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Background Mesenchymal stromal cells (MSCs) are able to migrate and engraft at sites of inflammation, injuries, and tumours, but little is known about their fate after local injection. The purpose of this study is to perform MSC tracking, combining in vivo 7-T magnetic resonance imaging (MRI) and histological assessment, following lung injection in a rat model. Methods Five lungs were injected with ferumoxide-labelled MSCs and five with perfluorocarbon-labelled MSCs and underwent 7-T MRI. MRI acquisitions were recorded immediately (T0), at 24 h (T24) and/or 48 h (T48) after injection. For each rat, labelled cells were assessed in the main organs by MRI. Target organs were harvested under sterile conditions from rats sacrificed 0, 24, or 48 h after injection and fixed for histological analysis via confocal and structured illumination microscopy. Results Ferumoxide-labelled MSCs were not detectable in the lungs, whereas they were not visible in the distant sites. Perfluorocarbon-labelled MSCs were seen in 5/5 injected lungs at T0, in 1/2 at T24, and in 1/3 at T48. The fluorine signal in the liver was seen in 3/5 at T0, in 1/2 at T24, and in 2/3 at T48. Post-mortem histology confirmed the presence of MSCs in the injected lung. Conclusions Ferumoxide-labelled cells were not seen at distant sites; a linear decay of injected perfluorocarbon-labelled MSCs was observed at T0, T24, and T48 in the lung. In more than half of the experiments, perfluorocarbon-labelled MSCs scattering to the liver was observed, with a similar decay over time as observed in the lung.

Aim: To evaluate the expression of candidate miRNAs in relation to diabetic polyneuropathy (DPN) and cardiovascular autonomic neuropathy (CAN). Materials & methods: The expression of six candidate miRNAs has been evaluated in 49 Type 2 diabetes patients with neurological evaluation. Results: A higher expression of miR-128a was seen in patients with DPN compared with those without DPN (p = 0.015). miR-155 and miR-499a seemed to be down-expressed in patients with DPN (p = 0.04 and p = 0.05, respectively). A lower expression of miR-155 (p = 0.05) was observed even in patients with CAN with respect to CAN-negative. A higher expression of miR-155 was associated with the rs767649 polymorphism variant allele compared with the wild-type allele (p = 0.03). Conclusion: miR-128a, miR-155 and miR-499a might be involved in diabetic neuropathies development.

Gut microorganisms (microbiota) live in symbiosis with the host and influence human nutrition, metabolism, physiology, and immune development and function. The microbiota prevents pathogen infection to the host, and in turn the host provides a niche for survival. The alteration of gut bacteria composition (dysbiosis) could contribute to the development of immune-mediated diseases by influencing the immune system activation and driving the pro- and anti-inflammatory responses in order to promote or counteract immune reactions. Probiotics are nonpathogenic microorganisms able to interact with the gut microbiota and provide health benefits; their use has recently been exploited to dampen immunological response in several experimental models of autoimmune diseases. Here, we focus on the relationships among commensal bacteria, probiotics, and the gut, describing the main interactions occurring with the immune system and recent data supporting the clinical efficacy of probiotic administration in rheumatoid arthritis, multiple sclerosis, and myasthenia gravis (MG) animal models. The encouraging results suggest that selected strains of probiotics should be evaluated in clinical trials as adjuvant therapy to restore the disrupted tolerance in myasthenia gravis.

LYVE-1 is 'on stage' now: an emerging player in dendritic cell docking to lymphatic endothelial cells

Gut microorganisms (microbiota) live in symbiosis with the host and influence human nutrition, metabolism, physiology, and immune development and function. The microbiota prevents pathogen infection to the host, and in turn the host provides a niche for survival. The alteration of gut bacteria composition (dysbiosis) could contribute to the development of immune-mediated diseases by influencing the immune system activation and driving the pro- and anti-inflammatory responses in order to promote or counteract immune reactions. Probiotics are nonpathogenic microorganisms able to interact with the gut microbiota and provide health benefits; their use has recently been exploited to dampen immunological response in several experimental models of autoimmune diseases. Here, we focus on the relationships among commensal bacteria, probiotics, and the gut, describing the main interactions occurring with the immune system and recent data supporting the clinical efficacy of probiotic administration in rheumatoid arthritis, multiple sclerosis, and myasthenia gravis (MG) animal models. The encouraging results suggest that selected strains of probiotics should be evaluated in clinical trials as adjuvant therapy to restore the disrupted tolerance in myasthenia gravis.

