Serum hyaluronate as a non-invasive marker of hepatic fibrosis and inflammation in HBeAg-negative chronic hepatitis B

Background: HBV infection is a serious global heath problem. It is crucial to monitor this disease more closely with a non-invasive marker in clinical trials. We aimed to evaluate the predictive value of serum hyaluronate for the presence of extensive liver fibrosis and inflammation. Methods: 28 healthy volunteers and 65 patients with HBeAg negative chronic hepatitis B were enrolled. Liver biopsies scored according to Ishak system. Association of serum hyaloronate with liver fibrosis and inflammation were assessed, and cut off points for serum hyaluronate levels were identified by receiver operating characteristics (ROC) curves and their values for prediction of fibrosis and inflammation were assessed. Results: In patients with CHB serum hyaluronate had the most significant correlation and predictive values for the liver fibrosis and inflammation comparing to the other variables. At the cut off point of 126.4 ngm/ml it could discriminate extensive fibrosis from milder ones with sensitivity of 90.9% and specificity of 98.1%. With the same value it could discriminate extensive inflammation from their milder counterparts with sensitivity of 63.6% and specificity of 92.6%. Conclusion: Serum hyaluronate was the best predictor of extensive liver fibrosis and inflammation and it could discriminate subgroups of patients with chronic hepatitis B. It could be used as a non-invasive test to monitor these patients more closely with developing anti viral agents in clinical trials

Wall-resolved versus wall-modeled LES of the flow field and surface forced convective heat transfer for a low-rise building

Large eddy simulation (LES) is widely used to investigate the aerodynamics and convective heat transfer (CHT) at the surfaces of sharp-edged bluff bodies for a wide range of Reynolds (Re) numbers. Due to the heavy computational costs associated with implicit filtering in LES at high Reynolds number flows (Re ≥ 105), wall-modeled (WM) rather than wall-resolved (WR) LES is often adopted. However, the performance of LES-WM for such applications has not yet been systematically investigated. Therefore, this study evaluates the performance of LES-WM and LES-WR for the flow and thermal field at the facades of a low-rise building immersed in an atmospheric boundary layer. Four grids are constructed for LES-WM, each employing different resolution at the building surfaces reaching maximum non-dimensional wall distance y+ = 43, 57, 70, and 95. In addition, the performance of two wall functions, namely the Werner and Wengle and the enhanced wall function is investigated. The results show that the use of LES-WM can result in significant deviations in the predicted near-facade flow pattern and the surface convective heat transfer coefficient (CHTC). Grid resolution significantly impacts the CHTC results and deviations go up to 88% (at the base of the windward facade). Considerable deviations among the employed wall functions are apparent only on the finest grid. In this case, the implementation of the enhanced wall function indicates better performance compared to the non-blended law of the wall (combined with the Werner and Wengle) for CHTC in the regions of the leeward facade where the flow remains attached to the wall. The deviation of the enhanced wall function for surface-averaged CHTC is found to be 10.8% against the wall-resolved LES results, while for the non-blended law of the wall this is 19.2%.</p

A seismic-driven 3D model of rock mechanical facies: An example from the Asmari reservoir, SW Iran

Asmari Formation is one of the most prolific and important hydrocarbon reservoirs in Iran. This formation in the Cheshmeh-Khosh oilfield shows mixed carbonate-siliciclastic lithology and its elastic modulus changes are correlatable with facies changes. To address these changes, we investigated the relation between sedimentary environment (facies) and texture with various elastic moduli. The Young's modulus shows higher correlation with the facies changes. Data from three wells are analyzed and used for the construction of rock mechanical facies. Based on elastic properties, facies and texture changes as well as petrophysical characteristics seven rock mechanical facies (RMFs) are recognized in the studied formation. To predict RMFs at inter-well spaces more efficiently and capturing the lateral formation property variationsa 3D rock mechanical facies model is constructed based on seismic attributes. In this method, RMFs are correlatable between the studied wells and mappable by seismic attribute in the field scale. Finally, the distribution of RMFs and their related properties is investigated in the studied field

Determinants of Early Marriage from Married Girls' Perspectives in Iranian Setting: A Qualitative Study

