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2-Hydroxypropyl-beta-cyclodextrin (HPBCD) is utilized in the formulation of pharmaceutical products and recently orphan designation was granted for the treatment of Niemann–Pick disease, type C. The exact mechanism of HPBCD action and side effects are not completely explained. We used fluorescently labelled hydroxypropyl-beta-cyclodextrin (FITC-HPBCD) to study its pharmacokinetic parameters in mice and compare with native HPBCD data. We found that FITC-HPBCD has fast distribution and elimination, similar to HPBCD. Interestingly animals could be divided into two groups, where the pharmacokinetic parameters followed or did not follow the two-compartment, first-order kinetic model. Tissue distribution studies revealed, that a significant amount of FITC-HPBCD could be detected in kidneys after 60 min treatment, due to its renal excretion. Ex vivo fluorescent imaging showed that fluorescence could be measured in lung, liver, brain and spleen after 30 min of treatment. To model the interaction and cellular distribution of FITC-HPBCD in the wall of blood vessels, we treated human umbilical vein endothelial cells (HUVECs) with FITC-HPBCD and demonstrated for the first time that this compound could be detected in the cytoplasm in small vesicles after 30 min of treatment. FITC-HPBCD has similar pharmacokinetic to HPBCD and can provide new information to the detailed mechanism of action of HPBCD.

Learn to use exciting new development tools and create applications for Windows 8 If you're a beginning developer, there's no better place to get up to speed on the Windows 8 SDK than this Wrox guide. A team of Microsoft experts provides a complete course in Windows 8 programming, helping you take full advantage of the innovative new SDK. Written in an easy-to-read style, this book is packed with reusable examples that showcase the endless possibilities of the Windows SDK and also introduces the new Windows 8 app store. It explains how to set up the development environment and covers user interface design, using special effects and graphics, working with C# and C++, and much more. Provides a complete introduction to the Windows SDK and Windows 8, starting with setting up the development environment and building your first application Covers user interface design, touch- and event-driven design elements, leveraging windows-based services, and offline application development with HTML 5 Explores creating C# applications for the Windows 8 system, XNA 4 and Silverlight 5 considerations, and the role of C++ Shows how to debug, certify and deploy your applications Introduces the new Windows 8 app store and offers advice on marketing your apps Beginning Windows 8 Application Development is perfect for anyone who's ready to get started developing apps for the exciting new Windows 8 OS.

Background Epidemiological evidence suggests that synchronous or metachronous presentation of breast and thyroid cancers exceeds that predicted by chance alone. The following potential explanations have been hypothesized: common environmental or hormonal factors, oncogenic effect of the treatment for the first cancer, closer follow-up of cancer survivors, shared underlying genetic risk factors. While some cases were found to be related to monogenic disorders with autosomal inheritance, the genetic background of most cases of co-occurring breast and thyroid cancer is thought to be polygenic. Methods In this retrospective case-control study we compared the genetic profile of patients with a history of breast cancer ( n  = 15) to patients with co-occurring breast and thyroid cancer ( n  = 19) using next generation sequencing of 112 hereditary cancer risk genes. Identified variants were categorized based on their known association with breast cancer and oncogenesis in general. Results No difference between patients with breast and double cancers was observed in clinical and pathological characteristics or the number of neutral SNPs. The unweighted and weighted number of SNPs with an established or potential association with breast cancer was significantly lower in the group with breast cancer only (mean difference − 0.58, BCa 95% CI [− 1.09, − 0.06], p  = 0.029, and mean difference − 0.36, BCa 95% CI [− 0.70, − 0.02], p  = 0.039, respectively). The difference was also significant when we compared the number of SNPs with potential or known association with any malignancy (mean difference − 1.19, BCa 95% CI [− 2.27, − 0.11], p  = 0.032 for unweighted, and mean difference − 0.73, BCa 95% CI [− 1.32, − 0.14], p  = 0.017 for weighted scores). Conclusion Our findings are compatible with the hypothesis of genetic predisposition in the co-occurrence of breast and thyroid cancer. Further exploration of the underlying genetic mechanisms may help in the identification of patients with an elevated risk for a second cancer at the diagnosis of the first cancer.

