Diseases Commons^™

Associations Between Contralesional Neuroplasticity And Motor Impairment Through Deep Learning-Derived Mri Regional Brain Age In Chronic Stroke (Enigma): A Multicohort, Retrospective, Observational Study, Gilsoon Park, Mahir Khan, Justin Andrushko, Nerisa Banaj, Michael Borich, Lara Boyd, Amy Brodtmann, Truman Brown, Cathrin Buetefisch, Adriana Conforto, Steven Cramer, Michael Dimyan, Martin Domin, Miranda Donnelly, Natalia Egorova-Brumley, Elsa Ermer, Wuwei Feng, Fatemeh Geranmayeh, Colleen Hanlon, Brenton Hordacre, Neda Jahanshad, Steven Kautz, Mohamed Salah Khlif, Jingchun Liu, Martin Lotze, Bradley Macintosh, Feroze Mohamed, Jan Nordvik, Fabrizio Piras, Kate Revill, Andrew Robertson, Christian Schranz, Nicolas Schweighofer, Na Jin Seo, Surjo Soekadar, Shraddha Srivastava, Bethany Tavenner, Gregory Thielman, Sophia Thomopoulos, Daniela Vecchio, Emilio Werden, Lars Westlye, Carolee Winstein, George Wittenberg, Jennifer Ferris, Chunshui Yu, Paul Thompson, Sook-Lei Liew, Hosung Kim

Department of Radiology Faculty Papers

BACKGROUND: Stroke leads to complex chronic structural and functional brain changes that specifically affect motor outcomes. The brain predicted age difference (PAD) has emerged as a sensitive biomarker of both sensorimotor and cognitive function after stroke. Our previous study showed a higher global brain PAD associated with poorer motor function after stroke. However, the association between local stroke lesion load, regional brain age, and motor impairment is unclear. This study aimed to investigate the associations between focal lesion damage, regional brain PAD in both hemispheres, and motor outcomes in chronic stroke, and to identify key predictors of motor impairment.

METHODS: …

Multiparametric Flow Cytometry Immune Profiling Of Pulmonary And Extra-Pulmonary Tuberculosis Reveals Distinct Blood-Based Biomarker Signatures, Kalaiarasan Ellappan, Prakash Babu Narasimhan, Harriet N. Garlant, Seshadri Vasan, Komal Jain, Saka Vinod Kumar, Vishnukanth Govindaraj, Vir Singh Negi, Karen E. Kempsell

Research outputs 2022 to 2026

This study investigated immune cell distributions, cell-specific immune markers, and selected biomarker targets in pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) using multiparametric flow cytometry (MFC). Whole blood was collected from 45 individuals, including healthy controls (HC), EPTB, and PTB patients (n = 15/group). Peripheral blood leukocytes were analysed by MFC to characterize CD4+ and CD8+ T cells, natural killer (NK), invariant NKT (iNKT) and NKT cells, classical (CM), intermediate (IM) and non-classical monocytes (NCM), and activated monocytes (AM). Expression of GBP1, CALCOCO2, IFIT3, SNX10, ARG1, PD-1, and PD-L1 was assessed across these immune subsets. Increased frequencies of NK, NKT, …

Oxytocin Dosing During Trial Of Labor After Cesarean To Minimize The Risk Of Uterine Rupture: A Systematic Review And Meta-Analysis, Pierpaolo Nicolì, Moti Gulersen, Jordan Beacham, Hila Hochler, Alessandra Familiari, Anna Locatelli, Cynthia Abraham, Ettore Cicinelli, Amerigo Vitagliano, Vincenzo Berghella

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: Oxytocin remains the mainstay for induction and for the management of labor arrest during trial of labor after cesarean (TOLAC). Therefore, the clinical question should be not whether to use oxytocin, but how to optimize its administration. This meta-analysis aimed to assess which oxytocin protocol, in terms of initial dose, amount of increase, timing to next increase, and maximum dose, may minimize the risk of uterine rupture (UR) during TOLAC.

DATA SOURCES: PubMed, Embase and Clinicaltrials.gov were searched up to September 21, 2024.

