The Impact of Web-Based Continuing Medical Education Using Patient Simulation on Real-World Treatment Selection in Type 2 Diabetes: Retrospective Case-Control Analysis.

Background: Despite guidelines recommending the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in certain patients with type 2 diabetes (T2D), they are not being prescribed for many of these patients. Web-based continuing medical education (CME) patient simulations have been used to identify clinicians' practice gaps and improve clinical decision-making as measured within a simulation, but the impact of this format on real-world treatment has not been researched.

Objective: This study aimed to evaluate the effect of a simulation-based CME intervention on real-world use of GLP-1 RAs by endocrinologists and primary care physicians.

Viral Shedding in Mice following Intravenous Adenovirus Injection: Impact on Biosafety Classification.

There have been numerous advances in gene therapy and oncolytic virotherapy in recent years, especially with respect to cutting-edge animal models to test these novel therapeutics. With all of these advances, it is important to understand the biosafety risks of testing these vectors in animals. We performed adenovirus-based viral shedding studies in murine models to ascertain when it is appropriate to downgrade the animals from Biosafety Level (BSL) 2 to BSL 1 for experimental handling and transport.

Determinants of Hormone Replacement Therapy Knowledge and Current Hormone Replacement Therapy Use.

: The use of hormone replacement therapy (HRT) to treat menopausal symptoms has declined since the early 2000s, and little is known about the contemporary determinants of use in the United States. We aim to understand women's knowledge of HRT as a treatment of menopausal symptoms and to assess the factors associated with HRT use. Weighted multivariate logistic regression models evaluated the correlates of high HRT knowledge and current HRT use among a sample of 2,548 women aged ≥45 years who participated in an online survey between August 2019 and May 2020.

Behaviors Related to Medication Safety and Use During Pregnancy.

Most women take medication during pregnancy despite limited scientific evidence on safety. We investigated medication use, including changes in and reasons for changes in use during pregnancy, with attention to medication use in pregnant women with chronic conditions. We conducted an online survey of pregnant women aged ≥18 years ( = 1,226).

Clinician knowledge and behaviors related to the 4Ms framework of Age-Friendly Health Systems.

Background: The Age-Friendly Health Systems (AFHS) aims to improve the experience of care for adults aged 65 years and older through the 4Ms framework, an evidence-based approach to care planning that emphasizes what matters most to the older person, mentation, mobility, and medication. The aim of this study was to examine clinicians' attitudes, knowledge, and practices concerning AFHS and the 4Ms.

Methods: We surveyed U.

Unmasking Arrhythmogenic Hubs of Reentry Driving Persistent Atrial Fibrillation for Patient-Specific Treatment.

Background Atrial fibrillation (AF) driver mechanisms are obscured to clinical multielectrode mapping approaches that provide partial, surface-only visualization of unstable 3-dimensional atrial conduction. We hypothesized that transient modulation of refractoriness by pharmacologic challenge during multielectrode mapping improves visualization of hidden paths of reentrant AF drivers for targeted ablation. Methods and Results Pharmacologic challenge with adenosine was tested in ex vivo human hearts with a history of AF and cardiac diseases by multielectrode and high-resolution subsurface near-infrared optical mapping, integrated with 3-dimensional structural imaging and heart-specific computational simulations.

Silencing miR-370-3p rescues funny current and sinus node function in heart failure.

Bradyarrhythmias are an important cause of mortality in heart failure and previous studies indicate a mechanistic role for electrical remodelling of the key pacemaking ion channel HCN4 in this process. Here we show that, in a mouse model of heart failure in which there is sinus bradycardia, there is upregulation of a microRNA (miR-370-3p), downregulation of the pacemaker ion channel, HCN4, and downregulation of the corresponding ionic current, I, in the sinus node. In vitro, exogenous miR-370-3p inhibits HCN4 mRNA and causes downregulation of HCN4 protein, downregulation of I, and bradycardia in the isolated sinus node.

Impaired neuronal sodium channels cause intranodal conduction failure and reentrant arrhythmias in human sinoatrial node.

