Search

This review concisely presents the chronology of events that shaped the development of echocardiography. The concept of 'seeing' structures using 'sound' dates back to the 1920s, when ultrasound produced by piezoelectric crystals was used to detect flaws in metals. In the early 1950s, Hertz and Edler described the use of ultrasound for assessing mitral-valve disease. Subsequently, Harvey Feigenbaum in the 1960s standardized the clinical use of M-mode echocardiography for quantitative assessment of left-ventricular dimensions. The advent of 2-dimensional echocardiography (1970s), pulsed Doppler (1970s), and color Doppler (1980s) introduced new methods for routine assessment of cardiac anatomy and hemodynamics at bedside. Flexible scopes and superior transducers further paved the way to the application of transesophageal echocardiography. Tissue Doppler and contrast echocardiography recently have emerged as important tools for evaluation of regional myocardial function and blood flow. Miniaturization and the ability to pack thousands of crystals in an electronic array have transformed the application of 3-dimensional echocardiography into a bedside tomographic tool. At the current pace of development, echocardiography will be able to provide complete assessment of the heart in terms of its anatomy, coronary flow, and physiology. Training people and making it available at every bedside may be the only remaining challenges. [ABSTRACT FROM AUTHOR]

Cultured human embryonic stem cells (hESCs) can develop genetic anomalies that increase their susceptibility to transformation. In this study, we characterized a variant hESC (vhESC) line and investigated the molecular mechanisms leading to the drift towards a transformed state. Our findings revealed that vhESCs up-regulate EMT-specific markers, accelerate wound healing, exhibit compromised lineage differentiation, and retain pluripotency gene expression in teratomas. Furthermore, we discovered an altered epigenomic landscape and overexpression of the lysine methyltransferases EHMT1, EHMT2, and NSD group of proteins in vhESCs. Remarkably, depleting NSD3 oncogene reversed the molecular and phenotypic changes in vhESCs. We identified a detailed mechanism where EHMT2 interacts and methylates NSD3 at lysine 477, stabilizing its protein levels in vhESCs. In addition, we showed that NSD3 levels are regulated by protein degradation in hESCs, and its stabilization leads to the emergence of the variant state. Overall, our study identify that misregulation of NSD3 in pluripotent stem cells, through methylation-mediated abrogation of its protein degradation, drives hESCs towards oncogenic transformation., (© 2024 Krishnamoorthy et al.)

Euchromatic histone methyltransferases (EHMTs), members of the KMT1 family, methylate histone and non-histone proteins. Here, we uncover a novel role for EHMTs in regulating heterochromatin anchorage to the nuclear periphery (NP) via non-histone methylation. We show that EHMTs methylate and stabilize LaminB1 (LMNB1), which associates with the H3K9me2-marked peripheral heterochromatin. Loss of LMNB1 methylation or EHMTs abrogates heterochromatin anchorage at the NP We further demonstrate that the loss of EHMTs induces many hallmarks of aging including global reduction of H3K27methyl marks and altered nuclear morphology. Consistent with this, we observe a gradual depletion of EHMTs, which correlates with loss of methylated LMNB1 and peripheral heterochromatin in aging human fibroblasts. Restoration of EHMT expression reverts peripheral heterochromatin defects in aged cells. Collectively, our work elucidates a new mechanism by which EHMTs regulate heterochromatin domain organization and reveals their impact on fundamental changes associated with the intrinsic aging process., (© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)

Purpose: This study aimed to identify findings on non-ECG-gated CT pulmonary angiography (CTPA) indicating decreased left ventricle (LV) systolic function, later confirmed by echocardiogram., Methods: After obtaining institutional review board approval, review was performed of emergency department (ED) patients who had CTPA and follow-up echocardiogram within 48 h, over 18 months. Patients with pulmonary embolus, suboptimal CTPA, arrhythmias or pericardial tamponade were excluded. One hundred thirty-seven patients were identified and divided into cases (LVEF <40%, n = 52) and controls (LVEF >50%, n = 85). Two reviewers performed these analyses: measurement of enhancement in main pulmonary artery (MPA), LV, and aorta; subjective enhancement of LV and aorta (Ao) relative to MPA using a four-point Likert scale; contrast transit time (TD) to trigger CTPA and LV short & long axis dimensions. When available, the most recent N-terminal pro-B-type natriuretic peptide (NT-proBNP) level was recorded., Results: Decreased aortic and LV subjective enhancement were the best predictors of LV systolic dysfunction. For Ao/MPA ratio, an optimal cutoff value of 0.20 resulted in a sensitivity of 0.54 and specificity of 0.93 (AUC = 0.83, 0.78-0.88 95% CI). A threshold of 86.7 HU for Ao enhancement resulted in a sensitivity of 0.68 and specificity of 0.90 (AUC = 0.82, 0.77-0.88 95% CI). A LV short axis diameter of more than 54.3 mm had a sensitivity of 0.62 and specificity of 0.98 (AUC = 0.88, 0.83-0.92 95% CI). For the LV long axis diameter, a cutoff of 87.5 mm resulted in a sensitivity of 0.66 and specificity of 0.84 (AUC = 0.78, 0.72-0.84 95% CI). With bolus timing, cases had a longer TD (13.4 vs. 10.4 s, p < 0.0001)., Conclusion: Unsuspected LV systolic dysfunction can be recognized on a CTPA by identification of decreased aortic enhancement, LV enlargement and increased TD. This has important diagnostic implications for the patient presenting with shortness of breath, chest pain, or dyspnea.

