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BACKGROUND: Anastomotic stricture is the most common postoperative complication in infants undergoing repair of esophageal atresia with or without tracheoesophageal fistula (EA/TEF). Stricture indices (SIs) are used to predict infants at risk for stricture requiring dilation. We sought to determine the most accurate SI and optimal timing for predicting anastomotic dilation. MATERIALS AND METHODS: A retrospective study of infants undergoing repair of EA/TEF between 2008 and 2013 was performed. Esophagrams were used to calculate four SIs (upper pouch esophageal anastomotic stricture index [U-EASI], lower pouch esophageal anastomotic stricture index [L-EASI], lateral SI, and anterior/posterior SI). The best performing SI was identified. Logistic regression analysis was performed to determine if a first or second esophagram SI threshold was associated with dilation. A receiver operating characteristic curve measured the accuracy of the model using SIs to predict dilation. RESULTS: Of 45 EA/TEF infants included, 20 (44%) had postoperative strictures requiring dilation. As the best performing SI, logistic regression analysis showed that U-EASI as a continuous variable was predictive of dilation (P = 0.03) but was not significant at U-EASI ≤ 0.37. However, U-EASI ≤ 0.37 was associated with needing earlier dilation. On second esophagram (median, 38 days), U-EASI of ≤0.39 was significantly associated with dilation (OR: 7.8, 95% CI: 1.05-57.58, P = 0.04). The area under the receiver operating characteristic curve of the U-EASI model controlling for days to esophagram demonstrated improved predictive ability from first (AUC 0.73) to second esophagram (AUC 0.81). CONCLUSIONS: Calculation of the SI utilizing a U-EASI ≤ 0.39 on the delayed esophagram is associated with future anastomotic dilation. A multi-institutional study is necessary to confirm the predictive ability of the U-EASI.
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Técnicas de Apoio para a Decisão , Atresia Esofágica/cirurgia , Estenose Esofágica/terapia , Esofagoplastia , Indicadores Básicos de Saúde , Complicações Pós-Operatórias/terapia , Fístula Traqueoesofágica/cirurgia , Anastomose Cirúrgica , Dilatação , Estenose Esofágica/diagnóstico , Estenose Esofágica/etiologia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Complicações Pós-Operatórias/diagnóstico , Curva ROC , Estudos RetrospectivosRESUMO
OBJECTIVES: Little is known about the personal readiness of hospital staff for disasters. As many as 30% of hospital staff say that they plan not to report for work during a large-scale disaster. We sought to understand the personal disaster preparedness for hospital staff. METHODS: Surveys were distributed to the staff of a large academic tertiary-care hospital by either a paper-based version distributed through the departmental safety coordinators or a Web-based version distributed through employee e-mail services, depending on employee familiarity with and access to computer services. Surveys assessed the demographic variables and characteristics of personal readiness for disaster. RESULTS: Of the individuals who accessed the survey, 1334 (95.9%) enrolled in it. Women made up 75% of the respondents, with a mean age of 43 years. Respondents had worked at the hospital an average of 9 years, with the majority (90%) being full-time employees. Most households (93%) reported ≤4 members, 6% supported a person with special medical needs, and 17% were headed by a single parent. A small number (24%) of respondents reported an established meeting place for reuniting households during a disaster. Many reported stockpiling a 3-day supply of food (86%) and a 3-day supply of water (51%). Eighteen percent of respondents were not aware of workplace evacuation plans. Most respondents were willing to report to work for natural disasters (eg, tornado, snowstorm; all categories >65%), but fewer respondents were willing to report during events such as an influenza epidemic (54%), a biological outbreak (41%), a chemical exposure, (40%), or a radiation exposure (39%). Multivariate analysis revealed being female, having a child in the household younger than 6 years old, and having a child in school lowered the likelihood of being willing to report to work in two or more event types, whereas pet ownership, being a clinical healthcare worker, and being familiar with the work emergency plan increased the likelihood. CONCLUSIONS: Despite being employed at the same facility for a prolonged period, employees reported being willing to report for work at a low rate in a variety of disasters. Subjects reported suboptimal personal preparedness for disaster, which may further limit the number of staff who will report for work. Hospitals should promote personal disaster preparedness for staff and explore staffing models with an understanding of reduced staff availability during disasters.
