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1.
Artículo en Inglés | MEDLINE | ID: mdl-38708143

RESUMEN

While minimally invasive laparoscopic surgery can help reduce blood loss, reduce hospital time, and shorten recovery time compared to open surgery, it has the disadvantages of limited field of view and difficulty in locating subsurface targets. Our proposed solution applies an augmented reality (AR) system to overlay pre-operative images, such as those from magnetic resonance imaging (MRI), onto the target organ in the user's real-world environment. Our system can provide critical information regarding the location of subsurface lesions to guide surgical procedures in real time. An infrared motion tracking camera system was employed to obtain real-time position data of the patient and surgical instruments. To perform hologram registration, fiducial markers were used to track and map virtual coordinates to the real world. In this study, phantom models of each organ were constructed to test the reliability and accuracy of the AR-guided laparoscopic system. Root mean square error (RMSE) was used to evaluate the targeting accuracy of the laparoscopic interventional procedure. Our results demonstrated a registration error of 2.42 ± 0.79 mm and a procedural targeting error of 4.17 ± 1.63 mm using our AR-guided laparoscopic system that will be further refined for potential clinical procedures.

2.
J Am Coll Emerg Physicians Open ; 5(2): e13140, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38567033

RESUMEN

Objective: Protocols to evaluate for myocardial infarction (MI) using high-sensitivity cardiac troponin (hs-cTn) have the potential to drive costs upward due to the added sensitivity. We performed an economic evaluation of an accelerated protocol (AP) to evaluate for MI using hs-cTn to identify changes in costs of treatment and length of stay compared with conventional testing. Methods: We performed a planned secondary economic analysis of a large, cluster randomized trial across nine emergency departments (EDs) from July 2020 to April 2021. Patients were included if they were 18 years or older with clinical suspicion for MI. In the AP, patients could be discharged without further testing at 0 h if they had a hs-cTnI < 4 ng/L and at 1 h if the initial value were 4 ng/L and the 1-h value ≤7 ng/L. Patients in the standard of care (SC) protocol used conventional cTn testing at 0 and 3 h. The primary outcome was the total cost of treatment, and the secondary outcome was ED length of stay. Results: Among 32,450 included patients, an AP had no significant differences in cost (+$89, CI: -$714, $893 hospital cost, +$362, CI: -$414, $1138 health system cost) or ED length of stay (+46, CI: -28, 120 min) compared with the SC protocol. In lower acuity, free-standing EDs, patients under the AP experienced shorter length of stay (-37 min, CI: -62, 12 min) and reduced health system cost (-$112, CI: -$250, $25). Conclusion: Overall, the implementation of AP using hs-cTn does not result in higher costs.

3.
Nat Commun ; 15(1): 3113, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600097

RESUMEN

Autophagy is a conserved, catabolic process essential for maintaining cellular homeostasis. Malfunctional autophagy contributes to neurodevelopmental and neurodegenerative diseases. However, the exact role and targets of autophagy in human neurons remain elusive. Here we report a systematic investigation of neuronal autophagy targets through integrated proteomics. Deep proteomic profiling of multiple autophagy-deficient lines of human induced neurons, mouse brains, and brain LC3-interactome reveals roles of neuronal autophagy in targeting proteins of multiple cellular organelles/pathways, including endoplasmic reticulum (ER), mitochondria, endosome, Golgi apparatus, synaptic vesicle (SV) for degradation. By combining phosphoproteomics and functional analysis in human and mouse neurons, we uncovered a function of neuronal autophagy in controlling cAMP-PKA and c-FOS-mediated neuronal activity through selective degradation of the protein kinase A - cAMP-binding regulatory (R)-subunit I (PKA-RI) complex. Lack of AKAP11 causes accumulation of the PKA-RI complex in the soma and neurites, demonstrating a constant clearance of PKA-RI complex through AKAP11-mediated degradation in neurons. Our study thus reveals the landscape of autophagy degradation in human neurons and identifies a physiological function of autophagy in controlling homeostasis of PKA-RI complex and specific PKA activity in neurons.


