Exosomal cancer immunotherapy is independent of MHC molecules on exosomes

Peptide-loaded exosomes are promising cancer treatment vehicles; however, moderate T cell responses in human clinical trials indicate a need to further understand exosome-induced immunity. We previously demonstrated that antigen-loaded exosomes carry whole protein antigens and require B cells for inducing antigen-specific T cells. Therefore, we investigated the relative importance of exosomal major histocompatibility complex (MHC) class I for the induction of antigen-specific T cell responses and tumour protection. We show that ovalbumin-loaded dendritic cell-derived exosomes from MHCI-/- mice induce antigen-specific T cells at the same magnitude as wild type exosomes. Furthermore, exosomes lacking MHC class I, as well as exosomes with both MHC class I and II mismatch, induced tumour infiltrating T cells and increased overall survival to the same extent as syngeneic exosomes in B16 melanoma. In conclusion, T cell responses are independent of exosomal MHC/peptide complexes if whole antigen is present. This establishes the prospective of using impersonalised exosomes, and will greatly increase the feasibility of designing exosome-based vaccines or therapeutic approaches in humans

Novel use of plga microspheres to create an animal model of glaucoma with progressive neuroretinal degeneration

Progressive degeneration of neuroretinal tissue with maintained elevated intraocular pressure (IOP) to simulate chronic glaucoma was produced by intracameral injections of poly (lactic-co-glycolic) acid (PLGA) microspheres (Ms) in rat eyes. The right eye of 39 rats received different sizes of PLGA-Ms (2 µL suspension; 10% w/v): 14 with 38–20 µm Ms (Ms38/20 model) and 25 with 20–10 µm particles (Ms20/10 model). This novel glaucoma animal model was compared to the episcleral vein sclerosis (EPI) model (25 eyes). Injections were performed at baseline, two, four and six weeks. Clinical signs, IOP, retina and optic nerve thicknesses (using in vivo optical coherence tomography; OCT), and histological studies were performed. An IOP increment was observed in all three groups, however, the values obtained from the PLGA-Ms injection resulted lower with a better preservation of the ocular surface. In fact, the injection of Ms20/10 created a gentler, more progressive, and more sustained increase in IOP. This IOP alteration was correlated with a significant decrease in most OCT parameters and in histological ganglion-cell count for the three conditions throughout the eight-week follow-up. In all cases, progressive degeneration of the retina, retinal ganglion cells and optic nerve, simulating chronic glaucoma, was detected by OCT and corroborated by histological study. Results showed an alternative glaucoma model to the well-known episcleral vein model, which was simpler to perform, more reproducible and easier to monitor in vivo

What do we evaluate in sport mindfulness interventions? A systematic review of commonly used questionnaires

Interest of the study: mindfulness is a concept describing the focus on the present moment, intentionally and without judgement. This approach has only recently been applied to sport psychology. Objectives: the aim of the current review is to investigate which indicators and questionnaires are used in mindfulness research in sport, being specifically interested in mindfulness assessment. Methods: PRISMA guidelines for systematic reviews and the recommendations of the Cochrane Collaboration were used. Literature searches were conducted in Psychinfo, PubMed, EMBASE and the Cochrane Library. Results: From 2, 203 records initially retrieved, 17 articles were included. The results show that mindfulness, anxiety and acceptance are the most commonly studied psychological indicators. The Five Facet Mindfulness Questionnaire is the most frequently used mindfulness scale. We also discuss the possibility of using physiological indicators as complementary assessment. Conclusions: It is recommended to specifically adapt some questionnaires, such is already done with the Sport Anxiety Scale or the Mindfulness Inventory for Sport, for their use in sport psychology

Recovery of early meteorological records from Extremadura region (SW Iberia): The ''CliPastExtrem'' (v1.0) database

In this work, we provide instrumental meteorological data recovered for the Extremadura region (interior SW Iberia), from 1826 to mid-20th century. Meteorological variables such as air temperature, atmospheric pressure, precipitation, wind direction and humidity, among others, were retrieved. In total, more than 750 000 instrumental data in 157 meteorological series belonging to 131 different locations throughout Extremadura were rescued. It must be noted that daily resolution data constitutes 80% of the database. This great effort of digitization and data collection has been carried out with the aim of contributing to a significant expansion of the length of the databases with meteorological information in this region. Therefore, this database will provide a better understanding of climate variability, trends and extreme events of the Extremadura region

Chronic glaucoma using biodegradable microspheres to induce intraocular pressure elevation. Six-month follow-up

