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Background: Cholestatic disorders are divided in the extra and intra-hepatic that created due to the severe liver diseases. ABCB11 encodes the bile salt export pump and this gene is mutated in several forms of intrahepatic cholestasis. So far, some molecular features of this gene was studies. Objective: Using a developed web server, we identified high number of rare codons in this gene, and four cases were related to BSEP-deficient patients which can be used for drug design. Material and Methods: By in-silico modelling of ABCB11, some of rare codons in different locations of ATP8b1 gene were identified and evaluated. Using several web servers a number of mutations that converted non-rare codons to rare codon in these patients were identified. Results: Some of these rare Codons were located at special positions by mutation of which, the new side chains do not seem suitable for protein structure and function. Furthermore, this mutation changed the protein folding rate that may have a critical role in proper folding. Thus, primary change of these codons contributes to BSEP deficiency. Conclusion: This work is a comprehensive analysis of rare codons of ABCB11 and assessment of a number of these rare codon in protein levels. Rare codons evaluation can enhance our understanding of ABCB11 structural protein of ABCB11, and help us to develop mutation-specific therapies in design of new drugs. Citation: Zarenezhad M, Dehghani S. M, Ejtehadi F, Fattahi M. R, Mortazavi M, Tabei S. M. B. Evaluation of Hidden Information in ABCB11 Gene Mutations. J Biomed Phys Eng. 2019;9(3):303-316. https://doi.org/10.31661/jbpe.v9i3Jun.680.

Background: Progressive familial intrahepatic cholestases (PFIC) are a spectrum of autosomal progressive liver diseases developing to end-stage liver disease. ATP8B1 deficiency caused by mutations in ATP8B1 gene encoding a P-type ATPase leads to PFIC1. The gene for PFIC1 has been mapped on a 19-cM region of 18q21- q22, and a gene defect in ATP8B1 can cause deregulations in bile salt transporters through decreased expression and/or activity of FXR. Point mutations are the most common, with the majority being missense or nonsense mutations. In addition, approximately 15% of disease-causing ATP8B1 mutations are annotated as splicing disrupting alteration given that they are located at exon-intron borders. Objective: Here, we describe the hidden layer of computational biology information of rare codons in ATP8B1, which can help us for drug design. Methods: Some rare codons in different locations of ATP8b1 gene were identified using several web servers and by in-silico modelling of ATP8b1 in Phyre2 and I-TASSER server, some rare codons were evaluated. Results: Some of these rare codons were located at special positions which seem to have a critical role in proper folding of ATP8b1 protein. Structural analysis showed that some of rare codons are related to mutations in ATP8B1 that are responsible for PFIC1 disease, which may have a critical role in ensuring the correct folding. Conclusion: Investigation of such hidden information can enhance our understanding of ATP8b1 folding. Moreover, studies of these rare codons help us to clarify their role in rational design of new and effective drugs.

Background: Considering the increasing prevalence of psychological problems, complications, and consequences of depression in patients undergoing hemodialysis (HD), the application of complementary therapies such as meditation counseling is highly important. Objectives: Therefore, this study aimed to investigate the effect of meditation on depression in patients undergoing HD. Methods: This clinical trial was conducted on 57 patients who met the inclusion criteria by the convenience sampling method. The participants were randomly allocated to intervention and control groups. Those in the intervention group attended three 15-20 minute educational practice sessions weekly offered over an eight weeks while the control group received no intervention. A validated questionnaire assessed depressive symptoms at baseline and after 4 and 8 weeks. In addition, the CONSORT statement was adhered to where possible. Finally, t-test, repeated-measures ANOVA, Fisher’s exact test, and Chi-square tests were used to analyze data using SPSS 16. Results: The mean depression score among the patients of the intervention group decreased from 85±1.56 at baseline to 70±1.27 at 8-week follow-up (P=0.003). Further, the mean score of depressive symptoms significantly decreased during eight weeks after the intervention (P

The seismic demands of the Reinforced Concrete Shear Walls (RCSWs) system are determined based on Canada's National Building Code (NBC). NBC 2020 features the revised Canadian Seismic Hazard Model and presents the possibility of enhancing demand's accuracy by determining design spectra based on the specific average shear wave velocity, instead of specified site classes. This paper investigates the changes in design demands for RCSWs compared to the previous edition. To do so, fifty-five RCSW prototypes were modelled using distributed mass and stiffness procedure, and their dynamic response was assessed through Modal Response Spectrum Analysis at five locations across Canada. The results highlight significant changes in deformation and force demands, where the majority of cases experienced an increase in 2020 compared to 2015 when demands were determined based on specified site classes. This study also evaluates the log-log interpolation method recommended by NBC 2020 for the design spectral acceleration. [ABSTRACT FROM AUTHOR]

