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Background: Many women of reproductive age experience adverse psychological and physiological premenstrual symptoms. These symptoms may last for most of the reproductive years and can negatively affect the quality of life of many women. Some studies have examined the role of micronutrients in premenstrual symptoms, but the research on iron has been limited.Objectives: The objective of this study was to evaluate the effects of genetic predictors of iron overload and low iron status on premenstrual symptoms using Mendelian randomization.Methods: We examined 254 White females aged 20-29 y from the Toronto Nutrigenomics and Health Study. DNA was isolated from peripheral white blood cells and genotyped for the homeostatic regulatory iron gene (HFE; rs1800562 and rs1799945), transmembrane protease serine 6 (TMPRSS6; rs482026), transferrin receptor 2 (TFR2; rs3811647), and transferrin (TF; rs738584) polymorphisms. Risk of iron overload or low iron status was determined based on combined genotypes. Binomial logistic regressions were carried out to examine the association between genetic risk of iron overload or low iron status and the presence of premenstrual symptoms.Results: Compared with participants with typical risk of iron overload, those with an elevated risk of iron overload were less likely to experience premenstrual symptoms of confusion (OR: 0.13; 95% CI: 0.02, 1.00), headaches (OR: 0.28; 95% CI: 0.08, 0.98), and nausea (OR: 0.13; 95% CI: 0.02, 0.99) after adjusting for BMI, age, and vitamin C and calcium intake. No associations were seen with the other symptoms. There were also no associations between low iron status genotypes and premenstrual symptoms.Conclusions: This Mendelian randomization study demonstrates that women with an elevated risk of iron overload may have a lower risk of experiencing some premenstrual symptoms (headache, confusion, and nausea), suggesting that iron status could impact the risk of certain premenstrual symptoms. [ABSTRACT FROM AUTHOR]

Gene therapy strategies for liver cancer have broad application prospects but still lack a stable and efficient delivery vehicle. To overcome this obstacle, we designed a multifunctional gene delivery vector, sTPssOLP, which was based on oleylamine (OA)-modified disulfide-containing polyethylenimine (PEI) and incorporated into lipids to prepare a lipid nanoparticle. sTPssOLP consisted of the core of PEI derivative and cationic lipids bound to siRNA. The modified polyethylene glycol (PEG) and transferrin (Tf) were partially embedded in the phospholipid bilayer through the lipid and the other as the outer shell. The aim was to use the redox responsiveness of disulfide to trigger siRNA release in cytoplasm to enhance transfection efficiency. Pegylated lipids and Tf focus on increasing cycle life in the body and increasing accumulation at the tumor site of the carrier. In addition, two vectors were prepared as controls, one based on a PEI derivative containing no disulfide bond (POLP) and the other on the surface of the carrier not linked to Tf (PssOLP). PEI derivatives effectively avoid the toxicity problems caused by the use of PEI alone (25 kDa). Meanwhile, it was confirmed by gel retardation experiments that in the presence of dithiothreitol (DTT), the disulfide bond can indeed be reduced and the siRNA entrapped in the vector can be released. Both HepG2 and SMMC had significant uptake of sTPssOLP. The results of intracellular and lysosomal co-localization indicated that sTPssOLP achieved lysosomal escape. RT-PCR and Western blot results also confirmed that sTPssOLP had the best gene silencing activity. In vivo, the tumor inhibition rate of sTPssOLP in nude mice carrying HepG2 xenografts was 56%, which was significantly greater than that of the saline control group. In vivo imaging results showed that fluorescently labeled siRNA loaded in sTPssOLP was able to deliver more to the tumor site. At the same time, it was observed that sTPssOLP did not show significant damage to normal tissues. Therefore, this multifunctional gene delivery vector warrants further investigation. [ABSTRACT FROM AUTHOR]

• A green-house test was led to examine the efficacy of heavy metal-tolerant plant growth promoting bacterial. • Using bacterial strains (HMT-PGPB) to alleviate the heavy metal's toxic effects on sorghum plant. • The oxidative enzymes, photosynthetic pigments, growth characteristics, were estimated in sorghum cultivated. • Also, heavy metals uptake and heavy metals translocation factor (TF) were tested in sorghum cultivated in soil. • This soil contaminated with heavy metals under green-house conditions. A green-house experiment was conducted to investigate the efficiency of three heavy metal-tolerant plant growth promoting bacterial strains (HMT-PGPB) (Alcaligenes faecalis MG257493.1, Bacillus cereus MG257494.1 and Alcaligenes faecalis MG966440.1 to alleviate the heavy metal's toxic effects on sorghum plant (Sorghum bicolor , L.) in addition to their ability to enhance plant growth. The oxidative enzymes, photosynthetic pigments, growth characteristics, heavy metals uptake and heavy metals translocation factor (TF) were estimated in sorghum cultivated in soil contaminated with heavy metals under green-house conditions. Results showed that the application of these HTM-PGPB strains as biofertilizer of sorghum help plant to ignore the toxic effects of heavy metals and enhance growth characteristics. [ABSTRACT FROM AUTHOR]

Abstract Mariculture wastewater treatment by nitrification requires a long start-up time due to high salinity stress. This study aimed to verify the faster start-up of a trickling filter (TF) compared to a moving bed bioreactor (MBBR) treating synthetic mariculture wastewater, and to investigate the feasibility of transferring mature biocarriers from the TF to a new MBBR (TF-MBBR). The nitrogen removal performance, biofilm physicochemical properties and microbial communities were investigated. The results obtained showed that, the TF started up 41 days faster than the MBBR, despite the richer microbial diversity in the latter. Lower biofilm roughness and protein content as well as higher adhesive force and polysaccharide content in the TF were obtained compared to the MBBR. Adhesive force was found to be negatively correlated with roughness (r = −0.630, p = 0.069). Transmittance assigned to amide II (1538 cm−1) and amid III (1243 cm−1) through Fourier transform infrared spectroscopy (FTIR) determination was only obtained in the TF, which was likely related to the faster start-up. Nitrosomonas and Nitrospira were detected as the predominant nitrifiers in both reactors. In addition, the new MBBR, incubated with the mature biocarriers transferred from the TF, had a satisfactory nitrification performance with no lag time. Interestingly, the transfer action increased the microbial diversity and made the biofilm physicochemical characteristics shift toward those of the MBBR. Taken together, the study confirmed that MBBR nitrification start-up can be accelerated via TF and biocarrier transfer. Graphical abstract Image Highlights • Transfer of mature biocarriers from TF to MBBR was studied. • TF had faster nitrification start-up by 41 days than MBBR under same NH 4 + N load. • New MBBR started up instantly when using mature biocarriers from TF. • Lower microbial diversity observed in the TF likely due to high water flow rate. • N. halophila and Nitrospira were the core nitrifiers in both reactors. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The blood-brain barrier (BBB) and low targeting are major obstacles for the treatment of gliomas. Accordingly, overcoming the BBB and enhancing the targeting of drugs to the glioma area are key to achieving a good therapeutic effect. Here, we have developed the mesoporous ruthenium nanosystem RBT@MRN-SS-Tf/Apt with dual targeting function. Transferrin (Tf) and aptamer AS1411 (Apt) are grafted on the surfaces of mesoporous ruthenium nanoparticles (MRN) with high loading capacity. This is achieved via redox-cleavable disulfide bonds, serving as both a capping agent and a targeting ligand, enabling the effective penetration of the blood-brain barrier and targeting the glioma. In addition, RBT@MRN-SS-Tf/Apt can specifically kill glioma cells in vitro and in vivo. Moreover, anti-tumor drugs [Ru(bpy) 2 (tip)]2+ (RBT) will produce reactive oxygen species and induce apoptosis of tumor cells under laser irradiation, providing photodynamic therapy (PDT) for the treatment of gliomas, and further prolonging the median survival period. The study shows that this chemical photodynamic therapy nanosystem can be used as an efficient and powerful synergistic system for the treatment of brain tumors and other brain diseases of the central nervous system. Statement of Significance In order to overcome the blood-brain barrier and low targeting, and enhance the anti-glioma activities of nanodrugs. We have developed RBT@MRN-SS-Tf/Apt with dual targeting function. It is achieved release drug via redox-cleavable disulfide bonds, and enable the effective penetration of the blood-brain barrier and targeting the glioma. Moreover, anti-tumor drugs RBT will produce reactive oxygen species and induce apoptosis of tumor cells under laser irradiation, providing photodynamic therapy (PDT) for the treatment of gliomas, and further prolonging the median survival period. Therefore, this chemical photodynamic therapy nanosystem can be used as an efficient and powerful synergistic system for the treatment of brain tumors and other brain diseases of the central nervous system. [ABSTRACT FROM AUTHOR]

