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Advances in melanoma research have unveiled critical insights into its genetic and molecular landscape, leading to significant therapeutic innovations. This review explores the intricate interplay between genetic alterations, such as mutations in BRAF, NRAS, and KIT, and melanoma pathogenesis. The MAPK and PI3K/Akt/mTOR signaling pathways are highlighted for their roles in tumor growth and resistance mechanisms. Additionally, this review delves into the impact of epigenetic modifications, including DNA methylation and histone changes, on melanoma progression. The tumor microenvironment, characterized by immune cells, stromal cells, and soluble factors, plays a pivotal role in modulating tumor behavior and treatment responses. Emerging technologies like single-cell sequencing, CRISPR-Cas9, and AI-driven diagnostics are transforming melanoma research, offering precise and personalized approaches to treatment. Immunotherapy, particularly immune checkpoint inhibitors and personalized mRNA vaccines, has revolutionized melanoma therapy by enhancing the body's immune response. Despite these advances, resistance mechanisms remain a challenge, underscoring the need for combined therapies and ongoing research to achieve durable therapeutic responses. This comprehensive overview aims to highlight the current state of melanoma research and the transformative impacts of these advancements on clinical practice.
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Trabecular bone score (TBS) is a tool to improve evaluation of DXA scans, barely used in children. We proposed to evaluate TBS with bone age (BA) compared to chronological age (CA). In girls, TBS value using BA is constant until age 8, and in boys until age 10, and then starts to increase steadily. This data may help widen TBS use in pediatric populations. INTRODUCTION: Trabecular bone score (TBS) is a software-based tool for the analysis of DXA images to assess bone microarchitecture in the lumbar region. It is used widely in adults to improve evaluation of fracture risk, yet it has been rarely studied in children and no normal curves have been developed for pediatrics. The purpose of this study was to evaluate bone (skeletal) age compared to chronological age to determine which is better in the pediatric population since both bone age (BA) and trabecular density are equally susceptible to change in response to similar factors. METHODS: Total body, lumbar region, and non-dominant hand scans were obtained with an iDXA device in all participants. DXA scans of lumbar region for TBS analysis and AP images of non-dominant hand-for-BA were obtained for 565 children (269 female) aged 4to 19. RESULTS: Simple correlation was calculated and r2 values for TBS and chronological age were obtained by linear regression, with low correlations (0.36 for boys and 0.38 for girls), and then we created Loess curves to show the change for consecutive ages. In girls, the curve forms a U shape with a nadir point at approximately age 10. We then replaced chronological age with BA, and significant change was seen in the girls' curve, where a turning point is seen at age 8. In boys, a similar trend shows a turning point at age 10. Finally, BA-corrected TBS curves were constructed using LMS, obtaining curves with percentiles. CONCLUSIONS: The use of BA in the analysis and interpretation of TBS may help widen its use in pediatric populations by enabling the appearance of normative data, but more information is needed to confirm this finding.
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Absorciometría de Fotón/estadística & datos numéricos , Determinación de la Edad por el Esqueleto/estadística & datos numéricos , Hueso Esponjoso/diagnóstico por imagen , Absorciometría de Fotón/métodos , Adolescente , Densidad Ósea/fisiología , Niño , Preescolar , Análisis Factorial , Femenino , Mano/diagnóstico por imagen , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/fisiología , Masculino , Valores de Referencia , Adulto JovenRESUMEN
In this work, we have genetically transformed tobacco (Nicotiana tabacum) plants with the peroxisome proliferator-activated receptor cDNA (xPPARalpha) from Xenopus laevis, which is a transcriptional factor involved in the peroxisomal proliferation and induction of fatty acid beta-oxidation in animal cells. Several transgenic lines were generated and one representative line (T) from the R2 generation was selected for further studies. Analysis of free fatty acids revealed that unsaturated fatty acids such as C16:2 and C16:3 were deficient in line T, whereas saturated fatty acids like C16:0, C18:0, and C20:0 were more abundant than in non-transformed plants. Acyl-CoA oxidase (ACOX) activity was assayed as a marker enzyme of beta-oxidation in crude leaf extracts and it was found that in line T there was a threefold increase in enzyme activity. We also found that the peroxisome population was increased and that catalase (CAT) activity was induced by clofibrate, a known activator of xPPARalpha protein, in leaves from line T. Taken together, these findings suggest that xPPARalpha is functional in plants and that its expression in tobacco leads to changes in general lipid metabolism and peroxisomal proliferation as reported in animal cells. Furthermore, it indicates that there is an endogenous ligand in tobacco cells able to activate xPPARalpha.
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Nicotiana/genética , PPAR alfa/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Acilcoenzima A/metabolismo , Animales , Biomarcadores , Catalasa/metabolismo , Clofibrato/farmacología , Ácidos Grasos no Esterificados/metabolismo , Hipolipemiantes/farmacología , Ligandos , PPAR alfa/genética , Peroxisomas/metabolismo , Peroxisomas/fisiología , Peroxisomas/ultraestructura , Hojas de la Planta/anatomía & histología , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/metabolismo , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/anatomía & histología , Plantas Modificadas Genéticamente/efectos de los fármacos , Nicotiana/anatomía & histología , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Xenopus laevisRESUMEN
Introducción: El Síndrome de Boerhaave se define como la rotura del esófago no relacionada con traumatismos, exploraciones invasivas, patología esofágica previa o cuerpos extraños. Es una ruptura barogénica y postemética.Objetivo: Revisión bibliográfica y presentación de caso.Lugar de Aplicación: Hospital Polivalente de Alta complejidad.Caso Clínico: masculino de 70 años ingresa por melena y hematemesis de escasa cantidad. Presenta rápidamente descompensación hemodinámica. Se constata enfisema subcutáneo. El paciente pasa a UTI en mal estado general requiriendo ARM. Se realiza RX de Tórax evidenciándose neumomediastino y opacidad difusa en ambos campos pulmonares. Se produce el óbito del paciente a las 24 hs. de su ingreso.Conclusión: La perforación espontánea de esófago es una patología poco frecuente con un curso rápido y de mal pronóstico sin un diagnóstico y una terapéutica precoz. Tiene un alto índice de mortalidad (36%) y el factor pronóstico más importante es el tiempo empleado en el tratamiento quirúrgico, ya sea con cierre primario, cierre reforzado, resección esofágica, exclusión o colocación de endoprótesis.
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Masculino , Femenino , Informes de Casos , Esófago/cirugía , Esófago/lesiones , Enfermedades del Esófago/cirugía , Rotura Espontánea/cirugía , Rotura Espontánea/diagnóstico , Rotura Espontánea/mortalidad , Vómitos/complicacionesRESUMEN
Our study was aimed to show if cadaver dissections are still important in the Anatomy Course for medical students or whether computerized resources could replace them. We followed three groups, one of them (698 students) proceeded through the Anatomy Course in a traditional way, meaning, with cadaver material enough to observe all the regions and structures; the second group (330 students) used many technological resources but not cadaver dissections; and the third group (145 students) followed the course, recently, with the same program but with both practical resources. Theoretical contents were developed in the same way and by the same professor. The traditional teaching group obtained better results than the technologically supported group, evaluated by the number of students that passed their exams. The third group results were better than the others, with regard to passed exams and marks. Even when computerized improvements have developed a new area giving students a lot of elements to facilitate their approach to imaging structures, the possibility of direct contact with tissues and anatomical elements cannot yet be replaced. We are demonstrating that the best possibility is the correct association of all these resources to complement one another.