Digital Commons Network^™

Perfluorooctanesulfonic Acid Exposure Leads To Downregulation Of 3-Hydroxy-3-Methylglutaryl-Coa Synthase 2 Expression And Upregulation Of Markers Associated With Intestinal Carcinogenesis In Mouse Intestinal Tissues, Josiane Weber Tessmann, Pan Deng, Jerika Durham, Chang Li, Moumita Banerjee, Qingding Wang, Ryan A. Goettl, Daheng He, Chi Wang, Eun Y. Lee, B. Mark Evers, Bernhard Hennig, Yekaterina Y. Zaytseva

Markey Cancer Center Faculty Publications

Perfluorooctanesulfonic acid (PFOS) is a widely recognized environment pollutant known for its high bio- accumulation potential and a long elimination half-life. Several studies have shown that PFOS can alter multiple biological pathways and negatively affect human health. Considering the direct exposure to the gastrointestinal (GI) tract to environmental pollutants, PFOS can potentially disrupt intestinal homeostasis. However, there is limited knowledge about the effect of PFOS exposure on normal intestinal tissues, and its contribution to GI- associated diseases remains to be determined. In this study, we examined the effect of PFOS exposure on the gene expression profile of intestinal tissues of …

Sedimentation Of Large, Soluble Proteins Up To 140 Kda For 1h-Detected Mas Nmr And 13c Dnp Nmr – Practical Aspects, Dallas Bell, Florian Lindemann, Lisa Gerland, Hanna Aucharova, Alexander Klein, Daniel Friedrich, Matthias Hiller, Kristof Grohe, Tobias Meier, Barth Van Rossum, Anne Diehl, Jon Hughes, Leonard J. Mueller, Rasmus Linser, Anne-Frances Miller, Hartmut Oschkinat

Markey Cancer Center Faculty Publications

Solution NMR is typically applied to biological systems with molecular weights < 40 kDa whereas magic-angle-spinning (MAS) solid-state NMR traditionally targets very large, oligomeric proteins and complexes exceeding 500 kDa in mass, including fibrils and crystalline protein preparations. Here, we propose that the gap between these size regimes can be filled by the approach presented that enables investigation of large, soluble and fully protonated proteins in the range of 40–140 kDa. As a key step, ultracentrifugation produces a highly concentrated, gel-like state, resembling a dense phase in spontaneous liquid-liquid phase separation (LLPS). By means of three examples, a Sulfolobus acidocaldarius bifurcat- ing electron transfer flavoprotein (SaETF), tryptophan synthases from Salmonella typhimurium (StTS) and their dimeric β-subunits from Pyrococcus furiosus (PfTrpB), we show that such samples yield well-resolved proton-detected 2D and 3D NMR spectra at 100 kHz MAS without heterogeneous broadening, similar to diluted liquids. Herein, we provide practical guidance on centrifugation conditions and tools, sample behavior, and line widths expected. We demonstrate that the observed chemical shifts correspond to those obtained from μM/low mM solutions or crystalline samples, indicating structural integrity. Nitrogen line widths as low as 20–30 Hz are observed. The presented approach is advantageous for proteins or nucleic acids that cannot be deuterated due to the expression system used, or where relevant protons cannot be re-incorporated after expression in deuterated medium, and it circumvents crystallization. Importantly, it allows the use of low-glycerol buffers in dynamic nuclear polarization (DNP) NMR of proteins as demonstrated with the cyanobacterial phytochrome Cph1.

Cooperative Nucleic Acid Binding By Poly Adp‑Ribose Polymerase 1, Manana Melikishvili, Michael G. Fried, Yvonne N. Fondufe‑Mittendorf

Markey Cancer Center Faculty Publications

Poly (ADP)‑ribose polymerase 1 (PARP1) is an abundant nuclear protein well‑known for its role in DNA repair yet also participates in DNA replication, transcription, and co‑transcriptional splicing, where DNA is undamaged. Thus, binding to undamaged regions in DNA and RNA is likely a part of PARP1’s normal repertoire. Here we describe analyses of PARP1 binding to two short single‑stranded DNAs, a single‑stranded RNA, and a double stranded DNA. The investigations involved comparing the wild‑ type (WT) full‑length enzyme with mutants lacking the catalytic domain (∆CAT) or zinc fingers 1 and 2 (∆Zn1∆Zn2). All three protein types exhibited monomeric characteristics in …