Probiotics beneficial effects on the host are associated with regulation of the intestinal microbial homeostasis and with modulation of inflammatory immune responses in the gut and in periphery. In this study, we investigated the clinical efficacy of two lactobacillus and two bifidobacterium probiotic strains in experimental autoimmune myasthenia gravis (EAMG) and experimental autoimmune encephalomyelitis (EAE) models, induced in Lewis rats. Treatment with probiotics led to less severe disease manifestation in both models; ex vivo analyses showed preservation of neuromuscular junction in EAMG and myelin content in EAE spinal cord. Immunoregulatory transcripts were found differentially expressed in gut associated lymphoid tissue and in peripheral immunocompetent organs. Feeding EAMG animals with probiotics resulted in increased levels of Transforming Growth Factor-β (TGFβ) in serum, and increased percentages of regulatory T cells (Treg) in peripheral blood leukocyte. Exposure of immature dendritic cells to probiotics induced their maturation toward an immunomodulatory phenotype, and secretion of TGFβ. Our data showed that bifidobacteria and lactobacilli treatment effectively modulates disease symptoms in EAMG and EAE models, and support further investigations to evaluate their use in autoimmune diseases.

This paper presents the Italian guidelines for autoantibody testing in myasthenia gravis that have been developed following a consensus process built on questionnaire-based surveys, internet contacts and discussions during dedicated workshops of the sponsoring Italian Association of Neuroimmunology (AINI). Essential clinical information on myasthenic syndromes, indications and limits of antibody testing, instructions for result interpretation and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

This document presents the guidelines for anti-aquaporin-4 (AQP4) antibody testing that has been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on neuromyelitis optica spectrum disorders, indications and limits of anti-AQP4 antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

Background Among the various stem cell populations used for cell therapy, adult mesenchymal stromal cells (MSCs) have emerged as a major new cell technology. These cells must be tracked after transplantation to monitor their migration within the body and quantify their accumulation at the target site. This study assessed whether rat bone marrow MSCs can be labelled with superparamagnetic iron oxide (SPIO) nanoparticles and perfluorocarbon (PFC) nanoemulsion formulations without altering cell viability and compared magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) results from iron-labelled and fluorine-labelled MSCs, respectively. Methods Of MSCs, 2 × 106 were labelled with Molday ION Rhodamine-B (MIRB) and 2 × 106 were labelled with Cell Sense. Cell viability was evaluated by trypan blue exclusion method. Labelled MSCs were divided into four samples containing increasing cell numbers (0.125 × 106, 0.25 × 106, 0.5 × 106, 1 × 106) and scanned on a 7T MRI: for MIRB-labelled cells, phantoms and cells negative control, T1, T2 and T2* maps were acquired; for Cell Sense labelled cells, phantoms and unlabelled cells, a 19F non-localised single-pulse MRS sequence was acquired. Results In total, 86.8% and 83.6% of MIRB-labelled cells and Cell Sense-labelled cells were viable, respectively. MIRB-labelled cells were visible in all samples with different cell numbers; pellets containing 0.5 × 106 and 1 × 106 of Cell Sense-labelled cells showed a detectable 19F signal. Conclusions Our data support the use of both types of contrast material (SPIO and PFC) for MSCs labelling, although further efforts should be dedicated to improve the efficiency of PFC labelling.

