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Iron-binding strategies in anticancer drug design target the key role of iron in cancer growth. The incorporation of a quinoline moiety in the design of tetrazolium-based prochelators facilitates their intracellular reduction/activation to iron-binding formazans. The new prochelators are antiproliferative at submicromolar levels, induce apoptosis and cell cycle arrest, and impact iron signaling in cancer cells. [ABSTRACT FROM AUTHOR]

This article reports on a study that investigated the use of blended sulfonated polymer membranes for fuel cell applications. The researchers blended a sulfonated poly(arylene ether) polymer material with an amine-based crosslinking agent in 1%–5% varying weight percentages. By replacing the sulfonates' hydrogen bonds with the amine groups in the crosslinking agent, the researchers were able to enhance the structure of the polymer material. This, in turn, can help resolve the issue of inadequate dimensional stability of SA8, thereby prolonging the lifespan of fuel cells. The resulting membranes showed improved dimensional stability, oxidative stability, and cell component efficiency, with the 5% crosslinking agent blend ratio demonstrating decrease 30.8 times in swelling ratio and a 4.9% increase in oxidative stability. Additionally, the fuel cell efficiency of the 1% crosslinking agent blend ratio membrane was 20.4% higher than that of the commercial membrane, with a power density of 1.21 W/cm2. The SA8+1P blend ratio had the highest ion exchange capacity and water uptake, resulting in increased proton conductivity and power density. Furthermore, the dimensional stability of the membranes improved with the blend ratio, with the SA8+5P membrane outperforming the commercial Nafion 211 membrane. The SA8+1P and SA8+5P membranes have been proven to demonstrate exceptional performance in terms of ion exchange capacity, conductivity, and dimensional stability. Furthermore, these membranes also show high efficiency in fuel cell efficiency. Overall, the results suggest that blending sulfonated polymer membranes with an amine-based crosslinking agent has the potential to improve the performance of fuel cell components. • SA8 exhibits outstanding membrane-forming properties and remarkable proton conductivity in fuel cells. • Amine-based Sulfonated poly(arylene ether) can increase the dimensional and cell component efficiency stability. • Membranes demonstrate excellent performance with SA8 blending ratios of 1% and 5% crosslinking. [ABSTRACT FROM AUTHOR]

This article proposes a new type of three-component optic fiber balance based on Fabry–Perot displacement measurement technology based on the structure of the pulse wind tunnel balance. This paper systematically introduces the force measurement principle and design process of a three-component optic fiber balance and conducts relevant simulation analysis and experimental verification. The simulation results show that the Fabry–Perot sensor can achieve significant sensitivity to cavity length changes, and when used in existing balance structures, sensitivity gains can be achieved by changing the probe height without the need to modify the original structure of the balance. Finally, the feasibility of the design method was verified through calibration experiments: the optic fiber balance has high sensitivity and good linearity compared to simulation sensitivity, the error is less than 6%, and the calibration accuracy of each component is better than 0.13%, which is better than the existing traditional strain balance (0.37%). The pulse wind tunnel force measurement test has a short test time and a large model mass, and the balance needs to have a large stiffness to meet the short-term force measurement requirements. The introduction of more sensitive optic fiber balance force measurement technology is expected to solve the contradiction between the stiffness and sensitivity of force measurement systems. [ABSTRACT FROM AUTHOR]

Maintaining gate bias stability under negative bias stress (NBS) and positive bias stress (PBS) is a long-standing issue in amorphous oxide semiconductor thin-film transistors (TFTs). The passivation of the channel layer is crucial for improving device stability. We show that amorphous gallium oxide, which possesses appropriate energy levels (lower electron affinity and higher ionization potential) for indium–tin–zinc oxide (ITZO) TFTs, can be etched selectively by tetramethyl ammonium hydroxide-containing developers that enable self-alignment passivation, such as easy contact hole formation during the drain and source lithography processes. The self-aligned passivation process led to a-ITZO TFTs with high mobility (>50 cm2 V−1 s−1) and low subthreshold swing (<90 mV/dec). The threshold voltage shifts under NBS and PBS using a bias gate voltage of ±20 V for 1 h were −0.09 and 0.15 V, respectively. This passivation can obviate the need for the conventional CVD-derived passivation process by utilizing the DC sputtering of gallium oxide, which may reduce hydrogen issues. [ABSTRACT FROM AUTHOR]

Metal halide perovskites (MHPs) are plausible candidates for practical p‐type semiconductors. However, in thin film transistor (TFT) applications, both 2D PEA2SnI4 and 3D FASnI3 MHPs have different drawbacks. In 2D MHP, the TFT mobility is seriously reduced by grain‐boundary issues, whereas 3D MHP has an uncontrollably high hole density, which results in quite a large threshold voltage (Vth). To overcome these problems, a new concept based on a 2D–3D core–shell structure is herein proposed. In the proposed structure, a 3D MHP core is fully isolated by a 2D MHP, providing two desirable effects as follows. (i) Vth can be independently controlled by the 2D component, and (ii) the grain‐boundary resistance is significantly improved by the 2D/3D interface. Moreover, SnF2 additives are used, and they facilitate the formation of the 2D/3D core–shell structure. Consequently, a high‐performance p‐type Sn‐based MHP TFT with a field‐effect mobility of ≈25 cm2 V−1 s−1 is obtained. The voltage gain of a complementary metal oxide semiconductor (CMOS) inverter comprising an n‐channel InGaZnOx TFT and a p‐channel Sn‐MHP TFT is ≈200 V/V at VDD = 20 V. Overall, the proposed 2D/3D core–shell structure is expected to provide a new route for obtaining high‐performance MHP TFTs. [ABSTRACT FROM AUTHOR]

Metal halide perovskites (MHPs) are plausible candidates for practical p‐type semiconductors. However, in thin film transistor (TFT) applications, both 2D PEA2SnI4 and 3D FASnI3 MHPs have different drawbacks. In 2D MHP, the TFT mobility is seriously reduced by grain‐boundary issues, whereas 3D MHP has an uncontrollably high hole density, which results in quite a large threshold voltage (Vth). To overcome these problems, a new concept based on a 2D–3D core–shell structure is herein proposed. In the proposed structure, a 3D MHP core is fully isolated by a 2D MHP, providing two desirable effects as follows. (i) Vth can be independently controlled by the 2D component, and (ii) the grain‐boundary resistance is significantly improved by the 2D/3D interface. Moreover, SnF2 additives are used, and they facilitate the formation of the 2D/3D core–shell structure. Consequently, a high‐performance p‐type Sn‐based MHP TFT with a field‐effect mobility of ≈25 cm2 V−1 s−1 is obtained. The voltage gain of a complementary metal oxide semiconductor (CMOS) inverter comprising an n‐channel InGaZnOx TFT and a p‐channel Sn‐MHP TFT is ≈200 V/V at VDD = 20 V. Overall, the proposed 2D/3D core–shell structure is expected to provide a new route for obtaining high‐performance MHP TFTs. [ABSTRACT FROM AUTHOR]

This article reports thin-film transistors (TFTs) with a low-cost, environmentally friendly and wide-bandgap amorphous Si-doped tin oxide (a-STO) semiconductor as the channel layer. To realize practical applications, a comprehensive investigation of a-STO TFTs was performed. The underlying carrier transport mechanism of a-STO TFTs analyzed via the temperature dependence of transfer characteristics is trap-limited conduction. The degradation of the a-STO TFTs induced by bias stress and light illumination is discussed. The results may not only provide a deeper understanding of the electrical properties of a-STO TFTs but also form a fundamental perspective for further improvement of the performance of similar devices. [ABSTRACT FROM AUTHOR]

