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Atherosclerosis evolves through dysregulated lipid metabolism interwoven with exaggerated inflammation. Previous work implicating the receptor for advanced glycation end products (RAGE) in atherosclerosis prompted us to explore if Diaphanous 1 (DIAPH1), which binds to the RAGE cytoplasmic domain and is important for RAGE signaling, contributes to these processes. We intercrossed atherosclerosis-prone Ldlr−/− mice with mice devoid of Diaph1 and fed them Western diet for 16 weeks. Compared to male Ldlr−/− mice, male Ldlr−/−Diaph1−/− mice displayed significantly less atherosclerosis, in parallel with lower plasma concentrations of cholesterol and triglycerides. Female Ldlr−/−Diaph1−/− mice displayed significantly less atherosclerosis compared to Ldlr−/− mice and demonstrated lower plasma concentrations of cholesterol, but not plasma triglycerides. Deletion of Diaph1 attenuated expression of genes regulating hepatic lipid metabolism, Acaca, Acacb, Gpat2, Lpin1, Lpin2 and Fasn, without effect on mRNA expression of upstream transcription factors Srebf1, Srebf2 or Mxlipl in male mice. We traced DIAPH1-dependent mechanisms to nuclear translocation of SREBP1 in a manner independent of carbohydrate- or insulin-regulated cues but, at least in part, through the actin cytoskeleton. This work unveils new regulators of atherosclerosis and lipid metabolism through DIAPH1.

Hypoxia is a crucial factor contributing to maintenance of atherosclerotic lesions. The ability of ABCA1 to stimulate the efflux of cholesterol from cells in the periphery, particularly foam cells in atherosclerotic plaques, is an important anti-atherosclerotic mechanism. The posttranscriptional regulation by miRNAs represents a key regulatory mechanism of a number of signaling pathways involved in atherosclerosis. Previously, miR-199a-5p has been shown to be implicated in the endocytic and retrograde intracellular transport. Although the regulation of miR-199a-5p and ABCA1 by hypoxia has been already reported independently, the role of miR-199a-5p in macrophages and its possible role in atherogenic processes such us regulation of lipid homeostasis through ABCA1 has not been yet investigated. Here, we demonstrate that both ABCA1 and miR-199a-5p show an inverse regulation by hypoxia and Ac-LDL in primary macrophages. Moreover, we demonstrated that miR-199a-5p regulates ABCA1 mRNA and protein levels by directly binding to its 3’UTR. As a result, manipulation of cellular miR-199a-5p levels alters ABCA1 expression and cholesterol efflux in primary mouse macrophages. Taken together, these results indicate that the correlation between ABCA1-miR-199a-5p could be exploited to control macrophage cholesterol efflux during the onset of atherosclerosis, where cholesterol alterations and hypoxia play a pathogenic role.

En la actualidad, comenzamos a reflexionar sobre una de las estrategias para enfrentar la pobreza y la pobreza extrema que se ha destacado en el Perú. Los emprendedores peruanos se caracterizan por el ingenio, la creatividad y siempre están dispuestos a encontrar soluciones en contextos financieros desfavorables. De hecho, aproximadamente la mitad de los negocios del país está impulsada por necesidades económicas. Ante esto, es necesario plantear una buena idea y desarrollar un plan para convertirla en una oportunidad de negocio. Es así que el proyecto Haku Wiñay entra a tallar, puesto que es un proyecto que tiene como objetivo desarrollar la capacidad productiva y el espíritu empresarial de familias pobres y extremadamente pobres que viven en áreas densamente pobladas con el fin de aumentar y diversificar los ingresos independientes sostenibles.

