Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
Más filtros

Tipo del documento
Intervalo de año de publicación
1.
Artículo en Inglés | MEDLINE | ID: mdl-38884530

RESUMEN

PURPOSE: Mohs micrographic surgery with immunohistochemistry allows for same-day comprehensive margin assessment of melanoma in situ prior to subspecialty reconstruction. This study describes the oncologic and reconstructive outcomes of eyelid and periorbital melanoma in situ and identifies risk factors for complex reconstructive demands. METHODS: Retrospective case series of all patients treated with Mohs micrographic surgery with immunohistochemistry for melanoma in situ affecting the eyelids or periorbital region from 2008 to 2018 at a single institution. Tumors were assigned to the eyelid group if the clinically visible tumor involved the skin inside the orbital rim. Reconstructive variables were compared between the eyelid and periorbital cohorts. RESULTS: There were 24 eyelid and 141 periorbital tumors included. The initial surgical margin for all tumors was 5.34 ± 1.54 mm and multiple Mohs stages were required in 24.2% of cases. Eyelid tumors included more recurrences (p = 0.003), and the average defect size was larger (14.0 ± 13.3 cm2 vs. 7.7 ± 5.4 cm2, p = 0.03). Risk factors for complex reconstruction included: initial tumor diameter >2 cm (odds ratio [OR]: 3.84, 95% confidence interval [CI]: 1.95-7.57) and eyelid involved by initial tumor (OR: 4.88, 95% CI: 1.94-12.28). At an average follow-up of 4.8 years, there were no melanoma-related deaths and 1 local recurrence (0.6% recurrence rate). CONCLUSIONS: Mohs micrographic surgery with immunohistochemistry achieves excellent local control rates for periocular melanoma in situ. An initial surgical margin of 5 mm is frequently insufficient to achieve clear margins. The resulting defects are large, and the complexity of reconstruction can be predicted by tumor size and clinical involvement of eyelid skin.

2.
Ophthalmic Plast Reconstr Surg ; 39(4): e115-e117, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36893059

RESUMEN

A 66-year-old immunocompromised man presented with cellulitis around the left eye that was initially concerning for necrotizing fasciitis. Exam findings were remarkable for exquisite periocular tenderness with rigid, immobile eyelids resulting from severe erythema, edema, and induration. Given the concern for orbital compartment syndrome and a necrotizing infection, the patient was taken urgently to the operating room for debridement of the eyelid skin as well as an urgent lateral canthotomy and cantholysis. His eye exam revealed 360° of hemorrhagic chemosis, no relative afferent pupillary defect, and an ipsilateral elevated intraocular pressure of 35 mm Hg. No visual acuity measurement could be obtained secondary to the patient's altered mental status. His intraocular pressure normalized after treatment with antihypertensive drops and further extension of the canthotomy. Histopathological analysis showed extensive neutrophilic infiltrate of the dermis which was compatible with a diagnosis of Sweet's syndrome.


Asunto(s)
Presión Intraocular , Síndrome de Sweet , Masculino , Humanos , Anciano , Síndrome de Sweet/diagnóstico , Síndrome de Sweet/complicaciones , Síndrome de Sweet/patología , Órbita/patología , Celulitis (Flemón)/complicaciones , Párpados/patología
3.
BMC Cancer ; 21(1): 320, 2021 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-33765961