Mechanisms for human sinoatrial node (SAN) dysfunction are poorly understood and whether human SAN excitability requires voltage-gated sodium channels (Nav) remains controversial. Here, we report that neuronal (n)Nav blockade and selective nNav1.6 blockade during high-resolution optical mapping in explanted human hearts depress intranodal SAN conduction, which worsens during autonomic stimulation and overdrive suppression to conduction failure.

Human Atrial Fibrillation Drivers Resolved With Integrated Functional and Structural Imaging to Benefit Clinical Mapping.

Objectives: This study sought to improve atrial fibrillation (AF) driver identification by integrating clinical multielectrode mapping with driver fingerprints defined by high-resolution ex vivo 3-dimensional (3D) functional and structural imaging.

Background: Clinical multielectrode mapping of AF drivers suffers from variable contact, signal processing, and structural complexity within the 3D human atrial wall, raising questions on the validity of such drivers.

Methods: Sustained AF was mapped in coronary-perfused explanted human hearts (n = 11) with transmural near-infrared optical mapping (∼0.

Redundant and diverse intranodal pacemakers and conduction pathways protect the human sinoatrial node from failure.

The human sinoatrial node (SAN) efficiently maintains heart rhythm even under adverse conditions. However, the specific mechanisms involved in the human SAN's ability to prevent rhythm failure, also referred to as its robustness, are unknown. Challenges exist because the three-dimensional (3D) intramural structure of the human SAN differs from well-studied animal models, and clinical electrode recordings are limited to only surface atrial activation.

Adenosine-Induced Atrial Fibrillation: Localized Reentrant Drivers in Lateral Right Atria due to Heterogeneous Expression of Adenosine A1 Receptors and GIRK4 Subunits in the Human Heart.

Background: Adenosine provokes atrial fibrillation (AF) with a higher activation frequency in right atria (RA) versus left atria (LA) in patients, but the underlying molecular and functional substrates are unclear. We tested the hypothesis that adenosine-induced AF is driven by localized reentry in RA areas with highest expression of adenosine A1 receptor and its downstream GIRK (G protein-coupled inwardly rectifying potassium channels) channels (IK,Ado).

Methods: We applied biatrial optical mapping and immunoblot mapping of various atrial regions to reveal the mechanism of adenosine-induced AF in explanted failing and nonfailing human hearts (n=37).

BMP-2 expression correlates with local failure in head and neck squamous cell carcinoma.

Objective: Preclinical data show that exogenous administration of recombinant human bone morphogenetic protein-2 (rhBMP-2) to human oral carcinoma cell lines increases pathogenicity using a nude mouse model. The objectives of this study are to (1) describe the characteristics of baseline protein expression of BMP-2 in head and neck squamous cell carcinomas (HNSCC) and (2) determine if BMP-2 expression level correlates with worse oncologic outcomes.

Study Design: Retrospective analysis of previously harvested patient samples.

PDCD2 knockdown inhibits erythroid but not megakaryocytic lineage differentiation of human hematopoietic stem/progenitor cells.

Programmed cell death-2 (PDCD2) protein is enriched in embryonic, hematopoietic, and neural stem cells, however, its function in stem/progenitor cell differentiation is unclear. We investigated the effects of PDCD2 knockdown on the development and differentiation of hematopoietic progenitor cells (HPC). CD34(+) cells derived from normal human bone marrow and K562 leukemic cells were effectively transduced with short-hairpin RNA to knockdown PDCD2.

Treatment effects of rhBMP-2 on invasiveness of oral carcinoma cell lines.

Objective: To determine if recombinant human bone morphogenetic protein-2 (rhBMP-2) has biological effects on the invasiveness of human oral squamous cell carcinoma (OSCCA) cell lines.

Study Design: Laboratory investigation using six human OSCCA cell lines, with three cell lines having baseline gene expression of BMP-2 and three cell lines without baseline gene expression of BMP-2.

Methods: The invasiveness of each cell line was measured using a matrigel invasion assay with or without stimulation by rhBMP-2.

rhBMP-2 has adverse effects on human oral carcinoma cell lines in vivo.