Background Aneurysm clipping requires the proficiency of several skills, yet the traditional way of practicing them has been recently challenged, especially by the growth of endovascular techniques. The use of simulators could be an alternative educational tool, but some of them are cumbersome, expensive to implement, or lacking in realism. The aim of this study is to evaluate a reusable low-cost 3-dimensional printed training model we developed for aneurysm clipping. Methods The simulator was designed to replicate the bone structure, arteries, and targeted aneurysms. Thirty-two neurosurgery residents performed a craniotomy and aneurysm clipping using the model and then filled out a survey. They were divided into Junior and Senior groups. Descriptive, exploratory, and confirmatory factor analysis was performed using IBM SPSS statistical software. Results The overall residents' response was positive, with high scores to face validity and content validity questions. There was no significant statistical difference between the Junior and Senior groups. The confirmatory factor and internal consistency analysis confirmed that the evaluation was highly reliable. Globally, 97% of the residents found the model was useful and would repeat the simulator experience. The financial cost is $2500 USD for implementation and only $180 USD if further training sessions are required. Conclusions The main strengths of our training model are its highlighted realism, adaptability to trainees of different levels of expertise, sustainability, and low cost. Our data support the concept that it can be incorporated as a new training opportunity during professional specialty meetings and/or within residency academic programs.

Pituitary abscesses (PAs) are a rare clinical entity which may arise from normal pituitary tissue or underlying lesions within the gland. Rathke’s cleft cysts (RCCs) are not commonly associated with the development of PA. Retrospective chart review of three patients with PAs within RCCs at a single university center and review of the literature. Three cases are reported. The first case presented with fever and headache and a history of prior surgery due to RCC and a recent respiratory tract infection. The second case had a history of recent skin infections and presented with sudden onset headache and hypopituitarism. In the third case, chronic visual field impairment prompted an ophthalmologic evaluation resulting in a diagnosis of an adenoma and an infected RCC. In all three cases, an endoscopic endonasal approach was performed to drain infected tissue and allowed microbiological identification of gram-positive cocci, followed by treatment with antibiotics for at least three weeks. Cases in the literature are scarce and the diagnosis is usually made intraoperatively due to non-specific manifestations and imaging. PAs arising from underlying pituitary lesions are less common than primary PAs. Differential diagnosis should include pituitary apoplexy, hypophysitis and other cystic lesions. PAs occurring in RCCs are infrequent. Clinical manifestations are commonly subacute, without septic symptoms. Imaging is usually non-specific. Preoperative diagnosis is infrequent and a broad differential diagnosis should be considered. Empirical antimicrobial therapy should be initiated and adjusted after obtaining cultures to reduce the rate of recurrence and improve clinical outcomes.