Takotsubo cardiomyopathy (TTS) has long been considered a benign condition, despite recurrent events and long-term adverse outcomes are often reported. Endothelial damage, blood hyperviscosity, and platelet activation described in acute phase persist in long-term follow-up; however, TTS pathophysiology is still not fully understood. Here, we explored the hemostatic system at a median of 3.1 years after TTS to uncover additional long-lasting changes in these patients. We assessed hemostatic parameters in women with TTS (n = 23) or coronary artery disease (CAD; n = 31) and in control women (n = 26) age-matched, by thromboelastographic analysis, prothrombin time (PT) and partial thromboplastin time (aPTT) coagulation assays and microparticle exposing Tissue Factor (MP-TF). Functional fibrinogen and fibrin polymerization were analyzed by Clauss method and spectrophotometry, respectively. Platelet reactivity was evaluated by light transmission aggregometry, whereas plasminogen activator inhibitor-1 (PAI-1) and brain-derived neurotrophic factor (BDNF) were measured by ELISA kit. Compared with control subjects, TTS patients exhibit an accelerated clot formation, higher percentage of fibrin polymerization and higher PAI-1 levels. Compared with CAD, TTS patients showed sustained residual platelet activation but decreased functional fibrinogen, fibrin polymerization and MP-TF levels, prolonged aPTT and a marked BDNF increase. The long-term activation of hemostatic system observed in TTS patients compared to control subjects suggests a persistent humoral abnormality that may be related to the propensity for TTS recurrence. The higher residual platelet activity observed in TTS than in CAD patients invites investigation on TTS-tailored antiplatelet therapy potentially needed to prevent TTS adverse outcomes. • Takotsubo syndrome has been recently indicated as a life-threatening condition. • Takotsubo patients exhibit hemostatic activation compared to control subjects. • Takotsubo patients show a residual platelet activation compared to CAD patients. [ABSTRACT FROM AUTHOR]

Epithelial to mesenchymal transition (EMT) is a phenomenon in which epithelial cells lose their cell to cell adhesion and detach from the base of the membrane. EMT is a fundamental process which occurs during tumor progression and metastasis. Cancer genomics is a complex network which involves a variety of factors such as transcription factors (TFs), coding genes and microRNAs (miRs). Both TFs and miRs are trans -regulatory elements that crosstalk. Due to a wide range of targets, TF-miR interaction provides a feedback or feedforward loop and cross-gene regulation consequently. In this review, we focused on the structure and function of two TF families involved in EMT, zinc finger and β helix loop helix and p53. Subsequently we analyzed recent findings on TF-miR interaction in EMT. [ABSTRACT FROM AUTHOR]

Heavy metal(loid)s (HMs) in organic fertilizer have become a primary source of HMs pollution of farmlands, which could cause deleterious health effects in people exposed through soil-plant systems via multi-pathways. This study investigated China's main grain production area (Henan Province) to evaluate the accumulation and transport characteristics of HMs (Cr, Mn, Ni, Cu, Zn, As, Cd and Pb) in a soil-wheat system and conduct a health risk assessment for wheat ( Triticum aestivum ) grain under different nitrogenous fertilizer treatments. The results indicated that the Cr, Cu, As and Cd contents in soil were 56.21–113.66, 13.97–58.72, 5.79–22.62 and 0.04–0.23 mg·kg − 1 , and the mean contents of Cr and As contents in wheat grains were 0.78 ± 0.31 and 0.49 ± 0.18 mg·kg − 1 , respectively, which exceeded the corresponding standards. The bio-concentration factor and transfer factor were lowest in response to N-fertilization with N8–N15. Health risk assessment showed that the local population who ingested grain from culture condition of N15 experienced the lowest non-cancer and cancer risks. Among different population groups, HMs posed relatively higher non-cancer and cancer risks to children aged 0–5 years. Furthermore, Cr and As exposure was the greatest contributor to Hazard Index (HI), accounting for 74.72–83.11%, while Cr exposure accounted for > 90% of the total potential cancer risk. Concluding, this study indicated that, to protect human health, the current application of nitrogenous fertilizer should be controlled to an appropriate level. [ABSTRACT FROM AUTHOR]

The health risk of triadimefon (TF) to cardiovascular system of human is still unclear, especially to pesticide suicides population, occupational population (farmers, retailers and pharmaceutical workers), and special population (young children and infants, pregnant women, older people, and those with compromised immune systems) who are at a greater risk. Therefore, firstly we explored the toxic effects and possible mechanism of cardiovascular toxicity induced by TF using zebrafish model. Zebrafish at stage of 48 h post fertilization (hpf) exposed to TF for 24 h exhibited morphological malformations which were further confirmed by histopathologic examination, including pericardial edema, circulation abnormalities, serious venous thrombosis and increased distance between the sinus venosus (SV) and bulbus arteriosus (BA) regions of the heart. In addition to morphological changes, TF induced functional deficits in the heart of zebrafish, including bradycardia and a significant reduced cardiac output that became more serious at higher concentrations. To better understand the possible molecular mechanisms underlying cardiovascular toxicity in zebrafish, we investigated the transcriptional level of genes related to calcium signaling pathway and cardiac muscle contraction. Q-PCR (quantitative real-time polymerase chain reaction) results demonstrated that the expression level of genes related to ATPase ( atp2a1l , atp1b2b , atp1a3b ), calcium channel ( cacna1ab , cacna1da ) and cardiac troponin C ( tnnc1a ) were significantly decreased after TF exposure. For the first time, the present study revealed that TF exposure had observable morphological and functional negative impacts on cardiovascular system of zebrafish. Mechanistically, this toxicity might result from the pressure of down-regulation of genes associated with calcium signaling pathway and cardiac muscle contraction following TF exposure. These findings generated here can provide information for better pesticide poisoning treatments, occupational disease prevention, and providing theoretical foundation for risk management measures. [ABSTRACT FROM AUTHOR]

