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1.
Proc Natl Acad Sci U S A ; 117(41): 25352-25359, 2020 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-32989151

RESUMEN

Electronic skins are essential for real-time health monitoring and tactile perception in robots. Although the use of soft elastomers and microstructures have improved the sensitivity and pressure-sensing range of tactile sensors, the intrinsic viscoelasticity of soft polymeric materials remains a long-standing challenge resulting in cyclic hysteresis. This causes sensor data variations between contact events that negatively impact the accuracy and reliability. Here, we introduce the Tactile Resistive Annularly Cracked E-Skin (TRACE) sensor to address the inherent trade-off between sensitivity and hysteresis in tactile sensors when using soft materials. We discovered that piezoresistive sensors made using an array of three-dimensional (3D) metallic annular cracks on polymeric microstructures possess high sensitivities (> 107 Ω â‹… kPa-1), low hysteresis (2.99 ± 1.37%) over a wide pressure range (0-20 kPa), and fast response (400 Hz). We demonstrate that TRACE sensors can accurately detect and measure the pulse wave velocity (PWV) when skin mounted. Moreover, we show that these tactile sensors when arrayed enabled fast reliable one-touch surface texture classification with neuromorphic encoding and deep learning algorithms.


Asunto(s)
Aprendizaje Automático , Dispositivos Electrónicos Vestibles , Humanos , Ciencia de los Materiales , Presión , Análisis de la Onda del Pulso
2.
J Environ Manage ; 301: 113751, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34628283

RESUMEN

Heat-related mortality is one of the leading causes of weather-related deaths in the United States. With changing climates and an aging population, effective adaptive strategies to address public health and environmental justice issues associated with extreme heat will be increasingly important. One effective adaptive strategy for reducing heat-related mortality is increasing tree cover. Designing such a strategy requires decision-support tools that provide spatial and temporal information about impacts. We apply such a tool to estimate spatially and temporally explicit reductions in temperature and mortality associated with a 10% increase in tree cover in 10 U.S. cities with varying climatic, demographic, and land cover conditions. Two heat metrics were applied to represent tree impacts on moderately and extremely hot days (relative to historical conditions). Increasing tree cover by 10% reduced estimated heat-related mortality in cities significantly, with total impacts generally greatest in the most populated cities. Mortality reductions vary widely across cities, ranging from approximately 50 fewer deaths in Salt Lake City to about 3800 fewer deaths in New York City. This variation is due to differences in demographics, land cover, and local climatic conditions. In terms of per capita estimated impacts, hotter and drier cities experience higher percentage reductions in mortality due to increased tree cover across the season. Phoenix potentially benefits the most from increased tree cover, with an estimated 22% reduction in mortality from baseline levels. In cooler cities such as Minneapolis, trees can reduce mortality significantly on days that are extremely hot relative to historical conditions and therefore help mitigate impacts during heat wave conditions. Recent studies project highest increases in heat-related mortality in the cooler cities, so our findings have important implications for adaptation planning. Our estimated spatial and temporal distributions of mortality reductions for each city provide crucial information needed for promoting environmental justice and equity. More broadly, the methods and model can be applied by both urban planners and the public health community for designing targeted, effective policies to reduce heat-related mortality. Additionally, land use managers can use this information to optimize tree plantings. Public stakeholders can also use these impact estimates for advocacy.


Asunto(s)
Calor , Árboles , Ciudades , Mortalidad , Salud Pública , Estaciones del Año , Estados Unidos
3.
Pancreatology ; 21(1): 144-154, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33309223

