Examining the impact of a 9-component bundle and the INICC multidimensional approach on catheter-associated urinary tract infection rates in 32 countries across Asia, Eastern Europe, Latin America, and the Middle East.

BACKGROUND: Catheter-Associated Urinary Tract Infections (CAUTIs) frequently occur in the intensive care unit (ICU) and are correlated with a significant burden. METHODS: We implemented a strategy involving a 9-element bundle, education, surveillance of CAUTI rates and clinical outcomes, monitoring compliance with bundle components, feedback of CAUTI rates and performance feedback. This was executed in 299 ICUs across 32 low- and middle-income countries. The dependent variable was CAUTI per 1,000 UC days, assessed at baseline and throughout the intervention, in the second month, third month, 4 to 15 months, 16 to 27 months, and 28 to 39 months. Comparisons were made using a 2-sample t test, and the exposure-outcome relationship was explored using a generalized linear mixed model with a Poisson distribution. RESULTS: Over the course of 978,364 patient days, 150,258 patients utilized 652,053 UC-days. The rates of CAUTI per 1,000 UC days were measured. The rates decreased from 14.89 during the baseline period to 5.51 in the second month (risk ratio [RR] = 0.37; 95% confidence interval [CI] = 0.34-0.39; P < .001), 3.79 in the third month (RR = 0.25; 95% CI = 0.23-0.28; P < .001), 2.98 in the 4 to 15 months (RR = 0.21; 95% CI = 0.18-0.22; P < .001), 1.86 in the 16 to 27 months (RR = 0.12; 95% CI = 0.11-0.14; P < .001), and 1.71 in the 28 to 39 months (RR = 0.11; 95% CI = 0.09-0.13; P < .001). CONCLUSIONS: Our intervention, without substantial costs or additional staffing, achieved an 89% reduction in CAUTI incidence in ICUs across 32 countries, demonstrating feasibility in ICUs of low- and middle-income countries.

Evaluating the outcome of a bundle with 11 components and the INICC multidimensional approach in decreasing rates of central line-associated bloodstream infections across nine Asian countries.

BACKGROUND: Central line-associated bloodstream infection (CLABSI) rates in intensive care units (ICUs) across Latin America exceed those in high-income countries significantly. METHODS: We implemented the INICC multidimensional approach, incorporating an 11-component bundle, in 122 ICUs spanning nine Asian countries. We computed the CLABSI rate using the CDC/NSHN definition and criteria. The CLABSI rate per 1000 CL-days was calculated at baseline and throughout different phases of the intervention, including the 2nd month, 3rd month, 4-16 month, and 17-29 month periods. A two-sample t-test was employed to compare baseline CLABSI rates with intervention rates. Additionally, we utilized a generalized linear mixed model with a Poisson distribution to analyze the association between exposure and outcome. RESULTS: A total of 124,946 patients were hospitalized over 717,270 patient-days, with 238,595 central line (CL)-days recorded. The rates of CLABSI per 1000 CL-days significantly decreased from 16.64 during the baseline period to 6.51 in the 2nd month (RR = 0.39; 95% CI = 0.36-0.42; p < 0.001), 3.71 in the 3rd month (RR = 0.22; 95% CI = 0.21-0.25; p < 0.001), 2.80 in the 4-16 month (RR = 0.17; 95% CI = 0.15-0.19; p < 0.001), and 2.18 in the 17-29 month (RR = 0.13; 95% CI = 0.11-0.15; p < 0.001) intervals. A multilevel Poisson regression model demonstrated a sustained, continuous, and statistically significant decrease in ratios of incidence rates, reaching 0.35 (p < 0.0001) during the 17-29 month period. Moreover, the all-cause in-ICU mortality rate significantly decreased from 13.23% to 10.96% (p = 0.0001) during the 17-29 month period. CONCLUSIONS: Our intervention led to an 87% reduction in CLABSI rates, with a 29-month follow-up.

Usefulness of Ultrasonography and Radiography in the Evaluation of Distal Forearm Fractures in Children: A Narrative Review / Utilidad de la ecografía y la radiografía en la evaluación de las fracturas distales del antebrazo en niños: una revisión narrativa

Pediatric fractures, especially distal forearm fractures, represent a significant global medical concern, affecting up to 50% of pediatric fracture cases. This narrative review aims to compare diagnostic modalities to determine which offers higher accuracy, minimizes radiation exposure, and is adaptable to diverse clinical settings. In the choice between ultrasound and X-ray for diagnosing distal forearm fractures in children, each modality has its merits. X-ray provides accuracy and value in wellequipped facilities, while ultrasound, being radiation-free, is effective in resourcelimited areas and is essential for pediatric patients to avoid radiation exposure. Professional training and continual updates are crucial. Moreover, it underscores that alongside diagnostic imaging, comprehensive clinical assessment remains pivotal for making informed medical decisions. The choice of method should consider individual case factors and prioritize patient safety. (AU)

Las fracturas pediátricas, especialmente las fracturas distales del antebrazo, representan una importante preocupación médica mundial y afectan hasta el 50% de los casos de fracturas pediátricas. Esta revisión narrativa tiene como objetivo comparar modalidades de diagnóstico para determinar cuál ofrece mayor precisión, minimiza la exposición a la radiación y es adaptable a diversos entornos clínicos. A la hora de elegir entre ecografía y rayos X para diagnosticar fracturas distales del antebrazo en niños, cada modalidad tiene sus ventajas. Los rayos X proporcionan precisión y valor en instalaciones bien equipadas, mientras que el ultrasonido, al no tener radiación, es eficaz en áreas con recursos limitados y es esencial para que los pacientes pediátricos eviten la exposición a la radiación. La formación profesional y la actualización continua son cruciales. Además, subraya que, junto con el diagnóstico por imágenes, la evaluación clínica integral sigue siendo fundamental para tomar decisiones médicas informadas. La elección del método debe considerar factores de cada caso individual y priorizar la seguridad del paciente. (AU)

Decreasing central line-associated bloodstream infections rates in intensive care units in 30 low- and middle-income countries: An INICC approach.

