Transseptal course of anomalous left main coronary artery originating from single right coronary orifice presenting as unstable angina.

Transseptal course of coronary artery has often been described as a benign entity; however, this report and literature analysis provides growing evidence of high risk of serious cardiovascular events in this anomaly. We present a case of unstable angina in a patient with anomalous common origin of left and right coronary arteries from a single coronary ostium at the right sinus of Valsalva, with subsequent transseptal course of the left main artery, review of relevant literature, and discussion of possible management options.

cUMP hydrolysis by PDE3B.

Previous results indicate that the phosphodiesterase PDE3B hydrolyzes cUMP. Also, almost 50 years ago, cUMP-hydrolytic activity was observed in rat adipose tissue. We intended to characterize the enzyme kinetics of PDE3B-mediated cUMP hydrolysis, to determine the PDE3B binding mode of cUMP, and to analyze cUMP hydrolysis in adipocyte preparations.

The Role of ExoY in an Acute Mouse Lung Infection Model.

The effector protein Exotoxin Y (ExoY) produced by is injected via the type III secretion system (T3SS) into host cells. ExoY acts as nucleotidyl cyclase promoting the intracellular accumulation of cyclic nucleotides. To what extent nucleotidyl cyclase activity contributes to the pathogenicity of ExoY and which mechanisms participate in the manifestation of lung infection is still unclear.

Health Care Utilization and Expenditures of Homeless Family Members Before and After Emergency Housing.

Objectives: To describe longitudinal health service utilization and expenditures for homeless family members before and after entering an emergency shelter.

Methods: We linked Massachusetts emergency housing assistance data with Medicaid claims between July 2008 and June 2015, constructing episodes of health care 12 months before and 12 months after families entered a shelter. We modeled emergency department visits, hospital admissions, and expenditures over the 24-month period separately for children and adults.

Exercise testing in patients with asymptomatic moderate or severe aortic stenosis.

Objective: To assess the safety and tolerability of treadmill exercise testing and the association of revealed symptoms with outcome in apparently asymptomatic patients with moderate to severe aortic stenosis (AS).

Methods: A retrospective cohort study of 316 patients (age 65±12 years, 67% men) with moderate and severe AS who underwent echocardiography and modified Bruce exercise treadmill tests (ETTs) at a specialist valve clinic. The outcome measures were aortic valve replacement (AVR), all-cause mortality or a composite of AVR and all-cause mortality.

Plasma methionine and risk of acute myocardial infarction: Effect modification by established risk factors.

Background And Aims: Methionine (Met) is an essential amino acid involved in methylation reactions and lipid metabolism. A Met-deficient diet may cause hepatic lipid accumulation, which is considered an independent risk factor for atherosclerosis. However, the prospective relationship between circulating Met and incident acute myocardial infarction (AMI) is unknown.

Fibrinogen and Neopterin Is Associated with Future Myocardial Infarction and Total Mortality in Patients with Stable Coronary Artery Disease.

Systemic fibrinogen and neopterin are related to inflammation. We investigated the prognostic utility and possible interactions of these biomarkers in stable coronary artery disease (SCAD) patients undergoing coronary angiography. We included 3,545 patients with suspected stable angina with a median follow-up of 7.

The ExoY phenotype of high-copy-number recombinants is not detectable in natural isolates.

The nucleotidyl cyclase ExoY is an effector protein of the type III secretion system of We compared the cyclic nucleotide production and lung disease phenotypes caused by the ExoY-overexpressing strain PA103Δ pUCP, its vector control strain PA103Δ pUCP18, its loss-of-function control PA103Δ pUCP K81M and natural ExoY-positive and ExoY-negative isolates in a murine acute airway infection model. Only the carrier of the plasmid produced high levels of cUMP and caused the most severe course of infection. The pathology ascribed to ExoY from studies using the high-copy-number plasmid on mammalian cells and was not observed with natural isolates.

Social Work's Role in Medicaid Reform: A Qualitative Study.

Objectives: To critically analyze social work's role in Medicaid reform.

Methods: We conducted semistructured interviews with 46 stakeholders from 10 US states that use a range of Medicaid reform approaches. We identified participants using snowball and purposive sampling.

Medication management in Minnesota schools: The need for school nurse-pharmacist partnerships.

Background: Pharmacist participation in school medication management (MM) is minimal. School nurses are responsible for increasingly complex medication administration and management in schools.

Objectives: The purpose of this study was to 1) assess the MM needs of school nurses in Minnesota, and 2) determine if and how interprofessional partnerships between nurses and pharmacists might optimize MM for students.

Neopterin as an Effect Modifier of the Cardiovascular Risk Predicted by Total Homocysteine: A Prospective 2-Cohort Study.

Background: Plasma total homocysteine (tHcy) is related to plasma neopterin, an indicator of interferon-γ-mediated immune activation, and both biomarkers positively predict cardiovascular risk. We examined whether the association between tHcy and subsequent risk of acute myocardial infarction (AMI) was modified by systemic concentrations of neopterin and C-reactive protein among patients with coronary heart disease.

Methods And Results: By Cox modeling, we explored the association between tHcy and risk of AMI in 4164 patients with suspected stable angina pectoris.

Association between Weight Change and Mortality in Community Living Older People Followed for Up to 14 Years. The Hordaland Health Study (HUSK).

Objectives: To study the importance of weight change with regard to mortality in older people.

