Medical Specialties Commons^™

Staphylococcus Aureus Encodes Four Differentially Regulated Pyruvate Transporters, Jennifer L. Endres, Cleofes Sarmiento, William Xiao, Marat R. Sadykov, Kenneth W. Bayles, Mckenzie K. Lehman

Journal Articles: Pathology and Microbiology

The success of Staphylococcus aureus as a pathogen is attributable, in part, to its ability to exploit the diverse nutrient sources available during infection. Critical to this success are the pathways involving pyruvate that serve as a nexus for energy production, oxidative metabolism, and biosynthetic processes. When available, bacteria acquire pyruvate from the environment to fuel growth. Recently, LrgAB was identified as a pyruvate transporter under microaerobic conditions, leading us to speculate that S. aureus encodes other pyruvate transporters that are active during aerobic growth. In this study, we used the toxic pyruvate analog, 3-fluoropyruvic acid (3-FP), to isolate mutants …

Artesunate Enhances The Efficacy Of Enzalutamide In Advanced Prostate Cancer, Xinyi Wang, Jinghui Liu, Fengyi Mao, Yifan Kong, Qiongsi Zhang, Chaohao Li, Daheng He, Chi Wang, Yanquan Zhang, Ruixin Wang, Sally R. Ellingson, Qiou Wei, Zhiguo Li, Xiaoqi Liu

Toxicology and Cancer Biology Faculty Publications

Prostate cancer (PCa) is one of the leading causes of death among men worldwide. Treatments targeting the androgen receptor pathway remain the standard therapy for PCa patients. Enzalutamide (ENZ), a second-generation androgen receptor inhibitor, was developed to treat castration-resistant prostate cancer. However, while patients initially respond to ENZ, drug resistance typically develops within a few months. Artesunate (ART), a semisynthetic derivative of the Artemisinin plant, is approved for antimalaria treatment. In this study, we conducted an FDA-approved drug screening and identified ART as a potential candidate for overcoming ENZ resistance in PCa. Mechanistically, ART induces the degradation of c-Myc, enhancing …

Hemifacial Spasm Due To Dolichoectasia Of Vertebral And Basilar Arteries, Meena Iyer, Shasthara Paneyala Dr.

Digital Journal of Clinical Medicine

Dolichoectasia refers to the non-focal dilatation and tortuosity of arteries, primarily affecting the vertebral and basilar arteries due to severe tunica intima degeneration. It is associated with genetic predisposition and atherosclerosis, leading to vessel wall weakening. Patients may remain asymptomatic or develop neurological deficits due to mass effect. We report a case of a 60-year-old male presenting with hemifacial spasm secondary to vertebral artery dolichoectasia. Magnetic Resonance Angiography (MRA) revealed ectatic and tortuous basilar and vertebral arteries, with the left vertebral artery compressing the left facial nerve complex. Using Smoker’s criteria, a diagnosis of dolichoectasia was confirmed. Dolichoectasia-induced hemifacial spasm …

Comparison Of The Effectiveness Of Preoperative Dexmedetomidine Nebulization Versus Lignocaine Nebulization In Attenuation Of Stress Response During Direct Laryngoscopy And Endotracheal Intubation In Elective Surgeries Under General Anaesthesia: A Randomised Control Study At A Tertiary Care Hospital, Mandya, Sumayya E., Kiran A V., Santhosh M C B., Shivakumar G

Digital Journal of Clinical Medicine

Introduction: Direct laryngoscopy and tracheal intubation are known to provoke harmful stimuli that can lead to transient, unpredictable, and variable hemodynamic alterations, primarily due to heightened sympathoadrenal activity.¹ Various pharmacological agents have been explored to mitigate this stress response; however, none have emerged as optimal.²

Aim: This study aims to compare the effects of nebulized dexmedetomidine in comparison to nebulized lignocaine on the hemodynamic stress response during direct laryngoscopy and tracheal intubation, including any adverse effects in patients undergoing general endotracheal anesthesia.

