Chemicals and Drugs Commons^™

Circulating Plasma Exosomal Proteins Of Either Shiv-Infected Rhesus Macaque Or Hiv-Infected Patient Indicates A Link To Neuropathogenesis, Partha K. Chandra, Stephen E. Braun, Sudipa Maity, Jorge A. Castorena-Gonzalez, Hogyoung Kim, Jeffrey G. Shaffer, Sinisa Cikic, Ibolya Rutkai, Jia Fan, Jessie J. Guidry, David K. Worthylake, Chenzhong Li, Asim B. Abdel-Mageed, David W. Busija

School of Medicine Faculty Publications

Despite the suppression of human immunodeficiency virus (HIV) replication by combined antiretroviral therapy (cART), 50–60% of HIV-infected patients suffer from HIV-associated neurocognitive disorders (HAND). Studies are uncovering the role of extracellular vesicles (EVs), especially exosomes, in the central nervous system (CNS) due to HIV infection. We investigated links among circulating plasma exosomal (crExo) proteins and neuropathogenesis in simian/human immunodeficiency virus (SHIV)-infected rhesus macaques (RM) and HIV-infected and cART treated patients (Patient-Exo). Isolated EVs from SHIV-infected (SHIV-Exo) and uninfected (CTL-Exo) RM were predominantly exosomes (particle size < 150 nm). Proteomic analysis quantified 5654 proteins, of which 236 proteins (~4%) were significantly, differentially expressed (DE) between SHIV-/CTL-Exo. Interestingly, different CNS cell specific markers were abundantly expressed in crExo. Proteins involved in latent viral reactivation, neuroinflammation, neuropathology-associated interactive as well as signaling molecules were expressed at significantly higher levels in SHIV-Exo than CTL-Exo. However, proteins involved in mitochondrial biogenesis, ATP production, autophagy, endocytosis, exocytosis, and cytoskeleton organization were significantly less expressed in SHIV-Exo than CTL-Exo. Interestingly, proteins involved in oxidative stress, mitochondrial biogenesis, ATP production, and autophagy were significantly downregulated in primary human brain microvascular endothelial cells exposed with HIV+/cART+ Patient-Exo. We showed that Patient-Exo significantly increased blood–brain barrier permeability, possibly due to loss of platelet endothelial cell adhesion molecule-1 protein and actin cytoskeleton structure. Our novel findings suggest that circulating exosomal proteins expressed CNS cell markers—possibly associated with viral reactivation and neuropathogenesis—that may elucidate the etiology of HAND.

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 …

Past, Present, And A Glance Into The Future Of Multiple Myeloma Treatment., Weam Othman Elbezanti, Kishore B Challagundla, Subash C. Jonnalagadda, Tulin Budak-Alpdogan, Manoj K Pandey

College of Science & Mathematics Departmental Research

Multiple myeloma (MM) is a challenging hematological cancer which typically grows in bone marrow. MM accounts for 10% of hematological malignancies and 1.8% of cancers. The recent treatment strategies have significantly improved progression-free survival for MM patients in the last decade; however, a relapse for most MM patients is inevitable. In this review we discuss current treatment, important pathways for proliferation, survival, immune suppression, and resistance that could be targeted for future treatments.

A New, Extremely Sensitive, Turn-Off Optical Sensor Utilizing Schiff Base For Fast Detection Of Cu(Ii), Lotfi M Aroua, Reham Ali, Abuzar E A E Albadri, Sabri Messaoudi, Fahad M Alminderej, Sayed M Saleh

Faculty, Staff and Student Publications

Throughout this research, a unique optical sensor for detecting one of the most dangerous heavy metal ions, Cu(II), was designed and developed. The (4-mercaptophenyl) iminomethylphenyl naphthalenyl carbamate (MNC) sensor probe was effectively prepared. The Schiff base of the sensor shows a "turn-off" state with excellent sensitivity to Cu(II) ions. This innovative fluorescent chemosensor possesses distinctive optical features with a substantial Stocks shift (about 114 nm). In addition, MNC has remarkable selectivity for Cu(II) relative to other cations. Density functional theory (DFT) and the time-dependent DFT (TDDFT) theoretical calculations were performed to examine Cu(II) chelation structures and associated electronic properties in …