RESUMEN

BACKGROUND: Recent studies have suggested the important roles of CD47 and tumor-associated macrophages in the prognosis and immunotherapy of various human malignancies. However, the clinical significance of CD47 expression and CD163+ TAMs in pancreatic neuroendocrine tumor (PanNET) remains unclear. METHODS: In this study, 47 well-differentiated PanNET resection specimens were collected. CD47 expression and CD163+ macrophages were evaluated using immunohistochemistry and correlated with clinicopathologic properties. RESULTS: Positive CD47 staining was seen in all PanNETs as well as adjacent normal islets. Compared to normal islets, CD47 overexpressed in PanNETs (p = 0.0015). In the cohort, lymph node metastasis (LNM), lymphovascular invasion (LVI), and perineural invasion (PNI) were found in 36.2, 59.6, and 48.9% of the cases, respectively. Interestingly, PanNETs with LNM, LVI, or PNI had significantly lower H-score of CD47 than those without LNM (p = 0.035), LVI (p = 0.0005), or PNI (p = 0.0035). PanNETs in patients with disease progression (recurrence/death) also showed a significantly lower expression of CD47 than those without progression (p = 0.022). In contrast, CD163+ macrophage counts were significantly higher in cases with LNM, LVI, and PNI. CONCLUSIONS: Our data suggest relative low CD47 expression and high CD163+ TAMs may act as indicators for poor prognosis of PanNETs.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Antígeno CD47/metabolismo , Recurrencia Local de Neoplasia/epidemiología , Tumores Neuroendocrinos/cirugía , Neoplasias Pancreáticas/cirugía , Macrófagos Asociados a Tumores/inmunología , Anciano , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Biomarcadores de Tumor/análisis , Antígeno CD47/análisis , Recuento de Células , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Metástasis Linfática/inmunología , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/inmunología , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Tumores Neuroendocrinos/inmunología , Tumores Neuroendocrinos/mortalidad , Tumores Neuroendocrinos/patología , Páncreas/citología , Páncreas/patología , Pancreatectomía , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Pronóstico , Receptores de Superficie Celular/metabolismo , Medición de Riesgo/métodos , Análisis de Supervivencia , Macrófagos Asociados a Tumores/metabolismo
4.
Ophthalmic Plast Reconstr Surg ; 36(5): e124-e126, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32134768

RESUMEN

Orbital actinomyces is a rare diagnosis with only a few cases reported in the literature. It can be difficult to diagnose due to its slow, indolent course, and nonspecific findings on imaging and clinical examination, and frequently it can masquerade as other pathologies such as neoplasm and inflammatory disease. The authors present a case of actinomyces masquerading as meningioma with findings of hyperostosis and a superior orbital roof interosseous tract on imaging.


Asunto(s)
Hiperostosis , Neoplasias Meníngeas , Meningioma , Actinomyces , Humanos , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Órbita
5.
Ann Plast Surg ; 82(5S Suppl 4): S320-S324, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30973838

RESUMEN

INTRODUCTION: Enhanced recovery after surgery pathways designed to optimize postoperative care have become increasingly popular across multiple surgical specialties with proven benefits. In this retrospective cohort study, we present a comparative evaluation of the impact of protocol-based postoperative care on free autologous breast reconstruction patients. METHODS: With institutional review board approval, we performed a chart review of patients who underwent breast reconstruction with free autologous tissue transfer by a single surgeon from 2006 to 2017. Patients were managed according to a postoperative protocol since 2006 that initially called for discharge home on postoperative day (POD) 4 for unilateral cases and POD 5 for bilateral cases. In May 2015, the protocol was revised to discharge home on POD 3 for all cases. Patients who underwent reconstruction before (2006 to April 2015) and after (May 2015 to 2017) the change in postoperative protocol were compared. RESULTS: A total of 432 patients (647 breasts) underwent free autologous breast reconstruction during the study period. Flaps were predominantly muscle-sparing transverse rectus abdominis myocutaneous (56.3%) or deep inferior epigastric perforator (30.3%) flaps. Average patient age was 51.6 years (range, 29.7-80.3 years). Unilateral reconstructions were performed for 167 patients before and 50 patients after the protocol change; average hospital length of stay (LOS) was 4.5 and 3.4 days, respectively (P < 0.001). Bilateral reconstructions were performed for 153 patients before and 62 patients after the protocol change; average hospital LOS was 5.1 and 3.5 days, respectively (P < 0.001). There was no significant increase in patients with major or minor complications. CONCLUSIONS: Revising our postoperative protocol to reduce expected LOS was associated with an overall faster time to discharge without negative consequences in patients who underwent unilateral and bilateral free autologous breast reconstruction. Use of protocols to guide behavior not only can improve the patient experience by promoting a quicker return home, but may also have the added benefit of decreasing healthcare expenditures through reduced inpatient utilization.


