Structures of activin ligand traps using natural sets of type I and type II TGFβ receptors.

The 30+ unique ligands of the TGFβ family signal by forming complexes using different combinations of type I and type II receptors. Therapeutically, the extracellular domain of a single receptor fused to an Fc molecule can effectively neutralize subsets of ligands. Increased ligand specificity can be accomplished by using the extracellular domains of both the type I and type II receptor to mimic the naturally occurring signaling complex.

Functionally diverse heteromeric traps for ligands of the transforming growth factor-β superfamily.

Ligands of the transforming growth factor-β (TGF-β) superfamily are important targets for therapeutic intervention but present challenges because they signal combinatorially and exhibit overlapping activities in vivo. To obtain agents capable of sequestering multiple TGF-β superfamily ligands with novel selectivity, we generated soluble, heterodimeric ligand traps by pairing the extracellular domain (ECD) of the native activin receptor type IIB (ActRIIB) alternately with the ECDs of native type I receptors activin receptor-like kinase 4 (ALK4), ALK7, or ALK3. Systematic analysis of these heterodimeric constructs by surface plasmon resonance, and comparison with their homodimeric counterparts, revealed that each type I receptor partner confers a distinct ligand-binding profile to the heterodimeric construct.

ActRIIB:ALK4-Fc alleviates muscle dysfunction and comorbidities in murine models of neuromuscular disorders.

Patients with neuromuscular disorders suffer from a lack of treatment options for skeletal muscle weakness and disease comorbidities. Here, we introduce as a potential therapeutic agent a heterodimeric ligand-trapping fusion protein, ActRIIB:ALK4-Fc, which comprises extracellular domains of activin-like kinase 4 (ALK4) and activin receptor type IIB (ActRIIB), a naturally occurring pair of type I and II receptors belonging to the TGF-β superfamily. By surface plasmon resonance (SPR), ActRIIB:ALK4-Fc exhibited a ligand binding profile distinctly different from that of its homodimeric variant ActRIIB-Fc, sequestering ActRIIB ligands known to inhibit muscle growth but not trapping the vascular regulatory ligand bone morphogenetic protein 9 (BMP9).

Naloxone counseling: Confidence and attitudes of student pharmacists after a volunteer syringe exchange experience.

Introduction: Our objective was to assess how a naloxone counseling experience impacted student pharmacists' confidence in counseling patients on naloxone use and their attitudes towards people who use drugs.

Methods: Students who completed a naloxone counseling experience at a syringe exchange program were recruited to conduct individual interviews. Investigators asked student participants open-ended questions to identify their perceptions in the following domains: experiences with naloxone, reported impact of naloxone counseling experience on confidence, experiences with people who use drugs, value of the experience, and suggestions for improvement for the experience.

Beta-lactam antibiotic test doses in the emergency department.

Background: Facilitating beta-lactam antibiotic use in patients reporting beta-lactam allergies in acute care settings is important to individual patient outcomes and public health; however, few initiatives have targeted the Emergency Department (ED) setting.

Methods: We implemented pathways for patients reporting prior penicillin and/or cephalosporin hypersensitivity as part of a hospital guideline in the ED of a large academic medical center in the United States. We described beta-lactam test doses, pathway compliance, hypersensitivity reactions (HSRs), and allergy record updating associated with ED-administered beta-lactam test doses from October 2016 to June 2018.

Thromboembolic Risk of 4-Factor Prothrombin Complex Concentrate versus Fresh Frozen Plasma for Urgent Warfarin Reversal in the Emergency Department.

Introduction: Warfarin is a potent anticoagulant used for the prevention and treatment of venous and arterial thrombosis. Occasionally, patients require emergent warfarin reversal due to active bleeding, supratherapeutic international normalized ratio, or emergent diagnostic or therapeutic interventions. Various agents can be used for emergent warfarin reversal, including fresh frozen plasma (FFP) and 4-factor prothrombin complex concentrate (4F-PCC).

Alternatives to opioids for pain management in the emergency department decreases opioid usage and maintains patient satisfaction.

Objective: The objective of this study was to assess opioid use in an emergency department following the development and implementation of an alternative to opioids (ALTO)-first approach to pain management. The study also assessed how implementation affected patient satisfaction scores.

Methods: This study compared data collected from October to December of 2015 (prior to implementation) to data collected between October and December of 2016 (after the intervention had been implemented).

A naloxone and harm reduction educational program across four years of a doctor of pharmacy program.

Background And Purpose: Naloxone distribution is an increasing service provided by pharmacists as more states enact laws enabling pharmacists to dispense naloxone without a prescription or per protocol to individuals in the wake of an opioid overdose epidemic. Education and training programs are necessary to ensure students and practicing pharmacists are able to effectively provide the service.

Educational Activity And Setting: All first, second, and third year students in the doctor of pharmacy (PharmD) program at The Ohio State University College of Pharmacy (OSUCOP) participated in a pilot naloxone and harm reduction educational program.

Banned and discouraged-use ingredients found in weight loss supplements.

Objectives: To identify banned and discouraged-use ingredients, such as ephedra, 1,3-dimethylamylamine, and beta-methyl-phenylethylamine, in readily available weight loss dietary supplements within a 10-mile radius of Regis University.

Methods: A list of banned and discouraged-use ingredients was compiled with the use of the Food and Drug Administration (FDA) dietary supplement website which provides information on supplement ingredients that are no longer legal or are advised against owing to adverse event reporting. Investigators visited all retail outlet stores within a 10-mile radius of Regis University in Denver, Colorado.

Impact of an Elective Course in Community and Ambulatory Care Pharmacy Practices on Student Perception of Patient Care.

Objective. To determine the impact of an elective course on students' perception of opportunities and of their preparedness for patient care in community and ambulatory pharmacy settings. Design.

Unexpected deaths of children and young people in the UK.

Aims and method To review the deaths of children and young people who took their own life. We conducted a retrospective analysis of serious incident reports from a National Health Service trust and reviews by the child death overview panels of the local safeguarding children boards. Results We identified 23 deaths, with annual rates varying considerably between local authorities and over time.

Implementation of targeted medication adherence interventions within a community chain pharmacy practice: The Pennsylvania Project.

Objective: To identify facilitators and barriers to implementing targeted medication adherence interventions in community chain pharmacies, and describe adaptations of the targeted intervention and organizational structure within each individual pharmacy practice.

Design: Qualitative study.

Setting: Central and western Pennsylvania from February to April 2012.

A clinically significant interaction between tacrolimus and multiple proton pump inhibitors in a kidney transplant recipient.

The shared metabolism of PPIs and tacrolimus through the CYP enzyme system has been associated with clinically significant drug interactions, especially in patients who are classified as CYP 2C19 PMs. However, existing data are conflicting, indicating that a single mechanism does not account for all interactions. A drug interaction between tacrolimus and omeprazole, esomeprazole, but not lansoprazole, occurred in an 18-yr-old female kidney transplant recipient classified as a CYP 2C19 extensive (normal) metabolizer.

Catalytically active MAP KAP kinase 2 structures in complex with staurosporine and ADP reveal differences with the autoinhibited enzyme.

MAP KAP kinase 2 (MK2), a Ser/Thr kinase, plays a crucial role in the inflammatory process. We have determined the crystal structures of a catalytically active C-terminal deletion form of human MK2, residues 41-364, in complex with staurosporine at 2.7 A and with ADP at 3.