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 …

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 …

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 …

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 …

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 …

Utilizing Speech Analysis To Differentiate Progressive Supranuclear Palsy From Parkinson’S Disease, Kyurim Kang, Adonay S Nunes, Mansi Sharma, A J Hall, Ram Kinker Mishra, Jose Casado, Rylee Cole, Marc Derhammer, Gregory Barchard, Bijan Najafi, Ashkan Vaziri, Anne-Marie Wills, Alexander Pantelyat

Center on Aging Staff Publications

Introduction: Distinguishing Parkinson's disease (PD) from Progressive supranuclear palsy (PSP) at early disease stages is important for clinical trial enrollment and clinical care/prognostication.

Methods: We recruited 21 participants with PSP(n = 11) or PD(n = 10) with reliable caregivers. Standardized passage reading, counting, and sustained phonation were recorded on the BioDigit Home tablet (BioSensics LLC, Newton, MA USA), and speech features from the assessments were analyzed using the BioDigit Speech platform (BioSensics LLC, Newton, MA USA). An independent t-test was performed to compare each speech feature between PSP and PD participants. We also performed Spearman's correlations to evaluate associations between …

Game-Based Intradialytic Non-Weight-Bearing Exercise Training On Gait Speed And Balance In Older Adults With Diabetes: A Single-Blind Randomized Controlled Trial, M G Finco, Bijan Najafi, He Zhou, Abdullah Hamad, Rania Ibrahim, Fadwa Al-Ali

Center on Aging Staff Publications

Older adults with diabetes receiving hemodialysis have impaired gait speed and balance compared to the general population, which have been associated with increased risks of falls and mortality. This study evaluated the effectiveness of a game-based intradialytic exercise training program (iExergame) on improving gait speed and balance. This was a single-blind randomized controlled trial. The intervention group (IG) received iExergame training using real-time audiovisual feedback with wearable inertial sensors. The control group (CG) received conventional training without any technology. Both trainings were intradialytic, non-weight-bearing, and used ankle range of motion. Gait and balance parameters were collected at baseline and 4-week …

Associations Between Cancer Predisposition Mutations And Clonal Hematopoiesis In Patients With Solid Tumors, Sebastià Franch-Expósito, Miika Mehine, Ryan N Ptashkin, Kelly L Bolton, Chaitanya Bandlamudi, Preethi Srinivasan, Linda Zhang, Margaret A Goodell, Erika Gedvilaite, Kamal Menghrajani, Pablo Sánchez-Vela, Diana Mandelker, Elizabeth Comen, Larry Norton, Ryma Benayed, Teng Gao, Elli Papaemmanuil, Barry Taylor, Ross Levine, Kenneth Offit, Zsofia Stadler, Michael F Berger, Ahmet Zehir

Center on Aging Staff Publications

Purpose: Clonal hematopoiesis (CH), the expansion of clones in the hematopoietic system, has been linked to different internal and external features such as aging, genetic ancestry, smoking, and oncologic treatment. However, the interplay between mutations in known cancer predisposition genes and CH has not been thoroughly examined in patients with solid tumors.

Methods: We used prospective tumor-blood paired sequencing data from 46,906 patients who underwent Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) testing to interrogate the associations between CH and rare pathogenic or likely pathogenic (P/LP) germline variants.

Results: We observed an enrichment of CH-positive patients among …

Mechanical And Contact Characteristics Of Foam Materials Within Wound Dressings: Theoretical And Practical Considerations In Treatment, Amit Gefen, Paulo Alves, Dimitri Beeckman, José Luis Lázaro-Martínez, Hadar Lev-Tov, Bijan Najafi, Terry Swanson, Kevin Woo

Center on Aging Staff Publications

In the treatment of acute and chronic wounds, the clinical performance of a given foam‐based dressing, and, ultimately, the wound healing and cost of care outcomes are strongly influenced by the mechanical performance of the foam material/s within that dressing. Most aspects of the mechanical performance of foam materials, for example, their stiffness, frictional properties, conformability, swelling characteristics and durability, and the overall mechanical protection provided by a foam‐based dressing to a wound strongly depend on the microstructure of the foam components, particularly on their microtopography, density and porosity. This article, therefore, provides, for the first time, a comprehensive, self‐inclusive …

Cellular Senescence And Frailty In Transplantation, Elizabeth C Lorenz, Latonya J Hickson, Pascale Khairallah, Bijan Najafi, Cassie C Kennedy

Center on Aging Staff Publications

Purpose of review: To summarizes the literature on cellular senescence and frailty in solid-organ transplantation and highlight the emerging role of senotherapeutics as a treatment for cellular senescence.

