Von Willebrand factor targeted thrombolysis in canine basilar artery occlusion.

Background And Purpose: Posterior circulation strokes, accounting for 20% of acute ischemic strokes, significantly contribute to morbidity and mortality. Fibrinolysis by rtPA improves outcomes in stroke but the risk of intracranial hemorrhage limits benefit. Arterial recanalization of basilar artery occlusion by thrombolysis or endovascular thrombectomy improves outcomes in posterior circulation strokes.

The process and outcomes of chronic low back pain treatment provided by osteopathic and allopathic physicians: a retrospective cohort study.

Context: Osteopathic physicians are trained to treat patients with musculoskeletal symptoms, to treat somatic dysfunction with osteopathic manipulative treatment (OMT), and to avoid unnecessarily prescribing drugs such as opioids. It is also generally believed that osteopathic physicians provide a unique patient-centered approach to medical care that involves effective communication and empathy. Such training and characteristics of osteopathic medical care (OMC) may enhance clinical outcomes among patients with chronic pain.

A canine thromboembolic model of anterior circulation large vessel occlusion stroke.

Purpose: To develop a large animal preclinical model of thromboembolic stroke with stable, protracted large vessel occlusion (LVO) utilizing an autologous clot.

Materials And Methods: A reproducible canine model of large vessel occlusion stroke was established by endovascular placement of an autologous clot into the middle cerebral artery (MCA) of six adult hounds and confirmed using digital subtraction angiography (DSA). Infarct volume and evidence of hemorrhage were determined by magnetic resonance imaging (MRI) 7 h after occlusion and Thrombolysis in Cerebral Infarction scale (TICI) was assessed before and after clot placement and at 1, 6, 7, and 9 h after middle cerebral artery occlusion (MCAO).

Magnetic Resonance Elastography (MRE) of Bleomycin-Induced Pulmonary Fibrosis in an Animal Model.

Background: Idiopathic pulmonary fibrosis is responsible for 40,000 deaths annually in the United States. A hallmark of idiopathic pulmonary fibrosis is elevated collagen deposition, which alters lung stiffness. Clinically relevant ways to measure changes in lung stiffness during pulmonary fibrosis are not available, and new noninvasive imaging methods are needed to measure changes in lung mechanical properties.

Ten-year incidence and treatment outcomes of closed degloving injuries (Morel-Lavallee lesions) in a level 1 trauma centre.

Introduction: Morel-Lavallée lesions (MLL), also referred to as closed degloving injuries, result from traumatic shearing forces with separation of the subcutaneous fat from the underlying fascia. The aim of this study was to determine the incidence and treatment of MLLs at a level 1 trauma centre.

Methods: Single-centre retrospective cross-sectional study of consecutive patients with an imaging diagnosis of a Morel-Lavallee lesion from 1/1/2010-31/12/2019.

Derivation and validation of a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality in 20 countries.

Introduction: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings.

Methods: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries.

Continual cerebrospinal fluid sampling in the neonatal domestic piglet for biomarker and discovery studies.

Background: Longitudinal access to cerebrospinal fluid (CSF) is useful for biomarker discovery in neurological disorders or diseases affecting CSF composition. Here, we aim to test a new method for insertion of a permanent intrathecal catheter, facilitating longitudinal collection of CSF.

New Method: We surgically placed a permanent intrathecal catheter into the cisterna magna of anesthetized neonatal piglets.

Risk Stratification of Elderly Patients Undergoing Spinal Surgery Using the Modified Frailty Index.

Study Design: Retrospective cohort.

Objectives: To validate the 11-item modified Frailty Index (mFI) as a perioperative risk stratification tool in elderly patients undergoing spine surgery.

Methods: All consecutive cases of spine surgery in patients aged 65 years or older between July 2016 and June 2018 at a state-wide trauma center were retrospectively reviewed.

Quantification of Cerebral Perfusion using Laser Speckle Imaging and Infarct Volume using MRI in a Pre-clinical Model of Posterior Circulation Stroke.