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 …

Addressing A Lack Of Education Surrounding Fentanyl Use And Recovery, Nicole Sala, Luciana Gonzalez, Caroline Dorvilien, Teo Keilwitz, Maddy Terhune, Portia Forson

Nursing Leadership in Community Engagement Projects

Nursing Leadership Executive Summary: Addressing a Lack of Education Surrounding Fentanyl Use and Recovery

Our project focused on assisting a nonprofit organization who exists to serve the most vulnerable of families in the Seattle area. They offer a number of programs including a mobile outreach team that seeks to bring resources to families, a program for families which provides the opportunity for new mothers to bond with their newborn, and another program which assists families with medically fragile children to find healthcare resources, and more. Our team was made up of six students from the Lydia Green Nursing Program at …

Sfd Indications And Technique: When And How To Use Sdf To Manage Caries Lesions, Margherita Fontana Dds, Phd

The Journal of the Michigan Dental Association

The aim of this article is to review indications for 38% SDF and the appropriate technique for use. Evidence-based recommendations by the American Dental Association and umbrella reviews of systematic reviews are summarized to provide indications for SDF use in primary and permanent teeth, including sound surfaces and those with non-cavitated and cavitated caries lesions. High-quality evidence supports that SDF is an effective treatment alternative for managing active cavitated coronal and root caries lesions and preventing root caries lesions. Dentists can help by incorporating SDF as an option into their caries prevention and management armamentarium and by helping to train …

Quantitative Phosphoproteomic Analysis Reveals Unique Camp Signaling Pools Emanating From Ac2 And Ac6 In Human Airway Smooth Muscle Cells, Isabella Cattani-Cavalieri, Yue Li, Jordyn Margolis, Amy S. Bogard, Moom R. Roosan, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Human airway smooth muscle (HASM) is the primary target of ßAR agonists used to control airway hypercontractility in asthma and chronic obstructive pulmonary disease (COPD). ßAR agonists induce the production of cAMP by adenylyl cyclases (ACs), activate PKA and cause bronchodilation. Several other G-protein coupled receptors (GPCR) expressed in human airway smooth muscle cells transduce extracellular signals through cAMP but these receptors elicit different cellular responses. Some G-protein coupled receptors couple to distinct adenylyl cyclases isoforms with different localization, partly explaining this compartmentation, but little is known about the downstream networks that result. We used quantitative phosphoproteomics to define the …

Burning Mouth Disorder And Parkinson's Disease: A Scoping Review Of The Literature, O. Guru, Ramesh Balasubramaniam, Gary D. Klasser

School of Dentistry Faculty Publications

Background: Burning mouth disorder (BMD) is a complex medical condition characterized by a burning sensation in the mouth of fluctuating intensity. BMD is considered a diagnosis of exclusion, as oral burning can occur secondary to local or systemic conditions. Parkinson's disease (PD) is one such condition. Objective: To provide a scoping review of the literature by assessing all articles written in English that investigated the relationship between BMD and PD. Materials and Methods: Various databases (PubMed, Ovid, Web of Science, Science Direct and Scopus) and a search platform (EBSCOhost) were searched following similar investigative approaches. Duplicates were removed and reference …

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 …

Rationale And Design Of The Restore Trial: A Multicenter, Randomized, Double-Blinded, Parallel-Group, Placebo-Controlled Trial To Evaluate The Effect Of Shenfu Injection On Myocardial Injury In Stemi Patients After Primary Pci, Xiao Wang, Ruifeng Guo, Yingying Guo, Qian Guo, Yan Yan, Wei Gong, Wen Zheng, Hui Wang, Lei Xu, Hui Ai, Bin Que, Xiaoyan Yan, Xin-Liang Ma, Shaoping Nie

Department of Emergency Medicine Faculty Papers

BACKGROUND: The mortality following ST-segment elevation myocardial infarction (STEMI) remains substantial in the reperfusion era. Shenfu injection, as a traditional Chinese herbal formula, can alleviate ischemia-reperfusion injury through multiple pharmacologic effects. However, no robust data are available regarding the role of Shenfu injection in reducing infarct size for patients with STEMI undergoing primary percutaneous coronary intervention (PPCI).

