Pharmacy and Pharmaceutical Sciences Commons^™

Differential Effect Of Proinflammatory Cytokines On Corneal And Conjunctival Epithelial Cell Mucins And Glycocalyx, Kiumars Shamloo, Priya Mistry, Ashley Barbarino, Christopher Ross, Vishal Jhanji

Pharmacy Faculty Articles and Research

Purpose: Ocular surface mucins and glycocalyx are critical for providing ocular hydration as well lubrication and repelling pathogens or allergens. Elevated levels of tear proinflammatory cytokines in dry eye may have detrimental effect on mucins and glycocalyx. The present study tested the effect of proinflammatory cytokines IL-6, TNF-α, and IFN-γ on membrane-tethered mucins expression, glycocalyx, and viability of ocular surface epithelial cells.

Methods: Stratified cultures of human corneal and conjunctival epithelial cells were exposed to different concentrations of IL-6, TNF-α, and IFN-γ for 24 hours. The mucins gene and protein expressions were quantified by real-time polymerase chain reaction …

Engineering And Characterization Of Human Β-Defensin-3 And Its Analogues And Microcin J25 Peptides Against Mannheimia Haemolytica And Bovine Neutrophils, Harpreet Dhingra, Kamaljit Kaur, Baljit Singh

Pharmacy Faculty Articles and Research

Mannheimia haemolytica-induced bovine respiratory disease causes loss of millions of dollars to Canadian cattle industry. Current antimicrobials are proving to be ineffective and leave residues in meat. Antimicrobial peptides (AMPs) may be effective against M. haemolytica while minimizing the risk of drug residues. Cationic AMPs can kill bacteria through interactions with the anionic bacterial membrane. Human β-Defensin 3 (HBD3) and microcin J25 (MccJ25) are AMPs with potent activity against many Gram-negative bacteria. We tested the microbicidal activity of wild-type HBD3, three HBD3 peptide analogues (28 amino acid, 20AA, and 10AA) derived from the sequence of natural HBD3, and MccJ25 …

Evaluation Of Somatic Mutations In Solid Metastatic Pan-Cancer Patients, Moom Roosan, Isa Mambetsariev, Rebecca Pharaon, Jeremy Fricke, Angel R. Baroz, Joseph Chao, Chen Chen, Mohd W. Nasser, Ramakanth Chirravuri-Venkata, Maneesh Jain, Lynette Smith, Susan E. Yost, Karen L. Reckamp, Raju Pillai, Leonidas Arvanitis, Michelle Afkhami, Edward W. Wang, Vincent Chung, Mihaela Cristea, Marwan Fakih, Marianna Koczywas, Erminia Massarelli, Joanne Mortimer, Yuan Yuan, Surinder K. Batra, Sumanta Pal, Ravi Salgia

Pharmacy Faculty Articles and Research

Metastasis continues to be the primary cause of all cancer-related deaths despite the recent advancements in cancer treatments. To evaluate the role of mutations in overall survival (OS) and treatment outcomes, we analyzed 957 metastatic patients with seven major cancer types who had available molecular testing results with a FoundationOne CDx^® panel. The most prevalent genes with somatic mutations were TP53, KRAS, APC, and LRP1B. In this analysis, these genes had mutation frequencies higher than in publicly available datasets. We identified that the somatic mutations were seven mutually exclusive gene pairs and an additional fifty-two co-occurring gene pairs. Mutations …

Racial And Ethnic Disparities In Opioid Use For Adolescents At Us Emergency Departments, Michael T. Phan, Daniel M. Tomaszewski, Cody Arbuckle, Sun Yang, Candice D. Donaldson, Michelle A. Fortier, Brooke Jenkins, Erik Linstead, Zeev N. Kain

Pharmacy Faculty Articles and Research

Background

Racial/ethnic disparities in the use of opioids to treat pain disorders have been previously reported in the emergency department (ED). Further research is needed to better evaluate the impact race/ethnicity may have on the use of opioids in adolescents for the management of pain disorders in the ED.