Asunto(s)
Protocolos Clínicos , Colgajos Tisulares Libres , Tiempo de Internación/estadística & datos numéricos , Mamoplastia/métodos , Cuidados Posoperatorios/métodos , Adulto , Anciano , Anciano de 80 o más Años , Autoinjertos , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos
6.
J Magn Reson Imaging ; 43(1): 11-27, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25857715

RESUMEN

Arterial spin labeling (ASL) is a completely noninvasive magnetic resonance imaging (MRI) perfusion method for quantitatively measuring cerebral blood flow utilizing magnetically labeled arterial water. Advances in the technique have enabled the major MRI vendors to make the sequence available to the clinical neuroimaging community. Consequently, ASL is being increasingly incorporated into the routine neuroimaging protocol. Although a variety of ASL techniques are available, the ISMRM Perfusion Study Group and the European ASL in Dementia Consortium have released consensus guidelines recommending standardized implementation of 3D pseudocontinuous ASL with background suppression. The purpose of this review, aimed at the large number of neuroimaging clinicians who have either no or limited experience with this 3D pseudocontinuous ASL, is to discuss the common and clinically significant artifacts that may be encountered with this technique. While some of these artifacts hinder accurate interpretation of studies, either by degrading the images or mimicking pathology, there are other artifacts that are of clinical utility, because they increase the conspicuity of pathology. Cognizance of these artifacts will help the physician interpreting ASL to avoid potential diagnostic pitfalls, and increase their level of comfort with the technique.


Asunto(s)
Artefactos , Circulación Cerebrovascular , Trastornos Cerebrovasculares/diagnóstico , Trastornos Cerebrovasculares/fisiopatología , Imagenología Tridimensional/métodos , Angiografía por Resonancia Magnética/métodos , Velocidad del Flujo Sanguíneo , Errores Diagnósticos/prevención & control , Pruebas Diagnósticas de Rutina/métodos , Humanos , Posicionamiento del Paciente/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Marcadores de Spin
7.
J Biol Chem ; 289(45): 31423-32, 2014 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-25193667

RESUMEN

Glycosylphosphatidylinositol-anchored neurotoxin-like receptor binding proteins, such as lynx modulators, are topologically positioned to exert pharmacological effects by binding to the extracellular portion of nAChRs. These actions are generally thought to proceed when both lynx and the nAChRs are on the plasma membrane. Here, we demonstrate that lynx1 also exerts effects on α4ß2 nAChRs within the endoplasmic reticulum. Lynx1 affects assembly of nascent α4 and ß2 subunits and alters the stoichiometry of the receptor population that reaches the plasma membrane. Additionally, these data suggest that lynx1 shifts nAChR stoichiometry to low sensitivity (α4)3(ß2)2 pentamers primarily through this interaction in the endoplasmic reticulum, rather than solely via direct modulation of activity on the plasma membrane. To our knowledge, these data represent the first test of the hypothesis that a lynx family member, or indeed any glycosylphosphatidylinositol-anchored protein, could act within the cell to alter assembly of a multisubunit protein.


Asunto(s)
Retículo Endoplásmico/metabolismo , Glicoproteínas de Membrana/fisiología , Neuropéptidos/fisiología , Receptores Nicotínicos/química , Acetilcolina/química , Proteínas Adaptadoras Transductoras de Señales , Animales , Línea Celular Tumoral , Membrana Celular/metabolismo , Cisteína/química , Transferencia Resonante de Energía de Fluorescencia , Proteínas Fluorescentes Verdes/química , Células HEK293 , Humanos , Ratones , Microscopía Confocal , Plásmidos/metabolismo , Unión Proteica , Multimerización de Proteína , Estructura Terciaria de Proteína
8.
J Refract Surg ; 31(5): 322-7, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25974971

