Opzioni chirurgiche nella terapia della Wobbler Syndrome: confronto clinico

In questo studio si mettono a confronto tre diverse tecniche chirurgiche adottate per trattare cani di varie razze affetti da Wobbler Syndrome, riportando 22 casi provenienti da tre unità operative in un arco di tempo di circa sei anni. Sono stati analizzati i risultati e i tempi di recupero dei diversi tipi di intervento con lo scopo di individuare la tecnica con maggiori percentuali di successo e gettare una base per stabilire la migliore terapia per questa patologia

Inflammatory bowel diseases in horses: What do we know?

SummaryChronic inflammatory bowel diseases (IBDs) are a group of gastrointestinal (GI) disorders described in both humans and animals, but unlike in other species, in horses they are poorly defined and there is a lack of standardisation of the method of diagnosis. Although there is an impellent need of consensus on the nomenclature, diagnostic work‐up, diet, treatment and management of horses with a suspected IBD, the aim of this review is to give initial guidelines for practitioners dealing with suspected cases. It provides a summary of the most relevant literature on the topic and presents the current knowledge on the clinical signs, diagnostic work‐up, treatment and prognosis of IBDs in horses

Government as a social machine - the implications of government as a social machine for making and implementing market-based policy

This is the second of two reports from the Government as a Social Machine project. The first report gave an overview of the evolution of electronic/digital government, and explored the concept of 21st century government as a \u27social machine\u27. This report identifies seven social machines developed by governments in Australia and New Zealand. These social machines harness digital technologies in order to deliver more effective and efficient services, develop better business practices, and enable better accountability and transparency. The report gives an overview of each social machine in context, describing the social need that is being met and the community that has developed it, and begins to unravel some of the socio-political consequences that might arise from the use of these social machines within the public policy context. These reports are not intended to be comprehensive (further educational materials are being developed as part of the ANZSOG Case Library), but they are intended to begin a conversation amongst those studying or practicing in public policy as to how governments can better understand, manage and employ these evolving social machines for better governance and social benefit

Senescence in human mesenchymal stem cells: Functional changes and implications in stem cell-based therapy

Regenerative medicine is extensively interested in developing cell therapies using mesenchymal stem cells (MSCs), with applications to several aging-associated diseases. For successful therapies, a substantial number of cells are needed, requiring extensive ex vivo cell expansion. However, MSC proliferation is limited and it is quite likely that long-term culture evokes continuous changes in MSCs. Therefore, a substantial proportion of cells may undergo senescence. In the present review, we will first present the phenotypic characterization of senescent human MSCs (hMSCs) and their possible consequent functional alterations. The accumulation of oxidative stress and dysregulation of key differentiation regulatory factors determine decreased differentiation potential of senescent hMSCs. Senescent hMSCs also show a marked impairment in their migratory and homing ability. Finally, many factors present in the secretome of senescent hMSCs are able to exacerbate the inflammatory response at a systemic level, decreasing the immune modulation activity of hMSCs and promoting either proliferation or migration of cancer cells. Considering the deleterious effects that these changes could evoke, it would appear of primary importance to monitor the occurrence of senescent phenotype in clinically expanded hMSCs and to evaluate possible ways to prevent in vitro MSC senescence. An updated critical presentation of the possible strategies for in vitro senescence monitoring and prevention constitutes the second part of this review. Understanding the mechanisms that drive toward hMSC growth arrest and evaluating how to counteract these for preserving a functional stem cell pool is of fundamental importance for the development of efficient cell-based therapeutic approaches

CAR-modified Cellular Therapies in Chronic Lymphocytic Leukemia: Is the Uphill Road Getting Less Steep?

The clinical development of chimeric antigen receptor (CAR) T-cell therapy has been more challenging for chronic lymphocytic leukemia (CLL) compared to other settings. One of the main reasons is the CLL-associated state of immune dysfunction that specifically involves patient-derived T cells. Here, we provide an overview of the clinical results obtained with CAR T-cell therapy in CLL, describing the identified immunologic reasons for the inferior efficacy. Novel CAR T-cell formulations, such as lisocabtagene maraleucel, administered alone or in combination with the Bruton tyrosine kinase inhibitor ibrutinib, are currently under investigation. These approaches are based on the rationale that improving the quality of the T-cell source and of the CAR T-cell product may deliver a more functional therapeutic weapon. Further strategies to boost the efficacy of CAR T cells should rely not only on the production of CAR T cells with an improved cellular composition but also on additional changes. Such alterations could include (1) the coadministration of immunomodulatory agents capable of counteracting CLL-related immunological alterations, (2) the design of improved CAR constructs (such as third- and fourth-generation CARs), (3) the incorporation into the manufacturing process of immunomodulatory compounds overcoming the T-cell defects, and (4) the use of allogeneic CAR T cells or alternative CAR-modified cellular vectors. These strategies may allow to develop more effective CAR-modified cellular therapies capable of counteracting the more aggressive and still incurable forms of CLL

