Prevalence of antimicrobial resistance in Helicobacter pylori isolates from Iran

Helicobacter pylori, a gram negative bacterium is capable of being resistant to a wide spectrum of antimicrobial drugs. The prevalence of antibiotic resistance in H. pylori strains differs amongst distinct geographical areas and has increased worldwide. Therefore, information concerning the prevalence of antimicrobial-resistant H. pylori strains is important in predicting therapeutic response. In this study, drug susceptibility of H. pylori in patients was investigated in Laleh hospital, Tehran, Iran from 2007 - 2008. 104 antral biopsies of patients with non ulcer dyspepsia and peptic ulcer were cultured. Susceptibility patterns were determined by disk diffusion method. Minimum inhibitory concentration (MIC) was performed for resistant isolates of H. pylori. In our study, 51.5% of clinical isolates showed resistance to metronidazole. All of the isolates were sensitive to other antibiotic disks including clarithromycin, amoxicillin, tetracycline and furazolidone. MIC was determined as 16 μg/ml in 5.8% and 32 μg/ml in 94.1% of isolates for metronidazole resistance isolates. The results indicated that the major drug resisted by H. pylori is metronidazole and it should be considered when recommending drugs to patients in this region.Keywords: Helicobacter pylori, antimicrobial resistance, MICAfrican Journal of Biotechnology Vol. 9(36), pp. 5962-5965, 6 September, 201

Negative Correlation Between Economic Structure of Rentier State and Non-Democratization (Case Study: Saudi Arabia)

The Saudi Arabia having patrimonial government politically system and unique nature of power structure that all political affairs set in Ale Saudi dynasty. Government system is traditional and dependent to person and persons of dynasty are absolute rulers and away from criticism and ruler willing prefer to law. Despite of authoritarian and monarchy system and non-democracy development in Saudi Arabia special now that kind of government system isn’t acceptable side of dominant discourse of global community, this country could rely on oil produce regarding to rentier state features have active representation in international communities and too in home sue achievement to legitimacy and vindication. the interests of state-building and to reinforce its legitimacy, which is hardly the act of a state free of interests. Saudi Arabia is also an archetypal example of a state that still faces influence from actors within the state and elite structures, i.e. princes, senior officials, and clerics, among others. In this article analysis rentier state effect on non-democracy development in case study of the Saudi Arabia and research claim is that in nature of relations between rentier state and non-democracy development exist negative correlation. Namely whatever government income dependent to oil export and state economic nature has been independent from peoples, will be decrease from democratic charge in political dimension. This country by oil produce and effect to world powers economies cause that be complex government structure under monarchy system and use endowment of oil rent. Now observe modern dictatorship that despite of economic and social reforms side if internal, regional and international pressures in general dimension of society, will be non-democratic politically structure

Mammographic density and ageing:A collaborative pooled analysis of cross-sectional data from 22 countries worldwide

BACKGROUND: Mammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known. METHODS AND FINDINGS: We examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35-85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of pooled data, adjusted for body mass index, reproductive factors, mammogram view, image type, and reader. In all, 4,534 women were premenopausal, and 6,481 postmenopausal, at the time of mammography. A large age-adjusted difference in percent MD (PD) between post- and premenopausal women was apparent (-0.46 cm [95% CI: -0.53, -0.39]) and appeared greater in women with lower breast cancer risk profiles; variation across population groups due to heterogeneity (I2) was 16.5%. Among premenopausal women, the √PD difference per 10-year increase in age was -0.24 cm (95% CI: -0.34, -0.14; I2 = 30%), reflecting a compositional change (lower dense area and higher non-dense area, with no difference in breast area). In postmenopausal women, the corresponding difference in √PD (-0.38 cm [95% CI: -0.44, -0.33]; I2 = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature. CONCLUSIONS: Declines in MD with increasing age are present premenopausally, continue postmenopausally, and are most pronounced over the menopausal transition. These effects were highly consistent across diverse groups of women worldwide, suggesting that they result from an intrinsic biological, likely hormonal, mechanism common to women. If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction

Deletion of Porcn in Mice Leads to Multiple Developmental Defects and Models Human Focal Dermal Hypoplasia (Goltz Syndrome)

