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PURPOSE: To evaluate ultrasound-accelerated, catheter-directed thrombolysis (CDT) for treatment of acute submassive pulmonary embolism (PE). MATERIALS AND METHODS: This single-center, retrospective study included patients who underwent CDT for acute submassive PE (N = 113, 52% men/48% women) from 2013 to 2017. Baseline characteristics included history of deep venous thrombosis (12%), history of PE (6%), and history of cancer (18%). Of cohort patients, 88% (n=99) had a simplified PE severity index score of ≥ 1 indicating a high risk of mortality. RESULTS: A technical success rate of 100% was achieved with 84% of patients having bilateral catheter placements. Average tissue plasminogen activator (tPA) therapy duration was 20.7 hours ± 1.5, and median tPA dose was 21.5 mg. Three patients (2.6%) experienced minor hemorrhagic complications. Mean hospital length of stay was 6 days. Mean pulmonary arterial pressure decreased from 55 mm Hg on presentation to 37 mm Hg (P < .01) 1 day following initiation of thrombolytic therapy. All-cause mortality rate of 4% (n = 4) was noted on discharge, which increased to 6% (n = 7) at 6 months. At 6-month follow-up compared with initial presentation, symptom improvements (93%), physiologic improvements (heart rate 72 beats/min vs 106 beats/min, P < .01), oxygen requirement improvements (fraction of inspired oxygen 20% vs 28%, P < .01), and right ventricular systolic pressure improvements by echocardiography (30 mm Hg vs 47 mm Hg, P < .01) were observed. CONCLUSIONS: CDT for acute submassive PE was associated with low complications and mortality, decreased right ventricular systolic pressure, high rates of clinical improvement, and improved intermediate-term clinical outcomes.
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Fibrinolíticos/administración & dosificación , Embolia Pulmonar/terapia , Terapia Trombolítica , Activador de Tejido Plasminógeno/administración & dosificación , Terapia por Ultrasonido , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Fibrinolíticos/efectos adversos , Hemodinámica , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/mortalidad , Embolia Pulmonar/fisiopatología , Estudios Retrospectivos , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/mortalidad , Factores de Tiempo , Activador de Tejido Plasminógeno/efectos adversos , Resultado del Tratamiento , Terapia por Ultrasonido/efectos adversos , Terapia por Ultrasonido/mortalidad , Función Ventricular Derecha , Adulto JovenRESUMEN
BACKGROUND: Mixed Lineage Leukemia 1 (MLL1) is a mammalian ortholog of the Drosophila Trithorax. In Drosophila, Trithorax complexes transmit the memory of active genes to daughter cells through interactions with Trithorax Response Elements (TREs). However, despite their functional importance, nothing is known about sequence features that may act as TREs in mammalian genomic DNA. RESULTS: By analyzing results of reported DNA binding assays, we identified several CpG rich motifs as potential MLL1 binding units (defined as morphemes). We find that these morphemes are dispersed within a relatively large collection of human promoter sequences and appear densely packed near transcription start sites of protein-coding genes. Genome wide analyses localized frequent morpheme occurrences to CpG islands. In the human HOX loci, the morphemes are spread across CpG islands and in some cases tail into the surrounding shores and shelves of the islands. By analyzing results of chromatin immunoprecipitation assays, we found a connection between morpheme occurrences, CpG islands, and chromatin segments reported to be associated with MLL1. Furthermore, we found a correspondence of reported MLL1-driven "bookmarked" regions in chromatin to frequent occurrences of MLL1 morphemes in CpG islands. CONCLUSION: Our results implicate the MLL1 morphemes in sequence-features that define the mammalian TREs and provide a novel function for CpG islands. Apparently, our findings offer the first evidence for existence of potential TREs in mammalian genomic DNA and the first evidence for a connection between CpG islands and gene-bookmarking by MLL1 to transmit the memory of highly active genes during mitosis. Our results further suggest a role for overlapping morphemes in producing closely packed and multiple MLL1 binding events in genomic DNA so that MLL1 molecules could interact and reside simultaneously on extended potential transcriptional maintenance elements in human chromosomes to transmit the memory of highly active genes during mitosis.
