Transcriptome-based reconstructions from the murine knockout suggest involvement of the urate transporter, URAT1 (slc22a12), in novel metabolic pathways.

URAT1 (slc22a12) was identified as the transporter responsible for renal reabsorption of the medically important compound, uric acid. However, subsequent studies have indicated that other transporters make contributions to this process, and that URAT1 transports other organic anions besides urate (including several in common with the closely related multi-specific renal organic anion transporters, OAT1 (slc22a6) and OAT3 (slc22a8)). These findings raise the possibility that urate transport is not the sole physiological function of URAT1. We previously characterized mice null for the murine ortholog of URAT1 (mURAT1; previously cloned as RST), finding a relatively modest decrement in urate reabsorptive capacity. Nevertheless, there were shifts in the plasma and urinary concentrations of multiple small molecules, suggesting significant metabolic changes in the knockouts. Although these molecules remain unidentified, here we have computationally delineated the biochemical networks consistent with transcriptomic data from the null mice. These analyses suggest alterations in the handling of not only urate but also other putative URAT1 substrates comprising intermediates in nucleotide, carbohydrate, and steroid metabolism. Moreover, the analyses indicate changes in multiple other pathways, including those relating to the metabolism of glycosaminoglycans, methionine, and coenzyme A, possibly reflecting downstream effects of URAT1 loss. Taken together with the available substrate and metabolomic data for the other OATs, our findings suggest that the transport and biochemical functions of URAT1 overlap those of OAT1 and OAT3, and could contribute to our understanding of the relationship between uric acid and the various metabolic disorders to which it has been linked

Attitude of pregnant women towards Normal delivery and factors driving use of caesarian section in Iran (2016)

© 2019 The Author(s). Background: Normal delivery is a natural and physiological process with numerous benefits for mother and baby. Giving birth by Caesarean Section (CS) should be limited to the cases in which normal delivery is not possible. The purpose of the study was to determine the attitudes of pregnant women towards Normal Delivery and factors driving the use of Caesarian Section in Kermanshah, Iran. Methods: This analytical-descriptive study was conducted on 410 pregnant women referred to the PHC centers in Kermanshah in western Iran. They had been selected through a multi-stage sampling method, including clustering, randomized, and proportional sampling, from among all eligible women. Data was collected using a questionnaire standardized by previous studies. The level of 0.05 was considered significance association, whenever applied. Results: The mean and standard deviation for participant age was 27.65 ± 5.37 years. The median score for participant attitude was 60.7 ± 9.5 (range from 22 to 85). Generally, 21.5% had a negative attitude toward normal delivery and preferred CS. Participant attitude was negatively correlated with a pregnant woman's age, lower age, and a more positive attitude towards vaginal childbirth. The attitude of women with a history of normal delivery was 63 ± 9 and for those with a history of CS was 56.7 ± 9.3, significantly different. Conclusion: Most women had a positive attitude towards normal delivery, particularly those who had experienced normal delivery in their previous childbirth. Although only a quarter of the participants had a negative attitude toward normal delivery, this figure still was of utmost significance, therefore educational interventions, specifically encouraging women with history of normal delivery to consult their peers, are recommended

A proximal femur aneurysmal bone cyst resulting in amputation: A rare case report

Aneurysmal bone cyst (ABC) is blood filled expansile cystic lesion that most commonly occurs in patients during the second decade of their lives. Traditionally it has been described as a benign lesion but can be locally aggressive and result in the destruction of the involved bone. Treatment methods include surgical excision and curettage with or without bone grafting. We report a proximal femur aneurysmal bone cyst, which resulted in the amputation of the lower extremity, even though all available classic methods of treatment were applied for it. © 2015 Tehran University of Medical Sciences. All rights reserved

Unusual presentation of synovial sarcoma as meniscal cyst: A Case Report

Periarticular cyst and cystic soft tissue lesion around the knee are common. Synovial sarcoma is a rare and malignant soft tissue tumor accounting for approximately 5 of soft tissue sarcoma. A case is presented where a lesion adjacent to the joint line of the knee was diagnosed clinically and on imaging as a meniscal cyst. MRI signal was homogenous and no concomitant meniscal tears were seen. The tissue diagnosis was monophasic synovial sarcoma. © 2015 BY THE ARCHIVES OF BONE AND JOINT SURGERY

Analysis of mitochondrial DNA sequences of Turcinoemacheilus genus (Nemacheilidae Cypriniformes) in Iran

