Integrating Pharmacogenomics into the Broader Construct of Genomic Medicine: Efforts by the ClinGen Pharmacogenomics Working Group (PGxWG).

Pharmacogenomics (PGx) is focused on the relationship between an individual's genetic makeup and their response to medications, with the overarching aim of guiding prescribing decisions to improve drug efficacy and reduce adverse events. The PGx and genomic medicine communities have worked independently for over 2 decades, developing separate standards and terminology, making implementation of PGx across all areas of genomic medicine difficult. To address this issue, the Clinical Genome Resource (ClinGen) Pharmacogenomics Working Group (PGxWG) was established by the National Institutes of Health (NIH)-funded ClinGen to initially create frameworks for evaluating gene-drug response clinical validity and actionability aligned with the ClinGen frameworks for evaluating monogenic gene-disease relationships, and a framework for classifying germline PGx variants similar to the American College of Medical Genetics (ACMG) and Association of Molecular Pathology (AMP) system for interpretation of disease-causing variants.

Racial, Socioeconomic, and Geographic Disparities in Preamputation Vascular Care for Patients With Chronic Limb-Threatening Ischemia.

Background: Black patients, those with low socioeconomic status (SES), and those living in rural areas have elevated rates of major lower extremity amputation, which may be related to a lack of subspecialty chronic limb-threatening ischemia care. We evaluated the association between race, rurality, SES, and preamputation vascular care.

Methods: Among patients aged 66 to 86 years with fee-for-service Medicare who underwent major lower extremity amputation for chronic limb-threatening ischemia from July 2010 to December 2019, we compared the proportion who received vascular care in the 12 months before amputation by race (Black versus White), rurality, and SES (dual eligibility for Medicaid versus no dual eligibility) using multivariable logistic regression adjusting for clinical and demographic covariates.

E-portfolio in Learning and Assessment of Community Medicine for Medical Undergraduate Students.

Background: A portfolio is a specific collection of student work and achievements in various areas. E-portfolio is an electronic collection that serves the purpose of storage and showcase with the ease of access for both students and evaluators. The knowledge and skills regarding immunization in medical students are of utmost importance for the successful implementation and conduction of the Universal Immunization Program in the country.

Impact of particle size on and fat fraction estimation for accurate assessment of hepatic iron overload and steatosis using MRI.

Purpose: To investigate the impact of iron particle size on and fat fraction (FF) estimations for coexisting hepatic iron overload and steatosis condition using Monte Carlo simulations and phantoms.

Methods: Three iron particle sizes (0.38, 0.

A genome-wide association study of high-sensitivity C-reactive protein in a large Korean population highlights its genetic relationship with cholesterol metabolism.

High-sensitivity C-reactive protein (hsCRP) is a representative biomarker of systemic inflammation and is associated with numerous chronic diseases. To explore the biological pathways and functions underlying chronic inflammation, we conducted a genome-wide association study (GWAS) and several post-GWAS analyses of the hsCRP levels. This study was performed on data from 71,019 Koreans and is one of the largest East Asian studies.

PeerPub: A Device for Concurrent Operant Oral Self-Administration by Multiple Rats.

The social environment has long been recognized to play an important role in substance use, which is often modeled in rodents using operant conditioning. However, most operant chambers only accommodate one rodent at a time. We present PeerPub-a unique social operant chamber.

Physiologically Based Pharmacokinetic Modeling and Simulation to Support a Change in the FDA-Labeled Dosing Frequency of RHB-105 Low-Dose Rifabutin Triple Therapy for Helicobacter pylori Eradication.

Patient adherence is vital for Helicobacter pylori eradication. Simplifying therapy dosing schedules may promote patient adherence, enhance treatment success rates, and help mitigate the development of antibiotic resistance. We aimed to assess plasma and intragastric rifabutin, amoxicillin, and omeprazole concentrations comparing two dosing schedules of RHB-105 (every 8 h and a more flexible three-times daily schedule, at 8 a.

A framework for sequential monitoring of individual N-of-1 trials and combining results across a series of sequentially monitored N-of-1 trials.

Background: N-of-1 trials compare two or more treatment options for a single participant. These trials have been used to study options for chronic conditions such as arthritis and attention deficit hyperactivity disorder. In addition, they have been suggested as a means to study interventions in rare populations that may not be tractable to include in standard clinical trials, such as treatment options for HIV-positive patients in need of organ transplant.

MiR-675 Inhibits Primary Ovarian Tumor Growth and Metastasis by Suppressing EMT and TGFβ Signaling.

MicroRNAs (miRNAs) can function as either tumor suppressors or oncogenes. This study explores the role of miR-675 in ovarian cancer (OC) using OC cell lines and an orthotopic mouse model. We demonstrate that miR-675 expression inhibits primary tumor growth and metastasis by targeting TGFβ1, suppressing epithelial to mesenchymal transition (EMT), and attenuating the TGFβ signaling pathway.

Inclined distance running at iso-efficient speeds: Effect on joint work.

Runners often reduce their pace during inclined running to maintain a constant metabolic workload, known as iso-efficiency speed (a speed-incline combination with the same metabolic intensity as level running). This study investigates changes in lower extremity (LE) joint work profiles when running on an incline at iso-efficiency speed. Eleven collegiate distance runners completed a treadmill running task under three conditions (0%, 4%, and 8% incline).

Proton Pump Inhibitor Use and Incident Cardiovascular Disease in Older Postmenopausal Women.

Background: Epidemiological studies have been inconsistent regarding an association between proton pump inhibitor (PPI) use and risk of primary cardiovascular disease (CVD) events.

Methods: We studied 85,189 postmenopausal women (mean age 63 years at baseline) without known CVD at enrollment into the Women's Health Initiative Observational Study (1993-1998). PPI use was determined from medication inventories at baseline and Year-3.

