RESUMO
Diabetic Macular Edema (DME) is the most common sight-threatening complication of type 2 diabetes. Optical Coherence Tomography (OCT) is the most useful imaging technique to diagnose, follow up, and evaluate treatments for DME. However, OCT exam and devices are expensive and unavailable in all clinics in low- and middle-income countries. Our primary goal was therefore to develop an alternative method to OCT for DME diagnosis by introducing spectral information derived from spontaneous electroretinogram (ERG) signals as a single input or combined with fundus that is much more widespread. Baseline ERGs were recorded in 233 patients and transformed into scalograms and spectrograms via Wavelet and Fourier transforms, respectively. Using transfer learning, distinct Convolutional Neural Networks (CNN) were trained as classifiers for DME using OCT, scalogram, spectrogram, and eye fundus images. Input data were randomly split into training and test sets with a proportion of 80 %-20 %, respectively. The top performers for each input type were selected, OpticNet-71 for OCT, DenseNet-201 for eye fundus, and non-evoked ERG-derived scalograms, to generate a combined model by assigning different weights for each of the selected models. Model validation was performed using a dataset alien to the training phase of the models. None of the models powered by mock ERG-derived input performed well. In contrast, hybrid models showed better results, in particular, the model powered by eye fundus combined with mock ERG-derived information with a 91 % AUC and 86 % F1-score, and the model powered by OCT and mock ERG-derived scalogram images with a 93 % AUC and 89 % F1-score. These data show that the spontaneous ERG-derived input adds predictive value to the fundus- and OCT-based models to diagnose DME, except for the sensitivity of the OCT model which remains the same. The inclusion of mock ERG signals, which have recently been shown to take only 5 min to record in daylight conditions, therefore represents a potential improvement over existing OCT-based models, as well as a reliable and cost-effective alternative when combined with the fundus, especially in underserved areas, to predict DME.
Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Edema Macular , Humanos , Edema Macular/diagnóstico por imagem , Retinopatia Diabética/diagnóstico por imagem , Diabetes Mellitus Tipo 2/complicações , Fundo de Olho , Tomografia de Coerência Óptica/métodosRESUMO
Background: Pterin profiles or molecular analyses of hyperphenylalaninemia (HPA) caused by phenylalanine hydroxylase (PAH) deficiency or tetrahydrobiopterin deficiency (BH4D) are not always available in low- or middle-income countries, including Mexico, limiting information regarding the phenotypic and genotypic characteristics of patients exhibiting BH4D. Objective: To report the genotypes underlying BH4D and the clinical presentation in unrelated Mexican HPA pediatric patients with normal PAH genotypes who attended a single metabolic reference center in Mexico. Methods: Automated Sanger sequencing of the PTS, QDPR, and PCBD1 genes of 14 HPA patients was performed. Predicted effects on protein structure caused by missense variants were assessed by in silico protein modeling. Results and discussion: A high prevalence of BH4D was noted in our HPA cohort (9.8%, N = 14/142). Clinically relevant biallelic genotypes were identified in the PTS (N = 7/14 patients), QDPR (N = 6/14 patients), and PCBD1 (N = 1/14 patients) genes. Four novel QDPR variants [c.714dup or p.(Leu239Thrfs*44), c.106-1G>T or p.(?), c.214G>T or p.(Gly72*), and c.187_189dup or p.(Gln63dup)] were identified. In silico protein modeling of six missense variants of PTS [p.(Thr67Met), p.(Glu81Ala), and p.(Tyr113Cys)], QDPR [p.(Cys161Phe) and p.(Pro172Leu)], and PCBD1 [p.(Glu97Lys)] supports their pathogenicity. Progressive neurological symptoms (mainly intellectual and motor impairment and even death in three patients) were noted in all patients with biallelic QDPR genotypes and in 5/7 patients bearing biallelic PTS genotypes. The single homozygous PCBD1 p.(Glu97Lys) patient remains asymptomatic. Conclusion: A higher proportion of BH4D (9.8 vs. 1%-2% worldwide), attributable to a heterogeneous mutational spectrum and wide clinical presentation, was noted in our Mexican HPA cohort, with the PTS-related HPA disorder being the most frequent. Sequencing-based assays could be a reliable approach for diagnosing BH4D in our population.
