Design and realization of the CUFF - clenching upper-limb force feedback wearable device for distributed mechano-tactile stimulation of normal and tangential skin forces

Rendering forces to the user is one of the main goals of haptic technology. While most force-feedback interfaces are robotic manipulators, attached to a fixed frame and designed to exert forces on the users while being moved, more recent haptic research introduced two novel important ideas. On one side, cutaneous stimulation aims at rendering haptic stimuli at the level of the skin, with a distributed, rather than, concentrated approach. On the other side, wearable haptics focuses on highly portable and mobile devices, which can be carried and worn by the user as the haptic equivalent of an mp3 player. This paper presents a light and simple wearable device (CUFF) for the distributed mechano-tactile stimulation of the user's arm skin with pressure and stretch cues, related to normal and tangential forces, respectively. The working principle and the mechanical and control implementation of the CUFF device are presented. Then, after a basic functional validation, a first application of the device is shown, where it is used to render the grasping force of a robotic hand (the Pisa/IIT SoftHand). Preliminary results show that the device is capable to deliver in a reliable manner grasping force information, thus eliciting a good softness discrimination in users and enhancing the overall grasping experience

The protein pheromone Er-1 of the ciliate Euplotes raikovi stimulates humanT-cell activity: Involvement of interleukin-2 system

Water-soluble protein signals (pheromones) of the ciliate Euplotes have been supposed to be functional precursors of growth factors and cytokines that regulate cell–cell interactionin multi-cellular eukaryotes.This work provides evidence that native preparations of the Euplotes raikovi pheromone Er-1 (a helical protein of 40 aminoacids) specifically increases viability, DNA synthesis, proliferation, and the production of interferon-g, tumor necrosis factor-a, interleukin (IL)-1b, IL-2, and IL-13 in human Jurkat T-cells. Also, Er-1 significantly decreases them RNA levels of the b and g subunits of IL-2 receptor(IL-2R), while them RNA levels of the a subunit appeared to be not affected. Jurkat T-cell treatments with Er-1 induced the down-regulation of the IL-2Ra subunit by a reversible and time-dependent endocytosis, and increased the levels of phosphorylation of the extracellular signal-regulated kinases (ERK). The cell-type specificity of these effects was supported by the finding that Er-1, although unable to directly influence the growth of human glioma U373 cells, induced Jurkat cells to synthesize and release factors that, in turn, inhibited the U373 cell proliferation. Overall, these findings imply that Er-1 coupling to IL-2R and ERK immuno-enhances T-cell activity, and that this effect likely translates to an inhibition of glioma cell growth

Design of an under-actuated wrist based on adaptive synergies

An effective robotic wrist represents a key enabling element in robotic manipulation, especially in prosthetics. In this paper, we propose an under-actuated wrist system, which is also adaptable and allows to implement different under-actuation schemes. Our approach leverages upon the idea of soft synergies - in particular the design method of adaptive synergies - as it derives from the field of robot hand design. First we introduce the design principle and its implementation and function in a configurable test bench prototype, which can be used to demonstrate the feasibility of our idea. Furthermore, we report on results from preliminary experiments with humans, aiming to identify the most probable wrist pose during the pre-grasp phase in activities of daily living. Based on these outcomes, we calibrate our wrist prototype accordingly and demonstrate its effectiveness to accomplish grasping and manipulation tasks

Gene- and variant-specific efficacy of serum/glucocorticoid-regulated kinase 1 inhibition in long QT syndrome types 1 and 2.

AIMS Current long QT syndrome (LQTS) therapy, largely based on beta-blockade, does not prevent arrhythmias in all patients; therefore, novel therapies are warranted. Pharmacological inhibition of the serum/glucocorticoid-regulated kinase 1 (SGK1-Inh) has been shown to shorten action potential duration (APD) in LQTS type 3. We aimed to investigate whether SGK1-Inh could similarly shorten APD in LQTS types 1 and 2. METHODS AND RESULTS Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and hiPSC-cardiac cell sheets (CCS) were obtained from LQT1 and LQT2 patients; CMs were isolated from transgenic LQT1, LQT2, and wild-type (WT) rabbits. Serum/glucocorticoid-regulated kinase 1 inhibition effects (300 nM-10 µM) on field potential durations (FPD) were investigated in hiPSC-CMs with multielectrode arrays; optical mapping was performed in LQT2 CCS. Whole-cell and perforated patch clamp recordings were performed in isolated LQT1, LQT2, and WT rabbit CMs to investigate SGK1-Inh (3 µM) effects on APD. In all LQT2 models across different species (hiPSC-CMs, hiPSC-CCS, and rabbit CMs) and independent of the disease-causing variant (KCNH2-p.A561V/p.A614V/p.G628S/IVS9-28A/G), SGK1-Inh dose-dependently shortened FPD/APD at 0.3-10 µM (by 20-32%/25-30%/44-45%). Importantly, in LQT2 rabbit CMs, 3 µM SGK1-Inh normalized APD to its WT value. A significant FPD shortening was observed in KCNQ1-p.R594Q hiPSC-CMs at 1/3/10 µM (by 19/26/35%) and in KCNQ1-p.A341V hiPSC-CMs at 10 µM (by 29%). No SGK1-Inh-induced FPD/APD shortening effect was observed in LQT1 KCNQ1-p.A341V hiPSC-CMs or KCNQ1-p.Y315S rabbit CMs at 0.3-3 µM. CONCLUSION A robust SGK1-Inh-induced APD shortening was observed across different LQT2 models, species, and genetic variants but less consistently in LQT1 models. This suggests a genotype- and variant-specific beneficial effect of this novel therapeutic approach in LQTS

NKX2-5 regulates human cardiomyogenesis via a HEY2 dependent transcriptional network.

