Nucleotide depletion promotes cell fate transitions by inducing DNA replication stress.

Control of cellular identity requires coordination of developmental programs with environmental factors such as nutrient availability, suggesting that perturbing metabolism can alter cell state. Here, we find that nucleotide depletion and DNA replication stress drive differentiation in human and murine normal and transformed hematopoietic systems, including patient-derived acute myeloid leukemia (AML) xenografts. These cell state transitions begin during S phase and are independent of ATR/ATM checkpoint signaling, double-stranded DNA break formation, and changes in cell cycle length. In systems where differentiation is blocked by oncogenic transcription factor expression, replication stress activates primed regulatory loci and induces lineage-appropriate maturation genes despite the persistence of progenitor programs. Altering the baseline cell state by manipulating transcription factor expression causes replication stress to induce genes specific for alternative lineages. The ability of replication stress to selectively activate primed maturation programs across different contexts suggests a general mechanism by which changes in metabolism can promote lineage-appropriate cell state transitions.

Aprendizagem sobre teleconsulta: representações de um grupo de alunos de um curso de Medicina / Learning about teleconsultation: representations of a group of Medical students / Aprendizaje sobre teleconsulta: representaciones de un grupo de alumnos de un curso de Medicina

Com o avançar da tecnologia, passou a fazer parte da graduação médica atual o aprendizado em teleconsultas. Esta pesquisa apresenta as representações de um grupo de alunos de um curso de Medicina localizado na capital do estado de São Paulo sobre suas experiências com a realização de teleconsultas síncronas supervisionadas durante estágio realizado em um ambulatório-escola, durante o segundo semestre de 2021. Trata-se de pesquisa qualitativa que utilizou o software IRaMuTeQ® e "Análise do Conteúdo". Esses educandos pontuam entraves para a utilização das teleconsultas, destacando preocupações com a humanização, segurança da pessoa atendida e qualidade da consulta, mas visualizam potencialidades tais como a facilidade de acesso e a comodidade. Reconhecem a importância da prática durante sua Graduação em um mundo cada vez mais tecnológico, mas trazem inquietações relacionadas à perda do exame físico e à mercantilização da Medicina.

With the progress of technology, teleconsultation has become part of medical degree courses. This article presents the representations of a group of medical students from a university in the capital of the state of São Paulo regarding their experiences with supervised synchronous teleconsultations during an internship in a teaching clinic in the second semester of 2021. We conducted a qualitative study using the software IRaMuTeQ® and content analysis. The students highlighted barriers to the use of teleconsultation, emphasizing concerns with humanization, patient safety and consultation quality, but also perceived strengths such as ease of access and convenience. They recognize the importance of practice on the degree course in an ever more technological world, but raise concerns about the lack of physical examination and the commodification of medicine.

Con el avance de la tecnología, el aprendizaje en teleconsultas pasó a formar parte de la graduación médica actual. Esta investigación presenta las representaciones de un grupo de alumnos de un curso de medicina localizado en la capital del estado de São Paulo sobre sus experiencias con la realización de teleconsultas sincronizadas supervisadas durante una pasantía realizada en un ambulatorio escuela, durante el segundo trimestre de 2021. Se traba de una investigación cualitativa que utilizó el software IRaMuTeQ® y Análisis de Contenido. Estos alumnos puntúan obstáculos para la utilización de las teleconsultas, destacando preocupaciones con la humanización, seguridad de la persona atendida y calidad de la consulta, pero visualizan potencialidades tales como la facilidad de acceso y la comodidad. Reconocen la importancia de la práctica durante su graduación en un mundo cada vez más tecnológico, pero presentan inquietudes relacionadas a la pérdida del examen físico y a la mercantilización de la medicina.

Valor prognóstico do escore SYNTAX residual nos desfechos clínicos intra- hospitalares e de acompanhamento em pacientes com infarto do miocárdio com supradesnivelamento do segmento ST submetidos à estratégia farmacoinvasiva / Prognostic value of residual SYNTAX score on in-hospital and follow-up clinical outcomes in patients with ST-segment elevation myocardial infarction undergoing pharmacoinvasive strategy

