Targeting DNMT3A-mediated oxidative phosphorylation to overcome ibrutinib resistance in mantle cell lymphoma.

The use of Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib achieves a remarkable clinical response in mantle cell lymphoma (MCL). Acquired drug resistance, however, is significant and affects long-term survival of MCL patients. Here, we demonstrate that DNA methyltransferase 3A (DNMT3A) is involved in ibrutinib resistance.

Predictive modeling of postpartum blood pressure spikes.

Background: Hypertensive disorders of pregnancy are one of the leading causes of maternal morbidity and mortality worldwide. Management of these conditions can pose many clinical dilemmas and can be particularly challenging during the immediate postpartum period. Models for predicting and managing postpartum hypertension are necessary to help address this clinical challenge.

What works in medication reconciliation: an on-treatment and site analysis of the MARQUIS2 study.

Background: The second Multicenter Medication Reconciliation Quality Improvement Study demonstrated a marked reduction in medication discrepancies per patient. The aim of the current analysis was to determine the association of patient exposure to each system-level intervention and receipt of each patient-level intervention on these results.

Methods: This study was conducted at 17 North American Hospitals, the study period was 18 months per site, and sites typically adopted interventions after 2-5 months of preintervention data collection.

External validation of a low fidelity dry-lab platform to enhance loupes surgical skills techniques for hypospadias repair.

Introduction: Hypospadias repair is an index pediatric urology procedure that requires trainee familiarity with surgical loupes. A previous low-fidelity, 6-step curriculum was proposed that deconstructed the most important steps of loupe surgery. We expanded on this curriculum with an intermediate-fidelity silicone hypospadias model and designed an abbreviated version of the 6-step curriculum to precede the hypospadias repair simulation.

CancelRx implementation: Observed changes to medication discontinuation workflows over time.

Introduction: When patients are seen in an ambulatory outpatient clinic, such as their primary care provider's office, the prescriber often stops or discontinues medications. Although medication discontinuations are documented in the clinic's health record, this information may not be communicated to the pharmacy. Within the last decade, CancelRx has attempted to address this issue by sending a message from the clinic to the pharmacy when a medication has been discontinued or changed.

Impact of CancelRx on discontinuation of controlled substance prescriptions: an interrupted time series analysis.

Background: Prescription opioid misuse is a serious national crisis; in 2018 the top drugs involved in prescription overdose deaths included pain medications (opioids), benzodiazepines, and stimulants. Health information technology (health IT) provides a means to address this crisis through technologies that streamline the prescribing and discontinuation process. CancelRx is a health IT function that communicates when medications, such as controlled substances, are discontinued at the clinic and therefore should not be filled at the pharmacy.

Diagnosis and Treatment of Right Heart Failure in Pulmonary Vascular Diseases: A National Heart, Lung, and Blood Institute Workshop.

Right ventricular dysfunction is a hallmark of advanced pulmonary vascular, lung parenchymal, and left heart disease, yet the underlying mechanisms that govern (mal)adaptation remain incompletely characterized. Owing to the knowledge gaps in our understanding of the right ventricle (RV) in health and disease, the National Heart, Lung, and Blood Institute (NHLBI) commissioned a working group to identify current challenges in the field. These included a need to define and standardize normal RV structure and function in populations; access to RV tissue for research purposes and the development of complex experimental platforms that recapitulate the environment; and the advancement of imaging and invasive methodologies to study the RV within basic, translational, and clinical research programs.

Droplet Size and Distribution of Nebulized 3% Sodium Chloride, Albuterol, and Epoprostenol by Phase Doppler Particle Analyzer.

Background: Aerosolized drug therapy administered to mechanically ventilated patients is a standard part of pulmonary critical care medicine. Aerosol particle size and distribution are important factors in the optimal delivery of aerosolized drugs to ventilated patients.

Objective: The objective of this study was to characterize aerosol droplet size and distribution with laser diffraction for nebulized 3% sodium chloride, albuterol, and epoprostenol sodium (containing glycine) delivered via Aeroneb Solo Mesh Nebulizers (Aerogen, Mountain View, California).

Exploring dementia family caregivers' everyday use and appraisal of technological supports.

Family caregivers provide the majority of care for people with dementia, often balancing multiple caregiving roles. Technology-based interventions have demonstrated strong potential for supporting family caregivers in navigating these roles, yet translational uptake of these interventions remains limited. A comprehensive understanding of how caregivers engage and evaluate everyday technological supports is necessary to foster broader adoption.

Age-based versus Risk-based Mammography Screening in Women 40-49 Years Old: A Cross-sectional Study.

Background Risk-based screening in women 40-49 years old has not been evaluated in routine screening mammography practice. Purpose To use a cross-sectional study design to compare the trade-offs of risk-based and age-based screening for women 45 years of age or older to determine short-term outcomes. Materials and Methods A retrospective cross-sectional study was performed by using a database of 20 539 prospectively interpreted consecutive digital screening mammograms in 10 280 average-risk women aged 40-49 years who were screened at an academic medical center between January 1, 2006, and December 31, 2013.

Pulmonary vascular mechanical consequences of ischemic heart failure and implications for right ventricular function.

Left heart failure (LHF) is the most common cause of pulmonary hypertension, which confers an increase in morbidity and mortality in this context. Pulmonary vascular resistance has prognostic value in LHF, but otherwise the mechanical consequences of LHF for the pulmonary vasculature and right ventricle (RV) remain unknown. We sought to investigate mechanical mechanisms of pulmonary vascular and RV dysfunction in a rodent model of LHF to address the knowledge gaps in understanding disease pathophysiology.

A How-To Guide for Promoting Diversity and Inclusion in Biomedical Engineering.

To accelerate the development of an inclusive culture in biomedical engineering (BME), we must accept complexity, seek to understand our own privilege, speak out about diversity, learn the difference between intent and impact, accept our mistakes, and learn how to engage in difficult conversations. In turn, we will be rewarded by the ideas, designs, devices and discoveries of a new generation of problem solvers and thought leaders who bring diverse experiences and perspectives.

Cardiovascular function and structure are preserved despite induced ablation of BMP1-related proteinases.

Introduction: Bone morphogenetic protein 1 (BMP1) is part of an extracellular metalloproteinase family that biosynthetically processes procollagen molecules. BMP1- and tolloid-like (TLL1) proteinases mediate the cleavage of carboxyl peptides from procollagen molecules, which is a crucial step in fibrillar collagen synthesis. Ablating the genes that encode BMP1-related proteinases ( and ) post-natally results in brittle bones, periodontal defects, and thin skin in conditional knockout (BT) mice.

Multiscale structure-function relationships in right ventricular failure due to pressure overload.

Right ventricular (RV) failure (RVF) is the major cause of death in pulmonary hypertension. Recent studies have characterized changes in RV structure in RVF, including hypertrophy, fibrosis, and abnormalities in mitochondria. Few, if any, studies have explored the relationships between these multiscale structural changes and functional changes in RVF.

Transcription control engineering and applications in synthetic biology.

In synthetic biology, researchers assemble biological components in new ways to produce systems with practical applications. One of these practical applications is control of the flow of genetic information (from nucleic acid to protein), a.k.

Right Ventricular-Pulmonary Vascular Interactions.

Accurate and comprehensive evaluation of right ventricular (RV)-pulmonary vascular (PV) interactions is critical to the assessment of cardiopulmonary function, dysfunction, and failure. Here, we review methods of quantifying RV-PV interactions and experimental results from clinical trials as well as large- and small-animal models based on pressure-volume analysis. We conclude by outlining critical gaps in knowledge that should drive future studies.

Pulmonary arterial strain- and remodeling-induced stiffening are differentiated in a chronic model of pulmonary hypertension.

Pulmonary hypertension (PH) is a debilitating vascular disease that leads to pulmonary artery (PA) stiffening, which is a predictor of patient mortality. During PH development, PA stiffening adversely affects right ventricular function. PA stiffening has been investigated through the arterial nonlinear elastic response during mechanical testing using a canine PH model.

17β-Estradiol mediates superior adaptation of right ventricular function to acute strenuous exercise in female rats with severe pulmonary hypertension.

17β-Estradiol (E2) exerts protective effects on right ventricular (RV) function in pulmonary arterial hypertension (PAH). Since acute exercise-induced increases in afterload may lead to RV dysfunction in PAH, we sought to determine whether E2 allows for superior RV adaptation after an acute exercise challenge. We studied echocardiographic, hemodynamic, structural, and biochemical markers of RV function in male and female rats with sugen/hypoxia (SuHx)-induced pulmonary hypertension, as well as in ovariectomized (OVX) SuHx females, with or without concomitant E2 repletion (75 μg·kg(-1)·day(-1)) immediately after 45 min of treadmill running at 75% of individually determined maximal aerobic capacity (75% aerobic capacity reserve).

Limiting collagen turnover via collagenase-resistance attenuates right ventricular dysfunction and fibrosis in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a severe form of pulmonary hypertension in which right ventricular (RV) afterload is increased and death typically occurs due to decompensated RV hypertrophy and failure. Collagen accumulation has been implicated in pulmonary artery remodeling, but how it affects RV performance remains unclear. Here, we sought to identify the role of collagen turnover, defined as the balance between collagen synthesis and degradation, in RV structure and function in PAH To do so, we exposed mutant (Col1a1(R/R)) mice, in which collagen type I degradation is impaired such that collagen turnover is reduced, and wild-type (Col1a1(+/+)) littermates to 14 days of chronic hypoxia combined with SUGEN treatment (HySu) to recapitulate characteristics of clinical PAH RV structure and function were measured by echocardiography, RV catheterization, and histology.

Identifying design considerations for a shared decision aid for use at the point of outpatient clinical care: An ethnographic study at an inner city clinic.

Background And Objective: Computerized decision aids could facilitate shared decision-making at the point of outpatient clinical care. The objective of this study was to investigate whether a computerized shared decision aid would be feasible to implement in an inner-city clinic by evaluating the current practices in shared decision-making, clinicians' use of computers, patient and clinicians' attitudes and beliefs toward computerized decision aids, and the influence of time on shared decision-making.

Methods: Qualitative data analysis of observations and semi-structured interviews with patients and clinicians at an inner-city outpatient clinic.

Potential roles for new communication technologies in treatment of addiction.

Information and communication technologies offer clinicians the opportunity to work with patients to manage chronic conditions, including addiction. The early research on the efficacy of electronic treatment and support tools is promising. Sensors have recently received increased attention as key components of electronic treatment and recovery management systems.