Short-term effects of 448 kilohertz radiofrequency stimulation on plantar fascia measured by quantitative ultrasound elastography and thermography on active healthy subjects: an open controlled clinical trial.

Objective: This study is an open clinical trial. The aim of this study was to show the changes that occur in the viscoelastic properties of the plantar fascia (twenty healthy volunteers) measured by SEL and the changes in the plantar fascia temperature measured by thermography after the application of a 448 kHz capacitive resistive monopolar radiofrequency (CRMR) in active healthy subjects immediately after treatment and at the 1-week follow-up.Methods: Furthermore, to analyze if an intervention with 448 kHz CRMR in the plantar fascia of the dominant lower limb produces a thermal response in the plantar fascia of the non-dominant lower limb. The final objective was to analyze the level of association between the viscoelastic properties of the PF and the temperature before and after the intervention with 448 kHz CRMR.Results: Our results showed that a temperature change, which was measured by thermography, occurred in the plantar fascia after a single intervention (T0-T1) and at the 1-week follow up (T1-T2).Conclusion: However, no changes were found in the viscoelastic properties of the plantar fascia after the intervention or at the 1-week follow up. This is the first study to investigate changes in both plantar fascia viscoelastic properties and in plantar fascia temperature after a radiofrequency intervention.

Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy.

Chimeric antigen receptor (CAR) T cells targeting CD19+ B cells have demonstrated efficacy in refractory systemic lupus erythematosus (SLE). Although initial clinical data suggest that anti-CD19 CAR T cell therapy is well tolerated and highly effective, the immunologic consequences of CAR T cell therapy in SLE patients remain unclear. We profiled serum in six refractory SLE patients prior to and 3 months following CAR T cell infusion. Three months post T cell infusion, the inflammatory cytokines IL-6 and TNFα decreased in patient sera. This was accompanied by elevations in serum IL-7 and BAFF. Furthermore, SLE-associated antibodies dropped profoundly in five of six patients. Last, consistent with other reports of CD19 CAR T therapy in B cell malignancies, we were able to show marginal impact of anti-CD19 CART therapy on pre-existing humoral immune responses in SLE patients. Together, these results provide insights into the mechanisms of efficacy of anti-CD19 CAR T cell therapy in SLE.

Mutations in the bZip region of the CEBPA gene: A novel prognostic factor in patients with acute myeloid leukemia.

BACKGROUND: Hematopoiesis, the process of blood cell formation involves on a complex network of transcription factors. Among them, the CCAAT-enhancer-binding protein alpha (CEBPA) plays a crucial role in maintaining the balance between myeloid proliferation and differentiation. Imbalances in this network can lead to disrupted differentiation and contribute to the development of malignant diseases. AIM: Understanding of disease development and explore potential therapeutic strategies for hematological disorders associated CEPBA gen. MATERIALS AND METHODS: The research involved a comprehensive analysis of CEBPA gene mutations in the context of acute myeloid leukemia (AML). This encompassed a thorough exploration of point mutations and double mutations in AML patients. RESULTS: In the context of acute myeloid leukemia (AML), mutations in the CEBPA gene, especially point mutations, are frequently observed. A significant number of AML patients present with double mutations in CEBPA, which have been linked to a more favorable prognosis in terms of overall survival and event-free survival. These patients also tend to exhibit enhanced responsiveness to treatment. DISCUSSION: Unraveling the intricate interplay of transcription factors, particularly CEBPA, holds significant implications for decoding the mechanisms governing hematopoiesis. This understanding offers a potential avenue for deciphering disease development and devising novel therapeutic strategies for hematological disorders. CONCLUSION: The findings underscore that CEBPA mutations correlate with enhanced overall survival and event-free survival, with relevance to those presenting within the bZip framework. This knowledge may contribute to advancing personalized treatments for hematological conditions.

Recent Photosensitizer Developments, Delivery Strategies and Combination-based Approaches for Photodynamic Therapy†.