Asunto(s)
Neuronas , Proteómica , Ratones , Animales , Humanos , Neuronas/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Autofagia/fisiología , Homeostasis
4.
SLAS Discov ; 28(5): 233-239, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36990319

RESUMEN

Galectin-3 is a beta-galactoside-binding mammalian lectin that is one of a 15-member galectin family that can bind several cell surface glycoproteins via its carbohydrate recognition domain (CRD). As a result, it can influence a range of cellular processes including cell activation, adhesion and apoptosis. Galectin-3 has been implicated in various diseases, including fibrotic disorders and cancer, and is now being therapeutically targeted by both small and large molecules. Historically, the screening and triaging of small molecule glycomimetics that bind to the galectin-3 CRD has been completed in fluorescence polarisation (FP) assays to determine KD values. Surface plasmon resonance (SPR) has not been widely used for compound screening and in this study it was used to compare human and mouse galectin-3 affinity measures between FP and SPR, as well as investigate compound kinetics. The KD estimates for a set of compounds selected from mono- and di-saccharides with affinities across a 550-fold range, correlated well between FP and SPR assay formats for both human and mouse galectin-3. Increases in affinity for compounds binding to human galectin-3 were driven by changes in both kon and koff whilst for mouse galectin-3 this was primarily due to kon. The reduction in affinity observed between human to mouse galectin-3 was also comparable between assay formats. SPR has been shown to be a viable alternative to FP for early drug discovery screening and determining KD values. In addition, it can also provide early kinetic characterisation of small molecule galectin-3 glycomimetics with robust kon and koff values generated in a high throughput manner.


Asunto(s)
Galectina 3 , Resonancia por Plasmón de Superficie , Humanos , Animales , Ratones , Galectina 3/genética , Galectina 3/química , Galectina 3/metabolismo , Cinética , Galectinas/química , Galectinas/metabolismo , Carbohidratos/química , Mamíferos/metabolismo
5.
BMJ Case Rep ; 14(10)2021 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-34667036

RESUMEN

Previous reports have described non-ischaemic cardiomyopathy related to a variety of autoimmune diseases. However, very few case reports describe Sjögren disease as a contributing factor to cardiomyopathy. We report the case of a 69-year-old woman with a history of Sjögren disease who presented with cardiogenic shock. Laboratory testing and cardiac MRI revealing apical septal late gadolinium enhancement were consistent with an autoimmune aetiology. After ruling out ischaemic, infectious and other possible causes, the patient's clinical presentation was thought to be related to underlying Sjögren disease. She was treated with intravenous steroids and evidence-based heart failure therapy, but she eventually died after having declined heart transplantation. Given the rarity of Sjögren disease, no diagnostic criteria or standard treatment has been established for cardiomyopathy related to this disease. Diagnosis should be considered in patients who show evidence of autoimmune processes after other possible causes are ruled out.


Asunto(s)
Cardiomiopatías , Síndrome de Sjögren , Anciano , Cardiomiopatías/complicaciones , Cardiomiopatías/diagnóstico , Medios de Contraste , Femenino , Gadolinio , Humanos , Choque Cardiogénico/diagnóstico , Choque Cardiogénico/etiología , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/tratamiento farmacológico
6.
J Ultrasound Med ; 40(1): 175-181, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32557791

RESUMEN

When evaluating patients with hip pain, clinicians may be trained to both evaluate for a hip effusion and perform ultrasound-guided arthrocentesis to evaluate the etiology of the effusion. We present a novel 3-dimensional-printed hip arthrocentesis model, which can be used to train clinicians to perform both tasks under ultrasound guidance. Our model uses a combination of a 3-dimensional-printed hip joint, as well as readily available materials such as an infant Ambu (Ballerup, Denmark) bag, syringe, intravenous line kit, and silicone. We present our experience so that others may use and adapt our model for their training purposes.