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Atitude do Pessoal de Saúde , Planejamento em Desastres , Desastres , Recursos Humanos em Hospital , Trabalho/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , AutorrelatoRESUMO
Fungal mesh infections are a rare complication of hernia repairs with mesh. The first case of Coccidioides spp. mesh infection is described, and a systematic literature review of all known fungal mesh infections was performed. Nine cases of fungal mesh infection are reviewed. Female and male patients are equally represented, median age is 49.5 years, and critical illness and preinfection antibiotic use were common. Fungal mesh infections are rare, but potentially fatal, complications of hernias repaired with mesh.
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Coccidioides/isolamento & purificação , Coccidioidomicose/microbiologia , Herniorrafia , Complicações Pós-Operatórias/microbiologia , Telas Cirúrgicas/microbiologia , Adenina/análogos & derivados , Idoso , Antifúngicos/uso terapêutico , Coccidioidomicose/tratamento farmacológico , Feminino , Fluconazol/uso terapêutico , Humanos , Hifas/crescimento & desenvolvimento , Hifas/ultraestrutura , Masculino , Pessoa de Meia-Idade , Piperidinas , Complicações Pós-Operatórias/tratamento farmacológico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêuticoRESUMO
Background: Altered coagulation is a striking feature of COVID-19. Adult patients with congenital heart disease (ACHD) are prone to thromboembolic (TE) and bleeding complications. Objectives: The purpose of this study was to investigate the prevalence and risk factors for COVID-19 TE/bleeding complications in ACHD patients. Methods: COVID-19-positive ACHD patients were included between May 2020 and November 2021. TE events included ischemic cerebrovascular accident, systemic and pulmonary embolism, deep venous thrombosis, myocardial infarction, and intracardiac thrombosis. Major bleeding included cases with hemoglobin drop >2 g/dl, involvement of critical sites, or fatal bleeding. Severe infection was defined as need for intensive care unit, endotracheal intubation, renal replacement therapy, extracorporeal membrane oxygenation, or death. Patients with TE/bleeding were compared to those without events. Factors associated with TE/bleeding were determined using logistic regression. Results: Of 1,988 patients (age 32 [IQR: 25-42] years, 47% male, 59 ACHD centers), 30 (1.5%) had significant TE/bleeding: 12 TE events, 12 major bleeds, and 6 with both TE and bleeding. Patients with TE/bleeding had higher in-hospital mortality compared to the remainder cohort (33% vs 1.7%; P < 0.0001) and were in more advanced physiological stage (P = 0.032) and NYHA functional class (P = 0.01), had lower baseline oxygen saturation (P = 0.0001), and more frequently had a history of atrial arrhythmia (P < 0.0001), previous hospitalization for heart failure (P < 0.0007), and were more likely hospitalized for COVID-19 (P < 0.0001). By multivariable logistic regression, prior anticoagulation (OR: 4.92; 95% CI: 2-11.76; P = 0.0003), cardiac injury (OR: 5.34; 95% CI: 1.98-14.76; P = 0.0009), and severe COVID-19 (OR: 17.39; 95% CI: 6.67-45.32; P < 0.0001) were independently associated with increased risk of TE/bleeding complications. Conclusions: ACHD patients with TE/bleeding during COVID-19 infection have a higher in-hospital mortality from the illness. Risk of coagulation disorders is related to severe COVID-19, cardiac injury during infection, and use of anticoagulants.
