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Articles 1 - 30 of 479
Full-Text Articles in Diseases
Sirt1 And Ifi16 Cooperatively Regulate Hbv Replication Via Epigenetic Modulation And Innate Immune Activation, Zahra Zahid Piracha, Umar Saeed, Neelam Abid, Syed Shahan Gilani, Hafiz Ahmad Bilal Akhtar Chughtai, Areesha Wasti, Muhammad Waseem, Dilber Uzun Ozsahin, Andromeda M. Nauli, Surya M. Nauli
Sirt1 And Ifi16 Cooperatively Regulate Hbv Replication Via Epigenetic Modulation And Innate Immune Activation, Zahra Zahid Piracha, Umar Saeed, Neelam Abid, Syed Shahan Gilani, Hafiz Ahmad Bilal Akhtar Chughtai, Areesha Wasti, Muhammad Waseem, Dilber Uzun Ozsahin, Andromeda M. Nauli, Surya M. Nauli
Pharmacy Faculty Articles and Research
Background
Hepatitis B virus (HBV) establishes persistent infection through the formation of a covalently closed circular DNA (cccDNA) minichromosome, which enables immune evasion and sustained viral replication. While SIRT1, IFI16, and STING are known to modulate antiviral pathways, their cooperative role in regulating HBV transcription and host immunity remains poorly defined.
Methods
We investigated the functional interplay between SIRT1, IFI16, and STING using confocal microscopy, chromatin immunoprecipitation (ChIP), gene silencing, and quantitative PCR in HBV-replicating cell models. Interactions with HBV cccDNA and effects on viral transcription and interferon-stimulated gene (ISG) expression were analyzed. Northern blotting and RT-qPCR were used to …
Lovastatin Potentiates The Function Of Α7-Nicotinic Acetylcholine Receptors, Dmytro Isaev, Keun-Hang Susan Yang, Murat Oz
Lovastatin Potentiates The Function Of Α7-Nicotinic Acetylcholine Receptors, Dmytro Isaev, Keun-Hang Susan Yang, Murat Oz
Pharmacy Faculty Articles and Research
Background/Objectives: Statins are currently one of the most commonly used cholesterol-lowering drugs. In recent years, in addition to their well-known effects on the cardiovascular system, statins have been shown to exert beneficial effects in the progression of various neuropsychiatric and neurodegenerative diseases. Methods: In this study, the effects of lovastatin on the function of α7-nicotinic acetylcholine (nACh) receptors expressed in rat hippocampus and Xenopus oocytes were investigated. Results: In whole-cell patch clamp studies in hippocampal neurons, 21-day chronic (20 mg/kg), but not acute (20 min), lovastatin treatment caused significant potentiation of choline (a selective agonist for α7 nACh receptors)-induced currents …
Expert Recommendations To Strengthen Chikungunya Outbreak Surveillance And Reporting For Traveler Health Protection, Daniel C. Payne, Karoun H. Bagamian, Jeffery Goad, Nathan D. Grubaugh, Michael A. Johansson, Moritz U. G. Kraemer, Eyal Leshem, Francesca F. Norman, Alfonso J. Rodríguez-Morales, Henrik Salje, Stephen Thomas, Scott C. Weaver, Lindsey A. Laytner, Rebecca Sturgis, Suzanne K. Scheele, Davidson H. Hamer
Expert Recommendations To Strengthen Chikungunya Outbreak Surveillance And Reporting For Traveler Health Protection, Daniel C. Payne, Karoun H. Bagamian, Jeffery Goad, Nathan D. Grubaugh, Michael A. Johansson, Moritz U. G. Kraemer, Eyal Leshem, Francesca F. Norman, Alfonso J. Rodríguez-Morales, Henrik Salje, Stephen Thomas, Scott C. Weaver, Lindsey A. Laytner, Rebecca Sturgis, Suzanne K. Scheele, Davidson H. Hamer
Pharmacy Faculty Articles and Research
Chikungunya, a debilitating mosquito-borne disease caused by chikungunya virus, has surged dramatically in the past two decades. Chikungunya outbreaks can intensify rapidly, with infections posing a significant endemic health burden in tropical/subtropical areas and for travelers. Health professionals require timely and accurate outbreak information to adequately protect travelers and assess chikungunya risk. However, detection is often insufficient in the areas most susceptible to outbreaks, leading to diagnostic and reporting delays. Consequently, travelers are often unaware of increased chikungunya infection risk at their destination. We assessed chikungunya surveillance and reporting resources, and we developed expert recommendations for traveler health protection. Because …
Mechanisms Of Binding And Immune Escape Resistance For Broadly Neutralizing Antibodies Targeting Distinct Conserved Sars-Cov-2 Spike Epitopes: A Hierarchical Approach Integrating Mutational Profiling And Energy Landscape Analysis, Mohammed Alshahrani, Will Gatlin, Max Ludwick, Lucas Turano, Brandon Foley, Gennady M. Verkhivker
Mechanisms Of Binding And Immune Escape Resistance For Broadly Neutralizing Antibodies Targeting Distinct Conserved Sars-Cov-2 Spike Epitopes: A Hierarchical Approach Integrating Mutational Profiling And Energy Landscape Analysis, Mohammed Alshahrani, Will Gatlin, Max Ludwick, Lucas Turano, Brandon Foley, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