Materials and Methods: Informed consent was obtained from 60 patients aged 18 to …

Lymphoma Chronicles: Insights From A Distinct Hodgkin's Lymphoma Case Report, Srirangam Shankaralingam, Vibha Nagaragatta

Digital Journal of Clinical Medicine

Hodgkin lymphoma (HL) is a kind of lymphatic malignancy distinguished by the presence of Reed-Sternberg cells. It often manifests as painless lymphadenopathy and systemic symptoms (B symptoms and can affect a variety of lymphoid tissues. The causes of HL are complicated and include genetic predisposition, environmental conditions and viral infections, particularly the Epstein-Barr virus (EBV). The diagnosis is primarily based on histological evaluation of lymph node samples, with immunophenotyping assisting classification. Herein, we report a case of classical Hodgkin’s lymphoma (HL) in an otherwise healthy 31-year-old male who had a mass per abdomen for a year and recently noticed a …

Felt Need For Psychiatry Clubs In Medical Colleges To Enhance Teaching-Learning, Aditya Rao, Sheryl Agarwal, Sharanya Bose, M Kishor

Digital Journal of Clinical Medicine

Mental health competence is critical for medical graduates, yet in India the treatment gap for common mental disorders remains substantial, with prevalence estimates indicating up to 80.4% of unmet need. Recent reforms under the Competency-based Medical Education (CBME) curriculum have expanded psychiatry training; however, deficiencies in applied skills, preventive psychiatry, and communication remain. Psychiatry clubs have been proposed as supplementary, student-led platforms to address these limitations. This cross-sectional study assessed the perceived need for psychiatry clubs among undergraduate medical students and explored their potential role in enhancing teaching–learning. A structured online survey was administered to 94 students across different phases …

Localized Reticulate Hyperpigmentation From Heater Use: A Case Of Erythema Ab Igne, Chitwan Kaur Ghuman, Monish Yarlagadda, Ashwini P K

Digital Journal of Clinical Medicine

Background: Erythema ab igne (EAI) is a reticulated, hyperpigmented dermatosis resulting from prolonged exposure to infrared radiation insufficient to cause burns. While increasingly rare due to central heating, it remains relevant in vulnerable populations, particularly the elderly and immobilized.

Case Summary: We report the case of an 83-year-old bedbound female who developed characteristic pigmentary changes over her right upper and lower limbs due to chronic proximity to a room heater.

Conclusion: Awareness of EAI is crucial to prevent unnecessary investigations and to emphasize the importance of appropriate thermal environment modifications, especially in bedbound geriatric patients.

Extracapsular Excision Of Retroperitoneal Ancient Schwannoma: A Case Report, Mayur Chaure, Shital Dharamkhele, Keval Dhone, Imran Ahmed Khan

Digital Journal of Clinical Medicine

Schwannomas are tumors originating from Schwann cells in the nerve sheath. They are generally solitary and encapsulated, but they are rarely seen in the retroperitoneal region. We report a 40-years-old woman with dull aching pain for two months without urinary symptoms. Following imaging studies, a well-encapsulated, retroperitoneal mass complicated with intratumoral bleed and necrosis was found.

Complete surgical resection was performed with preservation of adjacent viscera. The histopathology report confirmed the tumor as an ancient schwannoma. Careful preoperative surgical planning and meticulous surgical skill, along with the application of ERAS protocol, are essential to prevent morbidity and mortality. No evidence …

Prevalence Of Depression Among Type 2 Diabetes Mellitus Patients In Urban Mysuru – A Cross-Sectional Study, Jesymol Joy, Renuka M, Chiranjeevi G S

Digital Journal of Clinical Medicine

Background: Depression is a significant comorbidity among individuals with Type 2 Diabetes Mellitus (T2DM) adversely affecting disease management and overall quality of life. Diabetes and depression have a bidirectional relationship, where poorly managed diabetes increases the risk of depression, and depression exacerbates diabetes-related complications. Depression contributes to poor glycemic control, decreased adherence to treatment, increased risk of diabetes-related complications, and higher healthcare utilization.

Objectives: To determine the prevalence of depression and its associated factors among Type 2 Diabetes Mellitus patients in urban Mysuru.

