Background: Antibodies against aquaporin-4 (AQP4), a water channel particularly expressed on perivascular astrocytic podocytes, are proposed as a marker for the diagnosis of neuromyelitis optica ...(NMO). However, a consensus on seroprevalence and optimal detection method has not yet been reached.
Objectives: To investigate the performance of different assays to detect anti-AQP4 antibodies.
Methods: We set up five different assays. Two of them were capable to detect perivascular IgG reactivity on brain tissue by immunofluorescence (NMO-IgG). Other three assays have been set to detect anti-AQP4 antibodies: immunofluorescence and flow cytometry on AQP4-expressing cells, and a radioimmunoprecipitation assay. We assessed sensitivity and specificity of these assays by interrogating sera of 33 NMO patients, 13 patients at high risk to develop NMO (hrNMO), 6 patients affected by acute partial transverse myelitis (APTM), 20 patients with multiple sclerosis (MS), and 67 age- and sex-matched healthy controls.
Results: We found that the presence of serum NMO-IgG and anti-AQP4 reactivity is almost exclusively restricted to patients with NMO and hrNMO. Seroprevalence and sensitivity ranged from 30 to 47%, depending on the assay. Specificity ranged from 95 to 100%. Comparing results obtained in the five assays, we noticed lack of concordance in some samples.
Conclusions: Detection of NMO-IgG or anti-AQP4 antibodies may represent a valuable tool to assist neurologists in the differential diagnosis between patients with NMO, hrNMO, APTM, or MS. The current lack of a gold standard to detect anti-AQP4 antibodies implies the necessity to standardize the detection of these antibodies.
The aim of this study was to investigate liver microvascular adaptation following the intraportal infusion of pancreatic islets (pancreatic islet transplantation islet‐tx) in diabetic patients using ...dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI). DCE‐MRI was performed before and 7 days after islet‐tx in six diabetic patients. Initial area under curve (AUC60) and volume transfer coefficient (Ktrans) were assessed as markers of liver perfusion. Clinical and metabolic monthly follow‐up was performed in all patients, considering fasting C‐peptide and β‐score as main indices of graft function. High variability in the response of liver microvasculature to islet infusion was observed: two patients showed a significant reduction in liver perfusion after transplantation (pt.2: AUC60 = −23.4%, Ktrans = −31.7%; pt.4: AUC60 = −23.7%, Ktrans = −27.9%); three patients did not show any significant variation of liver perfusion and one patient showed a significant increase (pt.3: AUC60 = +31%, Ktrans = +42.8%). Interestingly, a correlation between DCE‐MRI parameters and indices of graft function was observed and, in particular, both patients with DCE‐MRI evidence of posttransplantation liver perfusion reduction experienced premature graft failure. Our preliminary study demonstrated that DCE‐MRI may identify different adaptive responses of liver microvasculature in patients submitted to islet‐tx. These different responses could have an impact on islet engraftment, although reported findings need confirmation from larger studies.
This study shows that dynamic contrast‐enhanced magnetic resonance imaging identifies various adaptive responses of the liver microvasculature in islet transplant recipients and that these responses might have an impact on islet engraftment.
A large number of people in the world need to use a wheelchair because of different disabilities. Driving a wheelchair requires complex physical and cognitive abilities which need to be trained. ...Virtual training helps users acquire driving skills in a safe environment. The aim of this paper is to describe and technically validate simulation models for both manual (MW) and powered wheelchairs (PW) based on immersive virtual reality CAVE (VR). As VR system, the Gait Real-time Analysis Interactive Lab (GRAIL) was used, a CAVE equipped with a motion platform with two degrees of freedom and an optoelectronic motion capture system. A real wheelchair was positioned onto the motion platform with rear wheels free to turn in MW modality, and a commercial joystick was installed on an armrest to simulate the PW modality. Passive markers were used to track the wheel rotation, the joystick and the user hand motion. Custom D-flow applications were developed to manage virtual scene response to user actions. Overground tests, based on single wheel rotation, were performed to verify the simulation model reliability. Quantitative results demonstrated that the MW simulator kinematics was consistent with a real wheelchair overground in the absence of wheel slip and inertia (median error for MW 0.40 °, no systematic bias
p
= 0.943, high correlation rho > 0.999,
p
< 0.01). The proposed solution is flexible and adaptable to different wheelchairs, joysticks and optoelectronic systems. The main limitation is the absence of force feedback. Nevertheless, it is a reliable prototype that can be used to validate new virtual scenarios as well as for wheelchair training. The next steps include the system validation with real end users and assessment of the simulator effectiveness as a training tool.
