Regulation of mitochondrial oxidative phosphorylation through tight control of cytochrome c oxidase in health and disease - Implications for ischemia/reperfusion injury, inflammatory diseases, diabetes, and cancer.

Mitochondria are essential to cellular function as they generate the majority of cellular ATP, mediated through oxidative phosphorylation, which couples proton pumping of the electron transport chain (ETC) to ATP production. The ETC generates an electrochemical gradient, known as the proton motive force, consisting of the mitochondrial membrane potential (ΔΨ, the major component in mammals) and ΔpH across the inner mitochondrial membrane. Both ATP production and reactive oxygen species (ROS) are linked to ΔΨ, and it has been shown that an imbalance in ΔΨ beyond the physiological optimal intermediate range results in excessive ROS production.

Phosphorylations and Acetylations of Cytochrome Control Mitochondrial Respiration, Mitochondrial Membrane Potential, Energy, ROS, and Apoptosis.

Cytochrome (Cyt) has both life-sustaining and cellular death-related functions, depending on subcellular localization. Within mitochondria, Cyt acts as a single electron carrier as part of the electron transport chain (ETC). When released into the cytosol after cellular insult, Cyt triggers the assembly of the apoptosome, committing the cell to intrinsic apoptosis.

High Sucrose Diet-Induced Subunit I Tyrosine 304 Phosphorylation of Cytochrome Oxidase Leads to Liver Mitochondrial Respiratory Dysfunction in the Cohen Diabetic Rat Model.

The mitochondrial oxidative phosphorylation process generates most of the cellular energy and free radicals in mammalian tissues. Both factors play a critical role in numerous human diseases that could be affected by reversible phosphorylation events that regulate the function and activity of the oxidative phosphorylation complexes. In this study, we analyzed liver mitochondria of Cohen diabetes-sensitive (CDs) and Cohen diabetes-resistant (CDr) rats, using blue native gel electrophoresis (BN-PAGE) in combination with mitochondrial activity measurements and a site-specific tyrosine phosphorylation implicated in inflammation, a known driver of diabetes pathology.

Complex patch geometry promotes species coexistence through a reverse competition-colonization trade-off.

Explaining the maintenance of diverse species assemblages is a central goal of ecology and conservation. Recent coexistence mechanisms highlight the role of dispersal as a source of the differences that allow similar species to coexist. Here, we propose a new mechanism for species coexistence that is based on dispersal differences, and on the geometry of the habitat patch.

Developing the VA Geriatric Scholars Programs' Clinical Dashboards Using the PDSA Framework for Quality Improvement.

Background: Involving clinician end users in the development process of clinical dashboards is important to ensure that user needs are adequately met prior to releasing the dashboard for use. The challenge with following this approach is that clinician end users can undergo periodic turnover, meaning, the clinicians that played a role in the initial development process may not be the same individuals that use the dashboard in future.

Objectives: Here, we summarize our Plan, Do, Study, Act (PDSA)-guided clinical dashboard development process for the VA Geriatric Scholars Program (GSP) and the value of continuous, iterative development.

Sometimes less is more: inhibitory infrared light during early reperfusion calms hyperactive mitochondria and suppresses reperfusion injury.

Ischemic stroke affects over 77 million people annually around the globe. Due to the blockage of a blood vessel caused by a stroke, brain tissue becomes ischemic. While prompt restoration of blood flow is necessary to save brain tissue, it also causes reperfusion injury.

Cell-free DNA ultra-low-pass whole genome sequencing to distinguish malignant peripheral nerve sheath tumor (MPNST) from its benign precursor lesion: A cross-sectional study.

Background: The leading cause of mortality for patients with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome is the development of malignant peripheral nerve sheath tumor (MPNST), an aggressive soft tissue sarcoma. In the setting of NF1, this cancer type frequently arises from within its common and benign precursor, plexiform neurofibroma (PN). Transformation from PN to MPNST is challenging to diagnose due to difficulties in distinguishing cross-sectional imaging results and intralesional heterogeneity resulting in biopsy sampling errors.

Quality Improvement Intervention for Universal Lipid Screening in Children Aged 9 to 11 Years.

We performed a quality improvement intervention to increase universal lipid screening in well-child visits (age 9 to 11 years): 12-month preintervention; phase 1 (8 months) with provider education, group monthly chart review with feedback, and electronic health record cues to order lipids; and phase 2 (16 months) with electronic health record cues and examination room phlebotomy. Outcomes were compared with clinics having no intervention. In phase 1, immediate treatment effect on the regression line for provider behavior (proportion of visits with lipids ordered) showed 34% increase in intervention and 7% decrease in comparison clinics; patient behavior (phlebotomy completed) showed 19% increase in intervention and 5% decrease in comparison clinics.

C-Reactive Protein and Ferritin Are Associated With Organ Dysfunction and Mortality in Hospitalized Children.