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PURPOSE: The purpose of this study was to establish normative values for the thoracic aorta diameter in pediatric patients from birth to 18 years of age using computed tomography (CT) measurements and to create nomograms related to body surface area (BSA). METHODS: A total of 623 pediatric patients without cardiovascular disease (42.1% females; from 3 d to 18 y old) with high-quality, non-electrocardiogram-gated, contrast-enhanced CT imaging of the chest were retrospectively evaluated. Systematic measurements of the aortic diameter at predetermined levels were recorded, and demographic data including age, sex, ethnicity, and BSA were collected. Reference graphs plotting BSA over aortic diameter included the mean and Z -3 to Z +3, where Z represents SDs from the mean. RESULTS: The study population was divided into 2 groups (below 2 and greater than or equal to 2 y old). There were no significant differences in average aortic measurements between males and females. Both age groups exhibited significant positive correlations among all size-related metrics (all P <0.001) with BSA having the highest correlation. For both groups, the average orthogonal thoracic aortic diameters at each level of the thoracic aorta were used to create nomograms. CONCLUSION: This study establishes clinically applicable, BSA-specific reference values of the normal thoracic aorta for the pediatric population from CT imaging.
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Aorta Torácica , Tomografia Computadorizada por Raios X , Fatores Etários , Aorta Torácica/diagnóstico por imagem , Superfície Corporal , Criança , Feminino , Humanos , Masculino , Valores de Referência , Estudos Retrospectivos , Fatores Sexuais , Tomografia Computadorizada por Raios X/métodosRESUMO
The bench-to-bedside development of pro-cognitive therapeutics for psychiatric disorders has been mired by translational failures. This is, in part, due to the absence of pharmacologically sensitive cognitive biomarkers common to humans and rodents. Here, we describe a cross-species translational marker of reward processing that is sensitive to the aminergic agonist, d-amphetamine. Motivated by human electroencephalographic (EEG) findings, we recently reported that frontal midline delta-band power is an electrophysiological biomarker of reward surprise in humans and in mice. In the current series of experiments, we determined the impact of parametric doses of d-amphetamine on this reward-related EEG response from humans (n = 23) and mice (n = 28) performing a probabilistic learning task. In humans, d-amphetamine (placebo, 10 mg, 20 mg) boosted the Reward Positivity event-related potential (ERP) component as well as the spectral delta-band representations of this signal. In mice, d-amphetamine (placebo, 0.1 mg/kg, 0.3 mg/kg, 1.0 mg/kg) boosted both reward and punishment ERP features, yet there was no modulation of spectral activities. In sum, the present results confirm the role of dopamine in the generation of the Reward Positivity in humans, and pave the way toward a pharmacologically valid biomarker of reward sensitivity across species.
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Anfetamina , Reforço Psicológico , Anfetamina/farmacologia , Animais , Biomarcadores , Eletroencefalografia , Humanos , Camundongos , RecompensaRESUMO
Lagging quality of care in the U.S. health care system has been a persistent problem and challenge. In the past, medical professionalism and professional certification have served as cornerstones for improving quality in health care. Among newer efforts to improve quality, pay for performance has been proposed to propel better results, but many observers are concerned that pay for performance is at odds with medical professionalism. The authors examine the potential conflicts between pay for performance and medical professionalism and conclude that properly designed pay-for-performance models can support professional objectives.