Photodynamic therapy of cancer (PDT) is a therapeutic technique, minimally invasive, which is currently used to treat cancerous lesions and tumors that have been in the spotlight for its potential over the recent decades. Nonetheless, PDT still needs further development to become a first-option treatment for patients. This review compiles recent progress in several aspects of the current research in the constantly growing area of PDT to overcome the main challenges as an attempt to serve as a guide and reference for newcomers into this research area. This review has been prepared to highlight the use of chemical modifications on photosensitizers to improve their solubility, photostability, selectivity and phototoxicity. Additionally, the use of liposomes and cavitands as drug delivery systems to aid in the biodistribution and bioaccumulation of photosensitizers is presented. Also, the combination of PDT with chemotherapy or immunotherapy as an option to boost and improve treatment outcomes is discussed. Finally, the inhibition of antioxidant enzymes as a strategy for a synergistic effect to ameliorate the performance of the photosensitizers in PDT is presented as an alternative for future researchers.

Fatty Acid Conjugates of Toluidine Blue O as Amphiphilic Photosensitizers: Synthesis, Solubility, Photophysics and Photochemical Properties†.

Toluidine blue O (TBO) is a water-soluble photosensitizer that has been used in photodynamic antimicrobial and anticancer treatments, but suffers from limited solubility in hydrophobic media. In an effort to incrementally increase TBO's hydrophobicity, we describe the synthesis of hexanoic (TBOC6) and myristic (TBOC14) fatty acid derivatives of TBO formed in low to moderate percent yields by condensation with the free amine site. Covalently linking 6 and 14 carbon chains led to modifications of not only TBO's solubility, but also its photophysical and photochemical properties. TBOC6 and TBOC14 derivatives were more soluble in organic solvents and showed hypsochromic shifts in their absorption and emission bands. The solubility in phosphate buffer solution was low for both TBOC6 and TBOC14, but unexpectedly slightly greater in the latter. Both TBOC6 and TBOC14 showed decreased triplet excited-state lifetimes and singlet oxygen quantum yields in acetonitrile, which was attributed to heightened aggregation of these conjugates particularly at high concentrations due to the hydrophobic "tails." While in diluted aqueous buffer solution, indirect measurements showed similar efficiency in singlet oxygen generation for TBOC14 compared to TBO. This work demonstrates a facile synthesis of fatty acid TBO derivatives leading to amphiphilic compounds with a delocalized cationic "head" group and hydrophobic "tails" for potential to accumulate into biological membranes or membrane/aqueous interfaces in PDT applications.

COVID-19 voluntary social isolation and its effects in sociofamily and children's behavior / Aislamiento social voluntario por COVID-19 y sus efectos en la conducta sociofamiliar e infantil

Abstract Introduction The main prevention strategy for reducing the dispersion of the SARS-CoV-2 has been social distancing. Several investigations began to explore its psychological impact since it began, but there are no data about its effect on social and family behavior. Objectives Were: First, to analyze the reliability of an ad-hoc designed questionnaire to measure sociofamily behavior changes in a sample of parents of children from one to twelve years old. Second, to characterize effects of voluntary social isolation by COVID-19 over sociofamily behavior at a personal level and over children's activities at home. Third, to determine vulnerability predictors for a negative experience by isolation itself. Method An online Questionnaire for Perceptions of Changes in Sociofamily Behavior was applied to 365 Mexican participants. Results Factor analysis showed a reliability of the ad-hoc designed questionnaire for this study. Correlations were found between voluntary social isolation and self-perceived experiences, such as sleep quality, irritability, emotional control, hope about the future, motivation, attention span, and problem solving. Discussion and conclusion The results of this study suggest that family well-being during voluntary social isolation is a complex and multifactorial phenomenon, which addresses specific effects in different domains, especially in sociofamily behavior.

Resumen Introducción La principal estrategia de prevención para frenar la dispersión del SARS-CoV-2 ha sido el distanciamiento social. Varias investigaciones han comenzado a explorar su impacto psicológico, pero no existen datos hasta el momento acerca del efecto en la conducta social y familiar. Objetivos Primero, analizar la confiabilidad de un cuestionario ad-hoc elaborado para medir los cambios sociofamiliares en una muestra de adultos padres de niños de uno a 12 años. Segundo, caracterizar los efectos del aislamiento social voluntario COVID-19 en la conducta sociofamiliar a nivel personal y sobre las actividades infantiles en casa. Tercero, determinar los predictores de vulnerabilidad para presentar una experiencia negativa del aislamiento. Método Se aplicó el Cuestionario de Percepción de Cambios en la Conducta Sociofamiliar en línea a 365 participantes mexicanos. Resultados El análisis factorial mostró que el cuestionario ad-hoc elaborado para este estudio es confiable. Además, los datos mostraron un efecto principal de variables como el nivel socioeconómico, la fuente de ingresos y el estado civil. También, se encontraron correlaciones entre la experiencia personal de aislamiento, como la calidad del sueño, la irritabilidad, el control emocional, las esperanzas sobre el futuro, la motivación, la capacidad de atención y la resolución de problemas. Discusión y conclusión Los resultados de este estudio sugieren que el bienestar familiar durante el aislamiento es un fenómeno complejo y multifactorial, que además revela efectos específicos en la conducta sociofamiliar.