A comprehensive assessment of metals in wetlands of Guwahati were done in three systems – water, sediments and aquatic plants. Enrichment factor calculated for sediment showed that lead is significantly enriched. HPI and HEI values indicate that both lotic and lentic water bodies were critically polluted. TF shows that the metals were mostly translocated to the aerial parts. The correlation calculated among metal pairs showed that they were of similar origin. analysis of variance (ANOVA) reveals that the source of metals in all the three matrices is similar. The SEM-EDX micrograph of root of Eichhornia crassipes revealed the accumulation of metals in the tissues and this confirms the internalization of the metals. The FT-IR spectra of Eichhornia crassipes may be attributed to the interaction of metal ions with the hydroxyl, amide, thiol, and amino groups present in the plant biomass. [ABSTRACT FROM AUTHOR]

Tissue Factor (TF) is the initiator of coagulation and Tissue Factor Inhibitor (TFPI) is the physiological inhibitor of the TF/FVIIa complex. Circulating levels of TF and TFPI were quantified in dengue patients and the relationships with disease severity and infecting serotype analysed. A significant decrease in TF and TPFI plasma levels was observed in mild DF patients compared with severe dengue. Furthermore, both factors were associated with haemorrhagic manifestations. Finally, TF levels were significantly increased in DENV-1/2 infected patients as compared with DENV-4. These findings suggest that activation of TF-pathway is an important component of DENV -related coagulation disorders. [ABSTRACT FROM AUTHOR]

Medicinal plants consumed in Bitlis were analysed for 226Ra, 232Th and 137Cs using HPGe gamma spectroscopy system. Both plant samples and the corresponding soils were analysed. Using these values, the transfer factors for 226Ra, 232Th and 137Cs were calculated in the ranges of (0.09–2.18), (0.01–0.19) and (0.01–2.8), respectively. Based on the plant concentrations observed, unless consumed in excessive amounts, these medicinal plants do not have any radiological harm to health. • IAEA values with the geometric mean TF values for 232Th and 137Cs were in close agreement. • The geometric mean TF value for 226Ra was higher than the reference value from the IAEA. • Plants represent useful species seldom reported in the literature. [ABSTRACT FROM AUTHOR]

Recent studies have shown that transcription factors (TFs) and microRNAs (miRNAs), while independently regulate their downstream targets, collaborate with each other to regulate gene expression. However, their synergistic roles in protein–protein interactions (PPIs) remain mostly unknown. In this paper, we present a novel framework (called CoRePPI) for inferring TF and miRNA co-regulation of PPIs. Particularly, CoRePPI is aimed at discovering the co-regulation specific to a condition of interest, by using heterogeneous data, including miRNA and messenger RNA (mRNA) expression profiles, putative miRNA targets, TF targets and PPIs. CoRePPI firstly finds the network motifs indicating the co-regulation of PPIs by TFs and miRNAs in tumor and normal conditions separately. Then by identifying the differential motifs found in one condition but not in the other, it builds the networks consisting of TFs, miRNAs and their co-regulated PPIs specific to different conditions respectively. To validate CoRePPI, we apply it to the Pan-Cancer dataset which includes the expression profiles of 12 cancer types from TCGA. Through network topology analysis, we found that the tumor and normal CoRePPI networks are scale-free. Furthermore, the results of differential and intersected network analysis between the tumor and normal CoRePPI networks suggest that only a small fraction of the regulatory relationships between TFs and miRNAs are conserved in both conditions but they co-regulate different downstream PPIs in tumor and normal conditions; and in different conditions the majority of the regulatory relationships between TFs and miRNAs are different although they may regulate the same PPIs in their respective conditions. The CoRePPI sub-networks constructed for the three types of cancers (breast cancer, lung cancer and ovarian cancer) are all scale-free, and the intersection of these CoRePPI sub-networks can be utilized as the biomarker CoRePPI sub-network of the three types of cancers. The PPI enrichment analyses of the tumor and normal CoRePPI networks suggest that the co-regulating TFs and miRNAs are significantly associated with the specific biological processes, diseases and pathways. In addition, comparing with the two non-condition-specific approaches, the tumor CoRePPI network is found to have the most enriched cancer-related PPIs. Altogether, the results uncover the combined regulatory patterns of TFs and miRNAs on the PPIs, and may provide new insights for research in cancer-associated TFs and miRNAs. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate chemopreventive and therapeutic efficacy of tea polyphenols epigallocatechin gallete (EGCG) and theaflavin (TF) on self-renewal Wnt and Hedgehog (Hh) pathways during CCl4/N-nitosodiethylamine-induced mouse liver carcinogenesis. For this purpose, the effect of EGCG/TF was investigated in liver lesions of different groups at pre-, continuous and post initiation stages of carcinogenesis. Comparatively increased body weights were evident due to EGCG/TF treatment than carcinogen control mice. Both EGCG and TF could restrict the development of hepatocellular carcinoma at 30th week of carcinogen application showing potential chemoprevention in continuous treated group (mild dysplasia) followed by pretreated (moderate dysplasia) and therapeutic efficacy in posttreated group (mild dysplasia). This restriction was associated with significantly reduced proliferation, increased apoptosis, decreased prevalence of hepatocyte progenitor cell (AFP) and stem cell population (CD44) irrespective of EGCG/TF treatments. The EGCG/TF could modulate the Wnt pathway by reducing β-catenin and phospho-β-catenin-Y-654 expressions along with up-regulation of sFRP1 (secreted frizzled-related protein 1) and adenomatosis polyposis coli during the restriction. In case of the Hh pathway, EGCG/TF could also reduce expressions of glioma-associated oncogene homolog 1 (Gli1) and SMO (smoothened homolog) along with up-regulation of PTCH1 (patched homolog 1). As a result, in Wnt/Hh regulatory pathways decreased expressions of β-catenin/Gli1 target genes like CyclinD1, cMyc and EGFR/phospho-EGFR-Y-1173 and up-regulation of E-cadherin were seen during the restriction. Thus, the restriction of liver carcinogenesis by EGCG/TF was due to reduction in hepatocyte progenitor cell/stem cell population along with modulation of Wnt/Hh and other regulatory pathways. [ABSTRACT FROM AUTHOR]