The objective of this retrospective case series was to report overall peri-operative complications, short- to mid-term outcome, and owner satisfaction of closing tibial wedge osteotomy (CTWO) using locking compression plates, in dogs weighing ≤ 20 kg, for the treatment of cranial cruciate ligament disease. Medical records from 2015 to 2020 were reviewed for surgical technique, intraoperative findings, and complications. Pre- and postoperative radiographs were evaluated for healing, complications, and tibial plateau angles (TPAs). A follow-up telephone questionnaire was used to evaluate patient outcome and owner satisfaction. Eighty-one client-owned dogs (12.0 kg ± 3.0 kg; 95% CI: 8.4 to 15.5) (N = 89 stifles) were included in the study. Mean tibial plateau angles at preoperative, postoperative, and 8-week follow-up were 29.7° ± 4.1° (95% CI: 25.5 to 33.8), 6.7° ± 2.6° (95% CI: 4.2 to 9.2), and 7.8° ± 2.4° (95% CI: 4.9 to 10.6), respectively. Tibial plateau angles had significantly increased at the 8-week follow-up assessment by 1.04° ± 1.8°; 95% CI: -0.8 to -2.8) compared to immediately postoperative. The postoperative complication rate was 4.49% (4 cases). Overall satisfaction was excellent with good return to limb function. Closing tibial wedge osteotomy can be performed in dogs ≤ 20 kg, using locking compression plates, achieving excellent overall owner satisfaction and return to function.L’objectif de cette série de cas rétrospectifs était de rapporter les complications peropératoires globales, les résultats à court et à moyen terme et la satisfaction du propriétaire de l’ostéotomie de fermeture du coin tibial (CTWO) à l’aide de plaques de compression verrouillables, chez les chiens pesant ≤ 20 kg, pour le traitement de pathologie du ligament croisé crânien.Les dossiers médicaux de 2015 à 2020 ont été examinés pour la technique chirurgicale, les résultats peropératoires et les complications. Les radiographies pré- et postopératoires ont été évaluées pour la guérison, les complications et les angles du plateau tibial (TPA). Un questionnaire téléphonique de suivi a été utilisé pour évaluer les résultats des patients et la satisfaction des propriétaires.Quatre-vingt-un chiens de clients (12,0 kg ± 3,0 kg; IC à 95 % : 8,4 à 15,5) (N = 89 grassets) ont été inclus dans l’étude. Les angles moyens du plateau tibial en préopératoire, postopératoire et à 8 semaines de suivi étaient de 29,7° ± 4,1° (IC à 95 % : 25,5 à 33,8), 6,7° ± 2,6° (IC à 95 % : 4,2 à 9,2) et 7,8° ± 2,4° (IC à 95 % : 4,9 à 10,6), respectivement. Les angles du plateau tibial avaient significativement augmenté lors de l’évaluation de suivi à 8 semaines de 1,04° ± 1,8°; IC à 95 % : −0,8 à −2,8) par rapport à immédiatement postopératoire. Le taux de complications postopératoires était de 4,49 % (quatre cas). La satisfaction globale était excellente avec un bon retour à la fonction des membres.L’ostéotomie de fermeture du coin tibial peut être réalisée chez les chiens ≤ 20 kg, à l’aide de plaques de compression verrouillables, ce qui permet d’obtenir une excellente satisfaction globale du propriétaire et un retour à la fonction.(Traduit par Docteur Serge Messier).

We establish a Quantitative Structure-Property Relationships study on the Henry’s law constant of 530 heterogeneous compounds, including pesticides, solvents, aromatic hydrocarbons and persistent pollutants. The multivariable linear regression models are established with the Replacement Method (RM) technique, by searching the best 1–8 molecular descriptors on 26,795 available non-conformational structural variables. These descriptors are derived from different freely available softwares, such as PaDEL, Mold2, DataWarrior, QuBiLs-MAS and CORAL. The present results are compared with the estimations provided by the HENRYWIN module of EPI Suite, and serve as a tool for predicting the Henry’s law constant on related chemical structures.