Asunto(s)
Artrocentesis , Artralgia , Articulación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/cirugía , Humanos , Ultrasonografía , Ultrasonografía Intervencional
7.
J Invasive Cardiol ; 32(3): 104-109, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31941835

RESUMEN

BACKGROUND: Recent studies suggest that primary percutaneous coronary intervention (PCI) and targeted temperature management (TTM) improve outcome in ST-segment elevation myocardial infarction (STEMI) complicated by out-of-hospital cardiac arrest (OHCA). The objective of this study was to evaluate a contemporary series of patients with STEMI and OHCA to characterize treatment approaches and predictors of neurologic outcome. METHODS: From January 2009 through November 2012, a total of 239 patients who underwent emergent coronary angiography at 10 medical centers across the United States were enrolled. All patients suffered OHCA with STEMI on either the prehospital or post-resuscitation electrocardiogram. Neurologic outcome was assessed using the cerebral performance category (CPC) score. Predictors of neurologic outcome were determined using multivariate logistic regression analysis. The primary endpoint was in-hospital survival with good neurologic function (CPC score 1 or 2). RESULTS: Mean age was 60 ± 13 years, 72% were male, and the majority of patients had a history of cardiovascular event. Initial rhythm was ventricular fibrillation in 72%. At hospital presentation, 76% of patients were intubated, 37% were in cardiogenic shock, and 33% were receiving vasopressors. Primary PCI was performed in 74%, with an average door-to-balloon time of 95 ± 77 minutes, and TTM was used in 51%. Forty-four percent of patients had full neurologic recovery (CPC score 1) and 55% had good neurologic function. Overall in-hospital survival rate was 66%. Independent predictors of in-hospital survival with good neurologic function were: receiving bystander cardiopulmonary resuscitation, location of arrest, receiving drug-eluting stents, and not experiencing a recurrent cardiac arrest. CONCLUSIONS: Short-term survival for patients with STEMI and OHCA undergoing emergent coronary angiography and revascularization with TTM in this contemporary, multicenter registry was high and neurologic outcome was good in more than half of patients.


Asunto(s)
Infarto del Miocardio , Paro Cardíaco Extrahospitalario , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paro Cardíaco Extrahospitalario/diagnóstico , Paro Cardíaco Extrahospitalario/terapia , Sistema de Registros , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/cirugía , Resultado del Tratamiento
8.
Sci Rep ; 9(1): 14645, 2019 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-31601934

RESUMEN

Multidomain proteins represent a broad spectrum of the protein landscape and are involved in various interactions. They could be considered as modular building blocks assembled in distinct fashion and connected by linkers of varying lengths and sequences. Due to their intrinsic flexibility, these linkers provide proteins a subtle way to modulate interactions and explore a wide range of conformational space. In the present study, we are seeking to understand the effect of the flexibility and dynamics of the linker involved in the STAM2 UIM-SH3 dual domain protein with respect to molecular recognition. We have engineered several constructs of UIM-SH3 with different length linkers or domain deletion. By means of SAXS and NMR experiments, we have shown that the modification of the linker modifies the flexibility and the dynamics of UIM-SH3. Indeed, the global tumbling of both the UIM and SH3 domain is different but not independent from each other while the length of the linker has an impact on the ps-ns time scale dynamics of the respective domains. Finally, the modification of the flexibility and dynamics of the linker has a drastic effect on the interaction of UIM-SH3 with Lys63-linked diubiquitin with a roughly eight-time weaker dissociation constant.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Ubiquitinas/metabolismo , Dominios Homologos src , Complejos de Clasificación Endosomal Requeridos para el Transporte/ultraestructura , Simulación de Dinámica Molecular , Resonancia Magnética Nuclear Biomolecular , Unión Proteica , Dispersión del Ángulo Pequeño , Ubiquitinas/ultraestructura , Difracción de Rayos X
9.
Cardiovasc Revasc Med ; 20(2): 133-136, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-29898868