Background: To compare two prolonged animal models of glaucoma over 24 weeks of follow-up. A novel pre-trabecular model of chronic glaucoma was achieved by injection of biodegradable poly lactic-co-glycolic acid (PLGA) microspheres (10–20 µm) (Ms20/10) into the ocular anterior chamber to progressively increase ocular hypertension (OHT). Methods: Rat right eyes were injected to induce OHT: 50% received a suspension of Ms20/10 in the anterior chamber at 0, 2, 4, 8, 12, 16 and 20 weeks, and the other 50% received a sclerosing episcleral vein injection biweekly (EPIm). Ophthalmological clinical signs, intraocular pressure (IOP), neuroretinal functionality measured by electroretinography (ERG), and structural analysis of the retina, retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) protocols using optical coherence tomography (OCT) and histological exams were performed. Results: Both models showed progressive neuroretinal degeneration (p < 0.05), and contralateral eye affectation. The Ms20/10 model showed a more progressive increase in IOP and better preservation of ocular surface. Although no statistical differences were found between models, the EPIm showed a tendency to produce thicker retinal and thinner GCL thicknesses, slower latency and smaller amplitude as measured using ERG, and more aggressive disturbances in retinal histology. In both models, while the GCL showed the greatest percentage loss of thickness, the RNFL showed the greatest and earliest rate of thickness loss. Conclusions: The intracameral model with biodegradable microspheres resulted more like the conditions observed in humans. It was obtained by a less-aggressive mechanism, which allows for adequate study of the pathology over longer periods. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Platelet serotonin levels are associated with plasma soluble leptin receptor concentrations in normoglycemic women

Most peripheral serotonin (5-hydroxytryptamine (5HT)) is synthetized in the gut with platelets being its main circulating reservoir. 5HT is acting as a hormone in key organs to regulate glucose and lipid metabolism. However, the relation between platelet 5HT levels and traits related to glucose homeostasis and lipid metabolism in humans remains poorly explored. The objectives of this study were (a) to assess the association between platelet 5HT levels and plasma concentration of nonesterified fatty acids (NEFAs) and some adipokines including leptin and its soluble leptin receptor (sOb-R), (b) to assess the association between platelet 5HT levels and anthropometric traits and indexes of insulin secretion/sensitivity derived from oral glucose tolerance test (OGTT), and (c) to evaluate changes in platelet 5HT levels in response to OGTT. In a cross-sectional study, 59 normoglycemic women underwent a standard 2-hour OGTT. Plasma leptin, sOb-R, total and high molecular weight adiponectin, TNFα, and MCP1 were determined by immunoassays. Platelet 5HT levels and NEFAs were measured before and after OGTT. The free leptin index was calculated from leptin and sOb-R measurements. Insulin sensitivity indexes derived from OGTT (HOMA-S and Matsuda ISICOMP) and plasma NEFAs (Adipose-IR, Revised QUICKI) were also calculated. Our data show that among metabolic traits, platelet 5HT levels were associated with plasma sOb-R (r = 0 39, p = 0 003, corrected p = 0 018). Platelet 5HT levels were reduced in response to OGTT (779 ± 237 vs 731 ± 217 ng/109 platelets, p = 0 005). In conclusion, platelet 5HT levels are positively associated with plasma sOb-R concentrations and reduced in response to glucose intake possibly indicating a role of peripheral 5HT in leptin-mediated appetite regulation

Preterm white matter injury : ultrasound diagnosis and classification

White matter injury (WMI) is the most frequent form of preterm brain injury. Cranial ultrasound (CUS) remains the preferred modality for initial and sequential neuroimaging in preterm infants, and is reliable for the diagnosis of cystic periventricular leukomalacia. Although magnetic resonance imaging is superior to CUS in detecting the diffuse and more subtle forms of WMI that prevail in very premature infants surviving nowadays, recent improvement in the quality of neonatal CUS imaging has broadened the spectrum of preterm white matter abnormalities that can be detected with this technique. We propose a structured CUS assessment of WMI of prematurity that seeks to account for both cystic and non-cystic changes, as well as signs of white matter loss and impaired brain growth and maturation, at or near term equivalent age. This novel assessment system aims to improve disease description in both routine clinical practice and clinical research. Whether this systematic assessment will improve prediction of outcome in preterm infants with WMI still needs to be evaluated in prospective studies

High Temperature Corrosion of Inconel 600 in NaCl-KCl Molten Salts

In this work the corrosion resistance of a high content nickel alloy, Inconel 600, was investigated in mixed NaCl-KCl salts at 700, 800, and 900°C for 100 hours in static air. Investigation was carried out using electrochemical techniques such as polarization curves, rest potential measurements, linear polarization resistance, and electrochemical impedance spectroscopy. Corroded specimens were analyzed by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). Electrochemical measurements showed an increased degradation rate of Inconel 600 with increasing test temperature. SEM and EDS analysis show that the damage experienced by Inconel 600 is greater than that determined by electrochemical measurements. This damage was identified as internal corrosion due to the reaction of Cl2 with the alloying elements (Cr and Fe); however, at 900°C the internal damage was minor and it was associated with the nickel content in the alloy