BACKGROUND: Central line (CL)-associated bloodstream infections (CLABSIs) occurring in the intensive care unit (ICU) are common and associated with a high burden. METHODS: We implemented a multidimensional approach, incorporating an 11-element bundle, education, surveillance of CLABSI rates and clinical outcomes, monitoring compliance with bundle components, feedback of CLABSI rates and clinical outcomes, and performance feedback in 316 ICUs across 30 low- and middle-income countries. Our dependent variables were CLABSI per 1,000-CL-days and in-ICU all-cause mortality rates. These variables were measured at baseline and during the intervention, specifically during the second month, third month, 4 to 16 months, and 17 to 29 months. Comparisons were conducted using a two-sample t test. To explore the exposure-outcome relationship, we used a generalized linear mixed model with a Poisson distribution to model the number of CLABSIs. RESULTS: During 1,837,750 patient-days, 283,087 patients, used 1,218,882 CL-days. CLABSI per 1,000 CL-days rates decreased from 15.34 at the baseline period to 7.97 in the 2nd month (relative risk (RR) = 0.52; 95% confidence interval [CI] = 0.48-0.56; P < .001), 5.34 in the 3rd month (RR = 0.35; 95% CI = 0.32-0.38; P < .001), and 2.23 in the 17 to 29 months (RR = 0.15; 95% CI = 0.13-0.17; P < .001). In-ICU all-cause mortality rate decreased from 16.17% at baseline to 13.68% (RR = 0.84; P = .0013) at 17 to 29 months. CONCLUSIONS: The implemented approach was effective, and a similar intervention could be applied in other ICUs of low- and middle-income countries to reduce CLABSI and in-ICU all-cause mortality rates.

How I Do It: Transcutaneous tibial nerve stimulation TENSI+ system.

Overactive bladder (OAB) is a common condition that significantly impacts the quality of life (QoL), well-being and daily functioning for both men and women. Among various treatments, peripheral tibial nerve stimulation (PTNS) emerges as an effective third-line treatment for OAB symptoms, with options for either a percutaneous approach (P-PTNS) or by transcutaneous delivery (T-PTNS). Recent studies have shown negligible differences between P-PTNS and T-PTNS efficacy in alleviating urinary urgency and frequency and QoL improvement and, overall no difference in efficacy over antimuscarinic regimens. The TENSI+ system offers a cutting-edge transcutaneous approach, allowing patients to self-administer treatment conveniently at home with electrical stimulation delivery through surface electrodes. It stands out for its ease of preparation, tolerability, and high levels of patient satisfaction. Prospective multicentric data highlights TENSI+ to be an effective and safe treatment for lower urinary tract symptoms with high treatment adherence at 3 months. This paper aims to familiarize readers with the TENSI+ system, current studies, device assembly, operation, and treatment recommendations.

Extrapulmonary bronchogenic cyst: A case report.

INTRODUCTION: Bronchogenic cysts (BCs) are rare congenital lesions that originate from the tracheobronchial bud and can be found in any organ derived from the embryonic foregut. Complete surgical excision is the treatment of choice, and the definitive diagnosis is established by histopathological examination. PRESENTATION OF THE CASE: 41-year-old female with diastolic arterial hypertension and a heterogeneous mass, with multiple calcifications and a solid component with well-defined regular contours. A biochemical study revealed no functionality. Intraoperatively we noticed an adrenal gland-dependent mass with a cystic component and an area of sebaceous content and histological examination confirmed a bronchogenic cyst. DISCUSSION: The majority of cases of BCs are asymptomatic. They can be intrapulmonary, mediastinal or ectopic, being the left adrenal region the most common retroperitoneal location. Symptomatic cysts should always be surgically resected either by thoracotomy or a minimally invasive technique, which has been shown to improve postoperative discomfort and shorten hospital stay with reliable postoperative outcomes. CONCLUSION: Despite their low incidence, it is important to consider BCs in the differential diagnosis of retroperitoneal masses, particularly in the left para-adrenal region.

Breaking the clean room barrier: exploring low-cost alternatives for microfluidic devices.

Microfluidics is an interdisciplinary field that encompasses both science and engineering, which aims to design and fabricate devices capable of manipulating extremely low volumes of fluids on a microscale level. The central objective of microfluidics is to provide high precision and accuracy while using minimal reagents and equipment. The benefits of this approach include greater control over experimental conditions, faster analysis, and improved experimental reproducibility. Microfluidic devices, also known as labs-on-a-chip (LOCs), have emerged as potential instruments for optimizing operations and decreasing costs in various of industries, including pharmaceutical, medical, food, and cosmetics. However, the high price of conventional prototypes for LOCs devices, generated in clean room facilities, has increased the demand for inexpensive alternatives. Polymers, paper, and hydrogels are some of the materials that can be utilized to create the inexpensive microfluidic devices covered in this article. In addition, we highlighted different manufacturing techniques, such as soft lithography, laser plotting, and 3D printing, that are suitable for creating LOCs. The selection of materials and fabrication techniques will depend on the specific requirements and applications of each individual LOC. This article aims to provide a comprehensive overview of the numerous alternatives for the development of low-cost LOCs to service industries such as pharmaceuticals, chemicals, food, and biomedicine.

