Digital Commons Network^™

Targeting Oxidative Stress In Cadasil: Case Insights And Therapeutic Approaches, Maria Meshreky, Richard Weinberger, Giana Johnson, Andrew Abraham, Jacob Rosendale

The Journal of Integrated Primary Care

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare hereditary small-vessel disease caused by NOTCH3 mutations, leading to recurrent ischemic strokes, cognitive decline, and early-onset dementia. Oxidative stress has been implicated in the pathophysiology of small-vessel cerebrovascular disease, but therapeutic strategies targeting oxidative injury remain limited. We present a 40-year-old female with recurrent ischemic strokes involving the right and left middle cerebral arteries, persistent hypercoagulability of unknown etiology, and no identifiable inherited or acquired thrombophilia. Despite well-controlled blood pressure and standard medical management, the patient remains at high risk for cerebrovascular injury. An extensive review of …

A Multilevel Analysis Of Prescriber-Reported Buprenorphine Induction Challenges In Fentanyl-Endemic Settings, Alyssa Vawn Long

Walden Dissertations and Doctoral Studies

The emergence of illicitly manufactured fentanyl has increased clinical uncertainty during buprenorphine induction in medication-assisted treatment for opioid use disorder. The purpose of this quantitative, retrospective cohort study, guided by the Transtheoretical Model (TTM), was to examine whether prescriber-level buprenorphine induction practices and experiences with precipitated withdrawal were associated with reported buprenorphine induction challenges, and whether county-level fentanyl prevalence contributed to these challenges after accounting for geographic clustering. Secondary, de-identified archival data were obtained from the National Institute on Drug Abuse Clinical Trials Network study CTN-0134 and included 64 prescribers practicing in fentanyl-endemic settings. Buprenorphine induction challenges were operationalized as …

Prmt5 Inhibition Impairs Fanconi Anemia Pathway-Mediated Homologous Recombination And Enhances The Antitumor Efficacy Of Temozolomide In Glioblastoma, Shumpei Onishi, Sridharan Jayamohan, Ashis Chowdhury, Sarah Rivas, Yoshihiro Otani, Celine Ertekin, Jean-Paul Bryant, Sara A Murphy, Kimberly A Rivera-Caraballo, Stuart Walbridge, Bayu Sisay, Dragan Maric, Abdel Elkahloun, Kory Johnson, Desmond A Brown, John D Heiss, Ashish H Shah, Tae Jin Lee, Sangamesh G Kumbar, Ji Young Yoo, Andrew J Brenner, Balveen Kaur, Gangadhara R Sareddy, Yeshavanth Kumar Banasavadi-Siddegowda

Faculty, Staff and Student Publications

Despite multimodal therapy of surgical resection, radiation, and chemotherapy, glioblastoma patients show a dismal prognosis. Protein Arginine Methyltransferase 5 (PRMT5) is overexpressed in glioblastoma, and its inhibition imparts an anti-tumor effect. Tumor cells invariably develop resistance to Temozolomide (TMZ), the standard chemotherapeutic agent for glioblastoma. However, the mechanistic role of PRMT5 in treatment-resistant glioblastoma is unknown. Patient-derived glioma stem-like cells (GSCs), treated with PRMT5 inhibitor (LLY-283) or transfected with PRMT5-target-specific siRNA, were treated with TMZ and subjected to in vitro functional and mechanistic studies. The intracranial mouse xenograft model was used to test the in vivo antitumor efficacy of combination …

Subchronic Oral Exposure To Propylparaben Induces Endocrine Disruption And Genotoxicity In Male Rats, Sarah M. Moud, Najiah M. Alyamani