Submitted by Boris Flegr (boris@uerj.br) on 2021-01-05T21:20:27Z No. of bitstreams: 2 Raquel Elena Rinaldi Maciel_Texto completo.pdf: 1191842 bytes, checksum: d476b9387dd8adee6893916a382a27cb (MD5) Raquel Elena Rinaldi Maciel_Parcial.pdf: 495978 bytes, checksum: 55d708ab1c12dfb04aae6e8ce2673ac2 (MD5) Made available in DSpace on 2021-01-05T21:20:27Z (GMT). No. of bitstreams: 2 Raquel Elena Rinaldi Maciel_Texto completo.pdf: 1191842 bytes, checksum: d476b9387dd8adee6893916a382a27cb (MD5) Raquel Elena Rinaldi Maciel_Parcial.pdf: 495978 bytes, checksum: 55d708ab1c12dfb04aae6e8ce2673ac2 (MD5) Previous issue date: 2015-08-26 El trabajo doméstico remunerado es una actividad socialmente devaluada porque concentra una serie de aspectos de la vulnerabilidad y la exclusión social. Tales elementos son revelados en la actividad empírica de esta tesis, y en su mayor parte se concentran en el trabajo de baja remuneración, a plena en las pinturas de explotación, en el desrespecto a los derechos y garantías legales en la discriminación racial y de género, en la falsa idea de que no contribuye a la economía del país, y los resquicios del patriarcado y la esclavitud. Con el hecho de explicar al lector que la categoría de los trabajadores domésticos sufre de insuficiencia de reconocimiento, traemos a la luz de esta tesis la teoría del reconocimiento de Axel Honneth, que trabaja lastres esferas del reconocimiento- el amor, el derecho y la estima social los cuales serán discutidos aquí. Además, la cuestión de trabajo es muy importante porque en el período post fordista está fuertemente marcado por la violación de los derechos laborales O trabalho doméstico remunerado é uma atividade socialmente desvalorizada pois concentra uma série de aspectos de vulnerabilidade e de exclusão social. Tais elementos são revelados na atividade empírica da presente dissertação, e em sua grande maioria concentram-se na baixa remuneração, na ampla jornada de trabalho, em quadros exploratórios, no desrespeito aos direitos e garantias legais, nas discriminações de raça e gênero, na falsa ideia de que não contribui com a economia do país, e, nos resquícios do patriarcado e da escravidão. A fim de explicar ao leitor que a categoria das empregadas domésticas sofre de reconhecimento insuficiente, trazemos a luz da presente dissertação a teoria do reconhecimento de Axel Honneth, que afirma serem três as esferas do reconhecimento - o amor, o direito e a estima social- que serão discutidos aqui. Além disso, a questão do trabalho é de suma importância, pois o período pós fordista é fortemente marcado pela violação dos direitos trabalhistas.

Highlights • Patients were frail and had a high prevalence of serious comorbidities. • Insulin treatment was the most important cause of severe hypoglycemia. • Among oral drugs, glibenclamide and repaglinide were the main used. • The rate of all-cause mortality was similar with that reported in other studies. • Liver and kidney diseases were the main predictors of hospitalization., Aims To describe the characteristics and associated risk factors of patients with established diabetes who required Emergency Department (ED) care for severe hypoglycemia. Methods We performed an observational retrospective study to identify all cases of severe hypoglycemia among attendees at the EDs of three Italian University hospitals from January 2010 to December 2014. Results Overall, 520 patients with established diabetes were identified. Mean out-of-hospital blood glucose concentrations at the time of the hypoglycemic event were 2.2 ± 1.3 mmol/L. Most of these patients were frail and had multiple comorbidities. They were treated with oral hypoglycemic drugs (43.6%), insulin (42.8%), or both (13.6%). Among the oral hypoglycemic drugs, glibenclamide (54.5%) and repaglinide (25.7%) were the two most frequently used drugs, followed by glimepiride (11.3%) and gliclazide (7.5%). Hospitalization rates and in-hospital deaths occurred in 35.4% and in 2.3% of patients, respectively. Cirrhosis (odds ratio [OR] 6.76, 95% confidence interval [CI] 1.24–36.8, p