The continued evolution of SARS-CoV-2 has enabled an escape from most monoclonal antibodies, yet a subset of broadly neutralizing antibodies targeting three newly identified super-conserved RBD epitopes—SCORE-A, SCORE-B, and SCORE-C—retains remarkable activity against even the most recent JN.1-derived sublineages. Here, we employed an integrated computational framework combining conformational dynamics, mutational scanning, MM-GBSA binding energetics, and frustration profiling to dissect the molecular mechanisms by which XGI antibodies achieve broad neutralization and resistance to immune escape. Structural analysis revealed that all three SCORE epitopes share a common architecture: a highly conserved, minimally frustrated core that provides stable anchoring, flanked by peripheral regions …
Brain Delivery Of Antibody-Derived Biologicals For Alzheimer’S Disease: An Updated Narrative Review, Rachita K. Sumbria, Ruben J. Boado
Brain Delivery Of Antibody-Derived Biologicals For Alzheimer’S Disease: An Updated Narrative Review, Rachita K. Sumbria, Ruben J. Boado
Pharmacy Faculty Articles and Research
Antibodies directed against β-amyloid (Aβ) have been developed for the treatment of Alzheimer’s disease (AD). However, the in vivo central efficacy is reduced by the poor penetration of antibodies across the blood–brain barrier (BBB). In addition, these antibodies have been associated with adverse effects like amyloid-related imaging abnormalities. Thus, the development of new antibody-based therapies for AD with improved transport across the BBB may improve efficacy and reduce adverse effects. Antibodies targeting the BBB transferrin receptor (TfR) are able to cross the BBB through receptor-mediated transcytosis, producing a global distribution throughout the brain. Along the same line, bispecific antibodies directed …
Sedentary Behavior Modifies The Effect Of Balance Rehabilitation On Balance Discordance In Parkinson’S Disease, Franziska Albrecht, Sarah J. Conklin, Andrew Hooyman, Daniel S. Peterson, Jason K. Longhurst, Erika Franzén
Sedentary Behavior Modifies The Effect Of Balance Rehabilitation On Balance Discordance In Parkinson’S Disease, Franziska Albrecht, Sarah J. Conklin, Andrew Hooyman, Daniel S. Peterson, Jason K. Longhurst, Erika Franzén
Physical Therapy Faculty Articles and Research
Individuals with Parkinson’s disease (PD) often experience a misalignment between their perceived and actual balance ability, known as balance discordance, which has been associated with falls. We examined whether high-intensity balance and gait training (HiBalance) alters balance discordance in individuals with PD, and whether baseline sedentary behavior influences these changes. A secondary analysis examining pre- to post-intervention discordance changes of two HiBalance clinical trials (N = 97) using linear regression with interactions between sedentary behavior and pre-intervention discordance. The sample included two cohorts: one clinical and one research based. The model including sedentary behavior and its interaction with pre-intervention …
Structural Transformation Of A Hydrogel-Forming Cell Division Protein Zapb Of Multidrug Resistant Klebsiella Pneumoniae With Small Molecules, Ayesha Khan, M. Iqbal Choudhary, Sumaira Javaid, Humaira Zafar, Innokentiy Maslennikov, Atia-Tul Wahab
Structural Transformation Of A Hydrogel-Forming Cell Division Protein Zapb Of Multidrug Resistant Klebsiella Pneumoniae With Small Molecules, Ayesha Khan, M. Iqbal Choudhary, Sumaira Javaid, Humaira Zafar, Innokentiy Maslennikov, Atia-Tul Wahab
Pharmacy Faculty Articles and Research
Septal ring assembly protein ZapB (EMR18431.1) is involved in Z-ring formation, and nucleoid segregation during the bacterial cell division . It promotes cell division in the initial stages of the cell cycle through direct interaction with FtsZ, thus stimulating Z-ring assembly. The ZapB inhibition can make bacterial cell susceptible to primary antibiotics, and therefore considered as an important approach for adjuvent therapy against MDR bacterial infections. Hence in the current study, ZapB protein of multidrug resistant Klebsiella pneumoniae was cloned, and expressed in E. coli system. To understand its role, and to assess the mechanism of ZapB activation, the characteristic …
Using Diffusion Mri To Relate Hippocampal Subfield Microstructure To Delayed Verbal Memory In Cognitively Intact Individuals At Genetic Risk For Developing Alzheimer's Disease, Jennapher Lingo Vangilder, Andrew Hooyman, Sasha Hakhu, Kurt G. Schilling, Leland S. Hu, Yuxiang Zhou, Richard J. Caselli, Leslie C. Baxter, Scott C. Beeman
Using Diffusion Mri To Relate Hippocampal Subfield Microstructure To Delayed Verbal Memory In Cognitively Intact Individuals At Genetic Risk For Developing Alzheimer's Disease, Jennapher Lingo Vangilder, Andrew Hooyman, Sasha Hakhu, Kurt G. Schilling, Leland S. Hu, Yuxiang Zhou, Richard J. Caselli, Leslie C. Baxter, Scott C. Beeman
Physical Therapy Faculty Articles and Research