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Prática Profissional/normas , Garantia da Qualidade dos Cuidados de Saúde/economia , Reembolso de Incentivo , Medicina Baseada em Evidências , Acessibilidade aos Serviços de Saúde/normas , Humanos , Relações Médico-Paciente , Estados UnidosRESUMO
BACKGROUND: Atrial fibrillation (AF) is less common in African Americans (AA) than Caucasians (C) despite a higher prevalence of risk factors such as hypertension (HTN). OBJECTIVE: Test the hypothesis that differences in extracellular matrix (ECM) between AA and C in response to HTN might attenuate atrial enlargement and alter myocardial fibrosis. METHODS: ECM-related plasma biomarkers and echo data were collected from 326 C and 129 AA subjects with no history of AF, stratified by the presence of HTN, HTN with left ventricular hypertrophy (LVH), or HTN with LVH and heart failure with preserved ejection fraction (HFpEF). RESULTS: Left atrial size was significantly smaller and the extent of enlargement in the presence of HTN was less in AA despite similar ventricular relative wall thickness, echocardiographic measures of diastolic function, and 6 minute-walk-test. AA had significantly lower levels of collagen I telopeptide and higher levels of collagen I propeptide among all strata, suggesting unique collagen homeostasis. Matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinase (TIMP) showed a distinctive response to HTN in AA, with significantly lower levels of MMP-2, MMP-3, and MMP-8 in AA with HTN and significantly lower levels of TIMP-1 and TIMP-3 in AA with HTN and AA with LVH. AA had significantly lower levels of NT-pro-BNP in all strata. CONCLUSION: This cross-sectional study demonstrates a racial disparity in ECM blood biomarkers and atrial remodeling in response to HTN and in the development of LVH and HFpEF that may partly help explain the decreased risk of AF in AA.
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Patients with congenitally-corrected transposition of the great arteries (ccTGA) commonly develop significant systemic tricuspid valve regurgitation and systemic right ventricular dysfunction in adulthood, both of which presenting a therapeutic dilemma for the care team. Here we describe the case of a 35-year-old male with congenitally-corrected transposition of the great arteries who presented with severe systemic tricuspid valve regurgitation, biventricular systolic failure, and pulmonary hypertension. Due to prohibitive surgical risk, he underwent percutaneous tricuspid valve repair via MitraClip placement. Post-procedure, he demonstrated rapidly improved symptoms and sustained echocardiographic and hemodynamic evaluations. Few reports exist describing the safety and feasibility of the MitraClip procedure on a systemic tricuspid valve, but to our knowledge, this is the first to describe invasive hemodynamic improvements in patients with this degree of cardiopulmonary sequelae from the congenital lesion. There may be optimism for the MitraClip procedure as "bridge to list" in patients with ccTGA otherwise initially ineligible for surgical valve intervention or transplant.
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Transposição dos Grandes Vasos , Insuficiência da Valva Tricúspide , Adulto , Artérias , Transposição das Grandes Artérias Corrigida Congenitamente , Hemodinâmica , Humanos , Masculino , Transposição dos Grandes Vasos/diagnóstico por imagem , Transposição dos Grandes Vasos/cirurgia , Resultado do Tratamento , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/cirurgiaRESUMO
There has been a fundamental failure to translate preclinically supported research into clinically efficacious treatments for psychiatric disorders. One of the greatest impediments toward improving this species gap has been the difficulty of identifying translatable neurophysiological signals that are related to specific behavioral constructs. Here, we present evidence from three paradigms that were completed by humans and mice using analogous procedures, with each task eliciting candidate a priori defined electrophysiological signals underlying effortful motivation, reinforcement learning, and cognitive control. The effortful motivation was assessed using a progressive ratio breakpoint task, yielding a similar decrease in alpha-band activity over time in both species. Reinforcement learning was assessed via feedback in a probabilistic learning task with delta power significantly modulated by reward surprise in both species. Additionally, cognitive control was assessed in the five-choice continuous performance task, yielding response-locked theta power seen across species, and modulated by difficulty in humans. Together, these successes, and also the teachings from these failures, provide a roadmap towards the use of electrophysiology as a method for translating findings from the preclinical assays to the clinical settings.