Effect of Relative Humidity and Air Temperature on the Results Obtained from Low-Cost Gas Sensors for Ambient Air Quality Measurements.

Using low-cost gas sensors for air quality monitoring promises cost effective and convenient measurement systems. Nevertheless, the results obtained have a questionable quality due to different factors that can affect sensor performance. The most discussed ones are relative humidity and air temperature. This investigation aimed to assess the behavior of B4-series low-cost gas sensors from Alphasense for measuring CO, NO, NO2, and O3 for different levels of relative humidity and temperature. These low-cost gas sensors were tested for six relative humidity levels from 10% to 85% with increasing steps of 15% and four temperature levels of 10 °C, 25 °C, 35 °C, and 45 °C against reference instruments in the laboratory. The effect of these parameters on low-cost gas sensors was quantified in laboratory from which a correction algorithm was calculated, which was then applied to the field data. The applied algorithm improved the data quality of the low-cost gas sensors in most of the cases. Additionally, a low-cost dryer was assessed to reduce the influence of these factors on the low-cost gas sensors, which also proved to be suitable to enhance the data quality.

Hallazgos estructurales en imágenes cerebrales de pacientes con diagnóstico de delirium en un hospital de alta complejidad de Bogotá / Structural findings in cerebral images of patients with diagnosis of delirium in a high-complexity hospital in Bogota

RESUMEN INTRODUCCIÓN: El delirium es una falla cerebral de origen multifactorial, común, y en ocasiones relacionada con un desenlace fatal. Afecta principalmente a la población hospitalizada mayor de 65 años. La realización de imágenes cerebrales en delirium se encuentra en discusión, porque en la mayoría de los casos no se pone en evidencia una correlación entre los hallazgos de la imagen y la enfermedad. La literatura médica actual muestra que las imágenes de rutina (tomografía o resonancia cerebral) resultan negativas para lesiones agudas hasta en el 94 % de los pacientes que cumplen criterios diagnósticos. En Colombia no hay estudios descriptivos en pacientes que presenten delirium. Por lo anterior, nuestra idea es describir los principales hallazgos radiológicos en imagen cerebral en pacientes con diagnóstico de delirium en urgencias u hospitalización en un hospital de alta complejidad de Bogotá, valorados por el departamento de neurología. MÉTODOS: Se realizó un estudio de corte transversal que incluyó a los pacientes con diagnóstico de delirium atendidos por neurología en hospitalización o urgencias entre octubre del 2015 y octubre del 2016. RESULTADOS: Se incluyeron 97 pacientes y se realizaron imágenes cerebrales a 79 (81 %). De estos, tan solo en ocho (10 %) se encontró lesión aguda en imágenes cerebrales. En los pacientes que tienen signos de focalización este porcentaje aumentó a tres pacientes (27 %), y en los que no tenían signos de focalización fue de cinco pacientes (7,3 %). CONCLUSIONES: La presencia de lesiones cerebrales agudas en pacientes con delirium es baja. El hecho de tener signos de focalización en el examen aumenta la posibilidad de tener lesiones agudas.