Intervention to delay the onset of Alzheimer's disease (AD) is an important treatment strategy but detecting at-risk individuals before significant disease progression remains challenging. This study evaluates the relationship between hippocampal microstructure and verbal cognition in cognitively intact older adults, focusing on the differences between APOΕ ε4 allele carriers and noncarriers. Participants (n = 41 noncarriers, 33 carriers) over 60 years old (mean ± SD: carriers 71 ± 6.6; noncarriers 71 ± 6.4 years) underwent diffusion-weighted magnetic resonance imaging (dMRI) and volumetric assessments. We assessed hippocampal structure, including microstructure, using Neurite Orientation Dispersion and Density Imaging (NODDI), diffusion tensor …
Multi-Modal Tensor Fusion For Alzheimer’S Disease Recognition, Mason Li, Tiffany Le, Jiajing Huang, Yuxin Wen
Multi-Modal Tensor Fusion For Alzheimer’S Disease Recognition, Mason Li, Tiffany Le, Jiajing Huang, Yuxin Wen
Engineering Faculty Articles and Research
Accurate and early diagnosis of Alzheimer’s disease (AD) is critical for effective intervention, disease monitoring, and patient care. Traditional diagnostic approaches rely on a single modality, such as clinical assessments, neuroimaging, or genetic markers, which may fail to capture the complex, multifaceted nature of AD. Multimodal learning has therefore been explored to integrate complementary information across data sources. However, conventional fusion strategies, including early feature concatenation and late decision-level fusion, often model modalities independently and fail to capture high-order cross-modal interactions. To address these limitations, we propose a multimodal tensor fusion network (MTFN) that integrates heterogeneous data sources, including visual …
Discordance Between Actual And Perceived Balance Ability Relates To Quality Of Life And Global Cognition In A Clinical Sample Of Parkinson Patients, Daniel S. Peterson, Jason K. Longhurst, Franziska Albrecht, Joanna Weller, Jennifer Vasquez, Myassar Zarif, Mark Gudesblatt, Andrew Hooyman
Discordance Between Actual And Perceived Balance Ability Relates To Quality Of Life And Global Cognition In A Clinical Sample Of Parkinson Patients, Daniel S. Peterson, Jason K. Longhurst, Franziska Albrecht, Joanna Weller, Jennifer Vasquez, Myassar Zarif, Mark Gudesblatt, Andrew Hooyman
Physical Therapy Faculty Articles and Research
Background
Misalignment between actual and perceived balance ability provides relevant information to understand functional deficits and fall risk. However, few studies have provided a continuous quantification of misalignment in neurological populations such as people with Parkinson's disease (PD).Objective
Determine whether a continuous quantification of misalignment between actual and perceived balance ability, discordance, relates to functional outcomes such as quality of life and cognition.Methods
Actual (gait velocity), and perceived (Activities of Balance Confidence) balance, cognition (measured via a computer-based cognitive assessment), and mobility-related quality of life were captured in a clinical sample of 95 people with PD. Primary outcomes …Periodontal Biomarkers In Cardiovascular Disease: Mechanisms, Diagnostics, And Clinical Implications, Max Foroughi, Keykavous Parang
Periodontal Biomarkers In Cardiovascular Disease: Mechanisms, Diagnostics, And Clinical Implications, Max Foroughi, Keykavous Parang
Pharmacy Faculty Articles and Research
Purpose
Periodontal disease is a chronic inflammatory condition increasingly associated with cardiovascular disease (CVD) beyond shared risk factors. This review evaluates evidence linking periodontal inflammation to cardiovascular outcomes and identifies periodontal biomarkers with potential relevance for cardiovascular risk assessment.
Methods
A narrative review was conducted using PubMed, Scopus, and Web of Science databases, including studies published between 1990 and 2025. Epidemiological, clinical, and mechanistic studies examining associations between periodontal disease, inflammatory and microbial biomarkers, and cardiovascular outcomes were included. Biomarkers were categorized as inflammatory cytokines, acute-phase proteins, oxidative stress markers, lipid mediators, and microbial indicators. Evidence regarding periodontal therapy and …
Heat And Socioeconomic Deprivation Compound To Drive Coronary Heart Disease In Los Angeles, Shutong Huo, Tessa R. Pulido, Reginald S. Archer, Joshua B. Fisher, Jason A. Douglas
Heat And Socioeconomic Deprivation Compound To Drive Coronary Heart Disease In Los Angeles, Shutong Huo, Tessa R. Pulido, Reginald S. Archer, Joshua B. Fisher, Jason A. Douglas
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Background:
Socioeconomic deprivation and environmental heat exposure each increase cardiovascular risk, yet evidence is limited on how these stressors co-occur and jointly shape disease burden within cities. Mapping their overlap can inform equity-oriented planning and needs-based allocation of health and social protection resources.