Introdução: A doença arterial coronariana multiarterial é um desafio na prática clínica. Uma abordagem individualizada deve considerar não apenas as características do paciente, mas também um enfoque multidisciplinar, com o Heart Team. Diversos escores angiográficos foram propostos com o objetivo de quantificar o risco associado à doença arterial coronariana multiarterial. O escore SYNTAX residual foi proposto como um método para caracterizar e quantificar a doença coronariana residual, de forma sistemática, após intervenção coronária percutânea. Existem poucos dados na literatura que correlacionam o escore SYNTAX residual em pacientes com infarto do miocárdio com supradesnivelamento do segmento ST submetidos a uma estratégia farmacoinvasiva. O objetivo deste estudo foi avaliar o escore SYNTAX e o escore SYNTAX residual como preditores de desfechos intra-hospitalares e de médio prazo (180 a 380 dias), em pacientes com doença coronária multiarterial no contexto de infarto do miocárdio com supradesnivelamento do segmento ST, após terapia fibrinolítica bem-sucedida. Métodos: Em um estudo transversal, analítico e prospectivo, avaliamos o escore SYNTAX residual como preditor de desfechos intra-hospitalares e de médio prazo (6 meses a 1 ano), em pacientes com doença arterial coronariana multiarterial, no contexto de infarto do miocárdio com supradesnivelamento do segmento ST após estratégia farmacoinvasiva. Resultados: Entre agosto de 2019 e dezembro de 2020, foram analisados 108 pacientes com infarto do miocárdio com supradesnivelamento do segmento ST após fibrinólise, com critérios de reperfusão. O escore SYNTAX médio foi 13,98 (±4,87) e o escore SYNTAX residual médio foi 7,56 (±4,47). O escore SYNTAX residual elevado foi associado à nefropatia induzida por contraste e evento cardíaco adverso maior. Também foi um preditor independente de evento cardíaco adverso maior, com risco aumentado 9,69 vezes (p=0,0274). Conclusão: O escore SYNTAX residual elevado confere pior prognóstico em pacientes com infarto do miocárdio com elevação do segmento ST após estratégia farmacoinvasiva.

Background: Multivessel coronary artery disease is a challenge in clinical practice. An individualized approach should consider not only the patient characteristics, but also a multidisciplinary approach, together with the Heart Team. Multiple angiographic scores have been proposed with the aim of quantifying the risk associated with multivessel coronary artery disease. Residual SYNTAX score has been proposed as a method to systematically characterize and quantify residual coronary disease after percutaneous coronary intervention. There are few data in the literature correlating the residual SYNTAX score in patients with ST-segment elevation myocardial infarction undergoing pharmacoinvasive strategy. The objective of this study was to evaluate the SYNTAX score and residual SYNTAX score as predictors of in-hospital and medium-term outcomes (180 to 380 days) in patients with multivessel coronary artery disease in the setting of ST-segment elevation myocardial infarction, after successful fibrinolytic therapy. Methods: In a cross-sectional, analytical, and prospective study, we evaluated residual SYNTAX score as predictor of in-hospital and medium-term outcomes (6 months to 1 year), in patients with multivessel coronary artery disease, in the setting of ST-segment elevation myocardial infarction after pharmacoinvasive strategy. Results: Between August 2019 and December 2020, 108 patients with ST-segment elevation myocardial infarction after fibrinolysis, with reperfusion criteria, were analyzed. The mean SYNTAX score was 13.98 (±4.87) and the mean residual SYNTAX score was 7.56 (±4.47). High residual SYNTAX score was associated with contrast-induced nephropathy and major adverse cardiac event. It was also an independent predictor of major adverse cardiac event with a 9.69-fold increased risk (p=0.0274). Conclusion: High residual SYNTAX score confers worse prognosis in patients with ST-segment elevation myocardial infarction after pharmacoinvasive strategy.

Systematic reviews on interventions for COVID-19 have rarely graded the certainty of the evidence

ABSTRACT BACKGROUND: Numerous systematic reviews on coronavirus disease-19 (COVID-19) treatment have been developed to provide syntheses of the large volume of primary studies. However, the methodological quality of most of these reviews is questionable and the results provided may therefore present bias. OBJECTIVE: To investigate how many systematic reviews on the therapeutic or preventive options for COVID-19 assessed the certainty of the evidence through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. METHODS: We conducted a sensitive search in MEDLINE (via PubMed) and included all systematic reviews that assessed any intervention for COVID-19. The systematic reviews included were examined to identify any planned and/or actual assessment using the GRADE approach (or absence thereof) regarding the certainty of the evidence. RESULTS: We included 177 systematic reviews and found that only 37 (21%; 37/177) assessed and reported the certainty of the evidence using the GRADE approach. This number reduced to 27 (16.2%; 27/167) when Cochrane reviews (n = 10), in which an evaluation using GRADE is mandatory, were excluded. CONCLUSION: Most of the systematic reviews on interventions relating to COVID-19 omitted assessment of the certainty of the evidence. This is a critical methodological omission that must not be overlooked in further research, so as to improve the impact and usefulness of syntheses relating to COVID-19.

