Pulmonary-delivered Anticalin Jagged-1 antagonists reduce experimental airway mucus hyperproduction and obstruction.

Mucus hypersecretion and mucus obstruction are pathogenic features in many chronic lung diseases directly linked to disease severity, exacerbation, progression, and mortality. The Jagged-1/Notch pathway is a promising therapeutic target that regulates secretory and ciliated cell trans-differentiation in the lung. However, the Notch pathway is also required in various other organs.

BPIFB1 loss alters airway mucus properties and diminishes mucociliary clearance.

Airway mucociliary clearance (MCC) is required for host defense and is often diminished in chronic lung diseases. Effective clearance depends upon coordinated actions of the airway epithelium and a mobile mucus layer. Dysregulation of the primary secreted airway mucin proteins, MUC5B and MUC5AC, is associated with a reduction in the rate of MCC; however, how other secreted proteins impact the integrity of the mucus layer and MCC remains unclear.

Factors Associated with Acute Injurious Falls in Elderly Hospitalized Patients: A Multicenter Descriptive Study.

Background: The Centers for Medicare & Medicaid Services Hospital-Acquired Conditions (CMS-HAC) links Medicare payments to health care quality. Experiencing a serious disability or death associated with a fall in a health care facility based on diagnosis codes has been identified as an opportunity for improvement. Multiple factors contribute to an inpatient fall, including medications that affect cognition in older adults.

Feasibility of a Novel Real-Time Provider Teaching Intervention in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Background: It is not known whether an intervention using real-time provider teaching in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) improves provider knowledge and/or patient outcomes.

Objective: To pilot the combination of a novel, real-time provider teaching intervention delivered by subspecialists to Internal Medicine trainees with a traditional patient education and medication reconciliation (PEMR) intervention and to assess the impact of these interventions on provider knowledge regarding COPD and patient care.

Methods: This was a single-center, nonrandomized, quality-improvement study.

A survey study examining the motivations, concerns, and perspectives of medical students engaging in neurosurgical research.

Background: In a competitive landscape for neurosurgical residency admission, research productivity is increasingly important. Medical school applicants to neurosurgery report high numbers of "scholarly products" as published by the National Residency Match Program. Despite increased student involvement in research and productivity, to the best of our knowledge, no previous reported studies have examined student perspectives on their involvement in neurosurgical research.

Risks and Preventive Strategies for Clostridioides difficile Transmission to Household or Community Contacts during Transition in Healthcare Settings.

The burden of Clostridioides difficile infection (CDI) has greatly increased. We evaluated the risks for CDI transmission to community members after hospitalized patients are discharged. We conducted a systematic literature review in MEDLINE/PubMed, EMBASE, CINAHL plus EBSCO, Web of Science, Cochrane Library, and gray literature during January 2000‒February 2019 and identified 4,798 citations were identified.

Rheumatic Care in Under-Resourced Areas Using the Extension for Community Healthcare Outcomes Model.

Objective: To demonstrate the effectiveness of the Extension for Community Healthcare Outcomes (Project ECHO) in educating primary care clinicians (PCCs) to provide best practice rheumatic care to patients in under-resourced communities in New Mexico.

Methods: Attendee data for weekly teleECHO sessions, lectures, grand rounds, and mini-residency trainings were evaluated from June 2006 to June 2014. Participant feedback was evaluated from January 2009 to December 2014, when the program was approved for continuing medical education (CME) credits.

A Fully Automated High-Throughput Flow Cytometry Screening System Enabling Phenotypic Drug Discovery.

The goal of high-throughput screening is to enable screening of compound libraries in an automated manner to identify quality starting points for optimization. This often involves screening a large diversity of compounds in an assay that preserves a connection to the disease pathology. Phenotypic screening is a powerful tool for drug identification, in that assays can be run without prior understanding of the target and with primary cells that closely mimic the therapeutic setting.

Comparison of Adherence to the 2013 ACC/AHA Cholesterol Guideline in a Teaching Versus Nonteaching Outpatient Clinic.

Background: Little information is available regarding prescribers' adherence rate to the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol guideline, especially that from a teaching versus a nonteaching setting.

Objectives: We aim to evaluate adherence rates to the 2013 ACC/AHA cholesterol guideline in a teaching versus a nonteaching practice site. In addition, the impact of a pharmacist-led seminar on adherence rate to the guideline was assessed.

Edoxaban: A Novel Factor Xa Inhibitor for the Management of Non-valvular Atrial Fibrillation and Venous Thromboembolism.

Warfarin has been a highly prevalent agent for over 70 years; however, its use has been limited by drug-drug interactions, adverse events, and the need for frequent monitoring. To minimize these complications, several non-vitamin K oral anticoagulants have been approved, including the latest agent, edoxaban. Edoxaban is a factor Xa inhibitor approved for the prevention of stroke/systemic embolism in patients with non-valvular atrial fibrillation and for the treatment of venous thromboembolism.