RESUMEN

PURPOSE: To compare the astigmatic outcomes of LASIK with a single excimer laser platform using either wavefront-guided (WFG) or wavefront-optimized (WFO) modes. METHODS: Sixty-eight eyes of 34 patients underwent LASIK for myopia with the Wavelight Allegretto Eye-Q 400-Hz laser platform (Alcon Laboratories, Inc., Hüenberg, Switzerland). One eye underwent WFG-LASIK and the contralateral eye underwent WFO-LASIK. Alpins vector analysis of astigmatism was performed using manifest refraction measured preoperatively and 12 months postoperatively and vertexed to the corneal plane. Eyes were stratified for subgroup analysis based on preoperative manifest astigmatism. RESULTS: WFG-LASIK and WFO-LASIK were similar with regard to surgically induced astigmatism, difference vector, magnitude of error, correction index, flattening index, and index of success. The angle of error was 80% less in the WFG group compared to the WFO group (1.92° ± 0.67º vs 9.66° ± 3.7º, P = .04). CONCLUSIONS: WFG-LASIK and WFO-LASIK using the Alcon WaveLight Allegretto Eye-Q 400-Hz excimer laser platform produce similar astigmatic results in myopic patients; however, the WFG mode may produce slightly more predictable astigmatic corrections.


Asunto(s)
Astigmatismo/fisiopatología , Córnea/fisiopatología , Queratomileusis por Láser In Situ/métodos , Láseres de Excímeros/uso terapéutico , Miopía/cirugía , Adulto , Sensibilidad de Contraste/fisiología , Femenino , Humanos , Masculino , Miopía/fisiopatología , Estudios Prospectivos , Refracción Ocular/fisiología , Resultado del Tratamiento , Agudeza Visual/fisiología
9.
Sci Adv ; 10(15): eadi5794, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38598626

RESUMEN

Histological hematoxylin and eosin-stained (H&E) tissue sections are used as the gold standard for pathologic detection of cancer, tumor margin detection, and disease diagnosis. Producing H&E sections, however, is invasive and time-consuming. While deep learning has shown promise in virtual staining of unstained tissue slides, true virtual biopsy requires staining of images taken from intact tissue. In this work, we developed a micron-accuracy coregistration method [micro-registered optical coherence tomography (OCT)] that can take a two-dimensional (2D) H&E slide and find the exact corresponding section in a 3D OCT image taken from the original fresh tissue. We trained a conditional generative adversarial network using the paired dataset and showed high-fidelity conversion of noninvasive OCT images to virtually stained H&E slices in both 2D and 3D. Applying these trained neural networks to in vivo OCT images should enable physicians to readily incorporate OCT imaging into their clinical practice, reducing the number of unnecessary biopsy procedures.


Asunto(s)
Redes Neurales de la Computación , Tomografía de Coherencia Óptica , Humanos , Tomografía de Coherencia Óptica/métodos , Biopsia , Imagenología Tridimensional
10.
Mol Pharm ; 10(5): 1557-65, 2013 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-23249146

RESUMEN

Amyloid-ß (Aß) deposition in the brain vasculature results in cerebral amyloid angiopathy (CAA), which occurs in about 80% of Alzheimer's disease (AD) patients. While Aß42 predominates parenchymal amyloid plaques in AD brain, Aß40 is prevalent in the cerebrovascular amyloid. Dutch mutation of Aß40 (E22Q) promotes aggressive cerebrovascular accumulation and leads to severe CAA in the mutation carriers; knowledge of how DutchAß40 drives this process more efficiently than Aß40 could reveal various pathophysiological events that promote CAA. In this study we have demonstrated that DutchAß40 shows preferential accumulation in the blood-brain-barrier (BBB) endothelial cells due to its inefficient blood-to-brain transcytosis. Consequently, DutchAß40 establishes a permeation barrier in the BBB endothelium, prevents its own clearance from the brain, and promotes the formation of amyloid deposits in the cerebral microvessels. The BBB endothelial accumulation of native Aß40 is not robust enough to exercise such a significant impact on its brain clearance. Hence, the cerebrovascular accumulation of Aß40 is slow and may require other copathologies to precipitate into CAA. In conclusion, the magnitude of Aß accumulation in the BBB endothelial cells is a critical factor that promotes CAA; hence, clearing vascular endothelium of Aß proteins may halt or even reverse CAA.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Barrera Hematoencefálica/metabolismo , Péptidos beta-Amiloides/sangre , Péptidos beta-Amiloides/genética , Animales , Bovinos , Células Cultivadas , Angiopatía Amiloide Cerebral Familiar/genética , Angiopatía Amiloide Cerebral Familiar/metabolismo , Células Endoteliales/metabolismo , Humanos , Modelos Neurológicos , Proteínas Mutantes/sangre , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Transporte de Proteínas , Transcitosis
11.
Adv Mater Technol ; 8(1)2023 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-37007916

