The Pharmacogenomics Global Research Network Implementation Working Group: global collaboration to advance pharmacogenetic implementation.

Pharmacogenetics promises to optimize treatment-related outcomes by informing optimal drug selection and dosing based on an individual's genotype in conjunction with other important clinical factors. Despite significant evidence of genetic associations with drug response, pharmacogenetic testing has not been widely implemented into clinical practice. Among the barriers to broad implementation are limited guidance for how to successfully integrate testing into clinical workflows and limited data on outcomes with pharmacogenetic implementation in clinical practice.

Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation: A Randomized, Controlled Study.

Stress-induced islet graft loss during the peri-transplantation period reduces the efficacy of islet transplantation. In this prospective, randomized, double-blind clinical trial, we evaluated the safety and efficacy of 60 mg/kg human alpha-1 antitrypsin (AAT) or placebo infusion weekly for four doses beginning before surgery in chronic pancreatitis (CP) patients undergoing total pancreatectomy and islet autotransplantation (TP-IAT). Subjects were followed for 12 months post-TP-IAT.

Comparison of variants in TPMT and NUDT15 between sequencing and genotyping methods in a multistate pediatric institution.

The risk of severe adverse events related to thiopurine therapy can be reduced by personalizing dosing based on TPMT and NUDT15 genetic polymorphisms. However, the optimal genetic testing platform has not yet been established. In this study, we report on the TPMT and NUDT15 genotypes and phenotypes generated from 320 patients from a multicenter pediatric healthcare system using both Sanger sequencing and polymerase chain reaction genotyping (hereafter: genotyping) methods to determine the appropriateness of genotyping in our patient population.

Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators.

Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.

Development of a Campus-Wide Community Service Initiative during a Pandemic.

Community service serves as a major aspect of pharmacy education; however, coronavirus disease 2019 (COVID-19) represented a significant disruption to student involvement. The College of Pharmacy student council, which serves as the local student government organization for the University of Florida College of Pharmacy, Jacksonville campus, developed a community service initiative to offer more consistent opportunities for students to participate in community service events, while adapting to COVID-19 restrictions. A retrospective, qualitative review of this initiative demonstrates the potential value of this model.

How to Integrate CYP2D6 Phenoconversion Into Clinical Pharmacogenetics: A Tutorial.

CYP2D6 genotype is increasingly being integrated into practice to guide prescribing of certain medications. The CYP2D6 drug metabolizing enzyme is susceptible to inhibition by concomitant drugs, which can lead to a clinical phenotype that is different from the genotype-based phenotype, a process referred to as phenoconversion. Phenoconversion is highly prevalent but not widely integrated into practice because of either limited experience on how to integrate or lack of knowledge that it has occurred.

Impact of the CYP2C19*17 Allele on Outcomes in Patients Receiving Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

Genotyping for CYP2C19 no function alleles to guide antiplatelet therapy after percutaneous coronary intervention (PCI) improves clinical outcomes. Although results for the increased function CYP2C19*17 allele are also reported, its clinical relevance in this setting remains unclear. A collaboration across nine sites examined antiplatelet therapy prescribing and clinical outcomes in 3,342 patients after implementation of CYP2C19-guided antiplatelet therapy.

Development of Customizable Implementation Guides to Support Clinical Adoption of Pharmacogenomics: Experiences of the Implementing GeNomics In pracTicE (IGNITE) Network.

Introduction: Clinical adoption of genomic medicine has lagged behind the pace of scientific discovery. Practice-based resources can help overcome implementation challenges.

Methods: In 2015, the IGNITE (Implementing GeNomics In pracTicE) Network created an online genomic medicine implementation resource toolbox that was expanded in 2017 to incorporate the ability for users to create targeted implementation guides.

Design and Early Implementation Successes and Challenges of a Pharmacogenetics Consult Clinic.

