Essential Role of Lyn in Fibrosis.

Fibrotic disorders involve replacement of normal parenchyma with myofibroblasts, which deposit connective tissue, leading to obliteration of the function of the underlying organ. The treatment options are inadequate and reflect the fact that signaling targets in myofibroblasts are unknown. Here we identify the hyperactive Lyn signaling in myofibroblasts of patients with chronic pancreatitis-induced fibrosis. Lyn activation coexpress with markers of activated myofibroblasts, and is increased ~11-fold in chronic pancreatitis compared to normal tissue. Inhibition of Lyn with siRNA or INNO-406 leads to the substantial decrease of migration and proliferation of human chronic pancreatitis myofibroblasts in vitro, while leaving migration and proliferation of normal myofibroblasts only slightly affected. Furthermore, inhibition of Lyn prevents synthesis of procollagen and collagen in myofibroblasts in a mouse model of chronic pancreatitis-induced fibrosis. We conclude that Lyn, as a positive regulator of myofibroblast migration, proliferation, and collagen production, is a key target for preventing fibrosis

Misalignment of hemodynamic forces in the left ventricle is associated with adverse remodeling following STEMI

Abstract Funding Acknowledgements Type of funding sources: None. Background Infarct size (IS), area at risk (AAR) and microvascular obstruction (MVO) are well known predictors of adverse remodeling (aLVr) following acute myocardial infarction, while the pathogenic role of left ventricular (LV) hemodynamic forces (HDFs) is still unknown. Recent evidence suggests the role of HDFs in negative remodeling after pathogenic events. Purpose To identify LV HDFs patterns associated with aLVr in reperfused ST-segment elevation MI (STEMI) patients. Methods Forty-nine acute STEMI patients underwent CMR at 1 week (baseline) and 4 months (follow-up) after MI. The following parameters were measured: left ventricular end-diastolic and end-systolic volume index for body surface area (LVEDVi and LVESVi), left ventricular ejection fraction (LVEF) and LV mass index, AAR and IS. LV HDFs were computed at baseline from cine CMR long axis datasets using a novel method based on LV endocardial boundary tracking. LV HDFs were calculated both in apex-base (A-B) and latero-septal (L-S) directions. The distribution of LV HDFs were evaluated by L-S over A-B HDFs ratio (L-S/A-B HDFs ratio %). All HDFs parameters are computed over the entire heartbeat, in systole and diastole. aLVr was defined as an absolute increase in LVESV of at least 15% (ΔLV-ESV ≥15%). Results Patients with aLVr (n = 18; 37%) had significant greater value of AAR (32 ± 23 vs 22 ± 18; p = 0.03) and slightly larger IS (23 ± 16 vs 15 ± 11; p= 0.07) at baseline. In patients with aLVr at FU, baseline systolic L-S HDF were lower (2.7 ± 0.9 vs 3.6 ± 1; p = 0.027) while diastolic L-S/A-B HDF ratio was significantly higher (28 ± 14 vs 19 ± 6; p = 0.03), reflecting higher grade of diastolic HDFs misalignment. At univariate logistic regression analysis, higher IS [Odd ratio (OR) 1.05; 95% confidence interval (95% CI) 1.01-1.1; p= 0.04] L-S HDFs (OR 0.41; 95% CI 0.2-0.9; p= 0.04] and higher diastolic L-S/A-B HDFs ratio (OR 1.1; 95% CI 1.01-1.2; p= 0.05) were associated with aLVr at FU (Table). At multivariate logistic regression analysis, L-S/A-B HDF ratio remained the only independent predictor of adverse LV remodeling after correction for other baseline determinants. Conclusion Misalignment of diastolic HDFs following STEMI is associated with aLVr observed after 4 months. Predictors of adverse remodeling Univariate Multivariate Parameter OR (95% CI) P OR (95% CI) P IS (%) 1.05 (1.01-1.1) 0.042 - - Systolic L-S HDF 0.41 (0.2-0.9) 0.04 - - Diastolic L-S/A-B HDF Ratio 1.1 (1.01-1.2) 0.05 1.1 (1.01-1.2) 0.04 A-B:apex-base; L-S: latero-septal; HDFs: hemodynamic forces Abstract Figure. Diastolic HDFs distribution and aLV

Exploratory Genome-Wide Association Analysis to Identify Pharmacogenetic Determinants of Response to R-CHOP in Diffuse Large B-Cell Lymphoma

