Blood pressure and heart failure

Background Hypertension is a leading cause of cardiovascular disease, stroke, and death. It affects a substantial proportion of the population worldwide, and remains underdiagnosed and undertreated. Body Long-standing high blood pressure leads to left ventricular hypertrophy and diastolic dysfunction that cause an increase in myocardial rigidity, which renders the myocardium less compliant to changes in the preload, afterload, and sympathetic tone. Adequate blood pressure control must be achieved in patients with hypertension to prevent progression to overt heart failure. Controlling blood pressure is also important in patients with established heart failure, especially among those with preserved ejection fractions. However, aggressive blood pressure lowering can cause adverse outcomes, because a reverse J-curve association may exist between the blood pressure and the outcomes of patients with heart failure. Little robust evidence exists regarding the optimal blood pressure target for patients with heart failure, but a value near 130/80 mmHg seems to be adequate according to the current guidelines. Conclusion Prospective studies are required to further investigate the optimal blood pressure target for patients with heart failure

Prevalence and socio-economic burden of heart failure in an aging society of South Korea

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background Heart failure (HF) is one of the leading causes of morbidity and mortality in South Korea. With the rapidly aging population in the country, the prevalence of HF and its associated costs are expected to rise continuously. This study was carried out to estimate the prevalence and economic burden of HF in order to understand its impact on our society. Methods A prevalence-based, cost-of-illness study was conducted using the 2014 Health Insurance Review and Assessment Service-National Patients Sample (HIRA-NPS) data. Adult HF patients were defined as those aged ≥19 years who had at least one insurance claim record with a primary or secondary diagnosis of HF (ICD-10 codes of I11.0, I13.0, I13.2, and I50.x). The costs consist of direct costs (i.e., medical and non-medical costs) and indirect costs (i.e., productivity loss cost due to morbidity and premature death). Subgroup analyses were conducted by age group, history of HF hospitalization, and type of universal health security program enrolled in. Results A total of 475,019 adults were identified to have HF in 2014. The estimated prevalence rate of HF was 12.4 persons per 1,000 adults. According to the base cases and the extended definition of the cases, the annual economic burden of HF from a societal perspective ranges from USD 1,414.0 to 1,560.5 for individual patients, and from USD 752.8 million to 1,085.6 million for the country. A high percentage (68.5 %) of this socioeconomic burden consist of medical costs, followed by caregivers cost (13.2 %), productivity loss costs due to premature death (10.8 %) and morbidity (4.2 %), and transportation costs (3.4 %). The HF patients with prior hospitalization due to HF annually spent 9.7 times more for National-Health-Insurance-covered medical costs compared to HF patients who were not previously hospitalized. Conclusions In the present study, HF patients who were older and had a history of prior hospitalization for HF as well as an indigent status were shown at high risk of spending more for healthcare to treat their HF. An effective disease management protocol should be employed to target this patient group

Crystal structures of murine norovirus-1 RNA-dependent RNA polymerase in complex with 2-thiouridine or ribavirin

AbstractMurine norovirus-1 (MNV-1) shares many features with human norovirus (HuNoV) and both are classified within the norovirus genus of Caliciviridae family. MNV-1 is used as the surrogate for HuNoV research since it is the only form that can be grown in cell culture. HuNoV and MNV-1 RNA dependent RNA polymerase (RdRp) proteins with the sequence identity of 59% show essentially identical conformations. Here we report the first structural evidence of 2-thiouridine (2TU) or ribavirin binding to MNV-1 RdRp, based on the crystal structures determined at 2.2Å and 2.5Å resolutions, respectively. Cellular and biochemical studies revealed stronger inhibitory effect of 2TU on the replication of MNV-1 in RAW 264.7 cells, compared to that of ribavirin. Our complex structures highlight the key interactions involved in recognition of the nucleoside analogs which block the active site of the viral RNA polymerase

Development of an easy-to-handle murine model for the characterization of radiation-induced gross and molecular changes in skin

Background Radiation-induced skin injury is a dose-limiting complication of radiotherapy. To investigate this problem and to develop a framework for making decisions on treatment and dose prescription, a murine model of radiation-induced skin injury was developed. Methods The dorsal skin of the mice was isolated, and irradiation was applied at single doses of 15, 30, and 50 Gy. The mice were followed for 12 weeks with serial photography and laser Doppler analysis. Sequential skin biopsy samples were obtained and subjected to a histological analysis, immunostaining against transforming growth factor beta (TGF-β), and Western blotting with Wnt-3 and β-catenin. Increases in the levels of TGF-β, Wnt, and β-catenin were detected after irradiation. Results All tested radiation doses caused progressive dermal thickening and fibrosis. The cause of this process, however, may not be radiation alone, as the natural course of wound healing may elicit a similar response. The latent appearance of molecular and histological markers that induce fibrosis in the 15 Gy group without causing apparent gross skin injuries indicates that 15 Gy is an appropriate dose for characterizing the effects of chronic irradiation alone. Thus, this model best mimics the patterns of injury that occur in human subjects. Conclusions This animal model can be used to elucidate the gross and molecular changes that occur in radiation-induced skin injury and provides an effective platform for studying this adverse effect without complicating the process of wound healing