Competing Interests: Competing interests: We have read and understood the BMJ policy on declaration of interests and declare no competing interests.

The protective potential of Emblica officinalis (amla) was investigated on metal-induced lipid per oxidation in human erythrocytes. Increases in the levels of MDA and catalase activity were assessed as lipid per oxidation. In addition, glutathione peroxidase (GPX), glutathione (GSH), and ascorbic acid levels were assessed as antioxidant indices. Preliminary investigation of the extract exhibited a significant reduction in lipid per oxidation and an increase in antioxidant abilities, such as a decrease in MDA, GPx and GSH (P<0.05). A significant reduction in erythrocyte hemolysis induced by hydrogen peroxide was observed using amla extract (P<0.05). These findings show that amla extract has significant protective potential against lipid per oxidation.

The function of the protein is primarily dictated by its structure. Therefore it is far more logical to find the functional clues of the protein in its overall 3-dimensional fold or its global structure. In this paper, we have developed a novel Support Vector Machines (SVM) based prediction model for functional classification and prediction of proteins using features extracted from its global structure based on fragment libraries. Fragment libraries have been previously used for abintio modelling of proteins and protein structure comparisons. The query protein structure is broken down into a collection of short contiguous backbone fragments and this collection is discretized using a library of fragments. The input feature vector is frequency vector that counts the number of each library fragment in the collection of fragments by all-to-all fragment comparisons. SVM models were trained and optimised for obtaining the best 10-fold Cross validation accuracy for classification. As an example, this method was applied for prediction and classification of Cell Adhesion molecules (CAMs). Thirty-four different fragment libraries with sizes ranging from 4 to 400 and fragment lengths ranging from 4 to 12 were used for obtaining the best prediction model. The best 10-fold CV accuracy of 95.25% was obtained for library of 400 fragments of length 10. An accuracy of 87.5% was obtained on an unseen test dataset consisting of 20 CAMs and 20 NonCAMs. This shows that protein structure can be accurately and uniquely described using 400 representative fragments of length 10.

Brain (B-type) natriuretic peptide (BNP) and tissue Doppler imaging may distinguish restrictive cardiomyopathy (RCMP) from idiopathic constrictive pericardial disease (CP). However, their comparative efficacy is unknown for patients with CP from secondary causes (e.g., surgery or radiotherapy). We compared the efficacy of tissue Doppler imaging and BNP for differentiation of RCMP (n = 15) and CP (n = 16) were compared. BNP was higher in patients with RCMP than CP (p = 0.008), but the groups overlapped, particularly for BNP <400 pg/ml. BNP was lower with idiopathic CP than secondary CP (139 +/- 50 vs 293 +/- 69 pg/ml; p <0.001) or RCMP (139 +/- 50 vs 595 +/- 499 pg/ml; p <0.001), but not significantly different between those with secondary CP and RCMP (293 +/- 69 vs 595 +/- 499 pg/ml; p = 0.1). Patients with CP and RCMP had less overlap in early diastolic and isovolumic contraction tissue Doppler imaging velocities compared with BNP, with clear separation of groups evident with mean early diastolic annular velocities (averaged from 4 walls). Early diastolic tissue Doppler imaging velocity was superior to BNP for differentiation of CP and RCMP (area under the curve 0.97 vs 0.76, respectively; p = 0.01). In conclusion, mean early diastolic mitral annular velocity correctly distinguished CP from RCMP even when there was a large overlap of BNP between the 2 groups.

