Geriatrics Commons^™

Advances In Immunocompetent Mouse And Rat Models, Wen Bu, Yi Li

Center on Aging Staff Publications

Rodent models of breast cancer have played critical roles in our understanding of breast cancer development and progression as well as preclinical testing of cancer prevention and therapeutics. In this article, we first review the values and challenges of conventional genetically engineered mouse (GEM) models and newer iterations of these models, especially those with inducible or conditional regulation of oncogenes and tumor suppressors. Then, we discuss nongermline (somatic) GEM models of breast cancer with temporospatial control, made possible by intraductal injection of viral vectors to deliver oncogenes or to manipulate the genome of mammary epithelial cells. Next, we introduce the …

The Application Of Digital Frailty Screening To Triage Nonhealing And Complex Wounds, Ram Kinker Mishra, Rasha O Bara, Alejandro Zulbaran-Rojas, Catherine Park, Malindu E Fernando, Jeffrey Ross, Brian Lepow, Bijan Najafi

Center on Aging Staff Publications

Objective: We investigated the association between the complexity of diabetic foot ulcers (DFUs) and frailty.

Research design and methods: Individuals (n = 38) with Grade 2 Wagner DFU were classified into 3 groups based on the Society for Vascular Surgery risk-stratification for major limb amputation as Stage 1 at very low risk (n = 19), Stage 2 at low risk (n = 9), and Stage 3 to 4 at moderate-to-high risk (n = 10) of major limb amputation. Frailty status was objectively assessed using a validated digital frailty meter (FM). The FM works by quantifying weakness, slowness, rigidity, and exhaustion …

Txnrd1 Drives The Innate Immune Response In Senescent Cells With Implications For Age-Associated Inflammation, Xue Hao, Bo Zhao, Martina Towers, Liping Liao, Edgar Luzete Monteiro, Xin Xu, Christina Freeman, Hongzhuang Peng, Hsin-Yao Tang, Aaron Havas, Andrew V Kossenkov, Shelley L Berger, Peter D Adams, David W Speicher, David Schultz, Ronen Marmorstein, Kenneth S Zaret, Rugang Zhang

Faculty, Staff and Student Publications

Sterile inflammation, also known as 'inflammaging', is a hallmark of tissue aging. Cellular senescence contributes to tissue aging, in part, through the secretion of proinflammatory factors collectively known as the senescence-associated secretory phenotype (SASP). The genetic variability of thioredoxin reductase 1 (TXNRD1) is associated with aging and age-associated phenotypes such as late-life survival, activity of daily living and physical performance in old age. TXNRD1's role in regulating tissue aging has been attributed to its enzymatic role in cellular redox regulation. Here, we show that TXNRD1 drives the SASP and inflammaging through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) …

Risk Factors For Post-Discharge Adverse Outcomes Following Hospitalization Among Older Adults Diagnosed With Elder Mistreatment, Monique R Pappadis, Leila Wood, Allen Haas, Jordan Westra, Yong-Fang Kuo, Charles P Mouton

Faculty, Staff and Student Publications

Using 100% Medicare data files, this study explored whether primary elder mistreatment (EM) diagnosis, EM type, and facility type were associated with 3-year mortality and 1-year unplanned hospital readmission among older patients diagnosed with EM with hospital discharge from 10/01/2015 through 12/31/2018 (n = 11,023). We also examined outcome differences between older patients diagnosed with EM and matched non-EM patient controls. Neglect by others was the most common EM diagnosis. Three-year mortality was 56.7% and one-year readmission rate was 53.8%. Compared to matched non-EM patient controls, older EM patients were at an increased risk of mortality and readmission. Among …

Harnessing Physical Activity Monitoring And Digital Biomarkers Of Frailty From Pendant Based Wearables To Predict Chemotherapy Resilience In Veterans With Cancer, Gozde Cay, Yvonne H Sada, Mohammad Dehghan Rouzi, Md Moin Uddin Atique, Naima Rodriguez, Mehrnaz Azarian, M G Finco, Sarvari Yellapragada, Bijan Najafi

Center on Aging Staff Publications

This study evaluated the use of pendant-based wearables for monitoring digital biomarkers of frailty in predicting chemotherapy resilience among 27 veteran cancer patients (average age: 64.6 ± 13.4 years), undergoing bi-weekly chemotherapy. Immediately following their first day of chemotherapy cycle, participants wore a water-resistant pendant sensor for 14 days. This device tracked frailty markers like cadence (slowness), daily steps (inactivity), postural transitions (weakness), and metrics such as longest walk duration and energy expenditure (exhaustion). Participants were divided into resilient and non-resilient groups based on adverse events within 6 months post-chemotherapy, including dose reduction, treatment discontinuation, unplanned hospitalization, or death. A …

The Role Of Lncrna-Mediated Pyroptosis In Cardiovascular Diseases, Aman Shrestha, Saruna Ghimire, Jennifer Kinney, Ranju Mehta, Sabuj Kanti Mistry, Shoko Saito, Binod Rayamajhee, Deepak Sharma, Suresh Mehta, Uday Narayan Yadav

Faculty, Staff and Student Publications

BACKGROUND: Nepal's low fertility rate and increasing life expectancy have resulted in a burgeoning older population. For millennia, filial piety shaped family cohesion and helped Nepali older adults achieve positive outcomes, but recently, it has been eroding. Furthermore, there are not enough institutional support options or alternatives to family-based care to deal with the biosocial needs of older adults. This study explored the association between family support and self-rated health among Nepali older adults.

METHODS: A community-based cross-sectional survey in eastern Nepal's two districts, Sunsari and Morang, interviewed 847 older adults (≥ 60 years). The final analytical sample was 844. …

G-Quadruplex Dna And Rna In Cellular Senescence, Rocio Diaz Escarcega, Paul Marshall, Andrey S Tsvetkov

Faculty, Staff and Student Publications

Normal cells divide, are damaged, and are repaired across their lifetime. As cells age, they enter cellular senescence, characterized by a permanent state of cell-cycle arrest triggered by various stressors. The molecular mechanisms that regulate senescent phenotypes have been actively investigated over the last several decades; however, one area that has been neglected is how G-quadruplex (G4) DNA and RNA (G4-DNA and G4-RNA) mediate senescence. These non-canonical four-stranded DNA and RNA structures regulate most normative DNA and RNA-dependent processes, such as transcription, replication, and translation, as well as pathogenic mechanisms, including genomic instability and abnormal stress granule function. This review …

Perceptions Of Acute Care Telemedicine Among Caregivers For Persons Living With Dementia: A Qualitative Study, Anita Chary, Norvin Hernandez, Ana Paulina Rivera, Vivian Ramont, Tracey Obi, Ilianna Santangelo, Christine Ritchie, Hardeep Singh, Emily Hayden, Aanand D Naik, Shan Liu, Maura Kennedy

Faculty, Staff and Student Publications

Persons living with dementia (PLWD) have high emergency department (ED) utilization. Little is known about using telemedicine with PLWD and caregivers as an alternative to ED visits for minor acute health problems. This qualitative interview-based study elicited caregivers' perspectives about the acceptability of telemedicine for acute complaints. We performed telephone interviews with 28 caregivers of PLWD from two academic EDs, one in the Northeast and another in the South. Using a combined deductive-inductive approach, we coded interview transcripts and elucidated common themes by consensus. All caregivers reported they would need to participate in the telemedicine visit to help overcome communication …

Association Of Risk Factors And Comorbidities With Chronic Pain In The Elderly Population, Neil Mookerjee, Nicole Schmalbach, Gianna Antinori, Subhadra Thampi, Dylan Windle-Puente, Amy Gilligan, Ha Huy, Megha Andrews, Angela Sun, Roshni Gandhi, William Benedict, Austin Chang, Ben Sanders, Justin Nguyen, Maanika Reddy Keesara, Janet Aliev, Aneri Patel, Isaiah Hughes, Ian Millstein, Krystal Hunter, Satyajeet Roy

Faculty, Staff and Student Publications

INTRODUCTION/OBJECTIVE: Chronic pain disorders affect about 20% of adults in the United States, and it disproportionately affects individuals living in the neighborhoods of extreme socioeconomic disadvantage. In many instances, chronic pain has been noted to arise from an aggregation of multiple risk factors and events. Therefore, it is of importance to recognize the modifiable risk factors. The aim of this study was to investigate the comorbid medical conditions and risk factors associated with chronic pain disorders in patients aged 65 years and older.

METHODS: Our team retrospectively reviewed medical records of elderly patients (65 years and older) who were evaluated …

Geriatric Trauma Triage: Optimizing Systems For Older Adults-A Publication Of The American Association For The Surgery Of Trauma Geriatric Trauma Committee, Tanya Egodage, Vanessa P Ho, Tasce Bongiovanni, Jennifer Knight-Davis, Sasha D Adams, Jody Digiacomo, Elisabeth Swezey, Joseph Posluszny, Nasim Ahmed, Kartik Prabhakaran, Asanthi Ratnasekera, Adin Tyler Putnam, Milad Behbahaninia, Melissa Hornor, Caitlin Cohan, Bellal Joseph

Faculty, Staff and Student Publications

BACKGROUND: Geriatric trauma patients are an increasing population of the United States (US), sustaining a high incidence of falls, and suffer greater morbidity and mortality to their younger counterparts. Significant variation and challenges exist to optimize outcomes for this cohort, while being mindful of available resources. This manuscript provides concise summary of locoregional and national practices, including relevant updates in the triage of geriatric trauma in an effort to synthesize the results and provide guidance for further investigation.