RESUMEN

BACKGROUND: Discontinuation of branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) surveillance after 5 years of no change remains controversial. Long-term outcomes of BD-IPMN without significant changes in the first 5 years were evaluated. METHODS: We performed a multi-center retrospective analysis of patients with BD-IPMN diagnosis from 2005 to 2011 (follow-up until 2017). Significant changes were defined as pancreatic cancer (PC), pancreatectomy, high-risk stigmata (HRS), worrisome features (WF) and worrisome EUS features (WEUS). RESULTS: Of 982 patients who had no significant changes, 5 (0.5%), 7 (0.7%), 99 (10.1%), 4 (0.4%) patients developed PC, HRS, WF, WEUS, respectively, post-5 years. PC and HRS/WF/WEUS incidences at 12 years were 1.0% and 29.0%, respectively. Patients that developed HRS/WF/WEUS had larger cyst size in first 5 years compared to those that did not [16 (12-23) vs. 12 (9-17) mm, p = 0.0001], cyst size of >15 mm having higher cumulative incidence of HRS/WF/WEUS. PC mortality was 0.8%; all-cause mortality was 32%. Incidence of mortality due to PC was higher in HRS/WF/WEUS group, p < 0.0001. The mortality rate at 12 years for ACCI (age-adjusted Charlson Comorbidity Index) of ≤3, 4-6, and ≥7 were 3.5%, 19.9%, and 57.6% (p < 0.0001), respectively. CONCLUSIONS: Incidence of PC in patients with BD-IPMN without significant changes in first 5 years of diagnosis remains low at 1.0%. Incidence of HRS/WF/WEUS was higher at 29.0%. PC-related mortality was higher in HRS/WF/WEUS group. These risks should be weighed against patients' overall mortality (utilizing scoring systems such as ACCI) when making surveillance decision of BD-IPMN beyond 5 years.


Asunto(s)
Carcinoma Ductal Pancreático/patología , Conductos Pancreáticos/patología , Neoplasias Pancreáticas/patología , Adenocarcinoma Mucinoso , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/mortalidad , Toma de Decisiones Clínicas , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pancreatectomía , Quiste Pancreático/epidemiología , Quiste Pancreático/patología , Neoplasias Pancreáticas/mortalidad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
4.
BMC Gastroenterol ; 20(1): 60, 2020 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-32143633

RESUMEN

BACKGROUND: Endoscopic mucosal resection (EMR) is a minimally invasive procedure used for the treatment of lesions in the gastrointestinal (GI) tract. There is increased usage of hemoclips during EMR for the prevention of delayed bleeding. This study aimed to evaluate the effect of hemoclips in the prevention of delayed bleeding after EMR of upper and lower GI tract lesions. METHOD: This is a retrospective cohort study using the Kaiser Permanente Southern California (KPSC) EMR registry. Lesions in upper and lower GI tracts that underwent EMR between January 2012 and December 2015 were analyzed. Rates of delayed bleeding were compared between the hemoclip and no-hemoclip groups. Analysis was stratified by upper GI and lower GI lesions. Lower GI group was further stratified by right and left colon. We examined the relationship between clip use and several clinically-relevant variables among the patients who exhibited delayed bleeding. Furthermore, we explored possible procedure-level and endoscopist-level characteristics that may be associated with clip usage. RESULTS: A total of 18 out of 657 lesions (2.7%) resulted in delayed bleeding: 7 (1.1%) in hemoclip group and 11 (1.7%) in no-hemoclip group (p = 0.204). There was no evidence that clip use moderated the effects of the lesion size (p = 0.954) or lesion location (p = 0.997) on the likelihood of delayed bleed. In the lower GI subgroup, clip application did not alter the effect of polyp location (right versus left colon) on the likelihood of delayed bleed (p = 0.951). Logistic regression analyses showed that the clip use did not modify the likelihood of delayed bleeding as related to the following variables: use of aspirin/NSAIDs/anti-coagulants/anti-platelets, pathologic diagnoses (including different types of colon polypoid lesions), ablation, piecemeal resection. The total number of clips used was 901 at a minimum additional cost of $173,893. CONCLUSION: Prophylactic hemoclip application did not reduce delayed post-EMR bleed for upper and lower GI lesions in this retrospective study performed in a large-scale community practice setting. Routine prophylactic hemoclip application during EMR may lead to significantly higher healthcare cost without a clear clinical benefit.


