Glucagon Receptor Antagonist for Heart Failure With Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is an emerging major unmet need and one of the most significant clinic challenges in cardiology. The pathogenesis of HFpEF is associated with multiple risk factors. Hypertension and metabolic disorders associated with obesity are the 2 most prominent comorbidities observed in patients with HFpEF.

Temporary Peripheral Nerve Stimulation as Treatment for Chronic Pain.

Introduction: Chronic pain is a growing problem across the world, and in the midst of an opioid epidemic, it is imperative that alternative treatment measures are identified to help alleviate the pain experienced by these patients. Chronic pain greatly affects ones quality of life and many patients do not experience adequate relief with conventional treatment measures. The purpose of this retrospective analysis is to assess the efficacy of peripheral nerve stimulation (PNS) therapy in adult patients suffering from chronic pain refractory to conventional treatment measures who underwent therapy on various anatomical locations.

Radiofrequency ablation of the occipital nerves for treatment of neuralgias and headache.

Objective: The purpose of this study was to retrospectively assess the efficacy of radiofrequency ablation (RFA) therapy as a treatment for occipital neuralgias and headaches at health clinics in the United States between January 1, 2015 and June 20, 2022. We hypothesize that RFA is a minimally invasive treatment that provides significant pain relief long-term for occipital neuralgias and associated headaches.

Methods: This retrospective analysis studies data collected from 277 occipital nerve RFA patients who had adequate pre-procedure and post-procedure follow-up for data analysis.

Cell-autonomous effect of cardiomyocyte branched-chain amino acid catabolism in heart failure in mice.

Parallel to major changes in fatty acid and glucose metabolism, defect in branched-chain amino acid (BCAA) catabolism has also been recognized as a metabolic hallmark and potential therapeutic target for heart failure. However, BCAA catabolic enzymes are ubiquitously expressed in all cell types and a systemic BCAA catabolic defect is also manifested in metabolic disorder associated with obesity and diabetes. Therefore, it remains to be determined the cell-autonomous impact of BCAA catabolic defect in cardiomyocytes in intact hearts independent from its potential global effects.

Lipid-independent activation of a muscle-specific PKCα splicing variant.

Protein kinase C-α (PKCα) plays a major role in a diverse range of cellular processes. Studies to date have defined the regulatory controls and function of PKCα entirely based upon the previously annotated ubiquitously expressed prototypical isoform. From RNA-seq-based transcriptome analysis in murine heart, we identified a previously unannotated PKCα variant produced by alternative RNA splicing.

Metal dependent protein phosphatase PPM family in cardiac health and diseases.

Protein phosphorylation and dephosphorylation is central to signal transduction in nearly every aspect of cellular function, including cardiovascular regulation and diseases. While protein kinases are often regarded as the molecular drivers in cellular signaling with high specificity and tight regulation, dephosphorylation mediated by protein phosphatases is also gaining increasing appreciation as an important part of the signal transduction network essential for the robustness, specificity and homeostasis of cell signaling. Metal dependent protein phosphatases (PPM, also known as protein phosphatases type 2C, PP2C) belong to a highly conserved family of protein phosphatases with unique biochemical and molecular features.

Oral 15-Hydroxyeicosatetraenoic Acid Induces Pulmonary Hypertension in Mice by Triggering T Cell-Dependent Endothelial Cell Apoptosis.

Pulmonary arterial hypertension (PAH) is a fatal disease characterized by increased mean pulmonary arterial pressure. Elevated plasma and lung concentrations of oxidized lipids, including 15-hydroxyeicosatetraenoic acid (15-HETE), have been demonstrated in patients with PAH and animal models. We previously demonstrated that feeding mice with 15-HETE is sufficient to induce pulmonary hypertension, but the mechanisms remain unknown.

Involvement of Low-Density Lipoprotein Receptor in the Pathogenesis of Pulmonary Hypertension.

Background Recently, we and others have reported a causal role for oxidized lipids in the pathogenesis of pulmonary hypertension (PH). However, the role of low-density lipoprotein receptor (LDL-R) in PH is not known. Methods and Results We examined the role of LDL-R in the development of PH and determined the efficacy of high-density lipoprotein mimetic peptide 4F in mitigating PH.

Experimental Pulmonary Hypertension Is Associated With Neuroinflammation in the Spinal Cord.

Rationale: Pulmonary hypertension (PH) is a rare but fatal disease characterized by elevated pulmonary pressures and vascular remodeling, leading to right ventricular failure and death. Recently, neuroinflammation has been suggested to be involved in the sympathetic activation in experimental PH. Whether PH is associated with neuroinflammation in the spinal cord has never been investigated.

Histological hallmarks and role of Slug/PIP axis in pulmonary hypertension secondary to pulmonary fibrosis.

Pulmonary hypertension secondary to pulmonary fibrosis (PF-PH) is one of the most common causes of PH, and there is no approved therapy. The molecular signature of PF-PH and underlying mechanism of why pulmonary hypertension (PH) develops in PF patients remains understudied and poorly understood. We observed significantly increased vascular wall thickness in both fibrotic and non-fibrotic areas of PF-PH patient lungs compared to PF patients.

A case of Hashimoto's encephalopathy: association with sensory ganglionopathy.

We report a case of Hashimoto's encephalopathy with prominent unsteadiness of gait. Nerve conduction studies and electromyographic findings were consistent with a sensory ganglionopathy. Symptoms and clinical findings resolved with high-dose corticosteroid therapy and paralleled the levels of anti-microsomal antibodies.

Recovery and prognosticators of paralysis in West Nile virus infection.

Previous studies have demonstrated that lesions of the anterior horn motor neurons are the primary pathology in patients with paralysis due to West Nile virus (WNV) infection. To characterize recovery and identify prognostic factors for the recovery of paralysis, we investigated 11 patients with electrophysiology testing and muscle biopsy, and one with autopsy. We found that limb weakness was markedly asymmetric and differed between upper and lower extremities, suggesting focal or segmental involvement of the spinal cord anterior horn.