Childhood medical history and psychosis in adult life: Findings from the Bologna EU-GEI incidence and case–control study

Aim: To estimate the association between the inpatient admissions and Emergency Department (ED) visits before age of 18 years and adulthood-onset first-episode psychosis (FEP). Methods: We conducted a FEP incidence and case–control study and calculated the odds ratios (ORs) for incident FEP associated with inpatient admissions and ED visits prior to age of 18 years, adjusting our results for cannabis use, parental socio-economic class and childhood trauma. Results: In multivariate logistic regression analysis, odds of FEP increased significantly if the participant had a history of at least one inpatient admission (OR = 3.52; 95% confidence interval [95%CI] 1.07-11.54; P =.04) or at least one ED visit (OR = 8.93; 95%CI 2.41-33.14; P =.001) before age of 18. The associations remained significant adjusting for cannabis use, education, parental socio-economic class and childhood trauma. Conclusion: Consistently with the socio-neurodevelopmental model, we found a significant association between a positive history of hospital care in childhood and adulthood-onset psychosis

Molecular Monitoring of BCR-ABL Transcripts after Allogeneic Stem Cell Transplantation for Chronic Myeloid Leukemia

AbstractThe monitoring of minimal residual disease (MRD) through low sensitivity real-time (RT) polymerase chain reaction (PCR) analysis of BCR-ABL transcripts allows early detection of chronic myeloid leukemia (CML) relapse after allogeneic hematopoietic stem cell transplantation (HSCT). The introduction of more sensitive techniques, such as RT quantitative (Q)-PCR, may lead to an overestimation of the risk of CML relapse. In this study, we reviewed the results of peripheral blood RT Q-PCR in CML patients who underwent allogeneic HSCT from 1983 to 2007. In our laboratory, RT Q-PCR analysis was routinely performed since 2002. Eighty-seven of 189 patients had available RT Q-PCR data; 63 patients had at least 3 RT Q-PCR analyses assessable. Fifty-two of 63 patients (83%) had, at least once, detectable transcript levels, but with an BCR-ABL/ABL ratio <.1% defined as .1% confirmed by the finding of Ph+ cells in bone marrow. No patients with persistent undetectable transcripts relapsed (P = .19). Relapse did not correlate with the number of occurrences o

Steps towards sustainable solid phase peptide synthesis: use and recovery ofN-octyl pyrrolidone

The investigation of new green biogenic pyrrolidinones as alternative solvents toN,N-dimethylformamide (DMF) for solid phase peptide synthesis (SPPS) led to the identification ofN-octyl pyrrolidone (NOP) as the best candidate. NOP showed good performances in terms of swelling, coupling efficiency and low isomerization generating peptides with very high purity. A mixture of NOP with 20% dimethyl carbonate (DMC) allowed a decrease in solvent viscosity, making the mixture suitable for the automated solid-phase protocol. Aib-enkephalin and linear octreotide were successfully used to test the methodologies. It is worth noting that NOP, DMC and the piperidine used in the deprotection step could be easily recovered by direct distillation from the process waste mixture. The process mass intensity (PMI), being reduced by 63-66%, achieved an outstanding value representing a clear step forward in achieving green SPPS

Sustainability in peptide chemistry: current synthesis and purification technologies and future challenges.

Developing greener synthesis processes is an inescapable necessity to transform the industrial landscape, mainly in the pharmaceutical sector, into a long-term, sustainable reality. In this context, the renaissance of peptides as medical treatments, and the enforcement of more stringent sustainability requirements by regulatory agencies, pushed chemists toward the introduction of sustainable processes to prepare highly pure, active pharmaceutical ingredients (APIs). Innovative upstream (synthesis) and downstream (purification) methodologies have been developed during the last 5 years with the introduction and optimization of several technologies in solid-phase peptide synthesis (SPPS), liquid-phase peptide synthesis (LPPS), chemoenzymatic peptide synthesis (CEPS), and chromatographic procedures. These innovations are also moving toward the introduction of continuous processes that represent one of the most important targets for iterative processes. This overview discusses the most recent efforts in making peptide chemistry greener. The extensive studies that were carried out on green solvents, reaction conditions, auxiliary reagents and purification technologies in the peptide segment can be useful to other fields of organic synthesi