The use of a new calcium mesoporous silica nanoparticle versus calcium and/or fluoride products in reducing the progression of dental erosion

Abstract Objective There is increasingly common the consumption more times a day of foods and acidic drinks in the diet of the population. The present study aimed to evaluate and compare the effects of a calcium mesoporous silica nanoparticle single application of other calcium and/or fluoride products in reducing the progression of dental erosion. Methodology Half of the eroded area was covered of 60 blocks of enamel, after which the block was submitted to the following treatments: (Ca2+-MSN), casein phosphopeptide-amorphous calcium phosphate (CPP-ACP); CPP-ACP/F-(900 ppm F−); titanium tetrafluoride (TiF4 1%) (positive control); sodium fluoride (NaF 1.36%) (positive control); and Milli-Q® water (negative control) before being submitted to a second erosive challenge. A surface analysis was performed via a three-dimensional (3D) noncontact optical profilometry to assess the volumetric roughness (Sa) and tooth structure loss (TSL) and and through scanning electron microscopy (MEV). An analysis of variance (ANOVA) and Tukey's test were performed. Results Regarding Sa, all experimental groups exhibited less roughness than the control (p<0.05). The TSL analysis revealed that the Ca2+-MSN and NaF groups were similar (p>0.05) and more effective in minimizing tooth loss compared with the other groups (p<0.05). Conclusions The Ca2+-MSN and NaF treatments were superior compared with the others and the negative control.

Fatores associados à peregrinação no anteparto das gestantes da Região Sudeste do Nascer no Brasil / Factors associated with antepartum pregnant women wandering in the Sunrise Southeast region in Brazil

Objetivo: Investigar os principais fatores e aspectos envolvidos na ocorrência da peregrinação no anteparto na Região Sudeste do Brasil. Material e Método: Foram utilizadas as informações da Pesquisa Nascer no Brasil, de 8.005 puérperas investigadas na Região Sudeste, no período entre fevereiro de 2011 e julho de 2012. Definiu-se a peregrinação no anteparto como o ato da gestante buscar assistência ao parto em mais de uma maternidade. Para estudar os fatores associados à peregrinação no anteparto, foi utilizado um modelo logístico multinível, com o tipo de hospital como o nível agregado e as gestantes como nível individual, dessa forma foi respeitada a representatividade da pesquisa. Resultados: Foi observada uma redução da peregrinação na Região Sudeste frente aos resultados apresentados na literatura. As caraterísticas socioeconômicas e demográficas, não se apresentaram como fatores associados à ocorrência da peregrinação, exceto pela situação conjugal, onde as gestantes sem companheiro apresentaram maiores chances de peregrinar que as gestantes com companheiro. As gestantes que tiveram conceptos prematuros apresentaram maiores chances de peregrinarem que as gestantes que pariram depois das 37 semanas de gestação. Outra característica que se destacou como importante fator para a ocorrência da peregrinação foi a paridade da mulher, as primíparas apresentaram maiores chances de peregrinarem que as multíparas. Dos resultados obtidos, a característica que se apresentou com grande associação para a ocorrência da peregrinação foi à falta da realização do pré-natal adequado. Como é conhecido a cobertura do pré-natal é universal, contudo isso não indica que o pré-natal foi realizado de forma adequada.

Assim, quando verificado o pré-natal como preconizado pelo Ministério da Saúde, as gestantes que realizaram pré-natal adequado têm 9 por cento menor chance de peregrinar que as gestantes que não o realizaram. Mais da metade das gestantes informaram que foram previamente avisadas sobre a maternidade que deveriam procurar no momento do parto, contudo essa informação não foi o suficiente para evitar que muitas peregrinassem. A principal justificativa para recusa dessas gestantes na maternidade foi à falta de vaga. Conclusão: A redução na ocorrência da peregrinação está associada à realização do pré-natal adequado. As características socioeconômicas não se apresentam como fatores associados à ocorrência da peregrinação, enquanto a atenção pré-parto se apresentou como importante fator para que a gestante não peregrine no momento do parto. Como confirmam as publicações do Ministério da Saúde, o atendimento em tempo oportuno e com qualidade são fundamentais para uma boa assistência ao parto, reduzindo assim os índices de mortalidade materna.

