Diagnosis of type III von Willebrand disease in a standard dachshund.

Type III von Willebrand disease is a rare coagulopathy, with published reports only existing for four canine breeds - Dutch Kooiker Hounds, Shetland Sheepdogs, Chesapeake Bay Retrievers and Scottish Terriers. A 2-year and 9-month-old male neutered standard dachshund was presented for hypovolaemic shock and a ventral neck mass. One previous bleeding episode following routine castration was reported.

No Difference in Short-Term Complications following Treatment of Closed Tibial Shaft Fractures with Intramedullary Nailing versus Plate Fixation.

Objectives: Tibial shaft fractures are treated with both intramedullary nailing (IMN) and plate fixation (ORIF). Using a large national database, we aimed to explore the differences in thirty-day complication rates between IMN and ORIF.

Methods: Patients in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database who had undergone either tibial IMN or ORIF for closed fractures from 2010 to 2018 were identified using current procedural terminology (CPT) codes.

Direct real-time measurements of superoxide release from skeletal muscles in rat limbs and human blood platelets using an implantable Cytochrome C microbiosensor.

Oxidative stress and excessive accumulation of the superoxide (O) anion are at the genesis of many pathological conditions and the onset of several diseases. The real time monitoring of (O) release is important to assess the extent of oxidative stress in these conditions. Herein, we present the design, fabrication and characterization of a robust (O) biosensor using a simple and straightforward procedure involving deposition of a uniform layer of L-Cysteine on a gold wire electrode to which Cytochrome C (Cyt c) was conjugated.

Predicting five-year mortality in soft-tissue sarcoma patients.

Aims: The aim of this study was to identify factors associated with five-year cancer-related mortality in patients with limb and trunk soft-tissue sarcoma (STS) and develop and validate machine learning algorithms in order to predict five-year cancer-related mortality in these patients.

Methods: Demographic, clinicopathological, and treatment variables of limb and trunk STS patients in the Surveillance, Epidemiology, and End Results Program (SEER) database from 2004 to 2017 were analyzed. Multivariable logistic regression was used to determine factors significantly associated with five-year cancer-related mortality.

Prediction of Non-Home Discharge Following Total Hip Arthroplasty in Geriatric Patients.

Introduction: The majority of total hip arthroplasty (THA) patients are discharged home postoperatively, however, many still require continued medical care. We aimed to identify important characteristics that predict nonhome discharge in geriatric patients undergoing THA using machine learning. We hypothesize that our analyses will identify variables associated with decreased functional status and overall health to be predictive of non-home discharge.

Safety, pharmacokinetics and CNS distribution of tralesinidase alfa administered via intracerebroventricular infusion to juvenile cynomolgus monkeys.

Mucopolysaccharidosis Type IIIB (MPS IIIB) is an ultrarare, fatal pediatric disease with no approved therapy. It is caused by mutations in the gene encoding for lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). Tralesinidase alfa (TA) is a fusion protein comprised of recombinant NAGLU and a modified human insulin-like growth factor 2 that is being developed as an enzyme replacement therapy for MPS IIIB.

Quantifying Radiation Doses in Common Endoscopic Retrograde Cholangiopancreatography Scenarios: An Evaluation of Radiation Safety Measures in a Real-World Environment.

Introduction Radiation safety training remains variable among gastroenterologists performing endoscopic retrograde cholangiopancreatography (ERCP). This study sought to ascribe dosimeter readings to various real-world ERCP scenarios to provide data supporting the 3 pillars of radiation safety: distance, time, and shielding. Methods An ERCP fluoroscopy unit was used to generate radiation scatter from 2 differently sized anthropomorphic phantoms.

Tralesinidase Alfa Enzyme Replacement Therapy Prevents Disease Manifestations in a Canine Model of Mucopolysaccharidosis Type IIIB.

Mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome B; OMIM #252920) is a lethal, pediatric, neuropathic, autosomal recessive, and lysosomal storage disease with no approved therapy. Patients are deficient in the activity of N-acetyl-alpha-glucosaminidase (NAGLU; EC 3.2.

Multi-institution consensus paper for acquisition of portable chest radiographs through glass barriers.

Background: To conserve personal protective equipment (PPE) and reduce exposure to potentially infected COVID-19 patients, several Californian facilities independently implemented a method of acquiring portable chest radiographs through glass barriers that was originally developed by the University of Washington.