METHODS: We conducted a review of geriatric triage in the United States (US) at multiple stages in the care of the older …

Optimizing Delirium Care In The Era Of Age-Friendly Health System, Min Ji Kwak, Sharon K Inouye, Donna M Fick, Alice Bonner, Terry Fulmer, Emily Carter, Victor Tabbush, Kerri Maya, Nicholas Reed, Christine Waszynski, Esther S Oh

Faculty, Staff and Student Publications

Delirium is a significant geriatric condition associated with adverse clinical and economic outcomes. The cause of delirium is usually multifactorial, and person-centered multicomponent approaches for proper delirium management are required. In 2017, the John A. Hartford Foundation and the Institute for Healthcare Improvement (IHI) launched a national initiative, Age-Friendly Health System (AFHS), promoting the use of a framework called 4Ms (what matters, medication, mentation, and mobility). The 4Ms framework's primary goal is to provide comprehensive and practical person-centered care for older adults and it aligns with the core concepts of optimal delirium management. In this special article, we demonstrate how …

In Sickness And In Health-Type I Interferon And The Brain, Wei Cao

Faculty, Staff and Student Publications

Type I interferons (IFN-I) represent a group of pleiotropic cytokines renowned for their antiviral activity and immune regulatory functions. A multitude of studies have unveiled a critical role of IFN-I in the brain, influencing various neurological processes and diseases. In this mini-review, I highlight recent findings on IFN-I's effects on brain aging, Alzheimer's disease (AD) progression, and central nervous system (CNS) homeostasis. The multifaceted influence of IFN-I on brain health and disease sheds light on the complex interplay between immune responses and neurological processes. Of particular interest is the cGAS-STING-IFN-I axis, which extensively participates in brain aging and various forms …

Harnessing Speech-Derived Digital Biomarkers To Detect And Quantify Cognitive Decline Severity In Older Adults, Gozde Cay, Valeria A Pfeifer, Myeounggon Lee, Mohammad Dehghan Rouzi, Adonay S Nunes, Nesreen El-Refaei, Anmol Salim Momin, Md Moin Uddin Atique, Matthias R Mehl, Ashkan Vaziri, Bijan Najafi

Center on Aging Staff Publications

Introduction: Current cognitive assessments suffer from floor/ceiling and practice effects, poor psychometric performance in mild cases, and repeated assessment effects. This study explores the use of digital speech analysis as an alternative tool for determining cognitive impairment. The study specifically focuses on identifying the digital speech biomarkers associated with cognitive impairment and its severity.

Methods: We recruited older adults with varying cognitive health. Their speech data, recorded via a wearable microphone during the reading aloud of a standard passage, were processed to derive digital biomarkers such as timing, pitch, and loudness. Cohen's d effect size highlighted group differences, and correlations …

Assessing The Acceptability And Effectiveness Of A Novel Therapeutic Footwear In Reducing Foot Pain And Improving Function Among Older Adults: A Crossover Randomized Controlled Trial, M G Finco, Abderrahman Ouattas, Nesreen El-Refaei, Anmol Salim Momin, Mehrnaz Azarian, Bijan Najafi

Center on Aging Staff Publications

Introduction: Nearly, a quarter of older adults suffer from frequent foot pain, impacting their quality of life. While proper footwear can alleviate this, design issues often hinder regular use. This study evaluated novel therapeutic footwear, designed for aesthetics and custom fit, to reduce foot pain. We hypothesized that older adults would experience less foot pain and favor the new footwear over their own.

