Tyrosine kinase inhibitors for the therapy of anaplastic thyroid cancer

Anaplastic thyroid cancer (ATC) is often incurable so new therapeutic approaches are needed. Tyrosine kinases inhibitors (such as imanitib, sunitinib or sorafenib) are under evaluation for the treatment of ATC. Other vascular disrupting agents, such as combretastatin A4 phosphate, and antiangiogenic agents, such as aplidin, PTK787/ZK222584 and human VEGF monoclonal antibodies (bevacizumab, cetuximab), have been evaluated. Small-molecule adenosine triphosphate competitive inhibitors directed intracellularly at EGFRs tyrosine kinase, such as erlotinib or gefitinib, are also studied. Furthermore, new molecules have been shown to be active against ATC, such as CLM94 and CLM3. However, more research is needed to finally identify therapies able to control and to cure this disease

Impact of a hospice rapid response service on preferred place of death, and costs

Background: Many people with a terminal illness would prefer to die at home. A new palliative rapid response service (RRS) provided by a large hospice provider in South East England was evaluated (2010) to provide evidence of impact on achieving preferred place of death and costs. The RRS was delivered by a team of trained health care assistants and available 24/7. The purpose of this study was to (i) compare the characteristics of RRS users and non-users, (ii) explore differences in the proportions of users and non-users dying in the place of their choice, (iii) monitor the whole system service utilisation of users and non-users, and compare costs. Methods: All hospice patients who died with a preferred place of death recorded during an 18 month period were included. Data (demographic, preferences for place of death) were obtained from hospice records. Dying in preferred place was modelled using stepwise logistic regression analysis. Service use data (period between referral to hospice and death) were obtained from general practitioners, community providers, hospitals, social services, hospice, and costs calculated using validated national tariffs. Results: Of 688 patients referred to the hospice when the RRS was operational, 247 (35.9 %) used it. Higher proportions of RRS users than non-users lived in their own homes with a co-resident carer (40.3 % vs. 23.7 %); more non-users lived alone or in residential care (58.8 % vs. 76.3 %). Chances of dying in the preferred place were enhanced 2.1 times by being a RRS user, compared to a non-user, and 1.5 times by having a co-resident carer, compared to living at home alone or in a care home. Total service costs did not differ between users and non-users, except when referred to hospice very close to death (users had higher costs). Conclusions: Use of the RRS was associated with increased likelihood of dying in the preferred place. The RRS is cost neutral

Addressing quality and usability of surface water bodies in semi-arid regions with mining influences

Water resources management has considerable importance, specifically in the context of climate change. This subject has introduced new challenges in semi-arid regions with water quality problems, such as the Iberian Pyrite Belt, which is one of the largest metallogenetic provinces in the world and one of the driest regions in Europe. Positioned in the Mediterranean context, the region has a high density of polymetallic sulphide mines that promote the degradation of water systems. The present study aims to assess the water quality in the Pyrite Belt, considering a total of 34 surface water bodies, including constructed reservoirs, permanent and ephemeral streams, and mining facilities with accumulated water (e.g., pit lakes and mining dams). The water samples were analysed for physico-chemical properties, including field parameters (pH, electrical conductivity), alkalinity/acidity, hardness, anions, and potential toxic elements. The results were used for hydrochemical classifications and the assessment of suitability for public uses. Statistical methods, such as hierarchical cluster analysis and nearest centroid classifier, were used for grouping and evaluating the similarity between water bodies. Two groups were generated from the analysis: i) constructed lakes with alkaline and sodium signatures; and ii) waters suffering from the influence of mining wastes, e.g., showing high acidity, sulphate and metal contents. Therefore, the loss of water quality in the vicinity of mines reflects the impact of acid mine drainage. The methodological approach used may be applied to the integrated management of water resources in regions with mining influences and where it is necessary to combat drought and water scarcity scenarios.Patricia Gomes acknowledge FCT (Science and Technology Foundation, Portugal) by the research fellowship under the POCH (Programa Operacional Capital Humano) supported by the European Social Fund and National Funds of MCTES (Ministerio da Ciencia, Tecnologia e Ensino Superior) with reference SFRH/BD/108887/2015. This work was co-funded by the European Union through the European Regional Development Fund, based on COMPETE 2020 (Programa Operacional da Competitividade e Internacionalizacao) - project ICT (UID/GEO/04683/2013) with reference POCI-01-0145-FEDER-007690 and project Nano-MINENV number 029259