Methods: A community-based cross-sectional study was conducted among 300 Type 2 Diabetes mellitus patients >18 years of …

Allergic Bronchopulmonary Aspergillosis In Pediatric Asthma : A Diagnostic Challenge Mimicking Tuberculosis, Praveen Das, Santosh Kondekar, Surbhi Rathi

Digital Journal of Clinical Medicine

Allergic bronchopulmonary aspergillosis (ABPA) is a rare hypersensitivity reaction to Aspergillus fumigatus, more commonly observed in adults and patients with cystic fibrosis. It can, however, present in pediatric asthmatics with refractory symptoms, leading to diagnostic challenges due to overlapping features with other pulmonary diseases, including tuberculosis. ABPA should be considered in children with uncontrolled asthma and atypical radiologic features, especially when unresponsive to standard therapies. Early recognition and appropriate management are critical to prevent irreversible lung damage and improve quality of life.

Pregnancy-Related Delusional Beliefs In Midlife And Late-Life Women: A Case Series, Dyuksha Arora, Ashita Adarsh, Kishor M. Manohar Rao, Anand R, Soumya Rajshekar Patil, Akshatha Cj

Digital Journal of Clinical Medicine

Pseudocyesis and delusional pregnancy represent rare but clinically significant presentations across psychiatric practice. While pseudocyesis involves a false belief of pregnancy accompanied by physical manifestations, delusion of pregnancy refers to a fixed belief of being pregnant despite clear contrary evidence. Both conditions pose considerable challenges as they involve close consultation and liaison between Obstetrics & Gynaecology and Psychiatry. There are a few studies from tertiary care general hospitals in India. Here we report two case series.

Case 1: A 43-year-old married woman from a rural background with an 8-year history of recurrent depressive disorder and dysthymia, presented with 3 months …

One Airway, One Disease In Pregnancy: A Prospective Observational Study On The Correlation Between Upper And Lower Airway Inflammation In Pregnant Women, Durga K, Yuvarajan S

Digital Journal of Clinical Medicine

Background: The well-established "One Airway, One Disease" concept recognizes the deep physiological and pathological connections between conditions affecting both the upper and lower respiratory tracts, most notably allergic rhinitis and asthma. During pregnancy, a woman's body undergoes significant immunological, hormonal, and physiological changes, which can profoundly influence and modulate existing or emerging airway inflammation.

Objective: This prospective observational study was designed with the primary objective of meticulously evaluating the correlation between upper and lower airway inflammation in pregnant women. We aimed to achieve this by assessing a range of clinical symptoms, objective functional parameters, and specific inflammatory markers.

Methods: We …

Comparision Of Buprenorphine Versus Butorphanol As An Adjuvant To Intrathecal Hyperbaric Bupivacaine For Elective Infraumbilical Surgeries : A Randomised Control Study At A Tertiary Care Hospital, Mandya, Surabhi C A, Dr. Kiran A V. Associate Professor, Dr. Shivakumar G Pofessor And Hod, Umesh N P

Digital Journal of Clinical Medicine

Introduction: Spinal anaesthesia is the most popularly performed procedure in the field of anaesthesiology. Hyperbaric bupivacaine, the local anaesthetic most commonly used, has limitation as its effect lasts only for 1.5-2 hours. Hence a lot of adjuvants have been tried to enhance the analgesic effect of bupivacaine.^[2] Opioids remain the mainstay among the various adjuvants to local anesthetics in spinal anaesthesia primarily by virtue of its various properties such as reducing the dose of local anaesthetic, minimizing side effects, and prolonging the duration of anaesthesia.^[3]

Aim: This study aims to compare the sensory and motor characteristics …

Diagnosis Of Hypertensive Disorders In Pregnancy, Rebecca Horgan, Yara Hage Diab, Maged Costantine, George Saade, Baha Sibai