Focal Dermal Hypoplasia (FDH) is a genetic disorder characterized by developmental defects in skin, skeleton and ectodermal appendages. FDH is caused by dominant loss-of-function mutations in X-linked PORCN. PORCN orthologues in Drosophila and mice encode endoplasmic reticulum proteins required for secretion and function of Wnt proteins. Wnt proteins play important roles in embryo development, tissue homeostasis and stem cell maintenance. Since features of FDH overlap with those seen in mouse Wnt pathway mutants, FDH likely results from defective Wnt signaling but molecular mechanisms by which inactivation of PORCN affects Wnt signaling and manifestations of FDH remain to be elucidated.We introduced intronic loxP sites and a neomycin gene in the mouse Porcn locus for conditional inactivation. Porcn-ex3-7flox mice have no apparent developmental defects, but chimeric mice retaining the neomycin gene (Porcn-ex3-7Neo-flox) have limb, skin, and urogenital abnormalities. Conditional Porcn inactivation by EIIa-driven or Hprt-driven Cre recombinase results in increased early embryonic lethality. Mesenchyme-specific Prx-Cre-driven inactivation of Porcn produces FDH-like limb defects, while ectodermal Krt14-Cre-driven inactivation produces thin skin, alopecia, and abnormal dentition. Furthermore, cell-based assays confirm that human PORCN mutations reduce WNT3A secretion.These data indicate that Porcn inactivation in the mouse produces a model for human FDH and that phenotypic features result from defective WNT signaling in ectodermal- and mesenchymal-derived structures

Discovery of novel hit compounds as potential HDAC1 inhibitors: The case of ligand- and structure-based virtual screening

Histone deacetylases (HDACs) as an important family of epigenetic regulatory enzymes are implicated in the onset and progression of carcinomas. As a result, HDAC inhibition has been proven as a compelling strategy for reversing the aberrant epigenetic changes associated with cancer. However, non-selective profile of most developed HDAC inhibitors (HDACIs) leads to the occurrence of various side effects, limiting their clinical utility. This evidence provides a solid ground for ongoing research aimed at identifying isoform-selective inhibitors. Among the isoforms, HDAC1 have particularly gained increased attention as a preferred target for the design of selective HDACIs. Accordingly, in this paper, we have developed a reliable virtual screening process, combining different ligand- and structure–based methods, to identify novel benzamide-based analogs with potential HDAC1 inhibitory activity. For this purpose, a focused library of 736,160 compounds from PubChem database was first compiled based on 80% structural similarity with four known benzamide-based HDAC1 inhibitors, Mocetinostat, Entinostat, Tacedinaline, and Chidamide. Our inclusive in-house 3D-QSAR model, derived from pharmacophore-based alignment, was then employed as a 3D-query to discriminate hits with the highest predicted HDAC1 inhibitory activity. The selected hits were subjected to subsequent structure-based approaches (induced-fit docking (IFD), MM-GBSA calculations and molecular dynamics (MD) simulation) to retrieve potential compounds with the highest binding affinity for HDAC1 active site. Additionally, in silico ADMET properties and PAINS filtration were also considered for selecting an enriched set of the best drug-like molecules. Finally, six top-ranked hit molecules, CID_38265326, CID_56064109, CID_8136932, CID_55802151, CID_133901641 and CID_18150975 were identified to expose the best stability profiles and binding mode in the HDAC1 active site. The IFD and MD results cooperatively confirmed the interactions of the promising selected hits with critical residues within HDAC1 active site. In summary, the presented computational approach can provide a set of guidelines for the further development of improved benzamide-based derivatives targeting HDAC1 isoform

Computer-driven development of an in silico tool for finding selective histone deacetylase 1 inhibitors