Laparoendoscopic assisted surgery for a gastrointestinal stromal tumor (GIST): A case report.

INTRODUCTION: Gastrointestinal stromal tumors (GIST) are infrequent, and clinical presentation varies between asymptomatic and diffuse symptoms such as abdominal pain and dyspepsia. Surgical approach depends on location and size of the tumor. There are some reports of the specific surgical approach for GIST located at the gastroesophageal junction. This is a case report of a patient with a GIST located specifically at the gastroesophageal junction and the surgical approach selected for the treatment. PRESENTATION OF THE CASE: A 70-year-old patient who developed an episode of upper gastrointestinal bleeding with hemorrhagic shock accompanied by elevated troponins that required transfusion therapy and whose endoscopic evaluation showed a subcardial ulcerated lesion of 16 × 5 mm, located 2 cm below the z-line. The lesion was biopsied and was negative for malignancy. A combined surgical approach for resection by combined laparoscopy and submucosal resection by upper gastrointestinal endoscopy was performed by the interventional gastroenterology service and surgical oncology service. DISCUSSION: Specific management of GISTs depends on the location of the tumor, even though, complete surgical resection remains the gold standard treatment. Minimally invasive techniques can be used to assess these tumors leading to shorter hospital stays and lesser risk of complications. Laparoendoscopic cooperative surgery is a promising approach for managing lesions near the gastroesophageal junction. CONCLUSION: GISTs located near the gastroesophageal junction require a complex approach. The laparaendoscopic approach seems to be a feasible approach for GIST in the gastroesophageal junction.

Laminin as a Biomarker of Blood-Brain Barrier Disruption under Neuroinflammation: A Systematic Review.

Laminin, a non-collagenous glycoprotein present in the brain extracellular matrix, helps to maintain blood-brain barrier (BBB) integrity and regulation. Neuroinflammation can compromise laminin structure and function, increasing BBB permeability. The aim of this paper is to determine if neuroinflammation-induced laminin functional changes may serve as a potential biomarker of alterations in the BBB. The 38 publications included evaluated neuroinflammation, BBB disruption, and laminin, and were assessed for quality and risk of bias (protocol registered in PROSPERO; CRD42020212547). We found that laminin may be a good indicator of BBB overall structural integrity, although changes in expression are dependent on the pathologic or experimental model used. In ischemic stroke, permanent vascular damage correlates with increased laminin expression (ß and γ subunits), while transient damage correlates with reduced laminin expression (α subunits). Laminin was reduced in traumatic brain injury and cerebral hemorrhage studies but increased in multiple sclerosis and status epilepticus studies. Despite these observations, there is limited knowledge about the role played by different subunits or isoforms (such as 411 or 511) of laminin in maintaining structural architecture of the BBB under neuroinflammation. Further studies may clarify this aspect and the possibility of using laminin as a biomarker in different pathologies, which have alterations in BBB function in common.

Drenaje percutáneo trans-gástrico de necrosis pancreática amurallada complicado en paciente pediátrico / WON transgastric percutaneous drainage complicated in a pediatric patient

Resumen Las complicaciones de la pancreatitis aguda se dividen en sistémicas y locales, y entre estas últimas se encuentran las colecciones líquidas pancreáticas agudas, la colección necrótica aguda, el pseudoquiste y la necrosis amurallada pancreática. Se reporta el caso de niña de nueve años con pancreatitis aguda idiopática severa, quien desarrolló una necrosis pancreática amurallada de 75 x 45 mm. Por la persistencia del dolor abdominal y la intolerancia a la vía oral, a pesar del manejo médico, se indicó un abordaje percutáneo transgástrico para su tratamiento. Se obtuvo éxito técnico y terapéutico a través del drenaje de la colección, permitiendo iniciar la vía oral y disminuyendo los requerimientos de analgesia. La paciente evolucionó satisfactoriamente, con alta quirúrgica a los 13 días y retiro del catéter a los 30 días. A los cuatro meses de seguimiento se evidenció una colección recidivante asintomática, manejándose de manera conservadora. Lo anterior permite considerar que el abordaje percutáneo transgástrico es una técnica segura y eficaz; sin embargo, evaluar la efectividad y morbimortalidad en población pediátrica requiere de otros estudios que posibiliten llegar conclusiones que generen mayor evidencia científica.