Mestrado em Contabilidade, Fiscalidade e Finanças Empresariais O propósito deste estudo é analisar a associação entre gestão de resultados e a divulgação de resultados non-GAAP tendo em conta o aparente aumento do desejo, por parte dos gestores, em divulgar este tipo de resultados. A amostra do estudo é composta por 2 122 empresas cotadas, de 14 países europeus, cobrindo um horizonte temporal dos anos de 2011 a 2018. De modo a calcular a medida de gestão de resultados, foi utilizado o modelo de Jones (1991), ajustado posteriormente por Kothari, Leone and Wasley (2005), de maneira a estimar accruals discricionários. Os resultados mostram que a divulgação de relatórios non-GAAP se rege por um motivo oportunista, tendo em conta que, forneço evidência empírica que indica que este tipo de divulgação está correlacionado com altos níveis de gestão de resultados baseada em accruals (AEM). Por outro lado, a prática de divulgação non-GAAP está relacionada com AEM negativa, indicando que são estrategicamente utilizadas como métodos complementares. Estes resultados não são consistentes com as conclusões obtidas por Doyle, Jennings and Soliman (2013) e Black, Christensen, Taylor e Schmardebeck (2017). Tendo em conta a direção da gestão de resultados baseada em accruals, os resultados obtidos indicam que os gestores que manipulam os seus resultados financeiros com o intuito de reduzi-los são mais propensos a divulgar relatórios non-GAAP. As conclusões obtidas através desta pesquisa permitem o desenvolvimento do conhecimento inerente a uma, até então debilmente explicada, associação entre dois campos académicos largamente abordados pela literatura existente. This study aims at analysing the association between Earnings Management and non-GAAP reporting practices taking into account an apparent increase of the managers´ desire in disclosing non-GAAP earnings (Jeanjean, Martinez and Davrinche, 2018). I perform a research based on data collected from Factiva and Amadeus databases. The study sample is composed by 2 122 listed companies, from 14 European countries, covering a time horizon from the years 2011 to 2018. To measure Earnings Management, I use the Jones model (1991), adjusted by Kothari, Leone and Wasley (2005), in order to estimate abnormal accruals. Empirical findings suggest that this kind of disclosures is correlated with higher levels of accrual-based earnings management (AEM) signifying that a disclosure of non-GAAP numbers follows an opportunistic motive. I also provide evidence indicating that the practice of non-GAAP reporting is correlated with downward AEM indicating that are strategically used as complement tools. This assumption is not consistent with Doyle, Jennings and Soliman (2013) and Black, Christensen, Taylor and Schmardebeck (2017) conclusions. Additionally, the obtained results suggest that executives who managed their earnings downwards are more likely to disclose non-GAAP reports. Moreover, the company´s complexity and the presence of a Big 4 auditing firm influence the practice of non-GAAP disclosures. My work contributes to extant research enabling the development of knowledge about an association of these two widely addressed academic fields, so far weakly explained by prior research. info:eu-repo/semantics/publishedVersion

Water solubility is a key physicochemical parameter in pesticide control and regulation, although sometimes its experimental determination is not an easy task. In this study, we present Quantitative Structure-Property Relationships (QSPRs) for predicting the water solubility at 20 °C of 1211 approved heterogeneous pesticide compounds, collected from the online Pesticides Properties Data Base (PPDB). Validated and generally applicable Multivariable Linear Regression (MLR) models were established, including molecular descriptors carrying constitutional and topological aspects of the analyzed compounds. The most representative descriptors were selected from the exploration of a large number of about 18,000 structural variables. A hybrid approach that involves a molecular descriptor, a fingerprint, and a flexible descriptor showed the best predictive performance. Fil: Fioressi, Silvina Ethel. Universidad de Belgrano. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bacelo, Daniel Enrique. Universidad de Belgrano. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Rojas, Cristian. Universidad del Azuay.; Ecuador Fil: Aranda, José Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Duchowicz, Pablo Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina

The present work describes the development of an in silico model to predict the retention time (tR) of a large Compound DataBase (CDB) of pesticides detected in fruits and vegetables. The model utilizes ultrahigh-performance liquid chromatography electrospray ionization quadrupole-Orbitrap (UHPLC/ESI Q-Orbitrap) mass spectrometry (MS) data. The available CDB was properly curated, and the pesticides were represented by conformation-independent molecular descriptors. In an attempt to improve the model predictions, the best four MLR models obtained were subjected to a consensus analysis. The optimal model was evaluated by means of the coefficient of determination and the residual standard deviation in calibration, validation, and prediction, along other internal and external validation criteria to accomplish the guidelines defined by the Organization for Economic Co-operation and Development. Finally, the in silico model was applied to predict the tR of an external set of 57 pesticides.

Non conformational QSPR models were built for the aqueous solubility (mol/L) at 25 °C of 5610 structurally heterogeneous compounds, including pesticides, drugs and solvents, among others, with a wide range of aqueous solubility. The experimental database was taken from the WATERNT module for solubility estimation of the EPI Suite program. A large set of 23,723 conformation-independent molecular descriptors was explored to obtain trustworthy but simple multivariable linear regression models. It is found that four selected molecular descriptors improve the predictive capacity of the WATERNT program, thus achieving satisfactory predictions for the water solubility through an alternative methodology.