Methods

This was a cross-sectional study using data from the National Hospital Ambulatory Medical Care Survey from 2006 to 2016. Multivariate models were used to evaluate the role of race/ethnicity in the receipt of opioid agonists while in the ED. All ED visits with patients aged 11–21 years old were analyzed. …

The Antibiogram: Key Considerations For Its Development And Utilization, William R. Truong, Levita Hidayat, Michael A. Bolaris, Lee Nguyen, Jason Yamaki

Pharmacy Faculty Articles and Research

The antibiogram is an essential resource for institutions to track changes in antimicrobial resistance and to guide empirical antimicrobial therapy. In this Viewpoint, data and examples from literature are presented that suggest institutions have not completely adopted the standardized approach in developing antibiograms, as variations in the development methodologies of antibiograms exist despite consensus guidelines (M39) published by CLSI. We emphasize developing antibiograms in line with the M39 recommendations will help ensure that they are accurate, reliable and valid, and highlight that understanding the limitations of antibiogram data is critical to ensuring appropriate interpretation and application to clinical decision-making. We …

Evaluation Of A Keratin 1 Targeting Peptide-Doxorubicin Conjugate In A Mouse Model Of Triple-Negative Breast Cancer, Azam Saghaeidehkordi, Shiuan Chen, Sun Yang, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Chemotherapy is the main treatment for triple-negative breast cancer (TNBC), a subtype of breast cancer that is aggressive with a poor prognosis. While chemotherapeutics are potent, these agents lack specificity and are equally toxic to cancer and nonmalignant cells and tissues. Targeted therapies for TNBC treatment could lead to more safe and efficacious drugs. We previously engineered a breast cancer cell targeting peptide 18-4 that specifically binds cell surface receptor keratin 1 (K1) on breast cancer cells. A conjugate of peptide 18-4 and doxorubicin (Dox) containing an acid-sensitive hydrazone linker showed specific toxicity toward TNBC cells. Here, we report the …

Apigenin And Structurally Related Flavonoids Allosterically Potentiate The Function Of Human Α7-Nicotinic Acetylcholine Receptors Expressed In Sh-Ep1 Cells, Waheed Shabbir, Keun-Hang Susan Yang, Bassem Sadek, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Phytochemicals, such as monoterpenes, polyphenols, curcuminoids, and flavonoids, are known to have anti-inflammatory, antioxidant, neuroprotective, and procognitive effects. In this study, the effects of several polyhydroxy flavonoids, as derivatives of differently substituted 5,7-dihydroxy-4H-chromen-4-one including apigenin, genistein, luteolin, kaempferol, quercetin, gossypetin, and phloretin with different lipophilicities (cLogP), as well as topological polar surface area (TPSA), were tested for induction of Ca²⁺ transients by α7 human nicotinic acetylcholine (α7 nACh) receptors expressed in SH-EP1 cells. Apigenin (10 μM) caused a significant potentiation of ACh (30 μM)-induced Ca²⁺ transients, but did not affect Ca²⁺ transients induced by high K^{+ …}

Compounded Gabapentin For Felines: Associated Metabolic Processes And Analysis Of Potency, Johnny Altwal

Student Scholar Symposium Abstracts and Posters

Pharmaceutical compounding provides pharmacists and clinicians the opportunity to create unique drug formulations that are better suited to a specific patient’s needs. This is especially prevalent in veterinary medicine where clinicians treat a variety of maladies in a large number of species, thereby requiring unique formulations to more easily deliver drugs to animals. Several examples of compounded veterinary formulations with sub-therapeutic potencies have been published, but none examine compounded gabapentin. Gabapentin is frequently compounded into an oral suspension for veterinary use from tablets or capsules for the purpose of pain management in felines and other small animals. The project’s goals …

Computational Design Of Β-Fluorinated Morphine Derivatives For Ph-Specific Binding, Nayiri Alexander, Makena Augenstein, Angelina Sorensen, Matthew Gartner

Student Scholar Symposium Abstracts and Posters

Opioids such as morphine are important pain-relieving drugs but also carry a risk of harmful side effects including addiction. Morphine is active in both healthy and inflamed tissue, however, decreasing the pKa of the biochemically-active amine group can promote selective binding in the more acidic conditions of inflamed tissue and reduce harmful side effects associated with opioids. Herein, we explore the impact of fluorination on the pKa of fluoromorphine derivatives to identify which will bind selectively in inflamed tissue. Theoretical pKa values are determined at the M06-2X(SMD)/aug-cc-pVDZ level of theory to calculate the ΔGaq" …

Ciliary Extracellular Vesicles Are Distinct From The Cytosolic Extracellular Vesicles, Ashraf M. Mohieldin, Rajasekharreddy Pala, Richard Beuttler, James J. Moresco, John R. Yates Iii, Surya M. Nauli