Abstract The complications of acute pancreatitis are divided into systemic and local such as acute pancreatic fluid collections, acute necrotic collection, pseudocyst and pancreatic walled necrosis. The case of a nine-year-old girl with idiopathic severe acute pancreatitis who developed a pancreatic walled necrosis of 75 x 45mm is reported. Due to the persistence of abdominal pain and intolerance to the oral route, despite medical treatment, a trans gastric percutaneous approach was indicated for the treatment of pancreatic walled necrosis. Technical and therapeutic success was obtained through the drainage of the collection, allowing to start the oral route and decreasing the analgesia requirements. The patient evolved satisfactorily, with surgical discharge after 13 days and removal of the catheter after 30 days. After 4 months of follow-up, a recurrent asymptomatic collection was evidenced, being handled in a conservative manner. The above mentioned allows considering that the trans-gastric percutaneous approach is a safe and effective technique; however, evaluating the effectiveness and morbimortality in pediatric population requires other studies that make possible to reach conclusions that generate more scientific evidence.

Sedación para procedimientos gastroenterológicos en tiempos de pandemia por SARS-CoV-2. Artículo de reflexión / Sedation in times of pandemic by SARS-CoV-2. Article of reflection

RESUMEN Introducción: el SARS-CoV-2 es un nuevo coronavirus descrito por primera vez en China y con alta capacidad de propagación. Su presentación clínica más frecuente son los síntomas respiratorios, aunque se han descrito otros como los gastrointestinales. La transmisión ocurre por gotas, aerosoles, vía fecal oral, conjuntiva, fómites y por contacto directo con fluidos corporales del paciente. En este sentido, los procedimientos realizados en las salas de endoscopia deben considerarse de alto riesgo. Objetivo: describir y analizar las medidas de prevención frente al SARS-CoV-2 para la práctica endoscópica-anestésica u otros procedimientos que requieran sedación, con el fin de disminuir la exposición y así minimizar el contagio del personal de salud. Resultados: la respuesta global se ha enfocado en la utilización de elementos de protección personal para tratar de disminuir el riesgo al que se encuentra expuesto el personal de salud. Sin embargo, debido a la prontitud de la emergencia, no se han podido generar evidencias de alta calidad que permitan dar recomendaciones definitivas. Reflexión: el personal de salud debe tomar todas las medidas de protección que puedan ser consideradas como efectivas, además deconstruir protocolos y fomentar la adherencia a los mismos.

SUMMARY Introduction: SARS-CoV-2 is a new coronavirus described for the first time in China, with high capacity of propagation. Its most frequent clinical presentation is respiratory symptoms; however, others have been described as gastrointestinal. Transmission occurs by droplets, aerosols, oral fecal route, conjunctiva, fomites and by direct contact with body fluids of the patient. In this sense, the procedures performed in endoscopy rooms should be considered high risk. Objective: To describe and analyze preventive measures against SARS-CoV-2 for endoscopic-anesthesia practice or other procedures that require sedation, in order to reduce exposure and thus minimize contagion of health personnel. Results: The global response has focused on the use of personal protective equipment to try to reduce the risk to which health care personnel are exposed, but due to the urgency of the emergency, it has not been possible to generate high quality evidence to give definitive recommendations. Reflection: Health personnel should take all protective measures that can be considered effective, and also deconstruct protocols and encourage adherence to them.

Síntomas neurológicos motores de inicio súbito en el síndrome de Leriche / Sudden onset motor neurological symptoms in Leriche's syndrome

Resumen El síndrome de Leriche es una enfermedad poco frecuente, con gran morbilidad y mortalidad, que ocurre debido a oclusión de las ramas principales de la aorta abdominal por debajo de la bifurcación de las arterias renales. Clínicamente, se caracteriza por la tríada de claudicación, impotencia y disminución de los pulsos femorales. El diagnóstico se confirma por ecografía Doppler abdominal o angiografía por tomografía computarizada y el tratamiento se basa en el restablecimiento del flujo por debajo del nivel de la oclusión. Se presenta el caso de un paciente con cuadro clínico atípico de dolor lumbar, paraparesia y livideces de miembros inferiores de inicio súbito, con rápido deterioro de su estado general que requirió intervención endovascular urgente. En esta ocasión, los síntomas neurológicos pueden ser explicados por la reducción del flujo sanguíneo de la arteria espinal magna, que en el 25 % de la población se origina en L1 o por debajo de ella y puede generar isquemia de la médula espinal. La presentación atípica de este reporte lo convierte en un desafío clínico de gran importancia.

Abstract Leriche syndrome is a rare disease with high morbidity and mortality that occurs due to occlusion of the main branches of the abdominal aorta below the bifurcation of the renal arteries. Clinically, it is characterized by the triad of claudication, impotence and decreased femoral pulses. Diagnosis is confirmed by abdominal Doppler ultrasound or computed tomography angiography and treatment is based on restoration of arterial flow below the level of occlusion. We present the case of a patient with an atypical clinical presentation of sudden onset of low back pain, paraparesis and lividity of the lower limbs, with rapid deterioration of his general condition that required urgent endovascular intervention. On this occasion, the neurological symptoms can be explained by reduced blood flow in the magna spinal artery, which in 25% of the population originates at or below L1 and can generate spinal cord ischemia. The atypical presentation of this report makes it a clinical challenge of great importance.