Asunto(s)
Resección Endoscópica de la Mucosa/efectos adversos , Enfermedades Gastrointestinales/cirugía , Técnicas Hemostáticas/instrumentación , Hemorragia Posoperatoria/prevención & control , Anciano , Análisis Costo-Beneficio , Femenino , Costos de la Atención en Salud , Técnicas Hemostáticas/economía , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo
5.
Am J Respir Crit Care Med ; 197(2): 235-243, 2018 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-28872353

RESUMEN

RATIONALE: Primary graft dysfunction (PGD) is a form of acute lung injury that occurs after lung transplantation. The definition of PGD was standardized in 2005. Since that time, clinical practice has evolved, and this definition is increasingly used as a primary endpoint for clinical trials; therefore, validation is warranted. OBJECTIVES: We sought to determine whether refinements to the 2005 consensus definition could further improve construct validity. METHODS: Data from the Lung Transplant Outcomes Group multicenter cohort were used to compare variations on the PGD definition, including alternate oxygenation thresholds, inclusion of additional severity groups, and effects of procedure type and mechanical ventilation. Convergent and divergent validity were compared for mortality prediction and concurrent lung injury biomarker discrimination. MEASUREMENTS AND MAIN RESULTS: A total of 1,179 subjects from 10 centers were enrolled from 2007 to 2012. Median length of follow-up was 4 years (interquartile range = 2.4-5.9). No mortality differences were noted between no PGD (grade 0) and mild PGD (grade 1). Significantly better mortality discrimination was evident for all definitions using later time points (48, 72, or 48-72 hours; P < 0.001). Biomarker divergent discrimination was superior when collapsing grades 0 and 1. Additional severity grades, use of mechanical ventilation, and transplant procedure type had minimal or no effect on mortality or biomarker discrimination. CONCLUSIONS: The PGD consensus definition can be simplified by combining lower PGD grades. Construct validity of grading was present regardless of transplant procedure type or use of mechanical ventilation. Additional severity categories had minimal impact on mortality or biomarker discrimination.


Asunto(s)
Causas de Muerte , Trasplante de Pulmón/efectos adversos , Disfunción Primaria del Injerto/mortalidad , Disfunción Primaria del Injerto/patología , Adulto , Biomarcadores/análisis , Estudios de Cohortes , Consenso , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Trasplante de Pulmón/métodos , Trasplante de Pulmón/mortalidad , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Factores de Tiempo , Estados Unidos , Adulto Joven
6.
J Card Surg ; 34(11): 1374-1376, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31421653

RESUMEN

BACKGROUND: Coarctation of the aorta is a congenital cardiac defect characterized by a narrowing of the proximal thoracic aorta. Despite excellent long-term results, surgical repair is rarely complicated by recoarctation. METHODS/RESULTS: We describe a case with the longest time to reintervention to date, featuring surgical repair of delayed aortic recoarctation and pseudoaneurysm 53 years after the initial operation. DISCUSSION: This case emphasizes the need for lifelong surveillance in this patient population and exemplifies a multidisciplinary approach in evaluating treatment options of complex aortic pathology, including open and endovascular considerations.


Asunto(s)
Aneurisma Falso , Aneurisma de la Aorta , Coartación Aórtica , Complicaciones Posoperatorias , Humanos , Recurrencia , Factores de Tiempo
8.
J Biol Chem ; 288(46): 33324-34, 2013 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-24081143

