A Metabolomics Approach for Predicting OATP1B-Type Transporter-Mediated Drug-Drug Interaction Liabilities

In recent years, various endogenous compounds have been proposed as putative biomarkers for the hepatic uptake transporters OATP1B1 and OATP1B3 that have the potential to predict transporter-mediated drug-drug interactions (DDIs). However, these compounds have often been identified from top-down strategies and have not been fully utilized as a substitute for traditional DDI studies. In an attempt to eliminate observer bias in biomarker selection, we applied a bottom-up, untargeted metabolomics screening approach in mice and found that plasma levels of the conjugated bile acid chenodeoxycholate-24-glucuronide (CDCA-24G) are particularly sensitive to deletion of the orthologous murine transporter Oatp1b2 (31-fold increase vs. wild type) or the entire Oatp1a/1b(-/-)cluster (83-fold increased), whereas the humanized transgenic overexpression of hepatic OATP1B1 or OATP1B3 resulted in the partial restoration of transport function. Validation studies with the OATP1B1/OATP1B3 inhibitors rifampin and paclitaxel in vitro as well as in mice and human subjects confirmed that CDCA-24G is a sensitive and rapid response biomarker to dose-dependent transporter inhibition. Collectively, our study confirmed the ability of CDCA-24G to serve as a sensitive and selective endogenous biomarker of OATP1B-type transport function and suggests a template for the future development of biomarkers for other clinically important xenobiotic transporters.</p

Efficacy of group behavioral activation on social anxiety, avoidance and negative evaluations among individuals whit social anxiety

Introduction:  Regarding to the importance of appropriate treatment for social anxiety, the present study aimed to assess the efficacy of group behavioral activation on social anxiety, avoidance and negative evaluations among individuals whit social anxiety. Materials and Methods: In this clinical trial in 2016, 30 cases with symptoms of social anxiety and other inclusion criteria entered to the research through convenient method of sampling and divided into two groups randomly. The experimental group received 8 weekly (ninety minutes) sessions of behavioral activation while control group received no treatment. The research instrument concluded social anxiety scale, cognitive-behavioral avoidance scale and questionnaire of negative social events fulfilled before and after intervention. Data analyzed through descriptive and explanatory statistics. Results: Behavioral activation can impact significantly on symptoms of social anxiety, cognitive-behavioral avoidance and negative evaluations (

The Effect of Selected Motor Games on Static and Dynamic Balance in Children with Specific Learning Disorder

Balance is one of the basic important principles of learning in children, and its disorder can negatively affect learning.The aim of this study was to investigate the effect of selected motor games on balance in children with specific learning disorder. This study was semi-experimental and application in terms of aims with pretest-posttest and a control group. 24 boys (7-9 years old) with specific learning disorder in Mashhad city were selected and assigned randomly to experimental and control groups. The experimental group performed selected motor games for 20 sessions, 30 minutes each sessions, 5 sessions per week. During this period, the control group performed its routine activities. Changes in the static balance of the subjects were measured by the Stork balance test and Sharpened Romberg test and dynamic balance of the subjects were measured by the heel-to-toe walk test and timed up-and-go test before and after the intervention. For statistical analysis, analysis of variance with repeated measures was used. Findings showed that selected motor games improved the static and dynamic balance of the experimental group. All these changes were significant in comparison with the control group (P<0.05). Based on these findings, it can be concluded that selected motor games help to improve static and dynamic balance in children with specific learning disorder

Identification of a mutation in TNRC18 in a patient with clinical features of Fazio‐Londe disease

Key Clinical Message Fazio‐Londe disease and Brown‐Vialetto‐Van Laere syndrome are rare related neurological disorders. Although SLC52A3 and SLC52A2 that encode riboflavin transporters are their only known causative genes, many patients without mutations in these genes have been reported. Clinical and genetic data of a patient with features suggestive of Fazio‐Londe disease are presented. Neurological examination revealed significant involvement of cranial nerves and weakness in the lower extremities. Pontobulbar presentations were prominent. EDX study suggested motor neuronopathy. Hearing was normal. She was diagnosed with FL disease. Response to riboflavin supplementation was not favorable. The patient's pedigree suggested recessive inheritance. SLC52A3 and SLC52A2 were screened and mutations were not observed. Results of exome sequencing and segregation analysis suggested that a mutation in TNRC18 is a candidate cause of disease in the patient. The three dimensional structure of the TNRC18 protein was predicted and it was noted that its two conserved domains (BAH and Tudor) interact and that the valine residue affected by the mutation is positioned close to both domains. A mutation in TNRC18 is cautiously reported as the possible cause of FL disease in the patient. The finding warrants further inquiries on TNRC18 about which little is presently known

Validity of a continuous metabolic syndrome score as an index for modeling metabolic syndrome in children and adolescents: the CASPIAN-V study

Abstract Background The purpose of the present study was to assess the validity of continuous metabolic syndrome score (cMetS) for predicting metabolic syndrome (MetS) and to determine the cutoff values in a representative sample of Iranian children and adolescents. Methods This national study was conducted among 3843 students, aged 7–18 years country during the fifth survey of a national school-based surveillance program. The cMetS was computed by standardizing the residuals of waist circumference, mean arterial blood pressure, high-density lipoprotein cholesterol, triglycerides, and glucose by regressing them according to age and sex and aggregating them. The optimal cut-off points of cMetS for predicting MetS were determined by the receiver operation characteristic (ROC) curve analysis in different gender and age categories. Results Totally, 3843 students (52.3% boys) with average age of 12.45 years were assessed. The mean of cMetS increased according to elevating the number of MetS components. The overall cMetS cut-off point was 1.76 (sensitivity 93% and specificity 82%) in total pediatrics. The area under the ROC curve was 94%. The values for boys and girls were 1.79 and 2.72, respectively. Conclusions cMetS performed highly accurate in predicting pediatrics with MetS in all gender and age groups and it appears to be a valid index in children and adolescents

Odds ratio and 95% confidence interval of metabolic syndrome and cardiovascular risk factors in children associated with parental weight status: The CASPIAN-V study.

<p>Odds ratio and 95% confidence interval of metabolic syndrome and cardiovascular risk factors in children associated with parental weight status: The CASPIAN-V study.</p

Correlations between parental anthropometric indices and children clinical characteristics: The CASPIAN-V study.

<p>Correlations between parental anthropometric indices and children clinical characteristics: The CASPIAN-V study.</p

Means of clinical and biochemical characteristics of children according to the parental weight status: The CASPIAN-V study.

<p>Means of clinical and biochemical characteristics of children according to the parental weight status: The CASPIAN-V study.</p