RESUMEN

INTRODUCTION: The purpose of the study is to develop an optimal TR-Band weaning strategy while minimizing vascular access site complications of hematoma or radial artery occlusion (RAO). METHODS: The trial was a randomized, prospective, single center study of 129 patients who underwent cardiac catheterization via the radial artery. Group A was an accelerated protocol in which weaning was initiated 20 min after sheath removal. Group B was an adjusted protocol, in which weaning was dependent on the amount of anti-platelet or anti-coagulation used. All patients underwent radial artery ultrasound to demonstrate arterial patency. RESULTS: Baseline characteristics were similar in both groups, and PCI was performed in 36.7% of patients in Group A and 37.7% of patients in Group B. RAO occurred in 7.7% of patients overall, with no statistical difference between groups (Group A 5% versus Group B 10.1%, p-value = 0.337). Hematoma formation >5 cm in diameter occurred in 4.6% of patients in the overall cohort, without statistical difference between groups (Group A 5% versus Group B 4.3%, p-value = 1). The TR-Band duration was significantly shorter in Group A compared to Group B (112.9 ±â€¯50.7 versus 130.7 ±â€¯51.1 in minutes, respectively, p-value = 0.013). CONCLUSION: We have demonstrated an accelerated weaning protocol is simple to utilize for nursing staff without increased vascular site complications of RAO or hematoma formation.


Asunto(s)
Cateterismo Cardíaco , Cateterismo Periférico , Hemorragia/prevención & control , Técnicas Hemostáticas/instrumentación , Arteria Radial , Anciano , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/etiología , Arteriopatías Oclusivas/fisiopatología , Cateterismo Periférico/efectos adversos , Femenino , Hematoma/etiología , Hemorragia/etiología , Técnicas Hemostáticas/efectos adversos , Humanos , Masculino , Michigan , Persona de Mediana Edad , Estudios Prospectivos , Punciones , Arteria Radial/diagnóstico por imagen , Arteria Radial/fisiopatología , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción Vascular
10.
Cardiovasc Revasc Med ; 18(5): 328-331, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28314674

RESUMEN

OBJECTIVES: To evaluate the success rates and outcome of the hybrid algorithm for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) by a single operator in two different clinical settings. METHODS: We compared 279 consecutive CTO PCIs performed by a single, high-volume operator using the hybrid algorithm in two different clinical settings. Data were collected through the PROGRESS CTO Registry. We compared 145 interventions performed in a community program (cohort A) with 134 interventions performed in a referral center (cohort B). RESULTS: Patient in cohort B had more complex lesions with higher J-CTO (3.0 vs. 3.41; p<0.001) and Progress CTO (1.5 vs.1.8, P=0.003) scores, more moderate to severe tortuosity (38% vs. 64%; p<0.001), longer total occlusion length (25 vs. 40mm; p<0.001) and higher prevalence of prior failed CTO PCI attempts (15% vs. 35%; p=0.001). Both technical (95% vs. 91%; p=0.266) and procedural (94% vs. 88%; p=0.088) success rates were similar between the two cohorts despite significantly different lesion complexity. Overall major adverse cardiovascular events were higher in cohort B (1.4% vs. 7.8%; p=0.012) without any significant difference in mortality (0.7% vs. 2.3%, p=0.351). CONCLUSIONS: In spite of higher lesion complexity in the setting of a quaternary-care referral center, use of the hybrid algorithm for CTO PCI enabled similarly high technical and procedural success rates as compared with those previously achieved by the same operator in a community-based program at the expense of a higher rate of MACE.


Asunto(s)
Algoritmos , Angiografía Coronaria , Oclusión Coronaria/cirugía , Intervención Coronaria Percutánea , Anciano , Anciano de 80 o más Años , Enfermedad Crónica/terapia , Estudios de Cohortes , Angiografía Coronaria/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/métodos , Sistema de Registros , Factores de Riesgo , Resultado del Tratamiento
11.
Sci Rep ; 7: 40948, 2017 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-28102317

RESUMEN

We present a combination of small-angle neutron scattering, deuterium labelling and contrast variation, temperature activation and fluorescence spectroscopy as a novel approach to obtain time-resolved, structural data individually from macromolecular complexes and their substrates during active biochemical reactions. The approach allowed us to monitor the mechanical unfolding of a green fluorescent protein model substrate by the archaeal AAA+ PAN unfoldase on the sub-minute time scale. Concomitant with the unfolding of its substrate, the PAN complex underwent an energy-dependent transition from a relaxed to a contracted conformation, followed by a slower expansion to its initial state at the end of the reaction. The results support a model in which AAA ATPases unfold their substrates in a reversible power stroke mechanism involving several subunits and demonstrate the general utility of this time-resolved approach for studying the structural molecular kinetics of multiple protein remodelling complexes and their substrates on the sub-minute time scale.