RESUMEN

Studies of electrosensory systems have led to insights into to a number of general issues in biology. However, investigations of these systems have been limited by the inability to precisely control spatial patterns of electrosensory input. In this paper, an electrode array and a system to selectively stimulate spatially restricted regions of an electroreceptor array is presented. The array has 96 channels consisting of chrome/gold electrodes patterned on a flexible parylene-C substrate and encapsulated with another parylene-C layer. The conformability of the electrode array allows for optimal current driving and surface interface conditions. Recordings of neural activity at the first central processing stage in weakly electric mormyrid fish support the potential of this system for high spatial resolution stimulation and mapping of electrosensory systems.

12.
J Am Coll Nutr ; 31(5): 301-10, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23529987

RESUMEN

OBJECTIVES: Limited information is available on the nutritional status and the impact of supplements on nutrient adequacy in college students. This study aimed to assess nutritional status and evaluate the contribution of supplement use to overall nutrient adequacy in a sample of healthy college students. METHODS: Sixty subjects (40 women and 20 men) were randomly recruited from those attending the University of Connecticut. Food records were collected over 30 consecutive days for each subject. In addition, health and lifestyle information was collected at the beginning and end of the study period. RESULTS: After excluding misreporting, only 44 subjects were eligible for assessing nutritional status. More than 40% of female students had intakes below the estimated average requirements for vitamins D and E, calcium, and magnesium. Supplement users had significantly higher average intakes than nonusers from dietary sources for protein, folate, niacin, vitamin E, magnesium, and zinc (p < 0.05). With the addition of supplements, supplement users consumed significantly more for all nutrient intakes except vitamin A than nonusers (p < 0.05). Nutritional adequacy of supplement users was significantly higher for vitamins D and E and magnesium compared with nonusers (p < 0.05). CONCLUSIONS: Overall, men and women were consuming intakes below adequacy for most nutrients, and supplement usage increased nutrient intake and adequacy levels in this young adult population.


Asunto(s)
Suplementos Dietéticos , Estado Nutricional , Adolescente , Adulto , Calcio de la Dieta/administración & dosificación , Dieta , Registros de Dieta , Encuestas sobre Dietas , Femenino , Ácido Fólico/administración & dosificación , Humanos , Estilo de Vida , Magnesio/administración & dosificación , Masculino , Niacina/administración & dosificación , Necesidades Nutricionales , Estudiantes , Vitamina A/administración & dosificación , Vitamina D/administración & dosificación , Vitamina E/administración & dosificación , Adulto Joven , Zinc/administración & dosificación
13.
Indian J Ophthalmol ; 70(7): 2335-2345, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35791115

RESUMEN

Thyroid eye disease (TED) is a rare disease that can lead to decreased quality of life, permanent disfigurement, and vision loss. Clinically, TED presents with exophthalmos, periorbital edema, extraocular muscle dysfunction, and eyelid retraction, and can lead to vision-threatening complications such as exposure to keratopathy and dysthyroid optic neuropathy (DON). Over the last several years, significant advancements have been made in the understanding of its pathophysiology as well as optimal management. Ethnic variations in the prevalence, clinical presentation, and risk of vision-threatening complications of TED are summarized, and risk factors associated with TED are discussed. Additionally, significant advances have been made in the management of TED. The management of TED traditionally included anti-inflammatory medications, orbital radiation therapy, orbital surgical decompression, and biologic therapies. Most recently, targeted therapies such as teprotumumab, an insulin-like growth factor-1 receptor antagonist, have been studied in the context of TED, with promising initial data. In this review, updates in the understanding and management of TED are presented with a focus on the international variations in presentation and management.