METHODS/DESIGN: This RESTORE trial is a multicenter, randomized, double-blind, parallel-group, placebo-controlled trial (NCT04493840). A total of 326 eligible patients with first-time anterior STEMI undergoing PPCI within 12 h of symptom onset will be enrolled from 10 centers in mainland China. Patients are randomized …

Vitamin C Contributes To Epigenetic Regulation Of Genes Related To Diabetic Retinopathy In Retinal Endothelial Cells, Elizabeth L. Turner, Jonathon Reynolds, Walker Kay, Marianne Becnel, Matthew Conway, Alexander Kim, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

No abstract provided.

The Effects Of Vitamin B1 Analog, Benfotiamine, On The Prevention Of Non-Small Cell Lung Cancer, Emely Fernandez, Hannah Christensen, Kota A. Ramana

Annual Research Symposium

No abstract provided.

Carvacrol Regulates Endotoxin -Induced Arachidonic Acid Metabolism., Aliea M. Jalali, Spencer Norton

Annual Research Symposium

Plant-derived essential oil prevents endotoxin-induced inflammatory response

The Role Of The Kcc2 In Substance Use And Abuse: A Systematic Review [Protocol], Alfred Amendolara, Steven Salazar, Chad Thompson, Hyrum Wright, Andrew Payne

Annual Research Symposium

This poster presents the protocol for an ongoing systematic review investigating the role of potassium chloride co-transporter 2 (KCC2) in substance use, abuse, and addiction.

Practice Of Building Biomedical Innovation Highland In The United States And Its Enlightenment To China, Xiaoling Ma

Bulletin of Chinese Academy of Sciences (Chinese Version)

The modern pharmaceutical industry began with the large-scale production of chemical drugs. With the radical innovation of basic sciences, such as life science, biomedicine has become the focus of the pharmaceutical industry, with broad prospects. Since World War II, the U.S. government, enterprises and scientific community have cultivated the biomedical industry and scientific foundation, created an environment for innovation, established an effective life science innovation system, and gradually become the innovation highland of biomedicine in the world. Building a biomedical innovation highland is an important part of China to become the world science center. China can learn from U.S. experience …

H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam

School of Medicine Faculty Publications

Endogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative …

Saliva As A Diagnostic Tool To Measure Polycyclic Aromatic Hydrocarbon Exposure In Dental Patients Exposed To Intimate Partner Violence (Ipv), Aramandla Ramesh, Leslie R. Halpern, Janet H. Southerland, Samuel E. Adunyah, Pandu R. Gangula

School of Dentistry Faculty Publications

Background: Social habits such as tobacco use, alcohol consumption, and chemically contaminated diet contribute to poor oral health. Intimate Partner Violence (IPV) is a global public health epidemic which can exacerbate the prevalence of health conditions affecting a victim's lifespan. This study investigates using saliva as a biomarker for detecting levels of benzo(a)pyrene [B(a)P]; a toxicant present in cigarette smoke and barbecued meat in a population of IPV + female patients. Methods: A cross-sectional IRB-approved study utilized 63 female participants (37 African Americans [AA], and 26 non-African Americans [NAA]), who provided consent for the study. Participants submitted samples of saliva, …

Modified Linear Peptides Effectively Silence Stat-3 In Breast Cancer And Ovarian Cancer Cell Lines, Dindyal Mandal, Sandeep Lohan, Muhammad Imran Sajid, Abdulelah Alhazza, Rakesh Kumar Tiwari, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

RNA interference (RNAi) has drawn enormous attention as a powerful tool because of its capability to interfere with mRNA and protein production. However, designing a safe and efficient delivery system in RNAi therapeutics remains challenging. Herein, we have designed and synthesized several linear peptides containing tryptophan (W) and arginine (R) residues separated by the β-alanine (βA) spacer and attached to a lipophilic fatty acyl chain, cholesterol, or PEG. The peptide backbone sequences were: Ac-C-βA-βA-W4-βA-βA-R4-CO-NH2 and Ac-K-βA-βA-W4-βA-βA-R4-CO-NH2, with only a difference in N-terminal amino acid. The cysteine side chain in the first sequence was used for the conjugation with PEG2000 and …

Riluzole And Novel Naphthalenyl Substituted Aminothiazole Derivatives Prevent Acute Neural Excitotoxic Injury In A Rat Model Of Temporal Lobe Epilepsy, Thomas Kyllo, Vikrant Singh, Heesung Shim, Singh Latika, Hai M. Nguyen, Yi Je Chen, Ellen Terry, Heike Wulff, Jeffrey D. Erickson