Asunto(s)
ATPasas Asociadas con Actividades Celulares Diversas/química , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Archaea/enzimología , Dispersión del Ángulo Pequeño , Proteínas Fluorescentes Verdes/metabolismo , Conformación Proteica , Pliegue de Proteína
12.
Biophys J ; 110(10): 2185-94, 2016 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-27224484

RESUMEN

Water molecules in the immediate vicinity of biomacromolecules, including proteins, constitute a hydration layer characterized by physicochemical properties different from those of bulk water and play a vital role in the activity and stability of these structures, as well as in intermolecular interactions. Previous studies using solution scattering, crystallography, and molecular dynamics simulations have provided valuable information about the properties of these hydration shells, including modifications in density and ionic concentration. Small-angle scattering of x-rays (SAXS) and neutrons (SANS) are particularly useful and complementary techniques to study biomacromolecular hydration shells due to their sensitivity to electronic and nuclear scattering-length density fluctuations, respectively. Although several sophisticated SAXS/SANS programs have been developed recently, the impact of physicochemical surface properties on the hydration layer remains controversial, and systematic experimental data from individual biomacromolecular systems are scarce. Here, we address the impact of physicochemical surface properties on the hydration shell by a systematic SAXS/SANS study using three mutants of a single protein, green fluorescent protein (GFP), with highly variable net charge (+36, -6, and -29). The combined analysis of our data shows that the hydration shell is locally denser in the vicinity of acidic surface residues, whereas basic and hydrophilic/hydrophobic residues only mildly modify its density. Moreover, the data demonstrate that the density modifications result from the combined effect of residue-specific recruitment of ions from the bulk in combination with water structural rearrangements in their vicinity. Finally, we find that the specific surface-charge distributions of the different GFP mutants modulate the conformational space of flexible parts of the protein.


Asunto(s)
Proteínas Fluorescentes Verdes/química , Agua/química , Electroforesis en Gel de Poliacrilamida , Escherichia coli , Proteínas Fluorescentes Verdes/genética , Interacciones Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Mutación , Difracción de Neutrones , Dispersión del Ángulo Pequeño , Propiedades de Superficie , Difracción de Rayos X
13.
Acta Crystallogr D Biol Crystallogr ; 71(Pt 1): 57-66, 2015 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-25615860

RESUMEN

Small-angle scattering (SAS) has witnessed a breathtaking renaissance and expansion over the past 15 years regarding the determination of biomacromolecular structures in solution. While important issues such as sample quality, good experimental practice and guidelines for data analysis, interpretation, presentation, publication and deposition are increasingly being recognized, crucial topics such as the uniqueness, precision and accuracy of the structural models obtained by SAS are still only poorly understood and addressed. The present article provides an overview of recent developments in these fields with a focus on the influence of complementary NMR restraints and of a hydration shell on the uniqueness of biomacromolecular models. As a first topic, the impact of incorporating NMR orientational restraints in addition to SAS distance restraints is discussed using a quantitative visual representation that illustrates how the possible conformational space of a two-body system is reduced as a function of the available data. As a second topic, the impact of a hydration shell on modelling parameters of a two-body system is illustrated, in particular on its inter-body distance. Finally, practical recommendations are provided to take both effects into account and promising future perspectives of SAS approaches are discussed.


Asunto(s)
Modelos Químicos , Resonancia Magnética Nuclear Biomolecular/métodos , Dispersión del Ángulo Pequeño , Agua/química
14.
RNA Biol ; 10(4): 579-89, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23603827

RESUMEN

The RNA-binding protein TIAR is an mRNA-binding protein that acts as a translational repressor, particularly important under conditions of cellular stress. It binds to target mRNA and DNA via its RNA recognition motif (RRM) domains and is involved in both splicing regulation and translational repression via the formation of "stress granules." TIAR has also been shown to bind ssDNA and play a role in the regulation of transcription. Here we show, using surface plasmon resonance and nuclear magnetic resonance spectroscopy, specific roles of individual TIAR domains for high-affinity binding to RNA and DNA targets. We confirm that RRM2 of TIAR is the major RNA- and DNA-binding domain. However, the strong nanomolar affinity binding to U-rich RNA and T-rich DNA depends on the presence of the six amino acid residues found in the linker region C-terminal to RRM2. On its own, RRM1 shows preferred binding to DNA over RNA. We further characterize the interaction between RRM2 with the C-terminal extension and an AU-rich target RNA sequence using NMR spectroscopy to identify the amino acid residues involved in binding. We demonstrate that TIAR RRM2, together with its C-terminal extension, is the major contributor for the high-affinity (nM) interactions of TIAR with target RNA sequences.