SUMMARY INTRODUCTION: Delirium is a brain failure of multifactorial origin, common and sometimes related to a fatal outcome. It mainly affects hospitalized population over 65 years. Work-up with cerebral images is in discussion, because in most of of the occasions it is not related to the pathology. Current medical literature shows that routine imaging (tomography or brain resonance) are negative for acute injuries in up to 94 % of patients that meets delirium diagnostic criteria. In Colombia there are no descriptive studies in patients with delirium. Therefore, our objective was to describe the main radiological findings in brain imaging in patients diagnosed with delirium in the emergency room or admitted subjects in a high complexity hospital in Bogotá-Colombia, assessed by the department of neurology between October 2015 and October 2016. METHODS: A cross-sectional study was carried out, including all patients diagnosed with delirium treated by neurology in hospitalization or emergencies. RESULTS: This research showed a total of 97 patients diagnosed with delirium; 79 (81 %) had brain images; of these, only 8 (10 %) showed acute injury in brain images, in patients who have signs of focalization this percentage was higher to 3 (27 %) than in those who did not have them 5 (7.3 %). CONCLUSIONS: The presence of acute brain injuries in patients with delirium is low. The fact of having signs of focal injury on examination increases the possibility of having acute injuries.

Systemic and local immunity following adoptive transfer of NY-ESO-1 SPEAR T cells in synovial sarcoma.

BACKGROUND: Gene-modified autologous T cells expressing NY-ESO-1c259, an affinity-enhanced T-cell receptor (TCR) reactive against the NY-ESO-1-specific HLA-A*02-restricted peptide SLLMWITQC (NY-ESO-1 SPEAR T-cells; GSK 794), have demonstrated clinical activity in patients with advanced synovial sarcoma (SS). The factors contributing to gene-modified T-cell expansion and the changes within the tumor microenvironment (TME) following T-cell infusion remain unclear. These studies address the immunological mechanisms of response and resistance in patients with SS treated with NY-ESO-1 SPEAR T-cells. METHODS: Four cohorts were included to evaluate antigen expression and preconditioning on efficacy. Clinical responses were assessed by RECIST v1.1. Engineered T-cell persistence was determined by qPCR. Serum cytokines were evaluated by immunoassay. Transcriptomic analyses and immunohistochemistry were performed on tumor biopsies from patients before and after T-cell infusion. Gene-modified T-cells were detected within the TME via an RNAish assay. RESULTS: Responses across cohorts were affected by preconditioning and intra-tumoral NY-ESO-1 expression. Of the 42 patients reported (data cut-off 4June2018), 1 patient had a complete response, 14 patients had partial responses, 24 patients had stable disease, and 3 patients had progressive disease. The magnitude of gene-modified T-cell expansion shortly after infusion was associated with response in patients with high intra-tumoral NY-ESO-1 expression. Patients receiving a fludarabine-containing conditioning regimen experienced increases in serum IL-7 and IL-15. Prior to infusion, the TME exhibited minimal leukocyte infiltration; CD163+ tumor-associated macrophages (TAMs) were the dominant population. Modest increases in intra-tumoral leukocytes (≤5%) were observed in a subset of subjects at approximately 8 weeks. Beyond 8 weeks post infusion, the TME was minimally infiltrated with a TAM-dominant leukocyte infiltrate. Tumor-associated antigens and antigen presentation did not significantly change within the tumor post-T-cell infusion. Finally, NY-ESO-1 SPEAR T cells trafficked to the TME and maintained cytotoxicity in a subset of patients. CONCLUSIONS: Our studies elucidate some factors that underpin response and resistance to NY-ESO-1 SPEAR T-cell therapy. From these data, we conclude that a lymphodepletion regimen containing high doses of fludarabine and cyclophosphamide is necessary for SPEAR T-cell persistence and efficacy. Furthermore, these data demonstrate that non-T-cell inflamed tumors, which are resistant to PD-1/PD-L1 inhibitors, can be treated with adoptive T-cell based immunotherapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01343043 , Registered 27 April 2011.

African Swine Fever Virus Armenia/07 Virulent Strain Controls Interferon Beta Production through the cGAS-STING Pathway.