Design: Prospective cohort study.

Participants: The cohort includes participants in the Hordaland Health Study, Norway, 1997-99 (N=2935, age 71-74 years) who had previously participated in a survey in 1992-93.

Lack of Histamine H-Receptor Expression Aggravates TNBS-Induced Acute Colitis Symptoms in Mice.

Inflammatory bowel diseases (IBD) are a growing health problem worldwide, severely affecting patients' life qualities and life expectancies. Therapeutic options, which are rare and focus on symptoms associated with the disease, suffer from increasing numbers of patients refractory to the established strategies. Thus, in order to generate new therapeutic regimens, the detailed understanding of the pathogenic mechanisms causing IBD is necessary.

Progressive hypoventilation due to mixed CD8 and CD4 lymphocytic polymyositis following tremelimumab - durvalumab treatment.

Background: The combination of CTLA-4 and PD-L1 inhibitors has a manageable adverse effect profile, although rare immune-related adverse events (irAE) can occur.

Case Presentation: We describe an autoimmune polymyositis following a partial response to combination tremelimumab and durvalumab for the treatment of recurrent lung adenocarcinoma. Radiography revealed significant reduction in all metastases; however, the patient developed progressive neuromuscular hypoventilation due to lymphocytic destruction of the diaphragmatic musculature.

Binding Kinetics and Pathways of Ligands to GPCRs.

Previously, drugs were developed focusing on target affinity and selectivity. However, it is becoming evident that the drug-target residence time, related to the off-rate, is an important parameter for successful drug development. The residence time influences both the on-rate and overall effectiveness of drugs.

Statistical Permutation-based Artery Mapping (SPAM): a novel approach to evaluate imaging signals in the vessel wall.

Background: Cardiovascular diseases are the leading cause of death worldwide. A prominent cause of cardiovascular events is atherosclerosis, a chronic inflammation of the arterial wall that leads to the formation of so called atherosclerotic plaques. There is a strong clinical need to develop new, non-invasive vascular imaging techniques in order to identify high-risk plaques, which might escape detection using conventional methods based on the assessment of the luminal narrowing.

cCMP and cUMP in Apoptosis: Concepts and Methods.

The cyclic nucleotides cAMP and cGMP are well-characterized second messenger molecules regulating many important intracellular processes, such as differentiation, proliferation, and apoptosis. The latter is a highly regulated process of programmed cell death wherein several regulatory proteins, like those belonging to the Bcl-2 family, are involved. The initiation of apoptosis is regulated by three different pathways: the intrinsic or mitochondrial, the extrinsic, and the ER stress pathway.

International Union of Basic and Clinical Pharmacology. CI. Structures and Small Molecule Modulators of Mammalian Adenylyl Cyclases.

Adenylyl cyclases (ACs) generate the second messenger cAMP from ATP. Mammalian cells express nine transmembrane AC (mAC) isoforms (AC1-9) and a soluble AC (sAC, also referred to as AC10). This review will largely focus on mACs.

Pharmacological Characterization of Human Histamine Receptors and Histamine Receptor Mutants in the Sf9 Cell Expression System.

A large problem of histamine receptor research is data heterogeneity. Various experimental approaches, the complex signaling pathways of mammalian cells, and the use of different species orthologues render it difficult to compare and interpret the published results. Thus, the four human histamine receptor subtypes were analyzed side-by-side in the Sf9 insect cell expression system, using radioligand binding assays as well as functional readouts proximal to the receptor activation event (steady-state GTPase assays and [S]GTPγS assays).

Inactivation of Non-canonical Cyclic Nucleotides: Hydrolysis and Transport.

This chapter addresses cNMP hydrolysis by phosphodiesterases (PDEs) and export by multidrug resistance associated proteins (MRPs). Both mechanisms are well-established for the canonical cNMPs, cAMP, and cGMP. Increasing evidence shows that non-canonical cNMPs (specifically cCMP, cUMP) are also PDE and MRP substrates.

cCMP and cUMP Across the Tree of Life: From cCMP and cUMP Generators to cCMP- and cUMP-Regulated Cell Functions.

The cyclic purine nucleotides cAMP and cGMP are well-established second messenger molecules that are generated by distinct nucleotidyl cyclases (NCs) and regulate numerous cell functions via specific effector molecules. In contrast, the existence of the cyclic pyrimidine nucleotides cCMP and cUMP has been controversial for many years. The development of highly specific and sensitive mass spectrometry methods has enabled the unequivocal detection and quantitation of cCMP and cUMP in biological systems.

PEEK versus titanium locking plates for proximal humerus fracture fixation: a comparative biomechanical study in two- and three-part fractures.

Introduction: The high rigidity of metal implants may be a cause of failure after fixation of proximal humerus fractures. Carbon fiber-reinforced polyetheretherketone (PEEK) plates with a modulus similar to human cortical bone may help to overcome this problem. The present study assesses the biomechanical behavior of a PEEK plate compared with a titanium locking plate.

cUMP hydrolysis by PDE3A.

As previously reported, the cardiac phosphodiesterase PDE3A hydrolyzes cUMP. Moreover, cUMP-degrading activity was detected in cow and dog hearts several decades ago. Our aim was to characterize the enzyme kinetic parameters of PDE3A-mediated cUMP hydrolysis and to investigate whether cUMP and cUMP-hydrolyzing PDEs are present in cardiomyocytes.