Cardiorespiratory profiling reveals primary breathing dysfunction in Kcna1-null mice: Implications for sudden unexpected death in epilepsy.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality, but the relative importance of underlying cardiac and respiratory mechanisms remains unclear. To illuminate the interactions between seizures, respiration, cardiac function, and sleep that contribute to SUDEP risk, here we developed a mouse epilepsy monitoring unit (EMU) to simultaneously record video, electroencephalography (EEG), electromyography (EMG), plethysmography, and electrocardiography (ECG) in a commonly used genetic model of SUDEP, the Kcna1 knockout (Kcna1) mouse. During interictal periods, Kcna1 mice exhibited an abnormal absence of post-sigh apneas and a 3-fold increase in respiratory variability.

Bioinformatics Analyses Determined the Distinct CNS and Peripheral Surrogate Biomarker Candidates Between Two Mouse Models for Progressive Multiple Sclerosis.

Previously, we have established two distinct progressive multiple sclerosis (MS) models by induction of experimental autoimmune encephalomyelitis (EAE) with myelin oligodendrocyte glycoprotein (MOG) in two mouse strains. A.SW mice develop ataxia with antibody deposition, but no T cell infiltration, in the central nervous system (CNS), while SJL/J mice develop paralysis with CNS T cell infiltration.

Potential therapeutic roles of stem cells in ischemia-reperfusion injury.

Ischemia-reperfusion injury (I/RI), produced by an initial interruption of organ blood flow and its subsequent restoration, contributes significantly to the pathophysiologies of stroke, myocardial infarction, renal I/RI, intestinal I/RI and liver I/RI, which are major causes of disability (including transplant failure) and even mortality. While the restoration of blood flow is required to restore oxygen and nutrient requirements, reperfusion often triggers local and systemic inflammatory responses and subsequently elevate the ischemic insult where the duration of ischemia determines the magnitude of I/RI damage. I/RI increases vascular leakage, changes transcriptional and cell death programs, drives leukocyte entrapment and inflammation and oxidative stress in tissues.

Ischemia-Reperfusion Injury in Sickle Cell Disease: From Basics to Therapeutics.

Sickle cell disease (SCD) is one of the most common hereditary hemoglobinopathies worldwide, affecting almost 400,000 newborns globally each year. It is characterized by chronic hemolytic anemia and endothelial dysfunction, resulting in a constant state of disruption of the vascular system and leading to recurrent episodes of ischemia-reperfusion injury (I/RI) to multiple organ systems. I/RI is a fundamental vascular pathobiological paradigm and contributes to morbidity and mortality in a wide range of conditions, including myocardial infarction, stroke, acute kidney injury, and transplantation.

Dose-Dependent Influences of Ethanol on Ischemic Stroke: Role of Inflammation.

Chronic ethanol consumption dose-dependently affects both incidence and prognosis of ischemic stroke. Our goal was to determine whether the influence of chronic ethanol consumption on ischemic stroke is related to an altered inflammatory profile in the brain. Male C57BL/6J mice were divided into six groups and gavage fed with 0.

What and how are EM residents being taught to respond to the next disaster?

Objective: Disasters, both natural and man-made, have become commonplace and emergency physicians serve on the front line. Residency may be the only time that emergency physicians are exposed to a disaster, through training, until one happens in their department; therefore, it is critical to provide residents with appropriate and timely disaster education. The goal of this study was to assess the current status of disaster education in emergency medicine (EM) residencies in the United States.

The CDR1 and Other Regions of Immunoglobulin Light Chains are Hot Spots for Amyloid Aggregation.

Immunoglobulin light chain-derived (AL) amyloidosis is a debilitating disease without known cure. Almost nothing is known about the structural factors driving the amyloidogenesis of the light chains. This study aimed to identify the fibrillogenic hotspots of the model protein 6aJL2 and in pursuing this goal, two complementary approaches were applied.

Doxorubicin-induced cardiomyopathy associated with inhibition of autophagic degradation process and defects in mitochondrial respiration.