Saudi Toxicology Journal

ropylparaben (PP) is widely employed as a preservative in consumer products such as cosmetics, pharmaceuticals, and food items, prompting increasing safety apprehensions due to its possible endocrine-disrupting properties. A controlled experimental investigation was conducted to assess the toxicological effects of sub-chronic propylparaben exposure on the testes of adult male rats. Twenty adult male rats (n = 20) were randomly assigned to two groups (10 rats per group): a control group receiving distilled water and a treated group receiving PP orally at a dosage of 100 mg/kg body weight once daily for four consecutive weeks. This dosage was selected based on …

Convergent Rna Pathophysiology In Amyotrophic Lateral Sclerosis, Hunter Lee Patterson

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation explores the connection between amyotrophic lateral sclerosis pathogenesis and RNA biology via two mechanisms: microRNA regulation of gene expression in the spinal cord and modulation of TDP-43 pathology through synthetic oligonucleotides. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective loss of motor neurons in the brain and spinal cord that leads to progressive weakness. However, despite this shared clinical pattern the known causes of ALS are extremely varied. Only about 10% of ALS cases are familial while the other 90% occur sporadically. Even among that small fraction of familial cases, researchers have identified dozens …

A Scoping Review Of The Objective Structured Assessment Of Technical Surgical Skills (Osats), David J. O'Regan, Christopher Caddy, Retnagowri Rajandram, Paul Barach

College of Population Health Faculty Papers

BACKGROUND: Objective structured assessment of technical skills (OSATS) offers an objective tool for assessing bowel anastomosis on a benchtop. It was developed in 1997 to set appropriate standards and expectations for the surgical trainee. OSATS have become the gold standard of assessment across many disciplines. A global Likert rating scale, including respect for tissues, instrument handling, economy of movement, and flow of the operation predominates the literature. This has led to many questioning OSATS objectivity, claiming the process to be time-consuming, subjective, demanding human resources, and requiring extensive training of the trainer. We believe OSATS scoring has omitted the 22-point …

Sex-Specific Autosomal Susceptibility Loci In Systemic Sclerosis: A Genome-Wide Association Study, Inmaculada Rodriguez-Martin, Martin Kerick, Carlos Rangel-Peláez, Carlos Rosa-Baez, Gonzalo Borrego-Yaniz, Lourdes Ortiz-Fernández, Alfredo Guillen-Del-Castillo, Carmen P Simeón-Aznar, José Luis Callejas, Oliver Distler, Susanna M Proudman, Mandana Nikpour, Nicolas Hunzelmann, Jeska K De Vries-Bouwstra, Ariane L Herrick, Yannick Allanore, Marta E Alarcón-Riquelme, Lorenzo Beretta, Shervin Assassi, Christopher P Denton, Maureen D Mayes, Javier Martin, Marialbert Acosta-Herrera

Faculty, Staff and Student Publications

Background: Systemic sclerosis is an immune-mediated inflammatory disease with marked sex differences in prevalence and severity. Although genome-wide association studies (GWAS) have advanced the understanding of systemic sclerosis genetics, sex-aware approaches remain scarce. We aimed to address this gap by examining autosomal sex-specific genetic factors in systemic sclerosis.

Methods: Based on a chromosomal definition of sex, we conducted a sex-stratified autosomal meta-analysis of GWAS in systemic sclerosis. We retrieved patient-level and control data from a previous GWAS for systemic sclerosis and newly recruited participants from an international multicentre collaboration (data cutoff June 1, 2024). Adult patients (aged ≥18 years) were …

Single-Nucleus Brain Transcriptomics Reveals Microglia Dysfunction In Multiple System Atrophy, Rasmus Rydbirk, Frederik Nørby Friis Sørensen, Jonas Folke, Henriette Haukedal, Andrea Asenjo Martinez, Irene Lisa Vargas, Simone Mcgarry, Oline Chantell Hollmann, Camila Gherardelli, Sofia Sepulveda, Adam T Szafran, Michael A Mancini, Sanne Simone Kaalund, Tomasz Brudek, Lisette Salvesen, Sara Bech, Justyna Okarmus, Peter Kharchenko, Morten Meyer, Claudio Soto, Kristine Freude, Abhisek Mukherjee, Susana Aznar, Konstantin Khodosevich

