Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

Microreactor technology and flow chemistry could play an important role in the development of green and sustainable synthetic processes. In this review, some recent relevant examples in the field of flash chemistry, catalysis, hazardous chemistry and continuous flow processing are described. Selected examples highlight the role that flow chemistry could play in the near future for a sustainable development

Whole-body magnetic resonance imaging for staging and follow-up of pediatric patients with Hodgkin's lymphoma: comparison of different sequences

OBJECTIVE: To compare the performance of the T1, T2, STIR and DWIBS (diffusion-weighted whole-body imaging with background body signal suppression) sequences in the staging and follow-up of pediatric patients with Hodgkin's lymphoma in lymph node chains, parenchymal organs and bone marrow, and to evaluate interobserver agreement. MATERIALS AND METHODS: The authors studied 12 patients with confirmed diagnosis of Hodgkin's lymphoma. The patients were referred for whole body magnetic resonance imaging with T1-weighted, T2-weighted, STIR and DWIBS sequences. RESULTS: The number of lymph node sites characterized as affected by the disease on T1- and T2-weighted sequences showed similar results (8 sites for both sequences), but lower than DWIBS and STIR sequences (11 and 12 sites, respectively). The bone marrow involvement by lymphoma showed the same values for the T1-, T2-weighted and DWIBS sequences (17 lesions), higher than the value found on STIR (13 lesions). A high rate of interobserver agreement was observed as the four sequences were analyzed. CONCLUSION: STIR and DWIBS sequences detected the highest number of lymph node sites characterized as affected by the disease. Similar results were demonstrated by all the sequences in the evaluation of parenchymal organs and bone marrow. A high interobserver agreement was observed as the four sequences were analyzed.OBJETIVO: Comparar o desempenho das sequências T1, T2, STIR e DWIBS (difusão de corpo inteiro com supressão do sinal de fundo) na identificação de sítios caracterizados como acometidos pelo linfoma de Hodgkin nas cadeias linfonodais, órgãos parenquimatosos e medula óssea, e avaliar a concordância entre os examinadores. MATERIAIS E MÉTODOS: Foram estudados 12 pacientes com diagnóstico confirmado de linfoma de Hodgkin. Os pacientes foram encaminhados para o exame de ressonância magnética, sendo realizadas as sequências ponderadas em T1, T2, STIR e DWIBS. RESULTADOS: O número de sítios linfonodais caracterizados como acometidos nas sequências ponderadas em T1 e T2 apresentaram resultados semelhantes (8 sítios), mas inferiores às sequências STIR e DWIBS (11 e 12 sítios, respectivamente). Quanto ao acometimento da medula óssea, observaram-se os mesmos valores para as sequências T1, T2 e DWIBS (17 lesões), superiores ao valor encontrado na sequência STIR (13 lesões). Quando realizada a comparação entre os examinadores, nota-se que há alta concordância entre as quatro sequências. CONCLUSÃO: As sequências STIR e DWIBS detectaram maior número de linfonodos caracterizados como acometidos. Todas as sequências apresentaram resultados semelhantes na avaliação dos órgãos parenquimatosos e medula óssea. Em todas as sequências analisadas houve alta concordância entre os examinadores.Universidade Federal de São Paulo (UNIFESP) Departamento de Diagnóstico por ImagemUniversidade Federal de São Paulo (UNIFESP) Instituto de Oncologia Pediátrica GRAACCClínica CentrusUniversidade Federal de São Paulo (UNIFESP) Instituto de Oncologia Pediátrica Centro de Diagnóstico por ImagemUNIFESP, Depto. de Diagnóstico por ImagemUNIFESP, Instituto de Oncologia Pediátrica GRAACCUNIFESP, Instituto de Oncologia Pediátrica Centro de Diagnóstico por ImagemSciEL

Identification of novel proteins binding the AU-rich element of \u3b1-prothymosin mRNA through the selection of open reading frames (RIDome)

We describe here a platform for high-throughput protein expression and interaction analysis aimed at identifying the RNA-interacting domainome. This approach combines the selection of a phage library displaying "filtered" open reading frames with next-generation DNA sequencing. The method was validated using an RNA bait corresponding to the AU-rich element of \u3b1-prothymosin, an RNA motif that promotes mRNA stability and translation through its interaction with the RNA-binding protein ELAVL1. With this strategy, we not only confirmed known RNA-binding proteins that specifically interact with the target RNA (such as ELAVL1/HuR and RBM38) but also identified proteins not previously known to be ARE-binding (R3HDM2 and RALY). We propose this technology as a novel approach for studying the RNA-binding proteome

