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1.
Front Cell Neurosci ; 18: 1340448, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38323188

RESUMO

Alzheimer's disease (AD), characterized by memory loss and cognitive decline, affects nearly 50 million people worldwide. Amyloid beta (Aß) plaques and intracellular neurofibrillary tangles (NFTs) of phosphorylated Tau protein (pTau) are key histopathological features of the disease in the brain, and recent advances have also identified AD histopathology in the retina. Thus, the retina represents a central nervous system (CNS) tissue highly amenable to non-invasive diagnostic imaging that shows promise as a biomarker for early AD. Given the devastating effects of AD on patients, their families, and society, new treatment modalities that can significantly alter the disease course are urgently needed. In this study, we have developed and characterized a novel human retinal organoid (RO) model derived from induced pluripotent stem cells (iPSCs) from patients with familial AD due to mutations in the amyloid precursor protein gene (APP). Using immunofluorescence and histological staining, we evaluated the cellular composition and AD histopathological features of AD-ROs compared to control ROs from healthy individuals. We found that AD-ROs largely resemble their healthy control counterparts in cellular composition but display increased levels of Aß and pTau. We also present proof of principle of an assay to quantify amyloid levels in whole ROs. This in vitro model of the human AD retina constitutes a new tool for drug screening, biomarker discovery, and pathophysiological studies.

2.
Nanomaterials (Basel) ; 13(19)2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37836355

RESUMO

In this work, we report the caloric effect for an electronic system of the antidot type, modeled by combining a repulsive and attractive potential (parabolic confinement). In this system, we consider the action of a perpendicular external magnetic field and the possibility of having an Aharonov-Bohm flux (AB-flux) generated by a current passing through a solenoid placed inside the forbidden zone for the electron. The energy levels are obtained analytically, and the model is known as the Bogachek and Landman model. We propose to control the caloric response of the system by varying only the AB-flux, finding that, in the absence of an external magnetic field, the maximization of the effect always occurs at the same AB-flux intensity, independently of the temperature, while fixing the external magnetic field at a non-zero value breaks this symmetry and changes the point where the caloric phenomenon is maximized and is different depending on the temperature to which the process is carried. Our calculations indicate that using an effective electron mass of GaAs heterostructures and a trap intensity of the order of 2.896 meV, the modification of the AB-flux achieves a variation in temperature of the order of 1 K. Our analysis suggests that increasing the parabolic confinement twofold increases the effect threefold, while increasing the antidot size generates the reverse effect, i.e., a strong decrease in the caloric phenomenon under study. Due to the great diversity in technological applications that have antidots in electronics, the possibility of controlling their thermal response simply by varying the intensity of the internal current inside the solenoid (i.e., the intensity of AB-flux) can be a platform of interest for experimental studies.

3.
J Phys Condens Matter ; 35(32)2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37146619

RESUMO

Core-shell nanoparticles (CSNPs) are a class of functional materials that have received important attention nowadays due to their adjustable properties by a controlled tuning of the core or shell. Understanding the thermal response and structural properties of these CSNPs is relevant to carrying out an analysis regarding their synthesis and application at the nanoscale. The present work is aimed to investigate the shell thickness effect on thermal stability and melting behavior of Al@Fe CSNPs by using molecular dynamics simulations. The results are discussed considering the influence of the Fe shell on the Al nanoparticle and analyzing the effect of different shell thicknesses in Al@Fe CSNPs. In general, calorific curves show a smooth energy decline for temperatures greater than room temperature for different shell thicknesses and sizes, corresponding to the inward and outward atomic movement of Al and Fe atoms, respectively, that produce a mixed Al-Fe nanoalloy. Here, the thermal stability of the Al@Fe nanoparticle is gradually lost passing to a liquid-Al@solid-Fe configuration and reaching a mixed Al-Fe state by an exothermic mechanism. Combining quantities of the atomic diffusion and structural identification, a stepped structural transition of the system is subsequently observed, where the melting-like point was estimated. Furthermore, it is observed that the Al@Fe CSNPs with greater stability are obtained with a thick shell and a large size. The ability to control shell thickness and vary the size opens up attractive opportunities to synthesize a broad range of new materials with tunable catalytic properties.