Assessment of Barriers and Enablers for Implementing a Population-Based Childhood Cancer Registry in Chennai, India.

Background: Despite most childhood cancer cases being diagnosed in low- and middle-income countries, there is a significant deficit of population-based childhood cancer registries (PBCCRs) in these regions. To address this critical gap, we established India's first dedicated PBCCR in Chennai on October 4, 2022, covering children aged 0-19. This study aims to identify the barriers and enablers to implementing the Chennai PBCCR.

Identifying Sequence Effects on Chain Dimensions of Disordered Proteins by Integrating Experiments and Simulations.

It has become increasingly evident that the conformational distributions of intrinsically disordered proteins or regions are strongly dependent on their amino acid compositions and sequence. To facilitate a systematic investigation of these sequence-ensemble relationships, we selected a set of 16 naturally occurring intrinsically disordered regions of identical length but with large differences in amino acid composition, hydrophobicity, and charge patterning. We probed their conformational ensembles with single-molecule Förster resonance energy transfer (FRET), complemented by circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy as well as small-angle X-ray scattering (SAXS).

Evaluation of methotrexate Pharmacogenomic variation to predict acute neurotoxicity in children with acute lymphoblastic leukemia.

Background: Methotrexate is an important component of curative therapy in childhood acute lymphoblastic leukemia (ALL), but the role of genetic variation influencing methotrexate clearance and transport in toxicity susceptibility in children with ALL is not well established. Therefore, we evaluated the association between suspected methotrexate pharmacogenomic variants and methotrexate-related neurotoxicity.

Methods: This study included children (aged 2-20 years) diagnosed with ALL (2005-2019) at six treatment centers in the southwest United States.

Association of COMT rs4680 Genotype With Chronic Neuropathic Pain Experience in Patients With Sickle Cell Disease.

Purpose: The pain experience of patients with sickle cell disease (SCD) frequently consists of episodes of acute exacerbation. However, recent studies suggest that many patients who suffer from SCD have symptoms of chronic neuropathic pain. Additional research is needed to determine what role genotype plays in the patient's pain phenotype experience in SCD.

Resazurin dye is an in vivo sensor of kidney tubular function.

Glomerular filtration rate (GFR) is the main functional index of kidney health and disease. Currently, no methods are available to directly measure tubular mass and function. Here, we report a serendipitous finding that the in vitro cell viability dye resazurin can be used in mice as an exogenous sensor of tubular function.

Familial Alzheimer's disease mutations in amyloid precursor protein impair calcineurin signaling to NMDA receptors.

Familial Alzheimer's disease (FAD) is frequently associated with mutations in the amyloid precursor protein (APP), which are thought to lead to cognitive deficits by impairing NMDA receptor (NMDAR)-dependent forms of synaptic plasticity. Given the reliance of synaptic plasticity on NMDAR-mediated Ca entry, shaping of NMDAR activity by APP and/or its disease-causing variants could provide a basis for understanding synaptic plasticity impairments associated with FAD. A region of APP (residues 639-644 within APP695) processed by the γ-secretase complex, which generates amyloid β (Aβ) peptides, is a hotspot for FAD mutations.

Male and female behavioral variability and morphine response in C57BL/6J, DBA/2J, and their BXD progeny following chronic stress exposure.

Drug addiction is a multifactorial syndrome in which genetic predispositions and exposure to environmental stressors constitute major risk factors for the early onset, escalation, and relapse of addictive behaviors. While it is well known that stress plays a key role in drug addiction, the genetic factors that make certain individuals particularly sensitive to stress and, thereby, more vulnerable to becoming addicted are unknown. In an effort to test a complex set of gene x environment interactions-specifically gene x chronic stress-here we leveraged a systems genetics resource: BXD recombinant inbred mice (BXD5, BXD8, BXD14, BXD22, BXD29, and BXD32) and their parental mouse lines, C57BL/6J and DBA/2J.

UPJE: Most pharmacy law educators have heard of it, but support remains divided.

Background: Most states require pharmacists to successfully pass the Multistate Pharmacy Jurisprudence Examination (MPJE) required by the National Association of Boards of Pharmacy (NABP) to obtain licensure as a pharmacist, though pass rates for the MPJE have declined in recent years. Meanwhile, NABP is pursing efforts to standardize the exam with the emergent Uniform Pharmacy Jurisprudence Examination (UPJE).

Objective: This study aimed to describe the current thinking of pharmacy law educators across the US on the UPJE.

Evaluating the impact of Canadian cannabis legalization on cannabis use outcomes in emerging adults: Comparisons to a US control sample via a natural experiment.

Background: Recreational cannabis legalization marked a significant policy shift in Canada, but has been difficult to evaluate because of the absence of a control group. Although it is unfeasible to evaluate legalization using a randomized controlled trial design, sophisticated statistical techniques can employ quasi-experimental designs using natural experiments. This study evaluates the impact of cannabis legalization in a longitudinal cohort of Canadian emerging adults by comparing changes in cannabis use frequency and related consequences over time to changes in a similar cohort in a United States jurisdiction where no policy change took place.

Avoidant Restrictive Food Intake Disorder in Pediatric Liver Transplant Patients.

Introduction: Following liver transplantation (LT), adequate nutrition is essential, as malnutrition may contribute to slower growth in pediatric patients and put patients at risk of complications following transplant. Avoidant Restrictive Food Intake Disorder (ARFID) is an eating disorder characterized by restrictive eating patterns that compromise nutrition. Patients with ARFID may have significant difficulty meeting nutritional needs due to fear of gastrointestinal distress, making it especially difficult to manage in patients following LT.