African swine fever virus (ASFV) is a complex, cytoplasmic double-stranded DNA (dsDNA) virus that is currently expanding throughout the world. Currently, circulating virulent genotype II Armenia/07-like viruses cause fatal disease in pigs and wild boar, whereas attenuated strains induce infections with various levels of chronic illness. Sensing cytosolic dsDNA, mainly by the key DNA sensor cyclic GMP-AMP synthase (cGAS), leads to the synthesis of type I interferon and involves signaling through STING, TBK1, and IRF3. After phosphorylation, STING translocates from the endoplasmic reticulum to the Golgi compartment and to the perinuclear region, acting as an indispensable adaptor connecting the cytosolic detection of DNA to the TBK1-IRF3 signaling pathway. We demonstrate here that attenuated NH/P68, but not virulent Armenia/07, activates the cGAS-STING-IRF3 cascade very early during infection, inducing STING phosphorylation and trafficking through a mechanism involving cGAMP. Both TBK1 and IRF3 are subsequently activated and, in response to this, a high level of beta interferon (IFN-ß) was produced during NH/P68 infection; in contrast, Armenia/07 infection generated IFN-ß levels below those of uninfected cells. Our results show that virulent Armenia/07 ASFV controls the cGAS-STING pathway, but these mechanisms are not at play when porcine macrophages are infected with attenuated NH/P68 ASFV. These findings show for the first time the involvement of the cGAS-STING-IRF3 route in ASFV infection, where IFN-ß production or inhibition was found after infection by attenuated or virulent ASFV strains, respectively, thus reinforcing the idea that ASFV virulence versus attenuation may be a phenomenon grounded in ASFV-mediated innate immune modulation where the cGAS-STING pathway might play an important role.IMPORTANCE African swine fever, a devastating disease for domestic pigs and wild boar, is currently spreading in Europe, Russia, and China, becoming a global threat with huge economic and ecological consequences. One interesting aspect of ASFV biology is the molecular mechanism leading to high virulence of some strains compared to more attenuated strains, which produce subclinical infections. In this work, we show that the presently circulating virulent Armenia/07 virus blocks the synthesis of IFN-ß, a key mediator between the innate and adaptive immune response. Armenia/07 inhibits the cGAS-STING pathway by impairing STING activation during infection. In contrast, the cGAS-STING pathway is efficiently activated during NH/P68 attenuated strain infection, leading to the production of large amounts of IFN-ß. Our results show for the first time the relationship between the cGAS-STING pathway and ASFV virulence, contributing to uncover the molecular mechanisms of ASFV virulence and to the rational development of ASFV vaccines.

Sesgo en la estratificación del síndrome coronario agudo al calcular el grace- score con 1ª, 2ª o troponina Δ / Grace score bias in acute coronary syndrome due to use 1th, 2th or troponin Δ

Introducción: el síndrome coronario agudo (SCA) es la primera causa de mortalidad en Colombia. Una estratificación de riesgo errónea, en la sala de emergencias (ER), afecta las intervenciones realizadas y la tasa de eventos adversos cardiovasculares puede ser mayor. El objetivo de esta investigación fue medir la diferencia en el puntaje GRACE y la estratificación del riesgo coronario, utilizando los resultados de las troponinas medidas secuencialmente durante la atención inicial. Metodología: con un diseño descriptivo retrospectivo, se evaluaron los registros clínicos de pacientes tratados por dolor precordial de probabilidad intermedia para SCA, sin indicación de manejo invasivo inmediato, atendidos en la sala de emergencias de una clínica del tercer nivel de Bogotá, durante el año 2017. Se determinó la diferencia entre la puntuación GRACE calculada con la primera troponina (GRACE-1), la segunda troponina (GRACE-2) o la troponina delta (GRACE-delta) [prueba T pareada], y la proporción de pacientes poco estratificados se midió al usar la primera troponina [X2, puntaje Z]. Resultados: se identificaron 44 pacientes en un período de 6 meses. La mayoría hombres con edad mediana de 73 años. El promedio (DE) de los puntajes GRACE-1, GRACE-2 y GRACE-delta, fue de 114.14 (30.73), 115.55 (30.14) y 111.11 (28.79), respectivamente; al comparar GRACE-delta con GRACE-1 y GRACE-2 se identificaron diferencias significativas (p:<0.05). Se identificó un error en la estratificación del riesgo coronario en 10/44 pacientes (22.7%) y 9/44 (20.4%) presentaron sobreestratificación. Conclusión: la estratificación del riesgo coronario con la primera troponina, a diferencia de la troponina delta (ítem no aclarado en las guías), evidenció una sobreestratificación en al menos 20% de los pacientes, estableciendo la necesidad de procedimientos más invasivos y posiblemente hospitalización más prolongada permanecer.

