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1.
Proc Natl Acad Sci U S A ; 120(46): e2302089120, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37931105

RESUMEN

Ongoing cell therapy trials have demonstrated the need for precision control of donor cell behavior within the recipient tissue. We present a methodology to guide stem cell-derived and endogenously regenerated neurons by engineering the microenvironment. Being an "approachable part of the brain," the eye provides a unique opportunity to study neuron fate and function within the central nervous system. Here, we focused on retinal ganglion cells (RGCs)-the neurons in the retina are irreversibly lost in glaucoma and other optic neuropathies but can potentially be replaced through transplantation or reprogramming. One of the significant barriers to successful RGC integration into the existing mature retinal circuitry is cell migration toward their natural position in the retina. Our in silico analysis of the single-cell transcriptome of the developing human retina identified six receptor-ligand candidates, which were tested in functional in vitro assays for their ability to guide human stem cell-derived RGCs. We used our lead molecule, SDF1, to engineer an artificial gradient in the retina, which led to a 2.7-fold increase in donor RGC migration into the ganglion cell layer (GCL) and a 3.3-fold increase in the displacement of newborn RGCs out of the inner nuclear layer. Only donor RGCs that migrated into the GCL were found to express mature RGC markers, indicating the importance of proper structure integration. Together, these results describe an "in silico-in vitro-in vivo" framework for identifying, selecting, and applying soluble ligands to control donor cell function after transplantation.


Asunto(s)
Retina , Células Ganglionares de la Retina , Recién Nacido , Humanos , Células Madre , Neurogénesis , Movimiento Celular
2.
Nucleic Acids Res ; 47(D1): D828-D834, 2019 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-30329093

RESUMEN

The REDfly database provides a comprehensive curation of experimentally-validated Drosophila transcriptional cis-regulatory elements and includes information on DNA sequence, experimental evidence, patterns of regulated gene expression, and more. Now in its thirteenth year, REDfly has grown to over 23 000 records of tested reporter gene constructs and 2200 tested transcription factor binding sites. Recent developments include the start of curation of predicted cis-regulatory modules in addition to experimentally-verified ones, improved search and filtering, and increased interaction with the authors of curated papers. An expanded data model that will capture information on temporal aspects of gene regulation, regulation in response to environmental and other non-developmental cues, sexually dimorphic gene regulation, and non-endogenous (ectopic) aspects of reporter gene expression is under development and expected to be in place within the coming year. REDfly is freely accessible at http://redfly.ccr.buffalo.edu, and news about database updates and new features can be followed on Twitter at @REDfly_database.


Asunto(s)
Bases de Datos Genéticas , Drosophila melanogaster/genética , Genoma de los Insectos/genética , Elementos Reguladores de la Transcripción/genética , Animales , Sitios de Unión/genética , Regulación de la Expresión Génica/genética , Programas Informáticos , Interfaz Usuario-Computador
3.
Cureus ; 15(5): e38614, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37288216

RESUMEN

Background Vancouver B2 periprosthetic femur fractures have traditionally been treated with revision arthroplasty. However, there is increasing evidence that open reduction and internal fixation (ORIF) may be a valid alternative treatment strategy. The purpose of this study was to compare the outcomes of ORIF versus revision arthroplasty for the treatment of Vancouver B2 fractures and evaluate the influence of the treating surgeon's fellowship training on treatment selection. Methodology This was a retrospective cohort study of 31 patients treated for Vancouver B2 periprosthetic fractures (16 ORIF and 15 revision arthroplasty) at a single academic Level 1 trauma center. Outcome measures included one-year mortality, revision, reoperation, infection, and blood loss. Results There were no statistically significant differences in revision, reoperation, or infection at an average follow-up of 65 weeks. Median estimated blood loss was higher in the arthroplasty group (700 cc versus 400 cc; P = 0.04). There were five deaths in the ORIF group versus one in the revision group (P = 0.18). Cases treated by surgeons with fellowship training in arthroplasty were more likely to be treated with revision arthroplasty (10/11, 90.9%) than those treated by surgeons with fellowship training in trauma (5/15, 33.3%; P < 0.01). Conclusions There was no difference in outcomes between the two treatment strategies, but revision was associated with higher blood loss. The appropriate treatment method should be based on surgeon familiarity and patients' characteristics.

4.
J Neurol ; 255(5): 710-5, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18283393

RESUMEN

OBJECTIVE: To report clinical and epidemiological data of Devic's disease in Mexico. DESIGN: Retrospective study of hospital case records. SETTING: The medical records were those of the National Institute for Neurology and Neurosurgery (INNN), a tertiary care referral center in Mexico City. PATIENTS: There were 424 medical histories available for review among 561 discharges with diagnoses of multiple sclerosis (MS), neuromyelitis optica (NMO), or equivalents. 390 met the diagnostic criteria of MS and 34 the NMO criteria. MAIN OUTCOME MEASURES: We recorded clinical signs, visual acuities, and the Expanded Disability Status Scale (EDSS) at the initial diagnostic admission and during follow-up. All patients had examination of cerebrospinal fluid (CSF) at diagnosis; head and spine magnetic resonance imaging (MRI) were performed at diagnosis and at follow-up. RESULTS: All 34 patients were Mexican Mestizos, who comprise 79 % of the residents of Mexico City. There were 23 monophasic and 11 relapsing cases. Intervals between initial and defining events for the 8 ON and 12 myelitis onsets were 17 and 24 months (means) and 15 and 17 months (medians), respectively. Mean follow- up from onset was 70.2 months and 42.9 months from diagnostic examination. No patient showed improvement in EDSS scores. Visual loss was severe. CONCLUSION: A provisional prevalence rate of about 1 per 100,000 population for NMO in Mexican Mestizos might be offered. The disease seems more severe in our population than in other recent series.