Secure tumor classification by shallow neural network using homomorphic encryption

Disclosure of patients genetic information in the process of applying machine learning techniques for tumor classification hinders the privacy of personal information. Homomorphic Encryption (HE), which supports operations between encrypted data, can be used as one of the tools to perform such computation without information leakage, but it brings great challenges for directly applying general machine learning algorithms due to the limitations of operations supported by HE. In particular, non-polynomial activation functions, including softmax functions, are difficult to implement with HE and require a suitable approximation method to minimize the loss of accuracy. In the secure genome analysis competition called iDASH 2020, it is presented as a competition task that a multi-label tumor classification method that predicts the class of samples based on genetic information using HE. We develop a secure multi-label tumor classification method using HE to ensure privacy during all the computations of the model inference process. Our solution is based on a 1-layer neural network with the softmax activation function model and uses the approximate HE scheme. We present an approximation method that enables softmax activation in the model using HE and a technique for efficiently encoding data to reduce computational costs. In addition, we propose a HE-friendly data filtering method to reduce the size of large-scale genetic data. We aim to analyze the dataset from The Cancer Genome Atlas (TCGA) dataset, which consists of 3,622 samples from 11 types of cancers, genetic features from 25,128 genes. Our preprocessing method reduces the number of genes to 4,096 or less and achieves a microAUC value of 0.9882 (85% accuracy) with a 1-layer shallow neural network. Using our model, we successfully compute the tumor classification inference steps on the encrypted test data in 3.75 minutes. As a result of exceptionally high microAUC values, our solution was awarded co-first place in iDASH 2020 Track 1: Secure multi-label Tumor classification using Homomorphic Encryption. Our solution is the first result of implementing a neural network model with softmax activation using HE. Also, HE optimization methods presented in this work enable machine learning implementation using HE or other challenging HE applications.This work was supported by Institute of Information & communications Technology Planning & Evaluation (IITP) grant funded by the Korea government(MSIT) (No.2020-0-00840, Development and Library Implementation of Fully Homomorphic ML Algorithms supporting Neural Network Learning over Encrypted Data)

Multimodality Imaging Can Help to Doubt, Diagnose and Follow-Up Cardiac Mass

Primary cardiac lymphoma is a very rare form of lymphoma primarily or mainly involving the heart, as in the two cases presented in this report. Various imaging modalities, including coronary computed tomography angiography, cardiac magnetic resonance imaging and positron emission tomography were useful for the characterization and diagnosis of cardiac mass. Pathologic confirmation was successful with endomyocardial biopsy under echocardiographic guidance, intra- and extracardiacally. In primary cardiac lymphoma, diagnosis using multiple modalities may be useful for mass characterization, and for response monitoring after chemotherapy

Role of host tissues for sustained humoral effects after endothelial progenitor cell transplantation into the ischemic heart

Noncellular differentiation effects have emerged as important mechanisms mediating therapeutic effects of stem or progenitor cell transplantation. Here, we investigated the expression patterns and sources of humoral factors and their regional and systemic biological effects after bone marrow (BM)-derived endothelial progenitor cell (EPC) transplantation into ischemic myocardium. Although most of the transplanted EPCs disappeared within a week, up-regulation of multiple humoral factors was sustained for longer than two weeks, which correlated well with the recovery of cardiac function. To determine the source of the humoral factors, we injected human EPCs into immunodeficient mice. Whereas the expression of human EPC (donor)-derived cytokines rapidly decreased to a nondetectable level within a week, up-regulation of mouse (recipient)-derived cytokines, including factors that could mobilize BM cells, was sustained. Histologically, we observed higher capillary density, a higher proliferation of myocardial cells, a lower cardiomyocyte apoptosis, and reduced infarct size. Furthermore, after EPC transplantation, BM-derived stem or progenitor cells were increased in the peripheral circulation and incorporated into the site of neovascularization and myocardial repair. These data indicate that myocardial EPC transplantation induces humoral effects, which are sustained by host tissues and play a crucial role in repairing myocardial injury