Effect of acute and repeated administration of paracetamol on opioidergic and serotonergic systems in rats.

Objective and design: We investigated the antinociceptiveeffect of paracetamol or morphine after repeatedadministration and the changes in the characteristics of centralμ-, κ- and 5-HT2 receptors.Treatment: Male rats were injected twice a day for sevendays with paracetamol (400 mg/kg, i. p.) or morphine (5 mg/kg, s. c.).Methods: The antinociceptive effect was evaluated 30 minafter single and multiple doses of paracetamol and morphinethrough the hot-plate test. Binding techniques were used toevaluate the receptor characteristics in the frontal cortex.Results: Both paracetamol and morphine induced an antinociceptiveeffect on day 1 but only paracetamol maintainedthis effect for seven days while morphine did not.The number of μ-opioid receptors decreased on days 1, 3,and 7 by a similar percentage after paracetamol administration(by 29, 31 and 34 %, respectively), while morphineproduced a progressive decrease in comparison with controls(by 37, 49 and 60 %, respectively) and κ-opioid receptorswere unaffected. Both drugs similarly decreased the 5-HT2receptor number on all days of treatment (by about 30 %).Conclusions: The opioidergic and serotonergic systems areinvolved in different ways in the induction and maintenanceof antinociception after paracetamol or morphine treatment

L’ESPERIENZA DELLA SICILIA QUALE REGIONE CAPOFILA NELLA INTRODUZIONE DELLA VACCINAZIONE UNIVERSALE CONTRO I ROTAVIRUS

La gastroenterite da rotavirus (GARV) rappresenta uno dei principali bisogni assistenziali durante l’età pediatrica. Purtroppo, in Italia, in assenza di notifica obbligatoria e di specifici sistemi di sorveglianza, le uniche valutazioni epidemiologiche disponibili sulle GARV sono rese possibili dall’analisi delle ospedalizzazioni. Il presente lavoro ha avuto l’obiettivo di valutare le ospedalizzazioni per GARV e per intussuscezione, avvenute in Sicilia in soggetti di età compresa tra 0 e 60 mesi, negli anni 2003-2012 (periodo prevaccinale) e 2013 (anno di introduzione della vaccinazione antirotavirus). Nel periodo in esame si sono osservate 9.886 ospedalizzazioni per GARV con una media annua di 899 casi. La maggior parte dei ricoveri (62,3%) è stata registrata nella fascia di età compresa tra 0 e 2 anni con una progressiva riduzione negli anni di vita successivi. Durante il 2013 si è osservata una copertura vaccinale regionale attestatasi tra il 30 ed il 40% per la prima dose ed il 25-35% per la seconda dose. Nello stesso anno si è assistito ad una riduzione dei casi di GARV di circa il 38,9% nei soggetti di età 0-5 anni (931 casi/anno nel 2003-2012 vs. 569 nel 2013) e superiore al 50% nella fascia di età 0-11 mesi (277 casi/anno nel 2003-2012 vs. 137 nel 2013). Diversamente, nel 2013 il numero di ospedalizzazioni per intussuscezione in soggetti di età compresa tra 0 ed 11 mesi si è mantenuta in linea con quanto osservato in epoca prevaccinale (15 casi nel 2013 vs. 15,4 casi/anno osservati in media tra 2003 e 2012). I dati presentati evidenziano l’importante peso assistenziale che le GARV hanno annualmente in Sicilia e supportano l’efficacia della vaccinazione nella riduzione significativa dei casi di ospedalizzazione per GARV in assenza di incrementi di rischio di intussuscezione

Anxiolytic-like effects of nociceptin/orphanin FQ in the elevated plus maze and in the conditioned defensive burying test in rats