Purpose: Cutaneous toxicities are common adverse effects following epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) therapy. Zinc deficiency causes diverse diseases, including skin toxicities. Therefore, this study aimed to investigate the role of zinc deficiency in patients with EGFR‐TKI‐induced skin toxicities. Experimental Design: This retrospective study enrolled 269 patients with diverse skin disorders who visited our hospital between January 2016 and December 2017. The skin toxicity severities and plasma zinc levels of 101 EGFR‐TKI‐treated cancer patients were analysed and compared with those of 43 non‐EGFR‐TKI‐treated cancer patients and 125 patients without cancer but presenting cutaneous manifestations. Additionally, the role of zinc in erlotinib‐induced skin eruptions was established in a 14‐day‐murine model. Clinical features were further evaluated following systemic zinc supplementation in EGFR‐TKI‐treated cancer patients. Results: EGFR‐TKI‐treated patients demonstrated severe cutaneous manifestations and a significant decrease in plasma zinc levels than those of the control groups. The serum zinc level and Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading of EGFR‐TKI‐induced skin toxicities showed a significant negative correlation (r = −0.29; p < 0.0001). Moreover, erlotinib treatment decreased the plasma zinc levels and induced periorificial dermatitis in rats confirming zinc deficiency following EGFR‐TKI treatment. Zinc supplementation to the EGFR‐TKI‐treated cancer patients showed a significant decrease in the CTCEA grading (p < 0.0005 for mucositis and p < 0.0.0001 for all other cases) after 8 weeks. Conclusions: Skin impairment following EGFR‐TKI therapy could be ameliorated through zinc supplementation. Thus, zinc supplementation should be considered for cancer patients undergoing EGFR‐TKI therapy. [ABSTRACT FROM AUTHOR]

Abstract: Percutaneous transluminal angioplasty (PTA) for thrombosed dialysis graft is both difficult and time-consuming that may increase radiation exposure. A predictor of PTA success and procedure time has not been identified yet. Sonography data and the PTA results of 88 grafts were reviewed retrospectively. The echogenicity of the majority of the intra-graft thrombus and the presence/absence of thrombus free space in the grafts were examined. The association between the sonography findings and PTA procedure success and procedure time was analyzed. The echogenicity of the intra-graft thrombus and presence/absence of thrombus free space were the major determinants of procedure success and procedure time. Higher intra-graft echogenicity and lack of thrombus free space were associated with more procedure failures (p < 0.01 vs. p = 0.04) and longer procedure times (p = 0.03 vs. p < 0.01). Thrombi from occluded dialysis grafts may differ in resistance to mechanical/pharmacological thrombolysis. Sonography characteristics of the intra-graft thrombus may help to differentiate them. [Copyright &y& Elsevier]

Thrombosed arteriovenous fistula for hemodialysis access is characterized by a marked inflammatory activity. Background. Thrombosis is the dominant cause of failure of arteriovenous fistulas for hemodialysis access. Vascular inflammation, an important pathologic change in various human vascular diseases, may be involved in the thrombotic process of arteriovenous fistulas. Methods. The inflammatory activities of 23 thrombosed and 13 nonthrombosed stenotic arteriovenous fistulas were compared by investigating the contents of macrophages and lymphocytes, and the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) using immunohistochemistry method. The expression of matrix metalloproteinase (MMP)-2 and MMP-9, which play important roles in thrombosis of human coronary artery, was also investigated. The immunoreaction results were characterized using a semiquantitative scoring system. Results. The macrophage and lymphocyte contents of the thrombosed group were abundant, and markedly greater than those of the nonthrombosed group ( P < 0.001 and P= 0.001, respectively). The infiltration of macrophages and neovasculature were spatially closely correlated. The expressions of VCAM-1, IL-6, and TNF-α, but not ICAM-1, were significantly higher in the thrombosed group ( P= 0.031, P= 0.010, P < 0.001, and P= 1.000, respectively). The expression of MMP-2 was not different in either groups ( P= 0. 344). Differential expression of MMP-9 by macrophages near the vascular lumen, but not those distant from the lumen, was observed in most thrombosed specimens. Conclusion. This study demonstrated that the thrombosed arteriovenous fistula was characterized by marked inflammation. We hypothesize that the preferential expression of MMP-9 at luminal edge may cause disruption of the anticoagulant endothelial barrier and contribute to luminal thrombosis of arteriovenous fistulas. [ABSTRACT FROM AUTHOR]

Increased expression of connexin43 gap junctions in smooth muscle cells (SMC) is implicated in the response to primary arterial injury and in the early stages of human coronary atherosclerosis, but the relevance of these findings to restenosis is unknown. Here we investigated the expression of connexin43 gap junctions in restenotic aortas of cholesterol-fed double injured rabbits. Immunofluorescence confocal microscopy was used to evaluate temporal and spatial expression patterns and to characterize the major expressing cell type. Parallel studies were conducted by electron microscopy, in situ hybridization and Northern blot analysis. Connexin43 gap junctions- and connexin43 mRNA-expressing cells were abundant in the media of non-injured control aorta. Following primary injury and 6 weeks cholesterol diet, connexin43 gap junctions were found distributed throughout the primary intimal layer; although medial expression was reduced, the overall mRNA expression level remained similar to that of non-injured controls. After secondary injury, no major change in distribution pattern of connexin43 gap junctions occurred up to day 10, when marked neointimal labeling was observed. This overall pattern persisted, though with some diminution, at later stages. On the mRNA level total connexin43 mRNA expression declined to about 40% of control values within 4 days after secondary injury (P&#60;0.05), but subsequently increased fourfold, attaining levels double that of non-injured controls in the 10-day group (P&#60;0.005 versus control and 4 days). At later stages mRNA expression levels returned to values similar to those of non-injured controls. At all stages, connexin43 gap junctions were localized to the SMC, not to macrophages. We conclude that the enhanced gap junction formation may contribute to the coordination of the response of SMC after secondary injury, particularly in the early phase of restenosis. [Copyright &y& Elsevier]

S. Wu, Y.-S. Ko, M.-S. Teng, Y.-L. Ko, L.-A. Hsu, C. Hsueh, Y.-Y. Chou, C.-C. Liew and Y.-S. Lee. Adriamycin-induced Cardiomyocyte and Endothelial Cell Apoptosis: In Vitro and In Vivo Studies. Journal of Molecular and Cellular Cardiology (2002)34 , 1595–1607. Adriamycin is a potent, broad-spectrum chemotherapeutic agent effective against solid tumors and malignant hematological disease. The major limiting factor for adriamycin is its cardiotoxicity. Thus, the objective of this study was to investigate the role of cardiomyocyte and endothelial cell apoptosis in adriamycin-induced cardiomyopathy, in vivo and in vitro. For in vivo study, intraperitoneal injections of adriamycin were administered to nine adult male Wistar rats and normal saline to six rats as control. Eight of the nine rats in the adriamycin group, but none in the control group, developed marked ascites and DNA ladders in agarose gel electrophoresis of genomic DNA extracted from the rat hearts (P<0.001). The ratio of apoptotic nuclei in the cardiomyocytes was significantly higher for the adriamycin-treated rats (162±149/106 cells) than for the controls (4.2±1.3/106 cells; P<0.01) by TUNEL assay. Increased endothelial cell apoptosis was detected in the small coronary vessels of the myocardium of the adriamycin-treated rats. Increased immuno-reactive Caspase-3 expression was also noted for both cardiomyocytes and endothelial cells of adriamycin-treated rats. In vitro adriamycin treatment for cultured neonatal rat cardiomyocytes and human umbilical vein endothelial cells, respectively, showed a dose-related increase in apoptosis as determined by flowcytometry, DNA ladder analysis, TUNEL assay and/or electron-microscope examination. A dose-related increase in the expression of Fas antigen, Bax and Caspase-3, as well as a decrease in the expression of Bcl-2, were determined for the adriamycin-treated cardiomyocytes using Northern blot analysis, reverse transcriptase polymerase chain reaction (RT-PCR) and ribonuclease protection assay. RT-PCR also revealed increased Fas antigen expression, decreased Bcl-2 expression, and no change in Bax expression for the adriamycin-treated human umbilical vein cells. Further, pretreatment with broad caspase inhibitor, but not neutralizing FasL antibody, resulted in inhibition of adriamycin-induced endothelial cell apoptosis. In conclusion, these results indicate that both adriamycin-induced cardiomyocyte and endothelial cell death can occur via apoptosis which is dose-related, and can occur both in vitro andin vivo with changes in the expression of the apoptosis-related genes. Adriamycin-induced endothelial cell apoptosis is mediated by caspase activation but is Fas/FasL signal pathway independent. Our data provides evidence that both cardiomyocyte and endothelial cell apoptosis may play an important role in adriamycin-induced cardiomyopathy. [Copyright &y& Elsevier]