Department of Obstetrics & Gynecology Faculty Publications

Hypertensive disorders of pregnancy, including chronic hypertension, superimposed preeclampsia, gestational hypertension, and preeclampsia, affect 10-20% of pregnancies and are a significant cause of maternal and perinatal mortality. The incidence of these disorders is rising due to factors such as advanced maternal age, obesity, assisted reproductive technology, and increased rates of preexisting comorbidities. Differentiating pregnancy-associated hypertension from pre-existing chronic hypertension is challenging, as the overlap between the two may be broadening due to the changing demographics of the pregnant population. This review critically evaluated the evidence regarding the current time periods recommended to make a diagnosis of a hypertensive disorder of …

Deep Dive In Sound Filtering, Cecilia Zoutewelle

A. The Science of Sound

A 7-page report, with illustrations and bullet-point summaries, on the ways we filter sounds as part of the standard process of hearing. Includes brief considerations of evolution, selective listening in conversations, and listening bias.

Resilience And Reality: Exploring The Lived Experiences Of People Living With Hiv In Texas During The Covid-19 Pandemic – A Qualitative Study., Ahmed F. Alanazi

Social Work Dissertations - Archive

This study investigated the lived experiences of individuals living with HIV (PLWH) in the Dallas-Fort Worth (DFW) area of Texas during the COVID-19 pandemic, using an Interpretative Phenomenological Analysis (IPA) framework. The research examined the intersection of health, social dynamics, and psychological resilience among PLWH, who faced compounded vulnerabilities due to systemic inequities and the dual public health crises of HIV and COVID-19. Through semi-structured interviews with ten participants from diverse backgrounds, the study captured the profound impacts of disrupted healthcare systems, heightened stigma, and social isolation on this marginalized population. The findings reveal that the pandemic exacerbated existing inequities …

Wrongful Migration: A Hidden Culprit Behind Flank Pain, Ryan Miller, Anjeza Cipi, Emma Pierce

Department of Emergency Medicine Faculty Publications

[Introduction] A 32-year-old woman with no significant past medical history presented to the emergency department with 11 days of fever, fatigue, chills, and new-onset fullness in her left flank. She denied dysuria, abdominal pain, or vaginal bleeding. Vital signs showed fever and mild hypotension, and the physical examination revealed left-sided abdominal distension. Laboratory results demonstrated leukocytosis and a lactate of 3.2 mmol/L. She appeared nontoxic but was persistently febrile despite initial fluids and antibiotics. Computed tomography—shown in Figure 1, and ultrasound—shown in Figure 2, were obtained and revealed the diagnosis.

Optimizing Decision-Making In A Cerebral Palsy Model Using Reinforcement Learning, Richard Ampah

Pitzer Senior Theses

This study presents an original interdisciplinary investigation into how reinforcement learning (RL) can model motor and cognitive defects and potentially improve motor and cognitive functions in individuals with cerebral palsy (CP), a non-progressive neurological disorder that impairs movement and adaptability. Integrating computational neuroscience and machine learning, the research applies policy gradient methods and Markov Decision Processes (MDPs) to simulate adaptive learning in agents with and without CP-related constraints.

The central aim is to compare the cumulative rewards of optimal policies, derived from value iteration, and human-like learning policies using the REINFORCE algorithm, both with and without the Bellman baseline. The …

Sex Differences In Brain Iron Deposition And Microglial Ferritin In Alzheimer’S Disease, Syed Mushfiqur Rahman, Chunfeng Tan, Akiyoshi Kakita, Jose Felix Moruno-Manchon

Faculty, Staff and Student Publications

Objective

Iron is the most abundant metal in the human brain, and plays a crucial role in many biological processes. However, disruptions in brain iron metabolism can lead to iron buildup, which occurs with aging and is linked to several brain disorders, including Alzheimer's disease. Microglia, the brain's resident immune cells, have the highest capacity to store iron, which is stored intracellularly within ferritin complexes. Importantly, women are at a higher risk of developing Alzheimer's disease and experience faster disease progression compared to men.