Non-Transcriptional Irf7 Interacts With Nf-Κb To Inhibit Viral Inflammation, Shumin Fan, Sonam Popli, Sukanya Chakravarty, Ritu Chakravarty, Saurabh Chattopadhyay

Markey Cancer Center Faculty Publications

Interferon (IFN) regulatory factors (IRF) are key transcrip- tion factors in cellular antiviral responses. IRF7, a virus- inducible IRF, expressed primarily in myeloid cells, is required for transcriptional induction of interferon α and antiviral genes. IRF7 is activated by virus-induced phosphory- lation in the cytoplasm, leading to its translocation to the nu- cleus for transcriptional activity. Here, we revealed a nontranscriptional activity of IRF7 contributing to its antiviral functions. IRF7 interacted with the pro-inflammatory tran- scription factor NF-κB-p65 and inhibited the induction of in- flammatory target genes. Using knockdown, knockout, and overexpression strategies, we demonstrated that IRF7 inhibited NF-κB–dependent inflammatory …

Foxs1 Is Increased In Liver Fibrosis And Regulates Tgfβ Responsiveness And Proliferation Pathways In Human Hepatic Stellate Cells, Evelyn A. Bates, Zachary A. Kipp, Wang-Hsin Lee, Genesee J. Martinez, Lauren Weaver, Kathryn N. Becker, Sally Pauss, Justin F. Creeden, Garrett B. Anspach, Robert N. Helsley, Mei Xu, Maria E. C. Bruno, Marlene E. Starr, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Liver fibrosis commences with liver injury stimulating transforming growth factor beta (TGFβ) activation of hepatic stellate cells (HSCs), causing scarring and irreversible damage. TGFβ induces expression of the transcription factor Forkhead box S1 (FOXS1) in hepatocytes and may have a role in the pathogenesis of hepatocellular carcinoma (HCC). To date, no studies have determined how it affects HSCs. We analyzed human livers with cirrhosis, HCC, and a murine fibrosis model and found that FOXS1 expression is significantly higher in fibrotic livers but not in HCC. Next, we treated human LX2 HSC cells with TGFβ to activate fibrotic pathways, and FOXS1 …

Nac1 Promotes Stemness And Regulates Myeloid-Derived Cell Status In Triple-Negative Breast Cancer, Chrispus Ngule, Ruyi Shi, Xingcong Ren, Hongyan Jia, Felix Oyelami, Dong Li, Younhee Park, Jinhwan Kim, Hami Hemati, Yi Zhang, Xiaofang Xiong, Andrew Shinkle, Nathan L. Vanderford, Sara Bachert, Binhua P. Zhou, Jianlong Wang, Jianxun Song, Xia Liu, Jin-Ming Yang

Markey Cancer Center Faculty Publications

Triple negative breast cancer (TNBC) is a particularly lethal breast cancer (BC) subtype driven by cancer stem cells (CSCs) and an immunosuppressive microenvironment. Our study reveals that nucleus accumbens associated pro- tein 1 (NAC1), a member of the BTB/POZ gene family, plays a crucial role in TNBC by maintaining tumor stemness and influencing myeloid-derived suppressor cells (MDSCs). High NAC1 expression correlates with worse TNBC prognosis. NAC1 knockdown reduced CSC markers and tumor cell proliferation, migration, and invasion. Addition- ally, NAC1 affects oncogenic pathways such as the CD44-JAK1-STAT3 axis and immunosuppressive signals (TGFβ, IL-6). Intriguingly, the impact of NAC1 on tumor …

Mir-27a-3p Regulates Intestinal Cell Proliferation And Differentiation Through Wnt/Β-Catenin Signalling, Chang Li, Yuning Zhou, Yinping Jiang, Zhijie Yin, Heidi L. Weiss, Qingding Wang, B. Mark Evers

