RESUMEN
T cell activation, a key early event in the adaptive immune response, is subject to elaborate transcriptional control. In the present study, we examined how the activities of eight major transcription factor (TF) families are integrated to shape the epigenome of naive and activated CD4 and CD8 T cells. By leveraging extensive polymorphisms in evolutionarily divergent mice, we identified the 'heavy lifters' positively influencing chromatin accessibility. Members of Ets, Runx and TCF/Lef TF families occupied the vast majority of accessible chromatin regions, acting as 'housekeepers', 'universal amplifiers' and 'placeholders', respectively, at sites that maintained or gained accessibility upon T cell activation. In addition, a small subset of strongly induced immune response genes displayed a noncanonical TF recruitment pattern. Our study provides a key resource and foundation for the understanding of transcriptional and epigenetic regulation in T cells and offers a new perspective on the hierarchical interactions between critical TFs.
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Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Epigenoma/inmunología , Activación de Linfocitos/inmunología , Factores de Transcripción/inmunología , Inmunidad Adaptativa/inmunología , Animales , Cromatina/inmunología , Epigénesis Genética/inmunología , Regulación de la Expresión Génica/inmunología , Masculino , RatonesRESUMEN
BACKGROUND: Necrotizing enterocolitis (NEC) alters intestinal microvascular control mechanisms causing significant vasoconstriction. Our prior work with intraperitoneal 2.5% dextrose solution demonstrated increased intestinal perfusion in experimentally induced NEC. In the current study, we examine whether a buffered solution with lower glucose and osmolar loads similarly increases intestinal blood flow. We hypothesized that buffered 1.5% dextrose solution would increase ileal blood flow compared with baseline in NEC. METHODS: We randomly assigned pregnant Sprague-Dawley rats to control (n = 103) or NEC (n = 123) groups, by litter. We induced NEC by previously published methods. Control pups were vaginally delivered and dam-fed. We used laser Doppler flowmetry to evaluate perfusion in the terminal ileum at 12, 24, 48, 72, or 96 h after delivery at baseline and after application of topical 1.5% dextrose solution. We evaluated differences between groups and time points by analysis of variance and Tukey post hoc test. RESULTS: Baseline blood flow in the terminal ileum increased with gestational age in both groups (P < 0.05). Control groups had significantly greater baseline blood flow than NEC groups (P < 0.05), and topical application of buffered 1.5% dextrose solution increased blood flow compared with baseline in both groups at all time points (P < 0.05). CONCLUSIONS: Topical 1.5% dextrose solution significantly enhanced blood flow in the terminal ileum to the same degree as 2.5% dextrose solution. Thus, the use of buffered 1.5% dextrose solution might be more beneficial in treating clinical NEC, because it places a lower glucose and osmotic load on NEC-injured intestine.
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Soluciones para Diálisis/administración & dosificación , Enterocolitis Necrotizante/fisiopatología , Enterocolitis Necrotizante/terapia , Glucosa/administración & dosificación , Íleon/irrigación sanguínea , Diálisis Peritoneal/métodos , Animales , Animales Recién Nacidos , Soluciones para Diálisis/efectos adversos , Modelos Animales de Enfermedad , Femenino , Glucosa/efectos adversos , Hiperglucemia/inducido químicamente , Infusiones Parenterales , Flujometría por Láser-Doppler , Concentración Osmolar , Cavidad Peritoneal , Espacio Personal , Embarazo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Vasoconstricción/fisiologíaRESUMEN
Neurofibromatosis type 1 is the most common inherited disorder of the nervous system, affecting approximately 1 in 3,000 people. A small but significant subset of these patients develop vasculopathies. We present the first reported case of neurofibromatosis type 1 presenting with obstructive jaundice secondary to multiple hepatic artery aneurysms. Therapy included staged coil embolization of the hepatic artery aneurysms and resection of a large retroperitoneal neurofibroma.