Methods: This 12-week crossover randomized controlled trial evaluated the effectiveness of OrthoFeet therapeutic footwear on reducing foot pain in older adults (n = 50, age = 65 ± 5, 18% male) with moderate to severe pain. Participants …

Tfeb-Vacuolar Atpase Signaling Regulates Lysosomal Function And Microglial Activation In Tauopathy, Baiping Wang, Heidi Martini-Stoica, Chuangye Qi, Tzu-Chiao Lu, Shuo Wang, Wen Xiong, Yanyan Qi, Yin Xu, Marco Sardiello, Hongjie Li, Hui Zheng

Center on Aging Staff Publications

Transcription factor EB (TFEB) mediates gene expression through binding to the coordinated lysosome expression and regulation (CLEAR) sequence. TFEB targets include subunits of the vacuolar ATPase (v-ATPase), which are essential for lysosome acidification. Single-nucleus RNA sequencing of wild-type and PS19 (Tau) transgenic mice expressing the P301S mutant tau identified three unique microglia subclusters in Tau mice that were associated with heightened lysosome and immune pathway genes. To explore the lysosome-immune relationship, we specifically disrupted the TFEB-v-ATPase signaling by creating a knock-in mouse line in which the CLEAR sequence of one of the v-ATPase subunits, Atp6v1h, was mutated. CLEAR mutant exhibited …

Age-Associated Temporal Decline In Butyrate-Producing Bacteria Plays A Key Pathogenic Role In The Onset And Progression Of Neuropathology And Memory Deficits In 3×Tg-Ad Mice, Paula M Chilton, Smita S Ghare, Benjamin T Charpentier, Scott A Myers, Aakarsha V Rao, Joseph F Petrosino, Kristi L Hoffman, John C Greenwell, Neetu Tyagi, Jyotirmaya Behera, Yali Wang, Lucy J Sloan, Jingwen Zhang, Christopher B Shields, Gregory E Cooper, Leila Gobejishvili, Scott R Whittemore, Craig J Mcclain, Shirish S Barve

Faculty, Staff and Students Publications

Alterations in the gut-microbiome-brain axis are increasingly being recognized to be involved in Alzheimer's disease (AD) pathogenesis. However, the functional consequences of enteric dysbiosis linking gut microbiota and brain pathology in AD progression remain largely undetermined. The present work investigated the causal role of age-associated temporal decline in butyrate-producing bacteria and butyrate in the etiopathogenesis of AD. Longitudinal metagenomics, neuropathological, and memory analyses were performed in the 3×Tg-AD mouse model. Metataxonomic analyses showed a significant temporal decline in the alpha diversity marked by a decrease in butyrate-producing bacterial communities and a concurrent reduction in cecal butyrate production. Inferred metagenomics analysis …

Acceptability And Use Of An Online Health Priorities Self-Identification Tool For Older Adults: A Qualitative Investigation, Emily L Mroz, Kizzy Hernandez-Bigos, Jessica Esterson, Eliza Kiwak, Aanand Naik, Mary E Tinetti

Faculty, Staff and Student Publications

OBJECTIVE: To examine the use of a web-based, self-directed health priorities identification tool for older adults with multiple chronic conditions (MCCs).

METHODS: We recruited a gender- and racially-diverse, highly educated sample of older adults with MCCs to engage with our My Health Priorities tool, then complete a semi-structured interview. Thematic analysis was used to examine interview transcripts.

RESULTS: Twenty-one participants shared perspectives on the acceptability and use of the tool. Three themes (with eleven subthemes) were generated to describe: website

CONCLUSION: Participants found this tool acceptable and easy to use, describing a variety of benefits of the priorities self-identification process …

Aging Differentially Affects Axonal Autophagosome Formation And Maturation, Heather Tsong, Erika Lf Holzbaur, Andrea Kh Stavoe

Faculty, Staff and Student Publications

Misregulation of neuronal macroautophagy/autophagy has been implicated in age-related neurodegenerative diseases. We compared autophagosome formation and maturation in primary murine neurons during development and through aging to elucidate how aging affects neuronal autophagy. We observed an age-related decrease in the rate of autophagosome formation leading to a significant decrease in the density of autophagosomes along the axon. Next, we identified a surprising increase in the maturation of autophagic vesicles in neurons from aged mice. While we did not detect notable changes in endolysosomal content in the distal axon during early aging, we did observe a significant loss of acidified vesicles …

Optimizing Tissue Oxygenation In Reduction Mammoplasty: The Role Of Continuous Diffusion Of Oxygen: A Feasibility Pilot Randomized Controlled Trial, Alejandro Zulbaran-Rojas, Rasha O Bara, Myeounggon Lee, Areli Flores-Camargo, Ramkinker Mishra, Sebastian Winocour, Alastair Thompson, Bijan Najafi

Center on Aging Staff Publications

Introduction: Bilateral reduction mammoplasty (BRM) aims to alleviate macromastia-related symptoms in women. This procedure involves a T-Junction suture at the medial inframammary fold that encompasses 12%-39% of wound breakdowns mainly due to reduced perfusion. Continuous diffusion of oxygen (CDO) may enhance breast tissue oxygenation to prevent such complication. We explored the feasibility of this therapy.