Members of Nemacheilidae Family, Turcinoemacheilus genus were subjected to molecular phylogenetic analysis in this study. This genus was reported in 2009 to inhabit in Karoon River drainage, in contrary to previous assumption that it was the endemic species in the Basin of Tigris River. It was sampled from three stations placed in different tributaries in Karoon drainage and evaluated to understand the molecular phylogenetic relationships of Turcinoemacheilus in Iran. The mitochondrial cytochrome b gene (cyt b) and control region were used to infer phylogenetic relationships. PCR amplification of control region was not carried out successfully, possibly due to the high divergence of this sequence in the studied genus. The amplified fragments of cyt b were sequenced then analyzed by the use of phylogenetic software. Only one divergent position was seen in all three samples stations located in amino acid position 365. GTR and p-distances of cytochrome b gene for T. kosswigi computed from different stations of running water in Karoon drainage showed these samples belong to different populations and fall in intraspecific differences. In this study, examination of the molecular phylogeny using Bayesian analysis, maximum parsimony or neighbor-joining define the phylogentics of Turcinoemacheilus genus as a monophyletic clade which is sister-clade of Nemacheilus and Schistura genera. This report is the first report of Turcinoemacheilus molecular data and could describe molecular phylogeny of this genus in loaches

Stage IE primary bone lymphoma: Limb salvage for local recurrence

Background: Primary bone lymphoma or non-Hodgkin lymphoma of bone is a rare disease. There are only a few case series of stage IE of this condition in medical literature. The aim of this study is to determine the rate of survival for stage IE after combined modality treatment, the rate of local recurrence, and the results of limb salvage in cases of local recurrence. Methods: We collected data from 61 patients with histologically confirmed PBL treated at the Musculoskeletal Oncology Department of our hospital from 2000 to 2010. Retrospective evaluation included demographics, symptoms, tumor locations, outcomes of surgical treatment for local recurrence and survival rates. Results: All patients received Combined Modality Therapy. Overall, five year survival was 89 and five year disease free survival rate was 78. Local recurrence occurred in 6 patients during follow up period, which was treated surgically by wide excision and reconstruction. The mean follow-up for the local recurrence group was 36(24-54) months and mortality rate in this group was 17. Conclusions: Combined Modality Therapy for stage IE primary bone lymphomaresults in good survival rate. In case of local recurrence, wide excision and reconstruction improves the outcomes. © 2015 BY THE ARCHIVES OF BONE AND JOINT SURGERY

Evaluation of rate law approximations in bottom-up kinetic models of metabolism.

BackgroundThe mechanistic description of enzyme kinetics in a dynamic model of metabolism requires specifying the numerical values of a large number of kinetic parameters. The parameterization challenge is often addressed through the use of simplifying approximations to form reaction rate laws with reduced numbers of parameters. Whether such simplified models can reproduce dynamic characteristics of the full system is an important question.ResultsIn this work, we compared the local transient response properties of dynamic models constructed using rate laws with varying levels of approximation. These approximate rate laws were: 1) a Michaelis-Menten rate law with measured enzyme parameters, 2) a Michaelis-Menten rate law with approximated parameters, using the convenience kinetics convention, 3) a thermodynamic rate law resulting from a metabolite saturation assumption, and 4) a pure chemical reaction mass action rate law that removes the role of the enzyme from the reaction kinetics. We utilized in vivo data for the human red blood cell to compare the effect of rate law choices against the backdrop of physiological flux and concentration differences. We found that the Michaelis-Menten rate law with measured enzyme parameters yields an excellent approximation of the full system dynamics, while other assumptions cause greater discrepancies in system dynamic behavior. However, iteratively replacing mechanistic rate laws with approximations resulted in a model that retains a high correlation with the true model behavior. Investigating this consistency, we determined that the order of magnitude differences among fluxes and concentrations in the network were greatly influential on the network dynamics. We further identified reaction features such as thermodynamic reversibility, high substrate concentration, and lack of allosteric regulation, which make certain reactions more suitable for rate law approximations.ConclusionsOverall, our work generally supports the use of approximate rate laws when building large scale kinetic models, due to the key role that physiologically meaningful flux and concentration ranges play in determining network dynamics. However, we also showed that detailed mechanistic models show a clear benefit in prediction accuracy when data is available. The work here should help to provide guidance to future kinetic modeling efforts on the choice of rate law and parameterization approaches

Orthogonal variability modeling to support multi-cloud application configuration

Cloud service providers benefit from a vast majority of customers due to variability and making profit from commonalities between the cloud services that they provide. Recently, application configuration dimensions has been increased dramatically due to multi-tenant, multi-device and multi-cloud paradigm. This challenges the configuration and customization of cloud-based software that are typically offered as a service due to the intrinsic variability. In this paper, we present a model-driven approach based on variability models originating from the software product line community to handle such multi-dimensional variability in the cloud. We exploit orthogonal variability models to systematically manage and create tenant-specific configuration and customizations. We also demonstrate how such variability models can be utilized to take into account the already deployed application parts to enable harmonized deployments for new tenants in a multi-cloud setting. The approach considers application functional and non-functional requirements to provide a set of valid multi-cloud configurations. We illustrate our approach through a case study