Modulation of Spontaneous Action Potential Rate by Inositol Trisphosphate in Myocytes from the Rabbit Atrioventricular Node.

The atrioventricular node (AVN) is a key component of the cardiac conduction system and takes over pacemaking of the ventricles if the sinoatrial node fails. IP (inositol 1,4,5 phosphate) can modulate excitability of myocytes from other regions of the heart, but it is not known whether IP receptor (IP-R) activation modulates AVN cell pacemaking. Consequently, this study investigated effects of IP on spontaneous action potentials (APs) from AVN cells isolated from rabbit hearts.

Does the Primary Tumor Site Drive Biology for Patients With Synovial Sarcoma?

Objective: We evaluated survival outcomes by primary tumor site in synovial sarcoma (SS) patients with localized and metastatic disease at diagnosis.

Methods: We conducted a retrospective review of 504 SS patients diagnosed from 1974 to 2020. Kaplan-Meier method, log-rank test, and Cox-proportional hazards regression were used.

Epidemiological trends of synovial sarcoma by primary tumor sites in the US from 2000 to 2020.

Background: Synovial sarcoma (SS) is a rare soft-tissue cancer. Existing literature encompasses Surveillance, Epidemiology, and End Results (SEER) data-based research on SS explaining the incidence-prevalence in general, by subtypes, and by age at diagnosis. Therefore, this study aimed to fill in the gap of knowledge about measures of disease occurrence and burden of SS by tumor site using the SEER database.

A collaboration between adult protective services and forensic accounting examiners to investigate complex financial exploitation: formative evaluation findings.

Financial exploitation (FE) is one of the most common reports to Adult Protective Services (APS) and the cases are often complex. Consequently, APS caseworkers report FE investigations to be among the most difficult while simultaneously reporting low confidence in productive outcomes for these investigations. This necessitates finding ways to support APS FE investigations.

Caregiving and all-cause mortality in postmenopausal women: Findings from the Women's Health Initiative.

Background: Caregiving is commonly undertaken by older women. Research is mixed, however, about the impact of prolonged caregiving on their health, well-being, and mortality risk. Using a prospective study design, we examined the association of caregiving with mortality in a cohort of older women.

Ca spark latency and control of intrinsic Ca release dyssynchrony in rat cardiac ventricular muscle cells.

Cardiac excitation-contraction coupling (ECC) depends on Ca release from intracellular stores via ryanodine receptors (RyRs) triggered by L-type Ca channels (LCCs). Uncertain numbers of RyRs and LCCs form 'couplons' whose activation produces Ca sparks, which summate to form a cell-wide Ca transient that switches on contraction. Voltage (V) changes during the action potential (AP) and stochasticity in channel gating should create variability in Ca spark timing, but Ca transient wavefronts have remarkable uniformity.

The Prevalence and Perceived Utility of Mobile Health Technology Among Recently Incarcerated Homeless Adults.

Mobile technologies can deliver physical and mental health services for recently incarcerated homeless adults (RIHAs). The purpose of this study was to examine the prevalence and perceived utility of mobile technology to support health behavior change among RIHAs. Participants ( = 324) from an ongoing clinical trial at a homeless shelter in Texas were included in the current descriptive cross-sectional analyses.

The activin receptor ligand trap ActRIIB:ALK4-Fc ameliorates cardiomyopathy induced by neuromuscular disease and diabetes.

Cardiomyopathies are ascribed to a variety of etiologies, present with diverse clinical phenotypes, and lack disease-modifying treatments. Mounting evidence implicates dysregulated activin receptor signaling in heart disease and highlights inhibition of this pathway as a potential therapeutic target. Here, we explored the effects of activin ligand inhibition using ActRIIB:ALK4-Fc, a heterodimeric receptor fusion protein, in two mechanistically distinct murine models of cardiomyopathy.

Improved Ca release synchrony following selective modification of I and phase 1 repolarization in normal and failing ventricular myocytes.