RESUMEN

Methamphetamine (METH) is a drug of abuse with neurotoxic and neuroinflammatory effects, which include disruption of the blood-brain barrier (BBB) and alterations of tight junction protein expression. This study focused on the actin cytoskeletal rearrangement as a modulator of METH-induced redistribution of tight junction protein occludin in brain endothelial cells. Exposure to METH resulted in a shift of occludin localization from plasma membranes to endosomes. These changes were accompanied by activation of the actin-related protein 2/3 (Arp2/3) complex, which stimulates actin polymerization by promoting actin nucleation. In addition, METH-induced coronin-1b phosphorylation diminishes the inhibitory effect of nonphosphorylated coronin-1b on actin nucleation. Blocking actin nucleation with CK-666, a specific inhibitor of the Arp2/3 complex, protected against METH-induced occludin internalization and increased transendothelial monocyte migration. Importantly, treatment with CK-666 attenuated a decrease in occludin levels in brain microvessels and BBB permeability of METH-injected mice. These findings indicate that actin cytoskeletal dynamics is detrimental to METH-induced BBB dysfunction by increasing internalization of occludin.


Asunto(s)
Complejo 2-3 Proteico Relacionado con la Actina/metabolismo , Actinas/metabolismo , Estimulantes del Sistema Nervioso Central/efectos adversos , Endocitosis/efectos de los fármacos , Células Endoteliales/metabolismo , Metanfetamina/efectos adversos , Ocludina/metabolismo , Complejo 2-3 Proteico Relacionado con la Actina/genética , Actinas/genética , Animales , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , Línea Celular Transformada , Estimulantes del Sistema Nervioso Central/farmacología , Endocitosis/genética , Células Endoteliales/patología , Humanos , Metanfetamina/farmacología , Ratones , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Monocitos/metabolismo , Monocitos/patología , Ocludina/genética , Ratas , Migración Transendotelial y Transepitelial/efectos de los fármacos , Migración Transendotelial y Transepitelial/genética
9.
Am J Gastroenterol ; 109(1): 121-9; quiz 130, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24080609

RESUMEN

OBJECTIVES: Pancreatic cystic neoplasms (PCNs) are being detected with increased frequency. The aims of this study were to determine the incidence of malignancy and develop an imaging-based system for prediction of malignancy in PCN. METHODS: We conducted a retrospective cohort study of patients ≥18 years of age with confirmed PCN from January 2005 to December 2010 in a community-based integrated care setting in Southern California. Patients with history of acute or chronic pancreatitis were excluded. Malignancy diagnosed within 3 months of cyst diagnosis was considered as pre-existing. Subsequent incidence of malignancy during surveillance was calculated based on person-time at risk. Age- and gender-adjusted standardized incidence ratio (SIR) was calculated with the non-cyst reference population. Recursive partitioning was used to develop a risk prediction model based on cyst imaging features. RESULTS: We identified 1,815 patients with confirmed PCN. A total of 53 (2.9%) of patients were diagnosed with cyst-related malignancy during the study period. The surveillance cohort consisted of 1,735 patients with median follow-up of 23.4 months. Incidence of malignancy was 0.4% per year during surveillance. The overall age- and gender-adjusted SIR for pancreatic malignancy was 35.0 (95% confidence level 26.6, 46.0). Using recursive partitioning, we stratified patients into low (<1%), intermediate (1-5%), and high (9-14%) risk of harboring malignant PCN based on four cross-sectional imaging features: size, pancreatic duct dilatation, septations with calcification as well as growth. Area under the receiver operator characteristic curve for the prediction model was 0.822 (training) and 0.808 (testing). CONCLUSIONS: Risk of pancreatic malignancy was lower than previous reports from surgical series but was still significantly higher than the reference population. A risk stratification system based on established imaging criteria may help guide future management decisions for patients with PCN.