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Reforço Psicológico , Recompensa , Animais , Biomarcadores , Camundongos , Motivação , Testes NeuropsicológicosRESUMO
BACKGROUND: Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications. OBJECTIVES: This study sought to define the impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes. METHODS: Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide. Data collection included anatomic diagnosis and subsequent interventions, comorbidities, medications, echocardiographic findings, presenting symptoms, course of illness, and outcomes. Predictors of death or severe infection were determined. RESULTS: From 58 adult CHD centers, the study included 1,044 infected patients (age: 35.1 ± 13.0 years; range 18 to 86 years; 51% women), 87% of whom had laboratory-confirmed coronavirus infection. The cohort included 118 (11%) patients with single ventricle and/or Fontan physiology, 87 (8%) patients with cyanosis, and 73 (7%) patients with pulmonary hypertension. There were 24 COVID-related deaths (case/fatality: 2.3%; 95% confidence interval: 1.4% to 3.2%). Factors associated with death included male sex, diabetes, cyanosis, pulmonary hypertension, renal insufficiency, and previous hospital admission for heart failure. Worse physiological stage was associated with mortality (p = 0.001), whereas anatomic complexity or defect group were not. CONCLUSIONS: COVID-19 mortality in adults with CHD is commensurate with the general population. The most vulnerable patients are those with worse physiological stage, such as cyanosis and pulmonary hypertension, whereas anatomic complexity does not appear to predict infection severity.
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COVID-19 , Procedimentos Cirúrgicos Cardíacos , Cianose , Cardiopatias Congênitas , Hipertensão Pulmonar , Adulto , COVID-19/mortalidade , COVID-19/terapia , Teste para COVID-19/métodos , Procedimentos Cirúrgicos Cardíacos/métodos , Procedimentos Cirúrgicos Cardíacos/estatística & dados numéricos , Causalidade , Comorbidade , Cianose/diagnóstico , Cianose/etiologia , Cianose/mortalidade , Feminino , Saúde Global/estatística & dados numéricos , Cardiopatias Congênitas/classificação , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/terapia , Hospitalização/estatística & dados numéricos , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/mortalidade , Masculino , Mortalidade , Gravidade do Paciente , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Avaliação de SintomasRESUMO
Scimitar syndrome is a rare congenital abnormality resulting from right-sided pulmonary venous return to the inferior vena cava rather than to the left atrium. It is usually detected in early childhood with symptoms of recurrent chest infection and finding of pulmonary hypertension due to left to right shunt. We report a case of a 40-year-old woman with scimitar syndrome discovered on chest X-ray during evaluation of recurrent pneumonia. Surgical correction was achieved with a novel technique of using a synthetic graft connecting the scimitar vein across the right atrium to the left atrium along with ligation of the scimitar vein connection to the inferior vena cava. The patient continues to do well 10 years after surgery, and the shunt graft shows good flow on echocardiogram. We present her clinical and imaging data and details of the surgical technique along with a brief review of surgical literature.
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Importance: Intracerebral hemorrhage (ICH) is a devastating stroke type that lacks effective treatments. An imaging biomarker of ICH expansion-the computed tomography (CT) angiography spot sign-may identify a subgroup that could benefit from hemostatic therapy. Objective: To investigate whether recombinant activated coagulation factor VII (rFVIIa) reduces hemorrhage expansion among patients with spot sign-positive ICH. Design, Setting, and Participants: In parallel investigator-initiated, multicenter, double-blind, placebo-controlled randomized clinical trials in Canada ("Spot Sign" Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy [SPOTLIGHT]) and the United States (The Spot Sign for Predicting and Treating ICH Growth Study [STOP-IT]) with harmonized protocols and a preplanned individual patient-level pooled analysis, patients presenting to the emergency department with an acute primary spontaneous ICH and a spot sign on CT angiography were recruited. Data were collected from November 2010 to May 2016. Data were analyzed from November 2016 to May 2017. Interventions: Eligible patients were randomly assigned 80 µg/kg of intravenous rFVIIa or placebo as soon as possible within 6.5 hours of stroke onset. Main Outcomes and Measures: Head CT at 24 hours assessed parenchymal ICH volume expansion from baseline (primary outcome) and total (ie, parenchymal plus intraventricular) hemorrhage volume expansion (secondary outcome). The pooled analysis compared hemorrhage expansion between groups by analyzing 24-hour volumes in a linear regression model adjusted for baseline volumes, time from stroke onset to treatment, and trial. Results: Of the 69 included patients, 35 (51%) were male, and the median (interquartile range [IQR]) age was 70 (59-80) years. Baseline median (IQR) ICH volumes were 16.3 (9.6-39.2) mL in the rFVIIa group and 20.4 (8.6-32.6) mL in the placebo group. Median (IQR) time from CT to treatment was 71 (57-96) minutes, and the median (IQR) time from stroke onset to treatment was 178 (138-197) minutes. The median (IQR) increase in ICH volume from baseline to 24 hours was small in both the rFVIIa group (2.5 [0-10.2] mL) and placebo group (2.6 [0-6.6] mL). After adjustment, there was no difference between groups on measures of ICH or total hemorrhage expansion. At 90 days, 9 of 30 patients in the rFVIIa group and 13 of 34 in the placebo group had died or were severely disabled (P = .60). Conclusions and Relevance: Among patients with spot sign-positive ICH treated a median of about 3 hours from stroke onset, rFVIIa did not significantly improve radiographic or clinical outcomes. Trial Registration: ClinicalTrials.gov identifier: NCT01359202 and NCT00810888.