Assuntos
Autoanticorpos/sangue , Membrana Basal Glomerular , Imunoglobulina G/sangue , Cadeias lambda de Imunoglobulina/sangue , Nefropatias , Paraproteinemias , Idoso , Feminino , Membrana Basal Glomerular/metabolismo , Membrana Basal Glomerular/patologia , Humanos , Nefropatias/sangue , Nefropatias/diagnóstico , Nefropatias/patologia , Nefropatias/terapia , Paraproteinemias/sangue , Paraproteinemias/diagnóstico , Paraproteinemias/patologia , Paraproteinemias/terapiaRESUMO
Background: Occlusal relationships in the primary dentition play an important role in the consequential final occlusion in permanent dentition. Therefore, good knowledge of occlusal relationships in children is essential for dental practitioners. Design: A descriptive, cross-sectional study done in randomly selected kindergartens in Khartoum State to determine the occlusal characteristics of primary dentition in a group of Sudanese children. Objective: To determine the occlusal characteristics feature of primary dentition in a group of Sudanese children. Methods: A sample of 381 children age 3-5 years old, randomly selected from kindergartens in Khartoum Stat. Clinical examination was done to all children fulfil the inclusion criteria in the teacher office and in natural day light. Prevalence of different types of terminal plane, types of primary canine relationship and spacing of the primary dentition were assessed. Results: Flush terminal plane was the most prevalent type of terminal plane (72.2%). Class I canine relationship was the most common type of primary canine relationships (95%). In the upper arch primate space and physiological spaces were present in 90.3% and 82.4% of the children, respectively. Nevertheless, the lower arch showed primate spaces in 70.1% and physiological spaces in 74.8% of the children. Conclusion: Large number of the examined children had flush terminal plane and spacing primary dentition that forecasts development of normal occlusion in their permanent dentition
Introdução: As relações oclusais na dentição decídua desempenham um papel importante na oclusão final, na dentição permanente. Portanto, um bom conhecimento das relações oclusais em crianças é essencial para os cirurgiões-dentistas. Foi realizado um estudo descritivo , transversal, em creches selecionadas aleatoriamente no estado de Khartoum (Sudão) para determinar as características oclusais de dentição decídua em um grupo de crianças sudanesas. Objetivo: Determinar as características oclusais de dentição decídua em um grupo de crianças sudanesas. Métodos: Uma amostra de 381 crianças com idade entre 3 e 5 anos foram selecionados aleatoriamente a partir creches no estado de Khartoum. O exame clínico foi feito em todas as crianças cumpriram os critérios de inclusão, na sala dos professores sob luz natural do dia. Foram avaliadas a prevalência dos diferentes tipos de plano terminal, tipos de relação canina e espaçamento da dentição decídua. Resultados: O plano terminal em topo foi o tipo mais prevalente de plano terminal (72,2%) . A relação canina de Classe I foi o tipo mais comum de relacionamentos nos caninos decíduos (95 %). Os espaços primatas e fisiológicas nos arcos superiores estavam presentes em 90,3% e 82,4 % das crianças , respectivamente. No entanto, os arcos inferiores mostraram espaços primatas em 70,1% e espaços fisiológicos em 74,8% das crianças. Conclusão: Grande número de crianças examinadas tinham plano terminal em topo e espaçamento dentição decídua, o que pode predizer um desenvolvimento da oclusão normal na sua dentição permanente.
