Plakophilin-2 truncating variants impair cardiac contractility by disrupting sarcomere stability and organization.

Progressive loss of cardiac systolic function in arrhythmogenic cardiomyopathy (ACM) has recently gained attention as an important clinical consideration in managing the disease. However, the mechanisms leading to reduction in cardiac contractility are poorly defined. Here, we use CRISPR gene editing to generate human induced pluripotent stem cells (iPSCs) that harbor plakophilin-2 truncating variants (tv), the most prevalent ACM-linked mutations.

Probing the subcellular nanostructure of engineered human cardiomyocytes in 3D tissue.

The structural and functional maturation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is essential for pharmaceutical testing, disease modeling, and ultimately therapeutic use. Multicellular 3D-tissue platforms have improved the functional maturation of hiPSC-CMs, but probing cardiac contractile properties in a 3D environment remains challenging, especially at depth and in live tissues. Using small-angle X-ray scattering (SAXS) imaging, we show that hiPSC-CMs matured and examined in a 3D environment exhibit a periodic spatial arrangement of the myofilament lattice, which has not been previously detected in hiPSC-CMs.

Mechanical dysfunction of the sarcomere induced by a pathogenic mutation in troponin T drives cellular adaptation.

Familial hypertrophic cardiomyopathy (HCM), a leading cause of sudden cardiac death, is primarily caused by mutations in sarcomeric proteins. The pathogenesis of HCM is complex, with functional changes that span scales, from molecules to tissues. This makes it challenging to deconvolve the biophysical molecular defect that drives the disease pathogenesis from downstream changes in cellular function.

Genetic Studies of Hypertrophic Cardiomyopathy in Singaporeans Identify Variants in and That Are Common in Chinese Patients.

Background: To assess the genetic architecture of hypertrophic cardiomyopathy (HCM) in patients of predominantly Chinese ancestry.

Methods: We sequenced HCM disease genes in Singaporean patients (n=224) and Singaporean controls (n=3634), compared findings with additional populations and White HCM cohorts (n=6179), and performed in vitro functional studies.

Results: Singaporean HCM patients had significantly fewer confidently interpreted HCM disease variants (pathogenic/likely pathogenic: 18%, <0.

Myosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is caused by pathogenic variants in sarcomere protein genes that evoke hypercontractility, poor relaxation, and increased energy consumption by the heart and increased patient risks for arrhythmias and heart failure. Recent studies show that pathogenic missense variants in myosin, the molecular motor of the sarcomere, are clustered in residues that participate in dynamic conformational states of sarcomere proteins. We hypothesized that these conformations are essential to adapt contractile output for energy conservation and that pathophysiology of HCM results from destabilization of these conformations.

Disrupted mechanobiology links the molecular and cellular phenotypes in familial dilated cardiomyopathy.

Familial dilated cardiomyopathy (DCM) is a leading cause of sudden cardiac death and a major indicator for heart transplant. The disease is frequently caused by mutations of sarcomeric proteins; however, it is not well understood how these molecular mutations lead to alterations in cellular organization and contractility. To address this critical gap in our knowledge, we studied the molecular and cellular consequences of a DCM mutation in troponin-T, ΔK210.

Effect of modest pay-for-performance financial incentive on time-to-discharge summary dictation among medical residents.

Objective: Evaluate the effect of a modest financial incentive on time-to-discharge summary dictation among medicine residents.

Background: Pay-for-performance incentives are used in a number of health care settings. Studies are lacking on their use with medical residents and other trainees.

Exploring front-line hospital workers' contributions to patient and worker safety.

Concerns about stubbornly persistent high rates both of error-related patient injuries and of occupational injuries among healthcare workers have generated intense exploration of etiologies, interventions, and the role of underlying safety culture. Much of this work has centered on the role of physicians and nurses in health care, and suggests common issues related to safety culture. However, the role of front-line health care workers, such as nursing assistants, ward clerks, environmental service workers, food workers and transportation workers, among others, has not been explored sufficiently.

Reducing 30-day readmissions: health literacy strategies.

The imperatives of the Affordable Care Act to reduce 30-day readmissions present challenges and opportunities for nurse administrators. The literature suggests success in reducing readmissions through enhancing patient-centered discharge processes, focusing on medication reconciliation, improving coordination with community-based providers, and effective patient self-management of their disease and treatment. Evidence-based interventions addressing low health literacy, when used with all patients, hold promise to promote understanding and self-management.

Improving student understanding of health literacy through experiential learning.