Loss of ventricular action potential (AP) early phase 1 repolarization may contribute to the impaired Ca release and increased risk of sudden cardiac death in heart failure. Therefore, restoring AP phase 1 by augmenting the fast transient outward K current (I) might be beneficial, but direct experimental evidence to support this proposition in failing cardiomyocytes is limited. Dynamic clamp was used to selectively modulate the contribution of I to the AP and Ca transient in both normal (guinea pig and rabbit) and in failing rabbit cardiac myocytes.

Popularity of Delta-8 THC on the Internet Across US States, 2021.

To assess the popularity of an emergent drug, delta-8 tetrahydrocannabinol (THC), and compare interest levels between US states with or without legalized recreational cannabis. We used Google Trends to assess the growth of interest among delta-8 THC-related search terms from May 17, 2020, to May 9, 2021. We examined differences between states with or without legalized cannabis using state-level Google Trends data from February 13 to May 13, 2021, and policy data from the National Conference of State Legislatures.

Acceptability of a real-time notification of stress and access to self-help therapies among law enforcement officers.

Background: Law enforcement officers (LEOs) are exposed to chronic stress throughout the course of their shift, which increases the risk of adverse events. Although there have been studies targeting LEO safety through enhanced training or expanded equipment provisions, there has been little attempt to leverage personal technology in the field to provide real-time notification of LEO stress. This study tests the acceptability of implementing of a brief, smart watch intervention to alleviate stress among LEOs.

Inducing I and phase 1 repolarization of the cardiac action potential with a Kv4.3/KChIP2.1 bicistronic transgene.

The fast transient outward potassium current (I) plays a key role in phase 1 repolarization of the human cardiac action potential (AP) and its reduction in heart failure (HF) contributes to the loss of contractility. Therefore, restoring I might be beneficial for treating HF. The coding sequence of a P2A peptide was cloned, in frame, between Kv4.

The "Network Effect" on Interfacility Transfers Among Regional Stroke Certified Hospitals.

Introduction And Purpose: Timely inter-facility transfer of thrombectomy-eligible patients is a mainstay of Stroke Systems of Care. We investigated transfer patterns among stroke certified hospitals in the Dallas-Fort Worth (DFW) Metroplex (19 counties, 9,286 sq mi, > 7.7 million people), by hospital network and stroke center status.

ActRIIB:ALK4-Fc alleviates muscle dysfunction and comorbidities in murine models of neuromuscular disorders.

Patients with neuromuscular disorders suffer from a lack of treatment options for skeletal muscle weakness and disease comorbidities. Here, we introduce as a potential therapeutic agent a heterodimeric ligand-trapping fusion protein, ActRIIB:ALK4-Fc, which comprises extracellular domains of activin-like kinase 4 (ALK4) and activin receptor type IIB (ActRIIB), a naturally occurring pair of type I and II receptors belonging to the TGF-β superfamily. By surface plasmon resonance (SPR), ActRIIB:ALK4-Fc exhibited a ligand binding profile distinctly different from that of its homodimeric variant ActRIIB-Fc, sequestering ActRIIB ligands known to inhibit muscle growth but not trapping the vascular regulatory ligand bone morphogenetic protein 9 (BMP9).

Nano-scale morphology of cardiomyocyte t-tubule/sarcoplasmic reticulum junctions revealed by ultra-rapid high-pressure freezing and electron tomography.

Detailed knowledge of the ultrastructure of intracellular compartments is a prerequisite for our understanding of how cells function. In cardiac muscle cells, close apposition of transverse (t)-tubule (TT) and sarcoplasmic reticulum (SR) membranes supports stable high-gain excitation-contraction coupling. Here, the fine structure of this key intracellular element is examined in rabbit and mouse ventricular cardiomyocytes, using ultra-rapid high-pressure freezing (HPF, omitting aldehyde fixation) and electron microscopy.

Socioecological indicators of senior financial exploitation: an application of data science to 8,800 substantiated mistreatment cases.