Background: Acute coronary syndrome (ACS) is the first cause of mortality in Colombia. An erroneous risk stratification, in the emergency room (ER), affects the interventions performed and the rate of major cardiovascular adverse events. We measured the difference in GRACE score and stratification of coronary risk, by using the results of troponins measured sequentially during initial care. Methods: With a retrospective descriptive design, clinical records of patients treated for precordial pain of ≥ intermediate probability for ACS were evaluated, without indication of immediate invasive management, attended in the ER of a clinic of the third level of Bogotá, during 2017. De-termined the difference between the GRACE score calculated with the first (GRACE-1), second (GRACE-2) or troponin delta (GRACE-delta [paired T-test], and the proportion of poorly stratified patients was measured when using the first troponin [X2, Z-score]. Results: 44 patients in a period of 6 months were identified. The majority men, older adults, middle age 73 years. The average (SD) of scores GRACE-1, GRACE-2 and GRACE-delta, was 114.14 (30.73), 115.55 (30.14) and 111.11 (28.79), respectively; when comparing GRACE-delta with GRACE-1 and GRACE-2 significant differences were identified (p:<0.05). Error in the stratification of coronary risk was identified in 10/44 patients (22.7%), and 9/44 (20.4%) presented over-stratification. Conclusion: The stratification of coronary risk using the first troponin, unlike the troponin delta (item not clarified in the guidelines), evidenced an over-stratification in at least 20% of the patients, establishing the need for more invasive procedures and possibly longer hospital stay.

Daño renal agudo secundario a nefritis tubulointersticial aguda por uso de medicamentos. Caso clínico / Acute renal damage secondary to acute tubulointerstitial nephritis drug use. Case report

Resumen Introducción: La nefritis tubulointersticial aguda (NTIA) es infrecuente en la edad pediátrica. Se caracteriza por la infiltración del parénquima renal por células mononucleares y/o polinucleares con afectación secundaria de los túbulos sin lesión glomerular, y puede ser producida por infecciones, enfermedades inmunológicas, fármacos, o ser de origen idiopático. Objetivo: Describir un caso de NTIA secundario a antiinflamatorios no esteroidales (AINE) en un lactante, con énfasis en esta aso ciación para ser considerada por los pediatras. Caso clínico: Lactante de 10 meses, sin antecedentes previos, trasladada a nuestro hospital por daño renal agudo estadio 3, clasificación KDIGO 2012. Los tres días previos recibió tratamiento con amoxicilina e ibuprofeno por otitis media aguda. En la exploración física destacaba leve edema palpebral con presión arterial normal. En la orina presentaba proteinuria no nefrótica con componente tubular, microhematuria y leucocituria. La ecografía renal no mostraba alteraciones. Ante la sospecha de NTIA se cambió el antibiótico a cefotaxima intrave nosa y se suspendió el ibuprofeno realizándose manejo conservador del daño renal agudo. Presentó aumento de la creatinina (4.14 mg/dL) y eosinofilia, siendo el estudio inmunológico negativo. Se trató con metilprednisolona, con normalización de la función renal. Conclusión: La NTIA se puede producir por cualquier medicamento mediante una reacción inmunológica idiosincrásica. Entre los medicamentos responsables se identifican fármacos de uso frecuente en la edad pediátrica, como los AINEs, por lo que se necesita una alta sospecha diagnóstica por parte de los pediatras.

Abstract Introduction: Acute tubulointerstitial nephritis (ATIN) is a rare entity in the pediatric age. It is de fined by the infiltration of the renal parenchyma by mononuclear and/or polynuclear cells with se condary involvement of the tubules, without glomerular injury. It can be triggered by infections or immunological diseases, drugs like NSAIDs or be of idiopathic origin. Objective: To raise awareness among pediatricians about the prescription of NSAIDs, especially to patients of less than a year old, since they can provoke renal damage. Case report: A ten month old child, with no nephrological an tecedents of interest, was transferred to our hospital due to acute renal failure stage 3 KDIGO 2012. The three previous days received treatment with amoxicillin and ibuprofen for acute otitis media. Physical examination revealed mild eyelid edema with normal blood pressure. In the urine analysis, there were non-nephrotic proteinuria with tubular component, microhematuria and leukocyturia. Renal ultrasound showed no abnormalities. ATIN was suspected and so the antibiotic was changed to intravenous cefotaxime and ibuprofen was discontinued, opting for conservative management of acute renal damage. There was an increase in the number of creatinine up to 4.14 mg/dL and eosinophilia, with the immunological study being negative. Treatment with methylprednisolone was initiated, achieving normalization of renal function. Discussion: NTIA can be produced by any me dication through an idiosyncratic immune reaction. Among the responsible drugs, there are ones commonly used in the pediatric age, such as NSAIDs. Therefore, the pediatricians should pay special attention during prescriptions and have a high diagnostic suspicion of this disease.