School of Medicine Faculty Publications

Epileptogenic seizures, or status epilepticus (SE), leads to excitotoxic injury in hippocampal and limbic neurons in the kainic acid (KA) animal model of temporal lobe epilepsy (TLE). Here, we have further characterized neural activity regulated methylaminoisobutryic acid (MeAIB)/glutamine transport activity in mature rat hippocampal neurons in vitro that is inhibited by riluzole (IC50 = 1 μM), an anti-convulsant benzothiazole agent. We screened a library of riluzole derivatives and identified SKA-41 followed by a second screen and synthesized several novel chlorinated aminothiazoles (SKA-377, SKA-378, SKA-379) that are also potent MeAIB transport inhibitors in vitro, and brain penetrant following systemic administration. When …

Predicting Survival Of Nsclc Patients Treated With Immune Checkpoint Inhibitors: Impact And Timing Of Immune-Related Adverse Events And Prior Tyrosine Kinase Inhibitor Therapy, Michael R. Sayer, Isa Mambetsariev, Kun-Han Lu, Chi Wah Wong, Ashley Duche, Richard Beuttler, Jeremy Fricke, Rebecca Pharaon, Leonidas Arvanitis, Zahra Eftekhari, Arya Amini, Marianna Koczywas, Erminia Massarelli, Moom Rahman Roosan, Ravi Salgia

Pharmacy Faculty Articles and Research

Introduction: Immune checkpoint inhibitors (ICIs) produce a broad spectrum of immune-related adverse events (irAEs) affecting various organ systems. While ICIs are established as a therapeutic option in non-small cell lung cancer (NSCLC) treatment, most patients receiving ICI relapse. Additionally, the role of ICIs on survival in patients receiving prior targeted tyrosine kinase inhibitor (TKI) therapy has not been well-defined.

Objective: To investigate the impact of irAEs, the relative time of occurrence, and prior TKI therapy to predict clinical outcomes in NSCLC patients treated with ICIs.

Methods: A single center retrospective cohort study identified 354 adult patients with NSCLC receiving ICI …

Challenging Breast Cancer Through Novel Sulfonamide–Pyridine Hybrids: Design, Synthesis, Carbonic Anhydrase Ix Inhibition And Induction Of Apoptosis., Amira Khalil, Nashwa H. Zaher, Reham Mm Elhazek, Ahmed E. Gouda, Marwa G. Elgazzar

Pharmacy

Background: Among the important key modulators of the tumor microenvironment and hypoxia is a family of enzymes named carbonic anhydrases. Herein, 11 novel sulfonamide–pyridine hybrids (2–12) were designed, synthesized and biologically evaluated for their potential use in targeting breast cancer. Methods & results: The para chloro derivative 7 reported the highest cytotoxic activity against the three breast cancer cell lines used. In addition, compound 7 was found to induce cell cycle arrest and autophagy as well as delaying wound healing. The IC50 of compound 7 against carbonic anhydrase IX was 253 ± 12 nM using dorzolamide HCl as control. Conclusion: …

Increasing Substance Safety Concentrating On The Fentanyl Epidemic, Rachael A. Geesaman

CAFE Symposium 2023

An action plan designed to combat the fentanyl epidemic, I plan to educate others on the dangers of fentanyl by sharing and debunking common misconceptions and research online in a digestible format. To do so, I plan to create a website and Instagram account that has a global outreach to educate others and alleviate the stigma around substance use and death by fentanyl poisoning. Furthermore, the project is to spread awareness of current efforts and resources in specific areas in South Central PA, such as Adams County, Franklin, and Cumberland Counties.

Combination Sodium Nitrite And Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity In A “2-Hit” Murine Model, Kyle B. Lapenna, Zhen Li, Jake E. Doiron, Thomas E. Sharp, Huijing Xia, Karl Moles, Kashyap Koul, John S. Wang, David J. Polhemus, Traci T. Goodchild, Ravi B. Patel, Sanjiv J. Shah, David J. Lefer