Asunto(s)
Quiste Pancreático/patología , Neoplasias Pancreáticas , Lesiones Precancerosas , Anciano , California , Estudios de Cohortes , Femenino , Humanos , Incidencia , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Conductos Pancreáticos/patología , Neoplasias Pancreáticas/clasificación , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/patología , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Medición de Riesgo , Factores de Riesgo , Tomografía Computarizada por Rayos X/métodos , Ultrasonografía/métodos
10.
Nat Biomed Eng ; 8(7): 909-923, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38898172

RESUMEN

Capturing the full complexity of the diverse hierarchical interactions in the protein interactome is challenging. Here we report a DNA-barcoding method for the multiplexed mapping of pairwise and higher-order protein interactions and their dynamics within cells. The method leverages antibodies conjugated with barcoded DNA strands that can bidirectionally hybridize and covalently link to linearize closely spaced interactions within individual 3D protein complexes, encoding and decoding the protein constituents and the interactions among them. By mapping protein interactions in cancer cells and normal cells, we found that tumour cells exhibit a larger diversity and abundance of protein complexes with higher-order interactions. In biopsies of human breast-cancer tissue, the method accurately identified the cancer subtype and revealed that higher-order protein interactions are associated with cancer aggressiveness.


Asunto(s)
Neoplasias de la Mama , Código de Barras del ADN Taxonómico , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Código de Barras del ADN Taxonómico/métodos , Mapeo de Interacción de Proteínas/métodos , Línea Celular Tumoral , ADN/química , ADN/metabolismo , ADN/genética , Femenino
11.
Clim Risk Manag ; 43: 1-18, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38515638

RESUMEN

The interplay of contaminated sites, climate change, and disadvantaged communities are a growing concern worldwide. Worsening extreme events may result in accidental contaminant releases from sites and waste facilities that may impact nearby communities. If such communities are already suffering from environmental, economic, health, or social burdens, they may face disproportionate impacts. Equitable resilience planning to address effects of extreme events requires information on where the impacts may be, when they may occur, and who might be impacted. Because resources are often scarce for these communities, conducting detailed modeling may be cost-prohibitive. By considering indicators for four sources of vulnerability (changing extreme heat conditions, contaminated sites, contaminant transport via wind, and population sensitivities) in one holistic framework, we provide a scientifically robust approach that can assist planners with prioritizing resources and actions. These indicators can serve as screening measures to identify communities that may be impacted most and isolate the reasons for these impacts. Through a transdisciplinary case study conducted in Maricopa County (Arizona, USA), we demonstrate how the framework and geospatial indicators can be applied to inform plans for preparedness, response, and recovery from the effects of extreme heat on contaminated sites and nearby populations. The indicators employed in this demonstration can be applied to other locations with contaminated sites to build community resilience to future climate impacts.

12.
Endoscopy ; 45(10): 799-805, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23897401

RESUMEN

BACKGROUND AND STUDY AIMS: Preliminary data suggested that simulation practice using an endoscopic retrograde cholangiopancreatography (ERCP) mechanical simulator (EMS) improved trainees' skill. The aims of the current study were to confirm the impact of coached EMS practice at the beginning of ERCP training and to investigate whether subsequent uncoached EMS practice provides additional benefit. METHODS: Trainees entering ERCP training in 2008 (n = 8) and 2009 (n = 8) at two referral medical centers were randomized to receive a coached EMS practice either with (2009) or without (2008) subsequent uncoached practices or only routine training (controls). The outcome measures were successful deep biliary cannulation by the trainee and overall performance score as rated by blinded trainers, during the subsequent 3 months of clinical practice. RESULTS: Trainees undergoing single and multiple EMS practices were more likely than controls to achieve successful biliary cannulation (single: adjusted odds ratio [aOR] 2.89, 95 % confidence interval [CI] 2.21 - 3.80 [P < 0.001]; multiple: 3.09, 95 %CI 1.13 - 8.46 [P = 0.028]) and to have superior overall performance scores (aOR 3.29, 95 %CI 1.37 - 7.91 [P = 0.008] and 6.92, 95 %CI 3.77 - 12.69 [P < 0.001], respectively). The benefit of single and multiple EMS practices on overall performance score remained significant after adjustment for success or failure of deep biliary cannulation (aOR 2.98, 95 %CI 1.38 - 6.43 [P = 0.005] and 6.09, 95 %CI 2.40 - 15.45 [P < 0.001], respectively). The benefits of single vs. multiple EMS practices were not statistically different. CONCLUSIONS: Coached simulation using EMS improved novice trainees' success of biliary cannulation and overall ERCP performance. Additional uncoached practices did not appear to provide further benefit. Trainees should undergo a coached EMS practice at the beginning of ERCP training.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica , Competencia Clínica , Educación de Postgrado en Medicina/métodos , Modelos Anatómicos , Enseñanza/métodos , Colangiopancreatografia Retrógrada Endoscópica/instrumentación , Colangiopancreatografia Retrógrada Endoscópica/normas , Humanos , Análisis de Intención de Tratar , Método Simple Ciego , Taiwán
13.
ACG Case Rep J ; 10(4): e01032, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37073379

