Subcellular Compartmentalization of Cyclic Adenosine Monophosphate in Heart Failure and Inotropic Pharmacology.

Cyclic adenosine monophosphate (cAMP) is a second messenger downstream of many G-protein coupled receptors, including the β1-adrenoceptor, which is the target of many clinically used inotropic agents. When the Gαs subunit of a heterotrimeric G-protein is activated, it causes a localized elevation of cAMP. The significance of the spatial distribution of the elevation in cAMP is increasingly recognized, as is the disturbance of these microdomains in diseased states.

Targeted delivery of a colchicine analogue provides synergy with ATR inhibition in cancer cells.

Despite significant preclinical promise as anticancer agents, vascular-disrupting agents have yet to fulfil their clinical potential due to systemic toxicities. ICT2588 is a tumour-selective MT1-MMP-targeted prodrug of azademethylcolchicine, ICT2552. We investigate activation of ICT2588 and subsequent release of ICT2552 in tumour cells, and examine its ability to induce G2/M cell cycle arrest.

A case of Bartonellosis presenting as a puzzling multisystem disorder complicated by nosocomial COVID-19 infection.

The most commonly considered infection with a species is cat-scratch disease caused by Here, we discuss a unique case of a 60-year-old man who presented with infection complicated by nosocomial COVID-19. He was admitted with a history of chest pain, persistent fever, rash and influenza-like symptoms. Positive serology confirmed diagnosis and the patient developed complications of pericardial effusion in addition to COVID-19 infection, requiring non-invasive ventilation and admission to the intensive care unit.

Biased Agonism: The Future (and Present) of Inotropic Support.

Biased agonism, which is the concept that different ligands activate different downstream signalling partners in different ratios to cause different functional effects, is yet to gain appropriate appreciation in the field of inotropic pharmacology. Biased agonism has already proven to be a clinically translatable technology in analgesic pharmacology, but this development is yet to be translated into inotropes. A better appreciation of bias in clinically used inotropes and a focus on bias when developing novel inotropes has the potential to lead to more targeted, personalized, and cleaner inotropes.

High-flow nasal cannula implementation has not reduced intubation rates for bronchiolitis in Canada.

Background And Objective: Bronchiolitis is the most common reason for admission to hospital in the first year of life, with increasing hospitalization rates in Canada. Respiratory support with high-flow nasal cannula (HFNC) is being routinely used in paediatric centres, though the evidence of efficacy is continuing to be evaluated. We examined the impact of HFNC on intubation rates, hospital and paediatric critical care unit (PCCU) length of stay (LOS), and PCCU admission rates in paediatric tertiary centres in Canada.

Recommendations for measuring whisker movements and locomotion in mice with sensory, motor and cognitive deficits.

Background: Previous studies have measured whisker movements and locomotion to characterise mouse models of neurodegenerative disease. However, these studies have always been completed in isolation, and do not involve standardized procedures for comparisons across multiple mouse models and background strains.

New Method: We present a standard method for conducting whisker movement and locomotion studies, by carrying out qualitative scoring and quantitative measurement of whisker movements from high-speed video footage of mouse models of Amyotrophic Lateral Sclerosis, Huntington's disease, Parkinson's disease, Alzheimer's disease, Cerebellar Ataxia, Somatosensory Cortex Development and Ischemic stroke.

Evaluation of Urology Residency Training and Perceived Resident Abilities in the United States.

Objective: To identify differences and potential deficiencies in urology residency training programs in the United States as they are perceived by residents/recent graduates and program directors.

Materials And Methods: A 45-question and 38-question survey was sent to chief residents/recent graduates and program directors, respectively, at all 120 US urology programs regarding prior medical education, urologic training curricula, and perceived surgical proficiency, among other topics.

Results: Survey response rate was 58% and 52% for residents and program directors, respectively.

Value of the Manual Dexterity Test as a Screening Tool for Dental School Admissions.

The Manual Dexterity Test (MDT) was originally developed in the 1940s as part of the American Dental Association's Dental Aptitude Test to assist in reducing high attrition rates in U.S. dental schools.

Characterisation of progressive motor deficits in whisker movements in R6/2, Q175 and Hdh knock-in mouse models of Huntington's disease.

Background: Motor dysfunction is a major component of the Huntington's disease (HD) phenotype, both in patients and animal models. Motor function in mice is usually measured using tests that involve a novel environment, or require a degree of learning, which creates potential confounds in animals, such as anxiety and/or learning.

New Method: We propose that studying whisker control provides a more naturalistic way to measure motor function in HD mice.

Effects of intraspecific diversity on survivorship, growth, and recruitment of the eastern oyster across sites.

Intraspecific diversity, particularly of foundation species, can significantly affect population, community, and ecosystem processes. Examining how genetic diversity relates to demographic traits provides a key mechanistic link from genotypic and phenotypic variation of taxa with complex life histories to their population dynamics. We conducted a field experiment to assess how two metrics of intraspecific diversity (cohort diversity, the number of independent juvenile cohorts created from different adult source populations, and genetic relatedness, genetic similarity among individuals within and across cohorts) affect the survivorship, growth, and recruitment of the foundation species Crassostrea virginica.

Drought Increases Consumer Pressure on Oyster Reefs in Florida, USA.

Coastal economies and ecosystems have historically depended on oyster reefs, but this habitat has declined globally by 85% because of anthropogenic activities. In a Florida estuary, we investigated the cause of newly reported losses of oysters. We found that the oyster reefs have deteriorated from north to south and that this deterioration was positively correlated with the abundance of carnivorous conchs and water salinity.

Diabetes in rat pregnancy alters renal calcium and magnesium reabsorption and bone formation in adult offspring.

