Evaluation of commercial ResPlex II v2.0, MultiCode®-PLx,and xTAG® respiratory viral panels for the diagnosis of respiratory viral infections in adults

BackgroundCommercial multiplex PCR panels for respiratory viruses (PRV) have been recently developed. ResPlex II Panel v2.0 (Qiagen), MultiCode^®-PLx (EraGen Biosciences), and xTAG^® (Luminex) PRV's were studied. All assays detect influenza A and B, adenovirus, parainfluenza 1–3, respiratory syncytial virus A and B, human metapneumovirus and human rhinovirus. The ResPlex II additionally detects coronavirus (229E, OC43, NL63, HKU1), coxsackie/echo virus, bocavirus and differentiates adenoviruses (B, E). The MultiCode-PLX assay detects 229E, OC43, and NL63, differentiates parainfluenza 4a, 4b and adenoviruses (B, C, E). The xTAG additionally subtypes influenza A as seasonal H1 and H3.Study design202 specimens collected from adult patients with signs of respiratory infection from November, 2008 to May, 2009 were used for evaluating the performance of the three commercial PRV assays. Viral culture and xTAG were used as the standards to assess sensitivity and specificity.ResultsThe PRV assays detected more viruses than culture. When compared to culture, the xTAG PRV showed a sensitivity and specificity of 100% and 91%, compared to MultiCode-PLx with 89% and 87%, and ResPlex II with 89% and 94%, respectively. Co-infection was detected in a small subset of patient specimens. Each panel showed differences in sensitivities for individual viruses.ConclusionsWhile the ResPlex II and MultiCode-PLx offer a broader virus detection range and greater ease of use, the xTAG PRV showed increased sensitivity to common viral targets represented in the assays, and also had the ability to differentiate human from non-human influenza A H1.     

Toll-like receptors: Significance,ligands, signaling pathways,and functions in mammals

This review attempts to cover the implication of the toll-like receptors (TLRs) in controlling immune functions with emphasis on their significance, function, regulation and expression patterns. The tripartite TLRs are type I integral transmembrane receptors that are involved in recognition and conveying of pathogens to the immune system. These paralogs are located on cell surfaces or within endosomes. The TLRs are found to be functionally involved in the recognition of self and non-self-antigens, maturation of DCs and initiation of antigen-specific adaptive immune responses as they bridge the innate and adaptive immunity. Interestingly, they also have a significant role in immunotherapy and vaccination. Signals generated by TLRs are transduced through NFκB signaling and MAP kinases pathway to recruit pro-inflammatory cytokines and co-stimulatory molecules, which promote inflammatory responses. The excess production of these cytokines leads to grave systemic disorders like tumor growth and autoimmune disorders. Hence, regulation of the TLR signaling pathway is necessary to keep the host system safe. Many molecules like LPS, SOCS1, IRAK1, NFκB, and TRAF3 are involved in modulating the TLR pathways to induce appropriate response. Though quantification of these TLRs helps in correlating the magnitude of immune response exhibited by the animal, there are several internal, external, genetic and animal factors that affect their expression patterns. So it can be concluded that any identification based on those expression profiles may lead to improper diagnosis during certain conditions.     

Direct structural insight into the substrate-shuttling mechanism of yeast fatty acid synthase by electron cryomicroscopy

Yeast fatty acid synthase (FAS) is a 2.6-MDa barrel-shaped multienzyme complex, which carries out cyclic synthesis of fatty acids. By electron cryomicroscopy of single particles we obtained a three-dimensional map of yeast FAS at 5.9-Å resolution. Compared to the crystal structures of fungal FAS, the EM map reveals major differences and new features that indicate a considerably different arrangement of the complex in solution compared to the crystal structures, as well as a high degree of variance inside the barrel. Distinct density regions in the reaction chambers next to each of the catalytic domains fitted the substrate-binding acyl carrier protein (ACP) domain. In each case, this resulted in the expected distance of ∼18 Å from the ACP substrate-binding site to the active site of the catalytic domains. The multiple, partially occupied positions of the ACP within the reaction chamber provide direct structural insight into the substrate-shuttling mechanism of fatty acid synthesis in this large cellular machine.     

Live/Real Time Three‐Dimensional Transesophageal Echocardiographic Findings in Caseous Mitral Annular Calcification

We describe a 77‐year‐old female with hypertrophic cardiomyopathy in whom live/real time three‐dimensional transesophageal echocardiography (3DTEE) provided incremental value over two‐dimensional transthoracic and transesophageal echocardiography (2DTTE, 2DTEE) and three‐dimensional transthoracic echocardiography (3DTTE) in making a more comprehensive assessment and a more confident diagnosis of caseous mitral annular calcification. 3DTEE revealed a portion of the mass to consist of small, multiple, highly echogenic discrete band‐like and punctate areas within a relatively much less echogenic stroma and surrounded by a well defined highly echogenic border. This appearance correlated with the pathological findings of calcific granules/strands located in a liquefied or semiliquefied interior providing a typical toothpaste like appearance. The highly echogenic outer border represented the residual outer portion or rim of the calcific mass which did not undergo liquefaction. These findings on 3DTEE which correlated with the toothpaste like appearance seen at surgery were not visualized on 2DTTE, 2DTEE, and 3DTTE. (Echocardiography 2010;27:1147‐1150)     

Transcatheter closure of perimembranous ventricular septal defect with amplatzer membranous occluder

BACKGROUND: Use of trancatheter device closure for membranous ventricular septal defect is still in evolving phase. We report the early and mid-term results of our experience with the new asymmetric Amplatzer membranous ventricular septal defect occluder. METHODS AND RESULTS: We attempted, transcatheter closure of perimembranous ventricular septal defect using asymmetric Amplatzer occluder in 26 patients. The patients were selected on the basis of transthoracic and transesophageal echocardiographic assessment of the ventricular septal defect. The procedure was successful in 21 (81%) patients. The age ranged from 3 to 23 years, weight from 10 to 59 kg and defect size ranged from 3 to 9 mm (mean: 5 +/- 1.8 mm). One patient had situs inversus with dextrocardia: 11 had aneurysmal tissue partly occluding the defect and the device was deployed either across (n=6) or within the aneurysmal sac (n=5). Three patients developed high degree atrioventricular block on attempts to cross the defect with the sheath and the procedure was discontinued. In two patients it was not possible to place the sheath in left ventricle despite repeated attempts. There was a residual flow in 4 (19%) patients at 24 hours. Two patients developed bundle branch block and none had complete heart block. At follow-up (1-9 months, n=20), residual flow was seen in two patients. None developed late conduction defect, aortic regurgitation, infective endocarditis or hemolysis. CONCLUSIONS: Transcatheter closure of perimembranous ventricular septal defect can be performed safely and effectively with the new asymmetric Amplatzer occluder device in selected patients with good short- and midterm results. These devices can be deployed safely in and across and the aneurysmal sacs. In selected cases, this procedure is a satisfactory alternative to surgery.