Methods: This work quantifies the transmission of radiation through a glass barrier using six radiographic systems at five facilities. Patient entrance air kerma (EAK) and effective dose were estimated both with and without the glass barrier.

Early postnatal exposure to a cafeteria diet interferes with recency and spatial memory, but not open field habituation in adolescent rats.

The cafeteria diet (CD), an experimental diet that mimics the obesogenic Western diet, can impair memory in adult rats. However, the suckling period is also particularly susceptible to diet-induced behavioural modification. Here, following exposure to CD feeding during lactation, 24- to 26-day-old offspring were tested to determine maternal dietary effects on either open field habituation, object location (OL) learning or on recency learning.

Central nervous system pathology in preclinical MPS IIIB dogs reveals progressive changes in clinically relevant brain regions.

Mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome B) is an autosomal recessive lysosomal storage disorder caused by the deficiency of alpha-N-acetylglucosaminidase activity, leading to increased levels of nondegraded heparan sulfate (HS). A mouse model has been useful to evaluate novel treatments for MPS IIIB, but has limitations. In this study, we evaluated the naturally occurring canine model of MPS IIIB for the onset and progression of biochemical and neuropathological changes during the preclinical stages (onset approximately 24-30 months of age) of canine MPS IIIB disease.

The Limited Role of Glucagon for Ketogenesis During Fasting or in Response to SGLT2 Inhibition.

Glucagon is classically described as a counterregulatory hormone that plays an essential role in the protection against hypoglycemia. In addition to its role in the regulation of glucose metabolism, glucagon has been described to promote ketosis in the fasted state. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a new class of glucose-lowering drugs that act primarily in the kidney, but some reports have described direct effects of SGLT2i on α-cells to stimulate glucagon secretion.

Translational studies of intravenous and intracerebroventricular routes of administration for CNS cellular biodistribution for BMN 250, an enzyme replacement therapy for the treatment of Sanfilippo type B.

BMN 250 is being developed as enzyme replacement therapy for Sanfilippo type B, a primarily neurological rare disease, in which patients have deficient lysosomal alpha-N-acetylglucosaminidase (NAGLU) enzyme activity. BMN 250 is taken up in target cells by the cation-independent mannose 6-phosphate receptor (CI-MPR, insulin-like growth factor 2 receptor), which then facilitates transit to the lysosome. BMN 250 is dosed directly into the central nervous system via the intracerebroventricular (ICV) route, and the objective of this work was to compare systemic intravenous (IV) and ICV delivery of BMN 250 to confirm the value of ICV dosing.

Glucagon lowers glycemia when β-cells are active.

Glucagon and insulin are commonly believed to have counteracting effects on blood glucose levels. However, recent studies have demonstrated that glucagon has a physiologic role to activate β-cells and enhance insulin secretion. To date, the actions of glucagon have been studied mostly in fasting or hypoglycemic states, yet it is clear that mixed-nutrient meals elicit secretion of both glucagon and insulin, suggesting that glucagon also contributes to glucose regulation in the postprandial state.

Performance Evaluation of Material Decomposition With Rapid-Kilovoltage-Switching Dual-Energy CT and Implications for Assessing Bone Mineral Density.

Objective: The purpose of this article is to quantitatively investigate the accuracy and performance of dual-energy CT (DECT) material density images and to calculate the areal bone mineral density (aBMD) for comparison with dual-energy x-ray absorptiometry (DEXA).

Materials And Methods: A rapid-kilovoltage-switching DECT scanner was used to create material density images of various two-material phantoms of known concentrations under different experimental conditions. They were subsequently also scanned by single-energy CT and DEXA.

Delayed contrast enhancement imaging of a murine model for ischemia reperfusion with carbon nanotube micro-CT.

We aim to demonstrate the application of free-breathing prospectively gated carbon nanotube (CNT) micro-CT by evaluating a myocardial infarction model with a delayed contrast enhancement technique. Evaluation of murine cardiac models using micro-CT imaging has historically been limited by extreme imaging requirements. Newly-developed CNT-based x-ray sources offer precise temporal resolution, allowing elimination of physiological motion through prospective gating.

Detection of aortic arch calcification in apolipoprotein E-null mice using carbon nanotube-based micro-CT system.

Background: We performed in vivo micro-computed tomography (micro-CT) imaging using a novel carbon nanotube (CNT)-based x-ray source to detect calcification in the aortic arch of apolipoprotein E (apoE)-null mice.

