Defective FoxP3+ Treg cell differentiation in the gut of Type 1 Diabetic patients

Environmental factors that act at the intestinal level such as diet, drugs, and microflora have a high impact on the pathogenesis of autoimmune Type 1 Diabetes (T1D), but it is still unclear how the gut milieu affects autoimmunity outside the intestine. Here we show that peripheral FoxP3+ Treg cell differentiation, a mechanism that takes place in the gut and is crucial to maintain systemic immune tolerance, is impaired in T1D patients. These results provide the first evidence that gut mucosa alteration could predispose to autoimmune T1D by affecting systemic immune regulation

Role of high dose octreotide LAR for the treatment of GEP-NETs

Neuroendocrine Tumours (NETs) are a heterogeneous group of rare neoplasms that account for 0,5% of all malignancies. The increased incidence observed in the last few decades may be accounted for by increased awareness, improved diagnostic tools and a revision in the definition. The main primary sites are the gastro-entero-pancreatic (GEP) tract (62-67%), and the lung (22-27%). In patients with GEP-NETs, the strongest predictor of 5-years survival is the staging. An adequate clinical management of GEP-NETs should be multidisciplinary and should aim at assuring a good quality of life. Somatostatin (sst) analogues are widely used in these tumours, which often express sst receptors, since they are demonstrated to reduce clinical symptoms and tumour growth. Herein we explore the usefulness of doubling octreotide LAR dose in selected patients after escaping from symptoms control and/or tumour stabilization in course of treatment with standard dose

Investigation of the Defatted Colostrum 1H-NMR Metabolomics Profile of Gilts and Multiparous Sows and Its Relationship with Litter Performance

The aim of the study was to characterize the soluble metabolomics profile of defatted colostrum of sows at different parity number (PA) and to correlate the metabolomics profile with the Brix percentage estimate of colostrum immunoglobulin G (IgG) and sow productive traits. A total of 96 Meidam (crossbreed Large White 7 Meishan) sows of PA from 1-4 (PA1: 28; PA2:26; PA3:12; PA4:26) were included, and their productive traits were recorded at 10 days post-farrowing. Colostrum IgG was quantified using a Brix refractometer, and metabolomics profile was assessed using 1H-NMR spectroscopy. Sows' PA slightly influenced the metabolomics profile of colostrum. lactose and glycine were higher in PA1 compared with PA4 (p 0.05) and N-acetylglucosamine (GlcNAc) tended to be higher in PA2 than PA3 and PA4 (p < 0.10). The Brix percentage of IgG was negatively associated with lactose and positively with creatine, myo-inositol, and O-phosphocholine (p < 0.05). Taurine was positively related to litter weight at birth. GlcNAc and myo-inositol were linked to piglet mortality at day 10 with a negative and positive trend, respectively. In conclusion, colostrum of gilts and multiparous sows had a similar metabolomics profile. Specific metabolites contributed to explanation of the variability in colostrum Brix percentage estimate of IgG concentration and the sows' productive performance

The SUCCESSO-TERRA Project: a Lesson of Sustainability from the Terramare Culture, Middle Bronze Age of the Po Plain (Northern Italy)

This backstory article deals with the SUCCESSO-TERRA Project (2017–2020), an interdisciplinary research program aiming at reconstructing the land-use transformations that occurred during the development of the Terramare culture in the southern-central Po Plain of Northern Italy. Topics include climate-environment changes, human impact and exploitation of natural resources that are interconnected topics in human ecology and environmental sciences. These topics can only be understood in a long-term perspective integrating archaeology, geology, botany and other sciences. The text includes the theoretical basis, the research strategy and the main methodological approaches given by geoarchaeology and palynology, the two research sides constituting the partnership of the project

Early peripheral clearance of leukemia-associated immunophenotypes in AML: centralized analysis of a randomized trial

Although genetics is a relevant risk factor in acute myeloid leukemia (AML), it can be minimally informative and/or not readily available for the early identification of patients at risk for treatment failure. In a randomized trial comparing standard vs high-dose induction (ClinicalTrials.gov 64NCT00495287), we studied early peripheral blast cell clearance (PBC) as a rapid predictive assay of chemotherapy response to determine whether it correlates with the achievement of complete remission (CR), as well as postremission outcome, according to induction intensity. Individual leukemia-associated immunophenotypes (LAIPs) identified pretherapy by flow cytometry were validated and quantified centrally after 3 days of treatment, expressing PBC on a logarithmic scale as the ratio of absolute LAIP1 cells on day 1 and day 4. Of 178 patients, 151 (84.8%) were evaluable. Patients in CR exhibited significantly higher median PBC (2.3 log) compared with chemoresistant patients (1.0 log; P<.0001). PBC<1.0 predicted the worst outcome (CR, 28%). With 1.5 log established as the most accurate cutoff predicting CR, 87.5% of patients with PBC .1.5 (PBChigh, n = 96) and 43.6% of patients with PBC 641.5 (PBClow, n = 55) achieved CR after single-course induction (P<.0001). CR and PBChigh rates were increased in patients randomized to the high-dose induction arm (P 5 .04) and correlated strongly with genetic/cytogenetic risk. In multivariate analysis, PBC retained significant predictive power for CR, relapse risk, and survival. Thus, PBC analysis can provide a very early prediction of outcome, correlates with treatment intensity and disease subset, and may support studies of customized AML therapy