Ficus carica L., commonly known as the fig tree, is a plant belonging to the Moraceae family whose fruits are traditionally used for edible and therapeutic purposes. The study aimed to investigate the lyophilized aqueous extracts of two native Algerian fig varieties, azendjar (Az) and taamriouth (Ta), as a potential source of antioxidant compounds for possible use as ingredients in pharmaceuticals or nutraceuticals. The HPLC-DAD analysis revealed the presence of two phenolic acids (3,4-dihydroxybenzoic acid and vanillic acid) and two flavonoids (rutin and quercetin) at levels 3.67, 4.80, 84.16, and 6.87 µg/g respectively for Az variety extract, and 6.90, traces, 7.46 and 3.37 µg/g respectively for Ta variety extract. Total phenolic content was determined using the Folin-Ciocalteu method at levels 951.06 ± 61.08 and 730.88 ± 45.25 GAE mg/100 g of the dry extract. In contrast, the total flavonoid content was determined using Christ-Müller's method at levels 428.34 ± 15.42 and 307.63 ± 7.94 QE mg/100 g of dry extract in the Az and Ta varieties, respectively. The total polyphenolic content of the extract may be responsible for its antioxidant action. The gathered results indicate that the extracts from the dark peel fig variety – azendjar, are characterized by a higher content of phenolic and flavonoid compounds and antioxidant activity than the extract from the light peel variety – taamriouth. In conclusion, the conducted studies and in vitro assays indicate that the studied extracts are a source of natural antioxidants and can be considered functional raw materials for producing food supplements and pharmaceuticals. [Display omitted] • Aqueous extracts of azendjar and taamriouth figs from Aghbal Algeria were studied. • Their phytochemical/phenolic profile and antioxidant activity were evaluated. • A new HPLC-DAD method was created and validated to analyze phenolic compounds. • 3,4-dihydroxybenzoic, vanillic acid, rutin, and quercetin were detected. • A dark peel variety contains more phenolics and shows a higher antioxidant capacity. [ABSTRACT FROM AUTHOR]

Macrophage-derived foam cell formation is a hallmark of atherosclerosis. It has been reported that oxidized low density lipoprotein (oxLDL) inducing formation of foam cells and expression of inflammatory molecules are partly mediated by toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway. However, whether oxLDL/β2-glycoprotein I/anti-β2-glycoprotein I (oxLDL/β2GPI/anti-β2GPI) complex enhanced formation of foam cells involving TLR4/NF-κB pathway or not has never been explored. In the current study, we focused on investigating the transformation of peritoneal macrophages from BALB/c mice into foam cells induced by the three complexes, and the involvement of TLR4 as well as its downstream signal molecule NF-κB. The results showed that treatment of macrophages with oxLDL/β2GPI/anti-β2GPI complex could markedly increase intracellular lipid loading and expression of TLR4, phosphorylated NF-κB p65 (p-NF-κB p65), monocyte chemoattractant protein-1 (MCP-1), as well as tissue factor (TF). The oxLDL and oxLDL/β2GPI/anti-β2GPI complex induced formation of foam cells and expression of p-NF-κB p65 were significantly reduced, while macrophages were pre-treated with TLR4 inhibitor TAK-242. Meanwhile, both TAK-242 and NF-κB inhibitor PDTC could remarkably inhibit oxLDL, oxLDL/β2GPI/anti-β2GPI complex, as well as LPS increased MCP-1 and TF levels. Nevertheless, β2GPI/anti-β2GPI complex-induced MCP-1 and TF mRNA expression were inhibited by TAK-242 rather than PDTC, although TF activity was significantly reduced by both of the inhibitors. In conclusion, our results indicate that oxLDL/β2GPI/anti-β2GPI complex could enhance the conversion of macrophages into foam cells and the process may be at least partly mediated by TLR4/NF-κB pathway, which may contribute to the accelerated development of atherosclerosis in APS. [ABSTRACT FROM AUTHOR]

Abstract: The activity concentrations of certain radionuclides were quantified in some plant foods cultivated around Kudankulam, where a mega-nuclear power plant is being established. The activity concentrations were found more in the ‘pulses’ group and were the lowest in ‘other vegetable’ category. The annual effective dose was computed based on the activity concentration of radionuclides and it was found to be higher due to the consumption of cereals and pulses. Other vegetables, cereals, pulses and nuts recorded high transfer factors for the radionuclide 228Ra. Fruits, leafy vegetables, tubers and roots, and palm embryo registered high transfer factors for 226Ra. Group-wise activity concentration, radiation dose to the public and soil-plant-to-transfer factor are discussed in detail. [Copyright &y& Elsevier]

Abstract: Introduction: Injury to the surrounding vessel wall is one of the major reasons for failure of implantable medical devices. The surgical procedure itself or the altered flow conditions after implantation can cause damage to the vessel wall. This damage exposes tissue factor (TF), the initiator of the extrinsic pathway of coagulation. One approach to combat thrombosis is to use an anticoagulant on the surface of the device. The primary aim of this study is to develop a simplified physiologically relevant in vitro model of vessel wall injury to study the mechanisms by which immobilized recombinant tissue factor pathway inhibitor (rTFPI) effectively inhibits TF initiated thrombosis. Materials and methods: A two well chamber slide was used for the study. Fibroblasts were cultured on the upstream portion of the slide. Fibroblast cells stimulated with TNF-α acted as a source of surface TF. The downstream portion of the slide was coated with rTFPI. A mixture of FX, FVIIa and calcium was perfused over the slides to generate FXa. Effluent collected at the outlet was used to analyze the inhibition of this surface generated FXa by the rTFPI present downstream. Results and conclusions: Different shear rates and rTFPI densities were used to study this effect. In most cases rTFPI inhibited FXa generated upstream as a function of the wall shear rate and rTFPI dosage (surface density). This study shows the effectiveness of the surface bound inhibitor when FXa is generated from an upstream injury site and the bulk of FXa is near the wall. [ABSTRACT FROM AUTHOR]

Abstract: Factor VIIa (FVIIa), a serine protease enzyme, coupled with tissue factor (TF) plays an important role in a number of thrombosis-related disorders. Inhibition of TF·FVIIa occurs early in the coagulation cascade and might provide some safety advantages over other related enzymes. We report here a novel series of substituted biphenyl derivatives that are highly potent and selective TF·FVIIa inhibitors. Parallel synthesis coupled with structure-based drug design allowed us to explore the S2 pocket of the enzyme active site. A number of compounds with IC50 value of <10nM were synthesized. The X-ray crystal structures of some of these compounds complexed with TF·FVIIa were determined and results were applied to design the next round of inhibitors. All the potent inhibitors were tested for inhibition against a panel of related enzymes and selectivity of 17,600 over thrombin, 450 over trypsin, 685 over FXa, and 76 over plasmin was achieved. Two groups, vinyl 36b and 2-furan 36ab, were identified as the optimum binding substituents on the phenyl ring in the S2 pocket. Compounds with these two substituents are the most potent compounds in this series with good selectivity over related serine proteases. These compounds will be further explored for structure–activity relationship. [Copyright &y& Elsevier]

