Although thyroid dyshormonogenesis (TDH) accounts for 10-20% of congenital hypothyroidism (CH), the molecular etiology of TDH is unknown in Bangladesh. Thyroid peroxidase (TPO) is most frequently associated with TDH and the present study investigated the spectrum of TPO mutations in Bangladeshi patients and analyzed the effects of mutations on TPO protein structure through in silico approach. Sequencing-based analysis of TPO gene revealed four mutations in 36 diagnosed patients with TDH including three nonsynonymous mutations, namely, p.Ala373Ser, p.Ser398Thr, and p.Thr725Pro, and one synonymous mutation p.Pro715Pro. Homology modelling-based analysis of predicted structures of MPO-like domain (TPO142-738) and the full-length TPO protein (TPO1-933) revealed differences between mutant and wild type structures. Molecular docking studies were performed between predicted structures and heme. TPO1-933 predicted structure showed more reliable results in terms of interactions with the heme prosthetic group as the binding energies were -11.5 kcal/mol, -3.2 kcal/mol, -11.5 kcal/mol, and -7.9 kcal/mol for WT, p.Ala373Ser, p.Ser398Thr, and p.Thr725Pro, respectively, implying that p.Ala373Ser and p.Thr725Pro mutations were more damaging than p.Ser398Thr. However, for the TPO142-738 predicted structures, the binding energies were -11.9 kcal/mol, -10.8 kcal/mol, -2.5 kcal/mol, and -5.3 kcal/mol for the wild type protein, mutant proteins with p.Ala373Ser, p.Ser398Thr, and p.Thr725Pro substitutions, respectively. However, when the interactions between the crucial residues including residues His239, Arg396, Glu399, and His494 of TPO protein and heme were taken into consideration using both TPO1-933 and TPO142-738 predicted structures, it appeared that p.Ala373Ser and p.Thr725Pro could affect the interactions more severely than the p.Ser398Thr. Validation of the molecular docking results was performed by computer simulation in terms of quantum mechanics/molecular mechanics (QM/MM) and molecular dynamics (MD) simulation. In conclusion, the substitutions mutations, namely, p.Ala373Ser, p.Ser398Thr, and p.Thr725Pro, had been involved in Bangladeshi patients with TDH and molecular docking-based study revealed that these mutations had damaging effect on the TPO protein activity.

The goal of this study was to establish a computational fluid dynamics model to investigate the effect of cyclic motion (i.e., bending and stretching) on coronary blood flow. The three-dimensional (3D) geometry of a 50-mm section of the left anterior descending artery (normal or with a 60% stenosis) was constructed based on anatomical studies. To describe the bending motion of the blood vessel wall, arbitrary Lagrangian-Eularian methods were used. To simulate artery bending and blood pressure change induced stretching, the arterial wall was modeled as an anisotropic nonlinear elastic solid using the five-parameter Mooney-Rivlin hyperelastic model. Employing a laminar model, the flow field was solved using the continuity equations and Navier-Stokes equations. Blood was modeled as an incompressible Newtonian fluid. A fluid-structure interaction approach was used to couple the fluid domain and the solid domain iteratively, allowing force and total mesh displacement to be transferred between the two domains. The results demonstrated that even though the bending motion of the coronary artery could significantly affect blood cell trajectory, it had little effect on flow parameters, i.e., blood flow velocity, blood shear stress, and wall shear stress. The shape of the stenosis (asymmetric or symmetric) hardly affected flow parameters either. However, wall normal stresses (axial, circumferential, and radial stress) can be greatly affected by the blood vessel wall motion. The axial wall stress was significantly higher than the circumferential and radial stresses, as well as wall shear stress. Therefore, investigation on effects of wall stress on blood vessel wall cellular functions may help us better understand the mechanism of mechanical stress induced cardiovascular disease.

Background and Objectives:Neurinoma arising from other than nonvestibular cranial nerves is less prevalent. Here we present our experiences regarding the clinical profile, investigations, microneurosurgical management, and the outcome of nonvestibular cranial nerve neurinomas.Materials and Methods:From January 2005 to December 2011, the recorded documents of operated nonvestibular intracranial neurinomas were retrospectively studied for clinical profile, investigations, microneurosurgical management, complications, follow-up, and outcomes.Results:The average follow-up was 24.5 months. Total number of cases was 30, with age ranging from 9 to 60 years. Sixteen cases were males and 14 were females. Nonvestibular cranial nerve schwannomas most commonly originated from trigeminal nerve followed by glossopharyngeal+/vagus nerve. There were three abducent nerve schwannomas that are very rare. There was no trochlear nerve schwannoma. Two glossopharyngeal+/vagus nerve schwannomas extended into the neck through jugular foramen and one extended into the upper cervical spinal canal. Involved nerve dysfunction was a common clinical feature except in trigeminal neurinomas where facial pain was a common feature. Aiming for no new neurodeficit, total resection of the tumor was done in 24 cases, and near-total resection or gross total resection or subtotal resection was done in 6 cases. Preoperative symptoms improved or disappeared in 25 cases. New persistent deficit occurred in 3 cases. Two patients died postoperatively. There was no recurrence of tumor till the last follow-up.Conclusion:Nonvestibular schwannomas are far less common, but curable benign lesions. Surgical approach to the skull base and craniovertebral junction is a often complex and lengthy procedure associated with chances of significant morbidity. But early diagnosis, proper investigations, and evaluation, along with appropriate decision making and surgical planning with microsurgical techniques are the essential factors that can result in optimum outcome.

Chemiluminescence immunoassay (CLIA) has been widely applied in different fields including environmental monitoring, liquid chromatography, clinical diagnosis; food safety, pharmaceutical analysis, immuno-and gene probe assays, as a promising approach for selective, sensitive, rapid and simple analysis. It is often necessary to detect a large number of complicated or low-abundance samples. However, traditional methods need great consumption of time, reagents and labor, which limit their clinical applications. As a result, rapid, high-throughput, sensitive and low-cost detection methods have become the development trend of CLIA. A new chemiluminescence immunoassay analyzer with advanced acridinium ester (AE) technology will be installed at the radioimmunoassy laboratory of National Institute of Nuclear Medicine and Allied Sciences (NINMAS) shortly. In conjunction with the existing Radioimmunoassay (RIA), Immunoradiometric assay (IRMA) and DissociationEnhanced Lanthanide Fluorescent Immunoassay (DELFIA), introduction of chemiluminescence immunoassay (CLIA) technology will expand the activities of in vitro immunoassay. It will also improve the research and development activities of in vitro division of NINMAS. In this review article, we have summarized the basic principle of chemiluminescence immunoassay and its applications. A comparison of RIA, CLIA and enzyme-linked immunosorbent assay (ELISA) was also briefly described in the article.