Faculty, Staff and Student Publications

Multiple system atrophy (MSA) is a rare, age-related neurodegenerative disease that shares clinical and pathological features with Parkinson's disease (PD) but presents a more devastating disease course. To elucidate the distinct cellular pathophysiology, we performed single-nucleus RNA sequencing on postmortem striatal brain tissue from 7 MSA and 12 PD patients, and 10 non-neurological cases. Here, we show significant compositional differences in astroglia and microglia subtypes, while oligodendroglia and neurons are comparable. PD brains show abundant microglia expressing MHC class II HLA haplotypes, indicative of a proinflammatory state, alongside more homeostatic astrocytes. In contrast, MSA lack activated microglia but has more …

A Digital Diabetes Prevention Program For Hispanic Adolescents (Fit24+): Protocol For A Feasibility Randomized Controlled Trial, Erica G Soltero, Marbelly Partida, Sandra Mihail, Lizette Villanueva, Callie Lopez, Salma M Musaad, Teresia M O'Connor, Maria J Redondo, Matthew Buman, Debbe Thompson

Faculty, Staff and Students Publications

Background: Hispanic youth are disproportionately impacted by obesity and subsequent type 2 diabetes (T2D) yet remain underrepresented in diabetes prevention research. Digital health interventions hold promise for increasing the accessibility to and engagement in disease prevention programming, particularly among high-risk populations. However, there is a significant gap in the literature regarding digital T2D prevention programs for adolescents or Hispanic youth.

Objective: The objective of this article is to describe the protocol for examining the feasibility of a 12-week digital diabetes prevention program among Hispanic adolescents with obesity.

Methods: Participants (N=40; aged 12-16 years) will be randomized (1:1) to a 12-week …

Inflammation- And Resolution-Programmed Myeloid Circuits Govern Therapeutic Resistance In Epithelial And Mesenchymal Triple-Negative Breast Cancer, Liqun Yu, Charlotte Rivas, Fengshuo Liu, Yichao Shen, Ling Wu, Zhan Xu, Yunfeng Ding, Xiaoxin Hao, Weijie Zhang, Hilda L Chan, Jun Liu, Bo Wei, Yang Gao, Luis Becerra-Dominguez, Yi-Hsuan Wu, Siyue Wang, Tobie D Lee, Xuan Li, Xiang Chen, David G Edwards, Xiang H-F Zhang

Faculty, Staff and Students Publications

Single-cell analysis of human triple-negative breast cancer revealed heterogeneous macrophage populations with opposing phenotypes - proinflammatory and proresolution of inflammation. Paradoxically, both subsets accumulated in therapy-refractory residual tumors but showed inverse correlations across patients, suggesting mutually exclusive resistance mechanisms. Inflammatory macrophages localized preferentially to epithelial-like tumors, whereas proresolution macrophages were enriched in mesenchymal-like tumors. Mouse models faithfully recapitulated these patterns. After chemoimmunotherapy, mesenchymal-like tumors expanded proresolution macrophages through phagocytosis/efferocytosis, ω-3 fatty acid uptake, and resolvin production. Macrophage-secreted C1q emerged as a principal antagonist of T cell function by targeting mitochondria and inducing metabolic dysfunction. By contrast, epithelial-like tumors accumulated inflammatory …

Ellagic Acid Reduces Inulin's Adverse Effects: A Combined Approach To Enhance Therapeutic Potential In Nonalcoholic Steatohepatitis, Tharani Senavirathna, Shafaei, Ricky Lareu, Lois Balmer