STUDY ELIGIBILITY CRITERIA: Randomized and nonrandomized studies evaluating the association between induction and/or augmentation with oxytocin …

Phentermine And The Failing Heart: A Case Of Phentermine Associated Cardiomyopathy Complicated By Pulmonary Hypertension, Nisha Puri, Cecil Jnawali, Ethan Wincler, Ryan Scagliarini, Dmitri Zbarsky, Julie Worthington

South Atlantic Division GME Research Days 2026

No abstract provided.

Assessment Of Skin In Patients With Systematic Sclerosis Using High-Frequency Ultrasound And Shear Wave Elastography: A Comparative Study With Histology, Molecular, And Clinical Parameters, Ruhani Desai, Filemon Tan, Minghua Wu, Jeffery L. Browning, Samuel Theodore, Meng Zhang, Brian Skaug, Harshdeep Singh Chawla, Manmohan Singh, Salavat Aglyamov, Kirill V. Larin, Maureen Mayes, Shervin Assassi

Department of Medicine Faculty Publications

Objective: Ultrasound (US) has been proposed as a potential tool for assessing skin fibrosis in systemic sclerosis (SSc). However, a large-scale comparison of US-based assessment with histologic markers of skin fibrosis has not been reported. We evaluated US-based skin assessments for their face validity (differentiation between involved SSc and healthy control [HC] skin), construct validity (comparison to modified Rodnan skin score [mRSS]), and criterion validity (comparison to histologic and gene expression fibrosis markers).

Methods: Twenty HCs and 52 patients with SSc underwent clinical and US assessment followed by a forearm skin biopsy. Predefined areas were assessed on the finger, hand, …

Educational Case: Meningioma, Ashley M. Carter, Harrison Dai, Harrison Klause, Alberto Musto, Richard M. Conran

Department of Medicine Faculty Publications

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology.

Ultra-Processed Foods And The Cardiovascular-Kidney-Metabolic Continuum: Integrating Epidemiological, Multi-Omics, And Translational Evidence, Saiful Singar, Amirhossein Ataei Kachouei, Leandro Lantigua-Somoano, David Manley, Anthony Cardinale, Muhammad Zulfiqah Sadikan, Saurabh Kadyan, Donya Shahamati, Lorena Dias, Amber Wood, Cinthia Chavarria, Sara K. Rosenkranz, Neda S. Akhavan

Department of Medicine Faculty Publications

Cardiovascular-kidney-metabolic (CKM) syndrome integrates excess adiposity, metabolic dysfunction, kidney impairment, subclinical cardiovascular diseases, and clinical events along a staged continuum that invites unified prevention and treatment. Ultra-processed foods (UPFs) are a complex, high-prevalence exposure that may influence risk across CKM stages through nutrient profiles, additives, processing-induced compounds, and packaging-related contaminants. This review synthesizes epidemiologic, mechanistic, and translational evidence with attention to exposure definition and analytic rigor. We summarize NOVA-based UPF operationalization across dietary assessment tools, highlighting misclassification of mixed dishes, brand heterogeneity, and energy under-reporting, and we propose further examination of energy-adjusted models, calibration, and harmonized metrics. Observational studies consistently …

The Gut-Heart Axis: Exploring The Role Of The Gut Microbiome In Cardiovascular Health-A Focused Systematic Review, Yahya Makkieh, Haider Hussain Shah, Sakan Binte Imran, Shadman Mahmood Mahmood Khan Pathan, Anagha Chirayath Saju, Mounica Majooju, Aastha Garg, Tarun Naag, Rabeeul Islam, Cheeranthodika Fahima, Ramsha Ali

Electrical & Computer Engineering Faculty Publications

This focused systematic review examines the role of the gut microbiota in cardiovascular disease (CVD). The review explores mechanisms linking gut dysbiosis with CVD via microbial metabolites such as trimethylamine-Noxide (TMAO) and short-chain fatty acids (SCFAs), which affect inflammation, endothelial function, and lipid metabolism. Interventions including dietary modifications, probiotics, prebiotics, fecal microbiota transplantation, and pharmacological agents such as statins, rifaximin, and empagliflozin are evaluated for their impact on microbial composition and cardiovascular outcomes. Probiotic strains and fiber-rich diets demonstrated modest improvements in blood pressure, lipid profiles, and inflammatory markers. Studies revealed that gut microbiome alterations influence drug metabolism and bleeding …