Methods And Results: We measured calcification volume of aortic arch plaques using CNT-based micro-CT in 16- to 18-month-old males on 129S6/SvEvTac and C57BL/6J genetic backgrounds (129-apoE KO and B6-apoE KO). Cardiac and respiratory gated images were acquired in each mouse under anesthesia.

Non-contact respiration monitoring for in-vivo murine micro computed tomography: characterization and imaging applications.

A cone beam micro-CT has previously been utilized along with a pressure-tracking respiration sensor to acquire prospectively gated images of both wild-type mice and various adult murine disease models. While the pressure applied to the abdomen of the subject by this sensor is small and is generally without physiological effect, certain disease models of interest, as well as very young animals, are prone to atelectasis with added pressure, or they generate too weak a respiration signal with this method to achieve optimal prospective gating. In this work we present a new fibre-optic displacement sensor which monitors respiratory motion of a subject without requiring physical contact.

Metabolic activation of mefenamic acid leading to mefenamyl-S-acyl-glutathione adduct formation in vitro and in vivo in rat.

Carboxylic acid-containing nonsteroidal anti-inflammatory drugs (NSAIDs) can be metabolized to chemically reactive acyl glucuronide and/or S-acyl-CoA thioester metabolites capable of transacylating GSH. We investigated the metabolism of the NSAID mefenamic acid (MFA) to metabolites that transacylate GSH, leading to MFA-S-acyl-GSH thioester (MFA-SG) formation in incubations with rat and human hepatocytes and in vivo in rat bile. Thus, incubation of MFA (1-500 μM) with rat hepatocytes led to the detection of MFA-1-β-O-acyl glucuronide (MFA-1-β-O-G), MFA-S-acyl-CoA (MFA-SCoA), and MFA-SG by liquid chromatography-tandem mass spectrometric analysis.

Discovery of AMG 853, a CRTH2 and DP Dual Antagonist.

Prostaglandin D2 (PGD2) plays a key role in mediating allergic reactions seen in asthma, allergic rhinitis, and atopic dermatitis. PGD2 exerts its activity through two G protein-coupled receptors (GPCRs), prostanoid D receptor (DP or DP1), and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2 or DP2). We report the optimization of a series of phenylacetic acid derivatives in an effort to improve the dual activity of AMG 009 against DP and CRTH2.

Stereoselective flunoxaprofen-S-acyl-glutathione thioester formation mediated by acyl-CoA formation in rat hepatocytes.

Flunoxaprofen (FLX) is a chiral nonsteroidal anti-inflammatory drug that was withdrawn from clinical use because of concerns of potential hepatotoxicity. FLX undergoes highly stereoselective chiral inversion mediated through the FLX-S-acyl-CoA thioester (FLX-CoA) in favor of the (R)-(-)-isomer. Acyl-CoA thioester derivatives of acidic drugs are chemically reactive species that are known to transacylate protein nucleophiles and glutathione (GSH).

Behaviour profiles after tuberculous meningitis.

The purpose of the study was to investigate child behaviour in children who recovered from tuberculous meningitis (TBM) and to compare behaviour profiles of stage II and stage III patients. The mean age of the cohort of 74 children at the time of evaluation was 10 years and 7 months. At follow-up all patients underwent a thorough neurological examination and a psychometric test battery, which included intellectual assessment and evaluation of behaviour by means of the CBCL/6-18.

Psychological adjustment to conjugal bereavement: do social networks aid coping following spousal death?

This research sought to investigate the role of social networks in coping and adjustment to spousal bereavement. A total of 198 Xhosa-speaking participants, drawn from the rural areas of the Eastern Cape Province, South Africa, took part in the study. Quantitative data analyses revealed significant correlations between perceived social support on Social Support Appraisals scale and the anxiety scores on the Beck Depression Inventory-Second Edition and the problem-solving coping strategy scale on the Coping Strategy Indicator.

Metabolism of [14C]gemopatrilat after oral administration to rats, dogs, and humans.

This study describes the pharmacokinetic parameters of gemopatrilat, a potent vasopeptidase inhibitor, in humans and the comparative biotransformation of the compound in rats, dogs, and humans after administration of a single oral dose of [14C]gemopatrilat. Gemopatrilat was rapidly absorbed in humans with an oral bioavailability of 49%. Within 5 h after dose, the mean concentrations of gemopatrilat were less than 1% of the mean Cmax values.