RESUMEN

Dieulafoy lesion is an aberrant submucosal vessel that can erode into the overlying tissue leading to hemorrhage. It is a rare but important cause of gastrointestinal bleeding. We present a case of a patient who developed an acquired Dieulafoy lesion 39 years after splenectomy. Abdominal computed tomography showed an aberrant vessel from a branch of the left phrenic artery, coursing through the gastric fundus to supply a splenule. Angiography with embolization of the aberrant vessel resulted in no further bleeding.

14.
Artículo en Inglés | MEDLINE | ID: mdl-37022033

RESUMEN

With the increasing pervasiveness of Artificial Intelligence (AI), many visual analytics tools have been proposed to examine fairness, but they mostly focus on data scientist users. Instead, tackling fairness must be inclusive and involve domain experts with specialized tools and workflows. Thus, domain-specific visualizations are needed for algorithmic fairness. Furthermore, while much work on AI fairness has focused on predictive decisions, less has been done for fair allocation and planning, which require human expertise and iterative design to integrate myriad constraints. We propose the Intelligible Fair Allocation (IF-Alloc) Framework that leverages explanations of causal attribution (Why), contrastive (Why Not) and counterfactual reasoning (What If, How To) to aid domain experts to assess and alleviate unfairness in allocation problems. We apply the framework to fair urban planning for designing cities that provide equal access to amenities and benefits for diverse resident types. Specifically, we propose an interactive visual tool, Intelligible Fair City Planner (IF-City), to help urban planners to perceive inequality across groups, identify and attribute sources of inequality, and mitigate inequality with automatic allocation simulations and constraint-satisfying recommendations (IF-Plan). We demonstrate and evaluate the usage and usefulness of IF-City on a real neighborhood in New York City, US, with practicing urban planners from multiple countries, and discuss generalizing our findings, application, and framework to other use cases and applications of fair allocation.

15.
bioRxiv ; 2023 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-36945454

RESUMEN

Axon initial segment (AIS) cell surface proteins mediate key biological processes in neurons including action potential initiation and axo-axonic synapse formation. However, few AIS cell surface proteins have been identified. Here, we used antibody-directed proximity biotinylation to define the cell surface proteins in close proximity to the AIS cell adhesion molecule Neurofascin. To determine the distributions of the identified proteins, we used CRISPR-mediated genome editing for insertion of epitope tags in the endogenous proteins. We found Contactin-1 (Cntn1) among the previously unknown AIS proteins we identified. Cntn1 is enriched at the AIS through interactions with Neurofascin and NrCAM. We further show that Cntn1 contributes to assembly of the AIS-extracellular matrix, and is required for AIS axo-axonic innervation by inhibitory basket cells in the cerebellum and inhibitory chandelier cells in the cortex.

16.
Nat Commun ; 14(1): 6797, 2023 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-37884508

RESUMEN

Axon initial segment (AIS) cell surface proteins mediate key biological processes in neurons including action potential initiation and axo-axonic synapse formation. However, few AIS cell surface proteins have been identified. Here, we use antibody-directed proximity biotinylation to define the cell surface proteins in close proximity to the AIS cell adhesion molecule Neurofascin. To determine the distributions of the identified proteins, we use CRISPR-mediated genome editing for insertion of epitope tags in the endogenous proteins. We identify Contactin-1 (Cntn1) as an AIS cell surface protein. Cntn1 is enriched at the AIS through interactions with Neurofascin and NrCAM. We further show that Cntn1 contributes to assembly of the AIS extracellular matrix, and regulates AIS axo-axonic innervation by inhibitory basket cells in the cerebellum and inhibitory chandelier cells in the cortex.