Estudio de mecanismos efectores y contra-reguladores mediados por la sobre-activación de inflamasoma durante la respuesta anti-tumoral / Study of effector and counter-regulatory mechanisms mediated by the over-activation of the inflammasome during the anti-tumor response

La manipulación del sistema inmune utilizando inmunoterapias para desencadenar respuestas anti-tumorales ha revolucionado el tratamiento de una variedad de cánceres, sin embargo, pocos pacientes se benefician de las terapias desarrolladas hasta el momento. Por este motivo, es necesario identificar nuevos blancos terapéuticos en la inmunidad anti-tumoral. En nuestro grupo demostramos que TMEM176B es un canal catiónico intracelular con capacidades inmunorreguladoras, y que la deleción génica de Tmem176bo su bloqueo farmacológico con el compuesto BayK8644, ocasiona una sobre-activación del inflamasoma, que favorece el rechazo de tumores trasplantables y mejora el efecto anti-tumoral de las terapias de bloqueo de puntos de control. A su vez, evidenciamos que la deleción génica de Tmem176b induce la acumulación de linfocitos Th17en el ganglio linfático drenante del tumor y el rechazo tumoral mediado por IL-17, cuya expresión por linfocitos T CD4+se ha asociado a la respuesta clínica al bloqueo de PD-1, en pacientes portadores de melanoma metastásico. Por otro lado, en mi tesina de grado demostramos que los tumores de ratones Tmem176b-/-presentan una mayor expresión y actividad enzimática de indoleamina 2,3-dioxigenasa (IDO1) respecto a ratones WT. IDO1 es una enzima capaz de degradar el triptófano por la vía de la quinurenina, y se ha identificado como un mecanismo contra-regulador relevante desencadenado durante las inmunoterapias anti-tumorales. Esto nos llevó a plantear la hipótesis de que la sobre-activación del inflamasoma, dada por la inhibición de TMEM176B, genera respuesta anti-tumoral a través de la activación de linfocitos Th17, pero que podrían existir mecanismos contra-reguladores mediados por IDO1 a nivel tumoral que pueden disminuir este efecto. Teniendo esta hipótesis en mente, nos planteamos como objetivos,por un lado, evaluar el rol de la IL-17 durante las terapias anti-tumorales basadas en la sobre-activación del inflamasoma y el bloqueo de puntos de control inmunológico, y por otro, estudiar la relevancia de los mecanismos contra-reguladores mediados por IDO1 durante la respuesta anti-tumoral generada por la sobre-activación del inflamasoma. En lo que refiere al primer objetivo, demostramos que durante el tratamiento con anti-PD-1, los animales Il-17a-/-presentan una mejor respuesta anti-tumoral, con una mayor sobrevida que los animales WT. Sin embargo, al evaluar estos parámetros en ratones tratados con anti-PD-1 en combinación con BayK8644, observamos que los animales con la deleción génica de Il-17aresponden peor al tratamiento, presentando una sobrevida significativamente menor que los animales WT. Estos resultados parecen indicar que en ausencia de la sobre-activación del inflamasoma mediada por el BayK8644, prevalecen los efectos pro-tumorales de la IL-17, siendo de esta forma perjudicial para el tratamiento con anti-PD-1. En contraste, en un contexto de sobre-activación del inflamasoma, la IL-17 parecería tener un efecto anti-tumoral, relevante para favorecer los efectos de la terapia con anti-PD-1. Respecto al segundo objetivo, evidenciamos que, al igual que como sucede para los animalesTmem176b-/-, los ratones con tumor trasplantado, tratados con BayK8644 presentan un aumento significativo en la expresión y actividad de IDO1a nivel tumoral, respecto a los animales tratados con vehículo. Además, identificamos a las células tumorales como las principales productoras de IDO1 a nivel tumoral, y demostramos que esta población celular es la única que presenta una expresión de IDO1 significativamente mayor en los animales Tmem176b-/-y tratados con BayK8644, respecto a su grupo control. En línea con estos resultados, observamos que la expresión basal de IDO1 a nivel de la célula tumoral parece ser necesaria para la expresión aumentada de IDO1 en los tumores de los animales Tmem176b-/-. Adicionalmente, evidenciamos que el infiltrado de células T CD8+a nivel tumoral se correlaciona de forma positiva con la expresión de IDO1 en células tumorales de animales tratados con BayK8644 o vehículo, pero no con la expresión de esta enzima en las células no tumorales. Además, demostramos que el aumento en la expresión de IDO1 en los tumores de ratones tratados con BayK8644 es dependiente de las células T CD8+, ya que su depleción in vivo lleva a una disminución en los niveles de expresión de esta enzima a nivel tumoral. Estos resultados demuestran que la sobre-activación del inflamasoma, mediada por la deleción génica de Tmem176bo por su inhibición farmacológica con BayK8644, genera un aumento en la expresión y actividad de IDO1 a nivel de la célula tumoral, constituyendo un mecanismo contra-regulador relevante, dependiente de células T CD8+

Ira y cyberbullying entre adolescentes: amistad, injusticia e imagen en entornos digitales / Ira e cyberbullying entre adolescentes: amizade, injustiça e imagem em ambientes digitais / Anger and cyberbullying among adolescents: friendship, injustice and image in digital environments

RESUMEN. El cyberbullying es un problema creciente, sobre todo entre la población adolescente. Este fenómeno amerita investigación científica que apunte a explicarlo en el mayor número de aspectos posibles, incluyendo las emociones. En este marco, la presente investigación se ocupa de analizar la ira en adolescentes involucrados en situaciones de cyberbullying. Se realizó un estudio con diseño cualitativo y método fenomenológico-hermenéutico, en el que se entrevistaron 31 adolescentes entre los 12 y 17 años de edad, implicados en situaciones de cyberbullying en los roles de víctimas o espectadores. Las víctimas de ciberacoso sienten ira, especialmente, cuando las agresiones provienen de parte de personas a quienes consideraban sus amigos. Esta emoción se experimenta junto con otros afectos como la tristeza y la vergüenza. Para los espectadores, la ira está asociada a situaciones de injusticia y a la percepción de que los agresores no tienen empatía hacia las víctimas. Los adolescentes reconocen los efectos negativos que el cyberbullying tiene sobre la imagen de las personas en entornos digitales. Comprender el lugar que ocupan las emociones en las agresiones mediadas por TIC es fundamental para generar conocimiento que sirva de base para el diseño e implementación de programas de intervención psicosocial del ciberacoso, y promover espacios de reflexión sobre de lo que significa la intimidad, la amistad y la confianza en la era digital.

