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Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by leukocytosis and left shift. The primary molecular alteration is the BCR::ABL1, chimeric oncoprotein with tyrosine kinase activity, responsible for the initial oncogenesis of the disease. Therapy of CML was revolutionized with the advent of tyrosine kinase inhibitors, but it is still not considered curative and may present resistance and serious adverse effects. Discoveries in CML inaugurated a new era in cancer treatment and despite all the advances, a new biomarker is needed to detect resistance and adverse effects. Circular RNAs (circRNAs) are a special type of non-coding RNA formed through a process called backsplicing. The majority of circRNAs are derived from protein-coding genes. CircHIPK3 is formed from the second exon of the HIPK3 gene and has been found in various pathologies, including different types of cancer. New approaches have demonstrated the potential of circular RNAs in cancer research, and circHIPK3 has shown promising results. It is often associated with cellular regulatory pathways, suggesting an important role in the molecular dynamics of tumors. The identification of biomarkers is an important tool for therapeutic improvement; thus we review the role of circHIPK3 and its potential as a biomarker in CML.
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Generating pairs of Raman beams for gravimetry with fiber phase modulators is quite convenient but generates additional frequencies that must be filtered. The frequency filtering could be achieved by using a long (dispersive) birefringent calcite crystal followed by a polarizer that blocks the transmission of certain laser frequencies, as has been shown before. Here, we present a method to tune such a filter to the desired frequency position. The correction signal for the feedback is obtained by comparing (subtracting) the transmission through the filter when sending light that has been phase modulated or not, taking advantage of the fiber modulator that is already installed in the system. The method allows for continuously alternating between using the modulator for monitoring the filter position and other uses, an important characteristic for the operation of a complete gravimetric sequence.
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BACKGROUND: Critical limb ischemia represents an advanced stage of peripheral arterial disease. Angioplasty improves blood flow to the limb; however, some patients progress irreversibly to lower limb amputation. Few studies have explored the predictive potential of biomarkers during postangioplasty outcomes. AIM: To evaluate the behavior of endothelial progenitor cells in patients with critical limb ischemia, in relation to their postangioplasty outcome. METHODS: Twenty patients with critical limb ischemia, candidates for angioplasty, were enrolled. Flow-mediated dilation, as well as endothelial progenitor cells (subpopulations CD45+/CD34+/CD133+/CD184+ and CD45+/CD/34+/KDR[VEGFR-2]+ estimated by flow cytometry) from blood flow close to vascular damage, were evaluated before and after angioplasty. Association with lower limb amputation during a 30-day follow-up was analyzed. RESULTS: Endothelial progenitor cells were related with flow-mediated dilation. A higher number of baseline EPCs CD45+CD34+KDR+, as well as an impaired reactivity of endothelial progenitor cells CD45+CD34+CD133+CD184+ after angioplasty, were observed in cases further undergoing major limb amputation, with a significant discrimination ability and risk (0.75, specificity 0.83 and RR 4.5 p < 0.05). CONCLUSIONS: Endothelial progenitor cells were related with endothelial dysfunction, whereas a higher baseline number of the subpopulation CD45+CD34+KDR+, as well as an impaired reactivity of subpopulation CD45+CD34+CD133+CD184+ after angioplasty, showed a predictive ability for major limb amputation in patients with critical limb ischemia.
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Células Progenitoras Endoteliais , Humanos , Isquemia Crônica Crítica de Membro , Antígenos CD34 , Angioplastia , Amputação CirúrgicaRESUMO
Background: The metabolic syndrome (MS) is associated with an increased production of nitrogen metabolites and elevated oxidative stress, which favors progression of nonalcoholic fatty liver disease (NAFLD). Subjects with the phenotype known as metabolically unhealthy obese (MUO) meet most of the MS cardiometabolic risk criteria and show a higher risk of advanced NAFLD severity, compared with the so-widely known metabolically healthy obese (MHO). Obese individuals with MS are more susceptible to abnormal lipid accumulation in different tissues, whereas oxidative stress and nitrogen metabolites are increased in MS and/or obesity. This study aimed to explore whether plasma- or liver tissue-determined biomarkers of nitrogen metabolism and oxidative stress relate to NAFLD severity and/or metabolic phenotype. Methods: This cross-sectional study included candidates for bariatric surgery with biopsy-proven NAFLD diagnosis and staging. For comparison, the study population was divided according to NAFLD damage (steatohepatitis F0-F1 vs. steatohepatitis F2-F4) and metabolic phenotype (MHO vs MUO, based on the MS criteria). Hepatic and plasma concentrations of nitrogen metabolites and oxidative stress biomarkers were determined by enzymatic kinetics assays, enzyme-linked immunosorbent assay, and Greiss reaction. Results: The study population (N = 45) was constituted by patients with obesity and higher prevalence of dyslipidemia, diabetes mellitus, and hypertension. According to plasma biomarkers, MUO phenotype was related to higher cardiometabolic risk; meanwhile, advanced NAFLD damage was related to higher glycated hemoglobin (HbA1c) and triglycerides. Elevated hepatic concentrations of ammonium, nitrites, arginine, and citrulline were found in MUO phenotype, but only higher plasma concentration of malondialdehyde was found as specifically related to advanced NAFLD damage. Conclusions: Circulating biomarkers of redox state were selectively related to advanced NAFLD damage, suggesting prognostic and therapeutic targets. Hepatic concentrations of nitrogen metabolism biomarkers may be more related to cardiometabolic risk.
