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PURPOSE: Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by pathogenic variants of genes encoding the enzyme complex NADPH oxidase. In countries where tuberculosis (TB) is endemic and the Bacillus Calmette-Guérin (BCG) vaccine is routinely administered, mycobacteria are major disease-causing pathogens in CGD. However, information on the clinical evolution and treatment of mycobacterial diseases in patients with CGD is limited. The present study describes the adverse reactions to BCG and TB in Mexican patients with CGD. METHODS: Patients with CGD who were evaluated at the Immunodeficiency Laboratory of the National Institute of Pediatrics between 2013 and 2024 were included. Medical records were reviewed to determine the clinical course and treatment of adverse reactions to BCG and TB disease. RESULTS: A total of 79 patients with CGD were included in this study. Adverse reactions to BCG were reported in 55 (72%) of 76 patients who received the vaccine. Tuberculosis was diagnosed in 19 (24%) patients. Relapse was documented in three (10%) of 31 patients with BGC-osis and six (32%) of 19 patients with TB, despite antituberculosis treatment. There was no difference in the frequency of BCG and TB disease between patients with pathogenic variants of the X-linked CYBB gene versus recessive variants. CONCLUSIONS: This report highlights the importance of considering TB in endemic areas and BCG complications in children with CGD to enable appropriate diagnostic and therapeutic approaches to improve prognosis and reduce the risk of relapse.
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Vacina BCG , Doença Granulomatosa Crônica , NADPH Oxidase 2 , Tuberculose , Humanos , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/complicações , Vacina BCG/efeitos adversos , Masculino , Feminino , Criança , Tuberculose/epidemiologia , Tuberculose/imunologia , Pré-Escolar , Lactente , Adolescente , NADPH Oxidase 2/genética , Estudos de Coortes , Mycobacterium bovis , México/epidemiologia , Antituberculosos/uso terapêutico , NADPH Oxidases/genéticaRESUMO
Abstract The objective of this research is to present a comparative analysis using various lengths of time windows (TW) during emotion recognition, employing machine learning techniques and the portable wireless sensing device EPOC+. In this study, entropy will be utilized as a feature to evaluate the performance of different classifier models across various TW lengths, based on a dataset of EEG signals extracted from individuals during emotional stimulation. Two types of analyses were conducted: between-subjects and within-subjects. Performance measures such as accuracy, area under the curve, and Cohen's Kappa coefficient were compared among five supervised classifier models: K-Nearest Neighbors (KNN), Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF), and Decision Trees (DT). The results indicate that, in both analyses, all five models exhibit higher performance in TW ranging from 2 to 15 seconds, with the 10 seconds TW particularly standing out for between-subjects analysis and the 5-second TW for within-subjects; furthermore, TW exceeding 20 seconds are not recommended. These findings provide valuable guidance for selecting TW in EEG signal analysis when studying emotions.
Resumen El objetivo de esta investigación es presentar un análisis comparativo empleando diversas longitudes de ventanas de tiempo (VT) durante el reconocimiento de emociones, utilizando técnicas de aprendizaje automático y el dispositivo de sensado inalámbrico portátil EPOC+. En este estudio, se utilizará la entropía como característica para evaluar el rendimiento de diferentes modelos clasificadores en diferentes longitudes de VT, basándose en un conjunto de datos de señales EEG extraídas de individuos durante la estimulación de emociones. Se llevaron a cabo dos tipos de análisis: entre sujetos e intra-sujetos. Se compararon las medidas de rendimiento, tales como la exactitud, el área bajo la curva y el coeficiente de Cohen's Kappa, de cinco modelos clasificadores supervisados: K-Nearest Neighbors (KNN), Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF) y Decision Trees (DT). Los resultados indican que, en ambos análisis, los cinco modelos presentan un mayor rendimiento en VT de 2 a 15 segundos, destacándose especialmente la VT de 10 segundos para el análisis entre los sujetos y 5 segundos intrasujetos; además, no se recomienda utilizar VT superiores a 20 segundos. Estos hallazgos ofrecen una orientación valiosa para la elección de las VT en el análisis de señales EEG al estudiar las emociones.