Inherited cardiac conduction disease (CCD) is rare; it is caused by a large number of mutations in genes encoding cardiac ion channels and cytoskeletal proteins. Recently, whole-exome sequencing has been successfully used to identify causal mutations for rare monogenic Mendelian diseases. We used trio-based whole-exome sequencing to study a Chinese family with multiple family members affected by CCD, and identified a heterozygous missense mutation (c.343C>T, p.Leu115Phe) in the desmin (DES) gene as the most likely candidate causal mutation for the development of CCD in this family. The mutation is novel and is predicted to affect the conformation of the coiled-coil rod domain of DES according to structural model prediction. Its pathogenicity in desmin protein aggregation was further confirmed by expressing the mutation, both in a cellular model and a CRISPR/CAS9 knock-in mouse model. In conclusion, our results suggest that whole-exome sequencing is a feasible approach to identify candidate genes underlying inherited conduction diseases. [ABSTRACT FROM AUTHOR]

The effects of human amniotic fluid stem cell (hAFSC) transplantation on bladder function and molecular changes in spinal cord-injured (SCI) rats were investigated. Four groups were studied: sham and SCI plus phosphate-buffered saline (SCI + PBS), human embryonic kidney 293 (HEK293) cells, and hAFSCs transplantation. In SCI + PBS rat bladders, cystometry showed increased peak voiding pressure, voiding volume, bladder capacity, residual volume, and number of non-voiding contractions, and the total elastin/collagen amount was increased but collagen concentration was decreased at days 7 and 28. Immunoreactivity and mRNA levels of IGF-1, TGF-β1, and β3-adrenoceptor were increased at days 7 and/or 28. M2 immunoreactivity and M3 mRNA levels of muscarinic receptor were increased at day 7. M2 immunoreactivity was increased, but M2/M3 mRNA and M3 immunoreactivity levels were decreased at day 28. Brain derived-neurotrophic factor mRNA was increased, but immunoreactivity was decreased at day 7. HEK293 cell transplantation caused no difference compared to SCI + PBS group. hAFSCs co-localized with neural cell markers and expressed BDNF, TGF-β1, GFAP, and IL-6. The present results showed that SCI bladders released IGF-1 and TGF-β1 to stimulate elastin and collagen for bladder wall remodelling, and hAFSC transplantation improved these changes, which involved the mechanisms of BDNF, muscarinic receptors, and β3-adrenoceptor expression. [ABSTRACT FROM AUTHOR]

Aims To explore perceptions of low-literate older adults with heart disease about their eating experiences. Background Heart disease has been closely linked with nutrition, and nutritional status is poor in patients with limited education, but no studies have explored the eating experiences of low-literate adults with heart disease. Design Qualitative descriptive study. Methods Data were collected in tape-recorded semi-structured interviews from March - June 2012. A convenience sample of 13 low-literate older adults with heart disease was recruited from a cardiovascular ward of a medical centre in northern Taiwan. Participants were recruited until findings reached saturation and data were analysed using qualitative content analysis. Findings Analysis of participants' interview data on eating experiences identified three main categories: (1) eating-related hardships because of low literacy; (2) eating adjustments due to low literacy; and (3) misinformation about dietary modifications for heart disease. Conclusion Because of their low literacy, these older adults had difficult life experiences, gained inappropriate or inadequate eating information and held a passive, fatalistic perspective about eating with heart disease. Healthcare practitioners caring for this population need to appreciate their unique eating challenges and respect their eating customs. Nurses could play a greater role in educating and supporting low-literate older adults in selecting appropriate foods and preparing meals. Strategies to help this population learn to select, prepare and cook their food should be easy and practical, using specific symbols, concrete signs and simple labels. [ABSTRACT FROM AUTHOR]

In this study, we proposed using the high-K polyvinyl alcohol (PVA)/low-K poly-4-vinylphenol (PVP) bilayer structure as the gate insulator to improve the performance of a pentacene-based organic thin-film transistor. The dielectric constant of the optimal high-K PVA/low-K PVP bilayer was 5.6, which was higher than that of the single PVP layer. It resulted in an increase in the gate capacitance and an increased drain current. The surface morphology of the bilayer gate dielectric could be suitable for pentacene grain growth because the PVP layer was deposited above the organic PVA surface, thereby replacing the inorganic surface of the ITO gate electrode. The device performances were significantly improved by using the bilayer gate dielectric based upon the high-K characteristics of the PVA layer and the enlargement of the pentacene grain. Notably, the field-effect mobility was increased from 0.16 to 1.12 cm2/(Vs), 7 times higher than that of the control sample. [ABSTRACT FROM AUTHOR]

Abstract: Aims: This study was designed to examine the mechanism of relaxation induced by CIJ-3-2F, a benzyl-furoquinoline antiarrhythmic agent, in rat thoracic aorta at the tissue and cellular levels. Main methods: Isometric tension of rat aortic ring was measured in response to drugs. Ionic channel activities in freshly dissociated aortic vascular smooth muscle cells (VSMCs) were investigated using a whole-cell patch-clamp technique. Key findings: CIJ-3-2F relaxed both phenylephrine (PE) and high KCl (60mM)-induced contractions with respective pEC50 (-log EC50) values of 6.91±0.07 and 6.32±0.06. Removal of endothelium or pretreatment with nitric oxide (NO)-pathway inhibitors N ω-nitro-l-arginine methyl ester (L-NAME), N G-monomethyl-l-arginine (L-NMMA), N 5-(1-iminoethyl)-l-ornithine (L-NIO), hemoglobin, methylene blue or 1H-[1,2,4]oxadiazolo[4,2-α]quinoxalin-1-one (ODQ) reduced the relaxant effect of CIJ-3-2F. Relaxation to CIJ-3-2F was also attenuated by K + channel blockers tetraethylammonium (TEA) or 4-aminopyridine (4-AP), but not by charybdotoxin plus apamin, iberiotoxin, glibenclamide, or BaCl2. CIJ-3-2F non-competitively antagonized the contractions induced by PE, Ca2+, and Bay K8644 in endothelium-denuded rings. In addition, CIJ-3-2F inhibited both the phasic and tonic contractions induced by PE but did not affect the transient contraction induced by caffeine. CIJ-3-2F reduced the Ba2+ inward current through L-type Ca2+ channel (IC50 =4.1μM) and enhanced the voltage-dependent K + (Kv) current in aortic VSMCs. Significance: These results suggest that CIJ-3-2F induced both endothelium-dependent and -independent vasorelaxation; the former is likely mediated by the NO/cGMP pathway whereas the latter is probably mediated through inhibition of Ca2+ influx or inositol 1,4,5-triphosphate (IP3)-sensitive intracellular Ca2+ release, or through activation of Kv channels. [Copyright &y& Elsevier]

Abstract: Preconditioning of gerbil brain with a sublethal forebrain ischemia is known to protect hippocampal CA1 neurons following a subsequent lethal ischemia (the second ischemia) which usually damages neurons (ischemic tolerance). Present report using a confocal laser scanning microscope demonstrated that the hippocampal cells of sham operation gerbils contained immunofluorescent NGF and BDNF and their high-affinity receptors (TrkA and TrkB). A 2-min ischemia caused little change of these proteins (ANOVA test, P <0.05). After the second lethal ischemia, in the CA1 area with ischemic preconditioning (2-min ischemia), only BDNF but not NGF and their high-affinity receptors showed a transient reduction at 4 h (ANOVA test, P <0.01) and improved from 1 day (ANOVA test, P <0.05). In the CA1 area without ischemic preconditioning (sham operation), NGF and its high-affinity TrkA receptor showed a consistent reduction from 4 h to 7 days (ANOVA test, P <0.05); BDNF and TrkB decreased transiently from 4 h to 1 day (ANOVA test, P <0.05) but were recovered in the surviving neurons from 3 days. At 3 and 7 days after the second lethal ischemia, apoptotic cell injury could be seen in the CA1 area without ischemic preconditioning but was sparsely noted in the CA1 area with ischemic preconditioning. In the ischemia-resistant CA3 and dentate gyrus areas, only BDNF decreased significantly at 7 days in the CA3 area without ischemic preconditioning (ANOVA test, P <0.01). However, no significant change occurred in NGF, TrkA and TrkB immunofluorescence from 4 h to 7 days after the second lethal ischemia in the CA3 and dentate gyrus areas with and without ischemic preconditioning. Western blot study showed that in the hippocampal formation with ischemic preconditioning, preconditioning prevented the decline of these protein levels from 1 day to 7 days after the second lethal ischemia (ANOVA test, P >0.05). Results of this study demonstrate that ischemic preconditioning recovers the initial decline in NGF and BDNF and their corresponding receptors in the vulnerable CA1 neurons after the second lethal ischemia, suggesting that growth factors might play a role in the protective mechanism of ischemic preconditioning. [Copyright &y& Elsevier]