Asunto(s)
Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/epidemiología , Nervio Óptico/patología , Médula Espinal/patología , Adulto , Edad de Inicio , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , México/epidemiología , Neuromielitis Óptica/fisiopatología , Nervio Óptico/fisiopatología , Prevalencia , Recurrencia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Médula Espinal/fisiopatología , Baja Visión/etiología , Baja Visión/fisiopatología
5.
Rev. inf. cient ; 101(3): e3847, mayo.-jun. 2022.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1409547

RESUMEN

RESUMEN Introducción: Entre los factores de riesgo que se asocian a complicaciones en el binomio madre-hijo se encuentran: antecedentes de trastornos hipertensivos, embarazo adolescente, consumo de drogas, historia obstétrica desfavorable con antecedentes de abortos u óbitos, enfermedades de transmisión sexual e infecciones del tracto urinario. Objetivo: Identificar el riesgo obstétrico en tiempos de pandemia por COVID-19 en el área de salud ¨Bastión Popular¨, Guayaquil, Ecuador, en el periodo enero-junio de 2021. Método: Se realizó una investigación de campo, de tipo descriptiva-transversal, con un enfoque cuantitativo, que propició el análisis de las categorías del riesgo obstétrico registradas en historias clínicas de 117 gestantes, con firma de consentimiento informado para la obtención de los datos en dicha localidad a través de visitas domiciliarias. Fue empleada la escala o score de riesgo obstétrico. Resultados: Se alcanzó como resultado fundamental que el grupo etario de riesgo obstétrico de mayor frecuencia correspondió a las edades comprendidas entre 20 y 24 años y la principal categoría identificada fue el Alto riesgo. El riesgo obstétrico aumentó de manera proporcional cuando el periodo intergenésico se redujo. Conclusiones: Las mujeres jóvenes de 20 a 24 años son las que presentaron mayor riesgo obstétrico, además que el riesgo obstétrico, el cual se encuentra correlacionado con un mayor número de gestas, abortos, partos y cesáreas, por ello, es necesario proporcionarle información a la mujer sobre la gestación y sus complicaciones, para que sean capaces de identificar los factores de riesgos durante el embarazo, parto y puerperio.


ABSTRACT Introduction: Risk factors associated with complications in the mother-child pair include: history of hypertensive disorders, adolescent pregnancy, drug use, unfavorable obstetric history with a background of miscarriages or abortions, sexually transmitted diseases and urinary tract infections. Objective: To identify the obstetric risk in times of COVID-19 pandemic at the ¨Bastión Popular¨ health area, Guayaquil, Ecuador, from January to June 2021. Method: A descriptive-transversal field research was carried out, with a quantitative approach, which favored the analysis of the obstetric risk categories recorded in the medical history of 117 pregnant women, who signed an informed consent, for the collection of data through home visits, using the obstetric risk scale or score. Results: Outcomes assessment showed, as main result, that the most frequent obstetric risk group was the age group 20 to 24 and the high risk factor was the main category identified. Obstetric risk increased proportionally when the interpregnancy interval was reduce. Conclusions: Young women between 20 and 24 years of age are those who presented the highest obstetric risk, which is correlate with a higher number of gestations, abortions, deliveries and cesarean sections. Therefore, it is necessary to provide women with information about pregnancy and its complications, so that they are able to identify risk factors during pregnancy, delivery and the puerperium.


RESUMO Introdução: Entre os fatores de risco que estão associados às complicações no binômio mãe-filho estão: histórico de doenças hipertensivas, gravidez na adolescência, uso de drogas, histórico obstétrico desfavorável com histórico de abortos ou óbitos, doenças sexualmente transmissíveis e infecções do trato urinário trato. Objetivo: Identificar o risco obstétrico em tempos de pandemia de COVID-19 na área de saúde "Bastión Popular", Guayaquil, Equador, no período janeiro-junho de 2021. Método: Foi realizada uma investigação de campo descritiva. com abordagem quantitativa, que levou à análise das categorias de risco obstétrico registradas nos prontuários de 117 gestantes, com consentimento informado assinado para obtenção dos dados na referida localidade por meio de visitas domiciliares. Foi utilizada a escala ou escore de risco obstétrico. Resultados: O principal resultado foi que a faixa etária de risco obstétrico mais frequente correspondeu às idades entre 20 e 24 anos e a principal categoria identificada foi Alto risco. O risco obstétrico aumentou proporcionalmente quando o período intergestacional foi reduzido. Conclusões: As mulheres jovens de 20 a 24 anos são as que apresentam maior risco obstétrico, além do risco obstétrico, que se correlaciona com maior número de gestações, abortos, partos e cesarianas, portanto, é necessário fornecer informações às mulheres sobre a gravidez e suas complicações, para que possam identificar os fatores de risco durante a gravidez, parto e puerpério.

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