RESUMO. O cyberbullying é um problema crescente, especialmente entre a população adolescente. Esse fenômeno merece pesquisas científicas que visam explicá-lo no maior número possível de aspectos, incluindo emoções. Dentro dessa estrutura, a presente investigação se preocupa em analisar a raiva em adolescentes envolvidos em situações de cyberbullying. Foi realizado um estudo com desenho qualitativo e método fenomenológico-hermenêutico, no qual foram entrevistados 31 adolescentes entre 12 e 17 anos de idade, envolvidos em situações de cyberbullying no papel de vítimas ou espectadores. As vítimas do cyberbullying sentem raiva, principalmente quando os ataques são de pessoas que consideram amigas. Essa emoção é experimentada junto com outros afetos, como tristeza e vergonha. Para os espectadores, a raiva está associada a situações de injustiça e à percepção de que os agressores não têm empatia pelas vítimas. Os adolescentes reconhecem os efeitos negativos que o cyberbullying tem sobre a imagem das pessoas em ambientes digitais. Compreender o lugar que as emoções ocupam nas agressões mediadas pelas TIC é essencial para gerar conhecimento que serve de base para o desenho e implementação de programas de intervenção psicossocial do cyberbullying e promover espaços de reflexão sobre o que significa intimidade, amizade e confie na era digital.

ABSTRACT. Cyberbullying is a growing problem, especially among the adolescent population. This phenomenon warrants scientific research that aims to explain it in as many aspects as possible, including emotions. In this context, this research deals with the analysis of anger in adolescents involved in cyberbullying situations. A study with qualitative design and the phenomenological-hermeneutic method was conducted, in which 31 adolescents between the ages of 12 and 17 were interviewed, involved in cyberbullying situations in the roles of victims or bystanders. Victims of cyberbullying feel angry, especially when the assaults come from people they considered their friends. This emotion is experienced along with other affections such as sadness and shame. For bystanders, anger is associated with situations of injustice and the perception that aggressors have no empathy for the victims. Adolescents recognize the negative effects that cyberbullying has on people's image in digital environments. Understanding the place of emotions in ICT-mediated aggressions is essential to generate knowledge that serves as the basis for the design and implementation of psychosocial intervention programs in cyberbullying, and to promote spaces for reflection on what intimacy, friendship, and trust mean in the digital age.

Targeting TMEM176B Enhances Antitumor Immunity and Augments the Efficacy of Immune Checkpoint Blockers by Unleashing Inflammasome Activation.

Although immune checkpoint blockers have yielded significant clinical benefits in patients with different malignancies, the efficacy of these therapies is still limited. Here, we show that disruption of transmembrane protein 176B (TMEM176B) contributes to CD8+ T cell-mediated tumor growth inhibition by unleashing inflammasome activation. Lack of Tmem176b enhances the antitumor activity of anti-CTLA-4 antibodies through mechanisms involving caspase-1/IL-1ß activation. Accordingly, patients responding to checkpoint blockade therapies display an activated inflammasome signature. Finally, we identify BayK8644 as a potent TMEM176B inhibitor that promotes CD8+ T cell-mediated tumor control and reinforces the antitumor activity of both anti-CTLA-4 and anti-PD-1 antibodies. Thus, pharmacologic de-repression of the inflammasome by targeting TMEM176B may enhance the therapeutic efficacy of immune checkpoint blockers.

Benzylglucosinolate Derived Isothiocyanate from Tropaeolum majus Reduces Gluconeogenic Gene and Protein Expression in Human Cells.

Nasturtium (Tropaeolum majus L.) contains high concentrations of benzylglcosinolate. We found that a hydrolysis product of benzyl glucosinolate-the benzyl isothiocyanate (BITC)-modulates the intracellular localization of the transcription factor Forkhead box O 1 (FOXO1). FoxO transcription factors can antagonize insulin effects and trigger a variety of cellular processes involved in tumor suppression, longevity, development and metabolism. The current study evaluated the ability of BITC-extracted as intact glucosinolate from nasturtium and hydrolyzed with myrosinase-to modulate i) the insulin-signaling pathway, ii) the intracellular localization of FOXO1 and, iii) the expression of proteins involved in gluconeogenesis, antioxidant response and detoxification. Stably transfected human osteosarcoma cells (U-2 OS) with constitutive expression of FOXO1 protein labeled with GFP (green fluorescent protein) were used to evaluate the effect of BITC on FOXO1. Human hepatoma HepG2 cell cultures were selected to evaluate the effect on gluconeogenic, antioxidant and detoxification genes and protein expression. BITC reduced the phosphorylation of protein kinase B (AKT/PKB) and FOXO1; promoted FOXO1 translocation from cytoplasm into the nucleus antagonizing the insulin effect; was able to down-regulate the gene and protein expression of gluconeogenic enzymes; and induced the gene expression of antioxidant and detoxification enzymes. Knockdown analyses with specific siRNAs showed that the expression of gluconeogenic genes was dependent on nuclear factor (erythroid derived)-like2 (NRF2) and independent of FOXO1, AKT and NAD-dependent deacetylase sirtuin-1 (SIRT1). The current study provides evidence that BITC might have a role in type 2 diabetes T2D by reducing hepatic glucose production and increasing antioxidant resistance.