Ibrutinib plus RICE or RVICI for relapsed/refractory mature B-cell non-Hodgkin lymphoma in children and young adults:SPARKLE trial

Part 1 results of the open-label, randomized, global phase 3 SPARKLE trial supported continued assessment of ibrutinib with either modified rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) in pediatric patients with relapsed/refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL). We report final results of Part 2 evaluating the efficacy of ibrutinib plus RICE or RVICI vs RICE/RVICI alone. Patients aged 1 to 30 years (initial diagnosis \u3c18 years) were randomized 2:1 to receive ibrutinib with or without RICE/RVICI. Primary endpoint was event-free survival (EFS) based on independent committee-confirmed events. Fifty-one patients were enrolled. Median age was 15 years; Burkitt lymphoma, Burkitt leukemia, and Burkitt-like lymphoma (total: 45%) and diffuse large B-cell lymphoma/primary mediastinal B-cell lymphoma (51%) were the most common subtypes. At the preplanned interim analysis, median EFS was 6.1 vs 7.0 months with ibrutinib plus RICE/RVICI vs RICE/RVICI, respectively (hazard ratio, 0.9; 90% confidence interval, 0.5-1.6; P = .387); further enrollment was ceased. With ibrutinib plus RICE/RVICI vs RICE/RVICI, median overall survival was 14.1 vs 11.1 months, overall response rate was 69% vs 81%, and 46% vs 44% proceeded to stem cell transplantation. In both treatment arms, 100% of patients experienced grade ≥3 treatment-emergent adverse events. No EFS benefit was seen with ibrutinib. Salvage was generally poor in patients who received prior rituximab, regardless of treatment arm. No new safety signals were observed. Ibrutinib exposure in pediatric patients fell within the target range of exposure in adults. Trial is registered on www.clinicaltrials.gov (NCT02703272)

Exploring the Universe of Protein Structures beyond the Protein Data Bank

It is currently believed that the atlas of existing protein structures is faithfully represented in the Protein Data Bank. However, whether this atlas covers the full universe of all possible protein structures is still a highly debated issue. By using a sophisticated numerical approach, we performed an exhaustive exploration of the conformational space of a 60 amino acid polypeptide chain described with an accurate all-atom interaction potential. We generated a database of around 30,000 compact folds with at least of secondary structure corresponding to local minima of the potential energy. This ensemble plausibly represents the universe of protein folds of similar length; indeed, all the known folds are represented in the set with good accuracy. However, we discover that the known folds form a rather small subset, which cannot be reproduced by choosing random structures in the database. Rather, natural and possible folds differ by the contact order, on average significantly smaller in the former. This suggests the presence of an evolutionary bias, possibly related to kinetic accessibility, towards structures with shorter loops between contacting residues. Beside their conceptual relevance, the new structures open a range of practical applications such as the development of accurate structure prediction strategies, the optimization of force fields, and the identification and design of novel folds

Non Hodgkin's lymphoma in childhood and adolescent: treatment experience and clinical, pathological and immunohistochemical correlation