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Angiografia Cerebral/métodos , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/tratamento farmacológico , Angiografia por Tomografia Computadorizada/métodos , Fator VIIa/uso terapêutico , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
This case report discusses the diagnosis of double-inlet left ventricle in a male adult patient in his 50s who presented with New York Heart Association class III heart failure.
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BACKGROUND: Risks associated with teen sexting draw increasing concern from teachers and communities as developments in communication software and devices make sharing private content faster and simpler each year. We examined rates, recipients, and predictors of teen sexting to better plan education and preventative policies and strategies. A comprehensive literature review was conducted to determine the most likely predictors of teen sexting using prior survey studies and theoretical conceptions. METHODS: We surveyed 314 high school students in an urban area of a large Midwestern city. RESULTS: Males were found to more frequently report sexting. Impulsivity, frequency of electronic communication, peer pressure, peer sexting, and social learning significantly predicted sexting beyond age, race, and sex. Self-esteem did not moderate the effect of peer pressure to sext. Structural predictive models attained good fit to the data, and neither were moderated by sex. CONCLUSIONS: Sexting was highly associated with reported peer pressure, perceived norms, and impulsive decision making. Adolescents in relationships may be at particular risk of sexting. These findings will help parents, teens, and educators take appropriate measures to inform about and encourage the safe use of technology.
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Comportamento do Adolescente , Instituições Acadêmicas/estatística & dados numéricos , Comportamento Sexual/estatística & dados numéricos , Estudantes/estatística & dados numéricos , Envio de Mensagens de Texto/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adolescente , Feminino , Humanos , Masculino , Meio-Oeste dos Estados Unidos , Grupo Associado , Influência dos Pares , Inquéritos e QuestionáriosRESUMO
Reactive oxygen species, including superoxide, are important mediators of the pathophysiology of hypertension. In the vasculature, superoxide antagonizes nitric oxide (NO*), resulting in increased vascular tone. The GTP binding protein Rac regulates a wide variety of cellular functions, including the activation of NADPH oxidase, the major source of O2*-in the blood vessel wall. An hypothesis is that Rac1 may act as an important regulator of vascular O2*- production, contributing to the balance between O2*- and NO* and maintaining consequent homeostasis of blood pressure. To alter the activity of vascular NADPH oxidase, the authors developed a transgenic animal model that overexpresses the human cDNA of the constitutively active mutant of Rac1 (RacCA) in smooth muscle cells using the smooth muscle +/--actin promoter. The RacCA transgenic had excessive amounts of O2*- in the vessel wall that, which led to heightened production of peroxynitrite, as detected by increased protein nitration and reduced NO* levels. RacCA mice developed moderate hypertension, which was corrected by N-acetyl-L-cysteine (NAC). RacCA transgenic mice also developed left ventricular hypertrophy as a secondary effect of pressure overload. The data suggest that Rac1 is a critical regulator of the redox state of blood vessels and homeostasis of blood pressure.