5.
Rev. esp. anestesiol. reanim ; 69(10): 663-673, dic. 2022. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-211944

RESUMO

Introducción: La secuencia de intubación rápida es una técnica de protección y rescate de la vía aérea que requiere el uso de sedantes para propiciar un adecuado escenario durante la intubación orotraqueal. Son utilizados diferentes sedantes inductores, siendo el etomidato el más común por sus cualidades farmacocinéticas y farmacodinámicas, donde resalta su estabilidad hemodinámica. Sin embargo, en comparación con otros sedantes esta superioridad es controvertida. Materiales y métodos: Se realizó un metaanálisis con un protocolo definido a priori y siguiendo las etapas de la guía PRISMA. Se calculó la diferencia de medias de la presión arterial sistólica antes y después de la administración del sedante, además de un metaanálisis de riesgos relativos de hipotensión. Resultados: Se incluyeron 10 estudios en los cuales la incidencia de hipotensión en el grupo de pacientes que recibió el etomidato osciló entre el 6,4% y el 75,2%, mientras que en los que recibieron otros sedantes osciló entre el 24,0% y el 65,9%. En los metaanálisis de diferencia de medias no se hallaron diferencias significativas de la presión arterial sistólica durante la preintubación 0,01mmHg (IC 95%: –0,90; 0,92), ni en la postintubación 0,98mmHg (IC 95%: –0,24; 2,20). Además, el metaanálisis de riesgos relativos indica que el riesgo de hipotensión es igual a un RR 1,19 (IC 95%: 0,92-1,54) entre quienes recibieron el etomidato y aquellos que recibieron los otros sedantes. Conclusiones: El riesgo de hipotensión posterior a la secuencia de intubación rápida con etomidato no presenta diferencias significativas comparado con otros sedantes. Sin embargo, hay heterogeneidad en los estudios incluidos.(AU)


Introduction: Rapid sequence intubation is an airway rescue and protection technique in which different sedatives are used to perform orotracheal intubation. Etomidate, due to its pharmacokinetic and pharmacodynamic qualities, particularly hemodynamic stability, is the most widely used sedative in this scenario. However, its superiority over other sedatives is controversial. Materials and methods: We performed a meta-analysis using a pre-designed protocol and PRISMA guidelines to evaluate the mean difference between systolic blood pressure before and after administration of the sedative. We also analyzed the relative risks of hypotension. Results: Ten studies were included. The incidence of hypotension in patients receiving etomidate ranged from 6.4% to 75.2%, and between 24.0% and 65.9% in patients receiving other sedatives. No significant differences were found in the mean difference in systolic blood pressure during pre-intubation 0.01mmHg (95% CI: –0.90; 0.92) or in post-intubation 0.98mmHg (95% CI: –0.24; 2.20). The relative risk analysis showed that the risk of hypotension is equal to an RR of 1.19 (95% CI: 0.92-1.54) between those who received etomidate and those who received the other sedatives. Conclusions: The risk of hypotension after rapid intubation sequence with etomidate does not differ significantly compared to other sedatives. However, the studies included in this review were heterogeneous.(AU)


Assuntos
Humanos , Hemodinâmica , Etomidato , Intubação , Hipnóticos e Sedativos , Hipotensão , Anestesiologia , Pressão Arterial
6.
Rev Esp Anestesiol Reanim (Engl Ed) ; 69(10): 663-673, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36241514

RESUMO

INTRODUCTION: Rapid sequence intubation is an airway rescue and protection technique in which different sedatives are used to perform orotracheal intubation. Etomidate, due to its pharmacokinetic and pharmacodynamic qualities, particularly hemodynamic stability, is the most widely used sedative in this scenario. However, its superiority over other sedatives is controversial. MATERIALS AND METHODS: We performed a meta-analysis using a pre-designed protocol and PRISMA guidelines to evaluate the mean difference between systolic blood pressure before and after administration of the sedative. We also analyzed the relative risks of hypotension. RESULTS: Ten studies were included. The incidence of hypotension in patients receiving etomidate ranged from 6.4% to 75.2%, and between 24.0% and 65.9% in patients receiving other sedatives. No significant differences were found in the mean difference in systolic blood pressure during pre-intubation 0.01 mm Hg (95% CI: -0.90; 0.92) or in post-intubation 0.98 mmHg (95% CI: -0.24; 2.20). The relative risk analysis showed that the risk of hypotension is equal to an RR of 1.19 (95% CI: 0.92-1.54) between those who received etomidate and those who received the other sedatives. CONCLUSIONS: The risk of hypotension after rapid intubation sequence with etomidate does not differ significantly compared to other sedatives. However, the studies included in this review were heterogeneous.


Assuntos
Etomidato , Hipotensão , Humanos , Etomidato/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Indução e Intubação de Sequência Rápida , Intubação Intratraqueal/métodos , Hipotensão/induzido quimicamente
7.
Transl Res ; 250: 98-111, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35690342

RESUMO

The ability to generate human retinas in vitro from pluripotent stem cells opened unprecedented opportunities for basic science and for the development of therapeutic approaches for retinal degenerative diseases. Retinal organoid models not only mimic the histoarchitecture and cellular composition of the native retina, but they can achieve a remarkable level of maturation that allows them to respond to light stimulation. However, studies evaluating the nature, magnitude, and properties of light-evoked responsivity from each cell type, in each retinal organoid layer, have been sparse. In this review we discuss the current understanding of retinal organoid function, the technologies used for functional assessment in human retinal organoids, and the challenges and opportunities that lie ahead.