Research outputs 2022 to 2026

This mouse study investigates the efficacy of ellagic acid (EA), a potent antioxidant in fruits and nuts, and inulin, a prebiotic known for gut microbiota benefits, in nonalcoholic steatohepatitis (NASH). A Western-style diet (WD) was used to induce NASH in C57BL/6J male mice for 16 weeks. Mice then received EA (100 mg/kg/day, oral gavage, 5 days/week) and/or 5% inulin (w/w in diet) for 12 weeks while continuing WD. Inulin increased energy intake and trended toward higher body weight and fasting glucose. EA reduced liver weights and restored the liver-to-body weight ratio. EA and inulin combined significantly reduced steatosis and hepatocyte …

Tremor Modulation: A Systematic Review Of Resetting By Single-Pulse Transcranial Magnetic Stimulation ​, Handan Uzunçakmak Uyanik, Çağri Mesut Temuçi̇n

Turkish Journal of Medical Sciences

Background/aim: Tremor arises from mechanical, reflex, or central oscillatory mechanisms. Transcranial magnetic stimulation (TMS) can transiently perturb ongoing tremor and enables the quantitative assessment of phase resetting, offering circuit-level insight into tremor types. Although numerous studies have applied TMS-induced resetting, the findings have not been systematically reviewed. This study systematically reviews human studies evaluating TMS-induced tremor resetting across tremor types.

Materials and methods: A systematic search of PubMed and Google Scholar identified human studies using TMS to perturb tremor or rhythmic movement. Search terms included “tremor resetting,” “resetting of tremor,” “tremor phase shift,” “tremor phase reset,” “transcranial magnetic stimulation,” and …

Effects Of Colchicine On Sah-Induced Vascular Damage In An Experimental Subarachnoid Hemorrhage Model ​, Emi̇ne Demi̇r, Cumaali̇ Demi̇rtaş, Cansu Sönmez, Eray Meti̇n Güler, Sarper Kocaoğlu, Hakan Beyaztaş, Eyüp Çeti̇n

Turkish Journal of Medical Sciences

Background/aim: Subarachnoid hemorrhage (SAH) is a severe cerebrovascular condition associated with high morbidity and mortality. Inflammation and oxidative stress play critical roles in its pathophysiology, especially in the development of secondary vascular damage. This study aimed to evaluate the protective effects of colchicine on vascular integrity and biochemical markers following SAH in an experimental rat model.

Materials and methods: Eighteen female Sprague Dawley rats were randomly divided into 3 groups: Control (no SAH), SAH (induced without treatment), and SAH + colchicine (received intraperitoneal colchicine at a dose of 1 mg/kg). SAH was induced by injecting autologous blood into the cisterna …

Sun-Macerated Hypericum Perforatum Oleates In Fixed Oils: Analytical Characterization And Comparative Wound-Healing Activity, Ci̇han Çapar, Esra Akkol, Ayli̇n Yaba, Ayhan Parmaksiz, Engi̇n Sümer, Erdem Yeşi̇lada

Turkish Journal of Medical Sciences

Background/aim: Hypericum perforatum L. oleates prepared in fixed oils have long been used for wound management due to their anti-inflammatory, antibacterial, and tissue-regenerative properties. The bioactivity of these oleates is mainly attributed to hypericin, hyperforin, and pseudohypericin. This study aimed to comparatively evaluate the wound-healing potential of H. perforatum oleates prepared in different fixed oils, including Olea europaea L. (olive), Sesamum indicum L. (sesame), Helianthus annuus L. (sunflower), and Nigella sativa L. (black seed).Materials and methodsFixed oils were characterized by GC–MS, while oleuropein in olive oil and thymoquinone in black seed oil were quantified by HPLC, and sesamin and sesamol …

The Importance Of Early Intraoperative Ultrasonography And The Relationship Between Surgical Technique And Allograft Function In Patients With Compartment Syndrome Following Renal Transplantation Surgery ​, Burak Yağdiran, Emre Karakaya, Ravana Ahmadli̇, Adem Şafak, Yağmur Kurtuluş, Nedi̇m Çekmen, Meri̇ç Yavuz Çolak, Mehmet Haberal

Turkish Journal of Medical Sciences

Background/aim: In rare cases, patients undergoing renal transplantation (RT) may develop renal allograft compartment syndrome (RACS) if the renal volume is larger than the retroperitoneal space prepared in the iliac fossa. In such cases, the optimal treatment is early decompression surgery. The primary aim of the present descriptive and comparative study is not to identify the optimal surgical technique, but rather to evaluate the role of early Doppler ultrasonography (DUSG) in the recognition of renal allograft compartment syndrome and to assess outcomes following timely decompressive interventions.