Early marriage is a worldwide problem associated with a range of health and social consequences for teenage girls. Designing effective health interventions for managing early marriage needs to apply the community-based approaches. However, it has received less attention from policymakers and health researchers in Iran. Therefore, the current study aimed to explore determinants of early marriage from married girls' perspectives. The study was conducted from May 2013 to January 2015 in Ahvaz, Iran. A purposeful sampling method was used to select fifteen eligible participants. Data were collected through face-to-face, semistructured interviews and were analyzed using the conventional content analysis approach. Three categories emerged from the qualitative data including "family structure," "Low autonomy in decision-making," and "response to needs." According to the results, although the participants were not ready to get married and intended to postpone their marriage, multiple factors such as individual and contextual factors propelled them to early marriage. Given that early marriage is a multifactorial problem, health care providers should consider a multidimensional approach to support and empower these vulnerable girls. � 2016 Simin Montazeri et al

Assessing breast cancer risk among Iranian women using the gail model

Background: Breast cancer risk assessment is a helpful method for estimating development of breast cancer at the population level. Materials and Methods: In this cross-sectional study, participants consisted of a group of 3,847 volunteers (mean ± SD age: 463 ± 7.59 years) in a convenience sample of women referred to health centers affiliated to Tehran University of Medical Sciences in Tehran, Iran. The risk of breast cancer was estimated by applying the National Cancer Institute's online version of the Gail Risk Assessment Tool. Results: Some 24.9 of women reported having one first-degree female relative with breast cancer, with 8.05 of them having two or more first-degree relatives with breast cancer. The mean five-year risk of breast cancer for all participants was 1.61±0.73, and 9.36 of them had a five-year risk of breast cancer > 1.66. The mean lifetime risk of breast cancer was 11.7±3.91. Conclusions: The Gail model is useful for assessing probability of breast cancer in Iranian women. Based on the their breast cancer risk, women may decide to accept further screening services

Interleukin-1 receptor antagonist mediates toll-like receptor 3-induced inhibition of trophoblast adhesion to endometrial cells in vitro

STUDY QUESTION Is interleukin-1 receptor antagonist (IL-1RA) involved in the toll-like receptor 3 (TLR 3)-induced inhibition of trophoblast cells' adhesion to endometrial cells in vitro? SUMMARY ANSWER IL-1RA mediates the TLR 3-induced inhibition of trophoblast cells' adhesion to endometrial cells in vitro. WHAT IS KNOWN ALREADY It is well documented that endometrial TLR 3 activation leads to impairment of trophoblast binding to endometrial cells in vitro. IL-1RA is known as an anti-implantation factor, as its injection significantly reduced implantation rates in mice by an effect on endometrial receptivity. STUDY DESIGN, SIZE, DURATION Poly I:C was used as a TLR3 specific ligand and endometrial cells were either treated or not with Poly I:C (treated versus control) in vitro. IL-1RA was applied to block IL-1 signal transduction. IL-1RA was knocked down by Accell Human IL1RN siRNA. Flagellin was used to stimulate TLR 5. SP600125 (JNK) was applied to inhibit the mitogen-activated protein kinases (MAPK) pathway. BAY11 -7082 was used to inhibit the nuclear factor-κB (NF-κB) pathway. The experiments were performed in three replicates on three separate days. PARTICIPANTS/MATERIALS, SETTING, METHODS An in vitro assay was developed using RL95-2 (an endometrial cell line) and JAr (a trophoblast cell line) cells. Initially, the production of IL-1RA in RL95-2 cells in response to TLR 3 activation was measured. To determine whether the TLR 3-induced inhibition of trophoblast binding was mediated through IL-1RA: (i) we evaluated the effect of IL-1RA on the attachment of trophoblast cells to endometrial cells; (ii) we knocked down TLR3-induced IL-1RA gene expression by IL-1RA Small interfering RNA (siRNA) and evaluated trophoblast attachment to endometrial cells. Finally, to clarify through which pathway TLR 3-induced inhibition of trophoblast binding occurs: (i) activation of NF-κB and MAPK was detected by transfecting the cells with secreted placental alkaline phosphatase reporter plasmids bearing promoter sequences for each transcription factor; (ii) the inhibitors for NF-κB and MAPK were used to block signaling; (iii) it was then investigated whether addition of these inhibitors could restore the TLR 3-induced impairment of trophoblast attachment to the endometrial cells. MAIN RESULTS AND THE ROLE OF CHANCE Our results showed that addition of polyinosinic:polycytidylic acid (Poly I:C) to RL95-2 cells significantly increased the production of IL-1RA (P < 0.05). Addition of human recombinant IL-1RA to RL95-2 cells remarkably decreased the adhesion rate of trophoblast cells to endometrial cells (P < 0.05). In addition, suppression of TLR3-induced IL-1RA gene expression in RL95-2 cells significantly restored trophoblast cells attachment to endometrial cells in the presence of Poly I:C (P < 0.05). Only TLR3 and not TLR5 induced MAPK activation (P < 0.05). TLR3 ligation did not affect NF-κB activation. Of NF-kB and MAPK inhibitors, only MAPK's inhibitor could achieve restoration of spheroid adhesion to endometrial cells (P < 0.05). LIMITATIONS, REASONS FOR CAUTION This study has been only done in vitro. Future in vivo studies will confirm our data. WIDER IMPLICATIONS OF THE FINDINGS The findings of this study have a potential clinical application in introducing IL-1RA as one of the diagnostic infertility markers in the endometrium, which can affect the process of embryo adhesion at the time of implantation. Moreover, based on the novel data obtained in the current study, blocking and regulating the MAPK pathway by its inhibitors can be used as a new strategy to prevent and treat virus-induced infertility cases in ART techniques. STUDY FUNDING/COMPETING INTEREST This study was partially funded by a Marie Curie IIF-253948 grant to I.C. and was partially funded by the author's institutions. The authors have no conflict of interest to declare