The Postsynaptic Scaffolding Protein Sapap3 Shapes Mitochondrial Activity: The Case Of Huntington's Disease, Patrícia Coelho, Ildete Luísa Ferreira, Ana Sofia Lourenço, Daniela Marinho, Sandra Isabel Anjo, Zongwei Fang, Lígia Fão, Sandra I. Mota, Philippe J. Mas, Mário Carvalho, Rui Jorge Nobre, Carina Henriques, Joana Fraga, Dongqing Wang, Sandra Macedo Ribeiro, Luís Pereira De Almeida, Patrícia Monteiro, Isaura Simões, Darren J. Hart, Bruno Manadas, João Peça, Pedro Castanheira, A. Cristina Rego

Biological Sciences Faculty Publications

Postsynaptic scaffolding protein SAP90/PSD95-associated protein 3 (SAPAP3) modulates cortico-striatal signalling and regulates the maintenance of synaptic structure. Notably, SAPAP3 defects have been reported in several human psychiatric disorders that share pathophysiological features with Huntington’s disease (HD), a neurodegenerative disorder characterized by the expression of mutant huntingtin (mHTT) and marked dysfunction of cortico-striatal synapses and mitochondria. However, the role of SAPAP3 in mitochondrial function and HD pathophysiology remains unexplored. SAPAP3 was extracted from striatal synaptoneurosomes and analyzed by SWATH-MS proteomics to identify potential interactors, revealing SAPAP3 association with several mitochondrial proteins, particularly Mic60. These data were further complemented with proximity ligation …

Micrornas Regulated By Pregnancy Target Antiviral And Cancer Immunity Overlapping With The Hiv Interactome, Paula F. T. Cezar-De-Mello, Jonathan M. Dreyfuss, Pai-Lien Chen, Hidemi Yamamoto, Xiaoming Gao, Hui Pan, Charles Morrison, Gustavo F. Doncel, Robert L. Barbieri, Raina N. Fichorova

CONRAD Publications

Innate immunity predictors of HIV-1 risk and pathogenesis vary with reproductive hormones, pregnancy, and lactation, yet the underlying mechanisms remain unclear. We hypothesized that pregnancy-associated physiological adaptations alter systemic microRNA (miRNA) expression, thereby regulating immunity, pathogenesis and susceptibility to infection. We analyzed 174 serum samples from 88 participants in a longitudinal cohort from Uganda and Zimbabwe across pre-pregnancy (PP), pregnancy (P), and postpartum breastfeeding (BF). Cell-free peripheral blood miRNAs (n = 2083) were profiled using HTG EdgeSeq. Pregnancy-specific miRNAs were identified by intersecting differentially expressed (DE) miRNAs from P vs. PP and P vs. BF comparisons. miRNA targets and pathways …

Investigating The Role Of Traditional Chinese Herbal Medicine For Cancer Symptom Management In Older Adults: A Rapid Review, Isabelle C. Karshner

Honors Undergraduate Theses

Background: Patients with cancer often experience symptoms related to disease, complications, and treatment. One potential method of alleviating these symptoms is traditional Chinese herbal medications (TCHM). This rapid review explores the role of traditional Chinese herbal medications in treating cancer-related symptoms in older adults.

Purpose: The purpose of this rapid review is to gain and provide a better understanding of the effects of TCHM on cancer-symptom management in the older adult population. This review explores the association between TCHM and effects on cancer symptoms in older adults, including interactions, toxicity, and signs/symptoms of TCHM use that may be useful information …

Dengue Fever With Normal Platelet Count In A Patient With Β-Thalassemia Trait: A Case Report., Pankaj Kumar Jain, Manoj Seval, Vikas Meena, Rajesh Kumar Yadav

Digital Journal of Clinical Medicine

Dengue fever is an arboviral infection caused by different serotypes of the dengue virus. Generally, it presents with a wide variety of symptoms ranging from undifferentiated fever to dengue shock syndrome associated with thrombocytopenia and hemoconcentration. But in patients with thalassemia, it presents with anemia due to hemolysis, rather than hemoconcentration. Here we present a case of an 18-year-old female diagnosed with Dengue fever with thalassemia trait, who presented with a normal platelet count and moderate microcytic anemia.

