Trifluoroacetic Acid Hydroxylamine System as Organocatalyst Reagent in a One-Pot Salt Free Process for the Synthesis of Caprolactam and Amides of Industrial Interest

Abstract In this work we studied the reactivity of the Trifuoroacetic acid hydroxylamine system in the one step salt free synthesis of amides from ketones. A particular regards was paid to the caprolactam synthesis because of its industrial relevance. Synthesis, reactivity and characterization of the hydroxylamine trifuoroacetate is given. Fast oximation reaction of several ketones was gained at room temperature (1 h of reaction quantitative conversion for several ketones). In the same reactor, by raising the temperature at 383 K, the Beckmann rearrangement of the so obtained oximes is easily accomplished in the presence of three equivalent of TFA. The possibility of obtaining the trifuoroacetate of the hydroxylamine with a modifed nitric acid hydrogenation reactions was verifed, too. Reuse of solvent and trifuoroacetic acid is easily achieved by distillation

Are Induced Pluripotent Stem Cells a Step towards Modeling Pediatric Leukemias?

Despite enormous improvements in pre-clinical and clinical research, acute leukemia still represents an open challenge for pediatric hematologists; both for a significant relapse rate and for long term therapy-related sequelae. In this context, the use of an innovative technology, such as induced pluripotent stem cells (iPSCs), allows to finely reproduce the primary features of the malignancy and can be exploited as a model to study the onset and development of leukemia in vitro. The aim of this review is to explore the recent literature describing iPSCs as a key tool to study different types of hematological malignancies, comprising acute myeloid leukemia, non-down syndrome acute megakaryoblastic leukemia, B cell acute lymphoblastic leukemia, and juvenile myelomonocytic leukemia. This model demonstrates a positive impact on pediatric hematological diseases, especially in those affecting infants whose onsets is found in fetal hematopoiesis. This evidence highlights the importance of achieving an in vitro representation of the human embryonic hematopoietic development and timing-specific modifications, either genetic or epigenetic. Moreover, further insights into clonal evolution studies shed light in the way of a new precision medicine era, where patient-oriented decisions and therapies could further improve the outcome of pediatric cases. Nonetheless, we will also discuss here the difficulties and limitations of this model

Interactions of Cr(VI) and Cr(III) with isolated rat live mitochondria.

The mechanism of interaction of Cr(VI) with isolated rat liver mitochondria was investigated in this study. The results suggest that Cr(VI) induces the opening of the membrane permeability transition pore (MPT). The phenomenon is cyclosporine-sensitive and is in agreement with the cyclosporine-sensitive apoptosis observed in the cells incubated with this compound. Moreover the action of Cr(III), that is formed in the cells by a reduction of Cr(VI), has been also analysed. The results obtained demonstrated that the Cr(III) does not induce the opening of the MPT in isolated mitochondria, but it has a protective effect in preventing Cr(VI) MPT opening. Therefore, these results suggest that apoptosis is regulated by a balance between Cr(VI) accumulation in the cytoplasm and Cr(III) formation

Tissue transglutaminase (TG2) enables survival of human malignant pleural mesothelioma cells in hypoxia

Malignant pleural mesothelioma (MPM) is an aggressive tumor linked to environmental/occupational exposure to asbestos, characterized by the presence of significant areas of hypoxia. In this study, we firstly explored the expression and the role of transglutaminase 2 (TG2) in MPM cell adaptation to hypoxia. We demonstrated that cells derived from biphasic MPM express the full-length TG2 variant at higher levels than cells derived from epithelioid MPM and normal mesothelium. We observed a significant induction of TG2 expression and activity when cells from biphasic MPM were grown as a monolayer in chronic hypoxia or packed in spheroids, where the presence of a hypoxic core was demonstrated. We described that the hypoxic induction of TG2 was HIF-2 dependent. Importantly, TGM2-v1 silencing caused a marked and significant reduction of MPM cell viability in hypoxic conditions when compared with normoxia. Notably, a TG2-selective irreversible inhibitor that reacts with the intracellular active form of TG2, but not a non-cell-permeable inhibitor, significantly compromised cell viability in MPM spheroids. Understanding the expression and function of TG2 in the adaptation to the hypoxic environment may provide useful information for novel promising therapeutic options for MPM treatment

Applied live art : co-authorship in socially engaged and site-responsive performance practice

