioblastoma patients lays the ground for their clinical use