Geriatrics Commons^™

Dnmt3a Regulates Murine Megakaryocyte-Biased Hematopoietic Stem Cell Fate Decisions, Sarah M Waldvogel, Virginia Camacho, Dandan Fan, Anna G Guzman, Alejandra Garcia-Martell, Elmira Khabusheva, Jacey Rodriguez Pridgen, Josephine De La Fuente, Rachel Rau, Ashlyn G Laidman, Maria N Barrachina, Estelle Carminita, Justin A Courson, Michael R Williamson, Joanne I Hsu, Chun-Wei Chen, Jaime Reyes, Subhashree Pradhan, Rolando E Rumbaut, Alan R Burns, Benjamin Deneen, Jianzhong Su, Kellie R Machlus, Margaret A Goodell

Center on Aging Staff Publications

Hematopoietic stem cells (HSCs) are defined by their capacity to regenerate all main components of peripheral blood, but individual HSCs exhibit a range of preferences for generating downstream cell types. Their propensities are thought to be epigenetically encoded, but few differential regulatory mechanisms have been identified. In this work, we explored the role of DNA methyltransferase 3A (DNMT3A) in the megakaryocyte-biased HSC population, which is thought to reside at the top of the hematopoietic hierarchy. We demonstrate that heterozygous loss of DNMT3A (Dnmt3a+/-) in these megakaryocyte-biased HSCs has distinct consequences compared with the rest of the HSC pool. These megakaryocyte-biased …

The Infected Diabetic Foot: Bacteraemia And Endocarditis Complicating Moderate And Severe Foot Infections, Mario C Reyes, Arthur N Tarricone, Mathew J Sideman, Michael C Siah, Bijan Najafi, Edgar J G Peters, Lawrence A Lavery

Center on Aging Staff Publications

To identify the incidence of blood stream infections (BSIs) and endocarditis in patients with diabetic foot infections (DFIs), risk factors and clinical outcomes. A post hoc analysis of 280 patients using pooled patient level data from three RTCs. Blood cultures were drawn at time of admission for DFI. Deep intraoperative cultures were obtained from infected foot wounds. Data from the 12-month follow-up were used to determine clinical outcomes. 77.1% (N = 216) had blood cultures of which 15.7% (n = 34) had BSI. One patient (3.3%) had endocarditis. Risk factors for BSI included Charcot Neuroarthropathy history (20.6% vs. 7.1%, p …

Clonal Dynamics And Somatic Evolution Of Haematopoiesis In Mouse, Chiraag D Kapadia, Nicholas Williams, Kevin J Dawson, Caroline Watson, Matthew J Yousefzadeh, Duy Le, Kudzai Nyamondo, Sreeya Kodavali, Alex Cagan, Sarah Waldvogel, Xiaoyan Zhang, Josephine De La Fuente, Daniel Leongamornlert, Emily Mitchell, Marcus A Florez, Krzysztof Sosnowski, Rogelio Aguilar, Alejandra Martell, Anna Guzman, David Harrison, Laura J Niedernhofer, Katherine Y King, Peter J Campbell, Jamie Blundell, Margaret A Goodell, Jyoti Nangalia

Center on Aging Staff Publications

Haematopoietic stem cells maintain blood production throughout life1. Although extensively characterized using the laboratory mouse, little is known about clonal selection and population dynamics of the haematopoietic stem cell pool during murine ageing. We isolated stem cells and progenitors from young and old mice, identifying 221,890 somatic mutations genome-wide in 1,845 single-cell-derived colonies. Mouse stem cells and progenitors accrue approximately 45 somatic mutations per year, a rate only approximately threefold greater than human progenitors despite the vastly different organismal sizes and lifespans. Phylogenetic patterns show that stem and multipotent progenitor cell pools are established during embryogenesis, after which …

The Dialysis Foot- The Impact Of Presenting Estimated Glomerular Filtration Rate On Clinical Outcomes In Patients Hospitalized With Diabetic Foot Infections, Arthur Tarricone, Tyler L Coye, Allen Gee, Bijan Najafi, Michael C Siah, Lawrence A Lavery