Limitations Of Plasma Exchange In Yellow Phosphorus-Induced Acute Liver Failure: A Case Report, Vihitha Vunnam, Swathi B.S

Digital Journal of Clinical Medicine

Yellow phosphorus is a highly toxic compound commonly used in rodenticides and is associated with significant morbidity and mortality following ingestion. Toxicity typically evolves through an initial gastrointestinal phase, a deceptive latent period, and a final phase characterized by fulminant hepatic failure and multiorgan dysfunction. We report the case of an 18-year-old male who intentionally ingested two tubes of Ratol containing 3% yellow phosphorus. After initial vomiting and transient clinical stability, he developed rapidly progressive acute liver failure with severe coagulopathy, conjugated hyperbilirubinemia, hepatic encephalopathy, acute pancreatitis, pancytopenia, acute kidney injury, metabolic derangements, and recurrent hypoglycemia. Serial laboratory trends demonstrated …

When Fever And Thrombocytopenia Are Not Infectious: A Case Of Vitamin B12 Deficiency Mimicking Tropical Fever, Ram Arvind Viswanathan Dr

Digital Journal of Clinical Medicine

Vitamin B12 deficiency is classically associated with megaloblastic anaemia and neurological manifestations; however, atypical presentations continue to pose diagnostic challenges. Fever in association with thrombocytopenia often prompts evaluation for infectious aetiologies such as dengue, malaria, or sepsis, particularly in tropical settings. We report a case of vitamin B12 deficiency presenting with pyrexia and isolated thrombocytopenia, initially suspected to be an infectious illness. Extensive evaluation failed to reveal an infective cause, and subsequent haematological workup demonstrated megaloblastic changes with low serum vitamin B12 levels. Remarkably, the patient showed rapid defervescence and normalisation of platelet counts following parenteral vitamin B12 therapy. This …

The Role Of Physicians In Society: Perspectives From First-Year Mbbs Aspirants, Jesymol Joy, Dr Rashmi S, Amogha Shree, Dr Sunil Kumar D

Digital Journal of Clinical Medicine

Background: Physicians occupy a pivotal role in society as healers and communicators, with ethical leadership embedded in professional practice. In India, this role is evolving in response to changes in healthcare systems, increasing commercialization, and shifting societal expectations. Understanding how medical students perceive the physician’s role at the onset of medical education is vital for early professional identity development.

Objectives: To assess the motivations, perceptions, and values of first-year MBBS students regarding the societal roles, qualities, and responsibilities of physicians.

Methods: A cross-sectional study was conducted among 430 first-year MBBS students at a tertiary medical college in Mysuru, Karnataka, using …

Do More Sexually Active Men Have Less Bothersome Lower Urinary Tract Symptoms Of Benign Prostatic Hypertrophy? – A Prospective Cross-Sectional Study, Sharad Kumar Sahai, Puneet Aggarwal, Satya Prakash Tripathi, Pushkar Mendiratta, Madhamshetty Ranjith

Digital Journal of Clinical Medicine

Objectives:

Lower urinary tract symptoms (LUTS) are common in adult males with benign prostatic hyperplasia (BPH) being a common cause, with significant effect on the patient’s quality of life and sexual function. Studies show that sexual dysfunction increases with increasing severity of LUTS. The present study aimed to analyse whether the severity of BPH symptoms assessed using scoring system had any association with ejaculation frequency and erectile function.

Methods:

This was a prospective cross-sectional study done over a period of 18 months. All consecutive patients reporting to the surgical department with BPH and meeting the inclusion criteria were enrolled for …

Stones, Bones, And Hormones: A Multisystem Presentation Of Primary Hyperparathyroidism Due To Parathyroid Adenoma, Gadgesh B, Varsha Tandure, Nandini K, Chandana Srinath

Digital Journal of Clinical Medicine

Primary hyperparathyroidism is an endocrine disorder characterized by excessive secretion of parathyroid hormone, most commonly due to a solitary parathyroid adenoma, resulting in hypercalcemia and multisystem involvement [1]. Although many patients are diagnosed incidentally, delayed recognition may lead to severe renal, skeletal, gastrointestinal, and cardiovascular complications.