Background: Basilar artery occlusion (BAO) is a subset of posterior circulation stroke that carries a mortality as high as 90%.  The current clinical standard to diagnose ischemic stroke include computerized tomography (CT), CT angiography and perfusion and magnetic resonance imaging (MRI). Large animal pre-clinical models to accurately reflect the clinical disease as well as methods to assess stroke burden and evaluate treatments are lacking.

In Vivo Aortic Magnetic Resonance Elastography in Abdominal Aortic Aneurysm: A Validation in an Animal Model.

Objectives: Using maximum diameter of an abdominal aortic aneurysm (AAA) alone for management can lead to delayed interventions or unnecessary urgent repairs. Abdominal aortic aneurysm stiffness plays an important role in its expansion and rupture. In vivo aortic magnetic resonance elastography (MRE) was developed to spatially measure AAA stiffness in previous pilot studies and has not been thoroughly validated and evaluated for its potential clinical value.

Evaluation of a novel esophageal retractor utilizing vacuum suction and mechanical force for deviating the esophagus.

Background: Deviation of the esophagus prevents esophageal injury during atrial fibrillation ablation.

Objectives: This study is to evaluate, in animals, safety and effectiveness of a novel esophageal retractor that utilizes vacuum suction and mechanical force to deviate the esophagus.

Methods: Following general anesthesia, a radiopaque ruler was placed behind the animal perpendicular to the esophagus.

Myeloid Krüppel-Like Factor 2 Critically Regulates K/BxN Serum-Induced Arthritis.

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease, and Krüppel-like factor 2 (KLF2) regulates immune cell activation and function. Herein, we show that in our experiments 50% global deficiency of KLF2 significantly elevated arthritic inflammation and pathogenesis, osteoclastic differentiation, matrix metalloproteinases (MMPs), and inflammatory cytokines in K/BxN serum-induced mice. The severities of RA pathogenesis, as well as the causative and resultant cellular and molecular factors, were further confirmed in monocyte-specific KLF2 deficient mice.

The Effect of Microbial Endophyte Consortia on and Survival, Growth, and Physiology Across Edaphic Gradients.

Increased frequency of droughts and degraded edaphic conditions decreases the success of many reforestation efforts in the Pacific Northwest. Microbial endophyte consortia have been demonstrated to contribute to plant growth promotion and protection from abiotic and biotic stresses - specifically drought conditions - across a number of food crops but for limited tree species. Our research aimed to investigate the potential to improve establishment of economically and ecologically important conifers through a series of field trials and simulations.

Nanofiber-expanded human CD34 cells heal cutaneous wounds in streptozotocin-induced diabetic mice.

Despite advances in diabetic wound care, the significant number of amputations that occur every year demands more effective therapeutics. Herein, we offer an aminated polyethersulfone nanofiber-expanded human umbilical cord blood-derived CD34 cells (henceforth CD34 cells) effective therapy, tested in cutaneous wounds developed in streptozotocin-induced diabetic NOD/SCID mice. We show that systemic administration of CD34 cells homed to the wound site and significantly accelerated wound closure.

Preclinical Development of a vWF Aptamer to Limit Thrombosis and Engender Arterial Recanalization of Occluded Vessels.

Endothelial surface and circulating glycoprotein von Willebrand factor (vWF) regulates platelet adhesion and is associated with thrombotic diseases, including ischemic stroke, myocardial infarction, and peripheral vascular disease. Thrombosis, as manifested in these diseases, is the leading cause of disability and death in the western world. Current parenteral antithrombotic and thrombolytic agents used to treat these conditions are limited by a short therapeutic window, irreversibility, and major risk of hemorrhage.

Pharmacist-Led Drug Therapy Problem Management in an Interprofessional Geriatric Care Continuum: A Subset of the PIVOTS Group.

Background: Drug therapy problems, which are adverse events involving medications that can ultimately interfere with a patient's therapeutic goals, occur frequently in older adults. If not identified, resolved, and prevented through clinical decision-making, drug therapy problems may negatively affect patient health outcomes.