Abstract: Introduction: Few studies have been carried out to investigate whether distinct areas of full term placenta express different amounts of markers involved in the placental haemostasis and angiogenesis. A possible relationship between the expression of genes involved in the haemostasis and angiogenesis of human placenta has not been investigated. Materials and methods: Twenty-eight fresh human placentas (35–41 weeks of gestation) from uneventful pregnancies were dissected with two different methods. Quantitative mRNA expression of the tissue factor (TF), TF pathway inhibitor (TFPI), TFPI-2, plasminogen activator inhibitor (PAI-2), annexin V (Anx V), vascular endothelial growth factor (VEGF), and thrombomodulin (TM) genes was evaluated by quantitative real time PCR system. Histology of each sample was graded. Results: Gene expression of all the considered markers was not significantly different in each area, using both the different methods of dissection. A significant correlation (p <0.05) was found between the expression of TF and TFPI-2. TF and TFPI-2 were significantly (p <0.05) associated with VEGF, whereas a stronger association (p <0.01) was found between TFPI and TFPI-2. TFPI and TFPI-2 were strongly associated with PAI-2 expression (p <0.01). Conclusions: In placentas with central cord insertion, gene expression is not dependent on the method of sampling site. A significant relationship between haemostasis and angiogenesis in at term placentas was shown. [Copyright &y& Elsevier]

Abstract: This report describes a female infant with cutis laxa, short stature, microcephaly, wide anterior fontanel and bifrontal cortical malformation. Isoelectrofocusing of plasma transferrin and apolipoprotein C-III showed abnormal patterns suggesting defective N- and O-glycosylation. Together with recently reported patients, this patient represents a novel type of congenital disorder of glycosylation. [Copyright &y& Elsevier]

Abstract: Cancer of the prostate gland (PCA) is the most common invasive malignancy and is the second leading cause of cancer-related death in males. The polyphenolic constituents of black tea have gained considerable attention as chemopreventive agents. Many studies have shown that black tea reduces the risk of several cancer types. In the present study, we studied the effect of a black tea polyphenol, theaflavin (TF), on cellular proliferation and cell death in the human prostate cancer cell line, PC-3. We showed that TF inhibits cell proliferation in a dose- and time-dependent manner. Studies on cell cycle progression have shown that the anti-proliferative effect of TF is associated with an increase in the G2/M phase of PC-3 cells. Western blot results showed that TF-induced G2/M phase arrest was mediated through the inhibition of cyclin-regulated signaling pathways. TF induces cyclin kinase inhibitor p21waf1/cip1 expression and inhibits cdc25C and cyclin B expression. Increased exposure time to TF caused apoptosis of PC-3 cells, which was associated with up-regulation of the pro-apoptotic proteins Bax, caspase-3 and caspase-9 and down-regulation of anti-apoptotic protein Bcl-2. The role of caspase-induced apoptosis was further confirmed by a reduction in mitochondria membrane potential and the appearance of a DNA laddering pattern. Thus, it can be concluded that TF acts as an effective anti-proliferative agent by modulating cell growth regulators in prostate cancer cells. [Copyright &y& Elsevier]

Abstract: Targeted gene therapy is essential if cancer treatment is to become a reality with this form of therapy. In the past few years, cationic liposomes, discovered 2 decades ago, and at present, the most commonly used class of transfection reagents, have been tested in various clinical trials for diseases not restricted to cancer. They have been shown to be selective for tumour vascular endothelial cells raising hopes for antiangiogenic and antivascular therapies. They are also capable of being selectively delivered to the lungs and liver when administered intravenously. These vesicles are also being targeted to the tumour in various parts of the body by using advanced liposomal systems such as antibody–antigen and ligand–receptor combinations. This review looks at the state of play in this rapidly growing field. [Copyright &y& Elsevier]

Abstract: Highly selective and potent factor VIIa–tissue factor (fVIIa·TF) complex inhibitors were generated through structure-based design. The pharmacokinetic properties of an optimized analog (9) were characterized in several preclinical species, demonstrating pharmacokinetic characteristics suitable for once-a-day dosing in humans. Analog 9 inhibited platelet and fibrin deposition in a dose-dependent manner after intravenous administration in a baboon thrombosis model, and a pharmacodynamic concentration–response model was developed to describe the platelet deposition data. Results for heparin and enoxaparin (Lovenox®) in the baboon model are also presented. [Copyright &y& Elsevier]

Abstract: Hemostatic parameters were examined before and during 102 courses of chemotherapy in 42 patients with malignant lymphoma with high risk for infection. The white blood cell count was significantly reduced in all patients at days 1 and 3, but significantly increased at days 7 and 9, compared to before chemotherapy. At day 7 of chemotherapy, tissue factor (TF) mRNA levels in leukocytes were significantly increased in all patients, especially those with infection. Plasma concentrations of granulocyte elastase derived-XDP (GE-XDP) levels correlated with d-dimer levels during chemotherapy in patients with malignant lymphoma, suggesting that the elevated d-dimer is fibrin products degraded by granulocyte elastase. GE-XDP, C-reactive protein (CRP), GE-XDP and d-dimer were significantly higher in patients with infection, disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS) than those without. In patients with DIC or ARDS, TF mRNA correlated with d-dimer, and GE-XDP correlated with leukocyte count, CRP and d-dimer, suggesting that inflammatory changes due to thrombosis may cause the activation of leukocytes in patients with malignant lymphoma during chemotherapy. Activated leukocytes and granulocyte elastase may elicit a hypercoagulable state and ARDS in patients with malignant lymphoma during chemotherapy. [Copyright &y& Elsevier]

Abstract: Tissue factor (TF) mRNA levels in leukocyte and TF antigen in plasma were examined in patients with deep vein thrombosis (DVT). Although TF mRNA levels in leukocytes were higher in patients with DVT than in healthy volunteers, they were lower in patients with DVT than in those with solid cancer and those with disseminated intravascular coagulation (DIC). On the other hand, the plasma levels of TF antigens were markedly high in patients with DVT/pulmonary embolism (PE). Analysis of the role of underlying disease of DVT showed no significant difference in TF mRNA levels and TF antigens among patients with solid cancer, post-surgical, other diseases and those free of underlying diseases. In patients with VTE, plasma levels of D-dimer, soluble fibrin, GE-XDP and plasminogen activator inhibitor-1 did not correlate with TF mRNA or TF antigen. In analysis of 18 patients with PE with and without DVT, TF mRNA levels in leukocytes correlated with the plasma levels of D-dimer. These findings suggest that TF in leukocytes is more likely to be involved in the development of thrombosis in PE than DVT. [Copyright &y& Elsevier]

There is increasing interest in the possibility that polymorphisms affecting gene expression are responsible for a significant proportion of heritable human phenotypic variation, including human disease. We have sought to determine if polymorphisms in the promoters of brain expressed genes are commonly functional. We screened for polymorphism 56 genes previously reported to be differentially expressed in the brains of schizophrenics [Y. Hakak, J.R. Walker, C. Li, W.H. Wong, K.L. Davis, J.D. Buxbaum, V. Haroutunian, A.A. Fienberg, Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc. Natl. Acad. Sci. 98 (2001) 4746–4751.]. We found 60 variants distributed across 31 of the genes. A total of 77 haplotypes representing 28 different putative promoters were analyzed in a reporter gene assay in two cell lines. Of a total of 54 sequence variants represented in the haplotypes, 12 (or around 22%) were functional according to a highly conservative definition. These were found in the promoters of eight genes: NPY, PCSK1, NEFL, KIAA0513, LMO4, HSPA1B, TF and MDH1. We therefore estimate that around 20–25% of promoter polymorphisms in brain expressed genes are functional, and this is likely to be an underestimate. Our data therefore provide for the first time empirical evidence that promoter element polymorphisms, at least in brain expressed genes, should be afforded a high priority for molecular genetic studies. [Copyright &y& Elsevier]