We report the case of a 44-year-old male who presented with sepsis and acute kidney injury, later found to have hypercalcemia with nephrocalcinosis, chronic calcific pancreatitis, skeletal deformities, and markedly elevated parathyroid hormone levels. Imaging localized a parathyroid adenoma, and the patient underwent successful parathyroidectomy with significant biochemical and clinical improvement.

This case emphasizes …

Clinical Correlates And Predictors Of Suicide Attempt Severity In Elderly Patients: A Cross-Sectional Study From South India, Rajamani Siddamallappa, Kiran Kumar Kadarappa Dr, Megha C N

Digital Journal of Clinical Medicine

Background: Suicide in late life is a major yet under-recognized public health problem in low- and middle-income countries. Elderly suicidal behaviour reflects interactions between psychiatric morbidity, substance use, psychological distress, intent, and method selection. Indian data examining these factors comprehensively remain limited.

Objectives: To assess psychiatric morbidity, hopelessness, suicide intent, planning patterns, methods, and independent predictors of suicide attempt severity among elderly suicide attempters.

Methods: This cross-sectional study included 75 elderly individuals (≥60 years) admitted following a suicide attempt to a tertiary care hospital in South India. Depression severity, hopelessness, and suicide intent were assessed using Beck’s Depression Inventory-21 (BDI-21), …

From Controversy To Comeback: The Renewed Role Of Pralidoxime In Op Poisoning, Dr Sanaa Jain, Dr Savitha V, Dr . Shashidhara K C

Digital Journal of Clinical Medicine

Organophosphorus compounds are commonly used as pesticides in agriculture, but they are responsible for approximately one-third of suicide deaths in Asian countries.The symptoms of organophosphate (OP) poisoning vary over time and are categorized into three phases: Acute Cholinergic Crisis (minutes to 24 hours), Delayed Phase (24 hours to 2 weeks), which may include intermediate syndrome, coma, and extrapyramidal symptoms, and Late Phase (OPIDP). Treatment typically involves Atropine, Pralidoxime, and symptomatic management, including airway support and mechanical ventilation.

Ropinirole-Induced Sleep-Related Behavioral Disturbances And Psychotic Symptoms In Parkinson's Disease: A Case Report, Kareena Arora, Akshatha C. J, Rajesh Raman, Vikrant Arora, Bindu Annigeri, Megha Sadashiv

Digital Journal of Clinical Medicine

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized primarily by motor symptoms such as bradykinesia, rigidity, and tremor. Though commonly associated with motor symptoms but can also present with significant non-motor symptoms such as sleep disturbances, psychosis, and cognitive decline. These symptoms may arise spontaneously or be medication-induced. We present the case of a 53-year-old male with Parkinson’s disease who developed nocturnal behavioural disturbances and psychotic features, likely secondary to dopaminergic agonist medication. Symptom resolution followed adjustment of antiparkinsonian medications and the introduction of antipsychotic medication

Unusual Case Of Pelvic Fracture Urethral Distraction Defect, Varuni Pragya, Madhukesh Rudramurthy, Siddalinga Murthy G

Digital Journal of Clinical Medicine

INTRODUCTION

Urinary bladder ruptures are an uncommon injury, occurring in less than 1% of all blunt abdominal trauma. Extraperitoneal bladder ruptures are generally associated with pelvic fractures and usually managed nonoperatively but open surgery is required when these injuries are associated with additional trauma to structures like prostate and urethra.

CASE PRESENTATION

We report our experience with a 32-year-old male who suffered a head on collision with a four-wheeler while driving a two-wheeler in a road traffic accident. He presented to the hospital with abdominal and pelvic pain, difficulty in passing urine and swelling of the scrotum. His X Ray …

Comparison Of Post Operative Analgesia Between Dexmedetomidine Versus Clonidine As Adjuvant To Ropivacaine In Ultrasound Guided Adductor Canal Block In Arthroscopic Knee Surgeries: A Randomized Controlled Study, Shwetha Arun, Archana B N, Dr. Shivakumar G Pofessor And Hod, Devika Lekshmi S