Strategies to inhibit tumour associated integrin receptors: rationale for dual and multi-antagonists

YesThe integrins are a family of 24 heterodimeric transmembrane cell surface receptors. Involvement in cell attachment to the extracellular matrix, motility, and proliferation identifies integrins as therapeutic targets in cancer and associated conditions; thrombosis, angiogenesis and osteoporosis. The most reported strategy for drug development is synthesis of an agent that is highly selective for a single integrin receptor. However, the ability of cancer cells to change their integrin repertoire in response to drug treatment renders this approach vulnerable to the development of resistance and paradoxical promotion of tumor growth. Here, we review progress towards development of antagonists targeting two or more members of the RGD-binding integrins, notably αvβ3, αvβ5, αvβ6, αvβ8, α5β1, and αIIbβ3, as anticancer therapeutics

ESPON Italian evidence in changing Europe

Il volume, che rientra nelle attività dell’ESPON Contact Point Italia, accoglie i risultati del contributo dei Partner Italiani allo sviluppo dei progetti del Programma ESPON 2013, acronimo di European Observation Network for Territorial Development and Cohesion. I testi sintetizzano ed evidenziano, tra l’altro, le relazioni con le politiche di sviluppo regionale dell’Italia, inserendole in un quadro di cooperazione transnazionale che coinvolge 28 + 4 paesi dell’Unione europea. Affrontando aspetti della politica territoriale europea che spaziano dall’innovazione e conoscenza all’accessibilità, dal policentrismo alle aree metropolitane, dalla migrazione alla globalizzazione, gli Autori mettono in luce la posizione dell’Italia e delle regioni anche rispetto agli obiettivi fissati da Europe 2020. Uno spazio è dedicato alle esperienze regionali che hanno trovato in ESPON uno stimolo e un’occasione di confronto; come pure ai concetti che sottendono il lessico, i principi di orientamento e i nuovi modelli della pianificazione in Europa; e alle esperienze formative rivolte alle giovani generazioni e ai decision maker Il libro si inquadra nelle iniziative del Semestre di Presidenza Italiana dell’Unione europea ed è cofinanziato dal Ministero delle Infrastrutture e dei Trasporti (MIT) responsabile nazionale del Programma ESPON. E’ rivolto ai ricercatori, agli utilizzatori istituzionali, ai policy maker, ai “practioner” e ai “non specialisti”, tra cui gli studenti, affinché possano fare propri i risultati dell’impegno costante, rigoroso e rispettoso delle diversità territoriali che hanno contraddistinto, dal 2007 ad oggi, il contributo della ricerca, anche sperimentale e applicata, alla crescita della società italiana come parte integrante del sistema europeo. L’Osservatorio ESPON, per chi ancora non lo conosce, può rappresentare un viaggio nel territorio europeo, nelle sue diversità territoriali, economiche, sociali, culturali da integrare e rendere coese, sostenibili, mantenendo e sviluppando potenziali di competitività crescenti e, nel contempo, innovando e diffondendo nuovi modi, metodologie, strumenti e prassi per fare del territorio un bene comune e condiviso. Dati, riferimenti e raccomandazioni politiche utili alla crescita del Paese completano il quadro. Presentazione del Ministro delle Infrastrutture, On. Maurizio Lupi Postfazione del Direttore della Coordination Unit del Programma ESPON, Peter MehlbyeThe book is part of the activities of ESPON Contact Point Italy. It includes the results of the contribution of the Italian partners in the development of projects under the ESPON 2013 Programme, which stands for European Observation Network for Territorial Development and Cohesion. The texts summarise and highlight, among other things, the relations with the regional development policies of Italy, placing them in a framework of transnational cooperation involving the 28 + 4 EU Countries. Addressing aspects of European territorial policy, ranging from innovation and knowledge accessibility, from the polycentrism to metropolitan areas, from migration to globalization, the authors highlight the position of Italy and of regions also in relation to the objectives set by Europe 2020. A place is devoted to the regional experiences that in the ESPON found a stimulus and an opportunity for discussion, as well as to the concepts behind the vocabulary, to the principles of guidance, and new planning models in Europe, and to the training experiences aimed at the younger generations and the decision makers The book forms part of the initiatives of the Italian Presidency of the European Union and is co-financed by the Ministry of Infrastructure and Transportation (MIT) in charge of the national ESPON Programme. It is aimed at researchers, institutional users, policy makers, at "practitioners" and "non-specialists" including students, so that they can make use of the results of the constant and rigorous work also respectful of the territorial diversities that have characterized the experimental and applied research since 2007, so contributing to the growth of Italian society as an integral part of the European system. The ESPON Monitoring Centre, for those who still do not know, can be a journey into the European territory, its territorial, economic, social, cultural diversities to integrate and make cohesive and sustainable, by maintaining and developing the increasing potentials of competitiveness and, at the same time, by innovating and disseminating new ways, methodologies, tools and practices to make the territory a common and shared good. Data, references and useful policy recommendations to the growth of the country are also included in the book. Presentation by the Minister of Infrastructure, Mr. Maurizio Lupi Afterword by the Director of the Coordination Unit ESPON Programme , Peter Mehlby