Correlation between visual field index and quality of life in glaucoma patients: a new tool to screen quality of life perception?

PurposeTo evaluate the correlation between the visual field index (VFI) and vision-related quality of life (QoL) considering several confounding variables that may have a positive or negative effect.MethodsWe conducted a cross-sectional, mono-centric study on glaucoma patients. Quality of life was examined with the NEI-VFQ 25 and the Glaucoma Symptom Scale (GSS). The visual field was examined with the Humphrey Field Analyzer. The variables considered were age, gender, comorbidities, years (at diagnosis and duration of the illness), treatment and related active principles, intraocular pressure, and visual acuity. The analysis was performed on both the better and the worse eye. The linear regression univariate analysis and the multivariate analyses were performed.ResultsIn total, 193 patients enrolled in the study. The mean age was 70.8 ± 10.4 years. The mean follow-up period since diagnosis 11.4 ± 9.2 years. Approximately 50% of the patients suffered from primary open angle glaucoma (POAG) and 45% were on monotherapy. The mean VFI was 81.3 ± 26. Regarding QoL, the NEI-VFQ total mean was 80.4 ± 17.8 and the GSS total score was 77.2 ± 21. Regarding NEI-VFQ 25, the single linear regression analysis found the following relations: age at time of visit (r = −0.30, p = 0.016), years of illness (r = −0.32, p = 0.020), the minimum and maximal visual acuity (r = 2.04 and r = 3.96, p < 0.001), the IOP min (r = 1.13, p = 0.002) and max (r = −0.52, p = 0.017), and the number of previous surgeries (r = −3.94, p < 0.001). The multivariate analysis found the following relations: gender (r = 5.13, p = 0.019), visual acuity max (r = 3.16, p < 0.001), and previous surgeries (r = −1.80, p = 0.032). Regarding GSS, the single linear regression analysis found relations with visual acuity (r = 2.37, p < 0.001), VFI (r = 0.41, p < 0.001), previous surgeries in the eye considered (r = −7.27, p < 0.001), and number of instillations (r = −3.67, p = 0.031). Data confirmed that a higher VFI has a positive impact on the score of both the NEI-VFQ 25 (r = 0.22, p = < 0.001) and the GSS questionnaire (r = 0.36, p < 0.001).ConclusionsThe study demonstrated a correlation between the VFI and QoL of patients and their visual and non-visual ocular symptoms and function both in the worst and in the better eye, even when accounting for several clinical and demographic confounding variables. Our data support that the visual field index is an important metric instrument in the follow up of patients with glaucoma

Exploiting natural polysaccharides to enhance in vitro bio-constructs of primary neurons and progenitor cells

Current strategies in Central Nervous System (CNS) repair focus on the engineering of artificial scaffolds for guiding and promoting neuronal tissue regrowth. Ideally, one should combine such synthetic structures with stem cell therapies, encapsulating progenitor cells and instructing their differentiation and growth. We used developments in the design, synthesis, and characterization of polysaccharide-based bioactive polymeric materials for testing the ideal composite supporting neuronal network growth, synapse formation and stem cell differentiation into neurons and motor neurons. Moreover, we investigated the feasibility of combining these approaches with engineered mesenchymal stem cells able to release neurotrophic factors. We show here that composite bio-constructs made of Chitlac, a Chitosan derivative, favor hippocampal neuronal growth, synapse formation and the differentiation of progenitors into the proper neuronal lineage, that can be improved by local and continuous delivery of neurotrophins. Statement of Significance In our work, we characterized polysaccharide-based bioactive platforms as biocompatible materials for nerve tissue engineering. We show that Chitlac-thick substrates are able to promote neuronal growth, differentiation, maturation and formation of active synapses. These observations support this new material as a promising candidate for the development of complex bio-constructs promoting central nervous system regeneration. Our novel findings sustain the exploitation of polysaccharide-based scaffolds able to favour neuronal network reconstruction. Our study shows that Chitlac-thick may be an ideal candidate for the design of biomaterial scaffolds enriched with stem cell therapies as an innovative approach for central nervous system repair