Different reports suggest that nociceptin/orphanin FQ (N/OFQ) may have either anxiolytic- or anxiogenic-like effect in rodents. Since N/OFQ elicits hypolocomotion, which undergoes rapid tolerance, and hypolocomotion may be associated to emotional consequences, the present study was designed to investigate the effect of N/OFQ on anxiety after development of tolerance to its hypolocomotor effect. The effect of single or double intracerebroventricular (i.c.v.) injection of N/OFQ was evaluated on anxiety-related behaviors in rats, in the elevated plus maze (EPM) and conditioned defensive burying (CDB) tests. After single administration, N/OFQ displayed an anxiogenic-like pattern of response on the elevated plus maze but hypolocomotion was also observed. Conversely, in the CDB test, N/OFQ induced a clear-cut anxiolytic pattern. To produce tolerance to N/OFQ-induced hypolocomotion the peptide was administered by two i.c.v. injections separated by 120 min; in these conditions it decreased the expression of anxiety-related behaviors in both tests without affecting locomotor activity. The nociceptin/orphanin FQ peptide (NOP) receptor antagonist UFP-101 significantly reduced the effects of N/OFQ to control values in either tests. Corticosterone levels were significantly increased after a single N/OFQ administration (not in a dose-dependent manner) but this increase did not reach significance after double administration (1 nmol/rat). Our results support the idea that N/OFQ may act as an anxiolytic-like agent in the rat; the apparent anxiogenic-like effect observed following its single administration in the EPM may be consequent to its, effect on locomotion. (c) 2006 Elsevier Inc. All rights reserved

Immunotherapeutic strategies in chronic lymphocytic leukemia: advances and challenges

Immune-based therapeutic strategies have drastically changed the landscape of hematological disorders, as they have introduced the concept of boosting immune responses against tumor cells. Anti-CD20 monoclonal antibodies have been the first form of immunotherapy successfully applied in the treatment of CLL, in the context of chemoimmunotherapy regimens. Since then, several immunotherapeutic approaches have been studied in CLL settings, with the aim of exploiting or eliciting anti-tumor immune responses against leukemia cells. Unfortunately, despite initial promising data, results from pilot clinical studies have not shown optimal results in terms of disease control - especially when immunotherapy was used individually - largely due to CLL-related immune dysfunctions hampering the achievement of effective anti-tumor responses. The growing understanding of the complex interactions between immune cells and the tumor cells has paved the way for the development of new combined approaches that rely on the synergism between novel agents and immunotherapy. In this review, we provide an overview of the most successful and promising immunotherapeutic modalities in CLL, including both antibody-based therapy (i.e. monoclonal antibodies, bispecific antibodies, bi- or tri- specific killer engagers) and adoptive cellular therapy (i.e. CAR T cells and NK cells). We also provide examples of successful new combination strategies and some insights on future perspectives

Multi-analytical investigation on felt-tip pen inks: Formulation and preliminary photo-degradation study

We present a multi-analytical study on the formulation of commercial felt-tip pens, introduced in the second half of the 20th century and commonly used by modern and contemporary artists. These media of both drawing and writing have not yet been fully investigated, but the degradation processes they might undergo, such as fading, are well-known and rather apparent.Twelve water-based felt-tip pens were investigated by the joint use of complementary analytical techniques, such as Thin Layer Chromatography, Nuclear Magnetic Resonance, Fourier transformed infrared spectroscopy, X-ray fluorescence spectrometry and Pyrolysis-Gas Chromatography/Mass Spectrometry.The obtained results provided crucial, preliminary data for the identification of dyes, solvents and additives present in the inks' formulations. Numerous synthetic food coloring agents and pigments were identified, such as Acid Yellow 23, Acid Red 18, Acid Blue 9, and Pigment Blue 15. In addition, glycols, fatty acids, 2-phenoxyethanol, colophony, benzotriazole derivatives and other solvents and additives were detected in the manufactured inks.Furthermore, the effects of photo-degradation on one emblematic ink sample were studied, highlighting in particular visual and aesthetical changes due to discoloration.This study demonstrates a methodology based upon the use of an integrated analytical approach for the characterization of commercial ink-based artistic media and their viable degradation patterns, which aims to develop suitable conservation treatments to assess modern and contemporary drawings and writings. (C) 2015 Elsevier B.V. All rights reserved