Assuntos
Humanos , Criança , Oclusão Dentária , DentiçãoAssuntos
Anomuros , Aquicultura/métodos , Penaeidae/enzimologia , Penaeidae/fisiologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/metabolismo , Trato Gastrointestinal/enzimologia , Regulação da Expressão Gênica , México , Análise de Sequência com Séries de Oligonucleotídeos/veterinária , Penaeidae/genética , Penaeidae/crescimento & desenvolvimento , Reação em Cadeia da Polimerase/veterináriaRESUMO
BACKGROUND: Several studies have shown the participation of MMPs in oral squamous cell carcinoma, the most frequent malignant neoplasm of the oral cavity. The expression of some MMPs correlates with a more aggressive biological behaviour. The objective of this study was to determine which MMPs and TIMPs were expressed in both neoplastic and peritumoural stromal cells in different histopathology areas. METHODS: Patients who underwent primary tumour neck dissection for oral squamous cell carcinoma were included. Immunoexpression of MMP-1, -2, -3, -7, -9, -11, -13, and TIMP-1 and -2 in different areas of pathologic specimens (in situ carcinoma, primary tumour, invasive front, distant invasion carcinoma, and lymph node metastasis) was evaluated. Enzyme expression on mucosa adjacent to tumour served as control. RESULTS: Thirty cases were included. Only 6 MMPs and 1 TIMP were expressed in the studied areas. Statistically significant differences in the number of cases with positive MMPs or TIMP expression, in both neoplastic and peritumoural cells, between control and the rest of the areas were observed. MMP-2 expression was constant in the areas with a more aggressive biological behaviour. CONCLUSIONS: MMP-2 expression may represent a dynamic interaction between host and tumour that favours the establishment of neoplastic cells at distant sites.
Assuntos
Carcinoma de Células Escamosas/enzimologia , Metaloproteinases da Matriz/metabolismo , Neoplasias Bucais/enzimologia , Células-Tronco Neoplásicas/enzimologia , Inibidores Teciduais de Metaloproteinases/metabolismo , Idoso , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , PrognósticoRESUMO
Metastases from infraclavicular neoplasms to the oral cavity are rare, and the anatomical structures most frequently affected are the maxillae. The primary sites that develop metastases to head and neck include lung, breast, liver, thyroid gland, kidney and melanomas, among others. The breast is one of the usual primary regions that can present them. In the literature, most metastases to these regions correspond to squamous cell carcinomas and adenocarcinomas; few studies report other type of neoplasms such as phyllodes tumour (PT) that present this behaviour. The importance of identifying metastatic disease to the oral cavity, be it as the first manifestation of a neoplasm from unknown origin or as a development in the course of the disease, is that it allows determination of adequate treatment, which has an effect on the patient's prognosis. The usual behaviour of PT is frequent recurrence and, when metastases are present, these are to lungs and bone. Two cases of malignant PT metastasising to tongue and lip are presented, as well as a review of the literature.
Assuntos
Neoplasias da Mama , Neoplasias Labiais/secundário , Tumor Filoide , Neoplasias da Língua/secundário , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Lábio/patologia , Neoplasias Labiais/diagnóstico , Neoplasias Labiais/mortalidade , Neoplasias Labiais/patologia , Mastectomia Radical Modificada , Mastectomia Segmentar , Pessoa de Meia-Idade , Metástase Neoplásica , Tumor Filoide/diagnóstico , Tumor Filoide/tratamento farmacológico , Tumor Filoide/mortalidade , Tumor Filoide/patologia , Tumor Filoide/secundário , Tumor Filoide/cirurgia , Língua/patologia , Neoplasias da Língua/diagnóstico , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologiaRESUMO
We study the transient regime of type-II biophysical neuron models and determine the scaling behavior of relaxation times tau near but below the repetitive firing critical current, tau approximately or equal to C(I(c)-I)(-Delta). For both the Hodgkin-Huxley and Morris-Lecar models we find that the critical exponent is independent of the numerical integration time step and that both systems belong to the same universality class, with Delta=1/2. For appropriately chosen parameters, the FitzHugh-Nagumo model presents the same generic transient behavior, but the critical region is significantly smaller. We propose an experiment that may reveal nontrivial critical exponents in the squid axon.