Senior financial exploitation (FE) is prevalent and harmful. Its often insidious nature and co-occurrence with other forms of mistreatment make detection and substantiation challenging. A secondary data analysis of N = 8,800 Adult Protective Services substantiated senior mistreatment cases, using machine learning algorithms, was conducted to determine when pure FE versus hybrid FE was occurring.

Arrhythmogenic late Ca sparks in failing heart cells and their control by action potential configuration.

Sudden death in heart failure patients is a major clinical problem worldwide, but it is unclear how arrhythmogenic early afterdepolarizations (EADs) are triggered in failing heart cells. To examine EAD initiation, high-sensitivity intracellular Ca measurements were combined with action potential voltage clamp techniques in a physiologically relevant heart failure model. In failing cells, the loss of Ca release synchrony at the start of the action potential leads to an increase in number of microscopic intracellular Ca release events ("late" Ca sparks) during phase 2-3 of the action potential.

Follistatin-based ligand trap ACE-083 induces localized hypertrophy of skeletal muscle with functional improvement in models of neuromuscular disease.

Skeletal muscle is under inhibitory homeostatic regulation by multiple ligands of the transforming growth factor-β (TGFβ) superfamily. Follistatin is a secreted protein that promotes muscle growth and function by sequestering these ligands extracellularly. In the present study, we evaluated the potential of ACE-083 - a locally acting, follistatin-based fusion protein - as a novel therapeutic agent for focal or asymmetric myopathies.

Is Interpersonal Abuse Associated with Sexual (Dis)satisfaction among Postmenopausal Women?

Purpose: To investigate associations between past-year verbal and/or physical abuse (VA/PA) and sexual (dis)satisfaction, that is, global or frequency-related (dis)satisfactions with sexual activity, among postmenopausal women in the Women's Health Initiative.

Procedures: A cross-sectional analysis of archival data was performed from the subset of 83,329 Women's Health Initiative participants (clinical trial and/or observational study components) who reported sexual activity in the year before baseline. Associations between VA/PA and global frequency (dis)satisfactions were modeled using logistic regression.

Cardiac-specific overexpression of caveolin-3 preserves t-tubular I during heart failure in mice.

New Findings: What is the central question of this study? What is the cellular basis of the protection conferred on the heart by overexpression of caveolin-3 (Cav-3 OE) against many of the features of heart failure normally observed in vivo? What is the main finding and its importance? Cav-3 overexpression has little effect in normal ventricular myocytes but reduces cellular hypertrophy and preserves t-tubular I , but not local t-tubular Ca release, in heart failure induced by pressure overload in mice. Thus Cav-3 overexpression provides specific but limited protection following induction of heart failure, although other factors disrupt Ca release.

Abstract: Caveolin-3 (Cav-3) is an 18 kDa protein that has been implicated in t-tubule formation and function in cardiac ventricular myocytes.

Follistatin-288-Fc Fusion Protein Promotes Localized Growth of Skeletal Muscle.

Follistatin is an endogenous glycoprotein that promotes growth and repair of skeletal muscle by sequestering inhibitory ligands of the transforming growth factor- superfamily and may therefore have therapeutic potential for neuromuscular diseases. Here, we sought to determine the suitability of a newly engineered follistatin fusion protein (FST288-Fc) to promote localized, rather than systemic, growth of skeletal muscle by capitalizing on the intrinsic heparin-binding ability of the follistatin-288 isoform. As determined by surface plasmon resonance and cell-based assays, FST288-Fc binds to activin A, activin B, myostatin (growth differentiation factor GDF8), and GDF11 with high affinity and neutralizes their activity in vitro.

Species differences in the morphology of transverse tubule openings in cardiomyocytes.

Aims: The ultrastructure of ventricular cardiomyocyte T-tubule connections with the outer cell surface ('mouth' regions) has been reported to differ between mice and rabbits. In mice, T-tubule mouths form convoluted narrow spaces filled with electron-dense matter that impedes diffusion between T-tubular lumen and bulk extracellular space. Here, we explore whether T-tubule mouths are also constricted in rat (another murine model used frequently for cardiac research) and whether pig and human T-tubule mouth configurations are structurally more similar to mice or rabbits.