Synthesis of new beta-amidodehydroaminobutyric acid derivatives and of new tyrosine derivatives using copper catalyzed C-N and C-O coupling reactions

Several beta-amidodehydroaminobutyric acid derivatives were prepared from N,C-diprotected beta-bromodehydroaminobutyric acids and amides by a copper catalyzed C-N coupling reaction. The best reaction conditions include the use of a catalytic amount of CuI, N,N’-dimethylethylenediamine as ligand and K2CO3 as base in toluene at 110 ºC. The stereochemistry of the products was determined using NOE difference experiments and the results obtained are in agreement with an E-stereochemistry. Thus, the stereochemistry is maintained in the case of the E-isomers of beta-bromodehydroaminobutyric acid dervatives, but when the Z-isomers were used as substrates the reaction proceeds with inversion of configuration. The use of beta-bromodehydrodipeptides as substrates was also tested. It was found that the reaction outcome depend on the stereochemistry of the beta-bromodehydrodipeptide and on the nature of the first amino acid residue. The products isolated were the beta-amidodehydrodipeptide derivatives and/or the corresponding dihydropyrazines. The same catalytic system (CuI/N,N’-dimethylethylene diamine) was used in the C-O coupling reactions between a tyrosine derivative and aryl bromides. The new O-aryltyrosine derivatives were isolated in moderate to good yields. The photophysical properties of two of these compounds were studied in four solvents of different polarity. The results show that these compounds after deprotection can used as fluorescence markers.This work was financed by FEDER through "Programa Operacional Factores de Competitividade"-COMPETE and by FCT-"Fundacao para a Ciencia e Tecnologia" through project "Projecto Estrategico-UI 686-2011-2012" Ref: PEst-C/QUI/UI0686/2011. The NMR spectrometer is part of the National NMR Network (RNRMN) and was purchased in the framework of the National Programme for Scientific Re-equipment, contract REDE/1517/RMN/2005, with funds from POCI 2010 (FEDER) and Fundacao para a Ciencia e a Tecnologia (FCT) and is supported with funds from FCT. G. P. acknowledges FCT for a PhD grant SFRH/BD/38766/2007. H. V. acknowledges FCT for a PhD grant SFRH/BD/7265/2010

Intracardiac mass from Burkitt's lymphoma in an immunocompromised patient: a very rare form of presentation

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Population-specific signatures of intra-individual mitochondrial DNA heteroplasmy and their potential evolutionary advantages

Heteroplasmy is the existence of more than one mitochondrial DNA (mtDNA) variant within a cell. The evolutionary mechanisms of heteroplasmy are not fully understood, despite being a very common phenomenon. Here we combined heteroplasmy measurements using high throughput sequencing on green turtles (Chelonia mydas) with simulations to understand how heteroplasmy modulates population diversity across generations and under different demographic scenarios. We found heteroplasmy to be widespread in all individuals analysed, with consistent signal in individuals across time and tissue. Significant shifts in haplotype composition were found from mother to offspring, signalling the effect of the cellular bottleneck during oogenesis as included in the model. Our model of mtDNA inheritance indicated that heteroplasmy favoured the increase of population diversity through time and buffered against population bottlenecks, thus indicating the importance of this phenomenon in species with reduced population sizes and frequent population bottlenecks like marine turtles. Individuals with recent haplotypes showed higher levels of heteroplasmy than the individuals with ancient haplotypes, suggesting a potential advantage of maintaining established copies when new mutations arise. We recommend using heteroplasmy through high throughput sequencing in marine turtles, as well as other wildlife populations, for diversity assessment, population genetics, and mixed stock analysis

The Role of Noninvasive Ventilation in Patients with "Do Not Intubate" Order in the Emergency Setting