Our objective was to determine if C-reactive protein (CRP) and ferritin values alone and in combination are associated with mortality among hospitalized children. All hospitalized patients at our institution with a CRP or ferritin assay in 2015 and 2016 were included. Area under the receiver operating curves (AUROC) were examined, optimal cut-points determined, and patients were stratified into low-, intermediate-, or high-risk groups based on elevation of zero, one, or both biomarkers.

Acute Neurologic Injury in Children Admitted to the Cardiac Intensive Care Unit.

Background: Children with acquired and congenital heart disease both have low mortality but an increased risk of neurologic morbidity that is multifactorial. Our hypothesis was that acute neurologic injuries contribute to mortality in such children and are an important cause of death.

Methods: All admissions to the pediatric cardiac intensive care unit (CICU) from January 2011 through January 2015 were retrospectively reviewed.

The Pediatric Emergency Care Applied Research Network Registry: A Multicenter Electronic Health Record Registry of Pediatric Emergency Care.

Background: Electronic health record (EHR)-based registries allow for robust data to be derived directly from the patient clinical record and can provide important information about processes of care delivery and patient health outcomes.

Methods: A data dictionary, and subsequent data model, were developed describing EHR data sources to include all processes of care within the emergency department (ED). ED visit data were deidentified and XML files were created and submitted to a central data coordinating center for inclusion in the registry.

Identification of Long Bone Fractures in Radiology Reports Using Natural Language Processing to support Healthcare Quality Improvement.

Background: Important information to support healthcare quality improvement is often recorded in free text documents such as radiology reports. Natural language processing (NLP) methods may help extract this information, but these methods have rarely been applied outside the research laboratories where they were developed.

Objective: To implement and validate NLP tools to identify long bone fractures for pediatric emergency medicine quality improvement.

MRI active guidewire with an embedded temperature probe and providing a distinct tip signal to enhance clinical safety.

Background: The field of interventional cardiovascular MRI is hampered by the unavailability of active guidewires that are both safe and conspicuous. Heating of conductive guidewires is difficult to predict in vivo and disruptive to measure using external probes. We describe a clinical-grade 0.

Active delivery cable tuned to device deployment state: enhanced visibility of nitinol occluders during preclinical interventional MRI.

Purpose: To develop an active delivery system that enhances visualization of nitinol cardiac occluder devices during deployment under real-time magnetic resonance imaging (MRI).

Materials And Methods: We constructed an active delivery cable incorporating a loopless antenna and a custom titanium microscrew to secure the occluder devices. The delivery cable was tuned and matched to 50Ω at 64 MHz with the occluder device attached.

Closed-chest transthoracic magnetic resonance imaging-guided ventricular septal defect closure in swine.

Objectives: The aim of this study was to close ventricular septal defects (VSDs) directly through the chest wall using magnetic resonance imaging (MRI) guidance, without cardiopulmonary bypass, sternotomy, or radiation exposure.

Background: Surgical, percutaneous, and hybrid management of VSD each have limitations and known morbidity.

Methods: Percutaneous muscular VSDs were created in 10 naive Yorkshire swine using a transjugular laser catheter.

Direct percutaneous left ventricular access and port closure: pre-clinical feasibility.

Objectives: This study sought to evaluate feasibility of nonsurgical transthoracic catheter-based left ventricular (LV) access and closure.

Background: Implanting large devices, such as mitral or aortic valve prostheses, into the heart requires surgical exposure and repair. Reliable percutaneous direct transthoracic LV access and closure would allow new nonsurgical therapeutic procedures.

A deflectable guiding catheter for real-time MRI-guided interventions.

Purpose: To design a deflectable guiding catheter that omits long metallic components yet preserves mechanical properties to facilitate therapeutic interventional MRI procedures.

Materials And Methods: The catheter shaft incorporated Kevlar braiding. A 180° deflection was attained with a 5-cm nitinol slotted tube, a nitinol spring, and a Kevlar pull string.

Limitations of closing percutaneous transthoracic ventricular access ports using a commercial collagen vascular closure device.

Introduction: Closed-chest access and closure of direct cardiac punctures may enable a range of therapeutic procedures. We evaluate the safety and feasibility of closing percutaneous direct ventricular access sites using a commercial collagen-based femoral artery closure device.

Methods: Yorkshire swine underwent percutaneous transthoracic left ventricular access (n = 13).

Cardiac repolarization instability during normal postnatal development.

Long QT syndrome is a disease characterized by abnormal lengthening of the QT interval and by sudden cardiac death. It is a disease of development, with the incidence of a sudden event increasing during childhood. Repolarization instability during postnatal development could make the substrate susceptible to a fatal arrhythmia.

Treatment with an estrogen receptor-beta-selective agonist is cardioprotective.

This study was designed to investigate whether treatment with an estrogen receptor-beta (ER-beta)-selective agonist (2,3-bis(4-hydroxyphenyl)-propionitrile, DPN) can provide cardioprotection in female mice lacking endogenous estrogen. To study the effect of ER-beta stimulation in ischemia-reperfusion injury, we treated ovariectomized (ovx) female mice with 0.1 mg/kg/day of 17beta-estradiol, 0.