Assuntos
Potenciais de Ação/fisiologia , Relógios Biológicos/fisiologia , Limiar Diferencial/fisiologia , Modelos Neurológicos , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Adaptação Fisiológica/fisiologia , Animais , Axônios/fisiologia , Simulação por Computador , Decapodiformes , Fatores de TempoRESUMO
The ras gene family (H, K and N-ras) encodes the Ras protein, a GTPase-activating protein that regulates several signal transduction pathways including cellular proliferation and differentiation. Mutations in codons 12, 13 and 61 of the ras genes constitute one of the most frequent alterations in human cancer. In the Western Hemisphere, a low frequency of mutations in these genes has been observed in head and neck carcinomas; a higher frequency has been found in countries such as India and Taiwan. Increased protein expression is a relatively frequent event in larynx carcinomas. This study was aimed to evaluate the participation of the k-ras gene and Ras expression in 20 Mexican patients with larynx squamous carcinoma, 2 with dysplasia and 4 with normal mucosa. Samples (of 26 patients) were embedded in paraffin and immunohistochemical analysis was performed for the Ras protein, as well as amplification of the k-ras gene exon 1 (108 bp) by laser capture microdissection. Then, DNA extraction, PCR and sequencing were performed looking for possible mutation in codons 12 and 13. All patients with larynx carcinoma were men, median age 62 years. Eighty-five percent of the patients had risk factors such as smoking and/or alcohol consumption, 25% were in clinical stages I and II, and 75% in stages III and IV; 45% of the patients presented tumor recurrence or persistence. In this study, no mutations were found in codons 12 or 13 of the k-ras gene; however, protein expression was observed in 95% of the samples and a higher expression of the protein was associated with tumor recurrence or persistence, although this was not statistically significant. Unexpectedly, well-differentiated carcinomas and dysplasias presented an increase in protein expression. These results suggest that ras may be involved in early stages of larynx carcinogenesis and may be activated by other mechanisms different from mutations, such as epigenetic events.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Análise Mutacional de DNA , Genes ras , Neoplasias Laríngeas/metabolismo , Proteína Oncogênica p21(ras)/metabolismo , Proteínas ras/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/genética , Epigênese Genética , Feminino , Humanos , Neoplasias Laríngeas/genética , Masculino , Pessoa de Meia-Idade , Proteína Oncogênica p21(ras)/genética , Transdução de SinaisRESUMO
La enfermedad coronaria es una de las primeras causas de morbilidad y mortalidad cardiovascular. Para su prevención es necesario diagnosticar y corregir con medidas farmacológicas y no farmacológicas los factores de riesgo cardivascular modificables. Nosotros hemos desarrollado un programa de diagnóstico precoz y tratamiento de factores que incrementan a desarrollar enfermedades cardiovasculares y metabólicas, en sujetos "sanos", asintomáticos. Hasta el presente hemos evaluado 153 sujetos. En este trabajo evaluamos la asociación a la sensibilidad a la sal con otros factores de riesgo cardiovascular silente e investigamos los posibles factores predictores de sensibilidad a la sal. La comparación de los sujetos sensibles a la sal (SS), con los sujetos sal resistentes (SR) demostró que los sujetos SS tienen mayor edad, peso corporal, cifras tensionales, niveles elevados de triglicéridos, niveles bajos de HDL-colesterol y de actividad físico. Adicionalmente estudiamos el papel de la hiperinsulinemia y de la hiperglicemia en la sensibilidad a la sal, a través de la medición de la incidencia (porcentaje de individuos SS y SR) y severidad de la sensibilidad a la sal en sujetos hiperinsulinémicos e intolerantes