Islet transplantation is an effective therapy for restoring normoglycemia in type‐1 diabetes, but long‐term islet graft function is achieved only in a minority of cases. Noninvasive magnetic ...resonance imaging of pancreatic islets is an attractive option for “real‐time” monitoring of graft evolution. So far, previous studies have been performed in the absence of a standardized labeling procedure and, besides a feasibility study in patients, the effectiveness and safety of various labeling approaches were tested only with high field magnets (4.7 T). In this study, we addressed: (a) standardization of a labeling procedure for human islets with clinically‐approved contrast agent Endorem®, (b) safety aspects of labeling related to inflammation and (c) quality of imaging both at 7 T and 1.5 T. We have highlighted that the ratio of Endorem®/islet is crucial for reproducible labeling, with a ratio of 2.24 ug/IEQ, allowing successful in vivo imaging both with 1.5 T and 7.0 T magnets up to 143 days after intrahepatic transplant. With this standardized labeling procedure, labeled islets are neither inflamed nor more susceptible to inflammatory insults than unlabeled ones. This report represents an important contribution towards the development of a standardized and safe clinical protocol for the noninvasive imaging of transplanted islets in humans.
A standardized labeling procedure proved to be both safe and effective for imaging transplanted islets by MRI.
Robot-assisted training is a widely used technique to promote motor re-learning on post-stroke patients that suffer from motor impairment. While it is commonly accepted that robot-based therapies are ...potentially helpful, strong insights about their efficacy are still lacking. The motor re-learning process may act on muscular synergies, which are groups of co-activating muscles that, being controlled as a synergic group, allow simplifying the problem of motor control. In fact, by coordinating a reduced amount of neural signals, complex motor patterns can be elicited. This paper aims at analyzing the effects of robot assistance during 3D-reaching movements in the framework of muscular synergies. 5 healthy people and 3 neurological patients performed free and robot-assisted reaching movements at 2 different speeds (slow and quasi-physiological). EMG recordings were used to extract muscular synergies. Results indicate that the interaction with the robot very slightly alters healthy people patterns but, on the contrary, it may promote the emergency of physiological-like synergies on neurological patients.
Aims/hypothesis We investigated, in three beta cell lines (INS-1E, RIN-5AH, betaTC3) and in human and rodent primary beta cells, the storage and release of chromogranin B, a secretory protein ...expressed in beta cells and postulated to play an autocrine role. We asked whether chromogranin B is stored together with and discharged in constant ratio to insulin upon various stimuli. Methods The intracellular distribution of insulin and chromogranin B was revealed by immunofluorescence followed by three-dimensional image reconstruction and by immunoelectron microscopy; their stimulated discharge was measured by ELISA and immunoblot analysis of homogenates and incubation media. Results Insulin and chromogranin B, co-localised in the Golgi complex/trans-Golgi network, appeared largely segregated from each other in the secretory granule compartment. In INS-1E cells, the percentage of granules positive only for insulin or chromogranin B and of those positive for both was 66, 7 and 27%, respectively. In resting cells, both insulin and chromogranin B were concentrated in the granule cores; upon stimulation, chromogranin B (but not insulin) was largely redistributed to the core periphery and the surrounding halo. Strong stimulation with a secretagogue mixture induced parallel release of insulin and chromogranin B, whereas with 3-isobutyl-1-methylxantine and forskolin ± high glucose release of chromogranin B predominated. Weak, Ca²⁺-dependent stimulation with ionomycin or carbachol induced exclusive release of chromogranin B, suggesting a higher Ca²⁺ sensitivity of the specific granules. Conclusions/interpretation The unexpected complexity of the beta cell granule population in terms of heterogeneity, molecular plasticity and the differential discharge, could play an important role in physiological control of insulin release and possibly also in beta cell pathology.
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