Histone deacetylases (HDACs) are a class of epigenetic modulators overexpressed in numerous types of cancers. Consequently, HDAC inhibitors (HDACIs) have emerged as promising antineoplastic agents. Unfortunately, the most developed HDACIs suffer from poor selectivity towards a specific isoform, limiting their clinical applicability. Among the isoforms, HDAC1 represents a crucial target for designing selective HDACIs, being aberrantly expressed in several malignancies. Accordingly, the development of a predictive in silico tool employing a large set of HDACIs (aminophenylbenzamide derivatives) is herein presented for the first time. Software Phase was used to derive a 3D-QSAR model, employing as alignment rule a common-features pharmacophore built on 20 highly active/selective HDAC1 inhibitors. The 3D-QSAR model was generated using 370 benzamide-based HDACIs, which yielded an excellent correlation coefficient value (R2 = 0.958) and a satisfactory predictive power (Q2 = 0.822; Q2F3 = 0.894). The model was validated (r2ext_ts = 0.794) using an external test set (113 compounds not used for generating the model), and by employing a decoys set and the receiver-operating characteristic (ROC) curve analysis, evaluating the Güner–Henry score (GH) and the enrichment factor (EF). The results confirmed a satisfactory predictive power of the 3D-QSAR model. This latter represents a useful filtering tool for screening large chemical databases, finding novel derivatives with improved HDAC1 inhibitory activity

The Impact of On-The-Job Pilates Exercise on Job Satisfaction Among the Female Employees of Urmia Electricity Distribution Company

This study intends to investigate the effect of on-the-job pilates exercise on job satisfaction. The study follows a quasi-experimental design with a pre-test and post-test method with a focus on control and experimental groups. The statistical population comprises of all female employees working at Urmia Electricity Distribution Company. The experimental group received 8 weeks of exercise doing sessions (3 sessions per week, 30 minutes per session) in Electricity Distribution Company gym while the control group did not receive any treatment.  According to the results obtained, one can conclude that on-the-job Pilates exercise as sports technology had an effect on the job satisfaction of female employees at Urmia Electricity Distribution Company

Molecular detection of rifampin, isoniazid, and ofloxacin resistance in Iranian isolates of Mycobacterium tuberculosis by high-resolution melting analysis

Mehrandokht Sirous,1,2 Azar Dokht Khosravi,1,2 Mohammad Reza Tabandeh,3 Shokrollah Salmanzadeh,1 Nazanin Ahmadkhosravi,4 Sirus Amini5 1Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 2Department of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 3Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran; 4Khuzestan Tuberculosis Regional Reference Laboratory, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 5Tehran Tuberculosis Regional Reference Laboratory, Tehran University of Medical Sciences, Tehran, Iran Background: The emergence of drug resistance among Mycobacterium tuberculosis (MTB) strains is a serious health concern worldwide. The development of rapid molecular diagnostic methods in recent years has a significant impact on the early detection of resistance to major anti-TB drugs in MTB isolates, which helps in employing appropriate treatment regimen and prevents the spread of drug-resistant strains. This study was designed to evaluate the efficacy of real-time PCR and high-resolution melting (HRM) curve analysis for the determination of resistance to rifampin (RIF), isoniazid (INH), and ofloxacin (OFX) in MTB isolates and to investigate their resistance-related mutations. Methods: HRM analysis was performed to screen 52 (32 drug-resistant and 20 fully susceptible) MTB clinical isolates for mutations in rpoB, katG, mab-inhA, and gyrA genes. The HRM results were then confirmed by DNA sequencing. Results: In total, 32 phenotypically resistant isolates, comprising 18 RIF-, 16 INH-, and five OFX- resistant strains, were investigated. HRM analysis successfully identified 15 out of 18 mutations in rpoB, 14 out of 16 mutations in katG and mab-inhA , and four out of five mutations in gyrA conferring resistance to RIF, INH, and OFX, respectively. The obtained sensitivity and specificity, respectively, for HRM in comparison with phenotypic susceptibility testing were found to be 83.3% and 100% for RIF, 87.5% and 100% for INH, and 80% and 100% for OFX. In five resistant strains (12.8%), no mutation was detected by using HRM and DNA sequencing. Conclusion: HRM assay is a rapid, accurate, and cost-effective method possessing high sensitivity and specificity for the determination of antibiotic resistance among MTB clinical isolates and screening of their associated mutations. This method can generate results in a shorter period of time than taken by the phenotypic susceptibility testing and also allows for timely treatment and prevention of the emergence of possible MDR strains. Keywords: Mycobacterium tuberculosis, drug resistance, high-resolution melting curve analysis, isoniazid, rifampin, ofloxaci