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Hipertensão , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Estudos Transversais , Obesidade/epidemiologia , Biomarcadores , Hipertensão/complicações , Oxirredução , Estresse OxidativoRESUMO
SUMMARY: The present research corresponds to a cross-sectional descriptive study in the anthropometric field, which allows coaches to develop standards to identify talent and optimize training in the discipline of beach volleyball. Its objective was to define the anthropometric profile and body composition of the Mexican Olympic beach volleyball teams in both sexes. The participants were couples one and two of Mexico in both sexes (defined by FIVB ranking), 4 women and 4 men with average age of 30.25±6.85 and 27.25±7.36 years. The technique used was Heath-Carter´s somatotype method and the anthropometric profile restricted ISAK protocol. Among the findings resulting from the research, unification can be observed in the male morphological characteristics (triceps skinfold, front thigh skinfold, calf skinfold, circumference of relaxed and contracted arm, waist, hip, femur diameter and BMI), as for the somatotype, both sexes of Mexican couples are positioned in mesomorphs-balanced. In relation to other studies consulted, balance in somatotype and muscular development is observed with high performance teams. Weight and height, as well as age, are important variables for the selection of talent and future optimal performance in world and professional volleyball.
La presente investigación corresponde a un estudio descriptivo transversal en el campo antropométrico, que permite a los entrenadores desarrollar estándares para identificar talentos y optimizar el entrenamiento en la disciplina de voleibol de playa. Su objetivo fue definir el perfil antropométrico y la composición corporal de las selecciones olímpicas mexicanas de voleibol de playa en ambos géneros. Los participantes fueron las parejas uno y dos de México en ambos géneros (definidos por ranking Fédération Internationale de Volleyball), 4 mujeres y 4 hombres con edad promedio de 30.25±6.85 y 27.25±7.36 años. La técnica utilizada fue el método del somatotipo de Heath-Carter y el protoolo ISAK del perfil antropométrico restringido. Entre los hallazgos resultantes de la investigación, se puede observar una unificación en las carácteristicas morfológicas masculinas (pliegue cuatáneotricipital, pliegue cutáneo anterior del muslo, pliegue citáneo de la pantorrila, circunferencia del brazo relajado y contraído, cintura, cadera, diámetro del fémur e IMC), en cuanto al somatotipo, ambos sexos de las parejas mexicanas se posicionan en mesomorfos-equilibrados. En relación a otros estudios consultados, se observa equilibrio en somatotipo y desarrollo muscular con equipos de alto rendimiento. El peso y la altura, así como la edad, son variables importantes para la selección del talento y en el futuro desempeño óptimo en el voleibol mundial y profesional.
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Humanos , Masculino , Feminino , Adulto , Composição Corporal , Antropometria , Voleibol , Somatotipos , Estudos Transversais , MéxicoAssuntos
Anafilaxia , Dermatologia , Humanos , Dermatologistas , Estudos Transversais , Porto Rico , Inquéritos e QuestionáriosRESUMO
Abstract This paper aims to introduce an innovative approach to semantic segmentation by leveraging a convolutional neural network (CNN) for predicting the shape and pose parameters of the left ventricle (LV). Our approach involves a modified U-Net architecture with a regression layer as the final stage, as opposed to the traditional classification layer. This modification allows us to predict all the shape and pose parameters of a statistical shape model, including rotation, translation, scale, and deformation. The adapted U-Net is trained using data from a point distribution model (PDM) of the LV. The experimental results demonstrate a mean Dice coefficient of 0.82 on good quality images, and 0.66 including mean and low-quality images. Our approach successfully overcomes a common issue encountered in CNN-based semantic segmentation. Unlike the inaccurate pixel classification that often leads to unwanted blobs, our CNN generates statistically valid shapes. These shapes hold significant potential in initializing other methods, such as active shape models (ASMs). Our novel CNN-based approach provides a novel solution for semantic segmentation, offering shapes and pose parameters that can enhance the accuracy and reliability of subsequent medical image analysis methods.
