Quercetin protects liver injury induced by bile duct ligation via attenuation of Rac1 and NADPH oxidase1 expression in rats

BACKGROUND:Bile duct ligation (BDL) and subsequent cholestasis are correlated with oxidative stress,hepatocellular injury and fibrosis.Quercetin is a flavonoid with antifibrotic,and hepatoprotective properties.However,the molecular mechanism underlying quercetin-mediated hepatoprotection is not fully understood.The current study was to evaluate mechanisms of hepatoprotective effect of quercetin in BDL rat model.METHODS:We divided male Wistar rats into 4 groups (n=8 for each):sham,sham+quercetin (30 mg/kg per day),BDL,and BDL+quercetin (30 mg/kg per day).Four weeks later,the rats were sacrificed,the blood was collected for liver enzyme measurements and liver for the measurement of Racl,Racl-GTP and NOX1 mRNA and protein levels by quantitative PCR and Western blotting,respectively.RESULTS:Quercetin significantly alleviated liver injury in BDL rats as evidenced by histology and reduced liver enzymes.Furthermore,the mRNA and protein expression of Racl,Racl-GTP and NOX1 were significantly increased in BDL rats compared with those in the sham group (P＜0.05);quercetin treatment reversed these variables back toward normal (P＜0.05).Another interesting finding was that the antioxidant markers e.g.superoxide dismutase and catalase were elevated in quercetin-treated BDL rats compared to BDL rats (P＜0.05).CONCLUSION:Quercetin demonstrated hepatoprotective activity against BDL-induced liver injury through increasing antioxidant capacity of the liver tissue,while preventing the production of Racl,Racl-GTP and NOX1 proteins.     

Knowledge and attitudes of physicians in private practice towards HIV/AIDS in Mashhad, Iran

Being responsible for providing care for HIV/AIDS in a society, physicians should be knowledgeable and have favourable attitudes. We designed a cross-sectional study to assess knowledge and attitudes towards HIV/AIDS of private practicing physicians in Mashhad, Iran. A total of 346 general practitioners and specialists completed anonymous self-administered questionnaires with response rate of 91.1%. For knowledge questions, the mean proportion of correct responses was 53.5% (±13.2). Misconceptions about HIV transmission were the main areas of insufficient knowledge. Surprisingly only 20% knew how to manage a patient who had experienced sexual contact with an HIV-positive partner. While 84% disagreed that 'HIV-infected individuals deserved to catch infection' owing to high-risk behaviours, 38% sympathized less with people who were infected via extramarital sex. It seems that knowledge and attitudes towards HIV/AIDS among the studied physicians is not favourable and is an area that requires attention to enable effective management of the disease in Iran.     

Childhood Sex-Typed Behavior and Gender Change in Individuals with 46,XY and 46,XX Disorders of Sex Development: An Iranian Multicenter Study

Disorders of sex development (DSD) are congenital conditions in which the typical genetic and hormonal profiles are affected and thereby the usual process of sexual differentiation. Most of these studies, however, have been conducted in Western countries. In the present study, preschool sex-typed activities of Iranian individuals with DSD and their age-matched non-affected male and female relatives were assessed using the Pre-School Activities Inventory (PSAI) modified for retrospective self-report. A total of 192 individuals participated in our study, including 33 46,XX individuals with congenital adrenal hyperplasia (CAH; M age?=?10.36, SD?=?5.52), 15 46,XY individuals with complete androgen insensitivity syndrome (CAIS; M age?=?19.8, SD?=?7.14), and 16 46,XY individuals with 5-alpha reductase deficiency type-2 (5α-RD-2; M age?=?17.31, SD?=?7.28), as well as one age-matched non-affected male and female relative for each patient. With regard to PSAI scores, male-identifying participants with 5α-RD-2 and male controls reported similar levels of male-typical childhood play. Female-identifying participants with 5α-RD-2 and CAH showed comparable scores: significantly less masculine and more feminine than male controls, but significantly more masculine and less feminine than females with CAIS and female controls. These findings support the role of androgens in the development of sex-typical childhood play behavior, with those being exposed to higher levels of fetal functional androgens expressing more masculine behavior at preschool ages.     