Background: Intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) is the standard treatment for acute ischemic stroke. Standard-dose rt-PA (0.9 mg/kg) is known to achieve good recanalization but carries a high bleeding risk. Lower dose of rt-PA has less bleeding risk but carries a high re-occlusion rate. We investigate if induced pluripotent stem cells (iPSCs) can improve the thrombolytic effect of low-dose rt-PA (0.45 mg/kg). Methods: Single irradiation with 6 mW/cm2 light-emitting diode (LED) for 4 h at rat common carotid artery was used as thrombosis model according to our previous report. Endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1), and interleukin 1 beta (IL-1 beta) were used as the inflammatory markers for artery endothelial injury. Angiopoietin-2 (AP-2), brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were examined in artery wall and iPSCs culture. Animal ultrasound was used to evaluate the stenosis degree of common carotid artery before and at 2 h, 24 h, 4 days and 7 days after LED irradiation. Results: After LED irradiation alone, there was a persistent occlusion from 2 h to 7 days. Standard-dose rt-PA alone could recanalize the occluded artery from 24 h to 7 days to stenotic degree ≤ 50%. Low-dose rt-PA or 1 × 106 mouse iPSCs alone could not recanalize the occluded arteries from 2 h to 7 days. Combination use of low-dose rt-PA plus 1 × 106 mouse iPSCs caused better recanalization from 24 h to 7 days. ET-1, ICAM-1 and IL-1 beta were strongly expressed after LED irradiation but reduced after iPSCs treatment. AP-2, BDNF and VEGF were rarely induced after LED irradiation but strongly expressed after iPSCs treatment. In vitro study showed iPSCs could express AP-2, BDNF and VEGF. Conclusion: The adjuvant use of iPSCs may help improving the thrombolytic effect of low-dose rt-PA by suppressing inflammatory factors and inducing angiogenic trophic factors. Stem cells could be a potential regimen in acute thrombolytic therapy to improve recanalization and reduce complications. [ABSTRACT FROM AUTHOR]

In practice, modeling an assembly system often requires assigning a set of operations to a set of workstations. The aim is to optimize some performance indices of an assembly line. This assignation is usually a tedious design procedure so a significant amount of manpower is required to obtain a good work plan. Poor assembly planning may significantly increase the cost of products and reduce productivity. However, these optimization problems fall into the class of NP-hard problems. Finding an optimal solution in an acceptable time is difficult, even using a powerful computer. This study presents a hybrid genetic algorithm approach to the problems of assembly planning with various objectives, including minimizing cycle time, maximizing workload smoothness, minimizing the frequency of tool change, minimizing the number of tools and machines used, and minimizing the complexity of assembly sequences. A self-tuning method was developed to correct infeasible chromosomes. Several examples were employed to illustrate the proposed approach. Experimental results indicated that the proposed method can efficiently yield many alternative assembly plans to support the design and operation of a flexible assembly system. [Copyright &y& Elsevier]

Background: High rates of posttreatment discomfort, infection, recurrence, and increased time to return to work have been noted after nail plate avulsion resulting from epidermal growth factor receptor tyrosine kinase inhibitor(EGFR‐TKI)‐induced paronychia, which may even interrupt the course of treatment for EGFR‐TKI therapy. Thus, we conducted this study to determine how effectively a topical β‐blocker, betaxolol, prevents EGFR‐TKI‐induced paronychia. Methods: This case–control cohort study included a total of 131 non‐small‐cell lung cancer patients. The prevention group comprised 40 patients treated with topical betaxolol 0.25% solution to prevent paronychia while they received EGFR‐TKI therapy. The control group comprised 91 patients who did not preventively use topical betaxolol 0.25% solution while receiving EGFR‐TKI therapy. The patients' age, gender, antineoplastic regimen, duration of antineoplastic treatment before the appearance of lesions, number of involved digits (fingernails or toenails) with lesions, grading of paronychia, and pain score were recorded. Results: In terms of the cumulative incidence of paronychia, significant differences (P < 0.01) were noted at both the 2nd and 3rd months after starting EGFR‐TKIs. Furthermore, the average visual analogue scale scores were 3.125 and 6.29 in the prevention group and control group, respectively (P < 0.01). The average grades of paronychia were 1.5 and 2.12 in the prevention group and control group, respectively (P < 0.01). The average numbers of involved digits were 2.25 (range: 1–5 digits) in the prevention group and 3.03 (range: 1–7) in the control group (P = 0.07). Conclusions: Preventively using topical betaxolol can significantly decrease the incidence, VAS score, and grading of EGFR‐TKI‐induced paronychia. [ABSTRACT FROM AUTHOR]

Background: Most studies of the predictors of systemic embolism in patients with mitral stenosis have been retrospective.Objective: To prospectively study factors associated with systemic embolism in mitral stenosis.Design: Prospective cohort study.Setting: University-affiliated medical institution with 3000 beds.Patients: 534 consecutive patients with a mitral valve area of 2.0 cm2 or less; 132 patients were in sinus rhythm, and 402 were in atrial fibrillation.Measurements: Nine clinical and 10 echocardiographic variables were assessed for prediction of systemic embolism over a mean (+/- SD) follow-up of 36.9 +/- 22.5 months. Diagnosis of systemic embolism was based on symptoms and signs (sudden onset of peripheral arterial ischemic or neurologic manifestations without prodromes) and on findings on computed tomography, angiography, and surgery.Results: For patients in sinus rhythm, age (relative risk [RR], 1.12 [95% CI, 1.04 to 1.21]), the presence of a left atrial thrombus (RR, 37.1 [CI, 2.82 to 487.8]), mitral valve area (RR, 16.9 [CI, 1.53 to 187.0]), and the presence of significant aortic regurgitation (RR, 22.4 [CI, 2.72 to 184.8]) were positively associated with embolism. For patients in atrial fibrillation, previous embolism (RR, 3.11 [CI, 1.66 to 5.85]) was positively associated with embolism; percutaneous balloon mitral commissurotomy (RR, 0.37 [CI, 0.18 to 0.79]) was a negative predictor.Conclusions: It may be prudent to give anticoagulants not only to patients in atrial fibrillation and patients with previous systemic embolism but also to those showing a left atrial thrombus or significant aortic regurgitation on echocardiography. Early percutaneous balloon mitral commissurotomy may also help prevent systemic embolism in patients with mitral stenosis. [ABSTRACT FROM AUTHOR]

Background: Paronychia is a common adverse event caused by epidermal growth factor receptor (EGFR) inhibitors. However, high rates of post‐treatment discomfort, infection, recurrence, and increased time to return to work have been noted after nail plate avulsion for EGFR inhibitor‐induced paronychia. Furthermore, poor wound healing and malnutrition were common conditions found in cancer patients. The aim of this study is to find an effective, pain‐relieving, and noninvasive treatment for patients with severe paronychia induced by EGFR inhibitors. Methods: Data from a series of 35 non‐small cell lung cancer cases suffering from EGFR inhibitor‐induced paronychia with pyogenic granuloma‐like lesions of digits treated with betaxolol 0.25% ophthalmic solution once daily were collected and analyzed. Results: Of the 35 patients suffering from grade 2 or 3 paronychia with pyogenic granuloma‐like lesions induced by EGFR inhibitors, 34 (97.1%) demonstrated complete resolution and only one (2.9%) had partial resolution after 12 weeks of topical betaxolol treatment. The grading of paronychia according to the Common Terminology Criteria for Adverse Events decreased from an average of 2.29 to 0.63 after 4 weeks of treatment (P = 5.55 × 10−16). All the patients had significant improvement (50% pain reduction), as their pain visual analogue scale scores decreased from an average of 7.06 to 2.26 after one week of treatment (P = 6.11 × 10−25). Conclusion: Betaxolol 0.25% ophthalmic solution is an effective, safe, and pain‐relieving treatment for patients suffering from EGFR inhibitor‐induced paronychia with pyogenic granuloma‐like lesions and deep fissures. [ABSTRACT FROM AUTHOR]

