NFAT5 Is Activated by Hypoxia: Role in Ischemia and Reperfusion in the Rat Kidney

The current hypothesis postulates that NFAT5 activation in the kidney's inner medulla is due to hypertonicity, resulting in cell protection. Additionally, the renal medulla is hypoxic (10–18 mmHg); however there is no information about the effect of hypoxia on NFAT5. Using in vivo and in vitro models, we evaluated the effect of reducing the partial pressure of oxygen (PO2) on NFAT5 activity. We found that 1) Anoxia increased NFAT5 expression and nuclear translocation in primary cultures of IMCD cells from rat kidney. 2) Anoxia increased transcriptional activity and nuclear translocation of NFAT5 in HEK293 cells. 3) The dose-response curve demonstrated that HIF-1α peaked at 2.5% and NFAT5 at 1% of O2. 4) At 2.5% of O2, the time-course curve of hypoxia demonstrated earlier induction of HIF-1α gene expression than NFAT5. 5) siRNA knockdown of NFAT5 increased the hypoxia-induced cell death. 6) siRNA knockdown of HIF-1α did not affect the NFAT5 induction by hypoxia. Additionally, HIF-1α was still induced by hypoxia even when NFAT5 was knocked down. 7) NFAT5 and HIF-1α expression were increased in kidney (cortex and medulla) from rats subjected to an experimental model of ischemia and reperfusion (I/R). 7) Experimental I/R increased the NFAT5-target gene aldose reductase (AR). 8) NFAT5 activators (ATM and PI3K) were induced in vitro (HEK293 cells) and in vivo (I/R kidneys) with the same timing of NFAT5. 8) Wortmannin, which inhibits ATM and PI3K, reduces hypoxia-induced NFAT5 transcriptional activation in HEK293 cells. These results demonstrate for the first time that NFAT5 is induced by hypoxia and could be a protective factor against ischemic damage

Clinical Presentation and Outcomes of Kawasaki Disease in Children from Latin America: A Multicenter Observational Study from the REKAMLATINA Network

Objetivos: Describir la presentación clínica, el manejo y los resultados de la enfermedad de Kawasaki (EK) en Latinoamérica y evaluar los indicadores pronósticos tempranos de aneurisma de la arteria coronaria (AAC). Diseño del estudio: Se realizó un estudio observacional basado en el registro de la EK en 64 centros pediátricos participantes de 19 países latinoamericanos de forma retrospectiva entre el 1 de enero de 2009 y el 31 de diciembre de 2013, y de forma prospectiva desde el 1 de junio de 2014 hasta el 31 de mayo de 2017. Se recopilaron datos demográficos, clínicos y de laboratorio iniciales. Se utilizó una regresión logística que incorporaba factores clínicos y la puntuación z máxima de la arteria coronaria en la presentación inicial (entre 10 días antes y 5 días después de la inmunoglobulina intravenosa [IGIV]) para desarrollar un modelo pronóstico de AAC durante el seguimiento (>5 días después de la IGIV). Resultados: De 1853 pacientes con EK, el ingreso tardío (>10 días tras el inicio de la fiebre) se produjo en el 16%, el 25% tuvo EK incompleta y el 11% fue resistente a la IGIV. Entre los 671 sujetos con puntuación z de la arteria coronaria notificada durante el seguimiento (mediana: 79 días; IQR: 36, 186), el 21% presentaba AAC, incluido un 4% con aneurismas gigantes. Un modelo pronóstico simple que utilizaba sólo una puntuación z de la arteria coronaria máxima ≥2,5 en la presentación inicial fue óptimo para predecir la AAC durante el seguimiento (área bajo la curva: 0,84; IC del 95%: 0,80, 0,88). Conclusiones: De nuestra población latinoamericana, la puntuación z de la arteria coronaria ≥2,5 en la presentación inicial fue el factor pronóstico más importante que precedió a la AAC durante el seguimiento. Estos resultados resaltan la importancia de la ecocardiografía temprana durante la presentación inicial de la EK. © 2023 Los autoresObjectives: To describe the clinical presentation, management, and outcomes of Kawasaki disease (KD) in Latin America and to evaluate early prognostic indicators of coronary artery aneurysm (CAA). Study design: An observational KD registry-based study was conducted in 64 participating pediatric centers across 19 Latin American countries retrospectively between January 1, 2009, and December 31, 2013, and prospectively from June 1, 2014, to May 31, 2017. Demographic and initial clinical and laboratory data were collected. Logistic regression incorporating clinical factors and maximum coronary artery z-score at initial presentation (between 10 days before and 5 days after intravenous immunoglobulin [IVIG]) was used to develop a prognostic model for CAA during follow-up (>5 days after IVIG). Results: Of 1853 patients with KD, delayed admission (>10 days after fever onset) occurred in 16%, 25% had incomplete KD, and 11% were resistant to IVIG. Among 671 subjects with reported coronary artery z-score during follow-up (median: 79 days; IQR: 36, 186), 21% had CAA, including 4% with giant aneurysms. A simple prognostic model utilizing only a maximum coronary artery z-score ≥2.5 at initial presentation was optimal to predict CAA during follow-up (area under the curve: 0.84; 95% CI: 0.80, 0.88). Conclusion: From our Latin American population, coronary artery z-score ≥2.5 at initial presentation was the most important prognostic factor preceding CAA during follow-up. These results highlight the importance of early echocardiography during the initial presentation of KD. © 2023 The Author(s