Noninvasive ventilation (NIV) is being used increasingly in patients who have a "do not intubate" (DNI) order. However, the impact of NIV on the clinical and health-related quality of life (HRQOL) in the emergency setting is not known, nor is its effectiveness for relieving symptoms in end-of-life care. OBJECTIVE: The aim of this prospective study was to determine the outcome and HRQOL impact of regular use of NIV outcomes on patients with a DNI order who were admitted to the emergency room department (ED). METHODS: Eligible for participation were DNI-status patients who receive NIV for acute or acute-on-chronic respiratory failure when admitted to the ED of a tertiary care, university-affiliated, 600-bed hospital between January 2014 and December 2014. Patients were divided into 2 groups: (1) those whose DNI order related to a decision to withhold therapy and (2) those for whom any treatment, including NIV, was provided for symptom relief only. HRQOL was evaluated only in group 1, using the 12-item Short Form Health Survey (SF-12). Long-term outcome was evaluated 90 days after hospital discharge by means of a telephone interview. RESULTS: During the study period 1727 patients were admitted to the ED, 243 were submitted to NIV and 70 (29%) were included in the study. Twenty-nine (41%) of the 70 enrollees received NIV for symptom relief only (group2). Active cancer [7% vs 35%, p = 0,004] and neuromuscular diseases [0% vs. 17%] were more prevalent in this group. NIV was stopped in 59% of the patients in group 2 due to lake of clinical benefit. The in-hospital mortality rate was 37% for group 1 and 86% for group 2 0,001). Among patients who were discharged from hospital, 23% of the group 1 and all patients in group 2 died within 90 days. Relative to baseline, no significant decline in HRQOL occurred in group 1 by 90 days postdischarge. CONCLUSION: The survival rate was 49% among DNI-status patients for whom NIV was used as a treatment in ED, and these patients did not experience a decline in HRQOL throughout the study. NIV did not provide significant relief of symptoms in more than half the patients who receive it for that purpose.Supported, in part, by grants from the Discipline of Initiation to Clinical Investigation (Disciplina de Iniciação à Investigação Clínica) of Instituto de Ciências Biomédicas Abel Salazar and in part by ASSUCIP (Associação dos Amigos da Unidade de Cuidados Intensivos Polivalente, Hospital de Santo António, Porto, Portugal).info:eu-repo/semantics/publishedVersio

Exploring blended learning tools to transform a laboratory course unit in engineering: Challenges, setbacks and rewards

To boost students engagement on learning outcomes, promote active peer learning, and adopt more dynamic teaching practices, a module of a laboratory course unit (TPL) in engineering was reformulated exploring blended learning. This reformulation was even more challenging than initially anticipated as it was implemented during the Covid-19 pandemic. As TPL learning practises are based on the operation of laboratory modules mimicking heat and mass transfer phenomena, asynchronous and on-line synchronous learning classes and face-to-face laboratory classes were outlined. To promote the asynchronous learning, a full script of TPL and pitch and longer videos presenting, respectively, each work and its practical operation process were formerly prepared and available online. Students were required to work in group to define the variables and conditions to be evaluated in each laboratory module, organize and plan the experimental activities, create data recording documents, and later present and argue their options in virtual synchronous classes. In the face-to-face classes, different activities were performed in a rotating system, scheduled and tuned in the online classes. It was also aimed in-situ promoting peer discussion of the data and reports elaboration, goals not attained due to the pandemic restrictions, as only two students of each group were present in each hands-on class and in sequential times. TPL reformulation was a tough and time-consuming task since 73 students were enrolled, divided into 3 shifts, each one with 5 groups of five students. Students individual learning evolution was inferred through online quizzes that were periodically made available. A final inquiry, launched to obtain students` opinion about this transformation endeavour highlighted the script, videos, and the prompt teachers feedback on the reports as the most fruitful and important aspects for students engagement and guide their learning pathway. The rationale behind this paper was to disclose this transformation experience and share information and strategies that can be used in the teaching/learning of laboratory classes. © 2021 University of Minho. All rights reserved.(undefined)info:eu-repo/semantics/publishedVersio

