Kinematics of aimed movements in ecological immersive virtual reality: a comparative study with real world

Virtual reality (VR) has recently emerged as a promising technology to rehabilitate upper limb functions after stroke. To promote the recovery of functions, retraining physiological movement patterns is essential. However, it is still unclear whether VR can elicit functional movements that are similar to those performed in the real world (RW). This study aimed to investigate the kinematics of reach-to-grasp and transport movements performed in the real world and immersive VR by examining whether kinematic differences between the two conditions exist and their extent. A within-subject repeated-measures study was conducted. A realistic setup resembling a supermarket shelf unit was built in RW and VR. The analysis compared reaching and transport gestures in VR and RW, also considering potential differences due to: (i) holding the controller needed to interact with virtual items, (ii) hand dominance, and (iii) target positions. Ten healthy young adults were enrolled in the study. Motion data analysis showed that reach-to-grasp and transport required more time in VR, and that holding the controller had no effects. No major differences occurred between the two hands. Joint angles, except for thorax rotation, and hand trajectory curvature were comparable across conditions, suggesting that VR has the potentialities to retrain physiological movement patterns. Results were satisfying, though they did not demonstrate the superiority of ecological environments in eliciting natural gestures. Further studies should determine the extent of kinematic similarity required to obtain functional gains in VR-based upper limb rehabilitation

TNFα expressed on the surface of microparticles modulates endothelial cell fate in rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is associated with a high prevalence of atherosclerosis. Recently increased levels of microparticles (MPs) have been reported in patients with RA. MPs could represent a link between autoimmunity and endothelial dysfunction by expressing tumor necrosis factor alpha (TNFα), a key cytokine involved in the pathogenesis of RA, altering endothelial apoptosis and autophagy. The aim of this study was to investigate TNFα expression on MPs and its relationship with endothelial cell fate. Methods: MPs were purified from peripheral blood from 20 healthy controls (HC) and from 20 patients with RA, before (time (T)0) and after (T4) 4-month treatment with etanercept (ETA). Surface expression of TNFα was performed by flow cytometry analysis. EA.hy926 cells, an immortalized endothelial cell line, were treated with RA-MPs purified at T0 and at T4 and also, with RA-MPs in vitro treated with ETA. Apoptosis and autophagy were then evaluated. Results: RA-MPs purified at T0 expressed TNFα on their surface and this expression significantly decreased at T4. Moreover, at T0 RA-MPs, significantly increased both apoptosis and autophagy levels on endothelial cells, in a dose-dependent manner. RA-MPs did not significantly change these parameters after 4 months of in vivo treatment with ETA. Conclusions: Our data demonstrate that MPs isolated from patients with RA exert a pathological effect on endothelial cells by TNFα expressed on their surface. In vivo and in vitro treatment with ETA modulates this effect, suggesting anti-TNF therapy protects against endothelial damage in patients with RA

PhotoMEA: development of optical tools for the study of the functional properties of neuronal networks

A large number of studies on neuronal physiology and plasticity have provided a detailed picture of the molecular machinery underlying the modulation of neuronal activity. On the contrary, the mechanisms controlling properties of complex neuronal networks remain poorly understood. At present, the neuronal functional properties are investigated either by a large-scale approach (i.e. MicroElectrode Array devices, MEAs) that enables the study of the general activity of a complex neuronal network, or alternatively by a micro-scale approach (i.e. intracellular or patch electrodes) suitable for the detailed analysis of the molecular mechanisms that actively contribute to the generation and modulation of the single neuron activity. Systems based on electrodes have yielded important results in neurophysiology, but now they start to show some severe limits, such as the possibility of inducing cellular damage in the case of intracellular electrodes and the poor spatial resolution in the case of MEAs. Optical methods for neuronal stimulation, e.g. using caged compounds, and for neuronal activity recording, e.g. using Voltage-Sensitive fluorescent Dyes (VSDs), can be useful tools to overcome these limits. Local light stimulations are obtained activating caged glutamate by UV light pulses. Single neurons or selected parts of them can be stimulated using optical fibres micro-positioned in the neuronal culture or optical waveguides micro-structured in the glass coverslip, on which the neurons are cultured, to precisely drive UV light. Optical recordings of the electrical activity from the entire network are performed using di-4-ANEPPS Voltage-Sensitive Dye and a standard epi-fluorescence microscope equipped with a dedicated large-sensor high-speed camera. Combining these two optical methods the micro-scale approach (stimulation) meets the large-scale approach (recording). This methodology may turn out to be extremely useful for testing the ability of drugs to affect neuronal properties as well as alterations in inter- and intra-neuronal communication

PhotoMEA: a new optical biosensor for the study of the functional properties of neuronal networks