Methods:
We conducted an ecological geospatial analysis of 2,513 census tracts in Los Angeles County. Adult coronary heart disease (CHD) prevalence was obtained from CDC Population Level Analysis and Community Estimates (2021). Socioeconomic deprivation was measured using the Social Deprivation Index (SDI), and heatwave surface heat hazard was measured using land surface temperature (LST) retrieved from the …
Improving Hba1c And Diabetes Preventative Screening Measures In Spanish-Speaking Patients With Clinical Pharmacist Care: A Quality Improvement Initiative, Jennifer Ko, Tila P. Nguyen, Bonnie K. Chen, Richard Beuttler
Improving Hba1c And Diabetes Preventative Screening Measures In Spanish-Speaking Patients With Clinical Pharmacist Care: A Quality Improvement Initiative, Jennifer Ko, Tila P. Nguyen, Bonnie K. Chen, Richard Beuttler
Pharmacy Faculty Articles and Research
Purpose:
To evaluate the impact of clinical pharmacist interventions on HbA1c and adherence to diabetes preventative screenings among Spanish-speaking adults with uncontrolled type 2 diabetes.Methods:
This retrospective evaluation of a quality improvement initiative included Spanish-speaking adults with baseline HbA1c of 8% or greater who received at least 1 clinical pharmacist visit at a Federally Qualified Health Center. Outcomes included changes in glycemic control and timely preventive care screenings (diabetic eye exam, diabetic foot exam, urine albumin-to-creatinine ratio [UACR] test, and statin use), analyzed using logistical regression and McNemar’s test.Results:
Among 70 included patients, the mean age was 55.6 …Selectivity Modulation Of Small Cationic Membrane-Active Cyclic Peptides With Broad-Spectrum Activity Against Bacteria And Fungi, Sandeep Lohan, Rakesh Kumar Tiwari, Innokentiy Maslennikov, Kaustav Das Gupta, Shakti Singh, Keykavous Parang
Selectivity Modulation Of Small Cationic Membrane-Active Cyclic Peptides With Broad-Spectrum Activity Against Bacteria And Fungi, Sandeep Lohan, Rakesh Kumar Tiwari, Innokentiy Maslennikov, Kaustav Das Gupta, Shakti Singh, Keykavous Parang
Pharmacy Faculty Articles and Research
To investigate how ring size and backbone flexibility influence antimicrobial potency and cytotoxicity, we synthesized a series of macrocyclic peptides of lead peptide p1 (c[Arg-Arg-arg-arg-dip-Trp-dip]) by incorporating Gly, 2-aminoethoxyacetic acid (EAA), or 2,4-diaminobutyric acid (Dab). Two optimized peptides, 6b and 10b, retained broad-spectrum activity against drug-resistant Gram-positive (MIC, 1.5–6.2 μg/mL) and Gram-negative bacteria (MIC, 4–25 μg/mL), as well as pathogenic fungi, while exhibiting enhanced selectivity for microbial cells. Their therapeutic indices (TI ∼407 and ∼394, respectively) were ∼2-fold higher than p1, indicating improved safety. Both peptides remained effective against Gram-negative pathogens beyond the reach of daptomycin, were rapidly bactericidal, and …
Evidentiary Standards For Newly Approved Antibiotics For Uncomplicated Urinary Tract Infections, Rosa Rodriguez-Monguio, Enrique Seoane-Vazquez, John H. Powers Iii
Evidentiary Standards For Newly Approved Antibiotics For Uncomplicated Urinary Tract Infections, Rosa Rodriguez-Monguio, Enrique Seoane-Vazquez, John H. Powers Iii
Pharmacy Faculty Articles and Research
Importance: Uncomplicated urinary tract infections (uUTIs) are among the most common bacterial infections and are typically treated with existing oral antibiotics. In 2024–2025, the FDA approved two new oral agents, sulopenem etzadroxil/probenecid and gepotidacin, via expedited review pathways, for the treatment of uUTIs. Objective: To assess the clinical significance and regulatory evidence supporting FDA approval of sulopenem/probenecid and gepotidacin for uUTI, and to analyze the adherence of pivotal phase III trials to regulatory standards for approval and FDA guidelines. Design, Setting, and Participants: Comparative descriptive analysis of publicly available data from phase 3 randomized, double-blind, active-controlled clinical …
Disruption Of Proteoglycan 4 (Prg4)-Cd44 Signaling Modulates Chronic Synovitis In Conditionally Inactivated Mice, Khaled A. Elsaid, Ling Zhang, Thomas Zhao, Ava Marks, Derek Jenkins, Gregory D. Jay
Disruption Of Proteoglycan 4 (Prg4)-Cd44 Signaling Modulates Chronic Synovitis In Conditionally Inactivated Mice, Khaled A. Elsaid, Ling Zhang, Thomas Zhao, Ava Marks, Derek Jenkins, Gregory D. Jay
Pharmacy Faculty Articles and Research
Background
Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. PRG4 inhibits synovial macrophage (SM) activation via xanthine oxidase (XO) and hypoxia inducible factor alpha (HIF-1α) suppression. We aimed to evaluate the contribution of PRG4-CD44 interaction to synovial homeostasis and investigate PRG4’s signaling dysfunction in synovial tissues from patients with osteoarthritis (OA). We hypothesized that CD44 mediates synovitis due to PRG4 loss and that PRG4 signaling dysfunction is associated with high-grade synovitis in OA.