Asunto(s)
Secuencias de Aminoácidos , Proteínas de Unión al ADN/metabolismo , ADN/metabolismo , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/química , Proteínas de Unión al ARN/metabolismo , Secuencia de Aminoácidos , Sitios de Unión , ADN/genética , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Regulación de la Expresión Génica , Humanos , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Unión Proteica , Empalme del ARN , ARN Mensajero/genética , Proteínas de Unión al ARN/genética , Alineación de Secuencia , Resonancia por Plasmón de Superficie
15.
Am J Cardiol ; 110(1): 124-8, 2012 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-22482864

RESUMEN

We evaluated preventive cardiology education in United States cardiology fellowship programs and their adherence to Core Cardiovascular Training Symposium training guidelines, which recommend 1 month of training, faculty with expertise, and clinical experience in cardiac rehabilitation, lipid disorder management, and diabetes management as a part of the prevention curricula. We sent an anonymous survey to United States cardiology program directors and their chief fellow. The survey assessed the program curricula, rotation structure, faculty expertise, obstacles, and recommended improvements. The results revealed that 24% of surveyed programs met the Core Cardiovascular Training Symposium guidelines with a dedicated 1-month rotation in preventive cardiology, 24% had no formalized training in preventive cardiology, and 30% had no faculty with expertise in preventive cardiology, which correlated with fewer rotations in prevention than those with specialized faculty (p = 0.009). Fellows rotated though the following experiences (% of programs): cardiac rehabilitation, 71%; lipid management, 37%; hypertension, 15%; diabetes, 7%; weight management/obesity, 6%; cardiac nutrition, 6%; and smoking cessation, 5%. The program directors cited "lack of time" as the greatest obstacle to providing preventive cardiology training and the chief fellows reported "lack of a developed curriculum" (p = 0.01). The most recommended improvement was for the American College of Cardiology to develop a web-based curriculum/module. In conclusion, most surveyed United States cardiology training programs currently do not adhere to basic preventive cardiovascular medicine Core Cardiovascular Training Symposium recommendations. Additional attention to developing curricular content and structure, including the creation of an American College of Cardiology on-line knowledge module might improve fellowship training in preventive cardiology.


Asunto(s)
Cardiología/educación , Curriculum/normas , Guías como Asunto , Internado y Residencia/normas , Cardiología/métodos , Recolección de Datos , Humanos , Estudios Retrospectivos , Estados Unidos
16.
Nucleic Acids Res ; 39(3): 1117-30, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21233170

RESUMEN

TIAR and HuR are mRNA-binding proteins that play important roles in the regulation of translation. They both possess three RNA recognition motifs (RRMs) and bind to AU-rich elements (AREs), with seemingly overlapping specificity. Here we show using SPR that TIAR and HuR bind to both U-rich and AU-rich RNA in the nanomolar range, with higher overall affinity for U-rich RNA. However, the higher affinity for U-rich sequences is mainly due to faster association with U-rich RNA, which we propose is a reflection of the higher probability of association. Differences between TIAR and HuR are observed in their modes of binding to RNA. TIAR is able to bind deoxy-oligonucleotides with nanomolar affinity, whereas HuR affinity is reduced to a micromolar level. Studies with U-rich DNA reveal that TIAR binding depends less on the 2'-hydroxyl group of RNA than HuR binding. Finally we show that SAXS data, recorded for the first two domains of TIAR in complex with RNA, are more consistent with a flexible, elongated shape and not the compact shape that the first two domains of Hu proteins adopt upon binding to RNA. We thus propose that these triple-RRM proteins, which compete for the same binding sites in cells, interact with their targets in fundamentally different ways.