Consistent and precise localization of brain activity in human primary visual cortex by MEG and fMRI

The tomographic localization of activity within human primary visual cortex (striate cortex or V1) was examined using whole-head magnetoencephalography (MEG) and 4-T functional magnetic resonance imaging (fMRI) in four subjects. Circular checkerboard pattern stimuli with radii from 1.8 to 5.2 degrees were presented at eccentricity of 8 degrees and angular position of 45 degrees in the lower quadrant of the visual field to excite the dorsal part of V1 which is distant from the V1/V2 border and from the fundus of the calcarine sulcus. Both fMRI and MEG identified spatially well-overlapped activity within the targeted area in each subject. For MEG, in three subjects a very precise activation in V1 was identified at 42 ms for at least one of the two larger stimulus sizes (radii 4.5 and 5.2 degrees ). When this V1 activity was present, it marked the beginning of a weak wave of excitations in striate and extrastriate areas which ended at 50 ms (M50). The beginning of the next wave of activations (M70) was also marked by a brief V1 activation, mainly between 50 and 60 ms. The mean separation between V1 activation centers identified by fMRI and the earliest MEG activation was 3-5 mm.     

Effectiveness of an interprofessional education model based on the transtheoretical model of behaviour change to improve interprofessional collaboration

This study aimed to assess the effectiveness of an interprofessional education model (IPE) based on the transtheoretical model to improve the participants’ interprofessional collaborative practice. The study was conducted in Iran using a controlled before-and-after study design. The participants (n = 91) were the residents of emergency medicine and nurses of the emergency units from two teaching hospitals affiliated to Iran University of Medical Sciences. The participants in the intervention group (n = 40) were 22 residents and 18 nurses. The control group (n = 51) consisted of 20 residents and 31 nurses. The participants were classified based on their stage of readiness to change. The interventions were two-day workshops for each stage (i.e., attitude and intention). We used the Interprofessional Collaborator Assessment Rubric (ICAR) to assess the effectiveness of the developed model. The interprofessional collaboration of the participants in the intervention and control groups was assessed at four time points before and after the intervention in the real emergency unit environment. Student’s t-test and repeated measures analysis of variance (RM-ANOVA) were used to analyse the data. We used partial eta-squared (η²) for effect size calculations. The mean values of ICAR scores in the intervention and control groups were 95.63 ± 19.14 and 89.19 ± 16.11 before the intervention. The mean values of ICAR scores at 3 months after the intervention were 99.82 ± 22.32 and 88.29 ± 16.87 in the intervention and control groups, respectively. After 6 months, the mean values of ICAR scores of the intervention and control groups were 98.6 ± 23.40 and 87.98 ± 16.01, respectively. The results showed that the intervention had a medium educational effect size (partial η² = 0.06) on performance of the participants. Our results showed that an IPE model that is tailored to the learners’ stage of readiness to change improves interprofessional collaboration in the participants. The developed model could be applied for improving interprofessional collaborative performance in other IPE programmes.     

Variants in FIX propeptide associated with vitamin K antagonist hypersensitivity: functional analysis and additional data confirming the common founder mutations

One of the most common and unwanted side effects during oral anticoagulant therapy (OAT) is bleeding complications. In rare cases, vitamin K antagonist (VKA)-related bleeding events are associated with mutations affecting the F9 propeptide at amino acid position 37 due to a substitution of alanine to either valine or threonine. Based on our actual cohort of 18 patients, we update the knowledge on this rare phenotype and its origin. A founder mutation for both variants was reconfirmed by haplotype analysis of intronic and extragenic short tandem repeat (STR) polymorphisms with a higher prevalence in Switzerland than in other regions of Europe. Screening of healthy individuals for the presence of these F9 gene mutations did not identify any of these variants, thus proving the rare occurrence of this genotype. Furthermore, both variants were expressed in vitro and warfarin dose responses were studied. Our warfarin dose response analysis confirmed higher sensitivity of both variants to warfarin with the effect being more apparent for Ala37Thr. Thus, although F9 propeptide mutation-associated hypersensitivity to VKA is a rare phenomenon, awareness towards this bleeding phenotype is important to identify patients at risk.