Pharmacy Faculty Articles and Research

Extracellular vesicles (EVs) are cell‐derived membrane vesicles that are released into the extracellular space. EVs encapsulate key proteins and mediate intercellular signalling pathways. Recently, primary cilia have been shown to release EVs under fluid‐shear flow, but many proteins encapsulated in these vesicles have never been identified. Primary cilia are ubiquitous mechanosensory organelles that protrude from the apical surface of almost all human cells. Primary cilia also serve as compartments for signalling pathways, and their defects have been associated with a wide range of human genetic diseases called ciliopathies. To better understand the mechanism of ciliopathies, it is imperative to know …

Suppression Of Human Coronavirus 229e Infection In Lung Fibroblast Cells Via Rna Interference, Hamidreza Montazeri Aliabadi, Jennifer Totonchy, Parvin Mahdipoor, Keykavous Parang, Hasan Uludağ

Pharmacy Faculty Articles and Research

Despite extensive efforts to repurpose approved drugs, discover new small molecules, and develop vaccines, COVID-19 pandemic is still claiming victims around the world. The current arsenal of antiviral compounds did not perform well in the past viral infections (e.g., SARS), which casts a shadow of doubt for use against the new SARS-CoV-2. Vaccines should offer the ultimate protection; however, there is limited information about the longevity of the generated immunity and the protection against possible mutations. This study uses Human Coronavirus 229E as a model coronavirus to test the hypothesis that effective delivery of virus-specific siRNAs to infected cells will …

Thyroid Hormone Synthesis Continues Despite Biallelic Thyroglobulin Mutation With Cell Death, Xiaohan Zhang, Aaron P. Kellogg, Cintia E. Citterio, Hao Zhang, Dennis Larkin, Yoshiaki Morishita, Héctor M. Targovnik, Viviana A. Balbi, Peter Arvan

Pharmacy Faculty Articles and Research

Complete absence of thyroid hormone is incompatible with life in vertebrates. Thyroxine is synthesized within thyroid follicles upon iodination of thyroglobulin conveyed from the endoplasmic reticulum (ER), via the Golgi complex, to the extracellular follicular lumen. In congenital hypothyroidism from biallelic thyroglobulin mutation, thyroglobulin is misfolded and cannot advance from the ER, eliminating its secretion and triggering ER stress. Nevertheless, untreated patients somehow continue to synthesize sufficient thyroxine to yield measurable serum levels that sustain life. Here, we demonstrate that TGW2346R/W2346R humans, TGcog/cog mice, and TGrdw/rdw rats exhibited no detectable ER export of thyroglobulin, accompanied by severe …

Usefulness Of Circulating Tumor Dna In Identifying Somatic Mutations And Tracking Tumor Evolution In Patients With Non-Small Cell Lung Cancer, Moom R. Roosan, Isa Mambetsariev, Rebecca Pharaon, Jeremy Fricke, Hatim Husain, Karen L. Reckamp, Marianna Koczywas, Erminia Massarelli, Andrea H. Bild, Ravi Salgia

Pharmacy Faculty Articles and Research

Background

The usefulness of circulating tumor DNA (ctDNA) in detecting mutations and monitoring treatment response has not been well studied beyond a few actionable biomarkers in non-small cell lung cancer (NSCLC).

Research Question

How does the usefulness of ctDNA analysis compare with that of solid tumor biopsy analysis in patients with NSCLC?

Methods

We retrospectively evaluated 370 adult patients with NSCLC treated at the City of Hope between November 2015 and August 2019 to assess the usefulness of ctDNA in mutation identification, survival, concordance with matched tissue samples in 32 genes, and tumor evolution.

Results

A total of 1,688 somatic …

Home Blood Pressure Monitoring To Improve Hypertension Control: A Narrative Review Of International Guideline Recommendations, John Andraos, Luma Munjy, Michael S. Kelly

Pharmacy Faculty Articles and Research

Home blood pressure monitoring (HBPM) is a convenient way to assess out-of-office blood pressure control and is recommended by numerous international guidelines to aid clinicians in the diagnosis and management of essential hypertension. Although available guidelines recommend the use of HBPM in patients receiving antihypertensive medication, their specific recommendations regarding optimal monitoring schedule, duration, and clinician interpretation of home blood pressure readings may differ among guidelines. Purpose: The purpose of this article is to review available international hypertension guideline recommendations related to the use of HBPM to improve hypertension control among patients receiving antihypertensive therapy. We also briefly highlight …

Effect Of Free Trade Agreements On Pharmaceutical Market Competition: The Case Of The 2009 Us-Peru Free Trade Agreement And Its Implementation As National Drug Policy, Lita Araujo, Enrique Seoane-Vazquez, Michael Montagne

Pharmacy Faculty Articles and Research

Free Trade Agreements (FTA) are controversial for threatening essential aspects of health, especially access to affordable medicines. The US-Peru FTA required changes in the Peruvian pharmaceutical legislation that resulted in the implementation of the National Drug Policy (NDP) of 2009. The NDP included more robust technical requirements for registration, a Peruvian Good Manufacturing Practices certificate, a longer timeline for drug registration, and an increase in registration fees. This study evaluated the impact of the FTA on the number of registrations and competition in the Peruvian pharmaceutical market.