Production of Highly Charged Pharmaceutical Aerosols Using a New Aerosol Induction Charger.

Purpose: Properly charged particles can be used for effective lung targeting of pharmaceutical aerosols. The objective of this study was to characterize the performance of a new induction charger that operates with a mesh nebulizer for the production of highly charged submicrometer aerosols to bypass the mouth-throat and deliver clinically relevant doses of medications to the lungs.

Methods: Variables of interest included combinations of model drug (albuterol sulfate) and charging excipient (NaCl) as well as strength of the charging field (1-5 kV/cm).

An image-based screen identifies a small molecule regulator of megakaryopoiesis.

Molecules that control the lineage commitment of hematopoietic stem cells (HSCs) may allow the expansion of enriched progenitor populations for both research and therapeutic uses. In an effort to better understand and control the differentiation of HSCs to megakaryocytes, we carried out an image-based screen of a library of 50,000 heterocycles using primary human CD34(+) cells. A class of naphthyridinone derivatives was identified that induces the differentiation of common myeloid progenitors (CMP) to megakaryocytes.

A gene expression signature of CD34+ cells to predict major cytogenetic response in chronic-phase chronic myeloid leukemia patients treated with imatinib.

In chronic-phase chronic myeloid leukemia (CML) patients, the lack of a major cytogenetic response (< 36% Ph(+) metaphases) to imatinib within 12 months indicates failure and mandates a change of therapy. To identify biomarkers predictive of imatinib failure, we performed gene expression array profiling of CD34(+) cells from 2 independent cohorts of imatinib-naive chronic-phase CML patients. The learning set consisted of retrospectively selected patients with a complete cytogenetic response or more than 65% Ph(+) metaphases within 12 months of imatinib therapy.

Acute dasatinib exposure commits Bcr-Abl-dependent cells to apoptosis.

Pioneering work with the Bcr-Abl inhibitor, imatinib, demonstrated a requirement for constant Bcr-Abl inhibition to achieve maximal therapeutic benefit in treating chronic myeloid leukemia (CML), establishing a paradigm that has guided further drug development for this disease. Surprisingly, the second-generation Bcr-Abl inhibitor, dasatinib, was reported to be clinically effective with once-daily dosing, despite a short (3- to 5-hour) plasma half-life. Consistent with this observation, dasatinib treatment of progenitor cells from chronic-phase CML patients for 4 hours, followed by washout, or continuously for 72 hours both resulted in an induction of apoptosis and a reduction in the number of clonogenic cells.

New strategies for the first-line treatment of chronic myeloid leukemia: can resistance be avoided?

Imatinib is well established as a safe, effective therapy for patients with chronic myeloid leukemia (CML). However, point mutations in the kinase domain of Bcr-Abl can lead to imatinib resistance and reactivation of kinase activity. The second-generation Abl kinase inhibitors nilotinib and dasatinib were developed to reestablish disease control.

A coupled chemical-genetic and bioinformatic approach to Polo-like kinase pathway exploration.

Protein phosphorylation is a ubiquitous mechanism for cellular signal propagation, and signaling network complexity presents a challenge to protein kinase substrate identification. Few targets of Polo-like kinases are known, despite their significant role in coordinating cell-cycle progression. Here, we combine chemical-genetic, bioinformatic, and proteomic tools for Polo-like kinase substrate identification.

Secondary syringe exchange among injection drug users.

Syringe-exchange programs (SEPs) have proven to prevent the spread of bloodborne pathogens, primarily human immunodeficiency virus (HIV), among injection drug users (IDUs). In the United States, only about 7% of IDUs have access to and use SEPs. Some IDUs engage in secondary syringe exchange (SSE), meaning that one IDU (a "provider") obtains syringes at an SEP to distribute to other IDUs ("recipients").

Evaluation of the forearm in untreated adult subjects with multiple hereditary osteochondromatosis.

Background: Limb-length discrepancy or angular deformities as a result of altered bone growth may lead to a decreased range of motion and impaired function as well as premature osteoarthritis in patients with multiple hereditary osteochondromatosis. The purpose of this study was to describe the function of the forearm in untreated patients in order to facilitate comparison with studies of the results of treatment of this condition.

Methods: The medical records of fifty-one pediatric patients were identified and served as the basis for identifying a cohort of adult relatives with the disorder.

Natural history of multiple hereditary osteochondromatosis of the lower extremity and ankle.

In this study the authors evaluated the natural history of the ankle joint in patients with multiple hereditary osteochondromatosis. Thirty-eight subjects with an average age of 42 years completed a detailed subjective questionnaire and underwent clinical and radiographic evaluation of their ankles. Three subjects (8%) indicated their ankle involvement affected their vocation, and 12 (32%) were limited in recreational sports.