Respiratory simulator for robotic respiratory tract treatments

Robotic healthcare is a growing and multi-faceted field where robots help perform surgery, remotely provide care to patients, aid in supplying various physical therapies and further medical research. Robotic simulators of human physiology provide a powerful platform to advance the development of novel treatments, prostheses and therapies. This study focuses on the design, building, testing and characterisation of a novel simulator of the human respiratory system. The comparison between healthy subjects breathing and coughing physiological values and the values achieved utilising our novel bioinspired respiratory simulator shows that the latter is able to reproduce peak flow rates and volumes

A Bioinspired Active Robotic Simulator of the Human Respiratory System

Pathologies affecting the respiratory system can lead to a debilitating decrease in quality of life and can be fatal. To test medical devices and implants for the human respiratory system, a simulation system that can reproduce multiple respiratory features is necessary. Currently available respiratory simulators only focus on reproducing flow rate profiles of breathing while coughing simulators focus on aerosol analysis. In this paper we propose a novel, bioinspired robotic simulator that can physically replicate both breathing and coughing flow rate characteristics of healthy adults. We conducted a study on 31 healthy adult participants to gather the flow rate measurement of normal breathing, deep breathing, breathing while running and coughing. Coughing flow rate profiles vary considerably between participants, making an accurate simulation of coughs a challenge. To enable cough flow rate simulation, a new methodology based on the identification of four cough phases, Attack, Decay, Sustain and Release (ADSR) and their parametrization was devised. This methodology leads to the unprecedented ability to reproduce diverse and complex coughing flow rate profiles. Our simulator is able to reproduce respiratory flows with a root mean square error (RMSE) of 1.8 L/min between normal participant breathing and its simulation, 5% of the maximum flow rate simulated for that participant (pMFR), an RMSE of 10.08 L/min for deep breathing, 18% of the pMFR and an RMSE of 13.29 L/min for exertion breathing, 17% of pMFR. For the simulation of an average cough we recorded an RMSE of 51.43 L/min, 13% of the pMFR and for a low flow rate cough an RMSE of 12.38 L/min, 9.5% of the pMFR. The presented simulator matches the fundamentals of human breathing and coughing, advancing the current capability of respiratory system simulators

Magnetic nanoparticles for magnetically guided therapies against neural diseases

Neurological pathologies and nerve damage are two problems of significant medical and economic impact because of the hurdles of losing nerve functionality in addition to significant mortality and morbidity, and demanding rehabilitation. There are currently a number of examples of how nanotechnology can provide new solutions for biomedical problems. Current strategies for nerve repair rely on the use of functionalized scaffolds working as nerve guidance channels to improve axonal regeneration and to direct axonal re-growth across the nerve lesion site. Since low invasiveness and high selectivity of the growth stimulation are usually conflicting requirements, new approaches are being pursued in order to overcome such limitations. Engineered magnetic nanoparticles (MNPs) have emerged from this need for noninvasive therapies for both positioning and guiding neural cells in response to an external magnetic field. Here, we review the current state of the use of MNPs for neuroprotective and magnetically guided therapies. We discuss some conceivable outcomes of current magnetically driven strategies seeking integrated platforms for regenerative action on damaged tissues

Focus on Human Monoamine Transporter Selectivity. New Human DAT and NET Models, Experimental Validation, and SERT Affinity Exploration

The most commonly used antidepressant drugs are the serotonin transporter inhibitors. Their effects depend strongly on the selectivity for a single monoamine transporter compared to other amine transporters or receptors, and the selectivity is roughly influenced by the spatial protein structure. Here, we provide a computational study on three human monoamine transporters, i.e., DAT, NET, and SERT. Starting from the construction of hDAT and hNET models, whose three-dimensional structure is unknown, and the prediction of the binding pose for 19 known inhibitors, 3D-QSAR models of three human transporters were built. The training set variability, which was high in structure and activity profile, was validated using a set of in-house compounds. Results concern more than one aspect. First of all, hDAT and hNET three-dimensional structures were built, validated, and compared to the hSERT one; second, the computational study highlighted the differences in binding site arrangement statistically correlated to inhibitor selectivity; third, the profiling of new inhibitors pointed out a conservation of the inhibitory activity trend between rabbit and human SERT with a difference of about 1 order of magnitude; fourth, binding and functional studies confirmed 4-(benzyloxy)-4-phenylpiperidine 20a-d and 21a-d as potent SERT inhibitors. In particular, one of the compounds (compound 20b) revealed a higher affinity for SERT than paroxetine in human platelets