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Abstract This systematic review aims to assess the extent to which biomedical engineering has been applied in the rehabilitation of patients suffering from Guillain-Barré Syndrome (GBS), given the scarcity of information on this topic. We conducted a thorough analysis of research articles, conference abstracts, and case reports published between 2000 and 2023, specifically from ScienceDirect, PubMed, IEEE Xplore, Springer, and Dimensions. 19 articles were extensively discussed, complemented by an additional 40 information sources providing supplementary information. Each paper underwent a meticulous review process by the four authors, where each separately examined the title and abstract of the papers and subsequently provided a thorough examination of the full text; when conflicts arose, a clear consensus was reached through discussion. The analysis of the articles revealed a notable improvement in upper and lower limb function of GBS patients that was facilitated by both custom-made and commercial devices. Likewise, a small handful of other devices have been used (e.g., to improve urinary retention issues). There is a clear opportunity for new research, innovation and applications.
Resumen Esta revisión sistemática tiene como objetivo evaluar hasta qué punto se ha aplicado la ingeniería biomédica en la rehabilitación de pacientes que padecen el Síndrome de Guillain-Barré (SGB), dada la escasez de información sobre este tema. Realizamos un análisis exhaustivo de artículos de investigación, resúmenes de conferencias e informes de casos publicados entre 2000 y 2023, específicamente de ScienceDirect, PubMed, IEEE Xplore, Springer y Dimensions. Se discutieron ampliamente 19 artículos, complementados con 40 fuentes de información adicionales. Cada artículo pasó por un meticuloso proceso de revisión por parte de los cuatro autores, donde cada uno examinó por separado el título y el resumen de los artículos y posteriormente proporcionó un examen exhaustivo del texto completo; cuando surgieron conflictos, se alcanzó un consenso mediante la discusión. El análisis de los artículos reveló una mejora notable en la función de las extremidades superiores e inferiores de los pacientes con SGB que fue facilitada por dispositivos tanto hechos a medida como comerciales. Asimismo, se han creado un pequeño puñado de otros dispositivos, (por ejemplo, para mejorar los problemas de retención urinaria). Existe una clara oportunidad para nueva investigación, innovación y aplicaciones.
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Genetic testing is crucial in inherited arrhythmogenic channelopathies; however, the clinical interpretation of genetic variants remains challenging. Incomplete penetrance, oligogenic, polygenic or multifactorial forms of channelopathies further complicate variant interpretation. We identified the KCNQ1/p.D446E variant in 2/63 patients with long QT syndrome, 30-fold more frequent than in public databases. We thus characterized the biophysical phenotypes of wildtype and mutant IKs co-expressing these alleles with the ß-subunit minK in HEK293 cells. KCNQ1 p.446E homozygosity significantly shifted IKs voltage dependence to hyperpolarizing potentials in basal conditions (gain of function) but failed to shift voltage dependence to hyperpolarizing potentials (loss of function) in the presence of 8Br-cAMP, a protein kinase A activator. Basal IKs activation kinetics did not differ among genotypes, but in response to 8Br-cAMP, IKs 446 E/E (homozygous) activation kinetics were slower at the most positive potentials. Protein modeling predicted a slower transition of the 446E Kv7.1 tetrameric channel to the stabilized open state. In conclusion, biophysical and modelling evidence shows that the KCNQ1 p.D446E variant has complex functional consequences including both gain and loss of function, suggesting a contribution to the pathogenesis of arrhythmogenic phenotypes as a functional risk allele.
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Arritmias Cardíacas , Canalopatias , Canal de Potássio KCNQ1 , Humanos , Alelos , Arritmias Cardíacas/genética , Proteínas Quinases Dependentes de AMP Cíclico , Células HEK293 , Canal de Potássio KCNQ1/genética , FenótipoRESUMO
BACKGROUND: Leukocyte adhesion deficiency type 1 (LAD-1) is an inborn error of immunity characterized by a defect in leukocyte trafficking. METHODS: Patients with clinical suspicion of LAD-1 were referred to our institution. Complete blood count and flow cytometric analysis, to identify the expression of CD18, CD11b, and the lymphocyte population phenotyping, were performed, and statistical analysis was completed. RESULTS: We report clinical manifestations and immunological findings of six Mexican patients diagnosed with LAD-1. The diagnosis was based on typical clinical presentation, combined with laboratory demonstration of leukocytosis, and significant reduction or near absence of CD18 and its associated molecules CD11a, CD11b, and CD11c on leukocytes. We found atypical manifestations, not described in other countries, such as early-onset autoimmunity or infections caused by certain microorganisms. CONCLUSIONS: Patients with LAD-1 may present with atypical manifestations, making flow cytometry an indispensable tool to confirm the diagnosis. We present the first report of LAD-1 patients in a Latin American country.