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Hipertensão/etiologia , Miócitos de Músculo Liso/metabolismo , Transgenes , Proteínas rac1 de Ligação ao GTP/metabolismo , Actinas/genética , Animais , Antioxidantes/metabolismo , Aorta/metabolismo , Pressão Sanguínea/genética , Feminino , Hipertrofia Ventricular Esquerda/genética , Camundongos , Camundongos Transgênicos , Óxido Nítrico/metabolismo , Regiões Promotoras Genéticas , Proteínas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Renina/metabolismo , Distribuição Tecidual , Proteínas rac1 de Ligação ao GTP/genéticaRESUMO
Thrombospondin 2 (TSP2) is a matricellular protein controlling the apoptosis-proliferation balance in endothelial cells. Little is known about its transcriptional regulation compared with that of TSP1. We found that overexpression of a constitutively active mutant of Rac (Rac(V12)) specifically increases TSP2 mRNA levels without affecting TSP1 in human aortic endothelial cells (HAEC). Moreover, TSP2 induction by Rac(V12) is dependent upon reactive oxygen species (ROS) production, as gp91ds-tat peptide, an inhibitor of NADPH oxidase, and the flavoprotein inhibitor diphenylene iodinium (DPI) block TSP2 synthesis. Furthermore, we found that increasing Rac(V12) expression results in a biphasic proliferative curve, with proliferation initially increasing as Rac(V12) expression increases and then returning to levels less than that of control cells at higher expression. This growth inhibition is mediated by TSP2, as either DPI treatment, which blocks TSP2 synthesis, or pan-TSP blocking antibodies restore the proliferative ability of HAEC with high expression. Mechanistically, we show that the effect of TSP2 on cell proliferation is independent of the antiangiogenic TSP2 Hep1 sequence, which is capable of altering actin cytoskeletal reorganization but not proliferation in our experimental conditions. Finally, we show in vivo that Rac-induced TSP2 expression is observed in the aorta of transgenic mice selectively expressing Rac(V12) in smooth muscle cells. These results identify Rac-induced ROS as a new pathway involved in the regulation of TSP2 expression.
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Oxirredução , Transdução de Sinais , Trombospondinas/fisiologia , Proteínas rac1 de Ligação ao GTP/metabolismo , Actinas/metabolismo , Animais , Aorta/citologia , Apoptose , Ciclo Celular , Divisão Celular , Linhagem Celular , Células Cultivadas , Citoesqueleto/metabolismo , DNA/biossíntese , Endotélio Vascular/citologia , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica , Humanos , Immunoblotting , Camundongos , Camundongos Transgênicos , Músculo Liso/citologia , NADPH Oxidases/metabolismo , Oniocompostos/farmacologia , RNA/metabolismo , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Distribuição Tecidual , Transcrição Gênica , Regulação para CimaAssuntos
Cardiopatias Congênitas , Hipertensão Arterial Pulmonar , Dispneia/etiologia , Hipertensão Pulmonar Primária Familiar , Feminino , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Humanos , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/etiologiaRESUMO
There has been tremendous growth in the population of adults with congenital heart disease (CHD) over the last few decades because of advances in medical care. Whereas some cases are cured during childhood, most patients instead undergo palliation, which leaves them at risk for late complications. Lifelong clinical follow-up involving serial multimodality imaging is helpful to monitor and guide the treatment of late complications. Imaging of these individuals is challenging because of their unique anatomy and therefore requires careful consideration on a case-by-case basis. Knowledge of late complications associated with various diseases and surgical palliations provides a basis for selection and interpretation of an appropriate imaging study. This review highlights the most common conditions in adult CHD and the clinical questions that imaging hopes to answer, as well as the advantages and disadvantages of available imaging modalities. We illustrate clinical scenarios and the use of noninvasive imaging modalities including echocardiography, computed tomography, and magnetic resonance imaging, as well as applications in the following CHDs: tetralogy of Fallot, transposition of the great arteries, coarctation of the aorta, shunts, functional single ventricle, and coronary anomalies.