Digital Journal of Clinical Medicine

The current study evaluated the analgesic efficacy of dexmedetomidine versus clonidine as adjuvants to 0.2% ropivacaine in ultrasound-guided adductor canal block. Effective postoperative pain management is essential for early mobilization and improved recovery following arthroscopic knee surgeries. Sixty ASA I–II patients aged 20–60 years undergoing elective arthroscopic knee procedures were randomized into two groups: Group D received ropivacaine 0.2% 30ml with dexmedetomidine 100 mcg, and Group C received ropivacaine 0.2% 30ml with clonidine 150 mcg. Duration of analgesia, pain scores, sedation levels, hemodynamic changes, and rescue analgesic requirements were recorded. Group D demonstrated significantly prolonged analgesia (18.08 ± 0.514 h) …

Pulmonary Hemosiderosis In A Young Child Presenting With Recurrent Respiratory Illness And Refractory Anemia: A Case Report, Praveen Das, Ratnapriya Chowdhry, Neha Bhongale, Poonam Wade

Digital Journal of Clinical Medicine

Pulmonary hemosiderosis (PH) is a rare cause of diffuse alveolar hemorrhage in children and often presents with nonspecific respiratory symptoms and refractory iron‑deficiency anemia. We report a 2.5‑year‑old girl with recurrent lower respiratory tract infections, severe transfusion‑dependent anemia, failure to thrive, and persistent bilateral pulmonary infiltrates since infancy. Bronchoalveolar lavage demonstrated hemosiderin‑laden macrophages, confirming pulmonary hemosiderosis. Further evaluation revealed C‑ANCA positivity and PR3‑ANCA negativity, raising suspicion for an ANCA‑associated vasculitis; however, there was no renal, ear‑nose‑throat, or other systemic involvement, and a lung biopsy could not be performed. The child was managed with systemic corticosteroids with clinical improvement. This case …

State Social Benefit Schemes For Women In Continuity Of Psychiatric Care: A Case Report, Mathumitha A, Kishor M. Manohar Rao Professor

Digital Journal of Clinical Medicine

Mental health disorders are a major global public health challenge. The disorders affect over a billion people worldwide, while depressive and bipolar spectrum disorders also contribute substantially to disability and reduced quality of life. According to the World Health Organization, major depression alone affects more than 300 million people globally and is considered a leading cause of years lived with disability. Beyond clinical morbidity, mental illnesses exert a profound economic impact, with depression and anxiety accounting for an estimated USD 1 trillion annually in lost productivity worldwide, while the overall global economic burden of mental disorders is projected to reach …

Dietary Micronutrients And The Risk Of Gestational Diabetes: Evidence From A Tertiary Care Setting In India, Sujatha Mahadevarao Premnath, Moneesh Sivasoupramaniane, Maghida S

Digital Journal of Clinical Medicine

Background: Gestational Diabetes Mellitus (GDM) is a significant health concern in India, affecting nearly 22.4% of pregnant women. While macronutrient roles are well explored, the impact of micronutrients on GDM risk, particularly with the Indian ethnic phenotype, requires exploration

Objectives: To compare the micronutrient intake between GDM and non-GDM pregnancies and evaluate the association between specific dietary micronutrients and GDM risk

Methods: An observational cross-sectional study was conducted among 115 South Indian pregnant women. Dietary history was taken using 24-hour recalls on two occasions and analysed via the Indian Food Composition Table (IFCT). GDM was diagnosed using International Association of …

A Comprehensive Overview Of Neurophysiological Correlates Of Cognitive Impairment In Amyotrophic Lateral Sclerosis, Seyyed Bahram Borgheai, Brie E. Achorn, Alyssa H. Zisk, Sarah M. Hosni, Karl E. G. Richter, Frank S. Menniti, Yalda Shahriari

Computer Science Faculty Publications

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to the gradual loss of motor control, typically resulting in paralysis and death within 3 to 5 years of diagnosis. ALS shares neuropathological and genetic associations with fronto-temporal dementia (FTD), a neurodegenerative condition primarily impacting cognitive functions. These two conditions are increasingly viewed as manifestations of a single molecular disease process that affects distinct brain systems, impacting motor neuronal pathways in ALS and fronto-cortical functions in FTD. However, this simple dichotomy belies the complexity of these conditions. In particular, patients with primary motor ALS can also experience significant cognitive …

Assessing Access To Orthopaedic Care For Patients With Osteogenesis Imperfecta, Annemarie K. Leonard, Kara Ayers, Lauren Faokunla, Kaeli Samson, Erika Carter, Tracy Hart, Maegen Wallace

Graduate Medical Education Research Journal

Background. Osteogenesis Imperfecta (OI) is a rare disorder caused by variations in collagen. Clinical manifestations include multiple fractures, short stature, scoliosis, blue sclera, hearing loss, and opalescent teeth. Patients often need many different medical providers frequently, which may place financial burdens on families. This study sought to identify and understand barriers to care for children with OI.