Center on Aging Staff Publications

To evaluate the association between presenting estimated glomerular filtration rate (eGFR) and clinical outcomes in patients hospitalized with diabetic foot infections. This retrospective cohort study included 344 patients with moderate to severe diabetic foot infections. Patients were categorized into three groups based on presenting estimated eGFR: eGFR ≥60 (eGFR >60 mL/min), eGFR 30-60 (eGFR 30-60 mL/min) and eGFR < 30 (eGFR < 30 mL/min). Outcomes assessed included wound healing, time to heal, re-infection, amputation, mortality and re-hospitalization for infection. Compared with patients with eGFR < 30, patients with eGFR ≥60 had significantly lower rates of retinopathy, peripheral arterial disease and use of beta blockers or calcium channel blockers. Glycated haemoglobin levels were inversely related to eGFR, decreasing as eGFR severity increased. Haemoglobin levels were significantly lower, and inflammatory markers (ESR and CRP) were significantly higher in patients with eGFR < 30. There were no significant differences among eGFR groups in rates of wound healing, time to heal, re-infection or amputation. However, mortality increased with decreasing eGFR (1.9% in eGFR ≥60 vs. 3.2% in eGFR 30-60 vs. 8.1% in eGFR < 30; p = 0.04). Similarly, re-hospitalization for infection at a different site also increased with decreasing eGFR (20.5% in eGFR ≥60 vs. 28.1% in eGFR 30-60 vs. 48.4% in eGFR < 30; p <  0.01). In diabetic foot infections, presenting eGFR severity did not affect rates of wound healing, time to heal, re-infection or amputation. However, decreasing eGFR was associated with increased mortality and re-hospitalization for infection at a different site. In this study, presenting eGFR was not a predictive value for wound healing or time until healing, however was associated with rehospitalization and overall mortality this diabetic foot population.

Optimizing The Well-Being Of Residents Diagnosed With Dementia: An Activities Calendar And Guide For Cognitive And Physical Engagement, Kaylex L. Monteagudo Parra

Undergraduate Theses

This thesis explores the critical role of structured activities in enhancing the cognitive, emotional, and physical well-being of individuals with dementia. Drawing on evidence-based research and practical experience as an Activities Assistant, it emphasizes how engaging, person-centered activities can mitigate symptoms, improve quality of life, and promote social interaction across the stages of disease progression. The research culminates in the development of an ideal activities calendar tailored to patients with dementia, accompanied by a comprehensive guide detailing activity benefits, implementation strategies, and required resources. This framework addresses the unique challenges of dementia care, offering practical tools for caregivers to adapt …

Inhibition Of Soluble Epoxide Hydrolase Confers Neuroprotection And Restores Microglial Homeostasis In A Tauopathy Mouse Model, Shuo Wang, Chuangye Qi, Chetan Rajpurohit, Baijayanti Ghosh, Wen Xiong, Baiping Wang, Yanyan Qi, Sung Hee Hwang, Bruce D Hammock, Hongjie Li, Li Gan, Hui Zheng

Center on Aging Staff Publications

Background: The epoxyeicosatrienoic acids (EETs) are derivatives of the arachidonic acid metabolism with anti-inflammatory activities. However, their efficacy is limited due to the rapid hydrolysis by soluble epoxide hydrolase (sEH). Inhibition of sEH has been shown to stabilize the EETs and reduce neuroinflammation in Aβ mouse models of Alzheimer's disease (AD). However, the role of the sEH-EET signaling pathway in other CNS cell types and neurodegenerative conditions are less understood.