The flavones apigenin and luteolin induce FOXO1 translocation but inhibit gluconeogenic and lipogenic gene expression in human cells.

The flavones apigenin (4',5,7,-trihydroxyflavone) and luteolin (3',4',5,7,-tetrahydroxyflavone) are plant secondary metabolites with antioxidant, antiinflammatory, and anticancer activities. We evaluated their impact on cell signaling pathways related to insulin-resistance and type 2 diabetes. Apigenin and luteolin were identified in our U-2 OS (human osteosarcoma) cell screening assay for micronutrients triggering rapid intracellular translocation of the forkhead box transcription factor O1 (FOXO1), an important mediator of insulin signal transduction. Insulin reversed the translocation of FOXO1 as shown by live cell imaging. The impact on the expression of target genes was evaluated in HepG2 (human hepatoma) cells. The mRNA-expression of the gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pc), the lipogenic enzymes fatty-acid synthase (FASN) and acetyl-CoA-carboxylase (ACC) were down-regulated by both flavones with smaller effective dosages of apigenin than for luteolin. PKB/AKT-, PRAS40-, p70S6K-, and S6-phosphorylation was reduced by apigenin and luteolin but not that of the insulin-like growth factor receptor IGF-1R by apigenin indicating a direct inhibition of the PKB/AKT-signaling pathway distal to the IGF-1 receptor. N-acetyl-L-cysteine did not prevent FOXO1 nuclear translocation induced by apigenin and luteolin, suggesting that these flavones do not act via oxidative stress. The roles of FOXO1, FOXO3a, AKT, sirtuin1 (SIRT1), and nuclear factor (erythroid-derived2)-like2 (NRF2), investigated by siRNA knockdown, showed differential patterns of signal pathways involved and a role of NRF2 in the inhibition of gluconeogenic enzyme expression. We conclude that these flavones show an antidiabetic potential due to reduction of gluconeogenic and lipogenic capacity despite inhibition of the PKB/AKT pathway which justifies detailed investigation in vivo.

Estudio piloto sobre selenio plasmático en personas sanas de Antioquia, Colombia / Pilot study on plasma selenium in healthy individuals of Antioquia, Colombia

Problema: en América Latina son muy pocos y en Colombia no existen estudios sobre el nivel de selenio sérico/plasmático. Objetivo: medir el selenio plasmático en un grupo de personas aparentemente sanas.Objetivo: medir el selenio plasmático en un grupo de personas aparentemente sanas. Materiales y metódos: se usó un diseño descriptivo transversal. Como indicadores de estado nutricional se midieron selenio, retinol, ferritina e índice de masa corporal. El selenio se cuantificó por espectrofotometría de absorción atómica con horno de grafito (atomización electrotérmica y corrección de fondo por efecto Zeeman). Resultados: se evaluaron 40 personas residentes en Turbo o El Bagre (Antioquia, Colombia). El selenio plasmático (µg/L) fue 43,5±12,7; intervalo de confianza 95% 39,5-47,5; 66% con <46 (límite inferior europeo). El retinol estuvo bajo (<20 µg/dL) en 11% de las personas y la ferritina fue baja en 44%. Conclusiones:se requieren más estudios y en grupos humanos de mayor tamaño y con apropiados criterios de selección, en diferentes regiones del país, con distintos sexos y edad, así como estudios de contenido de selenio en suelo y en alimentos, para construir un panorama adecuado en Colombia.

Problem: In Latin America are few and in Colombia there are no studies on the level of serum/plasma selenium. Objective: To measure selenium in plasma in a group of apparently healthy people. Methodology: A descriptive and longitudinal study in which plasma selenium, retinol, ferritin and body mass index were measured. Selenium was measured by Graphite Furnace Atomic Absorption Spectrometry (electrothermal atomization and background correction by Zeeman effect). Results: In total, 40 individuals from Turbo or El Bagre (Antioquia, Colombia) were evaluated. Selenium level (µg/L): 43,5±12,7; confidence interval 95% 39,5-47,5; in 66% was <46 (lowest European reference level). Retinol was low (<20 µg/dL) in 11% of the individuals and ferritin levels were very low in 44%. Conclusions: In order to build an adequate snapshot of the situation in Colombia, we must develop more studies with larger groups of individuals, with appropriate selection criteria in different regions of the country, with both genders and different ages. Also, studies of Se content in soil and food.

