Unlocking the Mysteries of Diastolic Function Deciphering the Rosetta Stone 10 Years Later

It has now been a quarter of a century since the first description by Kitabatake and his associates of the use of echo-Doppler to characterize the transmitral flow velocity curves in various disease states. A decade ago we described the role of echocardiography in the “Evaluation of Diastolic Filling of Left Ventricle in Health and Disease: Doppler Echocardiography Is the Clinician’s Rosetta Stone.” Over the ensuing decade, advances in echo-Doppler have helped to further decipher the morphologic and physiological expression of cardiovascular disease and unlock additional mysteries of diastology. The purpose of this review is to highlight the developments in echo-Doppler and refinements in our knowledge that have occurred over the past decade that enhance our understanding of diastology

Dectin-2 recognises mannosylated O-antigens of human opportunistic pathogens and augments lipopolysaccharide activation of myeloid cells

Lipopolysaccharide (LPS) consists of a relatively conserved region of lipid A and core-oligosaccharide, and a highly variable region of O-antigen polysaccharide. While lipid A is known to bind to the toll-like receptor 4 (TLR4)-myeloid differentiation factor 2 (MD2) complex, the role of the O-antigen remains unclear. Here we report a novel molecular interaction between dendritic cell-associated C-type lectin-2 (Dectin-2) and the mannosylated O-antigen found in a human opportunistic pathogen Hafnia alvei PCM 1223, which has a repeating unit of [-Man-α1,3-Man-α1,2-Man-α1,2-Man-α1,2-Man-α1,3-]. H. alvei LPS induced higher levels of TNFα and IL-10 from mouse bone marrow-derived dendritic cells (BM-DCs), when compared to Salmonella enterica O66 LPS which has a repeat of [-Gal-α1,6-Gal-α1,4-[Glc-β1,3]GalNAc-α1,3-GalNAc-β1,3-]. In a cell-based reporter assay, Dectin-2 was shown to recognise H. alvei LPS. This binding was inhibited by mannosidase treatment of H. alvei LPS and by mutations in the carbohydrate-binding domain of Dectin-2, demonstrating that H. alvei LPS is a novel glycan ligand of Dectin-2. The enhanced cytokine production by H. alvei LPS was Dectin-2 dependent, as Dectin-2 knockout BM-DCs failed to do so. This receptor crosstalk between Dectin-2 and TLR4 involved events including spleen tyrosine kinase (Syk) activation and receptor juxtaposition. Furthermore, another mannosylated LPS from Escherichia coli O9a, also bound to Dectin-2 and augmented TLR4 activation of BM-DCs. Taken together, these data indicate that mannosylated O-antigens from several gram-negative bacteria augment TLR4 responses through interaction with Dectin-2

Predicting postoperative systolic dysfunction in mitral regurgitation: CT vs. echocardiography

IntroductionVolume overload from mitral regurgitation can result in left ventricular systolic dysfunction. To prevent this, it is essential to operate before irreversible dysfunction occurs, but the optimal timing of intervention remains unclear. Current echocardiographic guidelines are based on 2D linear measurement thresholds only. We compared volumetric CT-based and 2D echocardiographic indices of LV size and function as predictors of post-operative systolic dysfunction following mitral repair.MethodsWe retrospectively identified patients with primary mitral valve regurgitation who underwent repair between 2005 and 2021. Several indices of LV size and function measured on preoperative cardiac CT were compared with 2D echocardiography in predicting post-operative LV systolic dysfunction (LVEFecho <50%). Area under the curve (AUC) was the primary metric of predictive performance.ResultsA total of 243 patients were included (mean age 57 ± 12 years; 65 females). The most effective CT-based predictors of post-operative LV systolic dysfunction were ejection fraction [LVEFCT; AUC 0.84 (95% CI: 0.77–0.92)] and LV end systolic volume indexed to body surface area [LVESViCT; AUC 0.88 (0.82–0.95)]. The best echocardiographic predictors were LVEFecho [AUC 0.70 (0.58–0.82)] and LVESDecho [AUC 0.79 (0.70–0.89)]. LVEFCT was a significantly better predictor of post-operative LV systolic dysfunction than LVEFecho (p = 0.02) and LVESViCT was a significantly better predictor than LVESDecho (p = 0.03). Ejection fraction measured by CT demonstrated significantly greater reproducibility than echocardiography.DiscussionCT-based volumetric measurements may be superior to established 2D echocardiographic parameters for predicting LV systolic dysfunction following mitral valve repair. Validation with prospective study is warranted

ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention - Summary article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention)