Aims/hypothesis: We tested the hypothesis that diabetes in pregnancy can result in the in-utero reprogramming of renal calcium and magnesium handling and of bone formation in the offspring, which persists into adulthood.

Methods: Male offspring of streptozotocin-treated diabetic rats (OD rats) and of control non-diabetic animals (OC rats) were investigated as neonates and at 8, 12 and 16 weeks of age.

Results: Compared with OC rats, urinary calcium and magnesium output was significantly reduced in OD rats at every age studied; Na+ and K+ outputs were unaffected.

gamma-Linoleic acid and ascorbic acid ameliorate the effects of experimental diabetes on electrolyte and bone homeostasis in pregnant rats.

Experimental diabetes in rats is associated with excessive electrolyte loss in the urine, which is further accentuated by pregnancy, particularly of Ca. Supplementation with essential fatty acids and antioxidants has proven beneficial in treating several types of complications, including nephropathy. The present study investigated the effect of gamma-linoleic acid (GLA; 500 mg/kg per day; group DG) and ascorbate (290 mg/kg per day; group DA), alone and in combination (group DGA), as well as ascorbyl-GLA (790 mg/kg per day; group DASG), on urinary electrolyte output and skeletal composition in pregnant streptozotocin-diabetic rats.

Gamma-linoleic acid and ascorbate improves skeletal ossification in offspring of diabetic rats.

Maternal diabetes causes a range of complications in offspring, including reduced skeletal ossification. This study examined whether feeding gamma-linoleic acid (GLA) and ascorbate, alone or in combination, to diabetic pregnant rats improves skeletal development in their offspring. In addition, Ca(2+) concentration was monitored in maternal plasma and fetal tissue, as well as placental mRNA expression of calbindin-D(9k).

Digital radiography and film scanners: automating the transition to filmless radiology.

To facilitate the integration of digital radiography (DR) and legacy film/screen technology, we have devised a methodology for film digitization that optimizes workflow and integrates well with the picture archiving and communication system (PACS). This work was performed at Mercy Medical Center (Cedar Rapids, IA) using a film digitizer with built-in Digital Imaging and Communications in Medicine (DICOM) communication. The radiology department at Mercy has one DR system and three separate film/screen systems.

Functional, molecular, and biochemical characterization of streptozotocin-induced diabetes.

Altered divalent cation homeostasis with bone mineral loss, hypercalciuria, and hypomagnesemia have been associated consistently with human diabetes mellitus. This study investigated functional, molecular, and biochemical determinants that accompany this condition in chronically (2 wk) streptozotocin (STZ)-diabetic rats. Catheterized, conscious, diabetic rats on servo-controlled fluid replacement exhibited an increased GFR (+70%) and a substantially raised urinary calcium output (+568%) when compared with control rats.

Failure of short-term gamma-linolenic acid treatment to reduce urinary calcium loss of diabetic rats.

Calcium re-absorption in the kidney is impaired in streptozotocin (STZ) diabetic rats, thereby causing hypercalciuria. Increased calcium loss starts within 1-2 days after induction of diabetes and reaches a plateau after 2 weeks. The excessive calcium excretion was previously shown to be reduced by treatment with gamma-linolenic acid (GLA) or evening primrose oil rich in GLA.

Upgrading legacy systems for the Integrating the Healthcare Enterprise (IHE) initiative.

As technology vendors have adopted standardized communication protocols, including Digital Imaging and Communications in Medicine (DICOM) and Health Level 7 (HL7), interconnectivity between various devices has been simplified. The recent Integrating the Healthcare Enterprise (IHE) initiative will further promote the use of standards for interconnectivity. Until these standards are universally accepted, we must live in a transitional world where some components will communicate without any modification, while others require upgrades to allow them to meet the new standards.

The web browser as a unifying agent for radiology and the health care enterprise.

A variety of information systems in the health care enterprise are used to store patient information. The hospital information system (HIS), the picture archiving and communications system (PACS), the radiology information systems (RIS), and patient records, for example, are often supported by separate and distinct systems. A referring physician reviewing a radiologist's report often does not have convenient access to the original radiologic images.

Localization of the nephron site of gentamicin-induced hypercalciuria in the rat: a micropuncture study.

In vivo renal micropuncture techniques were used to locate the nephron site of hypercalciuria induced by acute gentamicin infusion in anaesthetized Sprague Dawley rats. Three series of experiments were conducted. The effect of gentamicin on calcium reabsorption in the proximal tubule (Series I) and loop of Henle (Series II) was investigated using in vivo microperfusion whereas the effect on distal calcium handling (Series III) was studied using in vivo microinfusion.

Altered calbindin mRNA expression and calcium regulating hormones in rat diabetic pregnancy.

Offspring of rats with diabetes mellitus are at risk of reduced calcium and bone mineral content. Altered expression of the maternal calcium binding proteins, calbindin-D(9K) and calbindin-D(28K), which are involved in renal and placental calcium transport, may underlie these problems.We have investigated the effect of diabetes on circulating concentrations of regulatory hormones with respect to calbindin-D mRNA concentrations.

Renal function in chronically catheterized conscious diabetic rats using constant and servo-controlled infusion.

1. Infusion experiments were performed on chronically catheterized conscious rats to assess kidney function before and after the induction of diabetes mellitus with streptozotocin. 2.

Interfacing the radiology information system to the modality: an integrated approach.

The radiology information system (RIS) provides patient and examination information that is used in setting up and performing a radiologic procedure. In a digital imaging environment, information from the RIS can also be used to populate fields in the Digital Imaging and Communications in Medicine (DICOM) image header. Ideally, information from the RIS should be available at the modality at the time of the examination, and automatically be attached to the image in the appropriate DICOM fields before storage in the picture archiving and communications system (PACS).