Methods

We used postmortem brain samples from patients with Alzheimer's disease and small vessel disease patients …

Longitudinal Assessment Of Intravillous Arterioles In Normal Pregnancy Using Superb Microvascular Imaging, R. Horgan, E. Sinkovskaya, G. Saade, E. Kalafat, A. Heeze, A. Abuhamad

Department of Obstetrics & Gynecology Faculty Publications

Objective

To use superb microvascular imaging (SMI) to longitudinally evaluate blood flow in intravillous arterioles (IVA) in pregnancy, and to develop reference ranges for IVA pulsatility index (PI) and peak systolic velocity (PSV) from 12 to 38 weeks' gestation.

Methods

The data for this study were obtained from the National Institutes of Health-funded Human Placenta Project. Eligible for inclusion were women aged 18-35 years, with a body mass index of <  30 kg/m², without comorbidities, with a singleton pregnancy conceived spontaneously and a gestational age of ≤ 13 + 6 weeks. Exclusion criteria were maternal or neonatal complications, fetal or umbilical cord anomalies, abnormal placental implantation and delivery <  37 weeks. Each participant underwent eight ultrasound examinations during pregnancy. Using SMI technology, the total number of IVA identified was recorded in a sagittal placental section at the level of cord insertion. The PI and PSV were measured in a total of six IVA (two in the central portion of the placenta, two peripherally towards the uterine fundal portion and two peripherally towards the lower uterine segment). Umbilical artery (UA)-PI was also obtained. Multilevel regression models were used to create reference ranges for IVA-PI and IVA-PSV at 12-38 weeks' gestation.

Results

A total of 90 women fulfilled the study criteria. IVA-PI decreased throughout pregnancy from a mean ± SD of 1.04 ± 0.23 in the first trimester (at 12-13 weeks) …

Parenteral Nutritional Support In Surgical Patients: Expert Consensus Statements Regarding Intravenous Lipid Emulsions Containing Omega-3 Fatty Acids., Robert G Martindale, David C Evans, Dan Waitzberg, Malissa Warren, Manpreet S Mundi, Stanislaw Klek, Paul E Wischmeyer, Martin D Rosenthal

Surgery Articles

OBJECTIVES: The International Lipids in Parenteral Nutrition (PN) Summit was convened to offer practical guidance and expert consensus opinion regarding the use of intravenous lipid emulsions (ILEs) in various clinical settings. Herein, we briefly review aspects from this summit that are of particular importance for surgical/hospitalized patients.

METHODS: Summit participants identified and discussed new evidence, data, and analyses, that potentially influence the benefits and risks of ILEs in PN or their use in clinical practice. The summit meeting consisted of expert presentations that assessed recent clinical data and best practice, followed by periodic panel discussions to formulate consensus statements. Consensus …

Endoneurial Immune Interplay In Peripheral Nerve Repair: Insights And Implications For Future Therapeutic Interventions, Alina Sprenger-Svačina, Martin K R Svačina, Husniye G Otlu, Tong Gao, Kazim A Sheikh, Gang Zhang

Faculty, Staff and Student Publications

The mechanisms underlying axonal injury and repair in peripheral nerves, whether due to traumatic damage or autoimmune neuropathies, are complex and not yet fully understood. Recent research indicates that an orchestrated interplay between damaged neurons, Schwann cells, and especially endoneurial immune cells such as macrophages or T cells is crucial to achieve satisfactory nerve recovery. Following axonal injury, degenerating axons and reactive Schwann cells release chemoattractants and cytokines that recruit immune cells into the endoneurium. Among them, macrophages play a pivotal role by clearing axonal and myelin debris and subsequently creating a pro-regenerative microenvironment that supports axonal outgrowth. There is …

A 40-Week Phase 2b Randomized, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating The Safety And Efficacy Of Memantine In Amyotrophic Lateral Sclerosis, Salman Bhai, Todd Levine, Dan Moore, Robert Bowser, Andrew J. Heim, Maureen Walsh, Aziz Shibani, Zachary Simmons, James Grogan, Namita A. Goyal, Raghav Govindarajan, Yessar Hussain, Tania Papsdorf, Tiffany Schwasinger-Schmidt, Nick Olney, Kim Goslin, Michael Pulley, Edward J. Kasarskis, Michael Weiss, Susan W. Katz, Suzan Moser, Duaa Jabari, Omar Jawdat, Jeffrey Statland, Mazen M. Dimachkie, Richard Barohn, Neuromuscular Study Group And Western Als Consortium Memantine Als Study Group

Neurology Faculty Publications

Introduction: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with no known cure, limited treatment options with minimal benefits, and significant unmet need for disease modifying therapies.