Achalasia is the most common primary motor disorder of the esophagus. Its reported incidence is low, even more in pediatric patients. Laparoscopic Heller myotomy is the current stan dard of treatment. During the last years, per-oral endoscopic myotomy (POEM) has been positioned as a safe and effective therapeutic alternative as the Heller procedure for esophageal achalasia. Ob jective: To describe the POEM technique and report the first pediatric case in our country.11-year-old patient, previously healthy, who presented with progressive dysphagia for solids and liquids and weight loss. The study concluded a type II achalasia. The patient underwent a POEM and had a postoperative course without incidents. One year after the intervention, symptomatic, endoscopic and manometric resolution have been documented.The described case is the first POEM in a pediatric patient in our country. Esophageal achalasia is uncommon in pediatrics and POEM has demonstrated clinical success and safety comparable to laparoscopic Heller myotomy in short and medium term. Long-term follow-up will determine its definitive role in the treatment of pediatric patients with esophageal achalasia.

La presente tesis doctoral se enfoca en la construcción de modelos predictivos y que sean de utilidad como herramienta para asistir la búsqueda de estructuras químicas con valores favorables de la propiedad/actividad. La habilidad de predecir las propiedades fisicoquímicas y actividades biológicas de las sustancias químicas permite analizar de antemano las propiedades de compuestos nuevos, tóxicos o que demandan demasiado tiempo de evaluación experimental. Así, los modelos pueden ser utilizados para la predicción de las propiedades fisicoquímicas/actividades biológicas de nuevos compuestos químicos sintetizados en el laboratorio y carentes de datos experimentales. Entre los objetivos específicos del presente trabajo de tesis se citan: - desarrollar modelos matemáticos que resulten capaces de cuantificar relaciones hipotéticas entre la estructura química y la propiedad/actividad de pesticidas, a través de la técnica del análisis de regresión lineal multivariable aplicada a diferentes bases de datos de propiedades de interés agronómico extraídas de la literatura actualizada. Para ello, se utilizarán los mejores descriptores moleculares que surjan del análisis de miles de descriptores estructurales, obtenidos de programas computacionales de libre acceso - investigar el comportamiento de los descriptores flexibles u óptimos en los estudios QSPR-QSAR de pesticidas, e incorporarlos en los modelos en caso que resulten adecuados. Para ello, uno debe ser capaz de definir la construcción matemática del descriptor flexible, y debe elegir el procedimiento de ajuste de sus partes variables para alcanzar las mejores predicciones de la propiedad, evitando el sobreajuste del conjunto de calibración para así poder alcanzar una calidad predictiva aceptable y el modelo supere su validación externa - abordar el tratamiento de grandes conjuntos moleculares de alta diversidad estructural y que incluyan pesticidas - demostrar a través de los resultados encontrados que un enfoque basado en la representación estructural independiente de la conformación molecular permite alcanzar predicciones confiables de la propiedad/actividad estudiada La calidad de las predicciones conseguidas con estos estudios QSPR-QSAR de pesticidas se compara con la información experimental disponible y a través de las predicciones alcanzadas por metodologías teóricas alternativas de la literatura., Facultad de Ciencias Exactas

The ANTARES dataset is a large collection of known and verified experimental bioconcentrationfactor data, involving 851 highly heterogeneous compounds from which 159 of them arepesticides. In this Special Issue devoted to "Computational Toxicology and Fate of Pesticides?,we predict the Bioconcentration Factor of the ANTARES dataset by means of a conformationindependentQSPR approach. A large number of 27,017 molecular descriptors are explored, withthe main intention of capturing the most relevant structural characteristics affecting the studiedproperty. The structural descriptors are derived with different freewares, such as PaDEL, EpiSuite, CORAL, Mold2, RECON and QuBiLs-MAS, and so it is interesting to find out the way thatthe different descriptor softwares complement each other in order to improve the statistical qualityof the established QSPR. The best multivariable linear regression models are found with theReplacement Method variable subset selection technique. The proposed QSPR model improvesprevious reported models of the bioconcentration factor in the present dataset. Fil: Aranda, José Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Bacelo, Daniel Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Belgrano. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina Fil: Leguizamón Aparicio, María Silvia del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas "Dr. Jorge J. Ronco". Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Ciencias Aplicadas; Argentina Fil: Ocsachoque, Marco Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas "Dr. Jorge J. Ronco". Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Ciencias Aplicadas; Argentina Fil: Castro, Eduardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Duchowicz, Pablo Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina

We predict the soil sorption coefficient for a heterogeneous set of 643 organic non-ionic compounds by means of Quantitative Structure-Property Relationships (QSPR). A conformation-independent representation of the chemical structure is established. The 17,538molecular descriptors derived with PaDEL and EPI Suite softwares are simultaneously analyzed through linear regressions obtained with the Replacement Method variable subset selection technique. The best predictive three-descriptors QSPR is developed on a reduced training set of 93 chemicals, having an acceptable predictive capability on 550 test set compounds. We also establish a model with a single optimal descriptor derived from CORAL freeware. The present approach compares fairly well with a previously reported one that uses Dragon descriptors., Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas

Systemic lupus erythematosus (SLE) is an autoimmune disease that may be associated to high morbidity and mortality. Disease course is variable and unpredictable and although the prognosis and survival of these patients has dramatically improved, treatment of severe multiorganic organic affection in this condition remains a therapeutic challenge. Since B lymphocytes have an important role in the pathogenesis of SLE, it is expected that the targeting of these cells exerts a significant therapeutic effect in SLE patients with severe multiorganic manifestations. In an open clinical trial, we have explored the therapeutic potential of Rituximab (an anti-CD20 monoclonal antibody) administration in SLE patients with severe nephritis (n=22) or neuropsychiatric manifestations (n=6) or massive pulmonary hemorrhage (n=3). In most cases, we observed significant improvement in both clinical and laboratory parameters, with good tolerance and few side effects. Thus, patients with severe lupus nephritis showed improvement in disease activity (MEX-SLEDAI index) with a significant reduction (p

The Aragon Water Commission consists of 65 members and 17 groups of stakeholders: social, economic, sectoral and local organizations, neighbourhood movements, experts in water policy, and the university, among others. Yet, despite its wide-ranging membership, it has registered achievements that would have been unthinkable only a few years ago. It has passed judgement on the Aragon Water Infrastructure Plan; drawn up, and approved the Principles of Water Policy on the basis of consensus; and reached agreements that have broken the logjam on such controversial projects as the expansion of the Yesa reservoir. These successes have generated a scenario without winners or losers in which it will be possible to meet the expected future demand for water, and use it rationally, while respecting environmental values and permitting new developments free of the uncertainty that conflicts generate.

Caveolin-1 (Cav-1) is the major structural protein essential to the formation of the caveolae in endothelial cells. Cav-1 is thought to play an important role in the regulation of cellular cholesterol homeostasis, a process that needs to be properly controlled to limit and prevent cholesterol accumulation and eventually atherosclerosis. Genetic ablation of Cav-1 on an apoE knockout background inhibits the progression of atherosclerosis, while re-expression of Cav-1 in the endothelium promotes lesion expansion by affecting several processes including endothelial cell proliferation, migration, and nitric oxide production in vitro and increased expression of vascular cell adhesion molecule-1. Specifically, in vivo study shows that loss of Cav-1 reduces LDL infiltration into the artery wall and inhibits progression of atherosclerosis. However, surprisingly, we found that knock down of Cav-1 in human endothelial cells increases the binding and uptake of diI-LDL in vitro suggesting that Cav-1 decreases transcytosis of LDL. Moreover, Caveolin-1 has also been implicated in the regulation of inflammation in endothelial cells. Here we show that Cav-1 affects the induction of cell adhesion molecules in endothelial cells by inflammatory mediators including TLR2 ligand Pam3cys, IL-1B, and TNF. Specifically, knock-down of Cav-1 in human endothelial cells decreases the induction of ICAM-1, VCAM-1 and SELE in both mRNA and protein levels. Furthermore, we also show that silencing of Cav-1 attenuates the major signaling pathways that are involved in the induction of cell adhesion molecules including MAPK, AKT, JNK-AP1 and NF-κB pathways.