In our study, the operation of a smart system in current operation and the implementation plan of traffic management by traffic lights of a junction are presented. Public lighting has a major effect on the efficacy of cities and the well-being and safety of their inhabitants. The energy consumed for public lighting entails significant costs for the urban management. In our constantly evolving world, there is an ever-growing demand for lighting, leading to the increase in expenses, as well. Smart cities are dedicated to apply the most energy-efficient solution in order to decrease expenses in respect of the safety of all road users.

Human induced pluripotent stem cell-derived endothelial cells can be candidates for engineering therapeutic vascular grafts. Here, we studied the role of three-dimensional culture on their characteristics and function both and . We found that differentiated hPSC-EC can re-populate decellularized biomatrices; they remain viable, undergo maturation and arterial/venous specification. Human PSC-EC develop antifibrotic, vasoactive and anti-inflammatory properties during recellularization. , a robust increase in perfusion was detected at the engraftment sites after subcutaneous implantation of an hPSC-EC-laden hydrogel in rats. Histology confirmed survival and formation of capillary-like structures, suggesting the incorporation of hPSC-EC into host microvasculature. In a canine model, hiPSC-EC-seeded onto decellularised vascular segments were functional as aortic grafts. Similarly, we showed the retention and maturation of hiPSC-EC and dynamic remodelling of the vessel wall with good maintenance of vascular patency. A combination of hPSC-EC and biomatrices may be a promising approach to repair ischemic tissues.

Context Increasing diagnostic sensitivity in the detection of thyroid cancer has led to uncertainties in the optimal surgical approach of the smaller, low risk tumors. Current ATA guidelines consider lobectomy safe between 1 and 4 cm, while ETA advocates for primary total thyroidectomy to avoid reoperation, as final risk stratification is based on the histological results. Objective Our aim was to compare the differences in outcomes that are potentially achievable with adherence to the different guidelines, and also to examine the predictive value of clinical parameters on the incidence of postoperative risk factors. Methods We performed a retrospective cohort database analysis to identify the different surgical outcomes (based on postoperative risk factors) using ATA and ETA guidelines; the hypothetical rate of completion thyroidectomy when ATA or ETA recommends lobectomy; the accuracy of our preoperative evaluation; the utility of preoperative findings in predicting the optimal surgical strategy using binary logistic regression. Results Out of 248 patients, 152 (ATA) and 23 (ETA) cases would have been recommended for initial lobectomy. Following the guidelines, a postoperative risk factor would have been present in 61.8, and 65.2% of the cases, respectively. Except for angioinvasion, tumor size was not a significant predictor for the presence of postoperative risk factors. Conclusion Current pre-operative criteria are inadequate to accurately determine the extent of initial surgery and our postoperative findings verify the frequent need for completion thyroidectomy using both guidelines. As a consequence, in the absence of effective pre-operative set of criteria, we advocate primary total thyroidectomy in most cases.

Hungary is among the countries with the highest cancer mortality burden in Europe, consequently there is a crucial need to monitor changes in death rates in the population using appropriate surveillance tools. The Lexis diagram provides a means to depict age, period and cohort influences on long-term cancer mortality trends. Age-specific mortality rates for six cancer localizations were constructed based on the Deaths Register of the Hungarian Central Statistical Office and the Human Mortality Database, then smoothed (p-splines) within the cells of the Lexis diagram assuming Poisson distribution. After calculating the annual percentage change in mortality rates, the results were visualized using heat maps. Substantial reduction in mortality was observable from the mid-1990s in both sexes as a strong period effect, depicting two distinct epidemiological eras in Hungary. Since 2010, breast cancer mortality in women among ages 70–90 (those born between 1930 and 1950) has been rising. Women born between 1940 and 50 experienced two plateaus in lung cancer mortality, unlike men, emphasizing the delayed nature of the smoking epidemic. The results align with cancer transition patterns observed in similarly developed countries and emphasize a critical need to expand the implementation of effective primary and secondary prevention measures. This includes sustaining organized screening and anti-smoking programs, as well as introducing lung cancer screening with low-dose CT. •Lexis diagram offers a particularly detailed way to represent epidemiological transitions partitioned by cause of death.•This is an effective tool to analyze the situation in Hungary, which has one of the highest cancer mortality rates in Europe.•In Hungary the cancer transition is evident, however obstacles typical of post-socialist countries hinder the progress.•Our comparative analysis identified areas where the greatest progress can be made in reducing the cancer burden in Hungary.