Recent findings: Solid-organ transplant patients are aging. Many factors contribute to aging acceleration in this population, including cellular senescence. Senescent cells accumulate in tissues and secrete proinflammatory and profibrotic proteins which result in tissue damage. Cellular senescence contributes to age-related diseases and frailty. Our understanding of the role cellular senescence plays in transplant-specific complications such as allograft immunogenicity and infections is expanding. Promising treatments, including senolytics, senomorphics, cell-based regenerative therapies, and behavioral …

Daily Posture Behavior Patterns Derived From Multitime-Scale Topic Models Using Wearable Triaxial Acceleration For Assessment Of Concern About Falling, Changhong Wang, Yu Wang, Haitao Zhao, Guanzheng Liu, Bijan Najafi

Center on Aging Staff Publications

Concern about falling is prevalent in older population. This condition would cause a series of adverse physical and psychological consequences for older adults' health. Traditional assessment of concern about falling is relied on self-reported questionnaires and thus is too subjective. Therefore, we proposed a novel multi-time-scale topic modelling approach to quantitatively evaluate concern about falling by analyzing triaxial acceleration signals collected from a wearable pendent sensor. Different posture segments were firstly recognized to extract their corresponding feature subsets. Then, each selected feature related to concern about falling was clustered into discrete levels as feature letters of artificial words in different …

Pharmacological Management Of Disease By Overcoming Structural Adversity, Richard N Sifers

Center on Aging Staff Publications

In this issue of Cell Chemical Biology, Sun et al. utilize computational and protein expression analyses, plus pharmacological proteostasis network activation, to simultaneously correct two genetic diseases linked to a single protein rather than modify the responsible DNA.

Discovery Of Associative Patterns Between Workplace Sound Level And Physiological Wellbeing Using Wearable Devices And Empirical Bayes Modeling, Karthik Srinivasan, Faiz Currim, Casey M Lindberg, Javad Razjouyan, Brian Gilligan, Hyoki Lee, Kelli J Canada, Nicole Goebel, Matthias R Mehl, Melissa M Lunden, Judith Heerwagen, Bijan Najafi, Esther M Sternberg, Kevin Kampschroer, Sudha Ram

Center on Aging Staff Publications

We conducted a field study using multiple wearable devices on 231 federal office workers to assess the impact of the indoor environment on individual wellbeing. Past research has established that the workplace environment is closely tied to an individual's wellbeing. Since sound is the most-reported environmental factor causing stress and discomfort, we focus on quantifying its association with physiological wellbeing. Physiological wellbeing is represented as a latent variable in an empirical Bayes model with heart rate variability measures-SDNN and normalized-HF as the observed outcomes and with exogenous factors including sound level as inputs. We find that an individual's physiological wellbeing …

Dual-Task Upper Extremity Motor Performance Measured By Video Processing As Cognitive-Motor Markers For Older Adults, Changhong Wang, Mohsen Zahiri, Ashkan Vaziri, Bijan Najafi

Center on Aging Staff Publications

Introduction: The use of dual-task model such as dual-task gait has been extensively studied to assess cognitive-motor performance among older adults. However, space restriction and safety factor limit its applications in remote assessment. To address the gap, we propose a video processing-based approach to remotely quantify cognitive-motor performance using a 20-s repetitive elbow flexion-extension test with dual-task condition, called video-based motoric-cognitive meter (MCM).