Aims: This study investigated memantine's impact on ALS progression, with an additional focus on the effects of memantine on cognitive and behavioral changes associated with the disease.

Methods: A randomized, double-blind, placebo-controlled clinical trial was conducted from December 2018 to September 2020. ALS patients were enrolled in-person and remotely across 13 sites in the United States. Participants were randomized to memantine (20 mg twice daily) or placebo in a 2:1 ratio …

Ancestry-Dependent Immunologic And Prognostic Effects Characterize The Prostate Cancer Urinary Proteome, Annie Ha, Jaron Arbet, Zhuyu Qiu, Amanda Khoo, Brian P. Main, Meinusha Govindarajan, Matthew Waas, Stanley K. Liu, O. John Semmes, Julius O. Nyalwidhe, Paul C. Boutros, Thomas Kislinger

Leroy T. Canoles Jr. Cancer Research Center Faculty Publications

Urine is an attractive biomarker analyte for non-invasive longitudinal monitoring of health and disease, particularly for diseases of the genitourinary tract, like prostate and bladder cancer. The composition of an individual's urine reflects both genetic and lifestyle characteristics that differ across geographies and populations, like diet, hydration and other socio-economic factors. While men of African ancestry have elevated prostate cancer risk, it is unclear to what extent this influences urinary biomarkers. We therefore quantified the urinary proteomes of 329 localized prostate cancer patients: 135 self-identifying as White and 194 self-identifying as Black. We identified 110 proteins that significantly differed between …

Decoding Tattoo And Permanent Makeup Pigments: Linking Physicochemical Properties To Absorption, Distribution, Metabolism, And Elimination Profiles Using Quantitative Structure-Activity Relationship (Qsar)-Based New Approach Methodologies (Nams), Girija Bansod, Ajay Vikram Singh, Preeti Bhardwaj, Tulika Rai, Sweta Vijay Nakhale, Amruta Shelar, Rajendra Patil, Peter Laux, Andreas Luch, Christopher J. Osgood, Michael W. Stacey

Biological Sciences Faculty Publications

The safety and quality of tattoo and permanent makeup (PMU) pigments are subject to increased scrutiny due to their potential to cause adverse effects like anaphylaxis, photoallergic responses, and long-term toxicity. These undesirable reactions governed by their chemical structure possess varied physicochemical properties and absorption, distribution, metabolism, and elimination (ADME) characteristics. These properties control the pigment behavior during application, stability, and interaction with human tissue. The correlation between these physicochemical characteristics and ADME parameters of tattoo/PMU pigments remain under-explored despite the current advances in toxicology. Our study aims to address and bridge the gap by leveraging open-access QSAR computational toxicology …

Comparing Human Milk-Derived Vs Bovine-Derived Fortifiers In Formula-Fed Preterm Infants On The Incidence Of Necrotizing Enterocolitis, Maya C. Kern

Nursing | Student Research Posters

Necrotizing enterocolitis (NEC) is one of the leading causes of death in infants < 32 weeks gestation and/or < 1500g. Human breast milk lowers NEC rates through immunologic, microbial, and gut-protective mechanisms. When maternal or donor milk is unavailable, infants require formula with fortification but the safest type of fortifiers remains unclear. Bovine-derived fortifiers may increase gut inflammation; human milk-derived fortifiers may offer more protection. Limited research exists comparing these fortifiers when infants are exclusively formula fed. Determining if human milk-derived fortifiers still reduce NEC risk could influence NICU feeding guidelines and improve outcomes.