Methods: A 4-wk feasibility-pilot randomized controlled trial of women undergoing BRM was conducted. By internal randomization (left/right side), participants received standard of care (SOC) in one breast using topical skin adhesive, while their other breast received SOC + CDO at the T-junction covered by a …

Association Of Interleukin-6 And Interleukin-18 With Cardiovascular Disease In Older Adults: Atherosclerosis Risk In Communities Study, Xiaoming Jia, Leo Buckley, Caroline Sun, Mahmoud Al Rifai, Bing Yu, Vijay Nambi, Salim S Virani, Elizabeth Selvin, Kunihiro Matsushita, Ron C Hoogeveen, Josef Coresh, Amil M Shah, Christie M Ballantyne

Faculty, Staff and Students Publications

AIMS: Interleukin-6 (IL-6) and interleukin-18 (IL-18), important cytokines implicated in atherosclerosis and inflammaging, were assessed for associations with global cardiovascular disease (CVD), atrial fibrillation (AF), and death in older adults.

METHODS AND RESULTS: Participants from Atherosclerosis Risk in Communities study Visit 5 (mean age 75.4 ± 5.1 years) with IL-6 and IL-18 measurements were included (n = 5672). Cox regression models were used to assess associations of IL-6 and IL-18 with coronary heart disease (CHD), ischaemic stroke, heart failure (HF) hospitalization, global CVD (composite of CHD, stroke, and HF), AF, and all-cause death. Over a median follow-up of 7.2 years, …

Clinical Performance Characteristics For Bordered Foam Dressings In The Treatment Of Complex Wounds: An International Wound Dressing Technology Expert Panel Review, Nick Santamaria, Kevin Woo, 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

The aim of this article is to identify and describe clinical practice performance characteristics for bordered foam dressings in the treatment of complex wounds. Our recently published systematic review of outcomes and applied measurement instruments for the use of bordered foam dressings in complex wounds has led to us identifying a range of important clinical and patient-centred issues related to this dressing class. Specifically, here, we focus on an overview of performance criteria in the areas of application, adhesion, exudate management and debridement functions of bordered foam dressings. Our hope is that by highlighting the clinical performance criteria, future testing …

Diversity, Equity, And Inclusion: Considerations In The Geriatric Emergency Department Patient, Anita N Chary, Lauren Cameron-Comasco, Kalpana N Shankar, Margaret E Samuels-Kalow

Faculty, Staff and Students Publications

This article introduces core topics in health equity scholarship and provides examples of how diversity, equity, and inclusion impact the aging population and emergency care of older adults. It offers strategies for promoting diversity, equity, and inclusion to both strengthen the patient-clinician therapeutic relationship and to address operations and systems that impact care of the geriatric emergency department patient.

Emotional Barriers And Facilitators Of Deprescribing For Older Adults With Cancer And Polypharmacy: A Qualitative Study, Erika Ramsdale, Arul Malhotra, Holly M Holmes, Lisa Zubkoff, Jinjiao Wang, Supriya Mohile, Sally A Norton, Paul R Duberstein

Faculty, Staff and Student Publications

Purpose: To describe emotional barriers and facilitators to deprescribing (the planned reduction or discontinuation of medications) in older adults with cancer and polypharmacy.

Methods: Virtual focus groups were conducted over Zoom with 5 key informant groups: oncologists, oncology nurses, primary care physicians, pharmacists, and patients. All groups were video- and audio-recorded and transcribed verbatim. Focus group transcripts were analyzed using inductive content analysis, and open coding was performed by two coders. A codebook was generated based on the initial round of open coding and updated throughout the analytic process. Codes and themes were discussed for each transcript until consensus was …

Tuberculosis Presentation And Outcomes In Older Hispanic Adults From Tamaulipas, Mexico, Belinda A Medrano, Miryoung Lee, Gretchen Gemeinhardt, Javier E Rodríguez-Herrera, Moncerrato García-Viveros, Blanca I Restrepo

Faculty, Staff and Student Publications

Older people are at high risk of developing and dying from pulmonary infections like tuberculosis (TB), but there are few studies among them, particularly in Hispanics. To address these gaps, we sought to identify host factors associated with TB and adverse treatment outcomes in older Hispanics by conducting a cross-sectional study of TB surveillance data from Tamaulipas, Mexico (2006-2013; n = 8381). Multivariable logistic regressions were assessed for older adults (OA ≥65 years) when compared to young (YA, 18-39 years) and middle-aged adults (40-64 years). We found that the OA had features associated with a less complicated TB (e.g., lower …