Asunto(s)
Segmento Inicial del Axón , Fenómenos Biológicos , Segmento Inicial del Axón/metabolismo , Contactina 1/metabolismo , Biotinilación , Sinapsis/metabolismo , Axones/metabolismo , Proteínas de la Membrana/metabolismo , Anticuerpos/metabolismo
17.
Dig Endosc ; 24(3): 175-81, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22507092

RESUMEN

BACKGROUND AND AIM: The endoscopic retrograde cholangiopancreatography (ERCP) mechanical simulator (EMS) and computer simulator (ECS) are described herein. No direct hands-on comparison has been reported to reflect the perception of trainers and trainees regarding the efficacy of each model for trainee ERCP education. We compared the trainers' and trainees' assessments of the EMS and ECS for trainee education. METHODS: Eighteen gastrointestinal trainees and 16 trainers with varying ERCP experience completed a questionnaire survey before and after practice with each simulator at hands-on ERCP practice workshops. They carried out scope insertion, selective bile duct cannulation, guidewire negotiation of a bile duct stricture, biliary papillotomy and insertion of a single biliary stent using both simulators. Main outcome measurement was respondents' assessments of comparative efficacy of EMS and ECS practice for trainee education. RESULTS: Compared to pre-practice evaluation, both EMS and ECS received higher scores after hands-on practice. Both trainers and trainees showed significantly greater increases in scores for EMS when compared with ECS in facilitating understanding of ERCP procedure, enhancing confidence in carrying out ERCP and the simulator as a credible option for supplementing clinical ERCP training (P < 0.05). Participants also scored EMS significantly higher in realism and usefulness as an instructional tool. CONCLUSIONS: Both computer and mechanical simulators are accepted modalities for ERCP training. The current data (based on a head-to-head comparison of hands-on practice experience) indicate EMS practice is rated higher than ECS practice in supplementing clinical ERCP training. EMS offers the additional advantage of coordinated practice with real equipment and accessories.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica , Competencia Clínica , Simulación por Computador , Gastroenterología/educación , Femenino , Humanos , Masculino , Encuestas y Cuestionarios
18.
Am J Cardiol ; 170: 147-154, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35260240

RESUMEN

Acute type A aortic dissection requires timely diagnosis and intervention. Previous studies have examined risk factors associated with delayed diagnosis; however, the effect of socioeconomic status (SES) has not been previously studied. Our study examined the impact of various SES measures on time to diagnosis. We examined time to diagnosis in consecutive cases of acute type A aortic dissection at a single institution. SES variables included race/ethnicity, Medicaid eligibility, and residence in a zip code with an increased Distressed Communities Index-an aggregate measure of community SES. Delayed diagnosis was defined as time to diagnosis in the upper quartile of the study population (>6.6 hours). A model predicting risk factors for delayed diagnosis was created using multivariable logistic regression. Our study included 124 patients with a median time to diagnosis of 3.36 hours (interquartile range [IQR] 1.83 to 6.63). A total of 92 patients were in the nondelayed cohort (median diagnosis time of 2.59 hours, IQR 1.49 to 4.18) and 32 patients were in the delayed cohort (median diagnosis time of 15.57 hours, IQR 9.34 to 28.75). In multivariable logistic regression, residence in a high-Distressed Communities Index zip code was associated with diagnostic delay (adjusted odds ratio [aOR] 5.108, p = 0.008). Patient age (aOR 0.944, p = 0.011), chest pain at presentation (aOR 0.099, p = 0.004), back pain at presentation (aOR 0.247, p = 0.012), evidence of malperfusion syndrome (aOR 0.040, p <0.001), history of hyperlipidemia (aOR 3.507, p = 0.026), and history of congestive heart failure (aOR 0.061, p = 0.036) were also significantly associated. In conclusion, our findings suggest community-level SES affects time to diagnosis in acute type A aortic dissection.


