Acyl-Imidazoles A Privileged Ester Surrogate for Enantioselective Synthesis

International audienceSince the first report by Evans in asymmetric Friedel‐Crafts reactions, the use of acyl‐imidazoles has blossomed as powerful ester/amide surrogates. The imidazole scaffold indeed displays stability and special activation features allowing both better reactivity and selectivity in traditional ester/amide functionalizations: α‐(enolate chemistry), β‐(conjugate additions), α,β‐(cycloadditions) or γ/δ‐(vinylogous). An overview of the contemporary and growing interest in acyl‐imidazoles in metal‐ and organo‐catalyzed transformations (bio‐hybrid catalytic systems will be fully described in a back‐to‐back Minireview) will be highlighted. Moreover, post‐functionalization expediencies are also going to be discussed in this Minireview

Tempo de demora intra-hospitalar das síndromes coronárias agudas

TITULO: Tempo de Demora Intra-hospitalar das Síndromes Coronárias Agudas. ENQUADRAMENTO: A doença coronária, por si só, mantém-se no primeiro lugar das causas de morte na União Europeia. O enfarte agudo do miocárdio (EAM) constitui uma importante causa de morbilidade e mortalidade, sobretudo ao nível dos países industrializados, e resulta, habitualmente, de um processo progressivo de aterosclerose coronária. Todos os anos em Portugal ocorrem cerca de 10.000 EAM. Em doentes com enfarte do miocárdio com supradesnivelamento do segmento ST, a reperfusão precoce é o tratamento de eleição. Manter o menor intervalo de tempo desde o início dos sintomas até à reperfusão é realçado nas guidelines atuais como uma prioridade. OBJECTIVOS: Determinar o tempo de demora intra-hospitalar das Síndromes Coronárias Agudas e analisar a influência de determinadas variáveis no tempo de demora intra-hospitalar, como a idade, o sexo, a forma de admissão (proveniência e tipo de transporte), a prioridade do Sistema de Triagem de Manchester (STM), a dor torácica, o tipo de Síndrome Coronária Aguda (SCA) e a Via Verde Coronária (VVC). MÉTODOS: É um estudo quantitativo e transversal. Amostra constituída por 204 indivíduos com diagnóstico médico de SCA, internados na UCIC do CHTV, EPE, no período compreendido de 1 de Janeiro de 2010 a 30 de Setembro de 2010. A recolha de dados teve por base o registo informático do Sistema ALERT®. RESULTADOS: Os doentes são maioritariamente do sexo masculino (70,1%) com uma média de idades de 69,75 anos (dp=12,74). 63,2% são provenientes do domicílio, 34,8% foram referenciados pelo centro de saúde/SUB. A ambulância sem médico e os meios próprios são o tipo de transporte mais utilizado (44,1% e 42,6% respetivamente). 96,1% dos indivíduos apresentaram dor torácica. 49,0% dos indivíduos foi diagnosticado EAM sem Supra-ST, 32,4% dos indivíduos foi diagnosticado EAM com Supra-ST e 18,6% dos indivíduos foi diagnosticado angina instável. O tempo médio de demora pré-hospitalar (DPH) foi de 1043,11 minutos e o tempo médio entre o início da dor torácica e a admissão no Serviço de Urgência (TDH) foi de 1044,13 minutos; o tempo médio entre a admissão e a realização de triagem (DAT) foi de 8,60 minutos; o tempo médio entre a triagem e a realização do eletrocardiograma (DT-ECG) foi de 34,09 minutos; o tempo médio entre a realização do eletrocardiograma e a primeira observação médica (D-ECGMédico) foi de 20,48 minutos; o tempo médio entre a primeira observação médica e a administração da primeira terapêutica (D-Médico-Terapêutica) foi de 20,25 minutos; o tempo médio entre a admissão e a alta/internamento do doente (DIH-SU) foi de 281,91 minutos, com um tempo mínimo de 6 minutos e máximo de 1500 minutos. 64,7% dos indivíduos fizeram o 1.º ECG no SU num tempo superior a 10 minutos e apenas 35,3% dos indivíduos fizeram o 1.º ECG no SU num tempo 10 minutos. 74,5% dos indivíduos foram triados através do fluxograma Dor Torácica, 70,6% dos indivíduos foram triados com a prioridade laranja e 72,7% dos indivíduos do sexo masculino e 70,5% dos indivíduos do sexo feminino entraram pela VVC. Relativamente ao DIH-SU, o tempo médio foi de 126,71 minutos (dp=141,023) nos indivíduos com EAM com Supra-ST, 340,76 minutos (dp=246,71) nos indivíduos com EAM sem Supra-ST e 396,61 minutos (dp=324,50) nos indivíduos com angina instável. CONCLUSÃO: Os indivíduos do sexo masculino têm um tempo de demora intrahospitalar inferior aos indivíduos do sexo feminino (p> 0,05). Os indivíduos do grupo etário <55 anos apresentam melhores valores médios do tempo entre a admissão e a alta/internamento (p> 0,05). Os indivíduos transferidos do domicílio apresentam melhores valores médios no tempo de demora intra-hospitalar que os indivíduos que são referenciados por outra Instituição de Saúde (p> 0,05). Os indivíduos transportados em ambulância com médico apresentam melhores