Markey Cancer Center Faculty Publications

Intestinal stem cells differentiate into absorptive enterocytes, characterised by increased brush border enzymes such as intestinal alkaline phosphatase (IAP), making up the majority (95%) of the terminally differentiated cells in the villus. Loss of integ- rity of the intestinal epithelium plays a key role in inflammatory diseases and gastro- intestinal infection. Here, we show that the intestinal microRNA (miR)-27a-3p is an important regulator of intestinal epithelial cell proliferation and enterocyte differenti- ation. Repression of endogenous miR-27a-3p leads to increased enterocyte differen- tiation and decreased intestinal epithelial cell proliferation in mouse and human small intestinal organoids. Mechanistically, miR-27a-3p regulates intestinal cell …

Genotypes Of Snps Of Key Genes Regulate Susceptibility And Drug Sensitivity To Neovascular Amd, Jinglin Cui

Theses and Dissertations (ETD)

Age-related macular degeneration (AMD), particularly its neovascular form, stands as a leading cause of blindness globally, with its prevalence in our country on a steady rise. This underscores the critical impact of neovascular AMD (nAMD) management on patient quality of life and societal burden. Current optimal treatments hinge on anti-vascular endothelial growth factor (anti-VEGF) therapies, though their efficacy varies across different drugs and individuals, highlighting the importance of precise drug selection in clinical outcomes. Research suggests that factors such as baseline vision, age, disease duration, lesion size, central retina thickness, neovascularization type, and demographic differences influence nAMD prognosis. In addition, …

Acute Postoperative Pain And Dorsal Root Ganglia Transcriptomic Signatures Following Total Knee Arthroplasty (Tka) In Rats: An Experimental Study, Justice Achonu, David E. Komatsu, Sardar Mz Uddin, Chris Gordob, Martha Kanjiya, Diane Bogdan, Adriana Dibua, Hira Iftikhar, Amanda Ackermann, Rohan J. Shah, Jason Shieh, Agnieszka B. Bialkowska, Martin Kaczocha

Stony Brook Orthopaedic and Musculoskeletal Journal

Total knee arthroplasty (TKA) is the final treatment option for patients with advanced knee osteoarthritis (OA). Unfortunately, TKA surgery is accompanied by acute postoperative pain that is more severe than arthroplasty performed in other joints. Elucidating the molecular mechanisms specific to post-TKA pain necessitates an animal model that replicates clinical TKA procedures, induces acute postoperative pain, and leads to complete functional recovery. Here, we present a new preclinical TKA model in rats and report on functional and behavioral outcomes indicative of pain, analgesic efficacy, serum cytokine levels, and dorsal root ganglia (DRG) transcriptomes during the acute postoperative period. Following TKA, …

Image-Based Multiplex Immune Profiling Of Cancer Tissues: Translational Implications. A Report Of The International Immuno-Oncology Biomarker Working Group On Breast Cancer., Shahin Sayed, Chowdhury Arif Jahangir, David Page, Glenn Broeckx, Claudia Gonzalez, Caoimbhe Burke, Clodagh Murphy, Jorge Reis-Filho, Amy Ly, Paul Harms

Pathology, East Africa

Recent advances in thefield of immuno-oncology have brought transformative changes in the management ofcancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis andtreatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged aspotent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, therebyexpanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing thephenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinicallyrelevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential toguide appropriate treatment …

Etanercept-Induced Iga Vasculitis, Marshall Hall, Christian Scheufele, Christopher Wong, Michael Carletti, Stephen E. Weis

North Texas GME Research Forum 2024

Introduction: IgA vasculitis, formerly known as Henoch-Schoenlein purpura, is a subtype of leukocytoclastic vasculitis (LCV) and approximately 90% are seen in the pediatric population. In the adult population, it is more frequently associated with a more severe clinical course. Causes of IgA vasculitis may be idiopathic or may be secondary to infections or medications. Etanercept is a tumor necrosis factor-alpha fusion protein that has been rarely associated with LCV. Case presentation: A 59-year-old female with a 2-year history of red-to-violaceous purpuric papules on the bilateral lower extremities. She noted that after etanercept administration her lesions would get redder and would …

Cycle Synced Fitness: The Impact Of Menstrual Cycle Phases On Women's Exercise Performance And Health, Sabrina Galindo

Graduate Research Projects

No abstract provided.