The N-Terminal Phosphorylation of RB by p38 Bypasses Its Inactivation by CDKs and Prevents Proliferation in Cancer Cells.

Control of the G1/S phase transition by the Retinoblastoma (RB) tumor suppressor is critical for the proliferation of normal cells in tissues, and its inactivation is one of the most fundamental events leading to cancer. Cyclin-dependent kinase (CDK) phosphorylation inactivates RB to promote cell cycle-regulated gene expression. Here we show that, upon stress, the p38 stress-activated protein kinase (SAPK) maximizes cell survival by downregulating E2F gene expression through the targeting of RB. RB undergoes selective phosphorylation by p38 in its N terminus; these phosphorylations render RB insensitive to the inactivation by CDKs. p38 phosphorylation of RB increases its affinity toward the E2F transcription factor, represses gene expression, and delays cell-cycle progression. Remarkably, introduction of a RB phosphomimetic mutant in cancer cells reduces colony formation and decreases their proliferative and tumorigenic potential in mice.

CD2v Interacts with Adaptor Protein AP-1 during African Swine Fever Infection.

African swine fever virus (ASFV) CD2v protein is believed to be involved in virulence enhancement, viral hemadsorption, and pathogenesis, although the molecular mechanisms of the function of this viral protein are still not fully understood. Here we describe that CD2v localized around viral factories during ASFV infection, suggesting a role in the generation and/or dynamics of these viral structures and hence in disturbing cellular traffic. We show that CD2v targeted the regulatory trans-Golgi network (TGN) protein complex AP-1, a key element in cellular traffic. This interaction was disrupted by brefeldin A even though the location of CD2v around the viral factory remained unchanged. CD2v-AP-1 binding was independent of CD2v glycosylation and occurred on the carboxy-terminal part of CD2v, where a canonical di-Leu motif previously reported to mediate AP-1 binding in eukaryotic cells, was identified. This motif was shown to be functionally interchangeable with the di-Leu motif present in HIV-Nef protein in an AP-1 binding assay. However, we demonstrated that it was not involved either in CD2v cellular distribution or in CD2v-AP-1 binding. Taken together, these findings shed light on CD2v function during ASFV infection by identifying AP-1 as a cellular factor targeted by CD2v and hence elucidate the cellular pathways used by the virus to enhance infectivity.

Bioquímica de la caries dental / Biochemistry of dental caries

La caries dental constituye una de las enfermedades crónicas y transmisibles que con mayor frecuencia afecta a los seres humanos, por lo que es objeto de estudio de numerosos investigadores con el propósito de lograr su prevención y tratamiento. En el siguiente trabajo, realizamos una revisión bibliográfica con el objetivo de profundizar en los conocimientos teóricos acerca de la caries dental describiendo los factores y mecanismos que propician la aparición de esta patología, así como los mecanismos de acción de los fluoruros, los edulcorantes, los agentes antibacterianos y el ozono(AU)

The dental caries constitutes one of the chronic and transferable illnesses that affects the human beings with more frequency, for what is object of numerous investigators' study with the purpose of achieving its prevention and treatment. In the following work we carry out a bibliographical revision with the objective of deepening in the theoretical knowledge about the dental caries describing the actors and mechanisms that propitiate the appearance of this pathology, as well as the mechanisms of action of the fluorides, antibacterial agents, the edulcorating and the ozone(AU)

Aldosterone and tight junctions: modulation of claudin-4 phosphorylation in renal collecting duct cells.