Background: Capitalizing on mechanoenergetic coupling, we investigated whether strain echocardiography can noninvasively estimate the ratio of adenosine triphosphate (ATP) to adenosine diphosphate (ADP), a marker of energetic status during acute myocardial ischemia and reperfusion., Methods: Twenty-eight pigs were divided into 7 groups (1 baseline, 4 ischemic, and 2 reperfusion). Ischemia was induced by left anterior descending coronary artery occlusion. Longitudinal systolic lengthening (SL) and postsystolic shortening (PSS) strain were measured by echocardiography. The ATP/ADP ratio was obtained from myocardial biopsies in the ischemic and control regions., Results: SL and PSS strain and the ATP/ADP ratio progressively decreased (P < .05) with increased duration (12, 40, 120, and 200 minutes) of ischemia. A mathematical formula (ATP/ADP = -0.97 + 0.25 x PSS strain + 0.20 x SL strain) estimated best the ATP/ADP ratio (r = 0.94, P < .05). Reperfusion after 12 but not after 120 minutes of ischemia significantly improved the ATP/ADP ratio and decreased SL and PSS strain., Conclusions: Strain echocardiography closely reflected changes and enabled the noninvasive estimation of the ATP/ADP ratio. A higher ATP/ADP ratio is associated with functional improvement after reperfusion.

Objectives: The purpose of this study was to compare the longitudinal, circumferential, and radial mechanics of the left ventricle (LV) in patients with constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM)., Background: Diastolic dysfunction in CP is related to epicardial tethering and pericardial constraint, whereas in RCM it is predominantly characterized by subendocardial dysfunction. Assessment of variations in longitudinal and circumferential deformation of LV might be useful to distinguish these 2 conditions., Methods: Longitudinal, radial, and circumferential mechanics of the LV were quantified by 2-dimensional speckle tracking of B-mode cardiac ultrasound images in 26 patients with CP, 19 patients with RCM, and 21 control subjects., Results: In comparison with control subjects, patients with CP had significantly reduced circumferential strain (base; -16 +/- 6% vs. -9 +/- 6%; p < 0.016), torsion (3 +/- 1 degrees /cm vs. 1 +/- 1 degrees /cm; p < 0.016), and early diastolic apical untwisting velocities (E(r); 116 +/- 62 degrees /s vs. -36 +/- 50 degrees /s; p < 0.016), whereas longitudinal strains, displacement, and early diastolic velocities at the LV base (E(m)) were similar to control subjects. In contrast, patients with RCM showed significantly reduced longitudinal displacement (base; 14.7 +/- 2.5 cm vs. 9.8 +/- 2.8 cm; p < 0.016) and E(m) (-8.7 +/- 1.3 cm/s vs. -4.4 +/- 1.1 cm/s; p < 0.016), whereas circumferential strain and E(r) were similar to those of control subjects. For differentiation of CP from RCM, the area under the curve was significantly higher for E(m) in comparison with E(r) (0.97 vs. 0.76, respectively; p = 0.01). After pericardiectomy, there was a significant decrease in longitudinal early diastolic LV basal myocardial velocities (7.4 cm/s vs. 6.8 cm/s; p = 0.023). Circumferential strain, torsion, and E(r), however, remained unchanged., Conclusions: Deformation of the LV is constrained in the circumferential direction in CP and in the longitudinal direction in RCM. Subsequent early diastolic recoil of LV is also attenuated in each of the 2 directions, respectively, uniquely differentiating the abnormal diastolic restoration mechanics of the LV seen in CP and RCM.

Background: Sonomicrometry is a gold standard in experimental studies on myocardial motion. However, limited information exists regarding mechanical and biochemical changes produced by sonomicrometry crystal (SC) insertion into the myocardial wall., Methods: In 10 open-chest pigs, we implanted SCs into the inner half of apical anterior and midposterior regions. Longitudinal strains (systolic lengthening, end-systolic, peak shortening, and postsystolic shortening strains) and strain rate (SR) measurements (peak systolic ejection and early and late diastolic SRs) were obtained by Doppler SR echocardiography along with troponin I levels measured from peripheral blood before and after SC insertion., Results: SR and strain parameters did not change significantly after SC implantation. Troponin I levels increased significantly from less than 0.010 to 0.129 +/- 0.138 microg/L (P < .005) after SC implantation., Conclusions: Our study demonstrates that despite biochemical evidence of myocardial injury, carefully implanted SCs do not alter systolic or diastolic regional myocardial function assessed by Doppler echocardiography.

Doppler tissue imaging (DTI) and DTI-derived strain imaging are robust physiologic tools used for the noninvasive assessment of regional myocardial function. As a result of high temporal and spatial resolution, regional function can be assessed for each phase of the cardiac cycle and within the transmural layers of the myocardial wall. Newer techniques that measure myocardial motion by speckle tracking in gray-scale images have overcome the angle dependence of DTI strain, allowing for measurement of 2-dimensional strain and cardiac rotation. DTI, DTI strain, and speckle tracking may provide unique information that deciphers the deformation sequence of complexly oriented myofibers in the left ventricular wall. The data are, however, limited. This review examines the structure and function of the left ventricle relative to the potential clinical application of DTI and speckle tracking in assessing the global mechanical sequence of the left ventricle in vivo.