Malaria: eficacia de amodiaquina-sulfadoxina-pirimetamina, estado nutricional y variantes alélicas del gen CYP2C8 / Malaria: efficacy of amodiaquine-sulfadoxine-pyrimethamine, nutritional status and alellic variaton of CYP2C8 gen

Problema: La respuesta terapéutica antimalárica depende de múltiples determinantes asociados con el plasmodio (especie, mutaciones, cantidad, etc.) y al hospedero (nutrición, genes, metabolismo, etc.), pero los últimos son poco conocidos. Objetivos: Evaluar en pacientes con malaria falciparum no complicada, tratados con amodiaquina-sulfadoxina-pirimetamina (AQ-SP), algunas relaciones entre la respuesta terapéutica (RTA), el estado nutricional y las variaciones alélicas del gen CYP2C8. Metodología: Estudio clínico controlado, con asignación aleatoria, balanceado, no ciego. La RTA se evaluó según la Organización Mundial de la Salud. Se hizo análisis antropométrico, se midieron las concentraciones plasmáticas de retinol, ferritina y selenio; se analizaron las variantes 2C8*1 (silvestre), 2C8*2 (Il29F) y 2C8*3 (R139K y K399R) del gen CYP2C8. Resultados: Se evaluaron 33 pacientes, todos con respuesta terapéutica adecuada con AQ-SP; 10% presentó deficiencia de retinol, 25% de selenio y 40% de ferritina. Sólo un paciente presentó la variante CYP2C8*2 en forma heterozigótica y el resto fueron homocigóticos para el alelo silvestre de este gen. Ninguno presentó la mutación R139K en CYP2C8*3. Del alelo K339R de CYP2C8*3 no se pudieron obtener fragmentos aptos de digerir, aún haciendo adaptaciones del método y no fue posible conocer la razón de este hecho. Estos datos concuerdan con los resultados de otro análisis similar en 23 pacientes, tratados solo con amodiaquina: 22% presentaron alguna variante (5 con CYP2C8*2 y 2 con CYP2C8*3). En el gen CYP2C8*3 se identificó sólo la mutación R139K, presente en 2 individuos.Conclusión: Sólo uno de los 33 pacientes (3%) presentó la variante CYP2C8*2, en forma heterozigótica; el resto fueron homocigóticos para el alelo silvestre de esta variante. Ninguno presentó la mutación R139K de la variante CYP2C8*3. Es el primer informe para Latinoamérica.

Problem: Therapeutic response to antimalarials depends on multiple determinants associated with the parasite (species, mutations, parasitaemia, etc.) and the host (nutrition, genes, metabolism, etc.), but little is known about the host factors. Objectives: To evaluate in non-complicated falciparum malaria patients undergoing treatment with amodiaquine-sulfadoxine-pyrimethamine (AQ-SP), some relationships between treatment response, nutritional status and characteristics of the gen CYP2C8. Methodology: A randomly assigned, balanced, non blind, controlled clinical design. Treatment response was assessed according to WHO 1998 criteria. Analysis included anthropometry, plasma levels of retinol, ferritin and selenium, and assessment of 2C8*1 (wild), 2C8*2 (Il29F) and 2C8*3 variants of CYP2C8 (R139K y K399R). Results: 33 patients were studied, all of them evidenced adequate treatment response, 10% had retinol deficiency, 25% selenium deficiency and 40% low ferritine levels. One patient exhibited the variant Il29F of CYP2C8*2 in a heterozygous fashion, the remaining individuals were homozygous for the wild form of this gene. The mutant R139K of CYP2C8*3 was absent in all individuals. Amplification fragments obtained of K339R (CYP2C8*3 gen) were not suitable for digestion, regardless of the modifications performed. These results confirm previous findings made in 22% of 23 patients in whom some variation was observed (5 in CYP2C8*2 and 2 in CYP2C8*3). For CYP2C8*3 the mutant R139K, was observed in 2 individuals. Conclusion: only one of the 33 patients (3%) had CYP2C8*2 in a heterozygous fashion, the remaining were homozygous for the wild allele of this variant. None of the patients had the mutation R139K of the CYP2C8*3 variant. This is a novel report for Latin America.

Nasopharyngeal adenocarcinomas: a clinicopathologic study of 44 cases including immunohistochemical features of 18 papillary phenotypes.

Nasopharyngeal adenocarcinomas (NPACs) are uncommon neoplasms with a diverse histomorphology and clinical behavior. The purpose of our study was to better understand the clinicopathologic characteristics of NPACs and to identify the histologic and immunohistochemical features that distinguish the subtypes of papillary NPACs. We conducted a retrospective review of 44 cases of NPACs accessioned between 1985 and 2000. We obtained follow-up information for all patients. We identified 24 females and 20 males, ranging in age from 9 to 74 years (median, 50 years). There were 28 salivary gland type, 13 conventional low-grade papillary NPACs of surface origin, and 3 metastatic adenocarcinomas, 2 thyroid and 1 lung. We performed immunohistochemical studies in 18 papillary NPACs. Two of the low-grade papillary NPACs simulated thyroid carcinoma; they expressed CK7, CK19, and TTF-1 but were negative for thyroglobulin. Polymorphous low-grade papillary NPACs expressed diffuse reactivity to S-100, whereas low-grade papillary NPACs were negative or focally positive. All patients with low-grade NPACs were alive at 5 to 20 years. In contrast, 18 (64.2%) of the 28 patients with salivary gland-type NPACs had died of the disease or were living with disease at follow-up. Primary NPACs can be classified by their morphology and clinical behavior into 2 groups: surface origin type and salivary gland type. Papillary NPACs can be identified by their histology and selective immunohistochemical expression. Pathologist should distinguish the different types of NPACs because their treatment and prognosis differ.