Catalyzing Communities Of Research Rigour Champions, Audrey C Brumback, William X Q Ngiam, Dana M Lapato, David B Allison, Christin L Daniels, Michael Dougherty, Haley F Hazlett, Kara L Kerr, Susan Pusek, Naomi Schrag

Children’s Nutrition Research Center Staff Publications

The biomedical sciences must maintain and enhance a research culture that prioritizes rigour and transparency. The US National Institute of Neurological Disorders and Stroke convened a workshop entitled 'Catalyzing Communities of Research Rigor Champions' that brought together a diverse group of leaders in promoting research rigour and transparency (identified as 'rigour champions') to discuss strategies, barriers and resources for catalyzing technical, cultural and educational changes in the biomedical sciences. This article summarizes 2 days of panels and discussions and provides an overview of critical barriers to research rigour, perspectives behind reform initiatives and considerations for stakeholders across science. Additionally, we …

A Comprehensive Review Of Advances In Hepatocyte Microencapsulation: Selecting Materials And Preserving Cell Viability, Hailian Wang, Lebin Wen, Fengdi Jiang, Pengyu Ren, Yixin Yang, Siyuan Song, Zhengteng Yang, Yi Wang

Children’s Nutrition Research Center Staff Publications

Liver failure represents a critical medical condition with a traditionally grim prognosis, where treatment options have been notably limited. Historically, liver transplantation has stood as the sole definitive cure, yet the stark disparity between the limited availability of liver donations and the high demand for such organs has significantly hampered its feasibility. This discrepancy has necessitated the exploration of hepatocyte transplantation as a temporary, supportive intervention. In light of this, our review delves into the burgeoning field of hepatocyte transplantation, with a focus on the latest advancements in maintaining hepatocyte function, co-microencapsulation techniques, xenogeneic hepatocyte transplantation, and the selection of …

Sustainability Via Active Garden Education (Sage): The Process Of Incorporating Watering Into Structured Preschool Curriculum, Rebecca E Lee, Anel Arriola, Elizabeth Lorenzo, Erica G Soltero, Jacob Szeszuski

Children’s Nutrition Research Center Staff Publications

School gardens provide rich outdoor learning opportunities for young children. Practical considerations about garden maintenance, in particular, watering, can impeed success. This manuscript chronicles the development of garden maintenance strategies in Sustainability via Active Garden Education (SAGE). SAGE installed raised-bed gardens and provided a complete curriculum focused on increasing children's active time and improving healthy eating habits while fostering garden stewardship. SAGE was implemented by trained research personnel in four early care and education (ECE) facilities in Houston, Texas (SAGE 1, Summer, 2013), one ECE facility in Phoenix, Arizona (SAGE 2, Spring, 2017), and 24 ECE facilities in Phoenix, Arizona …

Combinatorial Atoh1, Gfi1, Pou4f3, And Six1 Gene Transfer Induces Hair Cell Regeneration In The Flat Epithelium Of Mature Guinea Pigs, Yujie Liu, Lin Yang, Sunita Singh, Lisa A Beyer, Diane M Prieskorn, Donald L Swiderski, Andrew K Groves, Yehoash Raphael

Children’s Nutrition Research Center Staff Publications

Flat epithelium (FE) is a condition characterized by the loss of both hair cells (HCs) and supporting cells and the transformation of the organ of Corti into a simple flat or cuboidal epithelium, which can occur after severe cochlear insults. The transcription factors Gfi1, Atoh1, Pou4f3, and Six1 (GAPS) play key roles in HC differentiation and survival in normal ears. Previous work using a single transcription factor, Atoh1, to induce HC regeneration in mature ears in vivo usually produced very few cells and failed to produce HCs in severely damaged organs of Corti, especially those with FE. Studies in vitro …

Advancing Kidney Xenotransplantation With Anesthesia And Surgery – Bridging Preclinical And Clinical Frontiers Challenges And Prospects, Xiaojian Zhang, Hailian Wang, Qin Xie, Yang Zhang, Yixin Yang, Man Yuan, Yuqi Cui, Si-Yuan Song, Jianzhen Lv, Yi Wang