Methods: Here we investigated the mechanisms and functional role of the sEH-EET axis in tauopathy by treating PS19 mice with a small molecule sEH inhibitor TPPU and by crossing the …

The Havcr1-Centric Host Factor Network Drives Zika Virus Vertical Transmission, Wenzhe Yu, Jun Tao, Hongmin Cao, Wanshan Zheng, Beiang Zhang, Yue Zhang, Peiqun Xu, Yiwei Zhang, Xuan Liu, Yinan Wang, Han Cai, Gang Liu, Fan Liu, Haibin Wang, Haiyan Zhao, Indira U Mysorekar, Xiaoqian Hu, Bin Cao

Center on Aging Staff Publications

Zika virus (ZIKV) vertical transmission results in devastating congenital malformations and pregnancy complications; however, the specific receptor and host factors facilitating ZIKV maternal-fetal transmission remain elusive. Here, we employ a genome-wide CRISPR screening and identify multiple placenta-intrinsic factors modulating ZIKV infection. Our study unveils that hepatitis A virus cellular receptor 1 (HAVCR1) serves as a primary receptor governing ZIKV entry in placental trophoblasts. The GATA3-HAVCR1 axis regulates heterogeneous cell tropism in the placenta. Notably, placenta-specific Havcr1 deletion in mice significantly impairs ZIKV transplacental transmission and associated adverse pregnancy outcomes. Mechanistically, the immunoglobulin variable-like domain of HAVCR1 binds to ZIKV via …

Incident Hearing Loss And Subsequent Risk Of Dementia: The Health And Retirement Study 2010-2018, Jingkai Wei, Youngran Kim, Yike Li, Donglan Zhang, Casey Crump

Faculty, Staff and Student Publications

Background and Objectives

Research Design and Methods

Histone H3 Cysteine 110 Enhances Iron Metabolism And Modulates Replicative Life Span In Saccharomyces Cerevisiae, Chen Cheng, Brenna S Mccauley, Nedas Matulionis, Maria Vogelauer, Dimitrios Camacho, Heather R Christofk, Weiwei Dang, Nicholas A T Irwin, Siavash K Kurdistani

Center on Aging Staff Publications

The discovery of histone H3 copper reductase activity provides a novel metabolic framework for understanding the functions of core histone residues, which, unlike N-terminal residues, have remained largely unexplored. We previously demonstrated that histone H3 cysteine 110 (H3C110) contributes to cupric (Cu2+) ion binding and its reduction to the cuprous (Cu1+) form. However, this residue is absent in Saccharomyces cerevisiae, raising questions about its evolutionary and functional significance. Here, we report that H3C110 has been lost in many fungal lineages despite near-universal conservation across eukaryotes. Introduction of H3C110 into S. cerevisiae increased intracellular Cu1+ levels and ameliorated the iron …

Aging-Related Hearing Decline And Resting State Networks, Cassidy S. T. Ellsworth

College of Education and Human Sciences: Dissertations, Theses, and Student Research

This study investigated the effects of age-related hearing decline on functional networks using resting-state functional magnetic resonance imaging (rs-fMRI). The main objective of the present study was to examine resting-state functional connectivity (rsFC) and graph theory-based network efficiency metrics in forty-nine adults categorized by age and hearing thresholds to identify the neural mechanisms of age-related hearing decline. RsFC within key brain networks and auditory-related brain regions, including the default mode network, salience network, dorsal attention network, and primary auditory cortices, was assessed using region-of-interest (ROI)-based and graph theory approaches. Functional metrics, such as rsFC strength and global and local efficiency, …

Quantitative Profiling Ph Heterogeneity Of Acidic Endolysosomal Compartments Using Fluorescence Lifetime Imaging Microscopy, Dinghuan Deng, Youchen Guan, Ayse Sena Mutlu, Baiping Wang, Shihong Max Gao, Hui Zheng, Meng C Wang

Center on Aging Staff Publications

The endolysosomal system plays a crucial role in maintaining cellular homeostasis and promoting organism fitness. The pH of its acidic compartments is a crucial parameter for proper function, and it is dynamically influenced by both intracellular and environmental factors. Here, we present a method based on fluorescence lifetime imaging microscopy (FLIM) for quantitatively analyzing the pH profiles of acidic endolysosomal compartments in diverse types of primary mammalian cells and in live organism Caenorhabditis elegans. This FLIM-based method exhibits high sensitivity in resolving subtle pH differences, thereby revealing heterogeneity within a cell and across cell types. This method enables rapid …