Methods
Prg4FrtloxP/FrtloxP are transgenic mice wherein tamoxifen (TAM) inactivates the Frt allele and creates a knockout state (Prg4FrtKO/FrtKO …
Biomarkers In Alzheimer's Disease Clinical Trials: 2025, Amanda M. Leisgang Osse, Yadi Zhou, Jefferson W. Kinney, Andrew Hooyman, Ayan Sengupta, Jorge Fonseca, Aaron H. Burstein, Laura Nisenbaum, Howard M. Fillit, Feixiong Cheng, Jeffrey L. Cummings
Biomarkers In Alzheimer's Disease Clinical Trials: 2025, Amanda M. Leisgang Osse, Yadi Zhou, Jefferson W. Kinney, Andrew Hooyman, Ayan Sengupta, Jorge Fonseca, Aaron H. Burstein, Laura Nisenbaum, Howard M. Fillit, Feixiong Cheng, Jeffrey L. Cummings
Physical Therapy Faculty Articles and Research
Biomarkers play an important role in Alzheimer's disease (AD) clinical trials in several contexts of use, including defining trial eligibility and serving as outcome measures. Utilizing clinicaltrials.gov, a registry of clinical trials, we assessed biomarker usage across all active AD disease-targeted therapeutic (DTT) trials. Biomarkers are widely used in AD DTT trials, with 84% including a fluid, imaging, and/or digital biomarker, either as an inclusion criterion or as an outcome measure. In DTT trials, biomarkers were included in 83% of Phase 3 trials, 91% of Phase 2 trials, and 72% of Phase 1 trials. Biomarkers were used for trial inclusion …
Pediatric Inflammatory Bowel Disease Tissue Classification From Pathology Slide Images: Detecting Phenotypes Using Computer Vision, Chloe Martin-King, Ali Nael, Louis Ehwerhemuepha, Blake Calvo, Quinn Gates, Jamie Janchoi, Elisa Ornelas, Melissa Perez, Andrea Venderby, John Miklavcic, Peter Chang, Aaron Sassoon, Brian Rubio, Ghislaine Barrigan, Kenneth Grant
Pediatric Inflammatory Bowel Disease Tissue Classification From Pathology Slide Images: Detecting Phenotypes Using Computer Vision, Chloe Martin-King, Ali Nael, Louis Ehwerhemuepha, Blake Calvo, Quinn Gates, Jamie Janchoi, Elisa Ornelas, Melissa Perez, Andrea Venderby, John Miklavcic, Peter Chang, Aaron Sassoon, Brian Rubio, Ghislaine Barrigan, Kenneth Grant
Food Science Faculty Articles and Research
Background and Aims
With the advent of computer vision algorithms, we hypothesize that histopathology images from endoscopic biopsies may be utilized for automated classification of histologic phenotypes, thus guiding Crohn’s disease and ulcerative colitis diagnosis and treatment. The aim of our study is to assess whether artificial intelligence can be used to improve pediatric inflammatory bowel disease outcomes by aiding pathologists with accurate detection of abnormal tissue sections.Methods
Three two-dimensional (2D) convolutional neural networks with multiple instance learning were developed to classify histopathology tissue sections as normal vs abnormal and as containing active inflammation and/or chronic changes/architectural distortion.Results …
Dual Tyk2/Jak1 Inhibition By Brepocitinib Reprograms Synoviocyte Pathobiology: Mechanistic Insights Into Targeted Therapy For Rheumatoid Arthritis, Umar Saeed, Zahra Zahid Piracha, Andromeda M. Nauli, Surya M. Nauli
Dual Tyk2/Jak1 Inhibition By Brepocitinib Reprograms Synoviocyte Pathobiology: Mechanistic Insights Into Targeted Therapy For Rheumatoid Arthritis, Umar Saeed, Zahra Zahid Piracha, Andromeda M. Nauli, Surya M. Nauli
Pharmacy Faculty Articles and Research
Background:
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial hyperplasia, persistent inflammation, and joint destruction. Targeted inhibition of intracellular signaling pathways, such as JAK-STAT, has improved RA treatment outcomes, though safety and selectivity remain as concerns. Brepocitinib, a dual TYK2/JAK1 inhibitor, has shown clinical efficacy in the management of autoimmune diseases, yet its mechanistic impact on synoviocytes remains underexplored.