Methods. We utilized an Institutional Review Board (IRB)-approved survey for primary caregivers of children with OI. Questions included demographic data, type of health insurance, history of and reasons for insurance denials, access to multidisciplinary OI care, and travel to receive OI care. The …

Inflammatory Co-Regulation Of Voltage-Gated Sodium Channels And Na,K-Atpase In Metastatic Breast Cancer, Steven D. Scahill, Kelly Jean Sherman, Dennis Paul

School of Graduate Studies Faculty Publications

Sodium regulation is a potentially major driver of cancer metastasis. Voltage-gated sodium channels (VGSCs) and Na,K-ATPase are sodium transporters that are upregulated in many advanced carcinomas and are implicated as metastatic drivers. However, little is known about what drives this overexpression, how these proteins influence metastatic behavior, or whether these complementary sodium transporters are co-regulated in cancer. Using sodium transporter regulation in healthy neurons as a model, the present study demonstrated that the inflammatory mediator tumor necrosis factor alpha (TNFα) affects the expression of VGSCs and Na,K-ATPase in an in vitro model of metastatic breast cancer. Acute TNFα challenge increased …

Disruption Of Protein-Protein Interaction Hotspots In The C-Terminal Domain Of Mlh1 Confers Mismatch Repair Deficiency, Keri M. Fishwick, Diego Gomez Vieito, Giada Greco, Giulio Collotta, Marco Gatti, Anastasija A. Kulik, Raphaël Guérois, Ivan Corbeski, Ashutosh S. Phadte, Issam Senoussi, Petr Cejka, Anna Pluciennik, Antonio Porro, Alessandro A. Sartori

Department of Biochemistry and Molecular Biology Faculty Papers

MutLα, a heterodimer of MLH1 and PMS2, plays a key role in DNA mismatch repair (MMR), which maintains genomic stability by correcting replication errors. Loss of MLH1 function causes MMR deficiency (MMRd), leading to elevated mutation rates and increased cancer susceptibility. However, MMRd can offer a therapeutic advantage, as high tumour mutational burden enhances the efficacy of immune checkpoint inhibition. MMR also drives somatic expansion of CAG repeats linked to Huntington’s disease (HD) pathogenesis. The C-terminal domain (CTD) of MLH1 contains at least two distinct protein–protein interaction (PPI) sites. The S1 site supports heterodimerization with the PMS2 endonuclease, whereas the …

Isg15 Dysregulates Endoplasmic Reticulum-Mitochondrial Contacts And Calcium Homeostasis In Ataxia Telangiectasia, Oygul Mirzalieva, Ryan E. Reed, Arthur L. Haas, Meredith A. Juncker, Patrick Logarbo, Jennifer M. Klein, David Worthylake, Shyamal D. Desai

School of Graduate Studies Faculty Publications

Dysregulation of endoplasmic reticulum and mitochondrial (ER:Mit) contacts and mitochondrial calcium (mitCa2+) homeostasis are found in several neurodegenerative disorders, including Ataxia Telangiectasia (A-T). However, the cellular basis of these defects remains unclear. Previously, we demonstrated that the aberrantly elevated Interferon-Stimulated Gene 15 (ISG15) pathway inhibits protein polyubiquitylation, its dependent protein turnover, and mitophagy pathways in A-T. Literature indicates that silencing of mitochondrial ubiquitin ligase 1 (MUL1) stabilizes mitofusin2 (MFN2) and attenuates mitCa2+ uptake from ER to Mit (mitCa2+influx) in primary neurons. We have replicated these findings in apparently healthy fibroblasts. We hypothesized that elevated ISG15 may inhibit ubiquitin-dependent MUL1-mediated degradation …