Salivary psoriasin (S100A7) correlates with diffusion capacity of carbon monoxide in a large cohort of systemic sclerosis patients

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive fibrosis of the skin and the internal organs. In a previous work we suggested a correlation between levels of salivary psoriasin (S100A7) and pulmonary involvement in SSc patients. The goals of this study are to determine the distribution characteristics of psoriasin in whole saliva (WS) of SSc and healthy donor populations and define its predictive value on diffusion capacity of carbon monoxide (DLCO), along with others clinical parameters. Methods: Salivary level of psoriasin was determined by ELISA kit in 134 SSc patients, 63 Raynaud syndrome patients, 40 patients affected by other connective diseases (non-case) and 74 healthy control subjects. Results: A significant increase of salivary psoriasin was observed in SSc patients when compared with other healthy and pathological controls. Moreover, we confirmed the efficacy of salivary psoriasin to correlate with DLCO in a large cohort of SSc patients. Conclusions: Overall our results suggest a rapid, non invasive and low costing method which can help clinicians in the evaluation of SSc pulmonary involvement

Effect of honey and syrup diets enriched with 1,3-1,6 β-glucans on honeybee survival rate and phenoloxidase activity (Apis mellifera l. 1758)

β-glucans can activate the animal innate immune system by acting as immune-modulators and inducing various stimulatory effects. The aim of this study was to investigate the effect of 1,3-1,6 β-glucans administered orally for 96 h on Apis mellifera workers (newly emerged and nurse bees). β-glucans were included in honey and syrup. Survival rate and phenoloxidase activity were measured. In both newly emerged and nurse bees, β-glucans supplementation did not affect survival rate (p > 0.05). Conversely, phenoloxidase activity was higher in both newly emerged bees (p = 0.048) and nurse bees (p = 0.014) fed with a honey diet enriched with β-glucans compared to those fed with only honey. In both the newly emerged and nurse bees, no statistical differences in phenoloxidase activity were recorded between the group fed with a syrup-based diet enriched with β-glucans and the control group (p > 0.05). The absence of significant variation in survival suggests that the potential negative effect of β-glucans in healthy bees could be mitigated by their metabolism. Conversely, the inclusion of β-glucans in a honey-based diet determined an increase of phenoloxidase activity, suggesting that the effect of β-glucan inclusion in the diet of healthy bees on phenoloxidase activity could be linked to the type of base-diet. Further investigations on β-glucans metabolism in bees, on molecular mechanism of phenoloxidase activation by 1,3-1,6 β-glucans, and relative thresholds are desirable. Moreover, investigation on the combined action of honey and β-glucans on phenoloxidase activity are needed

Design and control of a novel variable stiffness soft arm

Soft robot arms possess such characteristics as light weight, simple structure and good adaptability to the environment, among others. On the other hand, robust control of soft robot arms presents many difficulties. Based on these reasons, this paper presents a novel design and modelling of a fuzzy active disturbance rejection control (FADRC) controller for a soft PAM arm. The soft arm comprises three contractile and one extensor PAMs, which can vary its stiffness independently of its position in space. Force analysis for the soft arm is conducted, and stiffness model of the arm is established based on the relational model of contractile and extensor PAM. The accuracy of stiffness model for the soft arm was verified through experiments. Associated to this, a controller based on the fuzzy adaptive theory and ADRC, FADRC, has been designed to control the arm. The fuzzy adaptive theory is used to adjust the parameters of the ADRC, the control algorithm has the ability to control stiffness and position of the soft arm. In this paper, FADRC was further verified through comparative experiments on the soft arm. This paper reinforces the hypothesis that FADRC control, as an algorithm, indeed possesses good robustness and adaptive abilities. Key words: soft robot, variable stiffness, PAM, stiffness modelling, FADR

