Faecalibacterium prausnitzii Strain HTF-F and Its Extracellular Polymeric Matrix Attenuate Clinical Parameters in DSS-Induced Colitis

Date of Acceptance: 26/02/2015 Funding: The authors received no specific funding for this work.Peer reviewedPublisher PD

Tendon Healing Response Is Dependent on Epithelial–Mesenchymal–Tendon Transition State of Amniotic Epithelial Stem Cells

Tendinopathies are at the frontier of advanced responses to health challenges and sectoral policy targets. Cell‐based therapy holds great promise for tendon disorder resolution. To verify the role of stepwise trans‐differentiation of amniotic epithelial stem cells (AECs) in tendon regeneration, in the present research three different AEC subsets displaying an epithelial (eAECs), mesenchymal (mAECs), and tendon‐like (tdAECs) phenotype were allotransplanted in a validated experimental sheep Achilles tendon injury model. Tissue healing was analyzed adopting a comparative approach at two early healing endpoints (14 and 28 days). All three subsets of transplanted cells were able to accelerate regeneration: mAECs with a lesser extent than eAECs and tdAECs as indicated in the summary of the total histological scores (TSH), where at day 28 eAECs and tdAECs had better significant scores with respect to mAEC‐treated tendons (p < 0.0001). In addition, the immunomodulatory response at day 14 showed in eAEC‐transplanted tendons an upregulation of pro‐regenerative M2 macrophages with respect to mAECs and tdAECs (p < 0.0001). In addition, in all allotransplanted tendons there was a favorable IL10/IL12 compared to CTR (p < 0.001). The eAECs and tdAECs displayed two different underlying regenerative mechanisms in the tendon. The eAECs positively influenced regeneration mainly through their greater ability to convey in the host tissue the shift from pro‐inflammatory to pro‐regenerative responses, leading to an ordered extracellular matrix (ECM) deposition and blood vessel remodeling. On the other hand, the transplantation of tdAECs acted mainly on the proliferative phase by impacting the density of ECM and by supporting a prompt recovery, inducing a low cellularity and angle alignment of the host cell compartment. These results support the idea that AECs lay the groundwork for production of different cell phenotypes that can orient tendon regeneration through a crosstalk with the host tissue. In particular, the obtained evidence suggests that eAECs are a practicable and efficient strategy for the treatment of acute tendinopathies, thus reinforcing the grounds to move their use towards clinical practice

L’analisi del ciclo di vita come strumento di supporto alle decisioni evidence-based in agricoltura

Il presente articolo propone una discussione sul contributo del metodo Life Cycle Assessment alle politiche evidence-based, soprattutto per favorire l’adozione di innovazioni più ecologiche e ridurre l’asimmetria informativa B2C, nell’ottica degli obiettivi 2030 di sviluppo sostenibile (Sustainable Development Goals, SDGs)

Faecalibacterium prausnitzii A2-165 has a high capacity to induce IL-10 in human and murine dendritic cells and modulates T cell responses

Acknowledgements This work was financially supported by the EC FP7 Cross-talk project (PITN-GA-2008-215553). The authors thank the Histology Platform from GABI research unit and especially Abdelhak Boukadiri for their technical support in the histology sample preparation and Marlène Héry, Charline Pontlevoy, Jerome Pottier and André Tiffoche (UE0907 IERP, Jouy en Josas) for their help during animal experiments. The authors thank Rafael Muñoz-Tamayo (INRA) for his help in performing the PCA.Peer reviewedPublisher PD

Vectorial secretion of interleukin-8 mediates autocrine signalling in intestinal epithelial cells via apically located CXCR1

BACKGROUND: In the intestinal mucosa, several adaptations of TLR signalling have evolved to avoid chronic inflammatory responses to the presence of commensal microbes. Here we investigated whether polarized monolayers of intestinal epithelial cells might regulate inflammatory responses by secreting IL-8 in a vectorial fashion (i.e. apical versus basolateral) depending on the location of the TLR stimulus. RESULTS: In the Caco-2 BBE model of polarized villus-like epithelium, apical stimulation with TLR2 and TLR5 ligands resulted in the apical secretion of IL-8. The CXCR1 receptor for IL-8 was expressed only on the apical membrane of Caco-2 BBE cells and differentiated epithelial cells in the human small intestine and colon. Transcriptome analyses revealed that Caco-2 BBE cells respond to stimulation with IL-8 supporting the hypothesis that IL-8 induces G protein-coupled receptor signalling. CONCLUSIONS: These results show that IL-8 induces autocrine signalling via an apical CXCR1 in Caco-2 BBE intestinal epithelial cells and that this receptor is also expressed on the apical surface of differentiated human intestinal epithelial cells in vivo, suggesting an autocrine function for IL-8 secreted in the lumen

Italian Guidelines in diagnosis and treatment of alopecia areata

Alopecia areata (AA) is an organ-specific autoimmune disorder that targets anagen phase hair follicles. The course is unpredictable and current available treatments have variable efficacy. Nowadays, there is relatively little evidence on treatment of AA from well-designed clinical trials. Moreover, none of the treatments or devices commonly used to treat AA are specifically approved by the Food and Drug Administration. The Italian Study Group for Cutaneous Annexial Disease of the Italian Society of dermatology proposes these Italian guidelines for diagnosis and treatment of Alopecia Areata deeming useful for the daily management of the disease. This article summarizes evidence-based treatment associated with expert-based recommendations

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)