Robotic First Rib Resection With Adjuvant Endovascular Therapy For Chronic Paget-Schroetter Syndrome, Alejandro Zulbaran-Rojas, Miguel Montero-Baker, Nihanth Palivela, Catherine Park, Bijan Najafi, Jayer Chung, Joseph L Mills, Bryan M Burt

Center on Aging Staff Publications

Background: Patients with acute Paget-Schroetter syndrome (PSS) are treated with endovascular therapy and first rib resection (FRR); however the care of patients with chronic PSS is less well understood. This report describes an emerging approach of robotic-FRR, with adjuvant endovascular therapy, for chronic PSS.

Methods: A single-center, retrospective analysis was conducted of patients undergoing robotic-FRR for chronic PSS between 2017 and 2020. Chronic PSS was defined by subclavian vein (SCV) fibrosis identified on duplex ultrasound examination. Patency and clinical outcomes were compared before and after robotic-FRR.

Results: Fifteen robotic-FRRs in 14 patients with chronic PSS were analyzed. Median time between …

Associations Between Deficit Accumulation Frailty And Baseline Markers Of Lifestyle In The Us Pointer Trial, Mark A Espeland, Yitbarek N Demesie, Kayloni Olson, Samuel N Lockhart, Sarah E Tomaszewski Farias, Maryjo L Cleveland, Christy C Tangney, Lucia Crivelli, Heather M Snyder, Michele K York, Laura D Baker, Rachel A Whitmer, Rena R Wing, Katelyn R Garcia, Kathryn E Callahan

Faculty, Staff and Students Publications

BACKGROUND: Multidomain lifestyle interventions may have the potential to slow biological aging as captured by deficit accumulation frailty indices. We describe the distribution and composition of the 49-component frailty index developed by the U.S. POINTER clinical trial team of investigators and assess its cross-sectional associations with sociodemographic factors and markers chosen to be representative of behaviors targeted by the trial's multidomain interventions.

METHODS: We draw baseline data from the 2 111 volunteers enrolled in U.S. POINTER who were ages 60-79 years and at increased risk for cognitive decline. Frailty components were grouped into 9 domains. Associations that frailty index scores …

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 …

Flyphonedb2: A Computational Framework For Analyzing Cell-Cell Communication In Drosophila Scrna-Seq Data Integrating Alphafold-Multimer Predictions, Mujeeb Qadiri, Ying Liu, Ah-Ram Kim, Myeonghoon Han, Eric Zhou, Austin Veal, Tzu-Chiao Lu, Hongjie Li, Yanhui Hu, Norbert Perrimon

Center on Aging Staff Publications

Cell-cell communication (CCC) plays a critical role in the physiological regulation of organisms and has been implicated in numerous diseases. Previously, we introduced FlyPhoneDB, a tool designed to explore CCC in Drosophila single-cell RNA-sequencing datasets. The core algorithm of FlyPhoneDB infers tissue-specific signaling events between cell types by calculating cell-cell interaction scores based on curated ligand-receptor (L-R) expression across major signaling pathways. However, the utility of FlyPhoneDB was limited by the relatively small number of available L-R pairs.

Here, we present FlyPhoneDB2, a major upgrade featuring a significantly expanded knowledgebase that includes a greater number of L-R pairs, incorporating annotations …

The Infected Diabetic Foot: Risk Factors For Re-Infection After Treatment For Diabetic Foot Osteomyelitis, Lawrence A Lavery, Mario C Reyes, Bijan Najafi, Tyler L Coye, Matthew Sideman, Michael C Siah, Arthur N Tarricone