Pharmacogenetic testing (PGT) is increasingly being used as a tool to guide clinical decisions. This article describes the development of an outpatient, pharmacist-led, pharmacogenetics consult clinic within internal medicine, its workflow, and early results, along with successes and challenges. A pharmacogenetics-trained pharmacist encouraged primary care physicians (PCPs) to refer patients who were experiencing side effects/ineffectiveness from certain antidepressants, opioids, and/or proton pump inhibitors.

Thoughts on Writing for Review: An NSF Program Officer's Perspective.

This is an invited Account and Perspective, providing observations and advice derived from a 40 year academic career that has included over 14 years' service as a program officer at the National Science Foundation (NSF) and 27 years of service as an Associate Editor of the . This work describes the program officer's perspective, with observations on what reviewers look for in proposals, and what are some of the more common, best avoided mistakes. Emphasis is on NSF guidelines, but many elements are general and intended for use by both proposal authors and reviewers.

How to Transition from Single-Gene Pharmacogenetic Testing to Preemptive Panel-Based Testing: A Tutorial.

There have been significant advancements in precision medicine and approaches to medication selection based on pharmacogenetic results. With the availability of direct-to-consumer genetic testing and growing awareness of genetic interindividual variability, patient demand for more precise, individually tailored drug regimens is increasing. The University of Florida (UF) Health Precision Medicine Program (PMP) was established in 2011 to improve integration of genomic data into clinical practice.

Thoughts on Writing for Review: A Former Associate Editor's Perspective.

This is an invited Account and Perspective, providing observations and advice on writing for review derived from a 40-year academic career that has included 27 years' service as an Associate Editor for the () and nearly 14 years at the National Science Foundation. This work describes an Associate Editor's perspective. It offers observations on what editors and reviewers look for in manuscripts and some of the more common, best avoided mistakes.

Visualizing the Consistency of Thickened Liquids With Simple Tools: Implications for Clinical Practice.

Purpose: Accurate texture modifications to thin liquids are a critical aspect of patients' nutritional health and well-being. This study explored the use of 3 tools (2 distance- and 1 time-measuring devices) to characterize texture-modified liquids. The objectives were to use the tools to measure modified liquids, to determine if measurements differentiated nectar and honey levels of modification, and to compare measurements with other published reports.

Tests of Theories of Crime in Female Prisoners.

Several general theories of crime were tested with path models on 293 female prisoners in a U.S. State prison.

Fluorometric measurement and modeling of droplet temperature changes in an electrospray plume.

The evolution of droplet temperatures in an electrospray plume was measured via ratiometric fluorescence. Under typical operating conditions, droplet temperatures decrease ∼30 K over the first 5.0 mm along the spray axis, followed by a slight (∼2-3 K) rewarming.

Development of a multipoint quantitation method to simultaneously measure enzymatic and structural components of the Clostridium thermocellum cellulosome protein complex.

Clostridium thermocellum has emerged as a leading bioenergy-relevant microbe due to its ability to solubilize cellulose into carbohydrates, mediated by multicomponent membrane-attached complexes termed cellulosomes. To probe microbial cellulose utilization rates, it is desirable to be able to measure the concentrations of saccharolytic enzymes and estimate the total amount of cellulosome present on a mass basis. Current cellulase determination methodologies involve labor-intensive purification procedures and only allow for indirect determination of abundance.

Characterizing the range of extracellular protein post-translational modifications in a cellulose-degrading bacteria using a multiple proteolyic digestion/peptide fragmentation approach.

Post-translational modifications (PTMs) are known to play a significant role in many biological functions. The focus of this study is to optimize an integrated experimental/informatics approach to more confidently characterize the range of post-translational modifications of the cellulosome protein complex used by the bacterium Clostridium thermocellum to better understand how this protein machine is tuned for enzymatic cellulose solubilization. To enhance comprehensive characterization, the extracellular cellulosome proteins were analyzed using multiple proteolytic digests (trypsin, Lys-C, Glu-C) and multiple fragmentation techniques (collisionally activated dissociation, electron transfer dissociation, decision tree).