Objective: To quantify the impact of pharmacist interventions on the care of older adults by identifying the most common drug therapy problems, the medications most often involved in these problems, and the actions taken by pharmacists to resolve these problems.

Induction of Krüppel-like factor 2 reduces K/BxN serum-induced arthritis.

Krüppel-like factor 2 (KLF2) critically regulates activation and function of monocyte, which plays important pathogenic role in progressive joint destruction in rheumatoid arthritis (RA). It is yet to be established the molecular basis of KLF2-mediated regulation of monocytes in RA pathogenesis. Herein, we show that a class of compound, HDAC inhibitors (HDACi) induced KLF2 expression in monocytes both in vitro and in vivo.

Ferutinin directs dental pulp-derived stem cells towards the osteogenic lineage by epigenetically regulating canonical Wnt signaling.

Osteoporosis is a silent systemic disease that causes bone deterioration, and affects over 10 million people in the US alone. This study was undertaken to develop a potential stem cell therapy for osteoporosis. We have isolated and expanded human dental pulp-derived stem cells (DPSCs), characterized them, and confirmed their multipotential differentiation abilities.

Ferric Chloride-induced Canine Carotid Artery Thrombosis: A Large Animal Model of Vascular Injury.

Occlusive arterial thrombosis leading to cerebral ischemic stroke and myocardial infarction contributes to ~13 million deaths every year globally. Here, we have translated a vascular injury model from a small animal into a large animal (canine), with slight modifications that can be used for pre-clinical screening of prophylactic and thrombolytic agents. In addition to the surgical methods, the modified protocol describes the step-by-step methods to assess carotid artery canalization by angiography, detailed instructions to process both the brain and carotid artery for histological analysis to verify carotid canalization and cerebral hemorrhage, and specific parameters to complete an assessment of downstream thromboembolic events by utilizing magnetic resonance imaging (MRI).

Prognosis of Acute Subdural Hematoma in the Elderly: A Systematic Review.

Acute subdural hematoma (aSDH) is among the most common injury types encountered by neurosurgeons, and carries a poor prognosis, particularly in the elderly. As the incidence of aSDH in the elderly population rises, identifying those patients who may benefit from operative intervention is crucial. This systematic review aimed to identify data on prognostic factors or indices, such as the modified frailty index, that may help predict outcome, and hence guide management.

Retention of stemness and vasculogenic potential of human umbilical cord blood stem cells after repeated expansions on PES-nanofiber matrices.

Despite recent advances in cardiovascular medicine, ischemic diseases remain a major cause of morbidity and mortality. Although stem cell-based therapies for the treatment of ischemic diseases show great promise, limited availability of biologically functional stem cells mired the application of stem cell-based therapies. Previously, we reported a PES-nanofiber based ex vivo stem cell expansion technology, which supports expansion of human umbilical cord blood (UCB)-derived CD133(+)/CD34(+) progenitor cells ∼225 fold.

Real-time, in vivo determination of dynamic changes in lung and heart tissue oxygenation using EPR oximetry.

The use of electron paramagnetic resonance (EPR) oximetry for oxygen measurements in deep tissues (>1 cm) is challenging due to the limited penetration depth of the microwave energy. To overcome this limitation, implantable resonators, having a small (0.5 mm diameter) sensory loop containing the oxygen-sensing paramagnetic material connected by a pair of twisted copper wire to a coupling loop (8-10 mm diameter), have been developed, which enable repeated measurements of deep-tissue oxygen levels (pO2, partial pressure of oxygen) in the brain and tumors of rodents.

Induction of ATM/ATR pathway combined with Vγ2Vδ2 T cells enhances cytotoxicity of ovarian cancer cells.

Many ovarian cancer cells express stress-related molecule MICA/B on their surface that is recognized by Vγ2Vδ2 T cells through their NKG2D receptor, which is transmitted to downstream stress-signaling pathway. However, it is yet to be established how Vγ2Vδ2 T cell-mediated recognition of MICA/B signal is transmitted to downstream stress-related molecules. Identifying targeted molecules would be critical to develop a better therapy for ovarian cancer cells.