Background: Cirrhotic cardiomyopathy (CCM) refers to cardiac dysfunction in patients with liver cirrhosis, in the absence of other known cardiac disease. Methods: Control group and patients diagnosed of liver cirrhosis without known cardiac disease or hepatocellular carcinoma were enrolled for this clinical observation study. Patients with diabetes mellitus, hypertension were excluded. Absolute global longitudinal strain, one-point carotid pulse wave velocity (one-point PWV) and various parameters were measured in resting status. Results: There were 29 participants in the control group and 80 patients in the liver cirrhosis group. 27.8% of cirrhotic patients presented with normal systolic but abnormal diastolic functions and QTc prolongation that were compatible with CCM. 34.2% of cirrhotic patients presented with diastolic dysfunction in resting state comparing to 24.1% in control group. Systolic functions did not show conspicuous difference between cirrhosis and control group nor between compensated and decompensated cirrhosis, neither. Furthermore, one-point PWV was significantly higher in liver cirrhosis than in control group and higher in CCM than in non-CCM patients. One-point PWV predicted CCM and diastolic dysfunction in cirrhosis. Most importantly, its value > 1370cm/s predicted overall mortalities in decompensated cirrhosis (multivariable Cox analysis OR = 6.941) in addition to CTP score specifically in HCV related cirrhotic patients (AUC = 0.817). Conclusions: In patients with cirrhosis, 27.8% were diagnosed with CCM by resting cardiovascular parameters. One-point PWV increased in CCM, correlated with diastolic dysfunction. It also correlated with overall mortality in patients with hepatitis C virus (HCV) related decompensated cirrhosis. Further study may be needed to confirm its capability for assessing CV and mortality risks in HCV related decompensated cirrhotic patients. [ABSTRACT FROM AUTHOR]

Study Design: A retrospective study of patients who were hospitalized for infectious spondylodiscitis over a 13-year period.Objective: To elucidate the epidemiology and prognostic factors of infectious spondylodiscitis in hemodialysis (HD) patients and to identify the impact of HD on infectious spondylodiscitis.Summary Of Background Data: Only a few case studies of infectious spondylodiscitis in HD patients can be found in the literature. Reports of prognostic factors are limited and patients' outcomes have not been well described.Methods: The cases of 1402 patients who were hospitalized for infectious spondylodiscitis over a 13-year period were retrospectively reviewed. Of these, 102 patients on maintenance HD were enrolled in this study. Cox proportional hazard model was used to evaluate the risk factors of mortality and recurrence.Results: The 102 enrolled patients had an average age 63.3 ± 11.2 years old and male-to-female ratio of 1:1.04. Back pain was present in 75.5% of patients and the most commonly infected site was the lumbosacral spine. Infection associated with vascular access was identified in 31.4% of patients. The prevalence of dialysis via central venous catheters was higher than prevalent HD patients. Methicillin-resistant Staphylococcus aureus was the most common pathogen, followed coagulase-negative staphylococci. The patients' in-hospital survival rate was 82.4%; their vascular access survival rate was 75.5%; their 1-year survival rate was 78.4%, and their 1-year recurrence rate was 20.2%. Congestive heart failure was associated with an increased 1-year mortality. Other variables exhibited no significant relationship with patients' in-hospital mortality, 1-year mortality or recurrence.Conclusion: The characteristics and outcomes of infectious spondylodiscitis in HD patients were elucidated. Most of the demographic and clinical variables, evaluated upon admission, did not predict mortality or recurrence.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

BPC 157, a pentadecapeptide with extensive healing effects, has recently been suggested to contribute to angiogenesis. However, the underlying mechanism is not yet clear. The present study aimed to explore the potential therapeutic effect and pro-angiogenic mechanism of BPC 157. As demonstrated by the chick chorioallantoic membrane (CAM) assay and endothelial tube formation assay, BPC 157 could increase the vessel density both in vivo and in vitro, respectively. BPC 157 could also accelerate the recovery of blood flow in the ischemic muscle of the rat hind limb as detected by laser Doppler scanning, indicating the promotion of angiogenesis. Histological analysis of the hind limb muscle confirmed the increased number of vessels and the enhanced vascular expression of vascular endothelial growth factor receptor 2 (VEGFR2) in rat with BPC 157 treatment. In vitro study using human vascular endothelial cells further confirmed the increased mRNA and protein expressions of VEGFR2 but not VEGF-A by BPC 157. In addition, BPC 157 could promote VEGFR2 internalization in vascular endothelial cells which was blocked in the presence of dynasore, an inhibitor of endocytosis. BPC 157 time dependently activated the VEGFR2-Akt-eNOS signaling pathway which could also be suppressed by dynasore. The increase of endothelial tube formation induced by BPC 157 was also inhibited by dynasore. This study demonstrates the pro-angiogenic effects of BPC 157 that is associated with the increased expression, internalization of VEGFR2, and the activation of VEGFR2-Akt-eNOS signaling pathway. BPC 157 promotes angiogenesis in CAM assay and tube formation assay. BPC 157 accelerates the blood flow recovery and vessel number in rats with hind limb ischemia. BPC 157 up-regulates VEGFR2 expression in rats with hind limb ischemia and endothelial cell culture. BPC 157 promotes VEGFR2 internalization in association with VEGFR2-Akt-eNOS activation. Key message: [ABSTRACT FROM AUTHOR]

Genital calcinosis presents as single or multiple hard nodules in childhood and young adults. Although originally thought to represent an idiopathic condition, it is more likely that this disorder develops from dystrophic calcification of epidermoid cyst. No known publication has mentioned the relationship between scrotal calcinosis and human papillomavirus (HPV). An 18-year-old student suffered from sudden onset of multiple asymptomatic yellowish papules over the scrotum for 2 months. Skin biopsy using von Kossa stain and energy-dispersive spectrometry showing calcium deposition with a cyst formation, confirmed the diagnosis of scrotal calcinosis. The cyst wall was composed of koilocytes and multinuclear giant cells. Tissue HPV polymerase chain reaction, genotyping, and western blotting were arranged due to the above unusual observation. HPV-70 infection was detected in tissue genotyping. There were also some dilated eccrine ducts, denatured dartos muscles, and fibrous pseudocapuscule found in decalcified specimens. HPV infection over the genital area may play a role in pathogenesis of scrotal calcinosis. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to estimate the risk of hyperuricaemia and gout in people with hypothyroid or hyperthyroid status. Methods: This study analyzed data from individuals who participated in health screening programs at Chang Gung Memorial Hospital in northern Taiwan (2000–2010). Participants were categorized as having euthyroid, hypothyroid, or hyperthyroid status according to their thyroid-stimulating hormone (TSH) levels. Multinomial logistic regression models were used to calculate the odds ratios (95% CI) for hyperuricaemia and gout in participants with thyroid dysfunction compared to euthyroid participants. Results: A total of 87,813 (euthyroid, 83,502; hypothyroid, 1,460; hyperthyroid, 2,851) participants were included. The prevalence of hyperuricaemia was higher in hyperthyroid subjects (19.4%) than in euthyroid subjects (17.8%) but not in hypothyroid subjects (19.3%). The prevalence of gout was significantly higher in both hypothyroid (6.0%) and hyperthyroid (5.3%) subjects than in euthyroid subjects (4.3%). In men, hypothyroid or hyperthyroid status was not associated with hyperuricaemia. However, hypothyroid or hyperthyroid status was associated with ORs (95% CI) of 1.47 (1.10–1.97) and 1.37 (1.10–1.69), respectively, for gout. In women, hypothyroid status was not associated with hyperuricaemia or gout. However, hyperthyroid status was associated with ORs (95% CI) of 1.42 (1.24–1.62) for hyperuricaemia and 2.13 (1.58–2.87) for gout. Conclusions: Both hyperthyroid and hypothyroid status were significantly associated with gout and weakly associated with hyperuricaemia. A thyroid function test for gout patients may by warranted. [ABSTRACT FROM AUTHOR]