Early Changes In Inflammation-Related Proteins In The Cerebrospinal Fluid And Plasma Of Patients With Aneurysmal Subarachnoid Hemorrhage, David J. Braun, Kevin W. Hatton, Justin F. Fraser, Robert M. Flight, Hunter N. B. Moseley, Caleb S. Bailey, Josh M. Morganti, Bingqing Zhang, Ishara S. Ariyapala, Tae K. Kim, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Background

Aneurysmal subarachnoid hemorrhage (aSAH) is a relatively uncommon but high mortality form of stroke that can result in long-lasting disability. A better understanding of key neuroinflammatory changes during the early phase (< 72 h) may provide potential avenues of treatment.

Methods

In an attempt to understand these early changes, we recruited 7 aSAH patients for profiling of longitudinal plasma and cerebrospinal fluid (CSF) proteins at up to 72 h post injury. We additionally compared this to control plasma obtained previously from healthy elderly volunteers. Using the Alamar Biosciences NULISAseq platform, we obtained a comprehensive picture of early peripheral and central inflammatory changes after injury.

Results

This study …

Nicorandil Treatment Improves Survival And Spatial Learning In Aged Granulin Knockout Mice, Dana M. Niedowicz, Wang-Xia Wang, Paresh Prajapati, Yu Zhong, Shuling X. Fister, Colin B. Rogers, Pradoldej Sompol, David K. Powell, Indumati Patel, Christopher M. Norris, Kathryn E. Saatman, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Mutations in the human granulin (GRN) gene are associated with multiple diseases, including dementia disorders such as frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). We studied a Grn knockout (Grn-KO) mouse model in order to evaluate a potential therapeutic strategy for these diseases using nicorandil, a commercially available agonist for the ABCC9/Abcc9-encoded regulatory subunit of the “K⁺ATP” channel that is well-tolerated in humans. Aged (13 months) Grn-KO and wild-type (WT) mice were treated as controls or with nicorandil (15 mg/kg/day) in drinking water for 7 months, then tested for neurobehavioral …

Gait Variability As A Marker Of White Matter Integrity In Individuals With Down Syndrome, Elizabeth M. Leach, David K. Powell, Amanda C. Glueck, Elizabeth Head, Moaz W. Ibrahim, Amelia J. Anderson-Mooney, Kathryn L. Van Pelt, Jordan P. Harp, Frederick A. Schmitt, Ahmed A. Bahrani

Sanders-Brown Center on Aging Faculty Publications

Introduction: Individuals with Down syndrome (DS) face a significant risk of neurodegeneration, and gait variability may serve as a clinical biomarker of neurological health. This longitudinal parent substudy aimed to explore relationships between gait, white matter (WM) integrity, and cognitive function in DS.

Methods: The associations were investigated between magnetic resonance imaging diffusion tensor imaging (DTI), cognition, and self-paced gait data from 22 DS participants (mean age ± SD 37 ± 7.5 years).

Results: DTI measures, such as lower fractional anisotropy (FA) and higher mean diffusivity, were correlated with greater step time variability but not normalized velocities. Lower cognitive scores …

Disrupted Calcium Dynamics In Reactive Astrocytes Occur With End Feet–Arteriole Decoupling In An Amyloid Mouse Model Of Alzheimer’S Disease, Blaine Weiss, John C. Gant, Ruei-Lung Lin, Jenna L. Gollihue, Colin B. Rogers, Susan D. Kraner, Edmund B. Rucker, Yuriko Katsumata, Yang Jiang, Peter T. Nelson, Donna M. Wilcock, Pradoldej Sompol, Olivier Thibault, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

While cerebrovascular dysfunction and reactive astrocytosis are extensively characterized hallmarks of Alzheimer's disease (AD) and related dementias, the dynamic relationship between reactive astrocytes and cerebral vessels remains poorly understood. Here, we used jGCaMP8f and two-photon microscopy to investigate calcium signaling in multiple astrocyte subcompartments, concurrent with changes in cerebral arteriole activity, in fully awake 7- to 8-month-old male and female 5xFAD mice, a model for AD-like pathology, and wild-type (WT) littermates. In the absence of movement, spontaneous calcium transients in barrel cortex occurred more frequently in astrocyte somata, processes, and perivascular regions of 5xFAD mice. However, evoked arteriole dilations (in …