We give an overview on the development of “horizontal” European Committee for Standardisation (CEN) standards for characterising soils, sludges and biowaste in the context of environmental legislation in the European Union (EU). We discuss the various steps in the development of a horizontal standard (i.e. assessment of the possibility of such a standard, review of existing normative documents, pre-normative testing and validation) and related problems. We also provide a synopsis of European and international standards covered by the so-called Project HORIZONTAL. [Copyright &y& Elsevier]

BRE’s Microscopy unit have been extensively involved in the identification of new and unusual occurrences of the thaumasite form of sulfate attack (TSA) and thaumasite formation (TF). Using both optical and scanning electron microscopy a substantial database of information describing the location, form, composition and characteristics of TSA and TF in a series of different examples both within the UK and abroad has been developed. This paper describes the form taken by the TSA/TF within these various localities, and compares it with the characteristic taken by naturally occurring thaumasite.Earlier work on the M5 concrete bridges in Gloucestershire, UK defined a four-stage degradation process, resulting in the formation of at least three microscopically distinct forms of thaumasite. This paper takes these basic stages and assesses their presence and makes some revisions to the characteristics of the TSA reaction, and its evolution within lower quality cement-derived materials, such as mortars and masonry. Finally the observed strong association of TSA and TF, with the “Popcorn” calcite form of deposition within more depleted areas of affected cement paste from degraded concrete-based material is also discussed along with a proposed mechanism of deterioration. [Copyright &y& Elsevier]

Strong evidence has emerged over the last 15 years showing that the perirhinal and parahippocampal cortices play an important role in normal memory function. Despite our progress in understanding the mnemonic functions of these areas, controversy still exists concerning the precise location of the boundaries of these areas in the primate brain. To provide a context for understanding the current discrepancies in the literature, we present a historical overview of the different boundary schemes and nomenclatures that have been applied to the medial temporal lobe cortices in both humans and nonhuman primates. We describe how the boundaries and the names applied to these regions have evolved over time, starting with the classic cytoarchitectonisists working in the early 1900s, and ending with the various schemes being used in the contemporary literature. We show that the current controversies concerning the boundaries of the perirhinal and parahippocampal cortices can be traced directly to the classic cytoarchitectonic literature. [Copyright &y& Elsevier]

: ObjectivesWe hypothesized that combining functional assessment to perfusion enhances the ability of electrocardiographic gating Tc-99m sestamibi single photon emission computed tomography (gated SPECT) myocardial perfusion imaging (MPI) to detect defects in multiple vascular territories in patients with severe three-vessel coronary artery disease (3VD).: BackgroundIn patients with 3VD, perfusion defects in multiple vascular territories may not always be evident due to globally reduced perfusion.: MethodsGated SPECT MPIs were interpreted sequentially with perfusion first, followed by combined perfusion/function, in 143 patients with angiographic 3VD and a control group of 112 non-3VD patients. All patients underwent coronary arteriography within one month of MPI.: ResultsIn 3VD patients, combined perfusion/function analysis yielded significantly greater numbers of abnormal segments/patient (6.2 ± 4.7 vs. 4.1 ± 2.8, p < 0.001) and more defects in multiple vascular territories (60% vs. 46%, p < 0.05) than perfusion alone. In the control group, there were no differences between the combined perfusion/function and perfusion alone interpretations. Multivariate analysis of 15 different clinical, stress, and scintigraphic variables in all patients revealed age (p < 0.0001) and number of abnormal vascular territories by combined perfusion/function (p < 0.0001) to be the most powerful predictors of 3VD. Addition of functional data to clinical, stress, and perfusion yielded a significant increase in the predictive value of 3VD (global chi-square: 131.7 vs. 89.8, p < 0.00001). Specificity of combined perfusion/function analysis was not lower than perfusion alone (72% vs. 69%, p = NS).: ConclusionsAdjunctive assessment of function with perfusion by gated SPECT MPI enhances the detection of defects in multiple vascular territories in patients with severe 3VD, without adversely affecting its specificity. [Copyright &y& Elsevier]

: BackgroundIt has been proposed that partial fundoplication is associated with less incidence of postoperative dysphagia and consequently is more suitable for patients with gastroesophageal reflux disease (GERD) and impaired esophageal body motility. The aim of this study was to assess whether outcomes of Toupet fundoplication (TF) are better than those of Nissen-Rossetti fundoplication (NF) in patients with GERD and low-amplitude esophageal peristalsis.: Study designThirty-three consecutive patients with proved GERD and amplitude of peristalsis at 5 cm proximal to lower esophageal sphincter (LES) less than 30 mmHg were randomly allocated to undergo either TF (19 patients: 11 men, 8 women; mean age: 61.7 ± 8.7 SD years) or NF (14 patients: 7 men, 7 women; mean age: 59.2 ± 11.5 years), both by the laparoscopic approach. Pre- and postoperative assessment included clinical questionnaires, esophageal radiology, esophageal transit time study, endoscopy, stationary manometry, and 24-hour ambulatory esophageal pH testing.: ResultsDuration of operation was significantly prolonged in the TF arm (TF: 90 ± 12 minutes versus NF: 67 ± 15 minutes; p < 0.001). At 3 months postoperatively, the incidences of dysphagia (grades I, II, III) and gas-bloat syndrome were higher after NF than after TF (NF: 57% versus TF: 16%; p < 0.01 and NF: 50% versus TF: 21%; p = 0.02, respectively), but decreased to the same level in both groups at the 1-year followup (NF: 14% versus TF: 16% and NF: 21% versus TF: 16%, respectively). At 3 months postoperatively, patients with NF presented with significantly increased LES pressure than those with TF (p = 0.02), although LES pressure significantly increased after surgery in both groups, as compared with preoperative values. Amplitude of esophageal peristalsis at 5 cm proximal to LES increased postoperatively to the same extent in both groups (TF, preoperatively: 21 ± 6 mmHg versus postoperatively: 39 ± 12 mmHg; p < 0.001, and NF, preoperatively: 20 ± 8 mmHg versus postoperatively: 38 ± 12 mmHg; p < 0.001). Reflux was abolished in all patients of both groups.: ConclusionsBoth TF and NF efficiently control reflux in patients with GERD and low amplitude of esophageal peristalsis. Early in the postoperative period, TF is associated with fewer functional symptoms, although at 1 year after surgery those symptoms are reported at similar frequencies after either procedure. [Copyright &y& Elsevier]