Coronary computed tomography angiography (CCTA) is a widely used imaging modality for diagnosing coronary artery disease (CAD) but is limited by a high false positive rate when evaluating coronary arteries with stents and heavy calcifications. Virtual intravascular endoscopy (VIE) images generated from CCTA can be used to qualitatively assess the vascular lumen and might be helpful for overcoming this challenge. In this study, one hundred subjects with coronary stents underwent both CCTA and invasive coronary angiography (ICA). A total of 902 vessel segments were analyzed using CCTA and VIE. The vessel segments were first analyzed on CCTA alone. Then, using VIE, the segments were classified qualitatively as either negative or positive for in-stent restenosis (ISR) or CAD. These results were compared, using ICA as the reference, to determine the added diagnostic value of VIE. Of the 902 analyzed vessel segments, CCTA/VIE had sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (shown in %) of 93.9/90.2, 96.2/98.2, 96.0/97.7, 70.0/83.1, and 99.4/99.0, respectively, in diagnosing ISR or CAD, with significantly improved specificity (p = 0.025), accuracy (p = 0.046), and positive predictive value (p = 0.047). VIE can be a helpful addition to CCTA when evaluating coronary arteries. [ABSTRACT FROM AUTHOR]

Background. The cutaneous manifestations of human enterovirus (HEV) infection are usually limited, such as hand-foot-mouth disease. By comparison, Stevens-Johnson syndrome (SJS) is a life-threatening severe cutaneous adverse reaction (SCAR), mainly caused by drugs. During the HEV outbreaks in 2010-2012 in Taiwan, we identified 21 patients who developed widespread blistering mucocutaneous reactions without any suspected drug causality. Methods. We screened possible pathogen(s) for detecting human herpes virus (HHV1-HHV7), HEV, or Mycoplasma pneumoniae infections using throat swab virus cultures, real-time PCR, DNA sequencing, immunochemistry and electron microscopy analyses. Results. Coxsackievirus A6 (CVA6) DNA was identified in the blistering skin lesions in 6 of 21 patients. Cytotoxic T lymphocytes and natural killer cells expressing granulysin predominantly infiltrated into the skin lesions, sharing the histopathological features with SJS. Intact CVA6 viral particles were identified in the blister fluids and skin lesions by electron microscopy. The phylogenetic analysis of the viral genome showed the CVA6 DNA sequence sharing higher similarity (97.6%-98.1%) to CVA6 strains reported from Finland at 2008. Conclusions. This study identifies a new variant of CVA6 as the causative agent for severe mucocutaneous blistering reactions mimicking SCAR. An awareness of this unusual presentation of HEV infection is needed in the epidemic area. [ABSTRACT FROM AUTHOR]

Background. The cutaneous manifestations of human enterovirus (HEV) infection are usually limited, such as hand-foot-mouth disease. By comparison, Stevens-Johnson syndrome (SJS) is a life-threatening severe cutaneous adverse reaction (SCAR), mainly caused by drugs. During the HEV outbreaks in 2010–2012 in Taiwan, we identified 21 patients who developed widespread blistering mucocutaneous reactions without any suspected drug causality.Methods. We screened possible pathogen(s) for detecting human herpes virus (HHV1–HHV7), HEV, or Mycoplasma pneumoniae infections using throat swab virus cultures, real-time PCR, DNA sequencing, immunochemistry and electron microscopy analyses.Results. Coxsackievirus A6 (CVA6) DNA was identified in the blistering skin lesions in 6 of 21 patients. Cytotoxic T lymphocytes and natural killer cells expressing granulysin predominantly infiltrated into the skin lesions, sharing the histopathological features with SJS. Intact CVA6 viral particles were identified in the blister fluids and skin lesions by electron microscopy. The phylogenetic analysis of the viral genome showed the CVA6 DNA sequence sharing higher similarity (97.6%–98.1%) to CVA6 strains reported from Finland at 2008.Conclusions. This study identifies a new variant of CVA6 as the causative agent for severe mucocutaneous blistering reactions mimicking SCAR. An awareness of this unusual presentation of HEV infection is needed in the epidemic area. [ABSTRACT FROM PUBLISHER]

The objective of this study was to investigate the effects of two lasers (Er:YAG and CO) in enhancing skin permeation of three vitamin C derivatives, L-ascorbic acid 2-phosphate sesquimagnesium salt (MAP-1), magnesium L-ascorbic acid-2-phosphate (MAP-2), and 2-phospho-L-ascorbic acid trisodium salt (SAP). Dorsal skin of 1-week-old pathogen-free pigs was used for this in vitro study. Changes in permeation in laser-treated skin treated by the lasers were examined by confocal scanning electron microscopy. Transdermal flux of vitamin C derivatives was examined with a Franz diffusion cell. Fluxes of MAP-1, MAP-2, and SAP across Er:YAG laser-treated skin were 15-27-fold, 48-123-fold, and 22-56-fold higher, respectively, than their fluxes across intact skin. The fluxes of MAP-1, MAP-2, and SAP across CO laser-treated skin were 28-36-fold, 116-156-fold, and 79-102-fold higher, respectively, than their fluxes across intact skin. Optimal fluency for the Er:YAG laser was 3.8 J/cm for MAP-1 and 5 J/cm for MAP-2 and SAP. Optimal fluency for the CO laser was 5 W for all three derivatives. In conclusion, optimal fluency for all derivatives was 5 W for the CO laser and 3.8 to 5 J/cm for the Er:YAG laser. [ABSTRACT FROM AUTHOR]

Objective. To investigate the association between gout and myocardial infarction (MI) in a representative cohort in Taiwan.Methods. Data were collected from the Taiwan National Health Insurance database. Adults >20 years of age without history of MI were included. Patients were considered to have gout if they received a diagnosis of gout requiring medical treatment. Multivariate Cox proportional hazards models were used to evaluate the risk of MI in gout patients.Results. Of the 704 503 patients included, 26 556 (3.8%) had gout. In total, 3718 (with gout, n = 463; without gout, n = 3255) patients had an MI, 299 (with gout, n = 35; without gout, n = 264) of whom died. The incidence of MI was 2.20 and 0.60 per 1000 patient-years in individuals with and without gout, respectively (log-rank test, P < 0.001). After adjustment for age, sex and history of diabetes mellitus, hypertension, coronary heart disease (CHD), stroke and end-stage renal disease, gout was associated with MIs [hazard ratio (HR), 1.23] and non-fatal MIs (HR, 1.26). In individuals without cardiovascular risk factors, gout was associated with MIs (HR 1.84; 95% CI 1.51, 2.24) and non-fatal MIs (HR 1.80; 95% CI 1.49, 3.95), after adjustment for age and sex. Moreover, in our study population, the HRs for MI decreased as age increased.Conclusion. Gout is an independent risk factor for MI, and the increased risk of MI is present even in young people and those without cardiovascular risk factors. [ABSTRACT FROM PUBLISHER]

Background Topical treatment with vitamin C has been used to treat photoaged skin and as a skin whitener, but no standard procedure exists for percutaneous delivery. Objective To compare skin histology and the permeation of ascorbic acid 2-glucoside (AA2G) after fractional and conventional carbon dioxide (CO2) laser pretreatment. Methods The effect on porcine skin of treatment with different strengths of fractional and conventional CO2 laser treatment was examined using scanning electron microscopy and transmission electron microscopy. Permeation of AA2G through porcine skin was tested in vitro using a Franz diffusion chamber. In vivo changes in fluorescein thiocyanate permeability in nude mice were examined using confocal laser scanning microscopy. Results Fractional CO2 laser treatment with four or fewer passes caused less disruption than conventional laser treatment at the same fluence. AA2G permeation using four passes of fractional laser treatment was similar to that seen with conventional CO2 laser treatment of the same fluence. Changes in permeability and in depth of permeation were higher with conventional than fractional laser treatment. Conclusion Fractional CO2 laser treatment can cause similar transdermal delivery of AA2G to conventional laser treatment with less skin disruption and a different pattern of histologic change. [ABSTRACT FROM AUTHOR]