The tomato leafminer, Tuta absoluta is a devastating invasive pest that poses a serious threat to tomato crops worldwide. Its extensive global dispersion serves its capacity to adapt to variations in climate conditions. In this context, the pupa is the most resistant stage to prolonged exposure to cold temperatures. Therefore, indicators of cold resistance were studied in overwintering pupae collected from the field and pupae reared under two constant conditions, high temperature, and long day (25°C, 16:8 L:D and 65±5% RH), and low temperature and short day (15°C, 13:11 L:D and 65±5% RH). The results show that the super cooling point (SCP) significantly decreased in December (-20.5±1.2°C) and January (-20.26±0.78°C) with a decrease in temperature. In the laboratory, the decrease in temperature and photoperiod increased the tolerance of pupae to subzero temperatures. Lethal Temperature 50 (LT50) and LT90 of pupae collected in the field were recorded at -13.70 to -10.23°C and -18.73 to -15.37°C, respectively. A comparison of lethal temperatures with the lowest ambient temperature in December and January indicated that T. absoluta has a high overwintering potential in Karaj, Alborz Province, Iran, and can easily survive cold winters. [ABSTRACT FROM AUTHOR]

Background: Wilson disease (WD) is an autosomal recessive disorder of copper metabolism with an estimated prevalence of 1 in 30,000. Osteoarticular manifestations are common feature of WD and mainly involve osteopenia, osteoporosis, and arthropathy. Objective: This study aimed to investigate the prevalence of abnormal mineral density in a group of children with WD and evaluate if it is rational to recommend screening in pre-transplantation workups. Methods: This study included all the children with a confirmed diagnosis of WD, followed at Nemazee Hospital affiliated with Shiraz University of Medical Sciences between 2016 and 2018. The researchers also excluded patients with other underlying diseases, abnormalities of calcium, phosphorus, or vitamin D, or those who used other medications leading to osteoporosis. Bone mineral content (BMC)/Bone mineral density (BMD) of the lumbar spine (LS-BMD) was performed for all included patients with DXA scans. Results: Evaluation of z-scores showed osteopenia in 40% and osteoporosis in 53.33% of the patients. There was no significant association between the z-score values and cirrhosis in WD patients (P=0.559). There was a significant correlation between the value of z-scores with weight (P=0.007) and BMI (P=0.001) in patients with WD. Conclusion: The results suggest that WD is intrinsically associated with osteoporosis. Also, patients with WD are at risk of osteopenia and osteoporosis, and screening for evaluation of bone mineral density and prophylactic supplementation may be logical, especially for those who are candidates for liver transplant due to the probability of deterioration of osteopathy in the first few months after liver transplantation. [ABSTRACT FROM AUTHOR]

Background: Liver cirrhosis is an end stage liver damage. Biliary atresia (BA) and inherited syndromes of intrahepatic cholestasis are the most frequent causes of liver cirrhosis in children especially in the first year of life. Objective: To compare the prognostic value of albumin-bilirubin grade (ALBI), an alternative predictor of mortality in cirrhotic adults, with Child-Pugh and Pediatric End-Stage Liver Disease (PELD) scores in cirrhotic children with variceal bleeding. Methods: We analyzed the patients' data using MedCalc software, and calculated area under the curves (AUC) of receiving-operator characteristic (ROC). Results: All scores were higher in expired compared to survived patients (p<0.001). The AUC values for predicting mortality in all patients were 0.879±0.04 for Child-Pugh and PELD scores and 0.733±0.06 for ALBI. The prognostic values in two subgroups of BA and those with other underlying diseases (non-BA) showed that in BA group, ALBI score with AUC of 0.607±0.102, p<0.29, had no significant difference between survived and non-survived patients. ALBI in non-BA group, with AUC of 0.863±0.063 showed closer value to other scores (0.954), and was differed between survived and non-survived groups (p<0.001). Conclusion: Our results suggested that ALBI might be useful in predicting mortality in non-BA patients. [ABSTRACT FROM AUTHOR]