Optimizing the dialysate calcium concentration in bicarbonate haemodialysis

n/

Kidney involvement in the Schnitzler syndrome, a rare disease

The Schnitzler syndrome (SS) is a rare and underdiagnosed entity that associates a chronic urticarial rash, monoclonal IgM (or sometimes IgG) gammopathy and signs and symptoms of systemic inflammation. During the past 45 years, the SS has evolved from an elusive little-known disorder to the paradigm of a late-onset acquired auto-inflammatory syndrome. Though there is no definite proof of its precise pathogenesis, it should be considered as an acquired disease involving abnormal stimulation of the innate immune system, which can be reversed by the interleukin-1 receptor antagonist anakinra. It clearly expands our view of this group of rare genetic diseases and makes the concept of auto-inflammation relevant in polygenic acquired diseases as well. Increasing numbers of dermatologists, rheumatologists, allergologists, haematologists and, more recently, nephrologists, recognize the SS. The aim of this review is to focus on kidney involvement in the SS. Although the literature regarding kidney involvement in the SS is very poor it can be severe, as in our own case here reported, leading us to recommend the systematic search for nephropathy markers in the SS

Evidence for Two Modes of Synergistic Induction of Apoptosis by Mapatumumab and Oxaliplatin in Combination with Hyperthermia in Human Colon Cancer Cells

Colorectal cancer is the third leading cause of cancer-related mortality in the world-- the main cause of death from colorectal cancer is hepatic metastases, which can be treated with isolated hepatic perfusion (IHP). Searching for the most clinically relevant approaches for treating colorectal metastatic disease by isolated hepatic perfusion (IHP), we developed the application of oxaliplatin concomitantly with hyperthermia and humanized death receptor 4 (DR4) antibody mapatumumab (Mapa), and investigated the molecular mechanisms of this multimodality treatment in human colon cancer cell lines CX-1 and HCT116 as well as human colon cancer stem cells Tu-12, Tu-21 and Tu-22. We showed here, in this study, that the synergistic effect of the multimodality treatment-induced apoptosis was caspase dependent and activated death signaling via both the extrinsic apoptotic pathway and the intrinsic pathway. Death signaling was activated by c-Jun N-terminal kinase (JNK) signaling which led to Bcl-xL phosphorylation at serine 62, decreasing the anti-apoptotic activity of Bcl-xL, which contributed to the intrinsic pathway. The downregulation of cellular FLICE inhibitory protein long isoform (c-FLIPL) in the extrinsic pathway was accomplished through ubiquitination at lysine residue (K) 195 and protein synthesis inhibition. Overexpression of c-FLIPL mutant (K195R) and Bcl-xL mutant (S62A) completely abrogated the synergistic effect. The successful outcome of this study supports the application of multimodality strategy to patients with colorectal hepatic metastases who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway. © 2013 Song et al

Innovation Management Techniques and Tools: a review from Theory and Practice

Knowledge is considered to be an economic driver in today’s economy. It has become a commodity, a resource that can be packed and transferred. The objective of this paper is to provide a comprehensive review of the scope, trends and major actors (firms, organizations, government, consultants, academia, etc.) in the development and use of methods to manage innovation in a knowledge-driven economy. The paper identifies the main innovation management techniques (IMTs) aiming at the improvement of firm competitiveness by means of knowledge management. It will specifically focus on those IMTs for which knowledge is a relevant part of the innovation process. The research study, based on a survey at the European level, concludes that a knowledge-driven economy affects the innovation process and approach. The traditional idea that innovation is based on research (technology-push theory) and interaction between firms and other actors has been replaced by the current social network theory of innovation, where knowledge plays a crucial role in fostering innovation. Simultaneously, organizations in both public and private sectors have launched initiatives to develop methodologies and tools to support business innovation management. Higher education establishments, business schools and consulting companies are developing innovative and adequate methodologies and tools, while public authorities are designing and setting up education and training schemes aimed at disseminating best practices among all kinds of businesse

Launching a Novel Preclinical Infrastructure: Comparative Oncology Trials Consortium Directed Therapeutic Targeting of TNFα to Cancer Vasculature