Asunto(s)
Antígenos de Superficie/química , ADN/química , Proteínas de Unión al ARN/química , ARN/química , Adenina/análisis , Antígenos de Superficie/metabolismo , ADN/metabolismo , Proteínas ELAV , Proteína 1 Similar a ELAV , Cinética , Modelos Moleculares , Unión Proteica , Conformación Proteica , ARN/metabolismo , Proteínas de Unión al ARN/metabolismo , Dispersión del Ángulo Pequeño , Uracilo/análisis , Difracción de Rayos X
17.
Atherosclerosis ; 205(1): 107-12, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19144335

RESUMEN

Matrix metalloproteinase-9 (MMP-9) has been proposed to be an important modulator of atherosclerotic plaque vulnerability. We generated a transgenic (tg) model expressing human proMMP-9 in macrophages, using the scavenger receptor enhancer/promoter A. This model was crossed into the double Apoe/Timp-1 knockout background. After 16 weeks of a high-fat diet, there were no significant changes in plaque size in the proximal aortas between the four groups of the study population (Apoe(-/-), Apoe(-/-)/MMP-9tg, Apoe(-/-)/Timp-1(-/-), and Apoe(-/-)/MMP-9tg/Timp-1(-/-)), and, in the Timp-1 knockout background, MMP-9 transgenic mice and control littermates had similar micro-aneurysm formation. However, lesions in Apoe(-/-)/MMP-9tg/Timp-1(-/-) mice contained significantly more collagen compared to the three other groups (P<0.005). Culture supernatants from elicited Apoe(-/-)/MMP-9tg/Timp-1(-/-) macrophages contained higher levels of active TGF-beta than the three other groups (P<0.05), suggesting that augmented collagen deposition resulted from an increase in TGF-beta activation due to transgenic MMP-9 in the Timp-1(-/-) background. This study indicates that, in human atherosclerosis, increased MMP-9 activity could up-regulate collagen deposition, possibly through TGF-beta activation.


Asunto(s)
Aterosclerosis/enzimología , Aterosclerosis/genética , Colágeno/metabolismo , Metaloproteinasa 9 de la Matriz/biosíntesis , Metaloproteinasa 9 de la Matriz/genética , Transgenes , Animales , Aorta/patología , Regulación de la Expresión Génica , Humanos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Modelos Biológicos , Factor de Crecimiento Transformador beta/metabolismo
18.
J Thromb Thrombolysis ; 27(1): 18-23, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17898930

RESUMEN

BACKGROUND: The missed diagnosis of acute myocardial infarction has been studied in the Emergency Department, but few studies have investigated how often coronary ischemia is correctly identified in the outpatient setting. METHODS: This was a single center retrospective observational study of patients with Health Alliance Plan medical insurance hospitalized at a US tertiary center with acute myocardial infarction in 2004. Outpatient encounters in the 30 days preceding acute myocardial infarction were reviewed by two independent cardiologists for presenting symptoms and diagnostic decision-making in order to classify patient presentations as acute coronary ischemia, stable angina or neither. RESULTS: There were 331 patients with acute myocardial infarction, including 190 (57%) with a primary diagnosis of AMI and evaluated by a physician in the preceding 30 days. This group included 68 patients with 95 documented outpatient encounters by a primary care physician, cardiologist, or other internal medicine specialist which formed the final study population. Mean interval between these encounters and AMI was 17 +/- 11 days. Of these patients, 7 (10%) had symptoms of acute coronary ischemia, 5 (7%) had stable angina symptoms, and 56 (83%) had no symptoms of coronary ischemia at their outpatient encounters. Of the 7 patients with acute coronary ischemic symptoms, 5 were correctly identified and 2 were misidentified. CONCLUSION: A majority of patients with subsequent AMI visit an outpatient provider in the month preceding AMI. However, few present with symptoms of coronary ischemia in the outpatient setting (10%) and these symptoms are not always identified as such.