Assuntos
Organoides , Células-Tronco Pluripotentes , Humanos , Retina/metabolismo , Diferenciação Celular
8.
Rev. argent. dermatol ; 103(1): 11-20, feb. 2022. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1407159

RESUMO

Resumen Las verrugas plantares son una patología común en la población. Estas lesiones son a menudo dolorosas y recidivantes. Entre los tratamientos más utilizados están las terapias tópicas destructivas y menos frecuentemente el tratamiento quirúrgico. Sin embargo, con frecuencia recurren, por lo que representan un desafío para el dermatólogo. Presentamos 3 casos de pacientes varones adultos con verrugas plantares recalcitrantes que fueron tratadas exitosamente con una sola sesión de láser PDL, sin recidiva luego de 8 a 12 meses de seguimiento.


Abstract Plantar warts are a common pathology in the population. These lesions are often painful and recurring. Among the most used treatments are topical destructive therapies, and less frequently, surgical treatment. However, they frequently recur, so they represent a challenge for the dermatologist. We present 3 adult males with a recalcitrant plantar wart that were successfully treated with a single PDL laser session, without relapse after 8-12 months of follow-up.

9.
Front Cell Neurosci ; 15: 667880, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34025363

RESUMO

The cumulative knowledge of retina development has been instrumental in the generation of retinal organoid systems from pluripotent stem cells; and these three-dimensional organoid models, in turn, have provided unprecedented opportunities for retinal research and translational applications, including the ability to model disease in a human setting and to apply these models to the development and validation of therapeutic drugs. In this review article, we examine how retinal organoids can also contribute to our understanding of retinal developmental mechanisms, how this knowledge can be applied to modeling developmental abnormalities, and highlight some of the avenues that remain to be explored.

10.
Rev Esp Sanid Penit ; 23(3): 119-127, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35411915

RESUMO

Hepatitis B is a parenterally and sexually transmitted infection. Vaccination for the disease is highly effective, and its inclusion in Spain as part of a systematic and universal schedule for newborns has led to a significant decrease of incidence in the national population. However, the number of inmates born in other countries some from endemic areas of HBV infection -, the mechanisms of transmission and lack of vaccination in third world countries mean that its prevalence in the prison population is higher than in the general population. These institutions therefore play an essential role in detecting and managing hepatitis B. In this paper, the situation of hepatitis B in prisons is reviewed and recommendations are proposed to optimize its control.


Assuntos
Hepatite B , Infecções Sexualmente Transmissíveis , Hepatite B/diagnóstico , Hepatite B/prevenção & controle , Humanos , Recém-Nascido , Prisões , Espanha , Vacinação
11.
Rev Neurol ; 71(12): 431-437, 2020 12 16.
Artigo em Espanhol | MEDLINE | ID: mdl-33319345

RESUMO

INTRODUCTION: The coronavirus disease 2019 (COVID-19) caused a collapse situation in many hospitals around the world. The aim of this study is to analyse the utility of the electroencephalogram (EEG) in the management of the neurological patient during the COVID-19 pandemic. PATIENTS AND METHODS: The Clinical Neurophysiology Department of the Hospital Central de la Defensa Gomez Ulla was dissolved due to the hospital collapse situation. Therefore, the EEG was performed exceptionally in those cases with the greatest probability of providing a benefit in its management. We describe seven patients (four in ICU and three hospitalized) diagnosed with COVID-19, who underwent through an EEG. RESULTS: The EEG showed abnormalities in all cases, including one case of brain death. The EEG resulted in a change in clinical management in four of the patients (57%) and helped the clinician provide information to the family. In the other three cases, a toxic-metabolic origin was suspected before the EEG was performed, so it did not imply a change in the clinical management already proposed, although it facilitated a prognostic orientation. Slow polymorphic waves were evident in five cases. Five patients were unresponsive. Currently, one patient remain hospitalized and four have died. CONCLUSIONS: The EEG was useful and facilitated decision making in COVID-19 patients in whom it was requested. It guided the diagnosis in cases where CT was non-contributory and led to a change in therapeutic management in most patients. The most frequent findings were signs of encephalopathy and epileptiform discharges.