Tumors of skin appendages – A 10-year review

Introdução: Os tumores dos anexos cutâneos representam um grupo heterogéneo de neoplasias benignas e malignas com diferentes diferenciações morfológicas. Material e Métodos: Foi efectuado o estudo retrospectivo dos tumores dos anexos cutâneos diagnosticados na consulta externa do Serviço de Dermatologia do Centro Hospitalar do Porto, EPE-HSA entre 2000 a 2009. Resultados: Foram diagnosticados 404 tumores dos anexos cutâneos. Apenas 3% dos tumores eram malignos. A maioria apresentou uma diferenciação (62,6 %) folicular. Discussão: A revisão da literatura mostrou uma escassez de dados relativos a estudos retrospectivos dos tumores dos anexos cutâneos. Mais estudos são necessários para uma melhor caracterização epidemiológica destas entidades

Pellagra as the initial presentation of Crohn disease

Pellagra is a nutritional disease caused by the deficiency of niacin. We describe a case of pellagra as the initial presentation of Crohn disease, which has been rarely described in the literature

High yielding synthesis of oxazole-4-carboxylates from dehydroamino acid derivatives : application as fluorescent markers for peptides

This work was funded by Foundation for Science and Technology (FCT) and FEDER through CQ-UM, National NMR Network (Bruker 400), research project PTDC/QUI/81238/2006 and PhD grant of G.P. SFRH/BD/38766/2007

Desenvolvimento de sistema de genotipagem molecular, baseado em marcadores microssatélites, para determinar a identidade genética de cultivares de tabaco.

O desenvolvimento de sistemas de identificação molecular para determinar e rastrear a identidade genética de um cultivar vegetal representa um grande desafio frente aos sistemas de certificação e proteção de variedades utilizados no país, até então fundamentados em descritores fenotípicos. Além disso é uma questão estratégica para empresas detentoras de germoplasma, interessadas no desenvolvimento de ferramentas que permitam o monitoramento de pureza varietal e o rastreamento de materiais ao longo da cadeia produtiva e comercial. Entretanto, a utilização de análises de DNA para a proteção varietal ainda é limitada pela inexistência de sistemas padronizados e robustos de avaliação molecular para a maioria das espécies, a exemplo do que acontece para cultivares de tabaco (Nicotiana sp.). Esse trabalho teve como objetivo o desenvolvimento de sistema de genotipagem molecular, baseado em marcadores microssatélites, para a determinação de identidade genética de cultivares de tabaco de interesse comercial para a agroindústria. Foram selecionados 32 marcadores microssatélites na literatura, de acordo com seu índice de informatividade alélica e da cobertura do genoma da espécie, sendo selecionados tanto a partir do genoma nuclear quanto do cloroplasto. Para a seleção dos marcadores mais informativos, foram testados 49 genótipos de Nicotiana tabacum, dos grupos Burley e Virginia. Para assegurar boa representatividade da diversidade alélica de cada cultivar, foram analisadas 1350 amostras, com uma média de 27,5 indivíduos para cada genótipo, analisados em bulk. O DNA foi extraído pelo método do CTAB modificado, a partir de material foliar. Os produtos de PCR foram visualizados em géis de poliacrilamida corados com brometo de etídeo, e foram utilizados marcadores de tamanho molecular para monitoramento do número e tamanho dos alelos de cada genótipo. Para os marcadores polimórficos foram calculados o Conteúdo de Informação de Polimorfismo (PIC). Para compor um sistema de genotipagem molecular robusto e informativo, foram selecionados aqueles marcadores que apresentaram padrões consistentes de amplificação e interpretação e que evidenciaram polimorfismos alélicos bem definidos entre os genótipos. Assim, dez microssatélites foram selecionados para o grupo de cultivares analisados. Tais marcadores apresentaram de 2 a 3 alelos e um PIC que variou de 0,078 a 0,5487, com média de 0,3412. Do total de marcadores analisados foi possível selecionar um grupo que evidenciou alto padrão de polimorfismo entre os genótipos testados, além de garantir uma ampla cobertura do genoma de Nicotiana tabacum. A partir do grupo de marcadores selecionados, análises de agrupamento por similaridade genotípica, de genealogia e identidade genética inequívoca de cultivares poderão ser realizadas para genótipos de interesse, fornecendo uma ferramenta estratégica em processos de certificação de pureza genética, propriedade intelectual e rastreabilidade ao longo da cadeia produtiva