: ObjectivesWe sought to assess the clinical features of transient left ventricular (LV) apical ballooning.: BackgroundAlthough several cases regarding transient LV apical ballooning have been reported, the etiology remains unknown.: MethodsWe investigated 17 patients (14 women, median age 74 years old with a range of 54 to 91 years old) who fulfilled the following criteria: 1) transient LV apical ballooning; 2) ST-T segment change in several leads in electrocardiogram; and 3) no history of old myocardial infarction, valvular heart disease, subarachnoid hemorrhage, or pheochromocytoma.: ResultsEmotional and physical stress were observed in 16 patients (94%). Technetium-99m tetrofosmin tomographic imaging revealed decreased uptake at the apex of the left ventricle in 11 patients (85%) that later returned to uniform. No significant stenosis or angiographical slow flow in epicardial coronary arteries was observed (n = 9). Provocative focal vasospasm was induced in only one patient (14%) (n = 7). Moreover, no significant abnormality in the coronary microcirculation was detected by Doppler guidewire (n = 3) or contrast echocardiography (n = 1). No patients showed a rise in viral antibody titers. Biopsy specimens revealed interstitial fibrosis in six patients (100%) and slight cell infiltration in three others (50%) (n = 6).: ConclusionsThese findings suggested that neither abnormalities in the coronary circulation nor acute myocarditis was related to the etiology. Although neurogenic stunned myocardium induced by emotional or physical stress was suggested as the etiology, further investigations are necessary. [Copyright &y& Elsevier]

: ObjectivesThis study was designed to assess the effect of abciximab on platelet and leukocyte deposition 60 min after stent insertion in nonhuman primates.: BackgroundAlthough it is well established that abciximab improves both short- and long-term clinical outcomes after stent placement, there have been no studies assessing its effect on early platelet and leukocyte deposition.: MethodsCynomolgus monkeys were pretreated with aspirin and either saline or a 0.4 mg/kg bolus of abciximab, and then subjected to angioplasty and Palmaz-Schatz stent placement in the common iliac artery or abdominal aorta. After 60 min, animals were euthanized and the stented artery was evaluated by immunohistochemistry and morphometry.: ResultsComplete occlusion of the stented vessel with a thin fibrin(ogen) meshwork and trapped blood occurred in two saline-treated and two abciximab-treated animals. In the four remaining saline-treated animals, a layer of erythrocytes trapped in a network of fibrin(ogen) was noted close to the vessel wall, and this was covered by a layer of large, irregular platelet thrombi. Leukocytes formed a monolayer on top of the platelets and near stent struts. In the four remaining abciximab-treated animals, the mean erythrocyte area was 65% smaller (p = 0.070), the platelet aggregate area was 89% smaller (p = 0.049) and the luminal area was 59% larger (p = 0.004). A monolayer of leukocytes also formed on top of the platelets and near stent struts.: ConclusionsIn control stented blood vessels in this study, platelet thrombi formed not at the vessel wall, but on top of an erythrocyte-rich layer, and platelets recruited leukocytes. Abciximab decreased the size of platelet thrombi, but did not prevent leukocyte recruitment. [Copyright &y& Elsevier]

: ObjectivesThis study was undertaken to test the hypothesis that transplant coronary vasculopathy (CV) is associated with increased myocardial protein expression of both tissue factor (TF) and integrin αvβ3.: BackgroundThe vitronectin receptor (integrin αvβ3) and TF have recently been found to play a key role in apoptotic cell death and vascular endothelial cell injury.: MethodsA total of 77 heart transplant recipients underwent simultaneous endomyocardial biopsy and intravascular ultrasound (IVUS) at one year of transplant. Patients with pre-existing donor coronary atherosclerosis (n = 35) or with acute rejection (grade >1A, n = 10) at the time of the IVUS were excluded from the analysis. The remaining 32 patients constitute the cohort of the present study. A computerized biopsy score was derived based on the duration and severity of cellular rejection. Both TF and αvβ3 expression in the heart biopsy specimens were evaluated by immunoperoxidase histochemistry and Western blot analysis.: ResultsPatients with CV (n = 24) had increased expression of αvβ3 (2.7-fold, p = 0.003) and TF (7.9-fold, p = 0.04) compared with patients without evidence of vasculopathy (n = 8). In the absence of myocardial fibrosis, αvβ3 expression correlated significantly with the cellular rejection score (r = 0.58, p = 0.02).: ConclusionsTransplant vasculopathy is associated with increased expression of both TF and αvβ3. The significant correlation of αvβ3 with cellular rejection suggests an important role for this integrin in serving as a mechanistic link between cellular rejection and vasculopathy. [Copyright &y& Elsevier]

The role of CXC chemokine ligand 16 (CXCL16), oxidized LDL (ox-LDL), tissue factor (TF) and autophagy-induced beta cell death in type 1 diabetes mellitus (T1DM) pathogenesis is still unclear. We examined the therapeutic potential and mechanism of resveratrol (RES) against T1DM. Diabetes was induced in Balb/c mice by i. p. injection of 55 mg/kg streptozotocin (STZ) for five consecutive days. The control group received vehicles. RES or (RES + STZ) groups received RES (50 mg/kg, i. p.) daily for 12 days starting from the fourth day of buffer or STZ injections, respectively. Blood glucose, serum insulin, beta cell mass, serum lipid profiles, histological changes, oxidative stress biomarkers were determined. Moreover, CXCL16, TF, ox-LDL, P62 and LC3 tissue expression were also analyzed. Diabetic mice showed a marked deterioration in biochemical, physical and oxidative stress parameters. Interestingly, immunofluorescence analysis showed a remarkable elevation in CXCL16 (12 folds), ox-LDL (9 folds), TF (8.3 folds) in pancreatic B-cells. Moreover, western blotting revealed a profound increase in ox-LDL (2.6 folds), TF (3.2 folds), while a significant decline in P62 (0.34) and LC3 (0.25) when compared to control. RES mitigated biochemical, physical, oxidative imbalance and distorted pancreatic architecture in T1DM mice. Intriguingly, CXCL16, ox-LDL, TF and autophagic markers were also restored after RES treatment. Our data give the first direct evidence that beta cell–specific CXCL16/ox-LDL pathway activation is a potential trigger of TF activation and autophagic beta cell death in T1DM. Moreover, RES may have potential therapeutic applications for prevention of T1DM mainly via ameliorating this pathway. [ABSTRACT FROM AUTHOR]