Objective: To investigate the main factors and aspects involved in the occurrence of peregrination in the antepartum in Southeast Region of Brazil. Methods: Search “Birth in Brazil” information were used, of 8,005 puerperal surveyed in the Southeast Region, between February 2011 and July 2012. Peregrination in antepartum was determined as the act of pregnant women seeking care delivery in more than one hospital. To study the factors associated with peregrination in the antepartum was used a multilevel logistic model, whith the type of hospital as the aggregate level and pregnant women as individual level, thus has respected the representativeness of the survey. Results: Was observed a reduction of peregrination in the Southeast Region compared to the results reported in the literature. The socioeconomic and demographic characteristics are not presented as factors associated with the peregrination, except for marital status, where unmarried pregnant women were more likely to peregrination that pregnant women with a partner. Pregnant women who had preterm fetuses were more likely to peregrination that pregnant women who delivered after 37 weeks of pregnancy. Another feature that stood out as an important factor for the occurrence of the peregrination was the parity of women, primiparous were more likely to peregrination that multiparous. From the results, the characteristic that appeared as strong association for the occurrence of the peregrination was the lack of realization of adequate prenatal care. As is known prenatal coverage is universal, however this does not indicate that pre natal was performed appropriately.

So when checked prenatal as recommended by the Ministry of Health, pregnant women who underwent adequate prenatal has 9 percent lower odds of peregrination that pregnant women who did not undergo adequate prenatal care. More than half of the women reported that they were previously warned about motherhood that should look at in the moment of delivery, but this information was not enough to prevent many peregrination. The main reason for refusal of these pregnant women in the maternity was the lack of vacancy. Conclusion: The reduction in the occurrence of peregrination is associated with achievement of adequate prenatal care. The socioeconomic characteristics are not presented as factors associated with the peregrination, while the antenatal care was presented as an important factor for the pregnant woman not peregrine at birth As confirmed by the publications of the Ministry of Health, the appropriate time and quality are fundamental to good care delivery and thereby reducing maternal mortality rates.

Technetium-99m-labeled stealth pH-sensitive liposomes: a new strategy to identify infection in experimental model

The diagnosis of inflammatory and infectious processes is an important goal in medicine. The use of radiopharmaceuticals for identification of inflammation and infection foci has received considerable attention. The aim of this work was to evaluate the uptake and the imaging potential of stealth pH-sensitive liposomes radiolabelled with 99mTechnetium (99mTc) to identify infection sites in mice. The liposomes containing glutathione were labeled with 99mTc-Hexamethylpropyleneamine oxime (HMPAO) complex. The 99mTc-labeled stealth pH-sensitive liposomes (99mTc-SpHL) were injected in mice bearing infection in the right thigh muscle induced by Staphylococcus aureus. Biodistribution studies and scintigraphic imaging were performed at different times after injection of radiopharmaceutical. The 99mTc-SpHL was significantly uptaken by abscess when compared to the respective control. The abscess was visualized as early as 0.5 hours after injection of 99mTc-SpHL becoming more prominent with the time. These results indicate that 99mTc-SpHL is a promising radiopharmaceutical for visualizing infection foci in patients.

O diagnóstico de processos inflamatórios e infecciosos é um objetivo importante em medicina. O uso de radiofármacos para identificação de focos de inflamação e infecção tem recebido considerável atenção. O objetivo deste trabalho foi avaliar a captação e o potencial de imagem de lipossomas pH-sensíveis furtivos radiomarcados com 99mTecnécio (99mTc) para identificar sítios de infecção em camundongos. Os lipossomas contendo glutationa foram marcados com o complexo 99mTc-hexametilpropilenoamina oxima (HMPAO). Os lipossomas pH-sensíveis furtivos marcados com 99mTc (99mTc-LpHS) foram injetados em camundongos com infecção induzida por Staphylococcus aureus no músculo da coxa direita. Estudos de biodistribuição e imagem cintilográfica foram realizados em diferentes tempos após injeção do radiofármaco. Os 99mTc-LpHS foram captados significativamente pelo abscesso quando comparado ao respectivo controle. O abscesso foi visualizado rapidamente (0,5 horas) após injeção do 99mTc-LpHS tornando-se mais evidenciado com o tempo. Estes resultados indicam que 99mTc-LpHS é um promissor radiofármaco para identificação de focos inflamatórios e infecciosos em pacientes.