Human Trophoblast Cells Modulate Endometrial Cells Nuclear Factor kappa B Response to Flagellin In Vitro

Background: Implantation is a complex process that requires a delicate cooperation between the immune and reproductive system. Any interference in the fine balance could result in embryo loss and infertility. We have recently shown that Toll-like receptor 5 activation results in a decrease of trophoblast cells binding to endometrial cells in an in vitro model of human implantation. However, little is known about the downstream signalling leading to the observed failure in implantation and the factors that modulate this immune response. Methods and Principal Findings: An in vitro model of embryo implantation was used to evaluate the effect of trophoblasts and flagellin on the activation of NF-kappa B in endometrial cells and whether TLR5-related in vitro implantation failure is signalled through NF-kappa B. We generated two different NF-kappa B reporting cell lines by transfecting either an immortalized endometrial epithelial cell line (hTERT-EECs) or a human endometrial carcinoma cell line (Ishikawa 3-H-12) with a plasmid containing the secreted alkaline phosphatase (SEAP) under the control of five NF-kappa B sites. The presence of trophoblast cells as well as flagellin increased NF-kappa B activity when compared to controls. The NF-kappa B activation induced by flagellin was further increased by the addition of trophoblast cells. Moreover, blocking NF-kappa B signalling with a specific inhibitor (BAY11-7082) was able to restore the binding ability of our trophoblast cell line to the endometrial monolayer. Conclusions: These are the first results showing a local effect of the trophoblasts on the innate immune response of the endometrial epithelium. Moreover, we show that implantation failure caused by intrauterine infections could be associated with abnormal levels of NF-kappa B activation. Further studies are needed to evaluate the target genes through which NF-kappa B activation after TLR5 stimulation lead to failure in implantation and the effect of the embryo on those genes. Understanding these pathways could help in the diagnosis and treatment of implantation failure cases

Effect of Antioxidants on the Outcome of Therapy in Paraquat-intoxicated Patients

Purpose: The present study was conducted to determine the effect of vitamins C and E administration on the outcome of therapy in patients with paraquat intoxication admitted in the Poisoning EmergencyDepartment (PED) of Noor Teaching General Hospital, Isfahan, Iran.Methods: We studied retrospectively medical records of 186 patients admitted to the PED in two different study periods: 157 patients were evaluated from 1985 to 2001 (first study period) in which patients received conventional treatment protocol consisting of fluid replacement, oral absorbents, haemodialysis, etc, Also, 29 other patients were assessed from 2001 to 2005 (second study period) in which vitamins C and E had been administered to the patients, in addition to the conventional protocol.The patients' mortality rate after the first study period was compared to that of the second one, with regard to the impact of the additional therapeutic intervention (use of antioxidant vitamins).Results: Most of the patients (40.5 %) had ingested more than 20 mL of 20 % paraquat solution and were admitted to the hospital during the first 4 h after exposure. Paraquat poisoning was more common in men (76.6 %), young adults in the age group 19 - 34 (47 %) and during summer (43.3 %). Mean (± SE) length of hospital stay was 62.6 ± 15.6 h. Overall mortality rates were 31 and 55.2 % in the first and second periods, respectively.Conclusion: Although the addition of antioxidants (vitamins C and E) to the conventional therapy did not reduce the mortality rate, other dependent variables including different doses of antioxidants may beconsidered for future studies