In April 1991 was performed the first kidney transplant at the Hospital Central Dr. Ignacio Morones Prieto. In August 1999, formally started the kidney transplant program.To describe the experience in kidney transplant at HCIMP.Retrospective cohort study, which includes all kidney transplants performed during the period August 1999 to June 2011. We excluded patients whose medical record was eliminated or with incomplete data for analysis. It describes the general characteristics of kidney transplant recipients, transplant-related variables, initial immunosuppression and complications. The survival analysis was performed using the Kaplan-Meier method. The curves were compared using the log-rank test.From August 1999 to June 2011 were performed 517 kidney transplants at Central Hospital, of which 411 patients were analyzed. Ten years overall graft-survival was 73%. Both, the history of infection or acute rejection were associated with lower graft survival. The main cause of death, in our population, was infectious processes.Graft survival at 10 years was 73%, which is similar to that reported in the literature. A history of acute rejection and infection are factors associated with lower survival.

Preemptive therapy reduces the risk of cytomegalovirus disease in high-risk kidney transplant patients. The advantage of this strategy is that only a fraction of patients receive antiviral drugs for a limited time, which decreases costs and toxicity but requires frequent monitoring and may not prevent complications of asymptomatic cytomegalovirus replication.Long-term graft-function and patient survival of high-risk kidney transplant patients who received preemptive therapy guided by pp65 antigenemia was compared to those whose assay remained negative throughout the first post-transplant year.Between August 1997 and March 2005, 24 of 272 patients were CMV D+/R-. Thirteen of the 24 (54.2%) developed a positive CMV assay during follow-up; the time between transplant and first positive antigenemia was 66.7 +/- 58.3 days (range 29-251 days). Four patients developed symptoms associated with CMV, one of whom succumbed from complications of CMV neumonitis. Overall, no significant differences were observed in SCr, eGFR, delta SCr, and delta eGFR during a 60-month followup between patients who developed CMV infection or disease and those who remained pp65 antigenemia-negative throughout the first 12 post-transplant months. Additionally, no deaths or graft loss occurred during the long-term follow up of this cohort.Our results suggest that in this high risk group of kidney transplant recipients, treating CMV replication using a preemptive strategy during the first posttransplant year is associated with a low rate of CMV complications and probably interferes with the alleged long-term negative indirect effects of CMV on kidney function and survival.

POEMS is an acronym that stands for a multisystem disorder that includes progressive sensorimotor Polyneuropathy, Organomegaly, Endocrinopathy, an M component in blood and/or concentrated urine, and Skin changes. The morphology of the peripheral nerves was mentioned in some of these cases and ranged from normal to those with segmental demyelination and/or degeneration of myelinated axons. We analyzed quantitatively the sural nerves of two cases of POEMS syndrome. Both nerves showed a severe loss of myelinated fibers, with a minor degree of regeneration. Degeneration of unmyelinated axons was observed, but to a lesser degree. There was marked collagen deposition in the endoneurium. The pathogenesis of the changes in the peripheral nerves and other organs in POEMS syndrome is still to be elucidated.

