RESUMO
Our current understanding of epigenetic regulation is deeply rooted in the founding contributions of Dr C. David Allis. In 2002, Allis and colleagues first characterized the lysine methyltransferase activity of the mammalian KMT2A (MLL1), a paradigm-shifting discovery that brings epigenetic dysregulation into focus for many human diseases that carry KMT2A mutations. This review will discuss the current understanding of the multifaceted roles of KMT2A in development and disease, which has paved the way for innovative and upcoming approaches to cancer therapy.
Assuntos
Transformação Celular Neoplásica , Histona-Lisina N-Metiltransferase , Proteína de Leucina Linfoide-Mieloide , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Humanos , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Animais , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Epigênese Genética , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/enzimologiaRESUMO
AIM: The purpose of this study was to assess for an association between higher body mass index and disease severity, morbidity and mortality in children admitted for an acute respiratory distress and failure. METHODS: A single-institution retrospective cross-sectional study performed in the United States evaluating paediatric patients, 2-20 years of age, admitted for diagnoses related to acute respiratory distress and acute respiratory failure. Main outcomes include disease severity as assessed using the respiratory component of the Paediatric Early Warning Score (PEWS) with adjustment for altered mental status (Resp-PEWS + AMS), hospital or intensive care length of stay (LOS) and death. RESULTS: Children with obesity made up 42/334 (13%) of the cohort. There was no significant difference in Resp-PEWS + AMS between obese and non-obese cohorts (mean of 0.93, {standard deviation 1.11} vs. 1.13 {1.35}, range 0-6, rank sum p = 0.46). There was no significant difference in overall hospital LOS or intensive care LOS. Multivariate analysis including diagnosis as a control variable did not change the results. CONCLUSION: We found that body habitus was not an independent factor for illness severity or clinical outcomes.
Assuntos
Obesidade Infantil , Criança , Estudos Transversais , Hospitalização , Humanos , Tempo de Internação , Obesidade Infantil/complicações , Obesidade Infantil/epidemiologia , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
Accurate and timely interpretation of microcytic anemia can be diagnostically challenging in the primary care setting. We sought to develop a novel model for distinguishing iron-deficiency anemia from thalassemia trait in the modern pediatric population. Demographic history and red blood cell indices were retrospectively characterized for 76 children referred to our pediatric hematology clinic for evaluation of microcytic anemia. Statistically significant variables were sequentially added into a logistic regression model to develop the final model. The final discriminating model incorporates red cell distribution width, mean corpuscular hemoglobin concentration, and red blood cell values. Favorable predictive performance is seen in the initial (sensitivity 89.2%, specificity 92.3%) and external validation cohort (sensitivity 84.4%, specificity 88.9%). This novel tool may aid in determining the cause of hypochromic, microcytic anemia in the primary care setting. Finally, the study cohort reflects an underrepresented group in the development of screening tools, and thus offers generalizability.