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Antígenos CD18 , Síndrome da Aderência Leucocítica Deficitária , Humanos , Antígenos CD18/metabolismo , México , Síndrome da Aderência Leucocítica Deficitária/diagnóstico , LeucócitosRESUMO
Background: Specific antibody deficiency (SAD) is an inborn error of immunity, in patients older than 2 years, characterized by normal immunoglobulin levels and IgG subclasses, but with recurrent infections and decreased antibody responses to polysaccharide antigens. Case report: A 10-year-old female, previously healthy, with no significant family history. She is known in this institution for symptoms of headache, vomiting and paresis. A CT scan of the skull was performed, where 4 brain abscesses, edema and displacement of the midline were observed, a right frontal trephine was performed and abscess drainage, antimicrobial management for infectology, blood cultures, Gram staining and cultures of negative drainage material. Assessed for allergy and immunology, for abscesses in deep focus, an approach was performed to rule out inborn error of immunity, immunoglobulins, isohemagglutinins, flow cytometry and response to normal protein antigens. Antibodies against post-vaccination polysaccharide antigens are requested, where a response to only 2 serotypes (18.1% response) is observed, with normal IgG subclasses, a diagnosis of specific antibody deficiency is integrated and management with immuno- globulin at replacement doses is started, as well as annual vaccination with 13 valent. Conclusion: SAD has been considered a problem that can be resolved over time, especially in children, but in others it can evolve into more severe forms of humoral immunodeficiency. Decisions to treat with prophylactic antibiotics and/or gamma globulin are guided by clinical judgment, small studies, and recent consensus documents, which may evolve over time.
Antecedentes: La deficiencia especifica de anticuerpos (SAD) es un error innato de la inmunidad, en pacientes de más de 2 años, caracterizada por niveles de inmunoglobulinas y subclases de IgG normales, pero con infecciones recurrentes y respuestas de anticuerpos disminuidas a antígenos polisacáridos. Reporte de caso: Femenina de 10 años, previa sana, sin antecedentes heredofamiliares de importancia. Conocida en esta institución por cuadro de cefalea, vómi- tos y paresias. Se realiza TAC de cráneo, donde se observan 4 abscesos cerebrales, edema y desplazamiento de la línea media, se realiza trepano frontal derecha y drenaje de abscesos, manejo antimicrobiano por infectología, hemocultivos, tinción de Gram y cultivos de material de drenaje negativos. Valorado por alergia e inmunología, por abscesos en foco profundo, se realizó abordaje para descartar error innato de la inmunidad, inmunoglobulinas, isohemaglutininas, citometría de flujo y respuesta a antígenos proteicos normales. Se solicitan anticuerpos contra antígenos polisacáridos post vacunación, donde se observa respuesta a solo 2 serotipos (respuesta del 18.1%), con subclases de IgG normales, se integra diagnóstico de deficiencia especifica de anticuerpos y se inicia manejo con inmuno- globulina a dosis de reemplazo, asi como vacunación anual con 13 valente. Conclusión: El SAD se ha considerado un problema que puede resolverse con el tiempo, especialmente en niños, pero en otros puede evolucionar hacia formas más severas de inmunodeficiencia humoral. Las decisiones de tratar con antibióticos profilácticos y/o gammaglobulina están guiadas por el juicio clínico, estudios pequeños y documentos de consenso recientes, que pueden evolucionar con el tiempo.