Asunto(s)
Síndrome Coronario Agudo/diagnóstico , Atención Ambulatoria , Errores Diagnósticos , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/epidemiología , Anciano , Anciano de 80 o más Años , Algoritmos , Atención Ambulatoria/estadística & datos numéricos , Cardiología , Dolor en el Pecho/etiología , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Disnea/etiología , Diagnóstico Precoz , Femenino , Hospitales Urbanos/estadística & datos numéricos , Humanos , Medicina Interna , Masculino , Persona de Mediana Edad , Náusea/etiología , Atención Primaria de Salud , Estudios Retrospectivos , Síncope/etiología
19.
J Orthop Trauma ; 22(4): 258-63, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18404035

RESUMEN

OBJECTIVES: With the development and popularization of minimally invasive surgical methods and implants for fracture fixation, it is increasingly important that the available implants are precontoured to the specific anatomic location for which they are designed. The objective of this study was to develop a noninvasive method and criteria for quantifying the fit of a distal periarticular medial tibia plate and to test the method on a small set of tibia models. METHODS: The undersurface of the plate was extracted from a digital model of the plate. The surface of the plate was fitted to 21 computer tomography (CT)-based 3-dimensional (3-D) models of human tibiae. Four criteria were defined that constitute an anatomic plate fit and subsequently were applied for the quantitative fit assessment. The fitting of the plate undersurface to the bone was entirely conducted in a virtual environment. RESULTS: An anatomic fit of the plate was achieved for 4 of the models (19%). The individual categories generated fits of 62% (n = 13) for the proximal end; 43% (n = 9) for the proximal angle; 57% (n = 12) for the middle distance; and 57% (n = 12) for a distal fit. CONCLUSIONS: Although for the 4 individual criteria plate fits of 43%-62% were achieved, a global/anatomic fit only occurred for 19% of the bone models. This outcome is likely a result of bone morphology variations, which exist in a random population sample combined with the effects of a nonoptimized plate shape. Recommendations for optimizing the fit of the plate are discussed.


Asunto(s)
Diseño Asistido por Computadora , Fijación Interna de Fracturas/instrumentación , Fijadores Internos , Diseño de Prótesis/métodos , Tibia/lesiones , Implantes Absorbibles , Fracturas Óseas/cirugía , Humanos , Ajuste de Prótesis/métodos
20.
Clin Cardiol ; 31(2): 67-71, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18257021

RESUMEN

BACKGROUND: Elevated troponin I has been associated with increased mortality in critically ill patients without acute coronary syndrome (ACS). However, the prognostic significance of troponin elevation in patients with diabetic ketoacidosis (DKA) without evident ACS has not been studied. METHODS: Retrospective study of all patients admitted to a U.S. tertiary center between 01/98 and 12/00 with DKA and had troponin I level measured. Patients with evidence of ACS or who met the American College of Cardiology/European Society of Cardiology (ACC/ESC) definition for myocardial infarction were excluded. Baseline characteristics, cardiac evaluation and 2 year major adverse coronary event (MACE) rate were compared between patients with positive and negative troponin. RESULTS: Ninety-six patients fulfilled the inclusion criteria of this study, 26 had positive troponin. There were no differences in baseline characteristics between the two groups. After a 2 year follow-up, there was significantly increased mortality in patients with elevated troponin (50.0% versus 27.1%, hazard-ratio (HR) 2.3, 95% confidence interval (CI) 1.2-4.8, p = 0.02). Patients with elevated troponin also had significantly increased MACE rate at 2 years (50.0% versus 28.6%, HR 2.6, 95% CI 1.3-5.3, p = 0.007) driven primarily by mortality. Using Cox Proportional Hazard Analysis, elevated troponin was a predictor of increased MACE after adjusting for confounding variables. (Adjusted HR 2.3, 95% CI 1.1-4.6, p = 0.02) CONCLUSIONS: Elevated troponin I in diabetic patients admitted with DKA identifies a group at very high risk for future cardiac events and mortality. Whether cardiac risk stratification of these patients will improve long term outcome remains to be studied.


Asunto(s)
Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Cetoacidosis Diabética/sangre , Troponina I/sangre , Síndrome Coronario Agudo , Biomarcadores/sangre , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/mortalidad , Cetoacidosis Diabética/fisiopatología , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Proyectos de Investigación , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo
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