Resumen Este artículo tiene como objetivo introducir un enfoque innovador para la segmentación semántica utilizando una red neuronal convolucional (CNN) para predecir los parámetros de forma y posición del ventrículo izquierdo (VI). Nuestro enfoque implica una arquitectura U-Net modificada con una capa de regresión como etapa final, en contraposición a la capa de clasificación tradicional. Esta modificación nos permite predecir todos los parámetros de un modelo estadístico de formas que incluyen rotación, traslación, escala y deformación. La red convolucional se entrena utilizando datos de un modelo de distribución de puntos (PDM) del VI. Los resultados experimentales muestran un coeficiente Dice promedio de 0.82 para imágenes de buena calidad y de 0.66 cuando se incluyen imágenes de calidad media y baja. Nuestro enfoque supera con éxito un problema común en la segmentación semántica basada en CNNs. A diferencia de la clasificación inexacta de píxeles que a menudo conduce a elementos no deseados (blobs), nuestra CNN genera formas estadísticamente válidas. Estas formas tienen un gran potencial para inicializar otros métodos, como los modelos de forma activa (ASMs). En resumen, nuestro enfoque basado en CNN proporciona una solución innovadora para la segmentación semántica, ofreciendo formas y parámetros de posición que pueden mejorar la precisión y confiabilidad de otros métodos de análisis del VI.
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OBJECTIVES: To determine whether metabolic phenotype is associated with the change in carotid intima-media thickness (CIMT) in patients undergoing bariatric /metabolic surgery (BMS). METHODS: We performed a case-control study of BMS candidates who had metabolically unhealthy obesity (MUO) or metabolically healthy obesity (MHO). We measured the change in CIMT during the 9 months following BMS. The plasma tumor necrosis factor-α, interleukin-1ß, adiponectin, leptin, nitric oxide (NO), vascular endothelial growth factor A (VEGF-A), and malondialdehyde concentrations were determined, adipocyte area was measured histologically, and adipose tissue area was estimated using computed tomography. RESULTS: Fifty-six patients (mean age 44.5 years, mean body mass index 44.9 kg/m2, 53% women, and 53% had MUO) were studied. Nine months following BMS, the MUO phenotype was not associated with a significant reduction in CIMT, and that of the MHO group was larger. In addition, fewer participants achieved a 10% reduction in CIMT in the MUO group. A CIMT reduction was associated with lower VEGF-A and NO in the MUO group, while that in the MHO group was associated with a higher NO concentration. CONCLUSION: The metabolic phenotype of patients may influence their change in CIMT following BMS, probably through circulating vasodilatory and pro-inflammatory molecules.
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Cirurgia Bariátrica , Obesidade Metabolicamente Benigna , Feminino , Masculino , Humanos , Espessura Intima-Media Carotídea , Fator A de Crescimento do Endotélio Vascular , Estudos de Casos e Controles , Fatores de Risco , Obesidade Metabolicamente Benigna/metabolismo , Obesidade/metabolismoRESUMO
In a context of economic, political and humanitarian crisis, ensuring effective type 2 diabetes self-care management services in Venezuela has been an ongoing public health challenge. Repeated shortfalls in access to medicine, healthcare workers and food scarcity have hampered the ability of patients with diabetes to effectively manage their condition and receive the healthcare support that they deserve. With respect to methodology, the author relied on qualitative research methods, with a focus on in-depth document analysis. Primary and secondary document data sources were used through a systematic key word search in online search engines and library databases. While one may attribute these challenges in Venezuela to ongoing economic, political and humanitarian crisis, this article combines this perspective with health systems and institutional challenges that appear to have perpetuated and in fact worsened Venezuela's diabetic situation. Specifically, a weakened healthcare system, fragmentation in diabetic primary care services and corruption in a context of ongoing humanitarian crisis have contributed to these ongoing challenges. Within humanitarian and political crisis conditions, future research on type 2 diabetic treatment and self-care management may benefit from combining perspectives in political science institutional theory and public health systems analysis to explain why governments in these settings continue to fall short of providing effective and equitable diabetic care.
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Diabetes Mellitus Tipo 2 , Atenção à Saúde , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Humanos , Políticas , Política , Venezuela/epidemiologiaRESUMO
ABSTRACTAddressing the politics of corporate political activity and policy interference in response to non-communicable diseases (NCDs) is a new area of scholarly research. The objective of this article is to explain how, in Mexico and Brazil, the ultra-processed foods and beverages industry succeeded in creating the political and social conditions conducive for their on-going regulatory policy influence and manipulation of scientific research. In addition to establishing partnerships within and outside of government, industry representatives have succeeded in hampering civic opposition by establishing allies within academia and society. Ministries of Health have simultaneously neglected to work closely with civil society, while legislative representatives have continued to benefit from industry campaign contributions. Findings from this article suggest that ultra-processed foods and beverages industries wield on-going regulatory policy influence in Mexico and Brazil, and that government is still not fully committed to working with civil society on these issues.