Materials and methods: A total of 275 patients were examined retrospectively for the study, …

Role Of Novel Renal Biomarkers In Prognosticating Patients With Chronic Kidney Disease: A Prospective Cohort Study, Raghavan Padmanabhan, Kaviya Manoharan, Melina Sahay, Pooja Bhujangarao, Luxitaa Goenka, Solai Priya, Kumaraswamy Subramaniyan, Damal Kandadai Sriram, Melvin George

Turkish Journal of Medical Sciences

Background/aim: Several biomarkers have been assessed for the diagnosis of chronic kidney disease (CKD). However, limited data are available regarding their ability to predict mortality in CKD. The aim of this study was to assess the ability of lipocalin-2, receptor for advanced glycation end products (RAGE), tissue inhibitor of metalloproteinase 1 (TIMP-1), osteopontin, and trefoil factor 3 (TFF-3) in predicting the prognosis of patients with CKD.

Materials and methods: We included patients with CKD as defined by an estimated glomerular filtration rate of <60 mL/min/1.73 m2 of either sex who were above the age of 18 years. Patients with a history of acute-on-chronic kidney disease were excluded. The novel markers of interest were estimated from patients’ plasma samples using the multiplex enzyme-linked immunosorbent assay. These patients were followed for 1 year to assess mortality.

Results: The median (with interquartile range) plasma concentrations of lipocalin-2, RAGE, TIMP-1, osteopontin, and TFF-3 were 56.9 …

Artificial Intelligence-Assisted Neuropharmacology: Reshaping Drug Discovery And Translational Strategies For Neurological Diseases ​, Pri̇yanka Rathee, Suni̇thi̇ Lohan, Sari̇ta Khatkar, Neelam Mali̇k, Esra Akkol, Renu Sehrawat, Pooja Rathee, Anurag Khatkar

Turkish Journal of Medical Sciences

The rapid expansion of data-driven technologies, particularly machine learning (ML) and artificial intelligence (AI), has substantially influenced biomedical research and drug discovery. In neuropharmacology, the availability of large-scale genomic, proteomic, chemical, and clinical datasets has stimulated the adoption of AI-based approaches to address persistent challenges in neurological drug development, including high attrition rates and the scarcity of disease-modifying therapies. Unlike prior reviews that broadly discuss AI applications in drug discovery or neurology, this narrative review focuses specifically on neuropharmacology, with an emphasis on translational relevance, disease-oriented examples, and real-world constraints. We critically examine the application of AI and ML across …

Dasatinib And Quercetin Senolytic Treatment Delays Early Onset Intervertebral Disc Degeneration In Sm/J Mice, Emanuel J. Novais, Olivia K. Ottone, Sanjana Jagannath, Esther Jesutofunmi Akande, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Genetic background is a major determinant of disc degeneration, a leading cause of chronic back pain and disability. Herein, we demonstrate that premature disc cell senescence contributes to early-onset degeneration in SM/J mice and test two systemic senotherapeutic strategies to mitigate it: Navitoclax (Nav.) and a cocktail of Dasatinib and Quercetin (DQ). While Nav. treatment did not improve severe degeneration in SM/J mice or senescence status, DQ-treated mice showed lower grades of degeneration and a decreased abundance of senescence markers, including p19ARF, p21, and the senescence-associated secretory phenotype (SASP). DQ improved disc cell viability and phenotype retention and retarded fibrosis …