Doxorubicin (Dox) is a highly effective anticancer drug but cause acute ventricular dysfunction, and also induce late-onset cardiomyopathy and heart failure. Despite extensive studies, the pathogenic sequelae leading to the progression of Dox-associated cardiomyopathy remains unknown. We assessed temporal changes in autophagy, mitochondrial dynamics, and bioenergetics in mouse models of acute and chronic Dox-cardiomyopathy.

Novel Role of T Cells and IL-6 (Interleukin-6) in Angiotensin II-Induced Microvascular Dysfunction.

Hypertension is an established risk factor for subsequent cardiovascular diseases, with Ang II (angiotensin II) playing a major role in mediating thrombotic and inflammatory abnormalities. Although T cells and IL-6 (interleukin-6) play an important role in adaptive immune responses, little is known about their role(s) in the thromboinflammatory responses associated with Ang II. Here we show using intravital microscopy coupled with the light/dye injury model that Rag-1 deficient (Rag-1) and IL-6 deficient (IL-6) mice are afforded protection against Ang II-induced thrombosis.

Theiler's Virus-Mediated Immunopathology in the CNS and Heart: Roles of Organ-Specific Cytokine and Lymphatic Responses.

Theiler's murine encephalomyelitis virus (TMEV) induces different diseases in the central nervous system (CNS) and heart, depending on the mouse strains and time course, with cytokines playing key roles for viral clearance and immune-mediated pathology (immunopathology). In SJL/J mice, TMEV infection causes chronic TMEV-induced demyelinating disease (TMEV-IDD) in the spinal cord about 1 month post-inoculation (p.i.

Influence of low-dose alcohol consumption on post-ischemic inflammation: Role of cystathionine γ-lyase.

Low-dose alcohol consumption (LAC) has been shown to suppress post-ischemic inflammation and alleviate cerebral ischemia/reperfusion (I/R) injury. Cystathionine γ-Lyase (CSE) is one of the enzymes that endogenously produce hydrogen sulfide (HS), which has an anti-inflammatory property at low concentration. We determined the potential role of CSE in the protective effect of LAC.

Glucose-6-phosphate dehydrogenase deficiency increases cell adhesion molecules and activates human monocyte-endothelial cell adhesion: Protective role of l-cysteine.

Glucose-6-phosphate dehydrogenase is a major enzyme that supplies the reducing agent nicotinamide adenine dinucleotide phosphate hydrogen (NADPH), which is required to recycle oxidized/glutathione disulfide (GSSH) to reduced glutathione (GSH). G6PD-deficient cells are susceptible to oxidative stress and a deficiency of GSH. Endothelial dysfunction is characterized by the loss of nitric oxide (NO) bioavailability, which regulates leukocyte adhesion to endothelium.

Glutathione deficiency alters the vitamin D-metabolizing enzymes CYP27B1 and CYP24A1 in human renal proximal tubule epithelial cells and kidney of HFD-fed mice.

Chronic kidney disease (CKD) is a worldwide public health problem with an estimated prevalence of 8.2%. This study reports glutathione deficiency, excess oxidative stress, and altered vitamin D metabolism in the kidney of mice fed a high-fat diet (HFD).

Bone marrow metastases in salivary duct carcinoma of the parotid gland.

Salivary duct carcinoma (SDC) is a rare and extremely aggressive salivary gland cancer. An 81-year-old woman with SDC underwent a total parotidectomy with facial nerve sacrifice and a neck dissection. Following surgery, she was diagnosed with disseminated bone marrow metastases.

Routine DFT testing in patients undergoing ICD implantation does not improve mortality: A systematic review and meta-analysis.

Defibrillation threshold (DFT) testing has been an integral part of implantable cardioverter-defibrillator (ICD) implantation to confirm appropriate sensing of ventricular fibrillation and to establish an adequate safety margin for defibrillation. However, there is a lack of evidence regarding benefits of routine DFT testing. Therefore, we performed a meta-analysis to assess its mortality benefit.