Technological innovations in the fields of biomedical optics and electronics have lead to an extremely high level of miniaturization. These steps opened important perspectives to interface optoelectronic instruments with cellular systems. In this frame, a patent was registered for a novel optoelectronic technological solution, named PhotoMEA, for the study of the neuronal activity in culture, in order to understand the physiological and pathological functioning of neuronal networks. At present, the neuronal functional properties are investigated either by a large-scale approach (i.e. MicroElectrode Array devices, MEAs) that enables the study of the general activity of a complex neuronal network, or alternatively by a micro-scale approach (i.e. intracellular or patch electrodes) suitable for the detailed analysis of the molecular mechanisms that actively contribute to the generation and modulation of the single neuron activity. Systems based on electrodes have yielded important results in neurophysiology, but now they start to show some severe limits, such as the possibility of inducing cellular damage in the case of intracellular electrodes and the poor spatial resolution in the case of MEAs. The PhotoMEA device combines two optical tools for studying the functional properties of in-vitro neuronal networks. Light stimulation and optical recording of neuronal activity are promising approaches for investigating the molecular mechanisms at the basis of neuronal physiology. In particular, flash photolysis of caged compounds offers the unique advantage of allowing to quickly change the concentration of either intracellular or extracellular bioactive molecules, such as neurotransmitters or second messengers, for the stimulation or modulation of neuronal activity. Moreover, optical recordings of neuronal activity by Voltage-Sensitive Dyes (VSDs) allow to follow changes of neuronal membrane potential with high-spatial resolution. This enables the study of the sub-cellular responses and that of the entire network at the same time. Combining these two optical methods the micro-scale approach (stimulation) meets the large-scale approach (recording). This methodology may be extremely useful for testing the ability of drugs to affect neuronal properties as well as alterations in inter- and intra-neuronal communication

PhotoMEA: An opto-electronic biosensor for monitoring in vitro neuronal networks activity

PhotoMEA is a biosensor useful for the analysis of an in vitro neuronal network, fully based on optical methods. Its function is based on the stimulation of neurons with caged-glutamate and the recording of neuronal activity by fluorescence Voltage-Sensitive Dyes. The main advantage is that it will be possible to stimulate even at sub-single neuron level and to record with high resolution the activity of the entire network in the culture. A large-scale view of neuronal intercommunications offers a unique opportunity for testing the ability of drugs to affect neuronal properties as well as alterations in the behaviour of the entire network. The concept and a prototype for validation is described here in details

PhotoMEA: A New Step Towards Total Optical Analysis of In Vitro Neuronal Networks

Light stimulation of neurons is a promising approach for investigating the molecular mechanisms at the basis of neuronal physiology and plasticity. In particular, flash photolysis of caged compounds offers the unique advantage of allowing to quickly change the concentration of either intracellular or extracellular bioactive molecules, such as neurotransmitters or second messengers, for the stimulation or modulation of neuronal activity. In this field of research, we describe a simple laser-based set-up for the local activation of caged compounds. The coupling of a UV laser diode to a small-core optical fibre allows to reduce the uncaging area and to quickly change the stimulation point. The actual localisation of the light stimulation is determined using a caged fluorescent compound (dextran, DMNB-caged fluorescein). The efficiency of our set up for neuronal stimulation is tested with a caged neurotransmitter (MNI-caged-L-glutamate). Activation of caged glutamate evokes neuronal responses that are recorded using a MicroElectrode Array system and/or following the variations in the concentrations of the Cai 2+ . This work shows that our laser-based set-up is a powerful tool for local activation of caged compound allowing a unique opportunity to follow the effects of local neuronal pathways on neuronal network activity, for instance during pharmacological and toxicological treatments

A new optical tool to combine optical and electrical analysis in neuronal drug screening

Since their introduction 30 years ago, Micro-Electrode Arrays (MEAs) have been exploited as devices providing distributed information about learning, memory and information processing in a cultured neuronal network, thus changing the field of view from the scale of the single cell (glass pipettes) to the scale of the complex network properties. MEAs represent a growing technology for the study of the functional activity of neuronal networks in a large-scale view providing the possibility (a) to gain information about the spatio-temporal dynamics of the neuronal network, (b) to allow recordings of electrical activity over periods of time not compatible with conventional electrodes and (c) to monitor network activity at several sites in parallel. More recently, according to the trend aimed at the reduction of animal tests, MEAs have been exploited as in vitro biosensors to monitor both acute and chronic effects of drugs and toxins on neuronal networks in physiological or pathophysiological conditions. Now, optical methods for neuronal stimulation, e.g. using caged compounds, represent an useful tools to overcome the limits affecting the MEA technology. Here, local light stimulations were obtained switching caged glutamate in the active form by UV light pulses using optical fibres exactly aligned at the MEA electrodes. This approach allows us to activate the network or to delivery other active compounds in specific regions of the network and to monitor their effects on the overall network functioning. Combining these two optical (stimulation) and electrical (detection) methods a micro-scale approach (stimulation) meets a large-scale approach (detection). This methodology may turn out to be extremely useful for testing the ability of drugs and toxins to affect neuronal properties as well as alterations in inter- and intra-neuronal communication. In this frame, a patent was registered for this novel optoelectronic technological solution for the study of the neuronal activity in culture, in order to understand the physiological and pathological functioning of neuronal networks