Congenital heart defects can be caused by mutations in genes that guide cardiac lineage formation. Here, we show deletion of NKX2-5, a critical component of the cardiac gene regulatory network, in human embryonic stem cells (hESCs), results in impaired cardiomyogenesis, failure to activate VCAM1 and to downregulate the progenitor marker PDGFRα. Furthermore, NKX2-5 null cardiomyocytes have abnormal physiology, with asynchronous contractions and altered action potentials. Molecular profiling and genetic rescue experiments demonstrate that the bHLH protein HEY2 is a key mediator of NKX2-5 function during human cardiomyogenesis. These findings identify HEY2 as a novel component of the NKX2-5 cardiac transcriptional network, providing tangible evidence that hESC models can decipher the complex pathways that regulate early stage human heart development. These data provide a human context for the evaluation of pathogenic mutations in congenital heart disease.Nat Commun 2018 Apr 10; 9(1):1373

Chronically elevated branched chain amino acid levels are pro-arrhythmic

Aims. Cardiac arrhythmias comprise a major health and economic burden and are associated with significant morbidity and mortality, including cardiac failure, stroke, and sudden cardiac death (SCD). Development of efficient preventive and therapeutic strategies is hampered by incomplete knowledge of disease mechanisms and pathways. Our aim is to identify novel mechanisms underlying cardiac arrhythmia and SCD using an unbiased approach. Methods and results. We employed a phenotype-driven N-ethyl-N-nitrosourea mutagenesis screen and identified a mouse line with a high incidence of sudden death at young age (6–9 weeks) in the absence of prior symptoms. Affected mice were found to be homozygous for the nonsense mutation Bcat2p.Q300*/p.Q300* in the Bcat2 gene encoding branched chain amino acid transaminase 2. At the age of 4–5 weeks, Bcat2p.Q300*/p.Q300* mice displayed drastic increase of plasma levels of branch chain amino acids (BCAAs—leucine, isoleucine, valine) due to the incomplete catabolism of BCAAs, in addition to inducible arrhythmias ex vivo as well as cardiac conduction and repolarization disturbances. In line with these findings, plasma BCAA levels were positively correlated to electrocardiogram indices of conduction and repolarization in the German community-based KORA F4 Study. Isolated cardiomyocytes from Bcat2p.Q300*/p.Q300* mice revealed action potential (AP) prolongation, pro-arrhythmic events (early and late afterdepolarizations, triggered APs), and dysregulated calcium homeostasis. Incubation of human pluripotent stem cell-derived cardiomyocytes with elevated concentration of BCAAs induced similar calcium dysregulation and pro-arrhythmic events which were prevented by rapamycin, demonstrating the crucial involvement of mTOR pathway activation. Conclusions. Our findings identify for the first time a causative link between elevated BCAAs and arrhythmia, which has implications for arrhythmogenesis in conditions associated with BCAA metabolism dysregulation such as diabetes, metabolic syndrome, and heart failure

Predicting needlestick and sharps injuries in nursing students: Development of the SNNIP scale

© 2020 The Authors. Nursing Open published by John Wiley & Sons Ltd. Aim: To develop an instrument to investigate knowledge and predictive factors of needlestick and sharps injuries (NSIs) in nursing students during clinical placements. Design: Instrument development and cross-sectional study for psychometric testing. Methods: A self-administered instrument including demographic data, injury epidemiology and predictive factors of NSIs was developed between October 2018–January 2019. Content validity was assessed by a panel of experts. The instrument's factor structure and discriminant validity were explored using principal components analysis. The STROBE guidelines were followed. Results: Evidence of content validity was found (S-CVI 0.75; I-CVI 0.50–1.00). A three-factor structure was shown by exploratory factor analysis. Of the 238 participants, 39% had been injured at least once, of which 67.3% in the second year. Higher perceptions of “personal exposure” (4.06, SD 3.78) were reported by third-year students. Higher scores for “perceived benefits” of preventive behaviours (13.6, SD 1.46) were reported by second-year students

Development of a hybrid simulator for underwater vehicle

This work presents the study of a hybrid simulator for underwater vehicles (specifically Remotely Operated Vehicle). The document is divided in three parts. In the first one we will describe the state of the art and in particular the control systems necessary to perform specific tasks, then, the second one presents the simulator chosen - Virtual Robot Experimentation Platform - with preliminary tests carried out to validate its feasibility of use in marine environments and of complex structures. Finally we will describe the integration of the dynamic model of the vehicle - implemented in Simulink - and the simulator itself. In the last part, some of the controls highlighted above will be implemented, showing the proper functioning of the global system and the simulation in particular. In questa tesi viene presentato lo studio di un simulatore ibrido per veicoli sottomarini (nello specifico Remotely Operated Vehicle). Dopo una prima parte di approfondimento sullo stato dell'arte ed in particolare sulle metodologie di controllo necessarie per effettuare specifici task, verrà presentato il simulatore scelto - Virtual Robot Experimentation Platform - insieme a test preliminari effettuati per validare l'effettiva fattibilità di utilizzo in ambientazioni marine e su strutture complesse. Infine verrà descritta l'integrazione tra il modello dinamico del veicolo - implementato in Simulink - ed il simulatore stesso. Nell'ultima parte, alcuni dei controlli evidenziati in precedenza verranno implementati, mostrando il corretto funzionamento del sistema globale e della simulazione in particolare