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Aneurisma/complicaciones , Arteria Hepática , Ictericia Obstructiva/etiología , Neurofibromatosis 1/complicaciones , Adolescente , Aneurisma/terapia , Humanos , Ictericia Obstructiva/terapia , Masculino , Neurofibromatosis 1/terapiaRESUMEN
Meningococcal sepsis and purpura fulminans is a rare but highly lethal disease process that requires a multidisciplinary team of experts to optimise morbidity and mortality outcomes due to the breadth of complications of the disease. The surgical perspective involves the critical care management which utilises all currently available measured outcomes of critical care management as well as experimental therapies. Limb loss is common, and is reflective of the high incidence of compartment syndrome compounded by the significant soft tissue loss secondary to purpura and limb ischaemia, presumptively due to digital microemboli. A multidisciplinary approach involving current standards in critical care and early surgical evaluation are important in improving patient outcomes and limb salvage.
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Bacteriemia/cirugía , Cuidados Críticos/métodos , Recuperación del Miembro/métodos , Infecciones Meningocócicas/cirugía , Púrpura Fulminante/cirugía , Piel/irrigación sanguínea , Adulto , Amputación Quirúrgica , Antibacterianos/administración & dosificación , Bacteriemia/microbiología , Bacteriemia/fisiopatología , Femenino , Humanos , Comunicación Interdisciplinaria , Infecciones Meningocócicas/complicaciones , Infecciones Meningocócicas/fisiopatología , Púrpura Fulminante/etiología , Púrpura Fulminante/fisiopatología , Resultado del TratamientoRESUMEN
INTRODUCTION: The purpose of this study was to develop a multi-institutional registry to characterize the demographics, management, and outcomes of a contemporary cohort of children undergoing congenital lung malformation (CLM) resection. METHODS: After central reliance IRB approval, a web-based, secure database was created to capture retrospective cohort data on pathologically-confirmed CLMs performed between 2009 and 2015 within a multi-institutional research collaborative. RESULTS: Eleven children's hospitals contributed 506 patients. Among 344 prenatally diagnosed lesions, the congenital pulmonary airway malformation volume ratio was measured in 49.1%, and fetal MRI was performed in 34.3%. One hundred thirty-four (26.7%) children had respiratory symptoms at birth. Fifty-eight (11.6%) underwent neonatal resection, 322 (64.1%) had surgery at 1-12â¯months, and 122 (24.3%) had operations after 12 months. The median age at resection was 6.7â¯months (interquartile range, 3.6-11.4). Among 230 elective lobectomies performed in asymptomatic patients, thoracoscopy was successfully utilized in 102 (44.3%), but there was substantial variation across centers. The most common lesions were congenital pulmonary airway malformation (nâ¯=â¯234, 47.3%) and intralobar bronchopulmonary sequestration (nâ¯=â¯106, 21.4%). CONCLUSION: This multicenter cohort study on operative CLMs highlights marked disease heterogeneity and substantial practice variation in preoperative evaluation and operative management. Future registry studies are planned to help establish evidence-based guidelines to optimize the care of these patients. LEVEL OF EVIDENCE: Level II.
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Pulmón , Sistema de Registros , Anomalías del Sistema Respiratorio , Humanos , Lactante , Recién Nacido , Pulmón/anomalías , Pulmón/cirugía , Diagnóstico Prenatal , Anomalías del Sistema Respiratorio/diagnóstico , Anomalías del Sistema Respiratorio/epidemiología , Anomalías del Sistema Respiratorio/cirugía , Estudios RetrospectivosRESUMEN
PURPOSE: The purpose of this study was to evaluate the clinical presentation and operative outcomes of patients with congenital lobar emphysema (CLE) within a large multicenter research consortium. METHODS: After central reliance IRB-approval, a retrospective cohort study was performed on all operatively managed lung malformations at eleven participating children's hospitals (2009-2015). RESULTS: Fifty-three (10.5%) children with pathology-confirmed CLE were identified among 506 lung malformations. A lung mass was detected prenatally in 13 (24.5%) compared to 331 (73.1%) in non-CLE cases (pâ¯<â¯0.0001). Thirty-two (60.4%) CLE patients presented with respiratory symptoms at birth compared to 102 (22.7%) in non-CLE (pâ¯<â¯0.0001). The most common locations for CLE were the left upper (nâ¯=â¯24, 45.3%), right middle (nâ¯=â¯16, 30.2%), and right upper (nâ¯=â¯10, 18.9%) lobes. Eighteen (34.0%) had resection as neonates, 30 (56.6%) had surgery at 1-12â¯months of age, and five (9.4%) had resections after 12â¯months. Six (11.3%) underwent thoracoscopic excision. Median hospital length of stay was 5.0â¯days (interquartile range, 4.0-13.0). CONCLUSIONS: Among lung malformations, CLE is associated with several unique features, including a low prenatal detection rate, a predilection for the upper/middle lobes, and infrequent utilization of thoracoscopy. Although respiratory distress at birth is common, CLE often presents clinically in a delayed and more insidious fashion. LEVEL OF EVIDENCE: Level III.