Aldosterone classically modulates Na transport in tight epithelia such as the renal collecting duct (CD) through the transcellular route, but it is not known whether the hormone could also affect paracellular permeability. Such permeability is controlled by tight junctions (TJ) that form a size- and charge-selective barrier. Among TJ proteins, claudin-4 has been highlighted as a key element to control paracellular charge selectivity. In RCCD2 CD cells grown on filters, we have identified novel early aldosterone effects on TJ. Endogenous claudin-4 abundance and cellular localization were unaltered by aldosterone. However, the hormone promoted rapid (within 15-20 min) and transient phosphorylation of endogenous claudin-4 on threonine residues, without affecting tyrosine or serine; this event was fully developed at 10 nM aldosterone and appeared specific for aldosterone (because it is not observed after dexamethasone treatment and it depends on mineralocorticoid receptor occupancy). Within the same delay, aldosterone also promoted an increased apical-to-basal passage of 125I (a substitute for 36Cl), whereas 22Na passage was unaffected; paracellular permeability to [3H]mannitol was also reduced. Later on (45 min), a fall in transepithelial resistance was observed. These data indicate that aldosterone modulates TJ properties in renal epithelial cells.

12-Lipoxygenase metabolism in mouse distal convoluted tubule cells.

BACKGROUND: Several lines of evidence point to the 12-lipoxygenase (12-LOX) family as important mediators in hypertension, diabetes, and other cardiovascular diseases. The kidney has been a main focus for research of the role of this pathway in several disease models. While most of the studies have focused on mesangial or vascular cells, less is known about 12-LOX regulation at the renal tubular level. The aim of the study was to characterize the expression and regulation by hormones of the family of 12-LOX in mouse distal convoluted tubule at the molecular level. METHODS: An immortalized mouse distal convoluted tubule (mDCT) cell line was used. mRNA and protein levels were assessed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively, while 12(S)-HETE production was evaluated by enzyme-linked immunosorbent assay (ELISA). Cells were challenged with aldosterone, angiotensin II, 8Br-cAMP, and vasopressin. RESULTS: We showed that both platelet (P) and leukocyte (L)-type 12-LOX are expressed in the mDCT cell line, as well as in distal tubules of human kidneys. The production of 12(S)-HETE by mDCT cells was increased in response to cAMP (by two-fold) and by vasopressin (by 1.5-fold). In contrast, neither aldosterone nor angiotensin II exerted appreciable effects on 12(S)-HETE production. The mRNA and protein levels of P-12LOX and L-12LOX were not changed by the different hormones, suggesting that they may act by modulating enzyme activity. We further have demonstrated that this mDCT cell line also expressed the recently cloned 12(R)-LOX. CONCLUSION: mDCT cells show an active 12-LOX metabolism that appears to be modulated by cAMP and vasopressin.

In vitro characterization of aldosterone and cAMP effects in mouse distal convoluted tubule cells.

The distal nephron plays a capital role in the fine regulation of sodium reabsorption. Compared with the cortical collecting duct, much less information is available on the hormonal regulation of sodium transporter genes in the distal convoluted tubule (DCT), where the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC) is the major entry pathway for Na(+). The purpose of this study was to characterize the in vitro effects of aldosterone (Aldo; 1 microM) and cAMP (8-BrcAMP; 0.5 mM) on mouse DCT (mDCT) by using an immortalized mDCT cell line. Western blot analysis and semiquantitative RT-PCR were performed to analyze the expression of genes involved in sodium transport. The mDCTcell line expressed the 11 beta-hydroxysteroid dehydrogenase type 2 gene and both the mineralocorticoid and glucocorticoid receptor genes, suggesting Aldo responsiveness. In this sense, we found that mDCT cells expressed the amiloride-sensitive Na(+) channel (ENaC) and responded to Aldo by upregulating the alpha-subunit protein. Similarly, alpha(1) Na(+)-K(+)-ATPase protein was upregulated by Aldo and 8-BrcAMP. In addition, the Aldo intermediate gene sgk1 mRNA was increased in response to both Aldo and 8-BrcAMP, and the transcription factor HNF-3 alpha mRNA was induced by 8-BrcAMP. With respect to NCC regulation, although Aldo induced NCC protein levels in mice in vivo, neither Aldo nor 8-BrcAMP significantly induced the NCC mRNA or protein levels in mDCT cells. These results suggest that in mDCT, Aldo and cAMP modulate some downstream mediators and effectors in vitro but do not influence the expression of NCC in this cell model.