The American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI) 2005 Guideline Update for Percutaneous Coronary Intervention (PCI) contains changes in the recommendations, along with supporting text. For the purpose of comparison, this summary contains a list of the updated recommendations (middle column) alongside a list of the 2001 recommendations (left column), with each set accompanied by a comment (right column) that provides the rationale for the changes, additions, or deletions (see Table 1). References that support either the 2001 recommendations that have changed or the new or revised recommendations are cited in parentheses at the end of each recommendation or comment. A list of abbreviations is included in the Appendix. The reader is referred to the full-text guideline posted on the World Wide Web sites of the ACC, the AHA, and the SCAI for a more detailed explanation of the changes discussed here. Please note that we have changed the table of contents headings in the 2001 ACC/AHA Guidelines for Percutaneous Coronary Intervention from roman numerals to unique identifying numbers

A Second-Generation Device for Automated Training and Quantitative Behavior Analyses of Molecularly-Tractable Model Organisms

A deep understanding of cognitive processes requires functional, quantitative analyses of the steps leading from genetics and the development of nervous system structure to behavior. Molecularly-tractable model systems such as Xenopus laevis and planaria offer an unprecedented opportunity to dissect the mechanisms determining the complex structure of the brain and CNS. A standardized platform that facilitated quantitative analysis of behavior would make a significant impact on evolutionary ethology, neuropharmacology, and cognitive science. While some animal tracking systems exist, the available systems do not allow automated training (feedback to individual subjects in real time, which is necessary for operant conditioning assays). The lack of standardization in the field, and the numerous technical challenges that face the development of a versatile system with the necessary capabilities, comprise a significant barrier keeping molecular developmental biology labs from integrating behavior analysis endpoints into their pharmacological and genetic perturbations. Here we report the development of a second-generation system that is a highly flexible, powerful machine vision and environmental control platform. In order to enable multidisciplinary studies aimed at understanding the roles of genes in brain function and behavior, and aid other laboratories that do not have the facilities to undergo complex engineering development, we describe the device and the problems that it overcomes. We also present sample data using frog tadpoles and flatworms to illustrate its use. Having solved significant engineering challenges in its construction, the resulting design is a relatively inexpensive instrument of wide relevance for several fields, and will accelerate interdisciplinary discovery in pharmacology, neurobiology, regenerative medicine, and cognitive science

ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease)

"The ACC and the AHA have long been involved in the joint development of practice guidelines designed to assist healthcare providers in the management of selected cardiovascular disorders or the selection of certain cardiovascular procedures. The determination of the disorders or procedures to develop guidelines for is based on several factors, including importance to healthcare providers and whether there are sufficient data from which to derive accepted guidelines. One important category of cardiac disorders that affect a large number of patients who require diagnostic procedures and decisions regarding long-term management is valvular heart disease. During the past 2 decades, major advances have occurred in diagnostic techniques, the understanding of natural history, and interventional cardiology and surgical procedures for patients with valvular heart disease. These advances have resulted in enhanced diagnosis, more scientific selection of patients for surgery or catheter-based intervention versus medical management, and increased survival of patients with these disorders. The information base from which to make clinical management decisions has greatly expanded in recent years, yet in many situations, management issues remain controversial or uncertain. Unlike many other forms of cardiovascular disease, there is a scarcity of large-scale multicenter trials addressing the diagnosis and treatment of patients with valvular disease from which to derive definitive conclusions, and the information available in the literature represents primarily the experiences reported by single institutions in relatively small numbers of patients.

ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure)

"The committee elected to focus this document on the prevention of HF and on the diagnosis and management of chronic HF in the adult patient with normal or low LVEF. It specifically did not consider acute HF, which might merit a separate set of guidelines and is addressed in part in the ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (8) and the ACC/AHA 2003 Update of the Guidelines for the Management of Unstable Angina and Non-ST Elevation Myocardial Infarction (9). We have also excluded HF in children, both because the underlying causes of HF in children differ from those in adults and because none of the controlled trials of treatments for HF have included children. We have not considered the management of HF due to primary valvular disease [see ACC/AHA Guidelines on the Management of Patients With Valvular Heart Disease (10)] or congenital malformations, and we have not included recommendations for the treatment of specific myocardial disorders (e.g., hemochromatosis, sarcoidosis, or amyloidosis). These practice guidelines are intended to assist healthcare providers in clinical decision making by describing a range of generally acceptable approaches for the prevention, diagnosis, and management of HF. The guidelines attempt to define practices that meet the needs of most patients under most circumstances. However, the ultimate judgment regarding the care of a particular patient must be made by the healthcare provider in light of all of the circumstances that are relevant to that patient. These guidelines do not address cost-effectiveness from a societal perspective. The guidelines are not meant to assist policy makers faced with the necessity to make decisions regarding the allocation of finite healthcare resources. In fact, these guidelines assume no resource limitation. They do not provide policy makers with sufficient information to be able to choose wisely between options for resource allocation. The various therapeutic strategies described in this document can be viewed as a checklist to be considered for each patient in an attempt to individualize treatment for an evolving disease process. Every patient is unique, not only in terms of his or her cause and course of HF, but also in terms of his or her personal and cultural approach to the disease. Guidelines can only provide an outline for evidence-based decisions or recommendations for individual care; these guidelines are meant to provide that outline.