Dapk2 Regulates Pkm2 Phosphorylation At Threonine 45 To Facilitate Disturbed Flow-Induced Atherosclerosis, Shuai Guo, Long Xu, Yixin Chen, Yuan Zhao, Yuting Zhang, Runfa Yu, Kaixiang Cao, Litao Wang, Wenjia Ai, Jiang-Yun Luo, Lu Lu, Jun He, Yuan Zhou, Li Wang, Andrew H Baker, Yuqing Huo, Yiming Xu

Faculty, Staff and Students Publications

Background: Oscillatory shear stress (OSS), resulting from disturbed blood flow, is implicated in atherosclerotic plaque formation by incompletely understood mechanisms. This study aims to elucidate the involvement of death-associated protein kinase (DAPK) 2 in OSS-induced endothelial cell (EC) activation and atherosclerosis.

Methods: Publicly available resources, including genome-wide microarray, RNA sequencing, and single-cell RNA sequencing, were utilized to identify key OSS-sensitive regulatory factors. Techniques such as mass spectrometry, immunoprecipitation, proximity ligation assay, and RNA sequencing were employed to identify pyruvate kinase M2 (PKM2) as the binding protein of DAPK2 and determine the specific site of PKM2 phosphorylation by DAPK2. To assess …

Advancing Hand Therapy Practice Through Specialized Clinical Reasoning And Patient Education, Candace Heinlein

Capstone Projects

This doctoral capstone experience (DCE) was completed at Corewell Health Grand Rapids Hospitals Hand Therapy Clinic and focused on two ACOTE concentration areas including advanced clinical practice skills and education. The experience combined hands-on clinical practice in a specialized outpatient hand therapy setting with the development of high-quality client education materials and home exercise programs (HEPs). Objectives were created to address identified needs through the creation of client education handouts, development of diagnosis-specific Medbridge HEP templates, and creation of training resources to improve therapist efficiency with Medbridge use. Outcomes of the project included improved access to evidence-based educational materials, reduced …

Synthetic Lethality Of Decitabine Plus Atr Inhibition For Tp53-Mutated Aml, Jeremy T Baeten, Sumedha Agashe, Imene Tabet, Jack T Wooldridge, Amber Carter, Jamie N Butler, Christopher A Miller, Nicole Helton, Annabel Quinet, Kimberly B Johansson, Yichan Yang, Geoffrey L Uy, Alessandro Vindigni, Daniel C Link

2020-Current year OA Pubs

TP53 mutations are found in 10% to 15% of myeloid neoplasms and are associated with a dismal prognosis. Although hypomethylating agents (HMAs), such as decitabine, are active in TP53-mutated myeloid neoplasms (TP53-MN), mutation clearance is rarely complete and nearly all patients relapse. Molecular determinants of response to HMAs in TP53-MN are poorly understood. Here, we show that decitabine induces replicative stress with decreased replication fork progression, induction of single-strand DNA breaks, and activation of the ataxia telangiectasia mutated-Rad3-related (ATR) pathway. Resolution of decitabine-induced replication stress is impaired in TP53-mutated acute myeloid leukemia (AML) cells, representing a potential therapeutic vulnerability. Indeed, …

Enhanced Dietary Monitoring Using Fecal Genomics For Childhood Malnutrition Interventions, Ammara Aqeel, Najeeha T Iqbal, Sanam Iram Soomro, Sheraz Ahmed, Teresa K Mcdonald, Olivia Osborne, Sharon Jiang, Nolan Ives, Kazi Ahsan, Fayaz Umrani, Michael J Barratt, Jeffrey I Gordon, Syed Asad Ali, Lawrence A David