Introdução: O Linfoma nao Hodgkin (LNH) e a terceira neoplasia mais frequente na faixa etaria pediatrica e representa 10 por cento das doencas malignas da infancia. Objetivos: Descrever as caracteristicas do linfoma nao Hodgkin quanto ao tipo de apresentacao ao diagnostico, tratamento, evolucao clinica e fatores prognosticos; correlacionar as caracteristicas clinicas e a imuno-expressao das proteinas p53, p21, MDM2, Bcl-2, VEGF, o antigeno PCNA e o anticorpo monoclonal MIB1 (Ki-67) nos especimes tumorais com a sobrevida global e a sobrevida livre de doenca de criancas e adolescentes com linfoma nao Hodgkin. Metodos: No periodo de junho de 1988 a janeiro de 2003, foram tratados duzentos e quatro pacientes portadores de linfoma nao Hodgkin, de forma consecutiva, nao selecionada; 27 (13,23 por cento) com o protocolo LNH II 85, cento e setenta e um (83,82 por cento) com os protocolos do Grupo Brasileiro para Tratamento de Linfoma na Infancia (GBTLI) e seis (3 por cento) com outros protocolos. Dos 204 pacientes foram resgatados 90 blocos de parafina os quais possibilitaram inumeros cortes para revisao. O estudo imunoistoquimico foi realizado para os seguintes anticorpos: PCNA, p53, Ki-67, p21, Bcl2, MDM2 e VEGF. A imunoexpressao do Ki-67 e do PCNA foi avaliada quantitativamente contando-se no minimo 1000 celulas neoplasicas. A analise das laminas do p53, Bcl2, p21, MDM2 e VEGF foi realizada atraves do metodo semiquantitativo nas areas de hot spots. Resultados: A nossa casuistica mostrou que a maioria (82 por cento) dos pacientes apresentavam estadio avancado (III e IV); 61 por cento dos pacientes avaliados tinham DHL acima do normal ao diagnostico; em 51 pacientes (26 por cento) o nivel chegava ate a duas vezes o limite superior de normalidade, enquanto em 68 pacientes (35 por cento) os valores de DHL ultrapassavam duas vezes o limite superior de normalidade; o abdome (53 por cento), cabeca e pescoco (24,5 por cento), torax (14 por cento) e osso (7 por cento), foram os locais primarios mais frequentemente acometidos; houve um predominio dos linfomas de Burkitt (51,5 por cento), seguido pelos linfomas de grandes celulas (21,1 por cento) e os linfomas linfoblasticos (17,6 por cento). Conclusoes: Quase a totalidade dos pacientes (95 por cento) entrou em remissao. A sobrevida livre de doenca aos cinco anos foi de 81 por cento e a sobrevida livre de eventos de 80 por cento. Dos 31 pacientes recidivados e com falha de inducao, foram resgatados, com segundo tratamento, 10 criancas (32 por cento). Sete delas (22 por cento) estao vivas e livres de doenca. Nao houve correlacao entre as caracteristicas clinicas e a sobrevida global. As variaveis clinicas que mostraram influencia no tempo de sobrevivencia livre da doenca foram: o sitio do tumor primario, estadio e lise do tumor. Os pacientes que expressam Ki-67 maior que 66,18 por cento, tiveram maior sobrevida livre de doenca do que aqueles pacientes cuja expressao do Ki-67 foi menor que 66,18 por cento. Os pacientes que apresentaram sindrome da lise tumoral tiveram 2,8 vezes mais chances de recidivar do que pacientes que nao apresentaram lise tumoral; os pacientes que apresentaram Ki-67 menor ou igual a 66,18 por cento tem 4,2 vezes mais chance de recidivar do que pacientes que apresentaram Ki-67 maior que 66,18 por centoBV UNIFESP: Teses e dissertaçõe

Contribuição para o tratamento da náusea e do vômito, induzidos pela quimioterapia, em crianças e adolescentes com osteossarcoma

BV UNIFESP: Teses e dissertaçõe

Flow chemistry as enabling technology for controlling the reactivity of fluorocarbenoids

Fluorinated compounds have attracted a great deal of interest by scientists involved in many field of science and technology. However, despite their importance, the selective introduction of monofluoromethyl groups (-CH2F) into a small organic molecules is still a challenging task. Unlike the extensive use of other halocarbenoids in organic synthesis, fluorocarbenoids are still considered the "beast" in carbenoid chemistry due to their chemical instability that severely limited its use in synthetic process. In this communication, we report how we tried to face this challenge by employing flow microreactor technology. Fluorocarbenoids could be effectively generated and trapped with electrophiles providing a new successfully application of flash chemistry in short-lived intermediate reactions. Mechanistic insights and applications will be presented

Functionalization of four-membered cyclic sulfoximines by a convenient lithiation/trapping sequence

The functionalization of four-membered cyclic sulfoximine, based on a lithiation/electrophile trapping sequence, led to unprecedented C(2)-substituted N-Boc-1-imino-16-thietane 1-oxide in moderate to good yields. Interestingly, the reaction proceeded with high stereocontrol showing a preferential bias for an introduction of the electrophile syn to the oxygen on the sulfur. Starting from thietan- 1-one, by a combination of lithiation/electrophile trapping followed by N-transfer, it is possible to obtain the stereoisomer bearing the electrophile syn to the nitrogen on the sulfur. Thus, all stereoisomers can be accessible for medicinal chemistry studies