Data for the period January 2005 to April 2014 were provided by the …

Analysis Of Gabapentinoids Abuse-Reports In The Middle East And North Africa Region Utilizing The Food And Drug Administration Adverse Event Reporting System, Mona Yaser Alsheikh, Ali Mofleh Alshahrani, Reem Dhayan Almutairi, Hana Abdulmohsen Althobaiti, Ahmed Ibrahim Fathelrahman, Enrique Seoane-Vazquez, Moudi Mubarak Alasmari

Pharmacy Faculty Articles and Research

Objectives: The purpose of this study was to identify abuse-related post-marketing reports associated with gabapentinoids use in the Middle East and North Africa (MENA) region countries. Methods: A retrospective cross-sectional analysis of abuse-related adverse drug event (ADE) reports from the Middle East and North Africa (MENA) region. It was performed using the Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 2008 through June 2020. Abuserelated ADE reports for gabapentin and pregabalin were extracted from the FAERS database. Descriptive statistics were performed, and the proportional reporting ratio (PRR) was calculated to detect disproportional attribution of abuse-related ADEs …

Predisposing, Enabling, And Need Factors Associated With The Choice Of Pharmacy Type In The Us: Findings From The 2015/2016 National Consumer Survey On The Medication Experience And Pharmacists’ Roles, Mohamed Rashrash, Suhila Sawesi, Jon C. Schommer, Lawrence M. Brown

Pharmacy Faculty Articles and Research

Background: Knowing the type of pharmacy used by the patient is meaningful to the pharmacist. Previous studies have assessed different factors predicting the kind of pharmacy selection and reached inconsistent findings. Objectives: To identify patient and health-related factors associated with pharmacy type selection. Methods: The Andersen Behavioral Model of Health Service Use was used to organize the selection of patient characteristics and categorize them as predisposing, enabling, and need factors. The dependent variable was the type of pharmacy used. Logistic regression was used to predict the association between patient-related characteristics and the type of pharmacy used. Results: Older age respondents …

Drug-Drug Interactions In Subjects Enrolled In Swog Trials Of Oral Chemotherapy, Lauren A. Marcath, Colin M. Finley, Siu Fun Wong, Daniel L. Hertz

Pharmacy Faculty Articles and Research

Background

Patients with cancer are at increased risk of drug-drug interactions (DDI), which can increase treatment toxicity or decrease efficacy. It is especially important to thoroughly screen DDI in oncology clinical trial subjects to ensure trial subject safety and data accuracy. This study determined the prevalence of potential DDI involving oral anti-cancer trial agents in subjects enrolled in two SWOG clinical trials.

Methods

Completed SWOG clinical trials of commercially available agents with possible DDI that had complete concomitant medication information available at enrollment were included. Screening for DDI was conducted through three methods: protocol-guided screening, Lexicomp® screening, and pharmacist determination …

Data For "Subtype-Selective Positive Modulation Of Sk Channels Depends On The Ha/Hb Helices", Miao Zhang, Meng Cui

Pharmacy Faculty Data Sets

In the activated state of small-conductance Ca²⁺-activated potassium (SK) channels, calmodulin interacts with the HA/HB helices and the S4-S5 linker. CyPPA potentiates SK2a and SK3 channel activity but not the SK1 and IK subtypes. Here, we report that the subtype-selectivity of CyPPA relies on the HA/HB helices. Mutating residues in the HA (V420) and HB (K467) helices of SK2a channels to their equivalent residues in IK channels diminished the potency of CyPPA. CyPPA elicited prominent responses on mutant IK channels with an arginine residue in the HB helix substituted for its equivalent lysine residue in the SK2a channels …

Categorization Of Marketed Artificial Tear Formulations Based On Their Ingredients: A Rational Approach For Their Use, Avani Kathuria, Kiumars Shamloo, Vishal Jhanji, Ajay Sharma