Asunto(s)
Oftalmopatía de Graves , Descompresión Quirúrgica , Oftalmopatía de Graves/diagnóstico , Oftalmopatía de Graves/epidemiología , Oftalmopatía de Graves/terapia , Humanos , Músculos Oculomotores/cirugía , Prevalencia , Calidad de Vida , Trastornos de la Visión/etiología
14.
Sci Rep ; 12(1): 13130, 2022 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-35907928

RESUMEN

Optical coherence tomography (OCT) allows label-free, micron-scale 3D imaging of biological tissues' fine structures with significant depth and large field-of-view. Here we introduce a novel OCT-based neuroimaging setting, accompanied by a feature segmentation algorithm, which enables rapid, accurate, and high-resolution in vivo imaging of 700 µm depth across the mouse cortex. Using a commercial OCT device, we demonstrate 3D reconstruction of microarchitectural elements through a cortical column. Our system is sensitive to structural and cellular changes at micron-scale resolution in vivo, such as those from injury or disease. Therefore, it can serve as a tool to visualize and quantify spatiotemporal brain elasticity patterns. This highly transformative and versatile platform allows accurate investigation of brain cellular architectural changes by quantifying features such as brain cell bodies' density, volume, and average distance to the nearest cell. Hence, it may assist in longitudinal studies of microstructural tissue alteration in aging, injury, or disease in a living rodent brain.


Asunto(s)
Imagenología Tridimensional , Tomografía de Coherencia Óptica , Algoritmos , Animales , Imagenología Tridimensional/métodos , Ratones , Redes Neurales de la Computación , Neuroimagen/métodos , Tomografía de Coherencia Óptica/métodos
15.
Am J Ophthalmol Case Rep ; 24: 101202, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34585021

RESUMEN

PURPOSE: To report a case series of subjective and objective hearing function changes associated with teprotumumab treatment for thyroid eye disease. OBSERVATIONS: A 74-year-old female with a history of Graves' disease with thyroid eye disease was treated with teprotumumab. She had a history of bilateral tinnitus and noticed a subjective improvement in her tinnitus after the second infusion. Audiology testing obtained before, during, and after completion of infusions showed symmetric and rapidly progressive worsening of the patient's sensorineural hearing loss. In contrast, a 42-year-old male with a history of Grave's disease endorsed worsening intermittent tinnitus and low-pitched hearing loss after initiation of teprotumumab. Audiology testing before, during, and after completion of infusions showed stable and normal hearing function bilaterally. CONCLUSION AND IMPORTANCE: This case series highlights the importance of objective testing in patients prior to and after teprotumumab initiation as subjective hearing changes may not accurately reflect objective hearing function. In addition, this report suggests that teprotumumab may play a role in potentiating sensorineural hearing loss.