Current management of renal transplant recipients who are CMV seronegative (R-) and receive an organ from a seropositive donor (D+) is controversial. These patients are at high risk for CMV disease and are usually treated with ganciclovir prophylaxis at variable dose and duration. An alternative to this approach is to administer ganciclovir only to those patients who are identified by virological markers to be at the highest risk to develop the disease (preemptive therapy). This prospective trial was conducted to asses the value of preemptive therapy to prevent CMV disease in R-/D+ kidney transplant recipients on triple drug immunosuppression without antilymphocyte induction. Sixteen adults receiving their first kidney transplant were enrolled and followed with pp65 antigenemia assay performed biweekly for the first 16 postransplant weeks, and then monthly to complete 12 months. Ganciclovir (5 mg/kg/day i.v., for 15 days) was administered as preemptive therapy upon detection of one or more antigen-positive cells per 150 x 10(3) peripheral blood leucocytes examined. For those receiving preemptive therapy, pp65 antigenemia was also repeated after completion of the regimen. CMV antigenemia was detected in 7/16 patients. At mean follow-up of 9 months (4-12 m) none of the 16 patients developed CMV disease. CMV serology (IgM) became positive in all patients after the first antigenemia result. The last follow-up mean serum creatinine (SCr) level was similar in both groups (1.35 mg/dL). In CMV R-/D+, the use of preemptive therapy guided by pp65 antigenemia is effective in preventing CMV disease. By using this strategy, 9 of 16 patients were spared ganciclovir prophylaxis with no effect on rejection or CMV disease. The clinical benefit and cost/effectiveness of this strategy should be evaluated against universal prophylaxis in these high-risk patients.

The presence of myofibroblasts in the stroma of Phyllodes tumor of the breast has been documented in single cases by means of electron microscopy and immunohistochemistry. In this study, we re-evaluate the immunophenotype exhibited by 28 Phyllodes tumors (14 benign, 6 borderline and 8 malignant) in order to state the relevance of myofibroblasts as active stromal elements in these tumors. Vimentin showed positive immunostaining in the stroma of all the cases (100%), muscle-specific actin in 21 (75%), and desmin in 7 (25%). By contrast, stromal cells were uniformly negative for S-100 protein, keratins (AE1/AE3 and CAM 5.2), and epithelial membrane antigen (EMA). The epithelial component showed the typical two-layered arrangement of ducts in every case. Myoepithelial (outer) cells immunostained with muscle-specific actin and S-100 protein, and in some cases with EMA and keratins, whereas the epithelial (inner) layer did so with keratins and EMA. To conclude, we have found a prominent myofibroblastic differentiation in stromal cells of many of such tumors. Our results also prove that no differences in intensity or distribution of such actin-positive stromal cells are seen between benign, borderline or malignant counterparts.

Eric Sherman's Directing the Film: Film Directors on Their Art (Boston: Little, Brown, 1976---$15.00) Donald Spoto's The Art of Alfred Hitchcock: Fifty Years of His Motion Pictures (New York: Hopkinson and Blake, 1976---$13.00/8.95) Kemp R. Niver's D.W. Griffith: His Biograph Films in Perspective (Historical Films, P.O. Box 46505, Los Angeles, Calif. 90046---$12.00) Stephen Pendo's Raymond Chandler on Screen: His Novels into Film (Metuchen, N.J.: Scarecrow Press, 1976---$10.00) Ronald Lloyd's American Film Directors: The World as They See It (New York: New Viewpoints/Franklin Watts, 1976---price not given, paper) Maureen Lambray's The American Film Directors (New York: Whirlwind/Pathe Press, 1976---$22.50) Bob Thomas' Walt Disney: An American Original (New York: Simon and Schuster, 1976---$9.95) Richard Koszarski's Hollywood Directors, 1914-1940 (New York: Oxford University Press, 1976---$13.95/3.95) Philip Cecchettini and Don Whittemore's Passport to Hollywood: Film Immigramts (New York: McGraw-Hill, 197...

The case of a 42-year-old woman with no previous disease admitted for abdominal pain and ascites is presented. Analysis of the ascitic fluid demonstrated high concentrations of amylase with normal lipase. The diagnosis of peritoneal mesothelioma was obtained by laparotomy. This association has not been previously described. The authors suggest that this diagnostic possibility should be considered in patients without pancreatic disease and high amylase levels in ascitic fluid.