Quantitative real-time monitoring of chemical reactions by autosampling flow injection analysis coupled with atmospheric pressure chemical ionization mass spectrometry.

Although qualitative and/or semiquantitative real-time monitoring of chemical reactions have been reported with a few mass spectrometric approaches, to our knowledge, no quantitative mass spectrometric approach has been reported so far to have a calibration valid up to molar concentrations as required by process control. This is mostly due to the absence of a practical solution that could well address the sample overloading issue. In this study, a novel autosampling flow injection analysis coupled with an atmospheric pressure chemical ionization mass spectrometry (FIA/APCI-MS) system, consisting of a 1 μL automatic internal sample injector, a postinjection splitter with 1:10 splitting ratio, and a detached APCI source connected to the mass spectrometer using a 4.

Evaluation of direct analysis in real time mass spectrometry for onsite monitoring of batch slurry reactions.

Batch slurry reactions are widely used in the industrial manufacturing of chemicals, pharmaceuticals, petrochemicals and polymers. However, onsite monitoring of batch slurry reactions is still not feasible in production plants due to the challenge in analyzing heterogeneous samples without complicated sample preparation procedures. In this study, direct analysis in real time mass spectrometry (DART-MS) has been evaluated for the onsite monitoring of a model batch slurry reaction.

Ionization mechanism of positive-ion direct analysis in real time: a transient microenvironment concept.

A transient microenvironment mechanism (TMEM) is proposed to address matrix effects for direct analysis in real time (DART). When the DART gas stream is in contact with the sample, a transient microenvironment (TME), which can shield analytes from direct ionization, may be generated through the desorption of the matrix containing the analyte. The DART gas stream can directly ionize the matrix molecules, but the analytes will be ionized primarily through gas-phase ion/molecule reactions with the matrix ions.

Complementary peptide sequence coverage using alternative enzymes for on-line digestion with a triaxial electrospray probe.

Using alternative enzymes for on-line digestion with a triaxial electrospray probe extends sequence coverage. This is the first report of utilization of our triaxial probe for on-line analysis with enzymes other than pepsin, suggesting potential for broader application. The probe allows access to processes occurring on a timescale and/or involving substrate conformations complementary to those for conventional (off-line) digestion.

Oxidation artifacts in the electrospray mass spectrometry of Abeta Peptide.

Gradual corrosion of stainless steel electrospray emitters under conditions of normal use generates surface irregularities that can promote electrical discharge. The increased emission current affects the electrochemical reactions associated with the spray process. When sampling the peptide Abeta(1-40), this is manifest by oxidation of methionine at position 35 to methionine sulfoxide.

A triaxial probe for on-line proteolysis coupled with hydrogen/deuterium exchange-electrospray mass spectrometry.

An on-line proteolysis system utilizing a triaxial electrospray probe was developed to aid localization of the hydrogen-bonding interaction sites in hydrogen/deuterium exchange-mass spectrometry (HDX-MS) studies of Abeta (1-40) fibrils. The probe allows delayed introduction of the organic solvent component needed for stable electrospray, thus enhancing hydrolysis performance relative to that of a coaxial probe. Effective on-line digestion was accomplished in approximately 12 s.

Hydrogen/deuterium exchange mass spectrometry analysis of protein aggregates.

The elucidation of the structure of amyloid fibrils and related aggregates is an important step toward understanding the pathogenesis of diseases like Alzheimer's disease, which feature protein misfolding and/or aggregation. However, the large size, heterogeneous morphology, and poor solubility of amyloid-like fibrils make them resistant to high-resolution structure determination. Using amyloid fibrils and protofibrils of the Alzheimer's plaque peptide amyloid beta as examples, we describe here the use of hydrogen/deuterium exchange methods in conjunction with electrospray ionization mass spectrometry to determine regions of the peptide involved in beta-sheet network when it is incorporated into protein aggregates.