• The present study focused on extensive investigation of photon, neutron, alpha and proton shielding parameters for Bismuth Borate glass system using MCNPX, WinXCOM and SRIM Codes. • %25Bi 2 O 3 indicates the lowest value for HVL, MFP and TVL while μ / ρ value of the alloy is largest among the investigated alloys. • %25Bi 2 O 3 is the most effective material for photon, neutron, alpha and proton shielding among the rest of alloys. • According to MSP and PR results, %25Bi 2 O 3 has the best stopping values for proton particles (H1) and alpha particles (He+2). There has been an increasing number of research and development activities focusing on the use of different glass systems for their nuclear radiation shielding features. In this study a simulation study has been carried out at a wide photon energy region in order to investigate the radiation protection feature of bismuth borate glasses. This study has been conducted to evaluate the proficiency level of six different glass systems (70-x)B 2 O 3 + xBi 2 O 3 + 15ZnO + 15Na 2 O (where x = 0, 5, 10, 15, 20 and 25 mol%) exposed to photon, charged particle (H1) and (He+2) and neutron. For this investigation, transmission factors (TF), mass attenuation coefficient (MAC), half value layer (HVL), tenth value layer (TVL), mean free path (MFP), effective atomic number (Zeff), effective electron density (Neff) have been computed. The results confirm that the parameters of the examined glasses MAC, HVL, TVL, MFP, Z eff , and N eff are associated with photon energy and chemical composition. In addition, neutron effective cross-sections (∑R) have been computed for bismuth borates and it was seen a good harmony. The computations for present samples have been examined over a broad energy range from 0.01 to 20 MeV and theoretical results have been obtained by using MCNPX software for transmission factors. In addition, simulation results have been calculated with the WinXCom program. Furthermore, MSP and PR calculations of the bismuth borate glass have been performed to figure out the radiation shielding features. For that reason, the SRIM code has been used to simulate H1 and He+2 particles. Considering the results obtained from this research, which examines the radiation protection of bismuth borate glasses, indicates that the best shielding achievement (while the HVL, TVL, MFP, TF have the lowest and the highest (∑R) values) is reached at 25% Bi 2 O 3. As can be seen in the results, the addition of bismuth affirms that the use of such glass systems improves the radiation protection feature. In particular, 25%Bi 2 O 3 glass system has been proved to show superior shielding properties for gamma radiation in combination with charged particles. Since the glass sample with the highest bismuth additive is 25%Bi 2 O 3 , the most radiation protection effect is also seen in this example. The obtained material has a satisfactory radiation shielding property as bismuth is added to the mixture. [ABSTRACT FROM AUTHOR]

• The cold performance test under 4 K is crucial and essential for the most challenged TF prototype HTS current leads. Detailed test process and method are presented. • Many overcurrent and over cooling case were performed to study the TF current leads, and the 1-hand test results and some analysis were presented • The test process and result is important for all the series TF current leads and for the operation in the future. The Toroidal Field (TF) current leads which supply 68 kA DC current for the TF coils are the largest capacity High Temperature Superconducting (HTS) current leads among the three types of HTS current leads for ITER. Two TF HTS current leads prototypes have been successfully built and cold tested at the Institute of Plasma Physics of the Chinese Academy of Sciences (ASIPP). The cold performance test is a crucial step to verify the design parameters and manufacturing process before starting the series production. The cold performance test includes rated current steady state operation and Loss Of Flow Accident (LOFA) test, different Heat eXchanger (HX) boundary operation, over-current, joint resistance, and heat conduction tests. This paper will present the major results of those tests. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Heme oxygenase-1 (HO-1) is the rate limiting enzyme that catalyzes the conversion of heme into biliverdin, free iron, and carbon monoxide (CO). The first human case of HO-1 deficiency showed abnormalities in blood coagulation and the fibrinolytic system. Thus, HO-1 or HO-1 products, such as CO, might regulate coagulation and the fibrinolytic system. This study examined whether tricarbonyldichlororuthenium (II) dimer (CORM-2), which liberates CO, modulates the expression of tissue factor (TF) and plasminogen activator inhibitor type 1 (PAI-1) in human umbilical vein endothelial cells (HUVECs), and TF expression in peripheral blood mononuclear cells (PBMCs). Additionally, we examined the mechanism by which CO exerts its effects. Materials and Methods: HUVECs were pretreated with 50μM CORM-2 for 3hours, and stimulated with tumor necrosis factor-α (TNF-α, 10ng/ml) for an additional 0–5hours. PBMCs were pretreated with 50–100μM CORM-2 for 1hour followed by stimulating with lipopolysaccharid (LPS, 10ng/ml) for additional 0–9hours. The mRNA and protein levels were determined by RT-PCR and western blotting, respectively. Results: Pretreatment with CORM-2 significantly inhibited TNF-α-induced TF and PAI-1 up-regulation in HUVECs, and LPS-induced TF expression in PBMCs. CORM-2 inhibited TNF-α-induced activation of p38 MAPK, ERK1/2, JNK, and NF-κB signaling pathways in HUVECs. Conclusions: CORM-2 suppresses TNF-α-induced TF and PAI-1 up-regulation, and MAPKs and NF-κB signaling pathways activation by TNF-α in HUVECs. CORM-2 suppresses LPS-induced TF up-regulation in PBMCs. Therefore, we envision that the antithrombotic activity of CORM-2 might be used as a pharmaceutical agent for the treatment of various inflammatory conditions. [Copyright &y& Elsevier]

Abstract: Introduction: Normal pregnancy is associated with a local hypercoagulable state that becomes more profound in certain obstetric complications such pre-eclampsia (P-EC). Current literature on the levels of individual haemostatic factors in women with P-EC is limited and results are inconsistent. In this study we provide detailed investigation on the tissue factor (TF)-dependent pathway in women with P-EC. Materials and Methods: Enzyme-linked immunosorbent assays (ELISA) were used to measure plasma factor (F) FVII, FVIIa, TF and tissue factor pathway inhibitor (TFPI) in healthy non-pregnant women (n=22), normal pregnant women (n=15), and women with P-EC (n=20). All subjects were age matched. In addition, pregnant women were matched for gestational age, parity and were all at the third trimester. Results: Plasma FVII levels were significantly higher in women with P-EC compared to the healthy non-pregnant (P<0.001) or the normal pregnant groups (P<0.001). No such significant trends were observed for plasma FVIIa, TF or TFPI levels. Plasma FVII levels can distinguish women with P-EC from healthy non-pregnant women or normal pregnant women at the third trimester, with high sensitivity (90%), specificity (80%), positive and negative predictive values (86%). Conclusions: Plasma FVII levels are significantly elevated in women with P-EC, in the absence of comparable changes in other TF-dependent pathway factors (FVIIa, TF and TFPI). We propose the use of plasma FVII as a marker for P-EC. [Copyright &y& Elsevier]

Abstract: The human coagulation factor VIII (FVIII) and von Willebrand factor (VWF) are two distinct glycoproteins that circulate in the plasma as a non-covalently bound complex (VWF/FVIII complex). Deficiencies or structural defects in FVIII and VWF are responsible for the most common inherited plasma bleeding disorders haemophilia A and von Willebrand disease (VWD), respectively. Current therapies for the treatment of haemophilia have favourable efficacy, tolerability and safety profiles. However, multiple, frequent infusions are usually required to manage a bleeding episode, owing to the short half-life of FVIII. This makes treatment inconvenient and impacts patient quality of life. Several strategies are currently being pursued in an attempt to reduce the number of infusions required per bleeding episode. One of the more promising approaches involves prolonging the half-life of FVIII. This article summarizes the methods that are being used to extend FVIII half-life. [Copyright &y& Elsevier]