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Países em Desenvolvimento , Política , Bebidas , Brasil , Política de Saúde , Humanos , MéxicoRESUMO
BACKGROUND: Albumin, along with other proteins, is abnormally eliminated via the urine during early stages of diabetic nephropathy. Moreover, endothelial dysfunction (ED) accompanying early diabetic nephropathy may develop even before microalbuminuria is detectable. Transferrin has a molecular weight comparable to albumin, whereas transferrinuria and microalbuminuria in a 24-h urine sample may comparably reflect early diabetic nephropathy. Whereas transferrin metabolism is related with ED during very early diabetic nephropathy has not been elucidated yet. This case-control study aimed to evaluate the relation between ED and urine transferrin, even before early diabetic nephropathy is present. METHODS: Patients were enrolled from two study sites in Mexico City: Ticomán General Hospital (healthy controls); and a Specialized Clinic for the Management of the Diabetic Patient (cases). All patients provided written informed consent. The primary endpoint was the correlation between urinary transferrin concentration and ED measured in type 2 diabetic patients without albuminuria. ED was evaluated by ultrasonographic validated measurements, which included carotid intima-media thickness (CIMT) and flow mediated dilation (FMD). Plasma biomarkers included glycated hemoglobin, creatinine, cholesterol and triglycerides, as well as urine albumin, transferrin and evidence of urinary tract infection. RESULTS: Sixty patients with type 2 Diabetes Mellitus (t2DM; n = 30) or without t2DM (n = 30), both negative for microalbuminuria, were recruited. The group with t2DM were older, with higher values of HbA1c and higher ED. This group also showed significant differences in urine transferrin and urine/plasma transferrin ratio, as compared with healthy controls (14.4 vs. 18.7 mg/mL, p = 0.04, and 74.2 vs. 49.5; p = 0.01; respectively). Moreover, urine transferrin correlated with higher CIMT values (r = 0.37, p = 0.04), being particularly significant for t2DM population. CIMT also correlated with time from t2DM diagnosis (r = 0.48, p < 0.001) and HbA1c (r = 0.48; p < 0.001). CONCLUSION: Urine transferrin correlated with subclinical atherogenesis in patients with t2DM without renal failure, suggesting its potential to identify cardiovascular risk in patients at very early nephropathy stage without microalbuminuria.
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Compound heterozygous mutations, where two distinct mutated alleles are present within a particular gene, can give rise to the Bardet-Biedl syndrome (BBS). There is limited evidence suggesting that some compound heterozygotes can present with milder phenotypic characteristics than homozygotes. We report on the clinical characteristics of a 22-year-old Puerto Rican male who was compound heterozygous for the Bardet-Biedl syndrome type 1. Our patient had deteriorating visual acuity since early childhood. Clinical and ophthalmic examination revealed retinal dystrophy, polydactyly, and very mild learning disabilities. No additional systemic complications commonly observed in patients with the BBS were present. Allele-specific testing and DNA sequencing revealed compound heterozygous mutations (M390R and E549X) in the BBS1 gene. Our findings could suggest that patients who are compound heterozygotes for these specific BBS mutations can exhibit milder clinical signs than homozygous patients.
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Síndrome de Bardet-Biedl/genética , Síndrome de Bardet-Biedl/diagnóstico , Análise Mutacional de DNA , Humanos , Masculino , Proteínas Associadas aos Microtúbulos/genética , Mutação , Adulto JovemRESUMO
OBJECTIVE: This study aims to describe the frequency of biologic therapy failure in psoriasis patients along with associated patient demographics and characteristics. METHODS: This was a retrospective medical-record review of psoriasis patients evaluated from January 1st, 2013, through May 1st, 2018, and who failed at least once to adhere to their biologic therapy. RESULTS: Seventy-seven patients with psoriasis who had discontinued biologic therapy at least once were included in this study. Hypertension (58.4%), diabetes (37.7%), dyslipidemia (27.3%), and psoriatic arthritis (23.4%) were the main comorbidities observed. Adalimumab (ADA, 80.5%), ustekinumab (UST, 70.1%), and etanercept (ETA, 14.2%) were the most frequently used biologics in our cohort. The biologic with the longest mean duration of use prior to its discontinuation was UST (17.0 months), followed by ADA (15.9 months) and ETA (13.6 months). CONCLUSION: The most common reason for discontinuing biologic therapy was that said therapy was not effective, though for ETA and UST, the fact that biologic therapies are not universally covered by insurance company was found to be associated with their discontinuation, as well. There were no statistically significant associations found between biologic therapy discontinuation and age, gender, or comorbidities, which last included obesity, class I. Larger studies are warranted to identify risk factors associated with biologic therapy failure to help guide drug selection, decrease morbidity associated with such nonadherence and improve patient outcomes.