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Cromatina/genética , Cromatina/metabolismo , Islas de CpG , ADN/genética , ADN/metabolismo , Mitosis/fisiología , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Secuencia de Bases , Genoma Humano , N-Metiltransferasa de Histona-Lisina , Humanos , Datos de Secuencia Molecular , Motivos de Nucleótidos , Sistemas de Lectura Abierta , Regiones Promotoras Genéticas , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Mapeo de Interacción de Proteínas , ARN Polimerasa II/genéticaRESUMEN
Background: Proficiency in ultrasound usage is quickly becoming an expectation in multiple residency programs: emergency medicine, obstetrics-gynecology, surgery, and internal medicine. There is a lack of affordable training devices for ultrasound training and identification of superficial fluid collections. We sought to develop a model for trainee education in ultrasound usage, identification of superficial fluid collection, aspiration, and incision & drainage (I&D). Materials & methods: Commercially available products were used to develop a novel, low-cost model for ultrasound-guided aspiration and I&D of an abscess. A latex balloon embedded in silicone gel construct simulated a superficial fluid collection when examined with an ultrasound probe and monitor. A 18-gauge needle on a 10-cc syringe were used for aspiration, and a 15-blade disposal scalpel with 0.25â³ packing strip used for I&D. Results: Approximately six hours are required to generate 24 individual models of a superficial abscess. Following an initial investment, each model costs less than $1 USD to produce. Compared to commercially available models, this represents a significant savings. This model was utilized during the medical school academic year as a teaching aid for medical students to simulate ultrasound-guided identification, aspiration, and incision and drainage of a superficial abscess. Conclusions: We successfully produced an affordable, low-cost model of a superficial fluid collection for training in ultrasound usage, aspiration, and I&D. The model represents significant savings over commercially available alternatives and can be easily replicated for trainee education.
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INTRODUCTION: The childhood heart disease of Friedreich's Ataxia (FRDA) is characterized by hypertrophy and failure. It is caused by loss of frataxin (FXN), a mitochondrial protein involved in energy homeostasis. FRDA model hearts have increased mitochondrial protein acetylation and impaired sirtuin 3 (SIRT3) deacetylase activity. Protein acetylation is an important regulator of cardiac metabolism and loss of SIRT3 increases susceptibility of the heart to stress-induced cardiac hypertrophy and ischemic injury. The underlying pathophysiology of heart failure in FRDA is unclear. The purpose of this study was to examine in detail the physiologic and acetylation changes of the heart that occur over time in a model of FRDA heart failure. We predicted that increased mitochondrial protein acetylation would be associated with a decrease in heart function in a model of FRDA. METHODS: A conditional mouse model of FRDA cardiomyopathy with ablation of FXN (FXN KO) in the heart was compared to healthy controls at postnatal days 30, 45 and 65. We evaluated hearts using echocardiography, cardiac catheterization, histology, protein acetylation and expression. RESULTS: Acetylation was temporally progressive and paralleled evolution of heart failure in the FXN KO model. Increased acetylation preceded detectable abnormalities in cardiac function and progressed rapidly with age in the FXN KO mouse. Acetylation was also associated with cardiac fibrosis, mitochondrial damage, impaired fat metabolism, and diastolic and systolic dysfunction leading to heart failure. There was a strong inverse correlation between level of protein acetylation and heart function. CONCLUSION: These results demonstrate a close relationship between mitochondrial protein acetylation, physiologic dysfunction and metabolic disruption in FRDA hypertrophic cardiomyopathy and suggest that abnormal acetylation contributes to the pathophysiology of heart disease in FRDA. Mitochondrial protein acetylation may represent a therapeutic target for early intervention.