Objectives:
To investigate the molecular and functional effects of brepocitinib on MH7A and RA-FLS synoviocytes, a key effector cell type in RA pathogenesis.
Methods:
MH7A and RA-FLS cells were treated with brepocitinib (0.5 µM, 1 µM, and 5 …
P-78. Susceptibility Of Omadacycline In Bone And Joint Infections: Pathogen Susceptibility And Regimen Decisions From An Ongoing Randomized Controlled Trial, Amy Y. Kang, Evelyn A. Flores, Donna Phan Tran, Buchen (Olivia) Han, Isabel Payan, Guarina Garcia Delgado, Loren G. Miller
P-78. Susceptibility Of Omadacycline In Bone And Joint Infections: Pathogen Susceptibility And Regimen Decisions From An Ongoing Randomized Controlled Trial, Amy Y. Kang, Evelyn A. Flores, Donna Phan Tran, Buchen (Olivia) Han, Isabel Payan, Guarina Garcia Delgado, Loren G. Miller
Pharmacy Faculty Articles and Research
Background Treatment of Bone and joint infections (BJIs) with oral antibiotics may have benefits compared to IV therapy. Yet oral treatment options may be limited by lack of options due to antibiotic-resistant pathogens and tolerability concerns. Omadacycline has in vitro activity against common BJI pathogens, including MRSA and most Enterobacterales. However, real-world susceptibility data and implications for oral therapy are limited. Methods
We conducted a descriptive analysis of data from adult patients enrolled to date in an open-label, randomized controlled trial of comparing omadacycline-containing antibiotic regimen vs. standard of care (SOC) antibiotics for BJIs. Omadaycline susceptibility was assessed on available …
686. Antibiotic Prescribing For Urinary Tract Infections In Outpatient Settings: A Multicenter Assessment Based On The Five Ds Of Stewardship, Amy Y. Kang, Oliver Tan, Sunwoo Oh, Nikki Derleth, Megan Shieh, Helen Vu, Inna Tagarino, Audrey Harrington, Deborah Kupferwasser, Loren G. Miller
686. Antibiotic Prescribing For Urinary Tract Infections In Outpatient Settings: A Multicenter Assessment Based On The Five Ds Of Stewardship, Amy Y. Kang, Oliver Tan, Sunwoo Oh, Nikki Derleth, Megan Shieh, Helen Vu, Inna Tagarino, Audrey Harrington, Deborah Kupferwasser, Loren G. Miller
Pharmacy Faculty Articles and Research
Background Urinary tract infections (UTIs) are a leading cause of outpatient antibiotic use. Prior studies have documented inappropriate prescribing during outpatient UTI visits, but few have assessed intervention opportunities using a structured stewardship framework. We evaluated UTI prescribing practices in a healthcare system using the Five Ds framework: Diagnosis, Drug, Dose, Duration, and De-escalation. Methods
We conducted a retrospective study across 4 medical centers and > 20 outpatient clinics within the Los Angeles County Department of Health Services, the second largest U.S. safety net healthcare system. To ensure adequate representation across sites while maintaining feasibility for manual chart review, we reviewed …
Evaluating The Effect Of Ethnicity And Amyloid On Gait Speed In The Healthy Aging Brain Study-Health Disparities Study, Alexandra M. Reed, Andrew Hooyman, Edward Ofori, Sydney Y. Schaefer
Evaluating The Effect Of Ethnicity And Amyloid On Gait Speed In The Healthy Aging Brain Study-Health Disparities Study, Alexandra M. Reed, Andrew Hooyman, Edward Ofori, Sydney Y. Schaefer
Physical Therapy Faculty Articles and Research
Background
Many novel Alzheimer's disease (AD) biomarkers have been studied in non-Hispanic White populations, despite Hispanic/Latino adults being 1.5 times more likely to develop AD and receiving a later diagnosis. Equitable, accessible assessments are needed to identify individuals at risk earlier. While cognitive screening monitors early AD signs, neuropsychological tests are often inequitable across ethnicity, race, and other social determinants of health. However, we have shown that performance-based motor assessments may be less susceptible to demographic factors than memory tests, and may be more equitable for screening older adults. Gait speed has been linked to elevated amyloid in non-Hispanic White …
Hepatocyte-Specific Lrp1 Silencing Exacerbates Brain Amyloidosis Without Compensatory Ldl Receptor Family Involvement, Brian Carson, Josephine Chu, Devaraj V. Chandrashekar, Jerome Garcia, Rachita K. Sumbria, Derick Han
Hepatocyte-Specific Lrp1 Silencing Exacerbates Brain Amyloidosis Without Compensatory Ldl Receptor Family Involvement, Brian Carson, Josephine Chu, Devaraj V. Chandrashekar, Jerome Garcia, Rachita K. Sumbria, Derick Han
Pharmacy Faculty Articles and Research
Background
LDL receptor related protein 1 (LRP1) is a major hepatic receptor involved in lipoprotein metabolism, protease degradation, transmembrane receptor modulation, and clearance of excess protein, such as Aβ. Decreased expression of LRP1 due to liver injury can impair receptor-mediated clearance, increasing Aβ availability in the periphery. We investigated the effects of hepato-specific silencing of LRP1 on Aβ deposition in the brain. Additionally, other LDL family members (LRP5, LRP6, and LDLR) that may participate in Aβ clearance were monitored in the liver to ensure non-compensatory effects of LRP1 silencing.