TITLE: Utilidad y valor pronóstico del electroencefalograma en la COVID-19 y la encefalopatía: patrones electroencefalográficos en una serie de casos.Introducción. La enfermedad por coronavirus 2019 (COVID-19) causó el colapso de muchos hospitales. El objetivo de este estudio es analizar la utilidad del electroencefalograma (EEG) en el tratamiento del paciente neurológico durante la pandemia de COVID-19. Pacientes y métodos. El Servicio de Neurofisiología Clínica del Hospital Central de la Defensa Gómez Ulla fue disuelto debido a la situación de saturación hospitalaria. En consecuencia, se realizó un EEG excepcionalmente a los pacientes a los que tenía mayor probabilidad de aportar un beneficio en su tratamiento. Se describen siete pacientes (cuatro en cuidados intensivos y tres hospitalizados) diagnosticados con COVID-19 a quienes se les realizó un EEG. Resultados. El EEG mostró anormalidades en todos los casos, incluyendo un caso de muerte cerebral. El EEG supuso un cambio en el tratamiento clínico en cuatro de los pacientes (57%) y ayudó al clínico a informar a la familia. En los otros tres casos, se sospechó un origen tóxico-metabólico previo al EEG, por lo que no implicó un cambio en el tratamiento ya propuesto, aunque facilitó una orientación pronóstica. Se evidenciaron ondas lentas polimorfas en cinco casos. Actualmente, un paciente permanece hospitalizado y cuatro han fallecido. Conclusiones. El EEG fue de utilidad y facilitó la toma de decisiones en los pacientes con COVID-19 en los que se solicitó. Orientó al diagnóstico en casos en los que la tomografía computarizada no contribuyó y supuso un cambio en el tratamiento terapéutico en la mayoría de los pacientes. Los hallazgos más frecuentes fueron signos de encefalopatía y descargas epileptiformes.


Assuntos
COVID-19/fisiopatologia , Eletroencefalografia , Encefalite Viral/diagnóstico , SARS-CoV-2/isolamento & purificação , Idoso , COVID-19/complicações , COVID-19/diagnóstico , Teste de Ácido Nucleico para COVID-19 , Comorbidade , Transtornos da Consciência/etiologia , Transtornos da Consciência/fisiopatologia , Encefalite Viral/etiologia , Feminino , Parada Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/fisiopatologia , Nasofaringe/virologia , Pandemias , Prognóstico , Estudos Retrospectivos
12.
Rev. chil. obstet. ginecol. (En línea) ; 85(supl.1): S131-S147, set. 2020. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1138658

RESUMO

INTRODUCCIÓN Y OBJETIVO Una enfermedad nueva, COVID-19, está afectando dramáticamente al mundo. Conocer los riesgos para la salud reproductiva es un imperativo para la práctica obstétrica y ginecológica. Esta investigación analiza los riesgos maternos y perinatales asociados a COVID-19, con el objetivo de identificar desafíos que la enfermedad plantea a la práctica de la matronería. MÉTODOS Revisión narrativa. Se consultaron artículos científicos de fuentes primarias indexados en las bases Scielo, Pubmed, Scope, WOS, mediante los siguientes términos de búsqueda: "embarazo" "transmisión vertical" "salud materna y perinatal", "riesgos maternos y perinatales" "lactancia materna", COVID-19", "Coronavirus". Se realizaron 3 fases de selección. Los tópicos de análisis fueron: Transmisión vertical, Riesgo materno y perinatal, Lactancia materna. RESULTADOS. En mujeres embarazadas las formas severas de COVID-19 se presentan en presencia de enfermedades crónicas. A nivel perinatal el riesgo mayor es el parto prematuro, generalmente por indicación médica y por cesárea. Aunque no hay evidencias de transmisión vertical, tampoco puede descartarse. Los riesgos neonatales se relacionan con el contagio por proximidad y con medidas restrictivas que pueden afectar la lactancia materna y la interacción madre-hija(o). CONCLUSIONES. La COVID-19 aporta varios desafíos para la práctica de la matronería: implementación de métodos de prevención del contagio a la gestante y a su entorno cercano; adecuación de la preparación al parto en caso de positividad; prevención del estrés y desgaste emocional materno desde el inicio de la gestación hasta el postparto; adecuación de cuidados al recién nacido; investigación aplicada en Latinoamérica, y evaluación de nuevos protocolos.


INTRODUCTION AND OBJECTIVE A new disease, COVID-19, is dramatically affecting the world. Knowing the risks for the reproductive health is an imperative for the obstetric and gynecological practice. This research analyzes the maternal and perinatal risks associated with COVID-19, with the aim of identifying challenges that the disease poses to the practice of midwifery. METHODS Narrative review. Scientific articles from primary sources indexed in Scielo, Pubmed, Scope, and WOS, are consulted by using the following search terms: "pregnancy" "vertical transmission" "maternal and perinatal health", "maternal and perinatal risks" "breastfeeding", COVID-19", "Coronavirus". Three selection phases were carried out. The topics of analysis were vertical transmission, maternal and perinatal risk, breastfeeding. RESULTS In pregnant women severe forms of COVID-19 occur in the presence of chronic diseases. At the perinatal level, the biggest risk is premature delivery, generally for medical indications and by cesarean section. Although there is no evidence of vertical transmission, it cannot be ruled out either. Neonatal risks are related to transmission by proximity and restrictive measures that may affect breastfeeding and mother-child interaction. CONCLUSIONS COVID-19 brings several challenges to the practice of midwifery: implementation of methods to prevent infection of the pregnant woman and her close environment; adaptation of birth preparation in case of positivity; prevention of maternal stress and emotional distress from the beginning of pregnancy to postpartum; adequacy of care for the newborn; research in Latin America, and evaluation of new protocols.


