Diagnostic performance of chest radiography measurements for the assessment of cardiac chamber enlargement

Background:The cardiothoracic ratio (CTR) is commonly assessed on chest radiography for detection of cardiac chamber enlargement, but the traditional cutpoint of 0.5 has low specificity. We sought to evaluate the diagnostic accuracy of new measurement techniques for the detection of cardiac enlargement on chest radiographs.Methods:We obtained retrospective cross-sectional data on consecutive patients who underwent both chest radiography and cardiac magnetic resonance imaging (MRI) within a 14-day interval between 2006 and 2016 at a large academic hospital network. We established the presence of cardiac chamber enlargement using cardiac MRI as the reference standard. We evaluated the diagnostic performance of different techniques for measuring heart size and CTR on frontal chest radiographs.Results:Of 152 patients included, 81 (53%) were men and the mean age was 52 years. Maximum heart diameter had the highest area under the receiver operating characteristic curve for detection of cardiac enlargement (0.827, 95% confidence interval 0.760–0.894). In the subgroup of posteroanterior chest radiography studies (n = 101), a CTR cutpoint of 0.50 had only moderate sensitivity (72%) and specificity (72%). In men, a maximum heart diameter cutpoint of 15 cm had a sensitivity of 86% and a negative likelihood ratio of 0.24, and a cutpoint of 19 cm had a specificity of 100% and a positive likelihood ratio of infinity. In women, a maximum heart diameter cutpoint of 13 cm had a sensitivity of 91% and a negative likelihood ratio of 0.15, and a cutpoint of 17 cm had a specificity of 91% and a positive likelihood ratio of 3.5.Interpretation:A traditional CTR cutpoint of 0.5 has limited diagnostic value. Simple heart diameter measurements have higher diagnostic performance measures than CTR.

Cardiac chamber enlargement is important to identify, given that it is a predictor of poor outcomes and may reflect potentially treatable underlying disease.¹ Cardiac chamber size can be assessed using multiple imaging modalities, including chest radiography, echocardiography, computed tomography and cardiac magnetic resonance imaging (MRI).^2–4 Although cardiac MRI is considered the reference standard for the evaluation of cardiac size and function, it is rarely performed as an initial investigation because of its relatively high cost and limited availability.⁵ On the other hand, chest radiography is frequently performed as the initial imaging investigation for suspected pulmonary and cardiac disease, including in patients presenting with shortness of breath and chest pain.^6,7 Therefore, accurate and reproducible measures of cardiac enlargement on chest radiography would help to identify patients with underlying cardiac disease who might benefit from further investigation.Cardiac enlargement is frequently evaluated on chest radiography using the cardiothoracic ratio (CTR), which was originally described in 1919.⁸ Although this sign is an accepted and frequently used marker of cardiac enlargement, it has not been validated against cardiac MRI or other contemporary methods of objectively assessing cardiac chamber size. Some studies have shown that the CTR, as assessed using the originally described cutpoint of 0.5, has low specificity and diagnostic accuracy for cardiac enlargement, and therefore may be of limited clinical utility.^9–11 The purpose of this study was to evaluate new measurement techniques and cutpoints for the detection of cardiac chamber enlargement on chest radiography in comparison with MRI.     

Quantifying information transfer by protein domains: Analysis of the Fyn SH2 domain structure

Background  

Efficient communication between distant sites within a protein is essential for cooperative biological response. Although often associated with large allosteric movements, more subtle changes in protein dynamics can also induce long-range correlations. However, an appropriate formalism that directly relates protein structural dynamics to information exchange between functional sites is still lacking.     

Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

Background

Highly pathogenic avian influenza (HPAI) H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease.

Aim

To study influenza A (H5N1) virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease.

Methods

We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces.

Results

We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our data suggests that viremia, secondary to, for example, gastro-intestinal infection, can potentially lead to infection of the lung. HPAI H5N1 virus was a more potent inducer of cytokines (e.g. IP-10, RANTES, IL-6) in comparison to H1N1 virus in alveolar epithelial cells, and these virus-induced chemokines were secreted onto both the apical and basolateral aspects of the polarized alveolar epithelium.

Conclusion

The predilection of viruses for different routes of entry and egress from the infected cell is important in understanding the pathogenesis of influenza H5N1 infection and may help unravel the pathogenesis of human H5N1 disease.     

ETISEQ – an algorithm for automated elution time ion sequencing of concurrently fragmented peptides for mass spectrometry-based proteomics

Background  

Concurrent peptide fragmentation (i.e. shotgun CID, parallel CID or MS^E) has emerged as an alternative to data-dependent acquisition in generating peptide fragmentation data in LC-MS/MS proteomics experiments. Concurrent peptide fragmentation data acquisition has been shown to be advantageous over data-dependent acquisition by providing greater detection dynamic range and providing more accurate quantitative information. Nevertheless, concurrent peptide fragmentation data acquisition remains to be widely adopted due to the lack of published algorithms designed specifically to process or interpret such data acquired on any mass spectrometer.     