Pharmacy Faculty Articles and Research

Dry eye disease is a common ocular condition affecting millions of people worldwide. Artificial tears are the first line therapy for the management of dry eye disease. Artificial tear formulations contain a variety of active ingredients, biologically active excipients, and preservatives. Many of these formulations are also available as preservative-free. This study was conducted to inspect artificial tear formulations currently marketed in the United States for their active ingredients, biologically relevant excipients, and preservatives. The marketed artificial tears were examined at various US retail pharmacy chains and using the manufacturers’ website to compile information about active ingredients, inactive ingredients, and …

Nanomaterials As Novel Cardiovascular Theranostics, Rajasekharreddy Pala, Subhaswaraj Pattnaik, Siddhardha Busi, Surya M. Nauli

Pharmacy Faculty Articles and Research

Cardiovascular diseases (CVDs) are a group of conditions associated with heart and blood vessels and are considered the leading cause of death globally. Coronary heart disease, atherosclerosis, myocardial infarction represents the CVDs. Since CVDs are associated with a series of pathophysiological conditions with an alarming mortality and morbidity rate, early diagnosis and appropriate therapeutic approaches are critical for saving patients’ lives. Conventionally, diagnostic tools are employed to detect disease conditions, whereas therapeutic drug candidates are administered to mitigate diseases. However, the advent of nanotechnological platforms has revolutionized the current understanding of pathophysiology and therapeutic measures. The concept of combinatorial therapy …

Evaluating Opioid Dispensing Rates Among Pediatrics And Young Adults Based On Cures Data Reporting In California From 2015–2019, Michael T. Phan, Courtney Wong, Daniel M. Tomaszewski, Zeev N. Kain, Brooke Jenkins, Candice D. Donaldson, Michelle Fortier, Sun Yang

Pharmacy Faculty Articles and Research

Background

Receipt of opioid prescriptions in pediatric and young adult patients may be a risk factor for future opioid misuse. Data from prescription drug monitoring programs provide insight on outpatient opioid use. In our study, we analyzed the opioid dispensing rates for pediatrics and young adults in California. Methods

A secondary analysis was performed from 2015–2019 using Controlled Utilization Review and Evaluation System data. This database provides dispensing data of controlled substances in California. Patients younger than 25 years who were prescribed opiates were analyzed by county. We further divided them into two groups (children: ≤14 years; adolescents and young …

Stability Evaluation Of Extemporaneously Compounded Vancomycin Ophthalmic Drops: Effect Of Solvents And Storage Conditions, Christopher Ross, Basir Syed, Joanna Pak, Vishal Jhanji, Jason Yamaki, Ajay Sharma

Pharmacy Faculty Articles and Research

Vancomycin is the drug of choice for methicillin-resistant Staphylococcus aureus keratitis and other ocular infections. Vancomycin ophthalmic drops are not commercially available and require compounding. The present study was designed to investigate the stability of vancomycin ophthalmic drops in normal saline, phosphate-buffered saline (PBS), and balanced salt solution (BSS) while stored at room temperature or under refrigeration. Vancomycin ophthalmic drops (50 mg/mL) were aseptically prepared from commercially available intravenous powder using PBS, BSS, and saline. Solutions were stored at room temperature and in a refrigerator for 28 days. The vancomycin stability was tested by a microbiology assay and high-performance liquid …

Anti-Inflammatory Effects Of Α7-Nicotinic Ach Receptors Are Exerted Through Interactions With Adenylyl Cyclase-6, Simeng Zhu, Shiqian Huang, Guofang Xia, Jin Wu, Yan Shen, Ying Wang, Rennolds S. Ostrom, Ailian Du, Chengxing Shen, Congfeng Xu

Pharmacy Faculty Articles and Research

Background and purpose

Alpha 7 nicotinic acetylcholine receptors (CHRNA7) suppress inflammation through diverse pathways in immune cells, so is potentially involved in a number of inflammatory diseases. However, the detailed mechanisms underlying CHRNA7’s anti‐inflammatory effects remain elusive.

Experimental approach

The anti‐inflammatory effects of CHRNA7 agonists in both murine macrophages (RAW 264.7) and bone marrow‐derived macrophages (BMDM) stimulated with LPS were examined. The role of adenylyl cyclase 6 (AC6) in Toll‐like Receptor 4 (TLR4) degradation was explored via overexpression and knockdown. A mouse model of chronic obstructive pulmonary disease was used to confirm key findings.