Pathogen reduction/inactivation of products for the treatment of bleeding disorders:what are the processes and what should we say to patients?

Patients with blood disorders (including leukaemia, platelet function disorders and coagulation factor deficiencies) or acute bleeding receive blood-derived products, such as red blood cells, platelet concentrates and plasma-derived products. Although the risk of pathogen contamination of blood products has fallen considerably over the past three decades, contamination is still a topic of concern. In order to counsel patients and obtain informed consent before transfusion, physicians are required to keep up to date with current knowledge on residual risk of pathogen transmission and methods of pathogen removal/inactivation. Here, we describe pathogens relevant to transfusion of blood products and discuss contemporary pathogen removal/inactivation procedures, as well as the potential risks associated with these products: the risk of contamination by infectious agents varies according to blood product/region, and there is a fine line between adequate inactivation and functional impairment of the product. The cost implications of implementing pathogen inactivation technology are also considered

Asymmetric Synthesis of Three and Four Membered Ring Heterocycles - Chapter 1

Small heterocyclic rings constitute systems of central importance in theoretical, synthetic organic, bio-organic and medicinal chemistry, and in particular aziridines and azirines are very useful and interesting systems as they occur in a number of natural and biologically active substances and as they are useful building blocks and versatile synthetic intermediates. Therefore, the development of efficient and stereoselective methods for synthesis and elaboration of aziridines is an inviting ongoing challenge. Very often, stereogenic centers within such strained heterocycles can be used to direct the stereochemical outcome of subsequent transformations

Biologically active analogues of naturally occurring peptides

There are at least three general approaches to the synthesis of biologically active peptides or peptidomimetics. The first one concerns the synthesis of naturally occurring peptides containing unusual amino acids, whose availability from natural sources is too scarce for practical purposes. Apart from the need of a high yielding overall synthetic strategy, a methodology for the preparation of the unusual residues is also generally requested. On the other hand, one could be interested in the synthesis of modified versions of certain bioactive peptides, by substitution of the normal amino acids with unusual groups, aiming to obtain analogues displaying enhanced performances in term of activity, duration, etc. Finally, the search for promising drug leads for the development of potential therapeutic agents often requires the synthesis of new molecules, designed on the basis of native peptides, in which the peptidic part is no longer predominant. In this lecture, selected examples of each approach are given. The first part concerns the synthesis of fragments of lysobactin skeleton, a cyclic depsipeptide antibiotic containing five hydroxyamino acids, by way of the chemistry of aziridines and oxazolines.1 The second example describes the synthesis and the pharmacological characterization of analogues on endomorphin-1, a neuropeptide involved in the modulation of pain transmission, as potential analgesics devoid of secondary effects.2 Finally, the last part of the speech is related to the design of non peptidic RGD-sequence-mimetics as iintegrin-antagonists,3 based on dihydropyridinone scaffolds