16.
PLoS One ; 15(12): e0242884, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33315889

RESUMEN

Loss of retinal ganglion cells (RGCs) in optic neuropathies results in permanent partial or complete blindness. Myocyte enhancer factor 2 (MEF2) transcription factors have been shown to play a pivotal role in neuronal systems, and in particular MEF2A knockout was shown to enhance RGC survival after optic nerve crush injury. Here we expanded these prior data to study bi-allelic, tri-allelic and heterozygous allele deletion. We observed that deletion of all MEF2A, MEF2C, and MEF2D alleles had no effect on RGC survival during development. Our extended experiments suggest that the majority of the neuroprotective effect was conferred by complete deletion of MEF2A but that MEF2D knockout, although not sufficient to increase RGC survival on its own, increased the positive effect of MEF2A knockout. Conversely, MEF2A over-expression in wildtype mice worsened RGC survival after optic nerve crush. Interestingly, MEF2 transcription factors are regulated by post-translational modification, including by calcineurin-catalyzed dephosphorylation of MEF2A Ser-408 known to increase MEF2A-dependent transactivation in neurons. However, neither phospho-mimetic nor phospho-ablative mutation of MEF2A Ser-408 affected the ability of MEF2A to promote RGC death in vivo after optic nerve injury. Together these findings demonstrate that MEF2 gene expression opposes RGC survival following axon injury in a complex hierarchy, and further support the hypothesis that loss of or interference with MEF2A expression might be beneficial for RGC neuroprotection in diseases such as glaucoma and other optic neuropathies.


Asunto(s)
Factores de Transcripción MEF2/metabolismo , Traumatismos del Nervio Óptico/metabolismo , Traumatismos del Nervio Óptico/patología , Células Ganglionares de la Retina/patología , Alelos , Animales , Recuento de Células , Humanos , Factores de Transcripción MEF2/deficiencia , Factores de Transcripción MEF2/genética , Ratones , Traumatismos del Nervio Óptico/genética , Mutación Puntual , Transducción de Señal
17.
Invest Ophthalmol Vis Sci ; 59(1): 590-596, 2018 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-29372258

RESUMEN

Purpose: To develop an automated method of localizing and discerning multiple types of findings in retinal images using a limited set of training data without hard-coded feature extraction as a step toward generalizing these methods to rare disease detection in which a limited number of training data are available. Methods: Two ophthalmologists verified 243 retinal images, labeling important subsections of the image to generate 1324 image patches containing either hemorrhages, microaneurysms, exudates, retinal neovascularization, or normal-appearing structures from the Kaggle dataset. These image patches were used to train one standard convolutional neural network to predict the presence of these five classes. A sliding window method was used to generate probability maps across the entire image. Results: The method was validated on the eOphta dataset of 148 whole retinal images for microaneurysms and 47 for exudates. A pixel-wise classification of the area under the curve of the receiver operating characteristic of 0.94 and 0.95, as well as a lesion-wise area under the precision recall curve of 0.86 and 0.64, was achieved for microaneurysms and exudates, respectively. Conclusions: Regionally trained convolutional neural networks can generate lesion-specific probability maps able to detect and distinguish between subtle pathologic lesions with only a few hundred training examples per lesion.


Asunto(s)
Interpretación de Imagen Asistida por Computador , Redes Neurales de la Computación , Enfermedades de la Retina/diagnóstico por imagen , Algoritmos , Exudados y Transudados , Humanos , Aprendizaje Automático , Probabilidad , Curva ROC , Reproducibilidad de los Resultados
18.
Vínculo ; 20(1): 47-55, 20230000.
Artículo en Portugués | LILACS | ID: biblio-1513044

RESUMEN

experiência do Projeto Ponte no atendimento de grupos terapêuticos online mostra a potência deste dispositivo no atendimento aos migrantes; nosso projeto defronte à pandemia teve de se adaptar a novos parâmetros no atendimento virtual. Participamos de uma rede de serviços específica ao público migrante, essencial na pandemia de COVID-19, para o apoio e continuidade do trabalho. As referências do projeto são: o conceito de interculturalidade, o atendimento grupal no formato slow open, a língua portuguesa e a psicanálise de grupos e vínculos. Nos atendimentos clínicos com migrantes, consideramos os processos de ruptura da migração, a dupla pertença aos países de origem e destino, bem como a dificuldade de se instalar no país de destino, a estranheza da experiência e o lugar de estrangeiro que o migrante ocupa. Por isso adotamos o dispositivo grupal, onde o migrante encontra um lugar para a construção e elaboração da migração, bem como para estabelecer uma possível pertença.