Assuntos
Humanos , Feminino , Gravidez , Recém-Nascido , Pneumonia Viral/transmissão , Complicações Infecciosas na Gravidez , Infecções por Coronavirus/transmissão , Transmissão Vertical de Doenças Infecciosas , Betacoronavirus , Aleitamento Materno , Medição de Risco , Pandemias , Tocologia
13.
Toxicol In Vitro ; 68: 104947, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32679256

RESUMO

Few vaccine adjuvants have been approved for human use although several are currently being studied in preclinical and clinical trial. MPL is a toll-like receptor agonist able to trigger a high and persistent antibody response via-TLR-4 while QS-21 activates the NLRP3 inflammasome. Data suggest that there is a cross-talk between Notch and TLR signaling pathways modulating the polarization of the immune response in a MyD88-dependent manner. However, the role of Notch on the mechanism action of immunogenic adjuvants has not been addressed yet. This study aims to evaluate the in vitro toxicity and inflammatory response triggered by MPL and QS-21 using an in vitro human cell co-culture model and to determine whether NFκB or Notch signaling pathways are involved in their mechanism of immunotoxicity. In order to do this, we evaluated the effect of QS- 21/MPL alone or in combination using a co-culture of PBMC and HUVEC using cytotoxicity, surface expression of ECAMs, cell adhesion and cytokine release, NF-κB activation and NOTCH1 expression as observation endpoints. We found that both MPL and QS-21 were cytotoxic at concentrations over 5 µg/mL. Both adjuvants were able to trigger the expression of ECAMs and induce firm adhesion of PBMC to the endothelium. QS-21 and MPL combination demonstrated a synergistic effect on cellular recruitment and cytokine release generating a switch from Th2 to Th1 cytokine profile. Both MPL and QS-21 by themselves were able to generate significant NF-κB activation. However, this effect was not observed when both adjuvants were combined. On the contrary, the adjuvants alone and combined induced an overexpression of NOTCH-1. This is an important finding, as it provides new evidence that these adjuvants could modulate reactogenicity of vaccines through Notch signaling.


Assuntos
Adjuvantes Imunológicos/toxicidade , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Lipídeo A/análogos & derivados , Receptor Notch1/genética , Saponinas/toxicidade , Adesão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Citocinas/metabolismo , Interações Medicamentosas , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Leucócitos Mononucleares/fisiologia , Lipídeo A/toxicidade , NF-kappa B/metabolismo
14.
Chem Senses ; 45(7): 493-502, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-32556127

RESUMO

The chemical senses of taste and smell play a vital role in conveying information about ourselves and our environment. Tastes and smells can warn against danger and also contribute to the daily enjoyment of food, friends and family, and our surroundings. Over 12% of the US population is estimated to experience taste and smell (chemosensory) dysfunction. Yet, despite this high prevalence, long-term, effective treatments for these disorders have been largely elusive. Clinical successes in other sensory systems, including hearing and vision, have led to new hope for developments in the treatment of chemosensory disorders. To accelerate cures, we convened the "Identifying Treatments for Taste and Smell Disorders" conference, bringing together basic and translational sensory scientists, health care professionals, and patients to identify gaps in our current understanding of chemosensory dysfunction and next steps in a broad-based research strategy. Their suggestions for high-yield next steps were focused in 3 areas: increasing awareness and research capacity (e.g., patient advocacy), developing and enhancing clinical measures of taste and smell, and supporting new avenues of research into cellular and therapeutic approaches (e.g., developing human chemosensory cell lines, stem cells, and gene therapy approaches). These long-term strategies led to specific suggestions for immediate research priorities that focus on expanding our understanding of specific responses of chemosensory cells and developing valuable assays to identify and document cell development, regeneration, and function. Addressing these high-priority areas should accelerate the development of novel and effective treatments for taste and smell disorders.


Assuntos
Transtornos do Olfato/terapia , Distúrbios do Paladar/terapia , Congressos como Assunto , Terapia Genética , Humanos , Transtornos do Olfato/patologia , Medicina Regenerativa , Bibliotecas de Moléculas Pequenas/uso terapêutico , Transplante de Células-Tronco , Células-Tronco/citologia , Células-Tronco/metabolismo , Distúrbios do Paladar/patologia
15.
J Ocul Pharmacol Ther ; 36(1): 18-24, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31059378

RESUMO

Retinal disease represents a growing global problem, both in terms of quality of life and economic impact, yet new therapies are not being developed at a sufficient rate to meet this mounting need. In this context, retinal organoids derived from human induced pluripotent stem cells hold significant promise for improving upon the current drug development process, increasing the speed and efficiency of moving potential therapeutic agents from bench to bedside. These organoid systems display the cell-cell and cell-matrix interactions, cellular heterogeneity, and physiological responses reflective of human biology and, thus, have the ability to replicate retinal disease pathology in a way that 2-dimensional cell cultures and animal models have been heretofore unable to achieve. However, organoid technology is not yet mature enough to meet the high-throughput demands of the first stages of drug screening. Hence, the augmentation of the existing drug development pipeline with retinal organoids, rather than the replacement of existing pathway components, may provide a way to harness the benefits of this improved pathological modeling. In this study, we outline the possible benefits of such a symbiosis, discuss other potential uses, and highlight barriers that remain to be overcome.


Assuntos
Descoberta de Drogas , Organoides/metabolismo , Retina/metabolismo , Doenças Retinianas/tratamento farmacológico , Animais , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Organoides/citologia , Retina/citologia , Doenças Retinianas/metabolismo , Doenças Retinianas/patologia
16.
Arch Soc Esp Oftalmol (Engl Ed) ; 94(8): 367-376, 2019 Aug.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31266666

RESUMO

INTRODUCTION: Fluctuating elevated intraocular pressure (IOP) is one of the complications of an implantable collamer lens (ICL), and its alteration is a predictive factor for the development of glaucoma. MATERIAL AND METHODS: A prospective, cross-sectional analytic study was conducted on patients suitable for ICL implantation. Complete clinical and biometric work-ups were performed, as well as night-time IOP curve, in supine position, with 4 determinations, in order to assess fluctuation, considering abnormal with a value higher than 5 mmHg. Patients underwent surgery with conventional technique and three months after the work-ups were repeated, including a night-time IOP curve to assess any changes in IOP fluctuations. RESULTS: A total of 31 eyes of 16 patients were studied. Mean IOP fluctuation in the preoperative assessment was 3.35 ± 2 mmHg, whereas the postoperative mean was 3.0 ± 2.2 mmHg, with the difference not being statistically significant. Visual acuity and capacity, as well as spheric equivalent did show a statistically significant improvement. There were 6 cases of complications, which were related to a higher vault and a greater ICL size. There was no relationship between these findings and the angle grade, pigment, and the level of training of the surgeon. CONCLUSIONS: The effect of an ICL on IOP fluctuations, has been studied for the first time, which was found to be not statistically significant. As in previous publications, the procedure was safe and reproducible, adding the fact that the level of training of the surgeon is not a determining factor in these findings.


Assuntos
Pressão Intraocular/fisiologia , Hipertensão Ocular/fisiopatologia , Lentes Intraoculares Fácicas/efeitos adversos , Complicações Pós-Operatórias/fisiopatologia , Adulto , Estudos Transversais , Feminino , Seguimentos , Glaucoma/etiologia , Humanos , Implante de Lente Intraocular/métodos , Masculino , México , Período Pós-Operatório , Período Pré-Operatório , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Tempo , Acuidade Visual , Adulto Jovem
17.
Transl Psychiatry ; 9(1): 81, 2019 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-30745563

RESUMO

Abnormal levels of dopamine (DA) are thought to contribute to several neurological and psychiatric disorders including drug addiction. Extracellular DA levels are regulated primarily via reuptake by the DA transporter (DAT). Amphetamine, a potent psychostimulant, increases extracellular DA by inducing efflux through DAT. Recently, we discovered that G protein ßγ subunits (Gßγ) interact with DAT, and that in vitro activation of Gßγ promotes DAT-mediated efflux. Here, we investigated the role of Gßγ in the actions of amphetamine in DA neurons in culture, ex vivo nucleus accumbens (NAc), and freely moving rats. Activation of Gßγ with the peptide myr-Ser-Ile-Arg-Lys-Ala-Leu-Asn-Ile-Leu-Gly-Tyr-Pro-Asp-Tyr-Asp (mSIRK) in the NAc potentiated amphetamine-induced hyperlocomotion, but not cocaine-induced hyperlocomotion, and systemic or intra-accumbal administration of the Gßγ inhibitor gallein attenuated amphetamine-induced, but not cocaine-induced hyperlocomotion. Infusion into the NAc of a TAT-fused peptide that targets the Gßγ-binding site on DAT (TAT-DATct1) also attenuated amphetamine-induced but not cocaine-induced hyperlocomotion. In DA neurons in culture, inhibition of Gßγ with gallein or blockade of the Gßγ-DAT interaction with the TAT-DATct1 peptide decreased amphetamine-induced DA efflux. Furthermore, activation of Gßγ with mSIRK potentiated and inhibition of Gßγ with gallein reduced amphetamine-induced increases of extracellular DA in the NAc in vitro and in freely moving rats. Finally, systemic or intra-accumbal inhibition of Gßγ with gallein blocked the development of amphetamine-induced, but not cocaine-induced place preference. Collectively, these results suggest that interaction between Gßγ and DAT plays a critical role in the actions of amphetamine and presents a novel target for modulating the actions of amphetamine in vivo.


Assuntos
Anfetamina/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Dopamina/metabolismo , Subunidades beta da Proteína de Ligação ao GTP/metabolismo , Subunidades gama da Proteína de Ligação ao GTP/metabolismo , Anfetamina/efeitos adversos , Animais , Estimulantes do Sistema Nervoso Central/efeitos adversos , Cocaína/administração & dosagem , Neurônios Dopaminérgicos/metabolismo , Masculino , Atividade Motora/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Ratos , Ratos Sprague-Dawley
18.
Enferm. univ ; 15(4): 370-382, oct.-dic. 2018. tab
Artigo em Espanhol | LILACS-Express | LILACS, BDENF - Enfermagem | ID: biblio-989790

RESUMO

Objetivo Medir la Calidad de Vida en el trabajo (CVT) y sus factores asociados en profesores de colegios públicos de Concepción, Chile. Método Investigación cuantitativa, transversal, descriptiva. Muestra: 92 profesores. Instrumentos: Se empleó CVT-GOHISALO para evaluar CVT (Alpha de Cronbach 0.952) y un cuestionario biosociodemográfico diseñado por el primer autor. El procesamiento de datos se realizó con SPPS, empleándose Rho-Spearman, Rho-Pearson, ANOVA y pruebas no-paramétricas. Se contó con las autorizaciones de los comités de ética involucrados, así como de la Dirección de Administración de Educación Municipal de Concepción (DAEM), y con el consentimiento informado de los participantes. Resultados Promedio CVT global: 215.8 (DE=43.3), que indica nivel medio de CVT. Promedios CVT por dimensiones: Soporte institucional para el trabajo (SIT)=44.6 (DE=10.2), Seguridad en el trabajo (ST)=30 (DE=11.7), Integración al puesto de trabajo (IPT)=33.4 (DE=6.1), Satisfacción por el trabajo (SPT)=34.9 (DE=6.8), Bienestar logrado a través del trabajo (BAT)=36.6 (DE=5.7), Desarrollo personal (DP)=23.3 (DE=6.4) y Administración del tiempo libre (ATL)=12.7 (DE=4.2). Clasificación CVT por dimensiones: SIT: nivel alto; ST, IPT, SPT y DP: nivel medio; BAT y ATL: nivel bajo. Anova para prexistencia de trastorno en salud mental y CVT global, dimensiones SIT, ST, IPT, SPT, BAT, DP y ATL con valor p=0.000; p=0.000; p=0.017; p=0.005; p=0.000; p=0.001 y p=0.046 respectivamente. Conclusiones Los maestros se encuentran medianamente satisfechos con su CVT; existe asociación entre prexistencia de trastornos en salud mental y baja percepción de CVT. Es fundamental que enfermería vele por adecuadas condiciones laborales de profesores y alumnos con el fin de asegurar una CVT satisfactoria así como mejorar la calidad de la educación impartida.


Objective To assess the Quality of Life at Work (QLW) and associated factors among professors of public colleges in Concepción, Chile. Method This is a quantitative, transversal, and descriptive study using a sample of 92 professors. The CVT-GOHISALO instrument was administered to assess QLW (Cronbach Alpha = 0.952) in addition to a bio-social-demographic questionnaire specifically designed by the first author. Data were analyzed with SPSS calculating Rho-Spearman, Rho-Pearson, ANOVA, and non-parametric tests. The corresponding authorizations from involved ethics committees and the Direction of Management of Municipal Education of Concepcion were obtained as well as the inform consent from all the participants. Results The global average QLW score was 215.8 (SD=43.3), indicating a medium level. The related average scores by dimension were as follows: Institutional Support for Work (ISW)=30 (SD=11.7); Work Security (WS)=30 (SD=11.7); Integration to the Work Position (IWP)=33.4 (SD=6.1); Work Satisfaction (WS)=34.9 (DS=6.8); Wellbeing Achieved from Work (WAW)=36.6 (DS=5.7); Personal Development (PD)=23.3 (SD=6.4); and Free Time Management (FTM)=12.7 (SD=4.2). The QLW classification by dimension is as follows: ISW=high; WS, IWP, WS, and PD=medium; WAW, and FTM=low. ANOVA for pre-existing mental health issues and global QLV, dimensions ISW, WS, IWP, WS, WAW, PD, FTM had p=0.000; p=0.000; p=0.017; p=0.005; p=0.000; p=0.001 and p=0.046 respectively. Conclusions Teachers are satisfied in a medium level regarding their QLW. An association between pre-existing mental health issues and a low perception of QLW was found. It is fundamental that nursing organizations promote adequate working conditions for professors and students in order to foster their satisfaction at work and thus the quality of the education they impart.