Background: Under the direction and sponsorship of the National Cancer Institute, we report on the first pre-clinical trial of the Comparative Oncology Trials Consortium (COTC). The COTC is a novel infrastructure to integrate cancers that naturally develop in pet dogs into the development path of new human drugs. Trials are designed to address questions challenging in conventional preclinical models and early phase human trials. Large animal spontaneous cancer models can be a valuable addition to successful studies of cancer biology and novel therapeutic drug, imaging and device development. Methodology/Principal Findings: Through this established infrastructure, the first trial of the COTC (COTC001) evaluated a targeted AAV-phage vector delivering tumor necrosis factor (RGD-A-TNF) to αV integrins on tumor endothelium. Trial progress and data was reviewed contemporaneously using a web-enabled electronic reporting system developed for the consortium. Dose-escalation in cohorts of 3 dogs (n = 24) determined an optimal safe dose (5 x 1012 transducing units intravenous) of RGD-A-TNF. This demonstrated selective targeting of tumor-associated vasculature and sparing of normal tissues assessed via serial biopsy of both tumor and normal tissue. Repetitive dosing in a cohort of 14 dogs, at the defined optimal dose, was well tolerated and led to objective tumor regression in two dogs (14%), stable disease in six (43%), and disease progression in six (43%) via Response Evaluation Criteria in Solid Tumors (RECIST). Conclusions/Significance: The first study of the COTC has demonstrated the utility and efficiency of the established infrastructure to inform the development of new cancer drugs within large animal naturally occurring cancer models. The preclinical evaluation of RGD-A-TNF within this network provided valuable and necessary data to complete the design of first-in-man studies

Lo que la sociedad no quiere aceptar de algunas prácticas sexuales y sus implicaciones

Curso de Especial InterésEl objetivo del trabajo es promover la superación de estigmas y sesgos de algunas prácticas sexuales no aceptadas por la sociedad, a través de un curso dirigido a hombres y mujeres mayores de edad, el cual consiste en brindarle teorías, estadísticas y herramientas sobre cómo abordar temas tales como, derechos sexuales, reproductividad, género, erotismo y vinculación afectiva, además se recoge información sobre los tabúes y mitos a través de un formulario de tamizaje para personas mayores de 18 años.Resumen 1. Justificación 2. Marco Teórico 3. Marco metodológico 4. Criterios de inclusión y exclusión 5. Diseño y tamaño muestral 6. Consideraciones éticas 7. El producto 8. Resultados Conclusiones Referencias ApéndicesPregradoPsicólog

Impact of Intraoperative Parathyroid Hormone Monitoring on the Prediction of Multiglandular Parathyroid Disease

Optimal interpretation of the results of intraoperative parathyroid hormone (IOPTH) monitoring during neck exploration for primary hyperparathyroidism (pHPT) is still controversial. The reliability of the “50% rule” in multiglandular disease (MGD) is often disputed, mostly because of competing pathophysiologic paradigms. The aim of this study was to ascertain and corroborate the ability of IOPTH monitoring to detect MGD in a practice, combining conventional and alternative parathyroidectomy techniques. This is a retrospective single institution analysis of 69 consecutive patients undergoing cervical exploration for pHPT by various approaches. The IOPTH measurements were performed after induction of anesthesia but prior to skin incision and 10 minutes after excision of the first visualized enlarged parathyroid gland. In this series, 55 patients (80%) had single adenomas, and 14 patients (20%) had MGD. In 8 of the 14 patients with MGD, IOPTH levels were obtained sequentially after removal of every enlarged gland. Of these 8 patients, 6 (75%) had a false-positive decrease (decrease below 50% of baseline value in presence of another enlarged gland) failing to predict the presence of a second enlarged gland. In 2 cases IOPTH monitoring provided a true-negative result, correctly predicting MGD. If MGD is defined by gross morphologic criteria, IOPTH monitoring fails to predict the presence of MGD reliably. However, if MGD is defined by functional criteria, the course of these patients does not seem significantly affected. The importance of these findings must be further investigated, especially with regard to the outcome of minimally invasive parathyroid procedures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41301/1/268_2003_Article_7255.pd