Children’s Nutrition Research Center Staff Publications

Xenotransplantation is emerging as a vital solution to the critical shortage of organs available for transplantation, significantly propelled by advancements in genetic engineering and the development of sophisticated immunosuppressive treatments. Specifically, the transplantation of kidneys from genetically engineered pigs into human patients has made significant progress, offering a potential clinical solution to the shortage of human kidney supply. Recent trials involving the transplantation of these modified porcine kidneys into deceased human bodies have underscored the practicality of this approach, advancing the field towards potential clinical applications. However, numerous challenges remain, especially in the domains of identifying suitable donor-recipient matches and …

The Impact Of Telehealth-Based Behavioral Lifestyle Program On Hypertension Control In African American Participants: Results From The Heals Med-Tech Randomized Controlled Trial, Sunita Dodani Dodani, Amanda Clarke, Ismail El Moudden, Tharidu Gunawardena, Navdhit Bedi

Department of Medicine Faculty Publications

Introduction: The HEALS Med-Tech program offers a unique blend of lifestyle changes and technology to improve hypertension (HTN) management in African Americans (AAs), a group disproportionately affected by cardiovascular disease (CVD).

Methods: A randomized controlled trial compared HEALS Med-Tech against usual care for uncontrolled hypertension in AAs, focusing on diet, medication adherence, and telehealth.

Results: In a study of 61 participants, HEALS Med-Tech significantly reduced systolic blood pressure by 12.95 mm Hg (p = 0.008) and 9.19 mm Hg (p = 0.013) at 3 and 12 months, respectively, demonstrating improved hypertension control.

Conclusions: HEALS Med-Tech demonstrates potential in HTN management …

Ai And Radiologist Assessments On The Prevalence Of Tmj Osteoarthritis Using Radiographic Images: A Comparative Study, Louloua Mourad, Nayer Abo El Saad, Yehia El Mahallawy

International Arab Journal of Dentistry

Objectives: This study aims to address the significant discomfort and functional impairment associated with temporomandibular joint osteoarthritis (TMJ OA), which negatively impacts the quality of life. It emphasizes the importance of prompt diagnosis and explores the potential of an Artificial Intelligence (AI) system to enhance TMJ OA diagnosis.

Methods: The prevalence of TMJ OA was evaluated using 3 diagnostic tools: the gold standard, the AI model, and an examiner. In total, 132 patients who performed 190 cone-beam computed tomography (CBCT) images were included.

Results: The prevalence of TMJ OA was 62.11% using the gold standard, 63.68% using …

Plasma Growth Hormone As A Prognostic Biomarker To Durvalumab And Tremelimumab In Patients With Advanced Hepatocellular Carcinoma, Shadi Chamseddine, Michael Lapelusa, Lianchun Xiao, Yehia I Mohamed, Sunyoung S Lee, Zishuo Ian Hu, Rikita I Hatia, Manal Hassan, James C Yao, Dan G Duda, Saumil Datar, Hesham M Amin, Ahmed O Kaseb

Faculty, Staff and Student Publications

INTRODUCTION: In this study, we explored the potential of plasma growth hormone (GH) as a prognostic biomarker in patients with advanced HCC treated with durvalumab plus tremelimumab (D+T).

METHODS: In this study, we included 16 patients with advanced HCC who received D+T at MD Anderson Cancer Center between 2022 and 2023 and had plasma GH measurements recorded before treatment. Plasma GH levels were measured from prospectively collected blood samples and were correlated with progression-free survival (PFS) and overall survival (OS). The cutoff for normal GH levels in women and men was defined as ≤3.7 μg/L and ≤0.9 μg/L, respectively. The …

Circulating Sphingolipids In Relation To Cognitive Decline And Incident Dementia: The Cardiovascular Health Study, Kristine F Moseholm, Héléne T Cronjé, Manja Koch, Annette L Fitzpatrick, Oscar L Lopez, Marcia C De Oliveira Otto, W T Longstreth, Andrew N Hoofnagle, Kenneth J Mukamal, Rozenn N Lemaitre, Majken K Jensen

Faculty, Staff and Student Publications

INTRODUCTION: Whether circulating levels of sphingolipids are prospectively associated with cognitive decline and dementia risk is uncertain.