R-CHOP standard chemotherapy is successful in about 60% of diffuse large B-cell lymphoma (DLBCL) patients. Unresponsive patients have a poor prognosis, and predictive biomarkers of response to R-CHOP are lacking. We conducted the first prospective GWAS study aimed at exploring constitutional biomarkers predictive of R-CHOP efficacy and toxicity. Overall, 216 any-stage chemonaive DLBCL patients candidate to R-CHOP were enrolled. The median age of the 185 eligible patients was 59.2 years, 49.7% were women and 45.4% were stage I-II patients. According to the Revised International Prognostic Index (R-IPI), 14.1%, 56.8% and 29.2% were in the very good, good and poor prognosis groups, respectively. Of the patients, 85.9% produced a complete response. Highly significant associations (i.e., p < 5 x 10(-8)) were found between progression-free survival (PFS) and six SNPs (i.e., rs116665727, rs1607795, rs75614943, rs77241831, rs117500207, rs78466241). Additionally, five SNPs (i.e., rs74832512, rs117500207, rs35789195, rs11721010, rs12356569) were highly associated with overall survival (OS). Wild-type patients showed a prolonged PFS or OS compared with patients carrying deleterious alleles (p < 0.001). No association with the adequate significant threshold was observed between SNPs and the objective response or toxicity. In the future, these SNPs, alone or in combination, after a proper validation in an independent cohort, could contribute to improving the prediction of R-CHOP response

Usefulness of bronchoalveolar lavage in suspect COVID-19 repeatedly negative swab test and interstitial lung disease

The diagnosis of coronavirus disease 2019 (COVID-19) relies on nasopharyngeal swab, which shows a 20–30% risk of false negativity [1]. Bronchoalveolar lavage (BAL) is reported to be useful in patients with pulmonary interstitial infiltrates on high-resolution computed tomography (HRCT). We investigated the usefulness of BAL in symptomatic patients with positive HRCT and a repeatedly negative swab test (‘grey zone’)

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on fourteen research projects.National Institutes of Health Grant RO1 DC00117National Institutes of Health Grant RO1 DC02032National Institutes of Health/National Institute on Deafness and Other Communication Disorders Grant R01 DC00126National Institutes of Health Grant R01 DC00270National Institutes of Health Contract N01 DC52107U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-95-K-0014U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-96-K-0003U.S. Navy - Office of Naval Research Grant N00014-96-1-0379U.S. Air Force - Office of Scientific Research Grant F49620-95-1-0176U.S. Air Force - Office of Scientific Research Grant F49620-96-1-0202U.S. Navy - Office of Naval Research Subcontract 40167U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-96-K-0002National Institutes of Health Grant R01-NS33778U.S. Navy - Office of Naval Research Grant N00014-92-J-184

Mettere in atto un'attività pianificata - Unità formativa per docenti scuole superiori. - Scheda di progettazione per verifica di conoscenze e competenze di materia e trasversali, negli allievi delle scuole superiori. ReQuS -Polo Qualità di Milanowww.requs.it/

Scheda di progettazione di una unità formativa attraverso la quale verificare conoscenze e competenze di materia e trasversali, negli allievi delle scuole superiori: schema operativo per i docenti

Gestire informazioni a scuola nei diversi ambiti matematici- Unità formativa per docenti scuole superiori. ReQuS- Polo Qualità Lombardia . www.requs.it/

Percorsi per docenti delle scuole atti a verificare conoscenze e competene degli allievi nelle ultime classi delle scuole superiori; prove di tipo vario, percorsi logico-deduttivi, mappe concettuali, problemi a risposta aperta di algebra e geometria

Prognostic value of systemic inflammatory response syndrome after transcatheter aortic valve implantation

AIMS: Systemic inflammatory response syndrome (SIRS) could affect mortality after transcatheter aortic valve implantation (TAVI) up to 12 months of follow-up. The aim of this study was to evaluate the prevalence of SIRS after TAVI and its impact on all-cause mortality up to 24 months follow-up. METHODS: We retrospectively enrolled 132 patients with symptomatic severe aortic stenosis undergoing TAVI. SIRS development during the first 72 h after the intervention was evaluated. Other postoperative complications were defined according to the Valve Academic Research Consortium 2 (VARC2). All patients underwent follow-up at 30 days and 24 months. Endpoints were 30-days and 24-months mortality. RESULTS: Post-TAVI SIRS developed in 27 patients (20%). At 30-day follow-up, all-cause death occurred in 10 (8%) patients and SIRS occurred more frequently in patients with adverse short-term outcome (60 vs. 17%; P = 0.001). Twenty-four months all-cause death occurred in 25 (19%) patients. SIRS resulted as an independent predictor of long-term outcome [hazard ratio 3.7; 95% confidence interval (95% CI) 1.5-9; P = 0.004], along with major vascular complications (hazard ratio 4; 95% CI 1.6-9.9; P = 0.003), relevant bleedings (hazard ratio 6.4; 95% CI 1.5-28; P = 0.013) and baseline pulmonary hypertension (hazard ratio 2.4; 95% CI 1.05-5.6; P = 0.039). CONCLUSION: Postoperative SIRS was more frequent in patients who died at 30 days follow-up. Moreover, SIRS resulted as a predictor of 24-month mortality along with vascular complications, relevant bleedings and baseline pulmonary hypertension