This thesis looks at the ways in which performance can integrate participants and local context into the development of new devised work. This practice-led research is based on a methodology that grew out of three performance case studies completed in diverse international settings with a varied range of participants. The case studies are: Napoli Scorticata completed in 2007 in Naples, Italy; Youth Visions, completed in 2008 in Northeastern Ghana, West Africa; Triangulated City, completed in 2009 in Beirut, Lebanon. Within these diverse contexts the research questions the role of authorship when working in socially engaged practice, focusing on how practitioners can shift the focus from the artist to the body politic. Merging social engagement with a site-responsive approach, the research proposes that the artistic medium is the social system and as such argues that the modes of employment require a focus of appreciation on the generative process, context and product combined. The research is presented in two parts. Part I is an interactive DVD with images of the development process and final presentations as well as a video of each performance work. Part II is a written thesis that explores the modes of engagement, outlines the methods of development and structures a general working methodology that can be referenced by other performance practitioners. The thesis proposes Applied Live Art as a term to describe practices that include a hybrid of time-based media options, which include a social component as their primary focus. The research outcomes conclude with an analysis of place making and its importance when working with both site and society.EThOS - Electronic Theses Online ServiceBritish Council Middle EastBritish Council ItalyRoyal Holloway Drama DepartmentUniversity of London Central Research FundPresident's Emergency Fund for AIDS ReliefTheatre Communications GroupGBUnited Kingdo

The Italian National Register of infants with congenital hypothyroidism: twenty years of surveillance and study of congenital hypothyroidism

All the Italian Centres in charge of screening, diagnosis, and follow-up of infants with congenital hypothyroidism participate in the Italian National Registry of affected infants, which performs the nationwide surveillance of the disease. It was established in 1987 as a program of the Health Ministry and is coordinated by the Istituto Superiore di Sanità. The early diagnosis performed by the nationwide newborn screening programme, the prompt treatment and the appropriate clinical management of the patients carried out by the Follow-up Centres, and the surveillance of the disease performed by the National Register of infants with congenital hypothyroidism are the components of an integrated approach to the disease which has been successfully established in our country

Comparison of the efficacy of a neutral wrist splint and wrist splint with lumbrical unit for the treatment of patients with carpal tunnel syndrome

Purpose: The purpose of this study was to compare the effect of a neutral wrist splint or a wrist splint with an additional metacarpophalangeal (MCP) unit on pain, function, grip and pinch strength in patients with mild-to-moderate carpal tunnel syndrome (CTS). Methods: Twenty four patients received conservative treatment using either the neutral wrist splint or wrist splint with the MCP unit for a period of 6 weeks. Primary outcome measures were pain, function, grip and pinch strength. Data was collected immediately before and after using the two types of splints at baseline (0 weeks) and 6 weeks. Statistical analysis was performed using the paired t-test and independent T-test. Results: Compared to baseline, both the neutral wrist splint and the wrist splint with an MCP unit significantly decreased pain, increased function and pinch and grip strength. Comparisons of the two types of splints for grip (P =0.675) and pinch strength (P =0.650) revealed that there were no significant differences between the two after 6 weeks of wear. However, there were significant differences in pain levels (P =0.022) and the DASH score (P =0.027) between the two types of splints from baseline to 6 weeks. Conclusion: The wrist splint with an MCP unit was more effective than the neutral wrist splint in pain reduction and improvement of function

Pemetrexed single agent chemotherapy in previously treated patients with locally advanced or metastatic non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>The main objective of this study was to evaluate the safety of second-line pemetrexed in Stage IIIB or IV NSCLC.</p> <p>Methods</p> <p>Overall, 95 patients received pemetrexed 500 mg/m²i.v. over Day 1 of a 21-day cycle. Patients also received oral dexamethasone, oral folic acid and i.m. vitamin B12 supplementation to reduce toxicity. NCI CTC 2.0 was used to rate toxicity. All the adverse events were graded in terms of severity and relation to study treatment. Dose was reduced in case of toxicity and treatment was delayed for up to 42 days from Day 1 of any cycle to allow recovering from study drug-related toxicities. Tumor response was measured using the RECIST criteria.</p> <p>Results</p> <p>Patients received a median number of 4 cycles and 97.8% of the planned dose. Overall, 75 patients (78.9% of treated) reported at least one adverse event: 34 (35.8%) had grade 3 as worst grade and only 5 (5.2%) had grade 4. Drug-related events occurred in 57.9% of patients. Neutropenia (8.4%) and leukopenia (6.3 %) were the most common grade 3/4 hematological toxicities. Grade 3 anemia and thrombocytopenia were reported in 3.2% and 2.1% of patients, respectively. Diarrhea (6.3%), fatigue (3.2%) and dyspnea (3.2%) were the most common grade 3/4 non-hematological toxicities. The most common drug-related toxicities (any grade) were pyrexia (11.6%), vomiting, nausea, diarrhea and asthenia (9.5%) and fatigue (8.4%). Tumor Response Rate (CR/PR) in treated patients was 9.2%. The survival at 4.5 months (median follow-up) was 79% and the median PFS was 3.1 months. Twenty patients (21.1%) died mainly because of disease progression.</p> <p>Conclusion</p> <p>Patients with locally advanced or metastatic NSCLC could benefit from second-line pemetrexed, with a low incidence of hematological and non-hematological toxicities.</p