The experience of Ponte Project in attending therapeutic groups online shows the power that this device provokes in attending migrants; this work with the arrival of the COVID-19 pandemic had to adapt to the new parameters of virtual therapy. We also participate in a network in the psychological consultation of the migrant public, essential for the continuity of the project's work. The theoretical framework of the project has always been based on: the concept of interculturality, a slow-open group, Portuguese language and Psychoanalysis with groups and bonds. In clinical sessions with the migrants we will consider the processes of rupture caused by migration, the double belonging, as well as the difficulty of settling in the country of destination, all the strangeness caused by this experience and also the place of foreigner that the migrant occupies. That is why we chose to work with groups, where the migrant finds a place to elaborate the effects of migration, in addition to establishing a possible place of belonging.


La experiencia del Proyecto Puente en la atención terapéutica grupal en línea muestra la potencia de este dispositivo en la atención a migrantes. Nuestro proyecto, frente a la pandemia, tuvo que adaptarse a los nuevos parámetros para la atención virtual. Participamos en una red de servicios específicos para el público migrante, esencial en la pandemia del COVID-19, para brindar apoyo y continuidad al trabajo. Las referencias del proyecto son: el concepto de interculturalidad, la atención grupal en el formato slow open, la lengua portuguesa, el psicoanálisis de grupo y los vínculos. En las sesiones clínicas con migrantes consideramos los procesos de ruptura de la migración, la doble pertenencia a los países de origen y destino, la dificultad de integración en el país de destino, la extrañeza de la experiencia y el lugar de extranjero que ocupa el migrante. Por eso adoptamos el dispositivo grupal, donde el migrante encuentra un lugar para la construcción y elaboración de la experiencia migratoria, permitiéndole así establecer una posible pertenencia.


Asunto(s)
Humanos , Psicoterapia de Grupo , Migrantes , Sistemas en Línea , COVID-19
19.
PLoS One ; 13(1): e0191005, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29364897

RESUMEN

Idiopathic Parkinson's Disease (PD) is characterized by degeneration of dopaminergic and other neurons, leading to motor and non-motor deficits. Abnormal eye movements in PD, including fixations, saccades, and convergence, are well described. However, saccadic reading, which requires serial and alternating saccades and fixations, is not well studied, despite its obvious impact on the quality of life. In this study, we assessed saccadic reading using variations of the King-Devick (KD) test, a rapid single digit number naming test, as a way to assess the ability to make serial left-to-right ocular motor movements necessary for reading. We recruited 42 treated PD patients and 80 age-matched controls and compared their reading times with a variety of measures, including age, duration of disease, Unified Parkinson's Disease Rating Scale (UPDRS), the National Eye Institute 25-Item Visual Functioning Questionnaire 25 (VFQ-25), and Montreal Cognitive assessment (MoCA) test. The subjects performed 4 trials of reading 120 single digit numbers aloud as fast as possible without making errors. In each trial, they read 3 pages (KD1, KD2, and KD3), and each page contained 40 numbers per page in 8 lines with 5 numbers/line. We found that PD patients read about 20% slower than controls on all tests (KD1, 2, and 3 tests) (p < 0.02), and both groups read irregularly spaced numbers slower than regularly spaced numbers. Having lines between numbers to guide reading (KD1 tests) did not impact reading time in both PD and controls, but increased visual crowding as a result of decreased spacing between numbers (KD3 tests) was associated with significantly slower reading times in both PD and control groups. Our study revealed that saccadic reading is slower in PD, but controls and PD patients are both impacted by visuospatial planning challenges posed by increased visual crowding and irregularity of number spacing. Reading time did not correlate with UPDRS or MoCA scores in PD patients but significantly correlated with age, duration of disease, and VFQ-25 scores. The presence of convergence insufficiency did not significantly correlate with reading time in PD patients, although on average there was slower reading time in those with convergence insufficiency by 8 s (p = 0.2613). We propose that a simple reading task using 120 single-digit numbers can be used as a screening tool in the clinical setting to assess functional ocular motor difficulties in Parkinson's disease that can have a profound impact on quality of life.


Asunto(s)
Enfermedad de Parkinson/fisiopatología , Lectura , Movimientos Sacádicos , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA