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1.
Med Teach ; 45(10): 1108-1111, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37542360

RESUMO

What was the educational challenge?The complexity and variability of cross-sectional imaging present a significant challenge in imparting knowledge of radiologic anatomy to medical students.What was the solution?Recent advancements in three-dimensional (3D) segmentation and augmented reality (AR) technology provide a promising solution. These advances allow for the creation of interactive, patient-specific 3D/AR models which incorporate multiple imaging modalities including MRI, CT, and 3D rotational angiography can help trainees understand cross-sectional imaging.How was the solution implemented?To create the model, DICOM files of patient scans with slice thicknesses of 1 mm or less are exported to a computer and imported to 3D Slicer for registration. Once registered, the files are segmented with Vitrea software utilizing thresholding, region growing, and edge detection. After the creation of the models, they are then imported to a web-based interactive viewing platform and/or AR application.What lessons were learned that are relevant to a wider global audience?Low-resource 3D/AR models offer an accessible and intuitive tool to teach radiologic anatomy and pathology. Our novel method of creating these models leverages recent advances in 3D/AR technology to create a better experience than traditional high and low-resource 3D/AR modeling techniques. This will allow trainees to better understand cross-sectional imaging.What are the next steps?The interactive and intuitive nature of 3D and AR models has the potential to significantly improve the teaching and presentation of radiologic anatomy and pathology to a medical student audience. We encourage educators to incorporate 3D segmentation models and AR in their teaching strategies.


Assuntos
Realidade Aumentada , Radiologia , Humanos , Software , Radiografia , Radiologia/educação , Aprendizagem , Modelos Anatômicos
2.
FASEB J ; 33(12): 13294-13309, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31530014

RESUMO

Acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury, is associated with reduced lung compliance and hypoxemia. Curcumin exhibits potent anti-inflammatory properties but has poor solubility and rapid plasma clearance. To overcome these physiochemical limitations and uncover the full therapeutic potential of curcumin in lung inflammation, in this study we utilized a novel water-soluble curcumin formulation (CDC) and delivered it directly into the lungs of C57BL/6 mice inoculated with a lethal dose of Klebsiella pneumoniae (KP). Administration of CDC led to a significant reduction in mortality, in bacterial presence within blood and lungs, as well as in lung injury, inflammation, and oxidative stress. The expression of Klebsiella hemolysin gene; TNF-α; IFN-ß; nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3; hypoxia-inducible factor 1/2α; and NF-κB were also decreased following CDC treatment, suggesting modulation of the inflammasome complex and hypoxia signaling pathways as an underlying mechanism by which CDC reduces the severity of pneumonia. On a cellular level, CDC led to diminished cell death, improved viability, and protection of human lung epithelial cells in vitro. Overall, our studies demonstrate that CDC administration improves cell survival and reduces injury, inflammation, and mortality in a murine model of lethal gram-negative pneumonia. CDC, therefore, has promising anti-inflammatory potential in pneumonia and likely other inflammatory lung diseases, demonstrating the importance of optimizing the physicochemical properties of active natural products to optimize their clinical application.-Zhang, B., Swamy, S., Balijepalli, S., Panicker, S., Mooliyil, J., Sherman, M. A., Parkkinen, J., Raghavendran, K., Suresh, M. V. Direct pulmonary delivery of solubilized curcumin reduces severity of lethal pneumonia.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Curcumina/administração & dosagem , Infecções por Klebsiella/tratamento farmacológico , Pulmão/efeitos dos fármacos , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/microbiologia , Lesão Pulmonar Aguda/patologia , Animais , Anti-Inflamatórios/química , Curcumina/química , Feminino , Humanos , Infecções por Klebsiella/metabolismo , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/patologia , Klebsiella pneumoniae/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pneumonia/metabolismo , Pneumonia/microbiologia , Pneumonia/patologia , Pneumonia Bacteriana/metabolismo , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/patologia , Índice de Gravidade de Doença , Transdução de Sinais
3.
Gene Ther ; 25(5): 359-375, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29907877