Abstract: Background: To analyze the relationship between intraocular pressure, metabolic variables, and components of metabolic syndrome in different age and gender groups. Methods: We examined 10,491 Taiwanese adults aged 21 to 79years and categorized according to gender and age. All participants underwent examinations, including body mass index (BMI), waist circumference, blood pressure, intraocular pressure, and blood chemistry. Multiple linear regression analyses were performed to evaluate the relationships between intraocular pressure and these variables as well as to determine the relative influence of each component of metabolic syndrome. Results: Intraocular pressure showed a significant reduction with aging in men but not in women. BMI had a positive association with intraocular pressure in young adults and middle-aged men. Systolic blood pressure was positively associated with intraocular pressure in most groups, whereas diastolic blood pressure was positively associated with intraocular pressure only in middle-aged and elderly men. Fasting blood sugar levels showed a significant association with high intraocular pressure in middle-aged and elderly adults. All participants with metabolic syndrome had higher intraocular pressure levels, and each component of metabolic syndrome had a distinct effect on the intraocular pressure, with blood pressure being the strongest predictor. Conclusion: Elevated intraocular pressure is associated with a number of metabolic variables, and each component of metabolic syndrome has a distinct impact on the intraocular pressure in individual age- and gender-specific groups. The present results may allow internal medicine specialists to manage metabolic risk factors while considering possible ocular involvement and potential treatment interactions. [Copyright &y& Elsevier]

The objective of this study is to investigate the effects of two lasers (erbium:YAG and CO(2)) on the ability to enhance skin permeation of two vitamin C derivatives, 3-O-ethyl ascorbic acid (EAC) and ascorbic acid 2-glucoside (AA2G). The study was taken in the skin of a female nude mouse (Balb/c-nu strain, 8 weeks old) in vitro. The histologic and ultrastructural changes of the nude mouse skin treated by the lasers were examined under light microscopy and transmission electron microscopy, respectively. The in vitro permeation of vitamin C derivatives was performed in Franz cell. The stratum corneum (SC) layer in the skin was partly ablated by erbium:YAG laser treatment, resulting in greater permeation of both vitamin C derivatives. The flux of EAC and AA2G across erbium:YAG laser-treated skin was 105 to 189-fold and 35 to 78-fold higher, respectively, than their flux across intact skin. The increase in enhancement ratio with increase in fluency decreases markedly for both compounds at the last dose escalation (from 5.0 to 6.3 J/cm(2)). Both SC ablation and a thermal effect may contribute to the effect of the CO(2) laser on skin structure. The flux of EAC and AA2G across CO(2) laser-treated skin was 181 to 277-fold and 82 to 117-fold higher, respectively, than their flux across intact skin. We concluded that both erbium:YAG and CO(2) laser pretreatment increased the transdermal flux of two stable vitamin C derivatives, EAC and AA2G. The optimal fluency for the Er:YAG laser was 5 J/cm(2). [ABSTRACT FROM AUTHOR]

The effects of serum uric acid (SUA) and metabolic syndrome on chronic kidney disease (CKD) remain controversial. This study grouped subjects according to a combination of their uric acid and metabolic syndrome status and investigated the association between these groups and CKD to clarify the relationships of SUA and metabolic syndrome to CKD. This survey analyzed data from 81,799 adults (45,148 men and 36,651 women) who underwent health examinations at Chang Gung Memorial Hospital, in northern Taiwan, from 2000 through 2007. Hyperuricemia was defined as an SUA greater than 7.7 mg/dL in men or greater than 6.6 mg/dL in women. Patients were classified by uric acid-metabolic syndrome status as follows: A = no hyperuricemia and no metabolic syndrome, B = presence of metabolic syndrome but not hyperuricemia, C = presence of hyperuricemia but no metabolic syndrome, and D = presence of both hyperuricemia and metabolic syndrome. Kidney function was assessed in terms of the estimated glomerular filtration rate (eGFR) by using the Modification of Diet in Renal Disease Study equation modified for Chinese. CKD was defined as an eGFR <60 mL/min/1.73 m. The prevalences of hyperuricemia, metabolic syndrome, and CKD were 22.8% (26.3% in men and 18.6% in women), 13.5% (15.0% in men and 11.6% in women), and 2.2% (2.1% in men and 2.2% in women), respectively. In men, the age-adjusted odds ratios for CKD, with group A as reference, were 1.95 for group B, 4.86 for group C, and 5.85 for group D. In women, the age-adjusted odds ratios were 1.96 for group B, 6.66 for group C, and 9.01 for group D. Hyperuricemia is strongly associated with CKD, independent of the presence of metabolic syndrome. [ABSTRACT FROM AUTHOR]

Objectives. Hyperuricaemia has been linked to atherosclerosis; however, there is limited evidence about its association with arterial stiffness and cardiac hypertrophy, which are associated with adverse cardiovascular outcomes. We studied the association of hyperuricaemia with an increased risk of arterial stiffness and cardiac hypertrophy in a population participating in a health-screening programme. [ABSTRACT FROM PUBLISHER]

Objective. The relation of gout and hyperuricaemia to cardiovascular diseases has been well documented. This study investigates the survival impact of both gout and hyperuricaemia. Methods. The subjects of this study comprised participants of a health screening programme conducted by the Chang Gung Memorial Hospital in Taiwan from 2000 to 2006. The status and causes of death were ascertained by the Taiwan National Death Registry 2000-07. Cox proportional hazard model was performed to examine the association. Results. Among 61 527 subjects, 1383 deaths (198 cardiovascular deaths) were identified, corresponding to a crude mortality rate of 4.86 deaths per 1000 person-years. Crude mortality rates were 4.50, 5.61 and 10.46 deaths per 1000 person-years for subjects with normouricaaemia, hyperuricaemia and gout, respectively. Compared with subjects with normouricaemia, the hazard ratios (HRs) of all-cause mortality were 1.46 (95% CI 1.12, 1.91) for individuals with gout and 1.07 (95% CI 0.94, 1.22) for those with hyperuricaemia, respectively, after adjustments were made for age, sex, component number of metabolic syndrome and proteinuria. The adjusted HRs of cardiovascular mortality were 1.97 (95% CI 1.08, 3.59) for individuals with gout and 1.08 (95% CI 0.78, 1.51) for those with hyperuricaemia. Moreover, the risk of all-cause or cardiovascular mortality for gout remained unchanged when limiting the data to those with an estimated glomerular filtration of >60 ml/min/1.73m2. Conclusion. This study demonstrates a link of gout, not hyperuricaemia, with a higher risk of death from all causes and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Objective We studied the response of the superior vena cava (SVC) myocardial sleeve to atrial fibrillation (AF). Methods and results We examined adult male dogs without pacing (N=6) and after rapid atrial pacing (600 bpm) for 2 weeks (P2w; N=5) and 6-8 weeks (P6-8w; N=5). After pacing, the sleeve was increased in thickness (non-paced vs. either paced group, both P<0.05). This was associated with an increase in proliferative activity, which was higher in the P2w than the P6-8w animals (P < 0.05). In addition, collagen content increased, and the component cardiomyocytes become more unevenly oriented and shorter and narrower in shape (non-paced vs. either paced group, both P < 0.05). Pacing had different effects on connexin40 (Cx40) and Cx43 gap junctions. There was a 98% increase in Cx43 signal in P2w, and a 74% increase in P6-8w animals (non-paced vs. each paced group, both P < 0.05). In contrast, Cx40 signal decreased 47% in P2w but increased 44% in P6-8w animals (nonpaced vs. each paced group, both P < 0.05). Conclusions Rapid atrial pacing results in a specific pattern of remodeling of the canine SVC sleeve, including changes in size and shape, spatial orientation, and gap junction expression profile of the component cardiomyocytes. These changes may co-operatively affect the electrical properties and contribute to the formation and maintenance of the arrhythmogenic substrate of AF [ABSTRACT FROM AUTHOR]