Center on Aging Staff Publications

Our objective was to evaluate risk factors for re-infection in patients after treatment for diabetic foot osteomyelitis (OM). We used pooled patient level data from two RTCs that evaluated patients with diabetic foot infections. We evaluated 171 patients with OM. OM was confirmed with bone culture or histopathology. Data from the 12-month follow-up were used to determine clinical outcomes. Re-infection occurred in 47 (27.5%) patients. Risk factors for re-infection were Toe Brachial Index < 0.40 (25.7% vs. 9.8%, p = 0.02), skin perfusion pressure < 40 mmHg (6.3% vs. 5.9%, p = 0.04), wound healing (55.3% vs. 75.0%, p = 0.01), time to heal (156.0, 69.5-365 vs. 91.5, 38.8-365, p = 0.001), and history of MI (14.9% vs. 3.2%, p = 0.005). During 12-month follow-up, patients with re-infections were 198.8 times more likely to require a foot related hospitalisation (81.8% vs. 0.0%, p = 0.001), 10.4 times more likely have an all-cause hospitalisation (70.2% vs. 18.5%, p = 0.001) and 9.4 times more likely to need an amputation (36.2% vs. 5.6%, p = 0.001). Patients with re-infection had a significantly longer median length of hospitalisation (20.0, 13.5-34.5 vs. 14.0, 10.0-22.0, p = 0.003) and median length of antibiotic duration (55.0, 35.0-87.0 vs. 46.0, 22.8-68.0, p = 0.03). Patients with re-infection are less likely to heal and have more foot-related hospitalizations and amputations.

Toward Precision Longevity: Aging Interventions In The Single-Cell Atlas Era, Jason B Chen, Miranda C Wang, Shangyu Gong, Hongjie Li

Faculty, Staff and Students Publications

With growing global interest in extending not only lifespan but also healthspan, healthy aging has emerged as a central goal in biomedical research. This review provides an overview of current longevity interventions, including genetic manipulations, dietary restriction, exercise, pharmacological treatments, targeting senescence and cellular reprogramming strategies, as studied in key model organisms such as Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus. We examine the limitations and challenges associated with these approaches, particularly their variability across tissues and cell types. Furthermore, we emphasize the critical role of single-cell aging atlas technologies in uncovering cell-type–specific aging patterns and molecular …

The Infected Diabetic Foot: Incidence And Risk Factors For Dehiscence After Surgery For Diabetic Foot Infections, Lawrence A Lavery, Mario C Reyes, Bijan Najafi, Tyler L Coye, Jayer Chung, Michael C Siah, Arthur N Tarricone

Center on Aging Staff Publications

Our objective was to assess the incidence, risk factors and clinical outcomes of dehiscence after foot surgery in diabetic patients. We used pooled patient‐level data from two randomised clinical trials with 240 diabetic patients who required foot surgery for infections. Most patients (n = 180, 75.0%) had surgical wound closure. We defined dehisced surgical wounds (DSW) when the surgical site was not completely epithelialized with no drainage after sutures/staples were removed with a 2‐week validation of healing. We evaluated the time to heal, re‐infection, re‐ulceration, hospital admissions and amputations. Moderate and severe infection was based on criteria of the …

Il-12 Encoding Ondv Synergizes With Car-T Cells In Orthotopic Models Of Non-Small Cell Lung Cancer, Amanda Rosewell Shaw, Daisuke Morita, Caroline E Porter, Eric Tu, Greyson W Biegert, Sonia Agrawal, Nicholas Durham, Malcolm K Brenner, Masataka Suzuki

Faculty, Staff and Students Publications

Systemic administration of oncolytic viruses (OVs) is a promising approach for targeting metastatic solid tumors, but their anti-tumor activity is limited by pre-existing neutralizing antibodies against common human viruses. Therefore, investigators have developed OVs derived from non-human host viruses. Successful implementation of this strategy requires that the viral vector selectively infects and replicates within human cancer cells. Newcastle disease virus (NDV) is an avian paramyxovirus that, as NDV-based OVs (oNDVs), has demonstrated safety and activity against multiple human tumors in clinical trials. Their use as a single agent, however, is insufficient to cure tumors. Similarly, chimeric antigen receptor-modified T cells …