Method
4-month-old male double transgenic (APP/PS1) AD mice were injected with …
The Mitochondria Is The Source Of Hepatic Amyloid Precursor Protein And Peripheral Amyloid Beta: Implications Of Alcohol-Induced Liver Steatosis In Alzheimer's Disease, Josephine Chu, Ross A. Steinberg, Brian Carson, Devaraj Venkatapura Chandrashekar, Rachita K. Sumbria, Derick Han
The Mitochondria Is The Source Of Hepatic Amyloid Precursor Protein And Peripheral Amyloid Beta: Implications Of Alcohol-Induced Liver Steatosis In Alzheimer's Disease, Josephine Chu, Ross A. Steinberg, Brian Carson, Devaraj Venkatapura Chandrashekar, Rachita K. Sumbria, Derick Han
Pharmacy Faculty Articles and Research
Background
Alcohol-induced liver injury occurs in the pericentral region of the liver and can induce mitochondrial remodeling and exacerbate Alzheimer's Disease (AD) progression. Subpopulations of mitochondria: general mitochondria (GM), peridroplet mitochondria (PDM) and endoplasmic reticulum(ER)-bound mitochondria (ERM) maintain cellular homeostasis via energy synthesis, lipid homeostasis, and regulation of intracellular calcium. Hepatic amyloid precursor protein (APP) is a source of peripheral amyloid beta (aB) and affects AD pathology in the brain. Understanding the localization and expression of hepatic APP in mitochondrial subpopulations are critical to understanding aB metabolism and may play a role in identifying a potential mechanism for metabolic dysfunction. …
Manual Therapy In Conjunction With Other Multimodal Interventions In A Patient With Chronic Pain And Hypertension: A Case Report, Craig P. Hensley, Renzo Mendoza, Jennifer Ryan, Emmanuel Yung
Manual Therapy In Conjunction With Other Multimodal Interventions In A Patient With Chronic Pain And Hypertension: A Case Report, Craig P. Hensley, Renzo Mendoza, Jennifer Ryan, Emmanuel Yung
Physical Therapy Faculty Articles and Research
Chronic pain and hypertension (HTN) are worldwide epidemics that are difficult to manage and frequently encountered as comorbid conditions in patient care. There is a paucity of information regarding the effect that manual therapy has on blood pressure (BP), particularly in those with chronic pain and HTN. This case report describes the management of a patient with chronic pain and HTN. The patient was a 41-year-old female with chronic multisite pain and multiple comorbidities, including HTN. Her BP at the initial evaluation was 147/78 with an oscillated device and 142/82 with a sphygmomanometer in the right arm and 144/80 in …
Longitudinal Pharmacokinetic And Safety Studies Of An Antibody-Erythropoietin Fusion Protein For Alzheimer's Disease, Rudy Chang, Devaraj Venkatapura Chandrashekar, G. Chuli Roules, Nataraj Jagadeesan, Emi Iwasaki, Adenike Oyegbesan, Hayk Davtyan, Rachita K. Sumbria
Longitudinal Pharmacokinetic And Safety Studies Of An Antibody-Erythropoietin Fusion Protein For Alzheimer's Disease, Rudy Chang, Devaraj Venkatapura Chandrashekar, G. Chuli Roules, Nataraj Jagadeesan, Emi Iwasaki, Adenike Oyegbesan, Hayk Davtyan, Rachita K. Sumbria
Pharmacy Faculty Articles and Research
Erythropoietin (EPO) shows promise for Alzheimer's disease (AD) but has poor brain penetration, necessitating high doses that cause hematopoietic side effects. To improve brain delivery, EPO was fused to a transferrin receptor monoclonal antibody (TfRMAb), and this study evaluated the pharmacokinetics (PK), safety, and efficacy of repeated TfRMAb-EPO dosing in mice to further its preclinical development. C57BL/6J male mice (10 weeks old, n = 4–5/dose) received subcutaneous (SQ) low (1 mg/kg), mid (3 and 6 mg/kg), or high (20 mg/kg) TfRMAb-EPO doses for 4 weeks. The 1 mg/kg dose showed no adverse effects and resulted in sustained brain and plasma …
The Differential Effects Of Camp Mobilizing Agents On Tgf-Β-Induced Extracellular Matrix In Human Lung-Derived Fibroblasts: Insights Into Therapeutic Targets For Lung Fibrosis, Sarah Orfanos, Brian T. Deeney, Gaoyuan Cao, Nikhil Karmacharya, Anjani Ravi, Cynthia J. Koziol-White, Qi Yang, Rennolds S. Ostrom, Reynold A. Panettieri Jr.