Atrial Fibrillation Is Associated With Higher Overall Mortality in Patients With Implantable Cardioverter-Defibrillator: A Systematic Review and Meta-Analysis.

Background Implantable cardioverter-defibrillator ( ICD ) improves survival when used for primary or secondary prevention of sudden cardiac death. Whether the benefits of ICD in patients with atrial fibrillation ( AF) are similar to those with normal sinus rhythm ( NSR ) is not well established. The aim of this study is to investigate whether ICD patients with AF are at higher risk of mortality and appropriate shock therapy compared with patients with NSR .

Histone deacetylase inhibition disturbs the balance between ACE and chymase expression in endothelial cells: a potential mechanism of chymase activation in preeclampsia.

Chymase is a major angiotensin-converting enzyme (ACE)-independent angiotensin convertase, and its expression is upregulated in the maternal vascular endothelium in preeclampsia, a hypertensive disorder in human pregnancy. Increased chymase-dependent angiotensin II generation has been reported in several cardiovascular diseases, including atherosclerosis and aneurysmal lesions. However, it remains unclear how chymase is activated.

Inhibition of Epstein-Barr Virus Replication in Human Papillomavirus-Immortalized Keratinocytes.

Epstein-Barr virus (EBV) is implicated in the pathogenesis of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OSCC). EBV-associated cancers harbor a latent EBV infection characterized by a lack of viral replication and the expression of viral oncogenes. Cellular changes promoted by HPV are comparable to those shown to facilitate EBV latency, though whether HPV-positive cells support a latent EBV infection has not been demonstrated.

Cardiac Dysfunction in the Sigma 1 Receptor Knockout Mouse Associated With Impaired Mitochondrial Dynamics and Bioenergetics.

Background The Sigma 1 receptor (Sigmar1) functions as an interorganelle signaling molecule and elicits cytoprotective functions. The presence of Sigmar1 in the heart was first reported on the basis of a ligand-binding assay, and all studies to date have been limited to pharmacological approaches using less-selective ligands for Sigmar1. However, the physiological function of cardiac Sigmar1 remains unknown.

Cardiac Fibrosis in Proteotoxic Cardiac Disease is Dependent Upon Myofibroblast TGF -β Signaling.

Background Transforming growth factor beta ( TGF -β) is an important cytokine in mediating the cardiac fibrosis that often accompanies pathogenic cardiac remodeling. Cardiomyocyte-specific expression of a mutant αB-crystallin (Cry AB), which causes human desmin-related cardiomyopathy, results in significant cardiac fibrosis. During onset of fibrosis, fibroblasts are activated to the so-called myofibroblast state and TGF -β binding mediates an essential signaling pathway underlying this process.

A Morphometric Analysis for the Feasibility of Percutaneous Translacerum Access of the Internal Carotid Artery Based on Computed Tomography Angiography.

Background: The increasing frequency of elderly patients with severe tortuous anatomy, especially when combined with fibromuscular dysplasia, can make intracranial canalization severely difficult or impossible. Computed tomography angiography was used to determine the feasibility of accessing the internal carotid artery (ICA) via a percutaneous translacerum approach.

Methods: Twenty consecutive stroke activations with CT angiography were reconstructed in three-dimensional models to take measurements to assess if currently available technologies could safely provide access.

Guidance Molecules in Vascular Smooth Muscle.

Several highly conserved families of guidance molecules, including ephrins, Semaphorins, Netrins, and Slits, play conserved and distinct roles in tissue remodeling during tissue patterning and disease pathogenesis. Primarily, these guidance molecules function as either secreted or surface-bound ligands that interact with their receptors to activate a variety of downstream effects, including cell contractility, migration, adhesion, proliferation, and inflammation. Vascular smooth muscle cells, contractile cells comprising the medial layer of the vessel wall and deriving from the mural population, regulate vascular tone and blood pressure.