METHODS: We measured 14 sphingolipid species in plasma samples from 4488 participants (mean age 76.2 years; 40% male; and 25% apolipoprotein E (

RESULTS: Higher plasma levels of sphingomyelin-d18:1/16:0 (SM-16) were associated with a faster cognitive decline measured with 3MSE, in contrast, higher levels of sphingomyelin-d18:1/22:0 (SM-22) were associated with slower decline in cognition measured with DSST. In Cox regression, higher levels of SM-16 (hazard ration [HR] = 1.24 [95% confidence interval [CI]: 1.08-1.44]) and ceramide-d18:1/16:0 (Cer-16) (HR = 1.26 [95% CI: 1.10-1.45]) …

Variant Of The Lactase Lct Gene Explains Association Between Milk Intake And Incident Type 2 Diabetes, Kai Luo, Guo-Chong Chen, Yanbo Zhang, Jee-Young Moon, Jiaqian Xing, Brandilyn A Peters, Mykhaylo Usyk, Zheng Wang, Gang Hu, Jun Li, Elizabeth Selvin, Casey M Rebholz, Tao Wang, Carmen R Isasi, Bing Yu, Rob Knight, Eric Boerwinkle, Robert D Burk, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

Cow's milk is frequently included in the human diet, but the relationship between milk intake and type 2 diabetes (T2D) remains controversial. Here, using data from the Hispanic Community Health Study/Study of Latinos, we show that in both sexes, higher milk intake is associated with lower risk of T2D in lactase non-persistent (LNP) individuals (determined by a variant of the lactase LCT gene, single nucleotide polymorphism rs4988235 ) but not in lactase persistent individuals. We validate this finding in the UK Biobank. Further analyses reveal that among LNP individuals, higher milk intake is associated with alterations in gut microbiota (for …

Alopecia As An Early Clinical Marker For Azathioprine Induced Myelosuppression: A Case Report, Nilanjana Dutta , Final Year Mbbs, Dr. M Suresh Babu , Professor, Dr. Subramanian Ramaswamy , Professor, Dr. Mahabaleshwar Mamadapur , Assistant Professor

Digital Journal of Clinical Medicine

Azathioprine is a pro-drug and is metabolized by the TPMT enzyme in the body. In South Asians, Azathioprine is known to cause alopecia and bone marrow suppression in patients with TPMT enzyme deficiency. In India, the prevalence of TPMT mutation varies from 1.2- 10%. A new mutation was detected in 2014, NUDT15 whose incidence varies from 8.5-16%. Patients with mutation in both TPMT and NUDT15 develop myelosuppression faster. In our case, alopecia manifested as the first clinical feature of Azathioprine myelosuppression. Physicians need to recognize early clinical clues (alopecia) to avoid the impending development of myelosuppression and to look for …

Knowledge, Attitudes, And Practices Among Health Care Professionals In A Tertiary Care Teaching Hospital, Mysuru, Rakesh M, Dr Sunil Kumar D, Dr Shwethashree M, Kodeeswaran M, Aradhya M. Gowda

Digital Journal of Clinical Medicine

ABSTRACT

Background: Biomedical waste (BMW) refers to waste generated during the diagnosis, treatment, or immunization of humans or animals, posing risks to health and the environment if not managed properly. Proper knowledge, attitudes, and practices (KAP) among healthcare professionals are essential for effective BMW management. This study assessed the KAP of healthcare workers regarding BMW in a tertiary care teaching hospital.

Methods: A cross-sectional study was conducted among 149 healthcare professionals at a private medical college from April 10 to May 10, 2023. Participants were selected using simple random sampling, including consultants, postgraduates, interns, nursing staff, laboratory technicians, and housekeeping …

Clozapine And Modified Electroconvulsive Therapy (M-Ect) In Treatment Resistant Schizophrenia (Trs) – A Case Report, Kareena Arora, Kishor M, Murali M R, Suhas K Mr

Digital Journal of Clinical Medicine

Schizophrenia is psychiatric disorder affecting less than 1% of population that can be devastating, characterized by positive, negative and cognitive symptoms. This can lead to significant functional impairment. Despite intensive and ongoing research, outcomes from best-practice treatment are often suboptimal. Unfortunately, not all the patients respond to antipsychotic medications. Overall estimates suggest that one-fifth to one-half of patients have treatment resistant schizophrenia (TRS).