The Differential Effects Of Camp Mobilizing Agents On Tgf-Β-Induced Extracellular Matrix In Human Lung-Derived Fibroblasts: Insights Into Therapeutic Targets For Lung Fibrosis, Sarah Orfanos, Brian T. Deeney, Gaoyuan Cao, Nikhil Karmacharya, Anjani Ravi, Cynthia J. Koziol-White, Qi Yang, Rennolds S. Ostrom, Reynold A. Panettieri Jr.
Pharmacy Faculty Articles and Research
Background
Injury-repair responses typically induce tissue or organ scarring. Generally, cAMP-mobilizing agents inhibit the activation of fibroblasts and deposition of extracellular matrix. Some but not all cAMP-mobilizing agents inhibit fibrosis. Evidence suggests that inhaled treprostinil, a prostacyclin (IP) analog, increases intracellular cAMP levels [cAMP]I, and slows the decline in pulmonary function in patients with idiopathic pulmonary fibrosis (IPF). However, the molecular mechanisms by which cAMP-mobilizing agents, including treprostinil, alter the expression of matrix proteins in human lung fibroblasts (HLF) remain unclear. Unlike other Gαs -coupled receptors, we posit that the antifibrotic properties of treprostinil are driven by cAMP-mobilizing-dependent and -independent …
Guide For Selecting Experimental Models To Study Dietary Fat Absorption, Andromeda M. Nauli, Ann Phan, Karen Mai, Kathleen Tran, Surya M. Nauli
Guide For Selecting Experimental Models To Study Dietary Fat Absorption, Andromeda M. Nauli, Ann Phan, Karen Mai, Kathleen Tran, Surya M. Nauli
Pharmacy Faculty Articles and Research
Dietary fat absorption is a complex, multi-step process involving digestion, enterocyte uptake, intracellular trafficking, re-esterification, and transport via lipoproteins into circulation. Because dietary fat absorption plays a central role in lipid homeostasis, metabolic syndrome, and fat malabsorption disorders, its study has a broad biomedical significance. However, experimental investigation of this process is technically challenging due to the short lifespan of enterocytes, the dual lymphatic and portal transport routes, and the need to trace the metabolic fate of absorbed lipids. This review summarizes and critically evaluates the major experimental systems used to study dietary fat absorption, highlighting their respective strengths, limitations, …
Citronellol Reduces Sepsis-Induced Renal Inflammation Via Ap-1/Nf-Κb/Tnf-Α Pathway, Huda Rashid Atiyah, Sarmed H. Kathem, Surya M. Nauli
Citronellol Reduces Sepsis-Induced Renal Inflammation Via Ap-1/Nf-Κb/Tnf-Α Pathway, Huda Rashid Atiyah, Sarmed H. Kathem, Surya M. Nauli
Pharmacy Faculty Articles and Research
Sepsis is characterized by the over-production of pro-inflammatory cytokines. Cecal ligation and puncture (CLP) is a well-accepted model for recreating sepsis-induced renal injury in mice. The current study investigates how citronellol, a naturally occurring substance with a variety of biological characteristics, can prevent acute kidney inflammation brought on by CLP. In the CLP mouse model, citronellol was administered orally at doses of 50 and 100 mg/kg. Serum levels of creatinine and urea were used as markers of renal function, and the Murine Sepsis Score (MSS) was used to assess the severity of sepsis. According to our findings, CLP caused a …
Additive Effects Of N-Acetylcysteine And [R4W4] Combination Treatment On Mycobacterium Avium, Kayvan Sasaninia, Iffat Hasnin Era, Nezam Newman, Jesse Melendez, Wajiha Akif, Eashan Sharma, Omid Nikjeh, Ira Glassman, Cristián Jiménez, Navya Sharma, Ama Xu, Maria Lambros, Miou Zhou, Rakesh Tiwari, Vishwanath Venketaraman
Additive Effects Of N-Acetylcysteine And [R4W4] Combination Treatment On Mycobacterium Avium, Kayvan Sasaninia, Iffat Hasnin Era, Nezam Newman, Jesse Melendez, Wajiha Akif, Eashan Sharma, Omid Nikjeh, Ira Glassman, Cristián Jiménez, Navya Sharma, Ama Xu, Maria Lambros, Miou Zhou, Rakesh Tiwari, Vishwanath Venketaraman
Pharmacy Faculty Articles and Research
Mycobacterium avium is an opportunistic pathogen and a leading contributor to nontuberculous mycobacterial infections in immunocompromised individuals. However, treatment duration, antibiotic toxicity, and resistance present challenges in the management of mycobacterium infections, prompting the need for novel treatment. N-acetylcysteine (NAC) has demonstrated potent antimycobacterial activity, while antimicrobial peptides such as the cyclic [R4W4] have shown additive effects when combined with first-line antibiotics. This study aimed to investigate the mechanism and efficacy of NAC and [R4W4] combination therapy against M. avium. A membrane depolarization assay was used to evaluate the effects of …