Objectives/hypothesis: To establish the relevance of the bone morphogenetic protein (BMP) signaling pathway in human oral squamous cell carcinoma (OSCCA) cell lines and determine if there is a biologic impact of stimulating this pathway with recombinant human (rh) BMP-2.

Study Design: In vitro laboratory investigations and in vivo analysis using an orthotopic animal model for oral cancer.

Methods: Gene expression profiles for BMP-2 and components of the BMP-signaling pathway were determined using reverse transcriptase-polymerase chain reaction.

Expectations, validity, and reality in gene expression profiling.

Objective: To provide a critical overview of gene expression profiling methodology and discuss areas of future development.

Results: Gene expression profiling has been used extensively in biological research and has resulted in significant advances in the understanding of the molecular mechanisms of complex disorders, including cancer, heart disease, and metabolic disorders. However, translating this technology into genomic medicine for use in diagnosis and prognosis faces many challenges.

Urine metabolomics analysis for kidney cancer detection and biomarker discovery.

Renal cell carcinoma (RCC) accounts for 11,000 deaths per year in the United States. When detected early, generally serendipitously by imaging conducted for other reasons, long term survival is generally excellent. When detected with symptoms, prognosis is poor.

Microarray analysis.

Microarrays and related technologies have allowed investigators to ask biological questions in far greater detail than has previously been possible. Microarrays had a troubled beginning, but most of these problems resulted from the growing pains of this technology, which, like many new things, was initially more promise than delivery. Nevertheless, over the past few years, investigators have learned how to achieve optimal performance of technology, and now exciting discoveries are made using microarray-based research.

Optimal allocation of replicates for measurement evaluation studies.

Optimal experimental design is important for the efficient use of modern high-throughput technologies such as microarrays and proteomics. Multiple factors including the reliability of measurement system, which itself must be estimated from prior experimental work, could influence design decisions. In this study, we describe how the optimal number of replicate measures (technical replicates) for each biological sample (biological replicate) can be determined.

Stoichiometry of a pore mutation that abolishes picrotoxin-mediated antagonism of the GABAA receptor.

Picrotoxin, a potent antagonist of the inhibitory central nervous system GABAA and glycine receptors, is believed to interact with residues that line the central ion pore. These pore-lining residues are in the second transmembrane domain (TM2) of each of the five constituent subunits. One of these amino acids, a threonine at the 6' location, when mutated to phenylalanine, abolishes picrotoxin sensitivity.

Epistemological issues in omics and high-dimensional biology: give the people what they want.

Gene expression microarrays have been the vanguard of new analytic approaches in high-dimensional biology. Draft sequences of several genomes coupled with new technologies allow study of the influences and responses of entire genomes rather than isolated genes. This has opened a new realm of highly dimensional biology where questions involve multiplicity at unprecedented scales: thousands of genetic polymorphisms, gene expression levels, protein measurements, genetic sequences, or any combination of these and their interactions.

Sources of variation in Affymetrix microarray experiments.

Background: A typical microarray experiment has many sources of variation which can be attributed to biological and technical causes. Identifying sources of variation and assessing their magnitude, among other factors, are important for optimal experimental design. The objectives of this study were: (1) to estimate relative magnitudes of different sources of variation and (2) to evaluate agreement between biological and technical replicates.

Catechol-O-methyl-transferase functional polymorphism and nicotine dependence: an evaluation of nonreplicated results.

Review articles have focused attention on and cited possible reasons for the nonreplication of genetic association studies. Herein, we illustrate how one might work through these possible reasons to make a judgment about the most plausible reason(s) when faced with two or more studies which yield seemingly inconsistent results. In the first study, 342 treatment-seeking smokers were genotyped for the Val108Met polymorphism in the functional catechol-O-methyl-transferase (COMT) locus.

HDBStat!: a platform-independent software suite for statistical analysis of high dimensional biology data.

Background: Many efforts in microarray data analysis are focused on providing tools and methods for the qualitative analysis of microarray data. HDBStat! (High-Dimensional Biology-Statistics) is a software package designed for analysis of high dimensional biology data such as microarray data. It was initially developed for the analysis of microarray gene expression data, but it can also be used for some applications in proteomics and other aspects of genomics.