TRS include failure sequential trial of two different antipsychotics with sufficient dose, duration and adherence as a minimum criterion. TRS represents major clinical challenge.

Clozapine is the only drug approved for TRS as it is the drug …

High Stakes And Hidden Risks: A Case Series On Pathological Gambling In Context With Affective Disorders And Substance Abuse, Avni Gupta, Namita Deka, Mahesh Kumar

Digital Journal of Clinical Medicine

Background: Pathological gambling is a non–substance-related addictive disorder, characterized by persistent preoccupation with gambling, impaired control, and continuation despite negative consequences. It is associated with financial losses, social and occupational dysfunction, and psychiatric comorbidities, including affective and substance use disorders. Although international prevalence estimates range from 1–2%, research in India remains limited, particularly with the rise of online gambling.

Methods: We report a case series of three individuals presenting to a tertiary-care psychiatry outpatient department with pathological gambling. Clinical assessments included detailed psychiatric evaluation, mental status examination, and psychometric assessments using the Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory …

Frozen By Worry And Fatigue? A Mixed Methods Approach To Understanding The Lived Experiences Of Freezing Of Gait, Sarah M. Ghose

Theses and Dissertations

This study utilized a mixed methods emergent, phenomenological approach to (1) understanding the lived experience of freezing of gait for individuals diagnosed with Parkinson’s Disease and (2) determining the role of anxiety and sleep in freezing of gait outcomes. Participants included 13 adults diagnosed with Parkinson’s Disease (N=14 for qualitative data, N=13 for quantitative data; 23.1% female-identifying, 76.9% male-identifying) who were predominantly white (92.3%) with an average age of 69 years (SD = 6.73 years). Data collection consisted of semi-structured interviews, self-report measures, actigraphic sleep data, and salivary alpha amylase biomarker collection. Results are organized into …

The Patient Experience Of Language Discordance And Interpreter Services In The Emergency Department, Keri L. Baker

Theses and Dissertations

Background: Clear communication is critical to the interaction of a patient and medical provider. For non-English speaking patients, language discordance, described as the lack of proficiency in a shared language, with the medical team results in a poor patient experience and poor patient outcomes. The predominant solution to language discordance is the use of interpreter services, however these services are underused in the emergency department (ED). Studies examining underuse of interpreter services have primarily focused on the clinician and little is known about the patient’s influence on the use of interpreter services.

Methods: Semi-structured interviews were conducted with 12 Spanish-speaking …

The Genetic Architecture Of Cervical Change During Pregnancy: From Modeling To Mechanism — Does The Cervix Mediate Maternal Risk For Spontaneous Preterm Birth?, Hope M. Wolf

Theses and Dissertations

This project leverages clinical data and biospecimens from a prospective longitudinal cohort of pregnant women to study the genetic and phenotypic relationships between cervical shortening and the duration of pregnancy. Sonographic cervical length (CL) was measured throughout pregnancy in a cohort of 5,160 Black/African American women in Detroit, Michigan. Maternal DNA samples were sequenced with a next-generation low-pass whole genome platform. The heritability of cervical change during pregnancy and its genetic correlation with gestational age at delivery (GAD) were estimated using Genome-Wide Complex Trait Analysis. These estimates suggest that cervical change is heritable (h²CL = 51%) and highly polygenic trait. …

Dna Methylation In Aging And Alzheimer's Disease, Raymond Cheng, Jingmin Shu, Hai Chen, Ming Li, Xiaodong Cheng, Li Liu

The Brown Foundation: Institute of Molecular Medicine

DNA methylation undergoes significant changes with age. These alterations play a pivotal role in the development of age-related diseases, including Alzheimer's disease (AD). Recent advancements in DNA methylome profiling have revealed global hypomethylation patterns, particularly within repetitive elements, as well as gene-specific changes that are associated with neurodegeneration. Age-related alterations in DNA methylation have been implicated in the disruption of key cellular processes, such as inflammation and proteostasis, both central to AD pathology. However, several challenges persist in this field. One major issue is the inconsistency of findings across different brain regions and tissue types, which complicates result interpretation. Furthermore, …