Mid-line destructive syndrome secondary to infectionby paracoccidioides sp. A case report

Midline destructive disease is a group of severe and destructive inflammatory and tumor diseases of the midface area, among which paracoccidioidomycosis is one of the main etiologies in tropical countries. Paracoccidioidomycosis is an endemic mycosis caused by fungi of the genus Paracoccidioides. Its blastoconidia form favors hematogenous spread, affecting various tissues such as adrenal glands, reticulo-endothelial tissue, or oral mucosa, where it can manifest as a destructive midline syndrome. We present a case of paracoccidioidomycosis with affection in the oral cavity, which debuted as a chronic midline des-tructive disease with sever airway compromise that required surgical treatment for the risk of obstruction of the airway. The patient received systemic treatment with good response

Single Events in a COTS Soft-Error Free SRAM at Low Bias Voltage Induced by 15-MeV Neutrons

This paper presents an experimental study of the sensitivity to 15-MeV neutrons of Advanced Low Power SRAMs (A-LPSRAM) at low bias voltage little above the threshold value that allows the retention of data. This family of memories is characterized by a 3D structure to minimize the area penalty and to cope with latchups, as well as by the presence of integrated capacitors to hinder the occurrence of single event upsets. In low voltage static tests, classical single event upsets were a minor source of errors, but other unexpected phenomena such as clusters of bitflips and hard errors turned out to be the origin of hundreds of bitflips. Besides, errors were not observed in dynamic tests at nominal voltage. This behavior is clearly different than that of standard bulk CMOS SRAMs, where thousands of errors have been reported

Acute pancreatitis induced by hypertriglyceridemia and treatment with plasmapheresis : case report

ABSTRACT: Hypertriglyceridemia (HTG) is a potential cause of acute pancreatitis (AP), especially when its value is higher than 1.000 mg/dL. Different therapeutic measures have been proposed for patients with AP secondary to HTG, including the one that seems to be more effective: plasmapheresis. We report the case of a patient with severe HTG (triglycerides 6.480 mg/dL) that suffered from AP, and had favorable evolution with plasmapheresis.RESUMEN: La hipertrigliceridemia (HTG) es una causa potencial de pancreatitis aguda (PA), especialmente cuando su valor es mayor de 1.000 mg/dL. Se han propuesto diferentes medidas para el tratamiento de pacientes con PA secundaria a HTG, entre ellas la que parece ser más efectiva: la plasmaféresis. Se reporta el caso de un paciente con HTG grave (triglicéridos de 6.480 mg/dL) que presentó una PA y cuya evolución fue favorable con la plasmaféresis

Stabilization of LKB1 and Akt by neddylation regulates energy metabolism in liver cancer

The current view of cancer progression highlights that cancer cells must undergo through a post-translational regulation and metabolic reprogramming to progress in an unfriendly environment. In here, the importance of neddylation modification in liver cancer was investigated. We found that hepatic neddylation was specifically enriched in liver cancer patients with bad prognosis. In addition, the treatment with the neddylation inhibitor MLN4924 in Phb1-KO mice, an animal model of hepatocellular carcinoma showing elevated neddylation, reverted the malignant phenotype. Tumor cell death in vivo translating into liver tumor regression was associated with augmented phosphatidylcholine synthesis by the PEMT pathway, known as a liver-specific tumor suppressor, and restored mitochondrial function and TCA cycle flux. Otherwise, in protumoral hepatocytes, neddylation inhibition resulted in metabolic reprogramming rendering a decrease in oxidative phosphorylation and concomitant tumor cell apoptosis. Moreover, Akt and LKB1, hallmarks of proliferative metabolism, were altered in liver cancer being new targets of neddylation. Importantly, we show that neddylation-induced metabolic reprogramming and apoptosis were dependent on LKB1 and Akt stabilization. Overall, our results implicate neddylation/signaling/metabolism, partly mediated by LKB1 and Akt, in the development of liver cancer, paving the way for novel therapeutic approaches targeting neddylation in hepatocellular carcinoma

Stabilization of LKB1 and Akt by neddylation regulates energy metabolism in liver cancer

The current view of cancer progression highlights that cancer cells must undergo through a post-translational regulation and metabolic reprogramming to progress in an unfriendly environment. In here, the importance of neddylation modification in liver cancer was investigated. We found that hepatic neddylation was specifically enriched in liver cancer patients with bad prognosis. In addition, the treatment with the neddylation inhibitor MLN4924 in Phb1-KO mice, an animal model of hepatocellular carcinoma showing elevated neddylation, reverted the malignant phenotype. Tumor cell death in vivo translating into liver tumor regression was associated with augmented phosphatidylcholine synthesis by the PEMT pathway, known as a liver-specific tumor suppressor, and restored mitochondrial function and TCA cycle flux. Otherwise, in protumoral hepatocytes, neddylation inhibition resulted in metabolic reprogramming rendering a decrease in oxidative phosphorylation and concomitant tumor cell apoptosis. Moreover, Akt and LKB1, hallmarks of proliferative metabolism, were altered in liver cancer being new targets of neddylation. Importantly, we show that neddylation-induced metabolic reprogramming and apoptosis were dependent on LKB1 and Akt stabilization. Overall, our results implicate neddylation/signaling/metabolism, partly mediated by LKB1 and Akt, in the development of liver cancer, paving the way for novel therapeutic approaches targeting neddylation in hepatocellular carcinoma