Abstract: Recently, a T/C polymorphism of the promoter region of the APOA5 gene at position -1131 and a G/T polymorphism at position 553 were found to be associated with increased levels of plasma triglyceride. Triglyceride plays a role in coronary artery disease (CAD), so this case–control study tested for a possible link between these two APOA5 polymorphisms, their common haplotypes and the risk of CAD. The subjects included 211 CAD patients and 677 unrelated controls. A significantly higher level of triglycerides and a lower level of high-density lipoprotein cholesterol (HDL-C) were noted for carriers with -1131C than for non-carriers (P <0.001 and 0.013, respectively) among controls. Plasma triglyceride levels were significantly higher (P =0.014) in controls with genotypes that contained the c.553T allele than in homozygotes for the G allele. Subjects homozygous for the wild-type haplotype had significantly lower triglyceride levels and higher HDL-C levels than subjects with all other haplotype pairs. The -1131C homozygous carriers and c.553T heterozygous carriers were found more frequently in 211 patients with CAD than in the 317 age/sex-matched controls (P =0.008 and 0.023, respectively) in univariate analysis. The significant association between c.553T allele carriers with CAD remained in multivariate regression analysis (OR, 1.79; CI, 1.07–3.00; P =0.028), after adjustments were made for other risk factors. Notably, haplotype analysis further verified that the APOA5 -1131C and c.553T bi-loci haplotype was significantly overpresented in CAD, as compared to the controls. These results indicate that the variants of APOA5 gene modulate plasma triglyceride and may use them to predict CAD susceptibility in Taiwanese Chinese. [Copyright &y& Elsevier]

Gap junctions, assembled from connexins, form the cell-to-cell pathways for propagation of the precisely orchestrated patterns of current flow that govern the regular rhythm of the healthy heart. As in most tissues and organs, multiple connexin types are expressed in the heart; connexin43, connexin40 and connexin45 are found in distinctive combinations and relative quantities in different, functionally specialized subsets of cardiomyocyte. Alterations of gap junction organization and connexin expression are now well established as a consistent feature of human heart disease in which there is an arrhythmic tendency. These alterations may take the form of structural remodelling, involving disturbances in the distribution of gap junctions and/or alteration of the amount or type of connexin(s) expressed. In the diseased ventricles, the most consistent quantitative alteration involves heterogeneous reduction in connexin43 expression. In the atria, features of gap organization and connexin expression have been implicated in the initiation of atrial fibrillation and, once the condition becomes chronic, gap junction alterations associated with remodelling may contribute to persistence of the condition. By correlating data from studies on the human patient with those from animal and cell models, alterations in gap junctions and connexins have emerged as important factors to be considered in understanding the pro-arrhythmic substrate found in a variety of forms of heart disease. [Copyright &y& Elsevier]

We investigated the effect of nicotine on connexin43 (Cx43) expression and gap-junctional communication in human umbilical vein endothelial cells (HUVEC). We also evaluated whether the effect requires activation of acetyl choline receptors sensitive to nicotine (nAChRs) and is altered by statins. The results showed that expression of Cx43 protein is reduced by nicotine in a dose-dependent manner (6×10-4 M nicotine vs control, 33% reduction, p<0.01), though Cx43 mRNA is up-regulated (6×10-4 M nicotine vs control, 36% increase, p<0.01). Concomitantly, the communication function, determined by fluorescence recovery after photobleaching, is decreased (6×10-4 M nicotine vs control, 38% reduction, p<0.05). Such a down-regulation of Cx43 gap junctions by nicotine disappears in the presence of the nAChRs antagonist, dihydro-β-erythroidine, and protease inhibitors leupeptin plus N-acetyl-Leu-Leu-Norleu-al (ALLN). Similarly, the effect of nicotine is attenuated by statins, including fluvastatin, lovastatin, pravastatin, and simvastatin, even at the presence of mevalonate. We concluded that i) nicotine down-regulates Cx43 expression and gap-junctional communication in HUVEC via post-transcriptional modification, which involves enhancement of Cx43 proteolysis; ii) the effect of nicotine is mediated via activation of nAChRs; and iii) the effect of nicotine is attenuated by statins through mechanisms outside the hypolipidemic pathway. [ABSTRACT FROM AUTHOR]

We examined the effect of 2′,5′-dihydroxychalcone on connexin43 (Cx43) expression and gap-junctional communication in human umbilical vein endothelial cells (HUVEC). The result showed that expression of Cx43 is rapidly reduced by 2′,5′-dihydroxychalcone in a dose-dependent manner, Concomitantly, the communication function, determined by fluorescence recovery after photobleaching (FRAP), is decreased. We further investigated whether the mitogen-activated protein (MAP) kinase and the degradation pathway of gap junctions are involved in these processes. Although the change of Cx43 is not affected by the level of fetal calf serum (FCS) used in the medium, activation of MAP kinase varies, depending on the FCS level. At a low level (0.5%), the chalcone inhibits the activation, like PD98059, a specific inhibitor of MAP kinase kinase. However, at a high level (20%), MAP kinase is activated. On the other hand, the chalcone''s down-regulating effect on Cx43, while is totally blocked by protease inhibitors leupeptin and N-acetyl-leucyl-norleucinal (ALLN), persists in the presence of PD98059, We concluded that 2′,5′-dihydroxychalcone down-regulates Cx43 expression and gap-junctional communication in the HUVEC via enhancement of the proteolysis pathway, and this compound possesses dual effects on MAP kinase activation. [Copyright &y& Elsevier]

Discusses the use of on-line multiplane transesophageal echocardiography (TEE) for balloon mitral commissurotomy (BMC) in the treatment of mitral stenosis. Inherent limitations of BMC; Partial replacement of fluoroscopy by on-line TEE; Utilization of a multiplane transducer.

Iliacus abscess is an extremely rare complication of percutaneous transfemoral artery catheterization. This is a report of a case of iliacus abscess and Acinetobacter baumanii sepsis following percutaneous transfemoral artery catheterization. After a 43-day course of intravenous antibiotics treatment and repeated drainage, clinical recovery was achieved, though without complete radiologic resolution. [ABSTRACT FROM AUTHOR]

Background: Nail changes, including onychomadesis (nail shedding) and Beau's line, following hand-foot-mouth disease (HFMD) are a common emergence at the stage of late complications of HFMD. However, the exact mechanism is still unknown. Therefore, we conducted this study to elucidate the mechanism of nail changes following HFMD. Methods: We collected 11 patients suffering from onychomadesis following HFMD. Nail samples from all of them were collected. Real time reverse transcription polymerase chain reaction (RT-PCR) and sequencing for human enteroviruses (HEV) were performed. Throat swabs for RT-PCR and sequencing for HEV were performed for three cases. Results: RT-PCR demonstrated the presence of Coxackievirus A6 (CVA6) in nail samples from three patients and one with Echovirus. Conclusion: In conclusion, we believe that the major cause of onychomadesis following HFMD is that certain novel viruses, mostly CVA6, are virulent and may damage nail matrix. Direct injury caused by cutaneous lesions of HFMD around nail matrix is a minor cause. There are still other virulent HEV which may result in onychomadesis. In addition, the novel strain of CVA6 also causes atypical clinical presentations, such as adult involvement and delayed-onset palmar and plantar desquamation. Physicians should be familiar with atypical presentations caused by novel viruses to avoid misdiagnosis and even inform patients of the possibility of onychomadesis that may take place weeks later to reassure patients. [ABSTRACT FROM AUTHOR]

The transcatheter closure of atrial septal defects provides an alternative to surgery, and various devices, such as the Sideris buttoned device, have been prescribed. Late complications have been rare and have not yet been reported within 2 years of implantation. This report presents a case of delayed migration of a Sideris buttoned device occurring 6 years after successful implantation. In conclusion, this report provides a reminder of the need for careful long-term follow-up of patients receiving transcatheter closure of atrial septal defects, particularly in cases involving the implantation of early-generated devices. [Copyright &y& Elsevier]