940-73 Predictive Value for Major Arrhythmic Events of Ventricular Arrhythmias Detected in the Subacute Phase of a Fibrinolysed Myocardial Infarction. An Analysis of the GISSI-2 Data Base

The relationship between ventricular arrhythmias (VA) in the subacute phase of a myocardial infarction and subsequent major arrhythmic events (MAE) was mainly defined in the prefibrinolytic era, We examined the large population of patients enrolled in the GISSI-2 study in order to evaluate the significance and predictive power for MAE (sustained ventricular tachycardia -SVT-and sudden death -SD-) of VA detected by Holter monitoring during the subacute phase of a fibrinolysed acute myocardial infarction (AMI). Of the 12,381 pts. enrolled in the GISSI-2 study, an Holter monitoring was available in 8,676 and a six month follow-up was completed in 7,713. During the follow-up 84 pts. died suddenly and 26 experienced one or more SVT. The relationship between VA and MAE was evaluated by odds ratio (OR) and their 95% confidence intervals. OR for MAE was 4.5 (2.7–7.5) if the Holter showed > 10 ventricular ectopic beats per hour; 2.3 (1.5–3.7) if couplets were present; 3.3 (1.5–7.0) if nonsustained ventricular tachycardias (NSVT) were noticed; 3.0 12.0–4.5) if any complex VA was detected. A multivariate analysis (Cox modell including the major prognostic determinants confirmed the independent prognostic value of VA in the Holter recording except for NSVT. Any arrhythmic parameter had a very low positive predictive power (from 2.4 to 3.0%). In conclusion, our data show that VA still have, in the fibrinolytic era, a prognostic significance for MAE, but the predictive power is very low and is therefore mandatory to add other variables to identify the pts. more at risk

Influence of climate change on the frequency of daytime temperature inversions and stagnation events in the Po Valley: historical trend and future projections

This work analyzes the frequency of days characterized by daytime temperature inversion and air stagnation events in the Po valley area. The analysis is focused on both historical series and future projections under climate change. Historical sounding data from two different Italian stations are used as well as future projections data, provided by CMCC-CCLM 4-8-19 regional climate model (MED-CORDEX initiative). A new method to detect layers of temperature inversion is also presented. The developed method computes the occurrence of a temperature inversion layer for a given day at 12 UTC without a detailed knowledge of temperature vertical profile. This method was validated using sounding data and applied to the model projections, under two different emissions scenarios (RCP4.5 and RCP8.5). Under RCP4.5 intermediate emissions scenario, the occurrence of temperature inversions is projected to increase by 12 days/year (around + 10%) in the last decade of 21st century compared to 1986–2005 average. However, the increase in temperature inversions seems to be especially concentrated in the warm period. Under RCP8.5 extreme scenario, temperature inversions are still projected to increase, though to a lesser extent compared to RCP4.5 scenario (+ 6 days/year in the last decade of 21st century). A similar trend was found also for air stagnation events, which take into account the variation of precipitation pattern and wind strength. The expected increases are equal to + 13 days/year and + 11 days/year in the last decade of 21st century compared to 1986–2005 average, under RCP4.5 and RCP8.5 scenarios respectively

In vivo emergence of colistin resistance in Klebsiella pneumoniae producing KPC-type carbapenemases mediated by insertional inactivation of the PhoQ/PhoP mgrB regulator

Colistin is one of the few agents that retain activity against extensively drug-resistant strains of Klebsiella pneumoniae producing KPC-type carbapenemases (KPC-KP). However, resistance to colistin is increasingly reported among KPC-KP. Comparative genomic analysis of a pair of sequential KPC-KP isolates from the same patient including a colistin-susceptible isolate (KKBO-1) and a colistin-resistant isolate (KKBO-4) selected after colistin exposure revealed that insertional inactivation of the mgrB gene, encoding a negative regulator of the PhoQ/PhoP signaling system, is a genetic mechanism for acquired colistin resistance. The role of mgrB inactivation in acquired colistin resistance was confirmed by complementation experiments with wild-type mgrB, which restored colistin susceptibility in KKBO-4, and by construction of an mgrB deletion mutant from KKBO-1, which exhibited a colistin-resistant phenotype. Insertional mgrB inactivation was also detected in 60% of colistin-resistant mutants selected from KKBO-1 in vitro, following plating on colistin-containing medium, confirming the role (although not unique) of this mechanism in the emergence of acquired colistin resistance. In colistin-resistant mutants carrying insertional inactivation or deletion of the mgrB gene, upregulated transcription of phoP, phoQ, and pmrK (which is part of the pmrHFIJKLM operon) was detected. These findings confirmed the MgrB regulatory role in K. pneumoniae and were in agreement with the known association between upregulation of the PhoQ/PhoP system and activation of the pmrHFIJKLM operon, which eventually leads to resistance to polymyxins by modification of the lipopolysaccharide target