Rapid evolution of goat and sheep globin genes following gene duplication

Statistical analyses of DNA sequences of globin genes (beta A, beta C, and gamma) from goat and sheep (including new sequence information for the second intron of sheep beta A and gamma, kindly provided by A. Davis and A. W. Nienhuis) indicate that the rates of nonsynonymous substitution in these genes have been greatly accelerated following the gene duplication separating gamma and the ancestor of beta A and beta C and the gene duplication separating beta A and beta C. In both cases the acceleration was apparently due to relaxation of purifying selection (functional constraints) rather than advantageous mutations because acceleration occurred only in less important parts of the beta globin chain. The rates of nonsynonymous substitution in these genes are estimated to be about 2.3 x 10(-9) per site per year, which is three times higher than that for the divergence between human beta and mouse beta major globin genes. Our analyses further suggest that the rate of synonymous substitution in functional genes and the rate of substitution in pseudogenes are approximately equal and are between 2.8 x 10(-9) and 5.0 x 10(-9) and that the rate of substitution in introns is about 3.0 x 10(-9). The divergence time between beta A and beta C and that between gamma and the beta A-beta C pair are about 12 and 30 million years, respectively. The proportion of transition mutations is estimated to be 64%, two times higher than expected under random mutation but considerably lower than the 96% estimated for animal mitochondrial DNA.      

Genetic control of Endosperm Balance Number (EBN): three additive loci in a threshold-like system

Summary The genetic control of Endosperm Balance Number (EBN) was investigated by a complete diallel of four exceptional diploid Solanum commersonii-S. chacoense hybrids (1 1/2 EBN) and backcrosses to their species parents, S. commersonii (1 EBN) and S. chacoense (2 EBN). Crosses in which the female parent had a higher EBN value than the male, S. chacoense (2 EBN)XF₁ (11/2 EBN) and F₁ (11/2 EBN)X S. commersonii (1 EBN), produced viable seed to aborted seed ratios of 11.1 and 11.3, respectively, and had average to small sized viable seed. Crosses in which the female parent had a lower EBN value than the male, S. commersonii (1 EBN)XF₁ (11/2 EBN) and F₁ (11/2 EBN)XS. chacoense (2 EBN), produced viable seed to aborted seed ratios of 1 7.9 and 1 6.7, respectively, and had average to large sized viable seeds. The results of these crosses appear to be consistent with the relative EBN values of the male and female parent. A model is proposed for the system regulating endosperm development. The assumptions of this model are: (1) three unlinked loci control the system; (2) the loci are homozygous within a species; (3) the genes have additive effects and are of equal strength within a species; (4) the genes within S. chacoense have twice the effect with respect to endosperm regulation as those within S. commersonii; and (5) a slight excess maternal dosage will produce the qualitative effect of small but viable seed. This model, in which quantitative genes operate in a dosage dependent system bears many similarities to classical, threshold-type genetic models.     

Origin of chloroplast DNA diversity in the Andean potatoes

Summary Wide chloroplast DNA (ctDNA) diversity has been reported in the Andean cultivated tetraploid potato, Solanum tuberosum ssp. andigena. Andean diploid potatoes were analyzed in this study to elucidate the origin of the diverse ctDNA variation of the cultivated tetraploids. The ctDNA types of 58 cultivated diploid potatoes (S. stenotomum, S. goniocalyx and S. phureja), 35 accessions of S. sparsipilum, a diploid weed species, and 40 accessions of the wild or weed species, S. chacoense, were determined based on ctDNA restriction fragment patterns of BamHI, HindIII and PvuII. Several different ctDNA types were found in the cultivated potatoes as well as in weed and wild potato species; thus, intraspecific ctDNA variation may be common in both wild and cultivated potato species and perhaps in the higher plant kingdom as a whole. The ctDNA variation range of cultivated diploid potatoes was similar to that of the tetraploid potatoes, suggesting that the ctDNA diversity of the tetraploid potato could have been introduced from cultivated diploid potatoes. This provided further evidence that the Andean cultivated tetraploid potato, ssp. andigena, could have arisen many times from the cultivated diploid populations. The diverse but conserved ctDNA variation noted in the Andean potatoes may have occurred in the early stage of species differentiation of South American tuber-bearing Solanums.     

The origin and evolution of <Emphasis Type="Italic">ARGFX</Emphasis>homeobox loci in mammalian radiation

Background  

Many homeobox genes show remarkable conservation between divergent animal phyla. In contrast, the ARGFX (Arginine-fifty homeobox) homeobox locus was identified in the human genome but is not present in mouse or invertebrates. Here we ask when and how this locus originated and examine its pattern of molecular evolution.