Diagnostic yield of renal biopsies: a retrospective single center review

<p>Abstract</p> <p>Background</p> <p>Previous studies have examined the spectrum of diseases identified with a kidney biopsy and the complications of the procedure. However, few studies have examined the utility of the test to clarify the diagnosis and guide treatment of pediatric patients. This retrospective, single-center chart review was performed to test the hypothesis that at least 80% of native kidney biopsies provide clinically valuable information that rationally guides diagnosis and patient management.</p> <p>Methods</p> <p>200 biopsies performed between January 1, 2000 and June 30, 2008 were reviewed. A scheme composed of six categories was devised to classify the utility of each kidney biopsy.</p> <p>Results</p> <p>196 complete case files were available for review. Twenty-four (12.2%) biopsies did not shed light on the diagnosis and were unhelpful in patient management – 21 biopsies (10.7%) were non-diagnostic and 3 (1.5%) failed to yield enough tissue for examination. The number of unhelpful biopsies did not cluster in any specific disease entity.</p> <p>Conclusion</p> <p>Our findings provide guidance to nephrologists about the total risk of a kidney biopsy, including uninformative results, when seeking informed consent for the procedure. The results suggest an appropriate balance has been reached which maximizes the use of kidney biopsies while minimizing the risk of this invasive procedure (word count: 202).</p

Benign splenosis mimicking peritoneal seeding in a bladder cancer patient: a case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Asymptomatic papillary fibroelastoma of the Aortic valve in a young woman - a case report

Echocardiography represents an invaluable diagnostic tool for the detection of intracardiac masses while simultaneously provides information about their size, location, mobility and attachment site as well as the presence and extent of any consequent hemodynamic derangement

Snail1 factor behaves as a therapeutic target in renal fibrosis.

Kidney fibrosis is a devastating disease that leads to organ failure, and no specific treatment is available to preserve organ function. In fibrosis, myofibroblasts accumulate in the interstitium leading to massive deposition of extracellular matrix and organ disfunction. The origin of myofibroblasts is multiple and the contribution of renal epithelial cells after undergoing epithelial-to-mesenchymal transition (EMT) is still debated. In a model unable to reactivate the EMT inducer Snail1 upon damage, we show that Snail1 is required in renal epithelial cells for the development of fibrosis. Damage-mediated Snail1 reactivation induces a partial EMT that relays fibrotic and inflammatory signals to the interstitium through the activation of TGF-β and NF-B pathways. Snail1-induced fibrosis can be reverted in vivo and inhibiting Snail1 in a model of obstructive nephropathy highly ameliorates fibrosis. These results reconcile conflicting data on the role of EMT in renal fibrosis and provide avenues for the design of antifibrotic therapies.pre-print8435 K

Quasispecies Theory and the Behavior of RNA Viruses

A large number of medically important viruses, including HIV, hepatitis C virus, and influenza, have RNA genomes. These viruses replicate with extremely high mutation rates and exhibit significant genetic diversity. This diversity allows a viral population to rapidly adapt to dynamic environments and evolve resistance to vaccines and antiviral drugs. For the last 30 years, quasispecies theory has provided a population-based framework for understanding RNA viral evolution. A quasispecies is a cloud of diverse variants that are genetically linked through mutation, interact cooperatively on a functional level, and collectively contribute to the characteristics of the population. Many predictions of quasispecies theory run counter to traditional views of microbial behavior and evolution and have profound implications for our understanding of viral disease. Here, we discuss basic principles of quasispecies theory and describe its relevance for our understanding of viral fitness, virulence, and antiviral therapeutic strategy