Palmitate-induced lipotoxicity alters acetylation of multiple proteins in clonal β cells and human pancreatic islets

Type 2 diabetes is characterized by progressive β cell dysfunction, with lipotoxicity playing a possible pathogenetic role. Palmitate is often used to examine the direct effects of lipotoxicity and it may cause mitochondrial alterations by activating protein acetylation. However, it is unknown whether palmitate influences protein acetylation in β cells. We investigated lysine acetylation in mitochondrial proteins from INS-1E β cells (INS-1E) and in proteins from human pancreatic islets (HPI) after 24 h palmitate exposure. First, we confirmed that palmitate damages β cells and demonstrated that chemical inhibition of deacetylation also impairs INS-1E function and survival. Then, by 2-D gel electrophoresis, Western Blot and Liquid Chromatography-Mass Spectrometry we evaluated the effects of palmitate on protein acetylation. In mitochondrial preparations from palmitate-treated INS-1E, 32 acetylated spots were detected, with 13 proteins resulting over-acetylated. In HPI, 136 acetylated proteins were found, of which 11 were over-acetylated upon culture with palmitate. Interestingly, three proteins, glutamate dehydrogenase, mitochondrial superoxide dismutase, and SREBP-1, were over-acetylated in both INS-1E and HPI. Therefore, prolonged exposure to palmitate induces changes in β cell protein lysine acetylation and this modification could play a role in causing β cell damage. Dysregulated acetylation may be a target to counteract palmitate-induced β cell lipotoxicity

Melatonin and pro-hypnotic effectiveness of the antidepressant Trazodone: A preliminary evaluation in insomniac mood-disorder patients

Objective To preliminary investigate the link between the darkness hormone melatonin (MLT) and the pro-hypnotic effectiveness of the atypical antidepressant Trazodone (TRZ) in a group of mood disorder patients suffering of insomnia. Design and methods The study's design comprised: i) the enrolment of insomniac outpatients, ii) baseline (t0) psychiatric and biochemical examinations; iii) the subsequent patients' introduction into a treatment with TRZ for 3–4 weeks, followed by post-therapy re-evaluations (t1). The MLT function was investigated by t0/t1 ELISA determinations of 6-hydroxy-MLT sulfate (6-OH-MLTs) levels in early-morning urines and HPLC analysis of morning MLT serum amount. Concomitantly, TRZ and its metabolite m-chloro-phenylpiperazine (m-CPP) were measured by HPLC in serum to monitor patients' compliance/metabolism. Results Seventeen insomniac outpatients, displaying mild symptoms of depression/anxiety resistant to antidepressants, completed TRZ therapy (dose:10–20 mg/day, bedtime). Serum TRZ levels (127 ± 57 ng ml− 1, mean ± SD) confirmed patients' compliance, while the anxiogenic metabolite m-CPP resulting almost undetectable. Moreover, the 6-OH-MLTs output was found increased at t1 vs. baseline values (t1: 58.4 ± 45.02 ng ml− 1; t0: 28.6 ± 15.8 ng ml− 1; mean ± SD, P < 0.05) in 9 patients who recovered both insomnia and depression/anxiety (P < 0.01). Unresponsive subjects showed instead no post-therapy 6-OH-MLTs variation (t1: 48.53 ± 50.70 ng ml− 1; t0: 49.80 ± 66.53 ng ml− 1). Morning MLT in serum slightly diminished at t1 without reaching the statistical significance, not allowing therefore to define the patients' outcome. Conclusions This initial investigation encourages to explore MLT networks as possible correlates of TRZ pro-hypnotic responses