Relationship between retinal microvascular impairment and subclinical atherosclerosis in SLE

objectives: patients with SLE have higher cardiovascular (CV) risk compared with healthy controls (HC) and are characterised by accelerated atherosclerosis; intima media thickness (IMT), marker of subclinical atherosclerosis, is higher in patients with SLE than in HCs. Retinal microvascular impairment detected through optical coherence tomography angiography (OCTA) was investigated as a marker of systemic vascular involvement in SLE.the aim of the study was to evaluate the relationship between retinal vascular impairment and IMT in SLE. methods: cross-sectional study recruiting patients with SLE and HCs. Data of the study population were collected. CV risk was evaluated through the american college of cardiology/american heart association (ACC/AHA) guidelines, framingham and QRESEARCH risk estimator V.3 (QRISK3) scores. Both groups underwent OCTA and carotid ultrasound with IMT assessment.Statistical analysis was accomplished using Pearson/Spearman, t-test/Mann-Whitney or χ2 test. Variables statistically significant at univariate regression analysis were tested in an age-corrected and sex-corrected multivariate regression model. results: 43 patients with SLE and 34 HCs were recruited.patients with SLE showed higher triglycerides (p=0.019), triglycerides-glucose (TyG) Index (p=0.035), ACC/AHA guidelines (p=0.001), Framingham Risk Scores (p=0.008) and a reduced superficial (p<0.001) and deep (p=0.005) whole retinal vessel density (VD) compared with HCs.In SLE univariate analysis, deep whole VD showed a negative correlation with IMT (p=0.027), age (p=0.001), systolic blood pressure (p=0.011), QRISK3 Score (p<0.001), systemic lupus international collaborating clinics damage index (p=0.006) and apolipoprotein B (p=0.021), while a positive correlation was found with female sex (p=0.029). Age-adjusted and sex-adjusted multivariate analysis confirmed QRISK3 score (p=0.049) and IMT (p=0.039) to be independent risk factors for reduced retinal VD. conclusions: patients with SLE showed lower retinal VD and higher CV risk indicators compared with HCs. Among patients with SLE, QRISK3 Score and IMT were found to be independent risk factors for retinal vascular impairment, suggesting a role of OCTA in evaluating preclinical CV involvement in SLE. moreover, TyG index could represent a biomarker of CV risk in patients with SLE compared with HCs

Deep learning-based overall survival prediction model in patients with rare cancer: a case study for primary central nervous system lymphoma

Purpose Primary central nervous system lymphoma (PCNSL) is a rare, aggressive form of extranodal non-Hodgkin lymphoma. To predict the overall survival (OS) in advance is of utmost importance as it has the potential to aid clinical decision-making. Though radiomics-based machine learning (ML) has demonstrated the promising performance in PCNSL, it demands large amounts of manual feature extraction efforts from magnetic resonance images beforehand. deep learning (DL) overcomes this limitation.Methods In this paper, we tailored the 3D ResNet to predict the OS of patients with PCNSL. To overcome the limitation of data sparsity, we introduced data augmentation and transfer learning, and we evaluated the results using r stratified k-fold cross-validation. To explain the results of our model, gradient-weighted class activation mapping was applied.Results We obtained the best performance (the standard error) on post-contrast T1-weighted (T1Gd)-area under curve = 0.81(0.03), accuracy = 0.87(0.07), precision = 0.88(0.07), recall = 0.88(0.07) and F1-score = 0.87(0.07), while compared with ML-based models on clinical data and radiomics data, respectively, further confirming the stability of our model. Also, we observed that PCNSL is a whole-brain disease and in the cases where the OS is less than 1 year, it is more difficult to distinguish the tumor boundary from the normal part of the brain, which is consistent with the clinical outcome.Conclusions All these findings indicate that T1Gd can improve prognosis predictions of patients with PCNSL. To the best of our knowledge, this is the first time to use DL to explain model patterns in OS classification of patients with PCNSL. Future work would involve collecting more data of patients with PCNSL, or additional retrospective studies on different patient populations with rare diseases, to further promote the clinical role of our model