Vertidos tóxicos al río Guadiamar: propuestas técnicas para su corrección

Inmediatamente de producirse el vertido tóxico al río Guadiamar, el Grupo T.A.R. se lanzó sin pensarlo dos veces a la búsqueda de soluciones técnicas a un panorama desolador y de efectos desconocidos, todos ellos amenazantes. El ácido “se comía el suelo inundado” por la riada, el agua retenida en Entremuros a pH 3, y con un enorme contenido de metales pesados, ocupaba una extensión de kilómetros. Nos hundimos en el agua hasta el cuello, y cuando nos cubría cogimos la barca, metimos el río a pedazos en nuestro laboratorio, para trabajar todas las hipótesis, ensayar todas las posibilidades. Peleando con la realidad le sacamos datos al Guadiamar, diseñamos actuaciones, poniéndole ingeniería a cuantas hipótesis nos planteaba la situación. En primera fila observamos las mejores actuaciones que nadie diseñó. El propio río, activando sus defensas naturales, mejoró la calidad del agua retenida en el dique de Entremuros subiendo el pH y precipitando los metales pesados. Los mecanismos de entrada de los metales pesados en la cadena trófica parecían ser lentos, dando tiempo a que la retirada de los lodos tóxicos llevada a cabo por la Administración fuera eficaz y diera tiempo a realizar tanto esfuerzo. Aunque el Guadiamar ha trabajado muy duro en su propia recuperación, con su ayuda hemos elaborado una gran cantidad de propuestas técnicas; unas para actuaciones de emergencia, otras a corto, medio y largo plazo. También hemos dado forma a un Plan frente a las previsibles avenidas de este primer otoño después del vertido. Nuestro objetivo ha sido poner a disposición soluciones preparadas para todo tipo de problemas, en primera o en segunda instancia. Prevenir no solo una o dos contingencias, se ha tratado de estar preparado para la mayor cantidad de eventualidades posibles. Por ello algunas serán utilizables, otras estarán en reserva, y muchas irían al cajón de los papeles. Pero ahí están por si acaso. Este libro recoge los trabajos de campo, los ensayos de laboratorio y la ingeniería desarrollada en los primeros cuatro meses. Durante el siguiente preparamos la edición del mismo, mientras, en paralelo, continuábamos en el trabajo experimental y el diseño. Cuando se cumpla el quinto mes, el 25 de Septiembre de 1998, lo presentaremos, ciento cincuenta días después... Con la financiación de la Diputación de Sevilla hemos preparado la primera edición en formato CD Rom e Internet, con muy poco coste para acceder a su contenido. En poco tiempo saldrá la edición en papel, con la misma financiación que la primera. Nos gustaría que este documento fuera entendido como lo que es, en nuestra opinión, una llamada urgente al debate de las ideas. Tratamos de ofrecer la información necesaria y el foro donde recoger las propuestas que seguramente muchos pueden aportar sin saber como transmitir sus experiencias. El Grupo de Tratamiento de Aguas Residuales (T.A.R.) abre con este libro la MESA DE DISCUSIÓN, para buscar un poco de luz, avanzar en las soluciones técnicas a la inmensa tarea de recuperar el río Guadiamar. El libro presenta lagunas, unas por la enorme prisa, otra por falta de datos, muchas por nuestra escasez de conocimientos. Dicen en España que “lo mejor es enemigo de lo bueno”...,y nos gustaría recoger ideas hoy mejor que mañana, que podría ser tarde. Nos comprometemos a seguir trabajando en soluciones técnicas, innovaciones tecnológicas e investigación aplicada a la recuperación del Guadiamar, a conocer lo ocurrido y su remedio. Nos comprometemos a publicar de la misma forma los resultados obtenidos, de manera que la discusión y el debate sigan siempre abiertos. El grupo T.A.R. podría ser un punto de intercambio de conocimientos universal, abierto, respetuoso y tolerante, universitario en definitiva, y por tanto útil en el cumplimiento de sus obligaciones. La primera necesidad de responder urgentemente, está dando paso a unas actuaciones programadas, a medida de los efectos de las correcciones introducidas. Deben instaurarse políticas de prevención y nuevas actuaciones para recuperar el Guadiamar, mejorar urgentemente las condiciones del entorno. Aprender de las soluciones adoptadas y generar mejores prácticas, puede ser una buena conclusión del trabajo realizado por tanta gente. Lo que empezó siendo una carrera de velocidad se nos convierte en un maratón, ya no hay que correr explosivamente, hay que mantener un ritmo en la carrera; hay que persistir en el esfuerzo todos los días durante mucho tiempo. Este nuevo desafío sigue siendo duro y difícil. Podéis contar con el Grupo T.A.R. para recorrer el duro camino de la Recuperación

The mitochondrial negative regulator MCJ is a therapeutic target for acetaminophen-induced liver injury

Acetaminophen (APAP) is the active component of many medications used to treat pain and fever worldwide. Its overuse provokes liver injury and it is the second most common cause of liver failure. Mitochondrial dysfunction contributes to APAP-induced liver injury but the mechanism by which APAP causes hepatocyte toxicity is not completely understood. Therefore, we lack efficient therapeutic strategies to treat this pathology. Here we show that APAP interferes with the formation of mitochondrial respiratory supercomplexes via the mitochondrial negative regulator MCJ, and leads to decreased production of ATP and increased generation of ROS. In vivo treatment with an inhibitor of MCJ expression protects liver from acetaminophen-induced liver injury at a time when N-acetylcysteine, the standard therapy, has no efficacy. We also show elevated levels of MCJ in the liver of patients with acetaminophen overdose. We suggest that MCJ may represent a therapeutic target to prevent and rescue liver injury caused by acetaminophen

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe