Chemical Actions and Uses Commons^™

The Fight For Fluoridation In Stl, Noor Yousaf

Undergraduate Research Symposium

Fluoridation is the addition of fluoride to a source of drinking water. In St. Louis’s public water supply, the amount of fluoride remains the same since 1953 at 5ppm. Dr. Ralph Rosen and his team of dentists and researchers advocated for the fluoridation of the water because it reduced the frequency of dental caries occurring in children and adults alike, but the public had opinions on the sudden addition of chemicals to their water. This includes how the public’s health will be affected, how consumer products would change, and also how effective this addition of fluoride would be. This debate …

Stevens-Johnson Syndrome From Combined Allopurinol And Angiotensin-Converting Enzyme Inhibitors: A Narrative Review, Isabella M. Fabian, Kirsten Maddox, Cameron Robicheaux, Rahib K. Islam, Ahmed Anwar, Bradley Dorius, Christopher L. Robinson, Adam M. Kaye, Giustino Varrassi, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Stevens-Johnson syndrome (SJS) is a severe and potentially debilitating skin reaction frequently related to medication use. Allopurinol and angiotensin-converting enzyme (ACE) inhibitors are commonly prescribed medications for prevalent health conditions worldwide, and their interaction associated with SJS warrants further investigation. A comprehensive literature search was performed to investigate cases as studies related to SJS occurring in patients with concomitant use of allopurinol and ACE inhibitors. We identified case reports and studies detailing hypersensitivity reactions, including SJS, attributed to a combination of allopurinol and ACE inhibitors. Despite the drug-drug interactions or lack thereof seen in patient populations, there is no definitive …

Host-Defense Piscidin Peptides As Antibiotic Adjuvants Against Clostridioides Difficile, Adenrele Oludiran, Areej Malik, Andriana C. Zourou, Yonghan Wu, Steven P. Gross, Albert Siryapon, Asia Poudel, Kwincy Alleyne, Savion Adams, David S. Courson, Myriam L. Cotten, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The spore-forming intestinal pathogen Clostridioides difficile causes multidrug resistant infection with a high rate of recurrence after treatment. Piscidins 1 (p1) and 3 (p3), cationic host defense peptides with micromolar cytotoxicity against C. difficile, sensitize C. difficile to clinically relevant antibiotics tested at sublethal concentrations. Both peptides bind to Cu²⁺ using an amino terminal copper and nickel binding motif. Here, we investigate the two peptides in the apo and holo states as antibiotic adjuvants against an epidemic strain of C. difficile. We find that the presence of the peptides leads to lower doses of …

Topiramate (Topamax): Evolving Role In Weight Reduction Management: A Narrative Review, Irza Wajid, Alexis Vega, Katherine Thornhill, Jack Jenkins, Chandler Merriman, Debbie Chandler, Sahar Shekoohi, Elyse M. Cornett, Alan D. Kaye

School of Medicine Faculty Publications

Obesity has emerged as a widespread disease with epidemic proportions, necessitating effective management to enhance the overall health outcomes of patients. Medical intervention for weight loss becomes necessary when diet and exercise prove ineffective, and topiramate emerges as a potential treatment option for this global problem. Currently approved as an anti-epileptic and migraine prophylaxis medication, topiramate is frequently utilized as adjunctive therapy for patients with mood and eating disorders, as well as for alcohol use disorders. Its multifaceted mechanisms of action contribute to reducing neuronal excitation and enhancing neuronal inhibition. Given its variety of mechanisms, topiramate shows several off-label outcomes, …

Comparing Antimicrobial Resistant Genes And Phenotypes Across Multiple Sequencing Platforms And Assays For Enterobacterales Clinical Isolates, Rebecca Rose, David J. Nolan, Deborah Ashcraft, Amy K. Feehan, Leonor Velez-Climent, Christopher Huston, Benjamin Lain, Simon Rosenthal, Lucio Miele, Gary B. Fogel, George Pankey, Julia Garcia-Diaz, Susanna L. Lamers

School of Medicine Faculty Publications

Introduction: Whole genome sequencing (WGS) of bacterial isolates can be used to identify antimicrobial resistance (AMR) genes. Previous studies have shown that genotype-based AMR has variable accuracy for predicting carbapenem resistance in carbapenem-resistant Enterobacterales (CRE); however, the majority of these studies used short-read platforms (e.g. Illumina) to generate sequence data. In this study, our objective was to determine whether Oxford Nanopore Technologies (ONT) long-read WGS would improve detection of carbapenem AMR genes with respect to short-read only WGS for nine clinical CRE samples. We measured the minimum inhibitory breakpoint (MIC) using two phenotype assays (MicroScan and ETEST) for six antibiotics, …

Targeting Mcl-1 By A Small Molecule Nsc260594 For Triple-Negative Breast Cancer Therapy, Shengli Dong, Margarite D. Matossian, Hassan Yousefi, Maninder Khosla, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari

School of Graduate Studies Faculty Publications

Triple-negative breast cancers (TNBCs) are aggressive forms of breast cancer and tend to grow and spread more quickly than most other types of breast cancer. TNBCs can neither be targeted by hormonal therapies nor the antibody trastuzumab that targets the HER2 protein. There are urgent unmet medical needs to develop targeted drugs for TNBCs. We identified a small molecule NSC260594 from the NCI diversity set IV compound library. NSC260594 exhibited dramatic cytotoxicity in multiple TNBCs in a dose-and time-dependent manner. NSC260594 inhibited the Myeloid cell leukemia-1 (Mcl-1) expression through downregulation of Wnt signaling proteins. Consistent with this, NSC260594 treatment increased …

High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin

School of Graduate Studies Faculty Publications

Background: Nearly 80% of patients with pancreatic cancer suffer from glucose intolerance or diabetes. Pancreatic cancer complicated by diabetes has a more immunosuppressive tumor microenvironment (TME) and is associated with a worse prognosis. The relationship between glucose metabolism and programmed cell death-Ligand 1 (PD-L1) is close and complex. It is important to explore the regulation of high glucose on PD-L1 expression in pancreatic cancer and its effect on infiltrating immune effectors in the tumor microenvironment. Methods: Diabetic murine models (C57BL/6) were used to reveal different immune landscape in euglycemic and hyperglycemic pancreatic tumor microenvironment. Bioinformatics, WB, iRIP [Improved RNA Binding …

Enhancement Of Tki Sensitivity In Lung Adenocarcinoma Through M6a-Dependent Translational Repression Of Wnt Signaling By Circ-Fbxw7, Kai Li, Zi Yang Peng, Rui Wang, Xiang Li, Ning Du, Da Peng Liu, Jia Zhang, Yun Feng Zhang, Lei Ma, Ye Sun, Shou Ching Tang, Hong Ren, Yi Ping Yang, Xin Sun

School of Medicine Faculty Publications

Background: Tyrosine kinase inhibitors (TKIs) that specifically target mutational points in the EGFR gene have significantly reduced suffering and provided greater relief to patients with lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, Osimertinib, has been successfully employed in clinical treatments to overcome resistance to both original and acquired T790M and L858R mutational points. Nevertheless, the issue of treatment failure response has emerged as an insurmountable problem. Methods: By employing a combination of multiple and integrated approaches, we successfully identified a distinct population within the tumor group that plays a significant role in carcinogenesis, resistance, and recurrence. Our research suggests that addressing …

Parabens Promote Protumorigenic Effects In Luminal Breast Cancer Cell Lines With Diverse Genetic Ancestry, Jazma L. Tapia, Jillian C. Mcdonough, Emily L. Cauble, Cesar G. Gonzalez, Dede K. Teteh, Lindsey S. Treviño

Health Sciences and Kinesiology Faculty Articles

Context

One in 8 women will develop breast cancer in their lifetime. Yet, the burden of disease is greater in Black women. Black women have a 40% higher mortality rate than White women, and a higher incidence of breast cancer at age 40 and younger. While the underlying cause of this disparity is multifactorial, exposure to endocrine disrupting chemicals (EDCs) in hair and other personal care products has been associated with an increased risk of breast cancer. Parabens are known EDCs that are commonly used as preservatives in hair and other personal care products, and Black women are disproportionately exposed …

Ethical Issues And Standards Of Responsible Research Conduct And Monitoring In An Adventist Institution Of Higher Learning - The Babcock Experience, Kayode O. Ogunwenmo, Godswill N. Anyasor, Grace O. Tayo

Adventist Human-Subject Researchers Association

Ethical issues and standards of responsible research conduct involving human participants are important considerations in any institution of higher learning and in particular Adventist institutions. Research conduct and ethics are reviewed and approved before they begin by the Babcock University Health Research Ethics Committee (BUHREC)

The Role Of Alpha-2 Agonists For Attention Deficit Hyperactivity Disorder In Children: A Review, Elisa E. Neuchat, Brooke E. Bocklud, Kali Kingsley, William T. Barham, Patrick M. Luther, Shahab Ahmadzadeh, Sahar Shekoohi, Elyse M. Cornett, Alan D. Kaye

School of Medicine Faculty Publications

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders, characterized by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which is marked by symptoms such as inappropriate levels of inattention, hyperactivity, and impulsivity that can affect academic, social, and personal functioning in children and adolescents. This review summarizes clinical trials demonstrating the effectiveness of Alpha-2 agonists in reducing symptoms of inattention, hyperactivity, and impulsivity in children with ADHD. Studies were identified through a systematic search of PubMed and Cochrane databases. However, these medications’ long-term safety and efficacy remain uncertain, with a lack …

Comparison Of Clinical And Radiographic Efficacy Of Particles Versus Nbca/Onyx In Middle Meningeal Artery Embolization For Chronic Subdural Hematoma, Jane Khalife, Mohamed Salem, Victoria Wong, Allen Karimov, Brian Jankowitz, Jan Karl Burkhardt, Hamza Shaikh, Daniel Tonetti, Pratit Patel, Tudor Jovin, Ajith Thomas

Rowan-Virtua Research Day

Different embolic materials are utilized in MMA embolization of chronic subdural hematoma per operators’ discretion. We aim to compare the clinical and radiographic efficacy of different embolic materials in a pooled retrospective cohort of two US centers.

Chemical Restraints In The Emergency Department, Nicholas Noffsinger

Rowan-Virtua Research Day

Chemical restraint is a critical intervention used in emergency departments to manage acutely agitated or violent patients. It involves the administration of medication to induce sedation and control behavior, with the goal of ensuring patient and staff safety while allowing necessary medical interventions to be performed. However, the use of chemical restraints necessitates close observation of vital signs and any potential side effects, as well as careful consideration of patient-specific considerations.

Nicotinamide Riboside And Beta-Hydroxybutyrate Activate Parallel Pathways For C. Elegans Lifespan Extension, Mckenzie Peters

Undergraduate Honors Theses

Supplementation with nicotinamide riboside (NR), a form of vitamin B3 and a precursor of nicotinamide adenine dinucleotide (NAD⁺) extends lifespan in the nematode C. elegans and delays aging-related pathologies in mammals. During aging, levels of NAD⁺ decline causing metabolic dysfunction and oxidative damage. Studies in C. elegans found that when NR was administered during larval development it induced the mitochondrial unfolded protein response (UPR^mt), which is frequently associated with lifespan extension. Both calorie restriction (CR) and ketogenic diets (KD) have been shown to extend lifespan, in part through increasing NAD⁺ and through increasing levels …

The Developing Effects Of Potassium Ferricyanide On Tetrahymena, Katelyn Coronell

Whittier Scholars Program

Potassium Cyanide is a highly toxic chemical asphyxiant that interferes with the body's ability to use oxygen, typically by directly affecting the body by ingestion, inhalation, skin contact, or eye contact(CDC, 2011). Due to its high toxicity, the main effect that leads to the downfall of the organism begins with the cessation of aerobic metabolism; it does this by cyanide binding to the ferric ions and inhibiting cytochrome oxidase within the mitochondria (Zhang, 2015). There are no physical dangers the substance causes. Although, there are many chemical dangers. If used at temperatures higher than 70℉ The substance may produce toxic …

Various Synthetic Pathways Towards Efavirenz And Its Analogs; The Replacement Of The Side Chain, Elizabeth S. Bautista

Selected Honors Theses

Cyclopropyl acetylene (CA) is a key intermediate in the synthesis of the human immunodeficiency virus (HIV) reverse transcriptase inhibitor, Efavirenz (EFV), an antiviral drug used to treat HIV. CA is an expensive raw material, difficult to obtain, and employed in the preparation of medications to combat acquired immunodeficiency syndrome (AIDS). It was found that the structure could be synthesized by the utilization of PCl5; however, this resulted in unwanted ring opening products. To address this issue, a one pot synthesis was developed using Ph3PCl2 as a mild chlorinating agent. In addition, a new analog has been proposed substituting the cyclopropyl …

Preclinical Perspectives On The Mechanisms Underlying The Therapeutic Actions Of Psilocybin In Psychiatric Disorders, Andreas B. Wulff, Charles D. Nichols, Scott M. Thompson

School of Medicine Faculty Publications

Psychedelic compounds have shown extraordinary potential in treating a wide range of neuropsychiatric disorders. Psilocybin, for example, has now been shown in several clinical trials to induce a rapid (within days) and persistent (3–12 months) improvement in human treatment-resistant depression and other neuropsychiatric conditions. Here we review the preclinical models and experimental approaches that have been used to study the neurobiological actions of psychedelic drugs. We further summarize the insights these studies have provided into the possible mechanisms underlying the induction of their therapeutic actions, including the receptors to which psychedelics bind and the second messenger signaling cascades that they …

Induction Of Antimicrobial Protein S100a15 Expression By Oral Microbial Pathogens Is Toll-Like Receptors-Dependent Activation Of C-Jun-N-Terminal Kinase (Jnk), P38, And Nf-Κb Pathways, Denis Selimovic, Naji Kharouf, Florence Carrouel, Sofie Yasmin Hassan, Thomas W. Flanagan, Sarah Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis, Mohamed Hassan

School of Medicine Faculty Publications

The antimicrobial protein S100A15 belongs to the S100 family, which is differentially expressed in a variety of normal and pathological tissues. Although the function of S100A15 protein has been discussed in several studies, its induction and regulation in oral mucosa, so far, are largely unknown. In this study, we demonstrate that S100A15 is induced by the stimulation of oral mucosa with gram− or gram+ bacterial pathogens, as well as with the purified membrane components, namely lipopolysaccharides (LPS) and lipoteichoic acid (LTA). The stimulation of the human gingival fibroblast (GF) and the human mouth epidermal carcinoma (KB) cell lines with either …

Reasons For Ineligibility For Clinical Trials Of Patients With Medication-Resistant Epilepsy, Wesley T. Kerr, Hai Chen, Mariana Figuera Losada, Christopher Cheng, Tiffany Liu, Jaqueline French

School of Medicine Faculty Publications

Selection criteria for clinical trials for medication-resistant epilepsy are used to limit variability and to ensure safety. However, it has become more challenging to recruit subjects for trials. This study investigated the impact of each inclusion and exclusion criterion on medication-resistant epilepsy clinical trial recruitment at a large academic epilepsy center. We retrospectively identified all patients with medication-resistant focal or generalized onset epilepsy who attended an outpatient clinic over a consecutive 3-month period. We assessed each patient's eligibility for trials with commonly required inclusion and exclusion criteria to evaluate the proportion of eligible patients and the most common reasons for …

A Modern Multimodal Pain Protocol Eliminates The Need For Opioids For Most Patients Following Total Knee Arthroplasty: Results From A Retrospective Comparative Cohort Study, Leland Van Deventer, Amy Bronstone, Claudia Leonardi, Matthew Bennett, Peter Yager, Vinod Dasa

School of Medicine Faculty Publications

Purpose: Modern multimodal analgesia has been shown to significantly reduce opioid use following total knee arthroplasty (TKA). This study was conducted to determine if changing TKA discharge opioid prescriptions from automatic to upon request resulted in more opioid free recoveries without compromising pain control. Methods: Between December 2019 and August 2021, an orthopedic surgeon performed 144 primary unilateral TKAs; patients received the same multimodal analgesia protocol except for postoperative opioid prescribing. The first consecutively-treated cohort automatically received an opioid prescription following discharge (automatic group) and the second cohort received opioid prescriptions only upon request (upon request group). Opioid prescription data …