Asunto(s)
Disección Aórtica , Diagnóstico Tardío , Disección Aórtica/diagnóstico , Disección Aórtica/epidemiología , Humanos , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Clase Social , Factores Socioeconómicos
19.
IEEE Trans Biomed Eng ; 69(10): 3051-3063, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35302937

RESUMEN

OBJECTIVE: The next generation prosthetic hand that moves and feels like a real hand requires a robust neural interconnection between the human minds and machines. METHODS: Here we present a neuroprosthetic system to demonstrate that principle by employing an artificial intelligence (AI) agent to translate the amputee's movement intent through a peripheral nerve interface. The AI agent is designed based on the recurrent neural network (RNN) and could simultaneously decode six degree-of-freedom (DOF) from multichannel nerve data in real-time. The decoder's performance is characterized in motor decoding experiments with three human amputees. RESULTS: First, we show the AI agent enables amputees to intuitively control a prosthetic hand with individual finger and wrist movements up to 97-98% accuracy. Second, we demonstrate the AI agent's real-time performance by measuring the reaction time and information throughput in a hand gesture matching task. Third, we investigate the AI agent's long-term uses and show the decoder's robust predictive performance over a 16-month implant duration. Conclusion & significance: Our study demonstrates the potential of AI-enabled nerve technology, underling the next generation of dexterous and intuitive prosthetic hands.


Asunto(s)
Amputados , Miembros Artificiales , Inteligencia Artificial , Electromiografía , Mano , Humanos , Movimiento/fisiología , Redes Neurales de la Computación
20.
Am J Gastroenterol ; 106(2): 300-6, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20978485

RESUMEN

OBJECTIVES: The impact of endoscopic retrograde cholangiopancreatography (ERCP) mechanical simulator (EMS) practice on trainee clinical performance is unknown. The hypothesis that trainees with EMS practice (study group (SG)) have improved clinical outcomes compared with those without such practice (control group (CG)) is tested. METHODS: This was a randomized controlled trial involving six US academic centers. Sixteen trainees were randomized after ERCP didactic teaching. SG (n=8) participated in two sessions of EMS practice on selective cannulation; CG (n=8) did not undergo EMS practice. All participants' clinical performances were monitored in the subsequent 16 weeks. Intervention effects were assessed in multivariable regression models using generalizing estimating equations (GEE) to account for cluster randomization of trainees. The primary outcome was successful biliary cannulation, and secondary outcomes were cannulation time and competency score. RESULTS: Cannulation success rate was 47.1% for CG and 69.6% for SG. SG had higher odds of successful cannulation (adjusted odds ratio=3.01, P=0.021). SG trainees achieved faster cannulation time (min) (4.7±4.2 vs. 10.3±14.1, P<0.001). Trainee competency scores given by supervising physicians were comparable confirming adequate blinding of the trainers. Limitations included short observation period, small number of ERCPs performed by individual trainees, and variation in the number of ERCPs between trainees. CONCLUSIONS: In a prospective multicenter randomized controlled trial during early training, a significantly higher proportion of the biliary cannulations performed by trainees with EMS practice were successful and with faster cannulation time compared with those performed by trainees without such practice. The results provide objective evidence to support the continued evaluation of EMS practice to augment clinical training.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica/normas , Competencia Clínica , Educación de Postgrado en Medicina/métodos , Gastroenterología/educación , Colangiopancreatografia Retrógrada Endoscópica/instrumentación , Humanos , Distribución de Poisson , Estudios Prospectivos , Análisis de Regresión , Estados Unidos
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