Methods: Eighteen older participants (age: 78.6 ± 6.5 years) who were clinically diagnosed as having either mild cognitive impairment or dementia were included in this study. Participants were asked to perform 20-s repetitive elbow flexion-extension exercise with …

Home-Based Electrical Stimulation To Accelerate Wound Healing-A Double-Blinded Randomized Control Trial, Alejandro Zulbaran-Rojas, Catherine Park, Nesreen El-Refaei, Brian Lepow, Bijan Najafi

Center on Aging Staff Publications

Background: Electrical stimulation (E-Stim) may offer a unique adjunctive treatment to heal complicated diabetic foot ulcers (DFU). Our primary goal is to examine the effectiveness of daily home-based E-Stim therapy to speed-up wound healing.

Methods: Patients with chronic DFUs and mild to severe peripheral arterial disease (PAD) were recruited and randomized to either control (CG) or intervention (IG) groups. The IG received 1-hour home-based E-Stim therapy on daily basis for 4 weeks (4W). E-Stim was delivered through electrical pads placed above the ankle joint using a bio-electric stimulation technology (BEST®) platform (Tennant Biomodulator® PRO). The CG was provided with an …

Care4ad: A Technology-Driven Platform For Care Coordination And Management: Acceptability Study In Dementia, Ram Kinker Mishra, Catherine Park, Anmol Salim Momin, Nesreen El Rafaei, Mark Kunik, Michele K York, Bijan Najafi

Center on Aging Staff Publications

Introduction: The technology-driven solution can reduce the caregiving burden; however, the needs of dementia caregiving are unique, and attitudes towards adopting technology from the perspectives of all the stakeholders involved in dementia caregiving are unclear. This study aims to assess the acceptability and feasibility of a technology-driven platform to facilitate care coordination platform, Care4AD, from the end-user perspective.

Methods: Care4AD includes three components: (1) Care4AD app: the app is used by caregivers to coordinate care, monitor physical activity, and schedule reminders; (2) Care4AD tablet: a smart tablet is used by the care recipient to display scheduled reminders; and (3) Care4AD …

Neuronal Signal-Regulatory Protein Alpha Drives Microglial Phagocytosis By Limiting Microglial Interaction With Cd47 In The Retina, Danye Jiang, Courtney A Burger, Viktor Akhanov, Justine H Liang, Robert D Mackin, Nicholas E Albrecht, Pilar Andrade, Dorothy P Schafer, Melanie A Samuel

Center on Aging Staff Publications

Microglia utilize their phagocytic activity to prune redundant synapses and refine neural circuits during precise developmental periods. However, the neuronal signals that control this phagocytic clockwork remain largely undefined. Here, we show that neuronal signal-regulatory protein alpha (SIRPα) is a permissive cue for microglial phagocytosis in the developing murine retina. Removal of neuronal, but not microglial, SIRPα reduced microglial phagocytosis, increased synpase numbers, and impaired circuit function. Conversely, prolonging neuronal SIRPα expression extended developmental microglial phagocytosis. These outcomes depended on the interaction of presynaptic SIRPα with postsynaptic CD47. Global CD47 deficiency modestly increased microglial phagocytosis, while CD47 overexpression reduced it. …

Tele-Medicine Based And Self-Administered Interactive Exercise Program (Tele-Exergame) To Improve Cognition In Older Adults With Mild Cognitive Impairment Or Dementia: A Feasibility, Acceptability, And Proof-Of-Concept Study, Catherine Park, Ram Kinker Mishra, Michele K York, Ana Enriquez, Abigail Lindsay, Gregory Barchard, Ashkan Vaziri, Bijan Najafi

Center on Aging Staff Publications

Improved life expectancy is increasing the number of older adults who suffer from motor-cognitive decline. Unfortunately, conventional balance exercise programs are not tailored to patients with cognitive impairments, and exercise adherence is often poor due to unsupervised settings. This study describes the acceptability and feasibility of a sensor-based in-home interactive exercise system, called tele-Exergame, used by older adults with mild cognitive impairment (MCI) or dementia. Our tele-Exergame is specifically designed to improve balance and cognition during distractive conditioning while a telemedicine interface remotely supervises the exercise, and its exercises are gamified balance tasks with explicit augmented visual feedback. Fourteen adults …