School of Medicine Faculty Publications

BACKGROUND: Recent studies have suggested that cardiac nitrosative stress mediated by pathological overproduction of nitric oxide (NO) via inducible NO synthase (iNOS) contributes to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Other studies have suggested that endothelial NO synthase (eNOS) dysfunction and attenuated NO bioavailability contribute to HFpEF morbidity and mortality. We sought to further investigate dysregulated NO signaling and to examine the effects of a NO-based dual therapy (sodium nitrite+hydralazine) following the onset of HFpEF using a “2-hit” murine model. METHODS AND RESULTS: Nine-week-old male C57BL/6 N mice (n=15 per group) were treated concurrently with high-fat …

Endogenous Mirna-Based Innate-Immunity Against Sars-Cov-2 Invasion Of The Brain, Walter J. Lukiw, Aileen I. Pogue

School of Medicine Faculty Publications

The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger RNA (mRNA) possessing a 5′-methyl cap (m7GpppN), a 3′- and 5′-untranslated region (3′-UTR, 5′-UTR), and a poly-adenylated (poly-A+) tail. As such, the SARS-CoV-2 ssvRNA is susceptible to targeting by small non-coding RNA (sncRNA) and/or microRNA (miRNA), as well as neutralization and/or inhibition of its infectivity via the human body’s natural complement of about ~2650 miRNA species. Depending on host cell and tissue …

Formulation Of Encapsulated Nanoparticles Of Leek Extract As Antimicrobial And Anticancer Agent, Rawan Hassan Mohamed Elghanam

Theses and Dissertations

Leek extract (LEK) has broad therapeutic activity. However, plant extract use has many drawbacks, which could be resolved using nanocarriers. The purpose of this research work was to prepare chitosan nanoparticles (CS NPs) encapsulating LEK and investigate their antioxidant, antimicrobial, and anticancer activity. Gas chromatography-mass spectroscopy was used to determine the LEK components. The CS-LEK NPs were produced by tripolyphosphate (TPP) crosslinking with chitosan (CS) the ionic gelation methodology. The particle size was 331 nm, zeta potential (ZP) was 28.9 mv, polydispersity index (PDI) was 0.4, encapsulation efficiency (EE) was 65.6%, and loading capacity (LC) was 28.8 % of the …

Chimeric Antigen Receptor T-Cell Therapy And Hematopoiesis, Bryanna Reinhardt, Patrick Lee, Joshua P. Sasine

School of Medicine Faculty Publications

Chimeric Antigen Receptor (CAR) T-cell therapy is a promising treatment option for patients suffering from B-cell- and plasma cell-derived hematologic malignancies and is being adapted for the treatment of solid cancers. However, CAR T is associated with frequently severe toxicities such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), macrophage activation syndrome (MAS), and prolonged cytopenias—a reduction in the number of mature blood cells of one or more lineage. Although we understand some drivers of these toxicities, their mechanisms remain under investigation. Since the CAR T regimen is a complex, multi-step process with frequent adverse events, ways …

Patterns Of Cannabis- And Substance-Related Congenital General Anomalies In Europe: A Geospatiotemporal And Causal Inferential Study, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Introduction:

Recent series of congenital anomaly (CA) rates (CARs) have showed the close and epidemiologically causal relationship of cannabis exposure to many CARs. We investigated these trends in Europe where similar trends have occurred.

Methods:

CARs from EUROCAT. Drug use from European Monitoring Centre for Drugs and Drug Addiction. Income data from World Bank. Results: CARs were higher in countries with increasing daily use overall (p = 9.99 × 10⁻¹⁴, minimum E-value (mEV) = 2.09) and especially for maternal infections, situs inversus, teratogenic syndromes and VACTERL syndrome (p = 1.49 × 10⁻¹⁵, mEV = 3.04). In …

Second Generation Phenyloxadiazolyl Methyl Sulfones For Thiol-Specific Bioconjugations, Guillaume Dewaele-Le Roi

Dissertations, Theses, and Capstone Projects

The role of antibody-based molecular agents for diagnosis and therapy of cancer has expanded significantly over the past decades. However, most of these constructs are synthesized using traditional bioconjugation methods based on the random ligations between the molecular cargo and lysine residues within the protein. These non-specific approaches can create poorly defined conjugates with suboptimal immunoreactivity and in vivo performance while Site-specific approaches to antibody bioconjugation based on ligations between maleimides and free cysteine residues have long stood as attractive alternatives. Yet the inherent instability of the thiol-maleimide linkage has fueled the search for new, more stable thiol-reactive prosthetic groups. …