The investigation of the usability of solid insoluble β-cyclodextrin polymers (βCDP) in micro-sized, controlled drug delivery systems has only recently attracted interest. Our aim was to form complexes with poorly soluble active pharmaceutical ingredients (APIs) with two types of βCDP for drug delivery applications. Solid insoluble cyclodextrin polymer of irregular shape (βCDPIS) and cyclodextrin microbeads (βCDPB) were used in the experiments. Morphology, surface area, size distribution and swelling capacity of carriers were investigated. We created complexes with two APIs, curcumin and estradiol, and applied powder X-ray diffraction, FTIR and thermal analysis (TGA/DSC) to prove the complexation. Finally, the dissolution, biocompatibility and permeation of APIs on Caco-2 cells were investigated. The size of the beads was larger than 100 µm, their shape was spherical and surfaces were smooth; while the βCDPIS particles were around 4 µm with irregular shape and surface. None of the polymers showed any cytotoxic effect on Caco-2 cells. Both carriers were able to extract curcumin and estradiol from aqueous solutions, and the dissolution test showed prolonged estradiol release. Caco-2 permeability tests were in accordance with the complexation abilities and dissolution of the complexes. This study offers useful data for further pharmaceutical applications of insoluble cyclodextrin polymers.

Numerous clinical observations have confirmed that breakpoint cluster region-abelson fusion oncoprotein tyrosine kinase inhibitors used in leukemia treatment alter bone physiology in a complex manner. The aim of the present study was to analyze the whole transcriptome of cultured murine osteoblasts and determine the changes following treatment with imatinib and nilotinib using Sequencing by Oligonucleotide Ligation and Detection next generation RNA sequencing. This study also aimed to identify candidate signaling pathways and network regulators by multivariate Ingenuity Pathway Analysis. Based on the right-tailed Fisher's exact test, significantly altered pathways including upstream regulators were defined for each drug. The correlation between these pathways and bone metabolism was also examined. The preliminary results suggest the two drugs have different mechanisms of action on osteoblasts, and imatinib was shown to have a greater effect on gene expression. Data also indicated the potential role of a number of genes and signaling cascades that may contribute to identifying novel targets for the treatment of metabolic bone diseases.

The objective of the study was to examine proliferation and apoptosis associated gene expression in the whole sequence parathyroid lesions to reveal specific features of carcinoma. This study was based on surgically removed parathyroid tissues, gene expression analysis was performed both at gene and protein level. First, mRNA isolation was performed from deep-frozen tissue samples, and further apoptosis pathway-specific cDNA macroarray analysis was carried out. The results were validated with real-time PCR. Subsequently, protein expression was analyzed with immunhistochemistry on Tissue Micro Array multi-blocks derived from several paraffin-embedded samples. cDNA macroarrays revealed elevated expression of both pro-apoptotic ( FAS receptor, TRAIL ligand, CASPASE8 , and − 4 ) and anti-apoptotic ( cIAP1, APOLLON ) genes in benign proliferative lesions compared to that in normal gland. TMA studies showed overexpression of KI67, P53, SURVIVIN and APOLLON protein and failure of expression of P27, BCL2, BAX, CHROMOGRANIN-A, SYNAPTOPHYSIN, CYCLIND1, FLIP, TRAIL, CK8, CK18, CK19 in parathyroid carcinoma was detected. These alterations in gene expression of the investigated products could be used in differentiation between beningn and malignant proliferative processes of the parathyroid gland. Authors conclude that a series of alterations in gene expression such as overexpression of APOLLON, P53, KI67 and suppression of P27, BCL2, BAX lead to uncontrolled cell proliferation, but still not leading to increased apoptotic activity in parathyroid carcinoma.