tempos médios de demora intrahospitalar (p< 0,05). Os indivíduos com dor torácica apresentam piores tempos médios de demora intra-hospitalar que os indivíduos sem dor torácica, à exceção do tempo entre a triagem e o ECG (p< 0,05). Os indivíduos com EAM com Supra-ST são os indivíduos que apresentam melhores tempos médios de demora intra-hospitalar (p< 0,001). Os indivíduos que entraram na VVC são os indivíduos que apresentam melhores tempos médios de demora intra-hospitalar (p< 0,001). PALAVRAS-CHAVE: Síndrome coronária aguda, Tempo de demora intra-hospitalar, Triagem de Manchester, Dor torácica, Tipo de SCA, Via Verde Coronária, ECG.ABSTRACT TITLE: In-hospital delay time in Acute Coronary Syndrome FRAMEWORK: Coronary heart disease alone remains in the first cause of death in the European Union. The acute myocardial infarction (AMI) is an important cause of morbidity and mortality, especially at the level of industrialized countries, and usually results of a progressive process of coronary atherosclerosis. Every year in Portugal occur, about 10000 AMI. In patients with ST-segment elevation myocardial infarction, the early reperfusion therapy is the treatment of choice. Keep the shortest time interval from symptom onset to reperfusion is emphasized in current guidelines as a priority. OBJECTIVES: Determining the time delay of thein-hospital management of Acute Coronary Syndromes and analyze the influence of certain variables in the in-hospital delay time, such as age, sex, the form of admission (provenance and type of transport), the priority of the Manchester Triage System, chest pain, the type of Acute Coronary Syndrome (ACS) and VVC. METHODS: It is a quantitative cross-sectional, retrospective study. Sample of 204individuals, with diagnosis of acute coronary syndrome (ACS), hospitalized in the Coronary Care Unit of CHTV, EPE from the period 1 January 2010 to 30 September 2010. Data collection was based on the computer record ALERT ®System. RESULTS: Patients are mostly male (70.1%) with average age of 69,75. 63.2% came from home, 34.8% were referred by a health center. The type of transport used were, ambulance without doctor and by own means (44.1% and 42.6% respectively). 96.1%ofindividuals had chest pain. 49.0% of individuals were diagnosed with Non-STsegment elevation myocardial infarction, 32.4% of individuals were diagnosed with STsegment elevation myocardial infarction and 18.6%of individuals diagnosed unstable angina. The pre-hospital delay time average was 1043.11 minutes and the time of the beginning of chest pain and admission to hospital average was 1044.13 minutes; time average between admission and triage was 8.60 minutes; time between triage and application of ECG averaged 34.09 minutes; time between execution of ECG and the first medical observation averaged 20.48 minutes; time between the first observation and the first medical therapeutic averaged 20.25 minutes. The average time between admission and discharge/hospitalization was 281.91 minutes, with a minimum time of 6 minutes and a maximum of 1500 minutes. 64.7%of individual shad the first ECG in the emergency room at a time over 10 minutes and only 35.3% of individual shad the first ECG in the emergency room at a time 10 minutes. 74.5% of individuals were triaged through the flowchart chest pain, 70.6% of individuals were triaged with the priority orange and 72.7% of males and 70.5% of females entered the VVC. For the time between admission and discharge/hospitalization, the average time was 126.71 minutes (sd = 141.03) in individuals with ST-segment elevation myocardial infarction, 340.76 minutes (sd = 246.71) in individuals with Non-ST-segment elevation myocardial infarction and 396.61 minutes (sd = 324.50) in patients with unstable angina. CONCLUSION: The males have a lower in-hospital delay time than females (p>0.05). Individuals in the age group <55 year shave better average time between admission and discharge/hospitalization (p>0.05). Individuals transferred from home show better average in-hospital delay time than individuals that are referenced by other Health Institutions (p>0.05). Individuals transported by ambulance with a doctor have better average in-hospital delay time (p<0.05). Individuals with chest pain have worse average in-hospital delay time than individuals without chest pain, except for the time between triage and ECG (p <0.05). Individuals with ST-segment elevation myocardial infarction are the individuals with the best average in-hospital delay time (p <0.001). Individuals who entered the VVC are individuals who have better average in-hospital delay time (p <0.001). KEY WORDS: Acute coronary syndrome, in- hospital delay time, Manchester Triage system, chest pain, type of ACS, via verde coronária. Sd= standard deviation