Objetivo Medir a Qualidade de Vida no trabalho (CVT) e seus fatores associados em professores de escolas públicas de Concepción, Chile. Método Pesquisa quantitativa, transversal, descritiva. Amostra: 92 professores. Instrumentos: Empregou-se CVT-GOHISALO para avaliar CVT (Alpha de Cronbach 0.952) e um questionário biosociodemográfico desenhado pelo primeiro autor. O processamento de dados realizou-se com SPPS, empregou-se Rho-Spe arman, Rho-Pearson, ANOVA e provas não-paramétricas. Contou-se com as autorizações dos comités de ética envolvidos, assim como da "Dirección de Administración de Educación Municipal de Concepción" (DAEM), e com o consentimento informado dos participantes. Resultados Média CVT global: 215.8 (DE=43.3), que indica nível médio de CVT. Média CVT por dimensões: Suporte institucional para o trabalho (SIT)=44.6 (DE=10.2), Segurança no trabalho (ST)=30 (DE=11.7), Integração ao posto de trabalho (IPT)=33.4 (DE=6.1), Satisfação pelo trabalho (SPT)=34.9 (DE=6.8), Bem-estar atingido a través do trabalho (BAT)=36.6 (DE=5.7), Desenvolvimento pessoal (DP)=23.3 (DE=6.4) e Administração do tempo livre (ATL)=12.7 (DE=4.2). Classificação CVT por dimensões: SIT: nível alto; ST, IPT, SPT e DP: nível médio; BLT e ATL: nível baixo. Anova para preexistência de transtorno em saúde mental e CVT global, dimensões ST, IPT, SPT, BAT, DP e ATL com valor p=0.000; p=0.000; p=0.017; p=0.005; p=0.000; p=0.001 e p=0.046, respectivamente. Conclusões Os professores encontram-se medianamente satisfeitos com sua CVT; existe associação entre preexistência de transtornos em saúde mental e baixa percepção de CVT. É fundamental que a enfer magem garanta adequadas condições laborais de professores e alunos com o fim de segurar uma CVT satisfatória assim como melhorar a qualidade da educação ministrada.


Assuntos
Humanos , Masculino , Feminino , Qualidade de Vida , Trabalho , Professores Escolares
19.
Rev. int. med. cienc. act. fis. deporte ; 18(71): 493-505, sept. 2018. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-180227

RESUMO

El objetivo es: comparar la edad cronológica con la edad fitness obtenida por medio del VO2 máximo indirecto, de un grupo de personas sedentarias y no sedentarias. Método: 253 personas fueron evaluadas respecto a masa corporal, estatura, perímetro de cintura, frecuencia cardiaca basal y un cuestionario del modelo web "Fitness Calculator". Los resultados demostraron diferencias significativas en las variables antropométricas y fisiológicas entre personas sedentarias y no sedentarias (P<,001). Las personas no sedentarias tienen un mayor VO2máx en comparación con las personas sedentarias. Las personas sedentarias indican que presentan una edad fitness que se encuentra sobre 12 años cronológicos promedio de lo esperado. Conclusión: Las personas sedentarias tienen una mayor edad fitness, esto permite establecer que su cuerpo se deteriora más rápido que los no sedentarios. El bajo VO2 máx es un potente predictor de la capacidad cardiorrespiratoria y se establece como un predictor de enfermedades cardiovasculares


The purpose was to compare chronological age with fitness age obtained through indirect VO2max in a group of sedentary and non-sedentary people. Method: 253 people were evaluated for body mass, height, waist circumference, basal heart rate and a web model questionnaire "Fitness Calculator". The results: showed significant differences in anthropometric and physiological variables between sedentary and non-sedentary people (P <.001). Non-Sedentary people have a greater higher VO2máx group compared to sedentary people. This indicates that sedentary people have a fitness age 12 years over their expected chronological average age. Conclusion: Sedentary people have a higher fitness age; therefore your body deteriorates faster than the non-sedentary people. A low level of VO2máx is a powerful predictor of cardiorespiratory capacity and of cardiovascular diseases


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Comportamento Sedentário , Índice de Massa Corporal , Exercício Físico , Treinamento Intervalado de Alta Intensidade , Antropometria , Estudos Transversais , 28599
20.
Int J Dev Biol ; 62(6-7-8): 351-361, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29877565

RESUMO

The idea of regenerating injured body parts has captivated human imagination for centuries, and the topic still remains an area of extensive scientific research. This review focuses on the process of lens regeneration: its history, our current knowledge, and the questions that remain unanswered. By highlighting some of the milestones that have shaped our understanding of this phenomenon and the contributions of scientists who have dedicated their lives to investigating these questions, we explore how regeneration enquiry evolved into the science it is today, and how technological advances accelerated our understanding of these remarkable processes.


Assuntos
Proliferação de Células/fisiologia , Transdiferenciação Celular/fisiologia , Células Epiteliais/fisiologia , Cristalino/fisiologia , Regeneração/fisiologia , Animais , Biologia do Desenvolvimento/métodos , Biologia do Desenvolvimento/tendências , Humanos , Cristalino/citologia , Modelos Biológicos
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