Low health literacy is a pervasive yet under-appreciated issue in contemporary healthcare. It has a significant impact on cost and quality indicators, and affects patients and professionals along the entire care continuum. Educators must sensitize healthcare administration students to the complexity of low health literacy, and teach strategies to address it.

Low health literacy: a challenge to critical care.

Health literacy-"the degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions"-has been identified as a cross-cutting quality-of-care issue by the Institute of Medicine. This article defines the scope of the health literacy problem, discusses the literacy demands of critical care, and offers strategies for nurses to improve the quality of health communication with patients and families in the critical care environment.

An international programme in nursing and midwifery: building capacity for the new millennium.

Aim: The global economy is changing rapidly and frequently affects the ability of the health sector to respond to a variety of needs. Nurses and midwives are reaching across national boundaries to strengthen their ability to improve the health of populations. This article describes an innovative programme of collaboration among different nations to strengthen the capacity of nurses and midwives.

An organizational climate intervention associated with increased handwashing and decreased nosocomial infections.

Handwashing practices are persistently suboptimal among healthcare professionals and are also stubbornly resistant to change. The purpose of this quasi-experimental intervention trial was to assess the impact of an intervention to change organizational culture on frequency of staff handwashing (as measured by counting devices inserted into soap dispensers on four critical care units) and nosocomial infections associated with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). All staff in one of two hospitals in the mid-Atlantic region received an intervention with multiple components designed to change organizational culture; the second hospital served as a comparison.

Interdisciplinary education in clinical ethics: a work in progress.

Clinical decision making and, broadly speaking, patient care are increasingly collaborative endeavors dependent on the integration of the profession-specific knowledge, skills, and perspectives of physicians and nurses. Conflicts over the ethical dimensions of clinical decision making often arise from these differing but complementary perspectives. Neither medical nor nursing education adequately prepares future clinicians for these realities of practice.

Home health care agencies: what constitutes success?

Dramatic changes in the health care delivery system have produced a highly competitive environment for home health agencies. This study examined the characteristics perceived to be present in successful home health agencies. The results reflect both similarities and differences from studies of successful hospitals and businesses.

Graduate home health education: a survey of home health educators and agency personnel.

To determine if there is a body of essential content that should be common to master's-level home care programs, a purposive sample of 200 nurses involved in home health or community health nursing was selected. The respondents (N = 118), including faculty and educational administrators (N = 61) and supervisors and administrators of home health agencies (N = 57), were asked their perceptions of the knowledge needed and their priorities for curriculum content for master's-prepared home care specialists in both clinical and administrative roles. There was agreement in most content areas, but significant differences were found between faculty and agency personnel in their priorities for community health concepts, and in their evaluation of nursing theory and epidemiology as essential content in both roles.

Impact of Medicare payment policy on home health resources utilization.

In this study, the association between Medicare regulations and the provision of public home health care is examined. Medicare clients were compared with non-Medicare groups of those 65 years of age or over and those under 65. Results suggested that both age- and payer-related factors contribute to utilization of services.

A study of patients receiving no billed nursing care.

Although home health care traditionally is conceptualized as nursing care, in today's environment care at home may be delivered by a myriad of professional and nonprofessional practitioners. In fact, many patients who receive home care do not receive billed nursing visits. We studied a group of patients (n = 200) who received no billed nursing care, but rather received billed care from therapists, social workers and home health aides.

Home health nursing care: a comparison of not-for-profit and for-profit agencies.

The recent rapid growth in the numbers of for-profit and not-for-profit agencies delivering home health care raises questions about whether these agencies are serving different patient populations. Not-for-profit agencies were found to serve more indigent and medicaid patients than for-profits. Nurses from both kinds of agencies participated in this study and their patient case management activities are reported and compared for differences in their practice.

Care coordination: a resource-intensive component of home health nursing practice.

Coordinating patient care is an activity central to home health nursing practice. Nurses believe that this component of care contributes in a meaningful way to patient well-being. Yet changes in the home care environment at the patient, agency, and system levels could jeopardize nurses' care coordination activities.

Nonreimbursed home health care: beyond the bills.

The unprecedented growth in the home care industry over the past decade has produced a highly competitive environment for care delivery. To survive, most agencies are implementing strategies to maximize reimbursable care. This focus, while likely to improve an agency's financial situation, is fraught with potential problems.

Nursing activities and reimbursement in clinical case management.

If governmental agencies, third-party payers, and employers expect to obtain the benefits of clinical case management, then the indirect activities required for clinical case management and documented by this study must be considered in calculating home health care reimbursement rates.