Blood Biomarkers In Down Syndrome: Facilitating Alzheimer's Disease Detection And Monitoring, Melissa Petersen, Lisi Flores-Aguilar, Elizabeth Head, Laia Montoliu-Gaya, Andre Strydom, Sarah Pape, Juan Fortea, Nicholas Ashton, Chinedu Momoh, Sid O'Bryant

Brain and Mind Institute

Blood-based biomarkers continue to be explored for disease detection, monitoring of progression, and therapeutic outcomes as the diagnostic determination of Alzheimer's Disease in Down Syndrome (DS-AD) remains challenging in clinical settings. This perspective highlights the current status of this effort. Overall, amyloid (A), tau (T), and neurodegeneration (AT[N]) blood-based biomarkers have been shown to increase with disease pathology for individuals with DS. Phosphorylated tau biomarkers (p-tau217, p-tau181) have been consistently shown to track disease progression for DS-AD and are likely good candidates for use in clinical settings. Biomarkers of inflammation (glial fibrillary acidic protein) also show promise; however, additional work …

Efficacy And Feasibility Of Intradialytic Plantar Electrical Stimulation In Patients With Diabetes: A Randomized Double-Blind Controlled Trial, Myeounggon Lee, Abdullah Hamad, Mehrnaz Azarian, Jaewon Beom, Abderrahman Ouattas, Mohammad Dehghan Rouzi, Naima Rodriguez, Nhi Quach, Rania Ibrahim, Mincy Mathew, Talal Talal, Fadwa Al-Ali, Bijan Najafi

Center on Aging Staff Publications

Objective: This study investigates the efficacy and feasibility of electrical stimulation (E-Stim) on sensory fibers of the plantar region during hemodialysis sessions, aiming to improve mobility in patients with diabetes by providing a connection between E-Stim and enhanced mobility with minimal patient effort required.

Research design and methods: Participants aged ≥18 years with diabetes undergoing hemodialysis and able to walk at least 10 m with or without aid were recruited and divided into an intervention group receiving 1-h intradialytic E-Stim three times a week and a control group using an identical nonfunctional device for 12 weeks. Gait, physical activity, patient-reported …

The Infected Diabetic Foot: Does Negative Pressure Wound Therapy With Irrigation Reduce Bioburden And Improve Wound Healing?, Mehmet A Suludere, Matthew Malone, Michael C Siah, Arthur Tarricone, Tyler L Coye, Bijan Najafi, Lawrence A Lavery

Center on Aging Staff Publications

The aim of this study was to compare the microbial loads of patients with diabetic foot infections treated with negative pressure wound therapy (NPWT) with and without irrigation with polyhexamethylene biguanide (NPWTi-P). This is a post hoc analysis of combined data of two randomized clinical trials. We evaluated people with diabetes treated with moderate and severe diabetic foot infections that required surgery. Tissue specimens were obtained after the initial surgery and following a second planned return to the operating room after 48-72 h of NPWT or NPWTi-P, prior to the second surgery. We used quantitative polymerase chain reaction (qPCR) to …

Using Patient-Reported Experiences To Inform The Use Of Foam Dressings For Hard-To-Heal Wounds: Perspectives From A Wound Care Expert Panel, Kevin Woo, Nick Santamaria, Dimitri Beeckman, Paulo Alves, Breda Cullen, Amit Gefen, José Luis Lázaro-Martínez, Hadar Lev-Tov, Bijan Najafi, Andrew Sharpe, Terry Swanson

Center on Aging Staff Publications

Caring for patients with hard-to-heal (chronic) wounds requires a multifaceted approach that addresses their diverse needs, which can contribute to the complexity of care. Wound care providers must have a comprehensive understanding of the patient's comorbid conditions and psychosocial issues to provide personalised and effective treatment. Key quality indicators for effective wound care involves not only selecting appropriate local wound care products, such as foam dressings, but also addressing individual patient experiences of wound-related pain, odour, itch, excessive wound drainage, and self-care needs. The purpose of this review is to inculcate the wound care practice community, research scientists and healthcare …