glucosados y/o diabéticos comparándolos con su respectivos controles. No hubo diferencias en la distribución de sensibilidad a la sal entre los diferentes grupos (hiper y normo insulinémicos (insulina en ayunas < 15uUL/ml), glucotolerantes (glicemia en ayunas <110;2 horas post carga < 140 mg/d) y en los intolerantes glucosados y/o diabéticos. La severidad de la sensibilidad a la sal también fue similar entre grupos, de hecho, la reducción de la ingesta de sal de 316ñ13 a 26ñ3 mmol/día, produjo cambios similares en la presión arterial en sujetos hiperinsulinémicos o en sujetos con niveles normoinsulinémicos y en sujetos tolerantes e intolerantes glucosados y/o diabéticos. Adicionalmente no se encontró correlación entre la magnitud de los cambios de la presión arterial inducidos por la sal y los niveles de insulina y glucosa en ayunas, 2 horas después de la carga oral de glucosa o el área bajo la curva de insulina. En conclusión, nuestros resultados sugieren los niveles de glicemia y de insulina del paciente, no determinan su reactividad vascular a los cambios en ingesta de sal
Assuntos
Humanos , Doenças Cardiovasculares , Doença das Coronárias , Hiperinsulinismo , Doenças Metabólicas , Fatores de Risco , VenezuelaRESUMO
El aceite de oliva ha sido utilizado desde tiempos inmemoriales como agente cicatrizante. La separación química de sus constituyentes nos ha permitido aislar una fracción que hemos denominado FG-30, con potente efecto cicatrizante que en el presente estudio fue comparado con la Sulfadiacina de plata con respecto a la evolución y el porcentaje de disminución del área de quemadura de tercer grado en ratas. Para ello se estudiaron 22 ratas Sprague-Dawley, con pesos entre 225-250 g. con quemaduras de tercer grado, las cuales fueron divididas en tres grupos, uno control, sin tratamiento; uno experimental que recibió tratamiento tópico con FG-30, y otro experimental que recibió tratamiento tópico con Sulfadiacina. A los tres grupos se le midió el área de quemadura los días 1, 10, 20 y 35 luego de iniciado el tratamiento, además se procedió a la observación de los cambios macroscópicos de la lesión y comportamiento de las ratas. El tratamiento con FG-30 y con sulfadiacina produjo una mejoría significativa en el porcentaje de disminución del área de la quemadura a los 20 y 35 días. En cuanto a la observación clínica del grupo FG-30 se apreció poca secreción, costra hipotrófica y uniforme así como analgesia; el grupo Sulfadiacina presentó abundante secreción, costra hipertrófica, deforme, fétida, blanquecina, y dolor durante 35 días, todo esto comparado con el grupo control que no recibió ningún tipo de tratamiento. Las mejorías producidas por el FG-30 con respecto al porcentaje de disminución de la quemadura y la observación macroscópica, lo ubica como una alternativa potencial como cicatrizante en quemadura
Assuntos
Animais , Queimaduras , Óleos de Plantas , Sulfadiazina de Prata , Cicatrização , Endocrinologia , VenezuelaRESUMO
To assess the immunogenic and immunoprotective role of the extracellular lectin from Aeromonas veronii (MCBP), which has affinity for mucosal constituents such as mucin, lactoferrin, immunoglobulins and collagen, spotted sand bass (Paralabrax maculatofasciatus) were orally immunised either with soluble MCBP, adjuvant-conjugated MCBP or immobilised MCBP on latex microspheres. The results suggest that the MCBP is capable of eliciting protective immunity against A. veronii infections when administered orally. The highest mucosal immune response was elicited in fish immunised with MCBP covalently linked to cholera toxin B subunit (CTB) or to Escherichia coli heat-labile toxin (hLT). MCBP-CTB was found to elicit immunoprotection against a challenge with live Aeromonas cells with a relative percent survival of almost 70% and without the expression of the severe histopathological alterations induced by A. veronii.