Results

Anti‐inflammatory effects of CHRNA7 were …

Sars-Cov-2 Early Infection Signature Identified Potential Key Infection Mechanisms And Drug Targets, Yue Li, Ashley Duche, Michael R. Sayer, Don Roosan, Farid G. Khalafalla, Rennolds S. Ostrom, Jennifer Totonchy, Moom Roosan

Pharmacy Faculty Articles and Research

Background

The ongoing COVID-19 outbreak has caused devastating mortality and posed a significant threat to public health worldwide. Despite the severity of this illness and 2.3 million worldwide deaths, the disease mechanism is mostly unknown. Previous studies that characterized differential gene expression due to SARS-CoV-2 infection lacked robust validation. Although vaccines are now available, effective treatment options are still out of reach.

Results

To characterize the transcriptional activity of SARS-CoV-2 infection, a gene signature consisting of 25 genes was generated using a publicly available RNA-Sequencing (RNA-Seq) dataset of cultured cells infected with SARS-CoV-2. The signature estimated infection level accurately in …

Aacp Basic Resources For Pharmacy Education, Jason Guy, Ivan Portillo, Robert D. Beckett, Kayce Gill, Kimberly Mitchell, Jill Nissen, Priya Shenoy

Library Association/Organization Work

"The AACP Basic Resources for Pharmacy Education is produced as a guide for those developing or maintaining the library collections that serve colleges and schools of pharmacy. The goal of the Basic Resources list is to make recommendations of books and other works to be included in pharmacy libraries, but not all titles are required to be purchased. Each pharmacy college has its own mission and its own program(s), and so each college’s library collection must reflect that mission and support the college’s program(s). Excellent library collections are built by knowledgeable librarians and drug information specialists using their professional judgment …

Label‑Free Spectral Imaging To Study Drug Distribution And Metabolism In Single Living Cells, Qamar Alshammari, Rajasekharreddy Pala, Nir Katzir, Surya M. Nauli

Pharmacy Faculty Articles and Research

During drug development, evaluation of drug and its metabolite is an essential process to understand drug activity, stability, toxicity and distribution. Liquid chromatography (LC) coupled with mass spectrometry (MS) has become the standard analytical tool for screening and identifying drug metabolites. Unlike LC/MS approach requiring liquifying the biological samples, we showed that spectral imaging (or spectral microscopy) could provide high-resolution images of doxorubicin (dox) and its metabolite doxorubicinol (dox’ol) in single living cells. Using this new method, we performed measurements without destroying the biological samples. We calculated the rate constant of dox translocating from extracellular moiety into the cell and …

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …

Patterns Of Cilia Gene Dysregulations In Major Psychiatric Disorders, Wedad Alhassen, Siwei Chen, Marquis Vawter, Brianna Kay Robbins, Henry Nguyen, Thant Nyi Myint, Yumiko Saito, Anton Schulmann, Surya M. Nauli, Olivier Civelli, Pierre Baldi, Amal Alachkar

Pharmacy Faculty Articles and Research

Primary cilia function as cells' antennas to detect and transduce external stimuli and play crucial roles in cell signaling and communication. The vast majority of cilia genes that are causally linked with ciliopathies are also associated with neurological deficits, such as cognitive impairments. Yet, the roles of cilia dysfunctions in the pathogenesis of psychiatric disorders have not been studied. Our aim is to identify patterns of cilia gene dysregulation in the four major psychiatric disorders: schizophrenia (SCZ), autism spectrum disorder (ASD), bipolar disorder (BP), and major depressive disorder (MDD). For this purpose, we acquired differentially expressed genes (DEGs) from the …

Evaluating Risk Factors For Acute Graft Versus Host Disease In Pediatric Hematopoietic Stem Cell Transplant Patients Receiving Tacrolimus, Michael Phan, Rishikesh Chavan, Richard Beuttler, Nicole Benipayo, Grace Magedman, David Buchbinder, Daniel Tomaszewski, Sun Yang

Pharmacy Faculty Articles and Research

To identify the clinical and pharmacological risk factors associated with tacrolimus pharmacodynamics for acute graft-versus-host disease (aGVHD) in pediatric patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) from a matched related donor. A retrospective cohort single center chart review study was conducted with pediatric patients who received tacrolimus prophylaxis after allogeneic HSCT between January 1, 2017, and December 31, 2019. Potential risk factors were tested separately between aGVHD and non-aGVHD cohorts and were further analyzed in a logistic regression model with backward elimination and a partial least squares discriminant analysis. Thirty-three patient cases were included in our study and 52% …