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Síndromes de Imunodeficiência , Doenças da Imunodeficiência Primária , Criança , Feminino , Humanos , Imunoglobulina G , Vacinação , Polissacarídeos , Anticorpos AntibacterianosRESUMO
Pregnant women with diabetes often present impaired fetal growth, which is less common if maternal diabetes is well-controlled. However, developing strategies to estimate fetal body composition beyond fetal growth that could better predict metabolic complications later in life is essential. This study aimed to evaluate subcutaneous fat tissue (femur and humerus) in fetuses with normal growth among pregnant women with well-controlled diabetes using a reproducible 3D-ultrasound tool and offline TUI (Tomographic Ultrasound Imaging) analysis. Additionally, three artificial intelligence classifier models were trained and validated to assess the clinical utility of the fetal subcutaneous fat measurement. A significantly larger subcutaneous fat area was found in three-femur and two-humerus selected segments of fetuses from women with diabetes compared to the healthy pregnant control group. The full classifier model that includes subcutaneous fat measure, gestational age, fetal weight, fetal abdominal circumference, maternal body mass index, and fetal weight percentile as variables, showed the best performance, with a detection rate of 70%, considering a false positive rate of 10%, and a positive predictive value of 82%. These findings provide valuable insights into the impact of maternal diabetes on fetal subcutaneous fat tissue as a variable independent of fetal growth.
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This paper proposes a deep learning model based on an artificial neural network with a single hidden layer for predicting the diagnosis of multiple sclerosis. The hidden layer includes a regularization term that prevents overfitting and reduces the model complexity. The purposed learning model achieved higher prediction accuracy and lower loss than four conventional machine learning techniques. A dimensionality reduction method was used to select the most relevant features from 74 gene expression profiles for training the learning models. The analysis of variance test was performed to identify the statistical difference between the mean of the proposed model and the compared classifiers. The experimental results show the effectiveness of the proposed artificial neural network.
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The identification of brain dynamical changes under different cognitive conditions with noninvasive techniques such as electroencephalography (EEG) is relevant for the understanding of their underlying neural mechanisms. The comprehension of these mechanisms has applications in the early diagnosis of neurological disorders and asynchronous brain computer interfaces. In both cases, there are no reported features that could describe intersubject and intra subject dynamics behavior accurately enough to be applied on a daily basis. The present work proposes the use of three nonlinear features (recurrence rate, determinism, and recurrence times) extracted from recurrence quantification analysis (RQA) to describe central and parietal EEG power series complexity in continuous alternating episodes of mental calculation and rest state. Our results demonstrate a consistent mean directional change of determinism, recurrence rate, and recurrence times between conditions. Increasing values of determinism and recurrence rate were present from the rest state to mental calculation, whereas recurrence times showed the opposite pattern. The analyzed features in the present study showed statistically significant changes between rest and mental calculation states in both individual and population analysis. In general, our study described mental calculation EEG power series as less complex systems in comparison to the rest state. Moreover, ANOVA showed stability of RQA features along time.
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Eletroencefalografia , Dinâmica não Linear , Eletroencefalografia/métodos , Encéfalo , DescansoRESUMO
Acid Sensing Ion Channels (ASIC) are proton sensors involved in several physiological and pathophysiological functions including synaptic plasticity, sensory systems and nociception. ASIC channels have been ubiquitously localized in neurons and play a role in their excitability. Information about ASIC channels in cardiomyocyte function is limited. Evidence indicates that ASIC subunits are expressed in both, plasma membrane and intracellular compartments of mammalian cardiomyocytes, suggesting unrevealing functions in the cardiomyocyte physiology. ASIC channels are expressed in neurons of the peripheral nervous system including the nodose and dorsal root ganglia (DRG), both innervating the heart, where they play a dual role as mechanosensors and chemosensors. In baroreceptor neurons from nodose ganglia, mechanosensation is directly associated with ASIC2a channels for detection of changes in arterial pressure. ASIC channels expressed in DRG neurons have several roles in the cardiovascular function. First, ASIC2a/3 channel has been proposed as the molecular sensor of cardiac ischemic pain for its pH range activation, kinetics and the sustained current. Second, ASIC1a seems to have a critical role in ischemia-induced injury. And third, ASIC1a, 2 and 3 are part of the metabolic component of the exercise pressure reflex (EPR). This review consists of a summary of several reports about the role of ASIC channels in the cardiovascular system and its innervation.