2020-Current year OA Pubs

Ready-to-use therapeutic and supplementary foods (RUTF/RUSF) are a primary treatment for childhood malnutrition in Community Management of Acute Malnutrition (CMAM) programs. However, measuring intervention compliance is labor intensive and unreliable. We applied FoodSeq, a fecal genomic dietary assessment biomarker, in malnourished infants (3-15 months) from Matiari, Pakistan. FoodSeq identified a significant increase in the abundance of DNA from chickpea, a primary RUSF ingredient, during RUSF administration and captured region-specific complementary feeding practices, including age-inappropriate feeding practices such as wide-spread tea consumption. Our findings highlight the potential of dietary genomics as an empirical and scalable tool for compliance monitoring and dietary …

Herpes Simplex Virus Type 1 R-Loops Are Targets For Apobec-Mediated Mutagenesis, Márton Miskei, Dóra Varga, Lilla Hornyák, Éva Sipos, Éva Nagy, Qiuzhen Li, Zsolt Karányi, Zoltán Szabó, Rachel Deweerd, Abby M Green, Dávid Szüts, Eszter Csoma, Lóránt Székvölgyi

2020-Current year OA Pubs

APOBEC3 enzymes are key effectors of antiviral immunity that introduce mutations into viral genomes. We show that viral R-loops serve as preferred substrates for APOBEC3-mediated mutagenesis during herpes simplex virus type 1 (HSV-1) infection. APOBEC3 enzymes are recruited to viral R-loops, generating clustered C-to-T mutations in genes critical for viral assembly. Importantly, R-loops alone are not mutagenic, and APOBEC3 enzymes do not edit HSV-1 without an R-loop; mutagenesis occurs when R-loops and APOBEC3 enzymes interact. These findings identify endogenous R-loops formed during the HSV-1 life cycle as focal vulnerabilities and highlight R-loop-APOBEC3 coupling as a mechanism for antiviral mutagenesis.

Comparative Physicochemical Characterization Of Porcine, Fish, And Bovine Gelatin In Gummy Candies: Toward Halal Nutraceutical Development, Marlyn Dian Laksitorini, Cici Darsih, Nunung Yuniarti, Rumiyati Rumiyati, Mohammad Zainal Abidin

Pharmaceutical Sciences and Research

Gummy candies have emerged as one of the most popular dosage forms for multivitamins and nutraceutical supplements, including those for brain health. Gelatin is the primary gelling agent used to achieve the gummy texture; however, the influence of different gelatin sources on the physicochemical properties of gummies has not been systematically examined. This study investigated the physicochemical characteristics of gummies prepared with porcine, bovine, and fish gelatin. The gummies were evaluated for mechanical properties (gumminess, hardness, cohesiveness, springiness, adhesiveness, and stringiness), color, water activity, antioxidant activity, and protein content. Additionally, the effects of intentional adulteration—specifically the addition of porcine gelatin …

Three-Dimensional Imaging Of Neuronal Activation Patterns In Chronic Neuropathic Pain And Opioid Pharmacology, Madeline Martinez

Electronic Theses and Dissertations 2020 - Present

Chronic neuropathic pain severely diminishes quality of life, yet the supraspinal neural circuits that sustain pain perception and mediate analgesic relief remain incompletely characterized. While peripheral and spinal pain pathways are well established, relatively few studies have mapped pain- or opioid-related neuronal activation across the entire brain. This dissertation employed activity-dependent genetic labeling (TRAP2/Ai9), whole-brain tissue clearing, light sheet microscopy, and graph-theoretic network analysis to characterize brain-wide activation patterns across chronic pain and analgesic conditions in mice.