Evaluation of Serum Levels and Expression of Galectin-4 in Cervical Cancer

Galectin-4 has been reported to be altered in different cancer types. Its expression changes have been associated with early recurrence and metastasis. In cervical cancer (CC), galectin-4 has not been studied. The aim of the study was to determine the expression level and subcellular localization of galectin-4 in CC tissue and the concentration in the serum of patients with CC. For the analysis of serum levels of galectin-4, an ELISA assay was performed. To assess the expression in cervical tissue, immunohistochemical staining was performed. The results showed that the concentration of galectin-4 in the serum of patients with CC was higher (647.9 pg/ml) than that in the serum of women with normal cytology (382.1 pg/ml). The immunohistochemical analysis of CC samples showed a higher expression in keratinizing tumor than nonkeratinizing tumors and a trend of increased expression in tumors from patients with advanced clinical stage. In normal cervical tissue, galectin-4 was detected in the cytoplasm, and in tumor cells, the presence of galectin-4 was also detected in the nucleus, in both adenocarcinoma and squamous cervical cancer. The increase in serum concentration and different localization in the tumor cells suggest a possible role of galectin-4 in CC development

Evaluación de habilidades en matemática y comprensión lectora en estudiantes que ingresan a pedagogía en educación básica: un estudio comparativo en dos universidades del Consejo de Rectores Math reasoning and reading comprehension skills assessment of entrant students from the primary school teaching program: a comparative study in two universities of the Council of Rectors (CRUCH)

El artículo presenta los resultados de la evaluación realizada a estudiantes que ingresan a la carrera de Pedagogía en Educación General Básica, de dos instituciones universitarias regionales pertenecientes al Consejo de Rectores en Chile, en habilidades de razonamiento y conocimiento matemático y comprensión lectora. Corresponde a una evaluación diagnóstica de tipo descriptiva y comparativa de corte transversal, a una población compuesta por 80 alumnos, a quienes se les aplicó instrumentos debidamente validados con un Alfa de Cronbach &#945;=0.82 en Matemática y de &#945;=0.64 en Comprensión Lectora. Para el análisis de la información, se utilizaron métodos descriptivos univariados y multivariados. Los resultados evidencian, en general, un dominio descendido en ambas habilidades o por debajo de lo esperado al ingreso de la Educación Superior, especialmente en las habilidades matemáticas.<br>Based on a comparative cross-assessment diagnosis conducted in two Council of Rectors (CRUCH) universities in southern Chile in 2009, this paper shows the results of Math reasoning and reading comprehension skills assessment of entrant students from the Primary School Teaching Program. Data for this paper comes from a test with Cronbach's Alpha reliability of 0,82 in Math and 0,64 in Reading Comprehension, which was applied to a sample of 80 students. Data analysis required one-variable and multivariable descriptive methods and the results dramatically showed either a low command of both skills or far lower than expected performance for entrant students from the Primary School Teaching Program, especially in Maths

Use of Adjunctive Therapy in Acute Kawasaki Disease in Latin America.

Objective: To characterize the use of adjunctive therapy in Kawasaki disease (KD) in Latin America. Methods: The study included 1,418 patients from the Latin American KD Network (REKAMLATINA) treated for KD between January 1, 2009, and May 31, 2017. Results: Of these patients, 1,152 received only a single dose of IVIG, and 266 received additional treatment. Age at onset was similar in both groups (median 2 vs. 2.2 years, respectively). The majority of patients were male (58 vs. 63.9%) and were hospitalized with the first 10 days of fever (85.1 vs. 84.2%). The most common adjunctive therapy administered was steroids for IVIG-resistance, followed by additional doses of IVIG. The use of biologics such as infliximab was limited. KD patients who received adjunctive therapy were more likely to have a lower platelet count and albumin level as well as a higher Z score of the coronary arteries. Conclusion: This is the first report of adjunctive therapies for KD across Latin America. IVIG continues to be the initial and resistance treatment, however, steroids are also used and to a lesser extent, biological therapy such as infliximab. Future studies should address the barriers to therapy in children with acute KD throughout Latin America

Presentation and outcomes of Kawasaki Disease in Latin American infants younger than 6 months of age: A multinational multicenter study of the REKAMLATINA network

Objective:To characterize the clinical presentation and outcomes of Kawasaki disease (KD) in infants Methods:We evaluated 36 infants = 6 months old diagnosed with KD in Latin America. We compared differences in laboratory data, clinical presentation, treatment response, and coronary artery outcomes between the two cohorts. Results:The majority (78.1%) of infants and children >= 6 months of age were initially diagnosed with KD, as compared to only 38.2% of infants = 6 months treated at the same point in the course of illness [ 10 days (50 vs. 7.4%,P= 0.043)]. Conclusion:Our data show that despite treatment in the first 10 days of illness, infants <6 months of age in Latin America have a higher risk of developing a coronary artery aneurysm. Delay in the diagnosis leads to larger coronary artery aneurysms disproportionately in these infants. Thus, suspicion for KD should be high in this vulnerable population