RESUMO

Previously, we reported that electroporation-mediated (EP) delivery of the FER gene improved survival in a combined trauma-pneumonia model. The mechanism of this protective effect is unknown. In this paper, we performed a pneumonia model in C57/BL6 mice with 500 CFU of Klebsiella pneumoniae. After inoculation, a plasmid encoding human FER was delivered by EP into the lung (PNA/pFER-EP). Survival of FER-treated vs. controls (PNA; PNA/EP-pcDNA) was recorded. In parallel cohorts, bronchial alveolar lavage (BAL) and lung were harvested at 24 and 72 h with markers of infection measured. FER-EP-treated animals reduced bacterial counts and had better 5-day survival compared to controls (80 vs. 20 vs. 25%; p < 0.05). Pre-treatment resulted in 100% survival. With FER, inflammatory monocytes were quickly recruited into BAL. These cells had increased surface expression for Toll-receptor 2 and 4, and increased phagocytic and myeloperoxidase activity at 24 h. Samples from FER electroporated animals had increased phosphorylation of STAT transcription factors, varied gene expression of IL1ß, TNFα, Nrf2, Nlrp3, Cxcl2, HSP90 and increased cytokine production of TNF-α, CCL-2, KC, IFN-γ, and IL-1RA. In a follow-up experiment, using Methicillin-resistant Staphylococcus aureus (MRSA) similar bacterial reduction effects were obtained with FER gene delivery. We conclude that FER overexpression improves survival through STAT activation enhancing innate immunity and accelerating bacterial clearance in the lung. This constitutes a novel mechanism of inflammatory regulation with therapeutic potential in the setting of hospital-acquired pneumonia.


Assuntos
Eletroporação/métodos , Pneumonia Bacteriana/terapia , Proteínas Tirosina Quinases/genética , Animais , Carga Bacteriana , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Terapia Genética/métodos , Humanos , Imunidade Inata/genética , Klebsiella pneumoniae/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia Bacteriana/imunologia , Pneumonia Bacteriana/microbiologia , Proteínas Tirosina Quinases/administração & dosagem , Proteínas Tirosina Quinases/biossíntese , Proteínas Tirosina Quinases/imunologia , Fator de Necrose Tumoral alfa/metabolismo
4.
Neuroimaging Clin N Am ; 34(2): 175-189, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38604703

RESUMO

Computed tomography (CT), CT angiography (CTA), and CT perfusion (CTP) play crucial roles in the comprehensive evaluation and management of acute ischemic stroke, aneurysmal subarachnoid hemorrhage (SAH), and vasospasm. CTP provides functional data about cerebral blood flow, allowing radiologists, neurointerventionalists, and stroke neurologists to more accurately delineate the volume of core infarct and ischemic penumbra allowing for patient-specific treatment decisions to be made. CTA and CTP are used in tandem to evaluate for vasospasm associated with aneurysmal SAH and can help provide an insight into the physiologic impact of angiographic vasospasm, better triaging patients for medical and interventional treatment.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Humanos , Angiografia por Tomografia Computadorizada/métodos , Angiografia Cerebral/métodos , Tomografia Computadorizada por Raios X/métodos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico por imagem , Perfusão , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Vasoespasmo Intracraniano/etiologia , Vasoespasmo Intracraniano/complicações
5.
Shock ; 52(6): 612-621, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30601332

RESUMO

Acid aspiration-induced lung injury is a common disease in the intensive care unit (ICU) and acute respiratory distress syndrome (ARDS). Hypoxia-inducible factor (HIF)-1α is a major transcription factor responsible for regulating the cellular response to changes in oxygen tension. A clear understanding of the function of HIF-1α in lung inflammatory response is currently lacking. Here, we sought to determine the role of HIF-1α in type 2 alveolar epithelial cells (AEC) in the generation of the acute inflammatory response following gastric aspiration (GA). GA led to profound hypoxia at very early time points following GA. This correlated to a robust increase in HIF-1α, tissue albumin and pro-inflammatory mediators following GA in AECs. The extent of lung injury and the release of pro/anti-inflammatory cytokines were significantly reduced in HIF-1α (-/-) mice. Finally, we report that HIF-1α upregulation of the acute inflammatory response is dependent on NF-κB following GA.


Assuntos
Células Epiteliais Alveolares/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Pneumonia Aspirativa/metabolismo , Células Epiteliais Alveolares/patologia , Animais , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Inflamação/genética , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Knockout , Pneumonia Aspirativa/genética , Pneumonia Aspirativa/patologia
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