Cancer health disparities in racial/ethnic minorities in the United States

There are well-established disparities in cancer incidence and outcomes by race/ethnicity that result from the interplay between structural, socioeconomic, socio-environmental, behavioural and biological factors. However, large research studies designed to investigate factors contributing to cancer aetiology and progression have mainly focused on populations of European origin. The limitations in clinicopathological and genetic data, as well as the reduced availability of biospecimens from diverse populations, contribute to the knowledge gap and have the potential to widen cancer health disparities. In this review, we summarise reported disparities and associated factors in the United States of America (USA) for the most common cancers (breast, prostate, lung and colon), and for a subset of other cancers that highlight the complexity of disparities (gastric, liver, pancreas and leukaemia). We focus on populations commonly identified and referred to as racial/ethnic minorities in the USA—African Americans/Blacks, American Indians and Alaska Natives, Asians, Native Hawaiians/other Pacific Islanders and Hispanics/Latinos. We conclude that even though substantial progress has been made in understanding the factors underlying cancer health disparities, marked inequities persist. Additional efforts are needed to include participants from diverse populations in the research of cancer aetiology, biology and treatment. Furthermore, to eliminate cancer health disparities, it will be necessary to facilitate access to, and utilisation of, health services to all individuals, and to address structural inequities, including racism, that disproportionally affect racial/ethnic minorities in the USA.Fil: Zavala, Valentina A.. University of California; Estados UnidosFil: Bracci, Paige M.. University of California; Estados UnidosFil: Carethers, John M.. University of Michigan; Estados UnidosFil: Carvajal Carmona, Luis. University of California at Davis; Estados UnidosFil: Coggins, Nicole B.. University of California at Davis; Estados UnidosFil: Cruz Correa, Marcia R.. Universidad de Puerto Rico; Puerto RicoFil: Davis, Melissa. No especifíca;Fil: de Smith, Adam J.. University of California; Estados UnidosFil: Dutil, Julie. Ponce Research Institute; Puerto RicoFil: Figueiredo, Jane C.. Cedars Sinai Medical Center; Estados UnidosFil: Fox, Rena. University of California; Estados UnidosFil: Graves, Kristi D.. University Of Georgetown; Estados UnidosFil: Gomez, Scarlett Lin. University of California; Estados UnidosFil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Neuhausen, Susan L.. No especifíca;Fil: Newman, Lisa. No especifíca;Fil: Nguyen, Tung. University of California; Estados UnidosFil: Palmer, Julie R.. National Institutes of Health; Estados UnidosFil: Palmer, Nynikka R.. University of California; Estados UnidosFil: Pérez Stable, Eliseo J.. National Institutes of Health; Estados UnidosFil: Piawah, Sorbarikor. University of California; Estados UnidosFil: Rodriquez, Erik J.. National Institutes of Health; Estados UnidosFil: Sanabria Salas, María Carolina. Instituto Nacional de Cancerología; ColombiaFil: Schmit, Stephanie L.. University of Southern California; Estados UnidosFil: Serrano Gomez, Silvia J.. Instituto Nacional de Cancerología; ColombiaFil: Stern, Mariana Carla. University of Southern California; Estados UnidosFil: Weitzel, Jeffrey. No especifíca;Fil: Yang, Jun J.. St. Jude Children’s Research Hospital; Estados UnidosFil: Zabaleta, Jovanny. No especifíca;Fil: Ziv, Elad. University of California; Estados UnidosFil: Fejerman, Laura. University of California; Estados Unido

Shared heritability and functional enrichment across six solid cancers

Correction: Nature Communications 10 (2019): art. 4386 DOI: 10.1038/s41467-019-12095-8Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.Peer reviewe