Quantitative Biomechanical Analysis In Validating A Video-Based Model To Remotely Assess Physical Frailty: A Potential Solution To Telehealth And Globalized Remote-Patient Monitoring, Mohammad Dehghan Rouzi, Myeounggon Lee, Jaewon Beom, Sanam Bidadi, Abderrahman Ouattas, Gozde Cay, Anmol Momin, Michele K York, Mark E Kunik, Bijan Najafi

Center on Aging Staff Publications

Assessing physical frailty (PF) is vital for early risk detection, tailored interventions, preventive care, and efficient healthcare planning. However, traditional PF assessments are often impractical, requiring clinic visits and significant resources. We introduce a video-based frailty meter (vFM) that utilizes machine learning (ML) to assess PF indicators from a 20 s exercise, facilitating remote and efficient healthcare planning. This study validates the vFM against a sensor-based frailty meter (sFM) through elbow flexion and extension exercises recorded via webcam and video conferencing app. We developed the vFM using Google's MediaPipe ML model to track elbow motion during a 20 s elbow …

Human Embryonic Genetic Mosaicism And Its Effects On Development And Disease, Sarah M Waldvogel, Jennifer E Posey, Margaret A Goodell

Center on Aging Staff Publications

Nearly every mammalian cell division is accompanied by a mutational event that becomes fixed in a daughter cell. When carried forward to additional cell progeny, a clone of variant cells can emerge. As a result, mammals are complex mosaics of clones that are genetically distinct from one another. Recent high-throughput sequencing studies have revealed that mosaicism is common, clone sizes often increase with age and specific variants can affect tissue function and disease development. Variants that are acquired during early embryogenesis are shared by multiple cell types and can affect numerous tissues. Within tissues, variant clones compete, which can result …

Pkmyt1 Is A Marker Of Treatment Response And A Therapeutic Target For Cdk4/6 Inhibitor-Resistance In Er+ Breast Cancer, Anran Chen, Beom-Jun Kim, Aparna Mitra, Craig T Vollert, Jonathan T Lei, Diana Fandino, Meenakshi Anurag, Matthew V Holt, Xuxu Gou, Jacob B Pilcher, Matthew P Goetz, Donald W Northfelt, Susan G Hilsenbeck, C Gary Marshall, Marc L Hyer, Robert Papp, Shou-Yun Yin, Carmine De Angelis, Rachel Schiff, Suzanne A W Fuqua, Cynthia X Ma, Charles E Foulds, Matthew J Ellis

Faculty, Staff and Students Publications

Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients with 22 ER+ breast cancer demonstrated that protein kinase, membrane-associated tyrosine/threonine one (PKMYT1), a WEE1 homolog, is estradiol (E2) regulated in E2-dependent PDXs and constitutively expressed when growth is E2-independent. In clinical samples, high PKMYT1 mRNA levels associated with resistance to both ET and CDK4/6 inhibition. The PKMYT1 inhibitor lunresertib (RP-6306) with gemcitabine selectively and synergistically reduced the viability of ET and palbociclib-resistant ER+ breast …

Mesenchymal Stromal Cells Protect Combined Oncolytic And Helper-Dependent Adenoviruses From Humoral Immunity, Ada Irmak Özcan, Arianexys Aquino Lόpez, Alexandra N Wolff, Audrey Ma, Amanda Rosewell Shaw, Masataka Suzuki, Malcolm K Brenner, Mary K Mckenna

Faculty, Staff and Students Publications

Systemic delivery of oncolytic and immunomodulatory adenoviruses may be required for optimal effects on human malignancies. Mesenchymal stromal cells (MSCs) can serve as delivery systems for cancer therapeutics due to their ability to transport and shield these agents while homing to tumors. We now use MSCs to deliver a clinically validated binary oncolytic and helper-dependent adenovirus combination (CAdVEC) to tumor cells. We show successful oncolysis and helper-dependent virus function in tumor cells even in the presence of plasma from adenovirus-seropositive donors. In both two- and three-dimensional cultures, CAdVEC function is eliminated even at high dilutions of seropositive plasma but is …