Riflessioni su una nuova prospettiva: la cattedra mista

The aim of this article is to offer an help in understanding the difficult aspects involved in being a special education needs teacher in the Italian School, by a proposal that starts from examining this role’s weak points and go as far as thinking about a different upskill for the professional resources working for inclusion. If the bill C2444, promoted from the federation FISH and FAND, wants to relaunch the school inclusion by creating separate careers for special education needs teachers, then the here proposed theory is determined to reverse this view, considered as “non-inclusive”. The authors of this article think that if a teacher could teach a subject in part of his time and teach as special education teacher in the other part, he could be a positive change agent for all his students.The aim of this article is to offer an help in understanding the difficult aspects involved in being a special education needs teacher in the Italian School, by a proposal that starts from examining this role’s weak points and go as far as thinking about a different upskill for the professional resources working for inclusion. If the bill C2444, promoted from the federation FISH and FAND, wants to relaunch the school inclusion by creating separate careers for special education needs teachers, then the here proposed theory is determined to reverse this view, considered as “non-inclusive”. The authors of this article think that if a teacher could teach a subject in part of his time and teach as special education teacher in the other part, he could be a positive change agent for all his students

No difference in the outcome of metastatic thyroid cancer patients when using recombinant or endogenous TSH

Objective: At the present, recombinant TSH cannot be used for the treatment of metastatic differentiated thyroid cancer patients. Aim of this study was to evaluate if the type of TSH stimulation, recombinant or endogenous, had an impact on the outcome of these patients. Design and methods: We compared the outcome of two propensity score-matched groups of metastatic patients, stimulated by either only recombinant TSH (n=43) or only endogenous TSH (n=34). Results: As expected from the matching procedure, the clinical-pathological features and the cumulative 131I-activities administered of the two groups were very similar. After 4 years of follow-up 4% of patients were cured, 3% had biochemical disease and 93% had structural disease. However, 91% of patients obtained a clinical benefit from this therapy in terms of stabilization of the disease or complete remission or partial response. When considering the two groups separately we did not find any difference in their outcome. When considering the response to 131-I therapy of the single type of metastases, 8% of lymph node metastases and 8% of lung metastases disappeared but none of bone metastases. The response to 131-I therapy of the single type of metastases was similar when we looked at the two groups separately. Conclusions: this study shows a) an overall clinical benefit of the 131-I therapy since the majority of patients remained affected but with a stable disease b) the preparation with either recombinant or endogenous TSH has no impact on the 131-I therapy efficacy and the outcome of our two groups of patients

Alteration of Fecal Microbiota Profiles in Juvenile Idiopathic Arthritis. Associations with HLA-B27 Allele and Disease Status.