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Enfisema Pulmonar/congénito , Niño , Preescolar , Disnea , Humanos , Lactante , Medio Oeste de Estados Unidos/epidemiología , Enfisema Pulmonar/epidemiología , Enfisema Pulmonar/cirugía , Anomalías del Sistema Respiratorio , Estudios Retrospectivos , Toracoscopía/estadística & datos numéricosRESUMEN
PURPOSE: This study reviews contemporary management and follow-up of pediatric ovarian torsion. METHODS: This is a retrospective series of patients from birth to 19 years undergoing operative management of ovarian torsion from 2012 to 2016. RESULTS: We studied 43 girls who underwent 51 operations for ovarian torsion. The median age was 8.3 years. Ultrasound was utilized for diagnosis in 24/29 patients (83%) evaluated in a children's hospital. In contrast, computed tomography was used initially in 7 cases (50%) in children imaged at non-children's hospitals before transfer. Initial operation for ovarian torsion was completed laparoscopically in 38 (88%). Overall, ovarian preservation was performed in 37 (86%) patients, while 6 (13%) underwent oophorectomy. Indications for oophorectomy included 5 infants with in utero torsion and an 18-year-old with a suspected malignancy. In girls with acute ovarian torsion, the oophorectomy rate was reduced to 2%. Postoperatively, 1 patient developed a small bowel obstruction requiring operation after laparoscopic ovarian detorsion. Recurrent torsion occurred in 3 patients (7%). In total, 34 patients underwent postoperative ovarian imaging. A total of 25 (74%) had follicles visualized in the previously torsed ovary. CONCLUSION: Ovarian-sparing operations for acute torsion are safe and result in ovarian salvage and preservation of follicular development in more than 70% of children and adolescents.
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Laparoscopía , Enfermedades del Ovario/cirugía , Folículo Ovárico/crecimiento & desarrollo , Anomalía Torsional/cirugía , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Ovariectomía , Recurrencia , Estudios Retrospectivos , Anomalía Torsional/diagnóstico por imagen , Resultado del Tratamiento , Adulto JovenRESUMEN
Abdominal pain is a frequent problem encountered in the emergency department, and acute appendicitis is a well-recognized diagnosis. Laparoscopic appendectomy has become one of the most common surgical procedures in the United States. Patients with a history of appendectomy may experience recurrent right lower quadrant abdominal pain from an infrequently encountered complication that may occur when the residual appendix becomes obstructed and inflamed. We describe two cases of stump appendicitis in pediatric patients with a review of clinical and imaging findings and surgical management.