In Chapter 1, we mapped supraspinal neuronal activation in a bilateral spared nerve injury model of chronic neuropathic pain. Although no individual region …

Engineering Of Genetically Encoded Programmable Calcium Channel Inhibitory Binders, Xiaoxuan Liu, Sher Ali, Tien-Hung Lan, Decheng Wang, Brendan Mckee, Tatsuki Nonomura, Siyao Liu, Feng Zhao, Michael X Zhu, Yun Huang, Qing Deng, Guolin Ma, Yubin Zhou

Faculty, Staff and Student Publications

Store-operated Ca2+ release-activated Ca2+ (CRAC) channels, composed of STIM and ORAI, are essential for immune and developmental processes, and their dysregulation underlies channelopathies such as Stormorken syndrome. Here, we report the engineering of genetically encoded CRAC channel inhibitory binders (CRABs) derived from the ORAI C-terminal tail. Guided by deep mutational scanning, we optimize a membrane-anchored CRAB variant that potently inhibits Ca2+ influx and NFAT signaling, and rescues thrombocytopenia-like phenotypes in a zebrafish model of Stormorken syndrome. To enable tunable inhibition, we further design oligomeric, optogenetic (Opto-CRAB), and chemogenetic (Chemo-CRAB) variants, providing graded and real-time control of CRAC activity. Chemo-CRAB further …

Continuous Light And Pinealectomy: Two Models Of Melatonin Deficiency Revealing Distinct Interactions With Vitamin D Deficiency On Blood Parameters, Rebaz Sedeeq Shekh, Ismail Mustafa Maulood

Polytechnic Journal

Modern lifestyles reduce sunlight exposure and increase artificial light at night, potentially promoting vitamin D deficiency (VDD) and melatonin (MEL) suppression. The two hormones regulate immunity, erythropoiesis, and platelet (PLT) indices, but their combined hematological effects are not well characterized. We investigated the independent and combined effects of VDD and MEL deficiency on leukocyte profiles, erythrocyte indices, and PLT parameters in albino rats using two 12-week models (n = 8/group): continuous light (CL)-induced MEL suppression (Control, CL, VDD, and CL + VDD) and pinealectomy (Px)-induced MEL deficiency (Sham. Px, VDD, Px + VDD). Complete blood counts (CBCs) and inflammation-related ratios …

Adipocytes Signal To Recruit Specific Mrnas From Surrounding Cells To Restore Expression Deficits, Clair Crewe, Snigdha Tiash, Yun-Ling Pai, Marjori Russo, Saket Awadhesbhai Patel, Yi-Cian Zheng, Alex Larkin, Chun-Kan Chen, Et Al.

2020-Current year OA Pubs

Extracellular vesicles (EVs) are nano-sized, membrane-delimited, particles released by cells that carry signaling macromolecules. A major pathway of EV production is potentiated by neutral sphingomyelinase 2 (SMPD3/nSMAse2), an enzyme that generates ceramide from sphingomyelin. In our attempt to study this pathway in adipocytes of male mice, we discover that the elimination of SMPD3 from adipocytes in vivo triggers a signal to surrounding immune cell-like preadipocytes to release EVs that carry SMPD3 mRNA. This results in a widespread increase in SMPD3 mRNA in purified null adipocytes without a change in the transcripts of other enzymes involved in ceramide metabolism. These results …

"I Wasn't Broken": Addressing Stigma Associated With Dementia While Walking The Talk For Dementia, Kate Irving, Fernando Aguzzoli Peres, Walter D. Dawson, Jonathan Adrián Zegarra-Valdivia, Lingani Mbakile-Mahlanza, Sherril B. Gelmon

Institute on Aging Publications

INTRODUCTION:Walking the Talk for Dementia (WTD) convenes people from every continent and multiple perspectives, including people with lived experience, in a 40- km walk followed by a 2-day symposium. The aim is collective reflective dialogue about dementia stigma without the burden of professional hierarchies.

METHODS: Qualitative reflections during and immediately following the walk were analyzed using content analysis to identify common themes.

RESULTS: Three themes demonstrate an evolution of perspectives about dementia and stigma: “meeting the person not the label”, “a community in solidarity”, and “I wasn’t treated like I was broken, and I wasn’t broken.”

DISCUSSION: WTD created an …

The Hidden Cost Of Compassion In Veterinary Medicine, Lauren Dugger

Osmosis Magazine

No abstract provided.