Alteration of gut microbiota is involved in several chronic inflammatory and autoimmune diseases, including rheumatoid arthritis, and gut microbial pro-arthritogenic profiles have been hypothesized. Intestinal inflammation may be involved in spondyloarthropathies and in a subset of patients affected by Juvenile Idiopathic Arthritis (JIA), the most common chronic rheumatic disease of childhood. We compared the fecal microbiota composition of JIA patients with healthy subjects (HS), evaluating differences in microbial profiles between sub-categories of JIA, such as enthesitis-related arthritis (JIA-ERA), in which inflammation of entheses occurs, and polyarticular JIA, non-enthesitis related arthritis (JIA-nERA). Through taxon-level analysis, we discovered alteration of fecal microbiota components that could be involved in subclinical gut inflammation, and promotion of joint inflammation. We observed abundance in Ruminococcaceae in both JIA categories, reduction in Clostridiaceae and Peptostreptococcaceae in JIA-ERA, and increase in Veillonellaceae in JIA-nERA, respectively compared with HS. Among the more relevant genera, we found an increase in Clostridium cluster XIVb, involved in colitis and arthritis, in JIA-ERA patients compared with HS, and a trend of decrease in Faecalibacterium, known for anti-inflammatory properties, in JIA-nERA compared with JIA-ERA and HS. Differential abundant taxa identified JIA patients for the HLA-B27 allele, including Bilophila, Clostridium cluster XIVb, Oscillibacter and Parvimonas. Prediction analysis of metabolic functions showed that JIA-ERA metagenome was differentially enriched in bacterial functions related to cell motility and chemotaxis, suggesting selection of potential virulence traits. We also discovered differential microbial profiles and intra-group variability among active disease and remission, suggesting instability of microbial ecosystem in autoimmune diseases with respect to healthy status. Similarly to other chronic autoimmune and inflammatory diseases, different microbial profiles, as observed among different JIA subgroups compared to HS, and potential functional acquisition related to migration could promote inflammation and contribute to the disease pathogenesis

Prostaglandin E2 Stimulates the Expansion of Regulatory Hematopoietic Stem and Progenitor Cells in Type 1 Diabetes

Hematopoietic stem and progenitor cells (HSPCs) are multipotent stem cells that have been harnessed as a curative therapy for patients with hematological malignancies. Notably, the discovery that HSPCs are endowed with immunoregulatory properties suggests that HSPC-based therapeutic approaches may be used to treat autoimmune diseases. Indeed, infusion with HSPCs has shown promising results in the treatment of type 1 diabetes (T1D) and remains the only “experimental therapy” that has achieved a satisfactory rate of remission (nearly 60%) in T1D. Patients with newly diagnosed T1D have been successfully reverted to normoglycemia by administration of autologous HSPCs in association with a non-myeloablative immunosuppressive regimen. However, this approach is hampered by a high incidence of adverse effects linked to immunosuppression. Herein, we report that while the use of autologous HSPCs is capable of improving C-peptide production in patients with T1D, ex vivo modulation of HSPCs with prostaglandins (PGs) increases their immunoregulatory properties by upregulating expression of the immune checkpoint-signaling molecule PD-L1. Surprisingly, CXCR4 was upregulated as well, which could enhance HSPC trafficking toward the inflamed pancreatic zone. When tested in murine and human in vitro autoimmune assays, PG-modulated HSPCs were shown to abrogate the autoreactive T cell response. The use of PG-modulated HSPCs may thus provide an attractive and novel treatment of autoimmune diabetes

CGRP and migraine from a cardiovascular point of view: what do we expect from blocking CGRP?

Calcitonin gene-related peptide (CGRP) is a neuropeptide with a pivotal role in the pathophysiology of migraine. Blockade of CGRP is a new therapeutic target for patients with migraine. CGRP and its receptors are distributed not only in the central and peripheral nervous system but also in the cardiovascular system, both in blood vessels and in the heart. We reviewed the current evidence on the role of CGRP in the cardiovascular system in order to understand the possible short- and long-term effect of CGRP blockade with monoclonal antibodies in migraineurs. In physiological conditions, CGRP has important vasodilating effects and is thought to protect organs from ischemia. Despite the aforementioned cardiovascular implication, preventive treatment with CGRP antibodies has shown no relevant cardiovascular side effects. Results from long-term trials and from real life are now needed

T-REX OU4 HIRES: the high resolution spectrograph for the E-ELT

The goal of this unit was to consolidate the project for the construction of the high resolution spectrometer of the E-ELT (HIRES). The task included the development of scientific cases and tools to predict the instrumental performances. From the technical point of view it included several R&D activities in collaboration with highly specialized Italian companies; it culminated with the detailed design of a highly modular instrument based on well established technologies. From the management point of view it lead to the consolidation of a large international consortium that spans over 12 countries and includes most of the European and ESO-related institutes interested in high resolution spectroscopy. This consortium is led by INAF; its formal creation is awaiting the official call by ESO for the phase-A study for the HIRES instrument of the E-ELT