RESUMEN
PURPOSE: Intestinal vasoconstriction is a critical step in development of necrotizing enterocolitis (NEC). Relaxin (RLXN), a hormone found in breast milk but absent from formula, is a potent vasodilator. We hypothesized that relaxin-supplemented feeds with an NEC protocol would decrease NEC severity and increase intestinal blood flow. METHODS: Timed-pregnant Sprague-Dawley rats were randomly assigned to CONTROL, NEC, NEC+1xRLXN, or NEC+All Feeds RLXN, and all but CONTROL underwent NEC protocol. NEC+1xRLXN and NEC+All Feeds RLXN groups were fed relaxin-supplemented formula with the last feed or every feed. At 48h of life, intestinal blood flow was measured at baseline and after application of 2.5% Delflex® solution. RESULTS: The addition of relaxin to NEC group feeds (1x or All Feeds) improved the degree of ileal injury. Ileal blood flow was decreased in the NEC pups compared to the CONTROLS, but the addition of relaxin to one feed increased baseline ileal blood flow in the NEC group compared to NEC alone. Furthermore, the addition of relaxin to ALL feeds significantly increased baseline ileal blood flow. CONCLUSION: Pups who received relaxin with all feeds had substantially increased ileal perfusion compared to control pups. Our data suggest that relaxin supplementation maintains intestinal blood flow and results in less histologic NEC.
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Enterocolitis Necrotizante/tratamiento farmacológico , Intestinos/irrigación sanguínea , Microcirculación/fisiología , Preñez , Flujo Sanguíneo Regional/efectos de los fármacos , Relaxina/administración & dosificación , Administración Oral , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Enterocolitis Necrotizante/patología , Enterocolitis Necrotizante/fisiopatología , Femenino , Flujometría por Láser-Doppler , Microcirculación/efectos de los fármacos , Embarazo , Ratas , Ratas Sprague-Dawley , Vasoconstricción/efectos de los fármacosRESUMEN
PURPOSE: The spectrum of pediatric biliary tract disease is changing. The goal of this study was to examine the causes and comorbidities of pediatric gallbladder disease at our institution. METHODS: We performed a retrospective chart review on consecutive patient at Kosair Children's Hospital who underwent cholecystectomy over a 9-year time period ending in 2012. RESULTS: Among the 453 patients in the study group, the average age was 13.3 years and 67.2% were female. Indications for cholecystectomy were gallstones in 285 (63%) and biliary dyskinesia in 140 (33%). Of the patients with gallstones, 68 children (15%) had hemolytic disease. Although the number of cholecystectomies for hemolytic disease was relatively stable throughout our study, the number for biliary dyskinesia and non-hemolytic (cholesterol) cholelithiasis rose by 63% and 216%, respectively. Average body mass index (BMI) for patients with non-hemolytic (cholesterol) stones and biliary dyskinesia were significantly greater than the average BMI for patients with hemolytic stones (P < .0001). In addition, the average BMI for children with non-hemolytic (cholesterol) stones was greater than the average BMI with biliary dyskinesia (P < .0001). CONCLUSION: Symptomatic gallbladder disease increased over the study period. Biliary dyskinesia and children with non-hemolytic disease are responsible for this increase.
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Enfermedades de la Vesícula Biliar/etiología , Adolescente , Índice de Masa Corporal , Niño , Colangiopancreatografia Retrógrada Endoscópica , Colecistectomía , Femenino , Enfermedades de la Vesícula Biliar/epidemiología , Enfermedades de la Vesícula Biliar/cirugía , Humanos , Iminoácidos , Incidencia , Masculino , Estudios RetrospectivosRESUMEN
The transition to motherhood results in a number of hormonal, neurological, and behavioral changes necessary to ensure offspring survival. Once motherhood is established, further neurological and behavioral changes may result with additional parity and mothering. Recent research has shown that motherhood enhances both hippocampal-dependent learning and memory and oxytocin-induced long-term potentiation, suggesting that the hippocampus is affected by mothering. In turn, degree of maternal behavior, either high or low, has been shown to affect spatial learning and memory performance in adult offspring. The present experiment aimed to investigate the effect of reproductive experience (nulli-, primi-, and multiparity and mothering) and degree of maternal behavior on hippocampus-dependent learning and memory in the mother. Results show that regardless of error type, primiparous rats make fewer errors compared to nulliparous rats, while multiparous rats show a trend towards making fewer errors compared to nulliparous rats. In addition, mothers who spend less time licking and nursing offspring had fewer reference memory errors. Perhaps the enhanced learning and memory in the inexperienced, new mother allows her to effectively acquire the suite of maternal behaviors necessary to ensure offspring survival and achieve reproductive success with subsequent reproductive experience.