Medicine and Health Sciences Commons^™

Protocol For A Pilot Clinical Trial Of The Senolytic Drug Combination Dasatinib Plus Quercetin To Mitigate Age-Related Health And Cognitive Decline In Mental Disorders [Version 2; Peer Review: 1 Approved, 2 Approved With Reservations], Abigail Schweiger, Breno Diniz, Ginger Nicol, Julie Schweiger, Andes E Dasklakis-Perez, Eric J Lenze

2020-Current year OA Pubs

BACKGROUND: Major depressive disorder (MDD) and schizophrenia are linked to accelerated aging leading to reduced lifespan, health span and cognitive decline. Cellular senescence, in which cells lose proliferative capacity and develop a senescence-associated secretory phenotype (SASP), plays a role in this process. Emerging research suggests that the senolytic regimen of dasatinib+quercetin (D+Q) reduces senescent cells, potentially mitigating age-related health and cognitive decline. This pilot study aims to assess the feasibility and safety of D+Q in older adults with schizophrenia, schizoaffective disorder, and treatment-resistant depression (TRD).

METHODS: This single-center study will recruit 30 participants total aged 50 years or older with …

Tourette Syndrome Research Highlights From 2023 [Version 2; Peer Review: 3 Approved], Andreas Hartmann, Per Andrén, Cyril Atkinson-Clement, Virginie Czernecki, Cécile Delorme, Nanette Mol Debes, Simon Morand-Beaulieu, Kirsten Müller-Vahl, Peristera Paschou, Natalia Szejko, Apostolia Topaloudi, Kevin J Black

2020-Current year OA Pubs

In this, the tenth annual update for the F1000Research Tics collection, we summarize research reports from 2023 on Gilles de la Tourette syndrome and other tic disorders. The authors welcome article suggestions and thoughtful feedback from readers.

Ivsight As An Infusion Monitor For Patients Receiving Intravenous Therapy: An Exploratory, Unblinded, Single-Center Trial, Carlos Mejia-Chew, Brett Heuring, Jeffrey Salmons, Lori Weilmuenster, Joe Beggs, Glen Kleinschmidt, Jake Eshelman, Sai Dodda

2020-Current year OA Pubs

BACKGROUND: Intravenous (IV) infusion therapy is commonly used in health care settings. However, IV therapy at home can be challenging because it relies on the patient's ability to manage multiple medications correctly, which may lead to decreased treatment adherence.

OBJECTIVE: We aimed to assess the usability and accuracy of the IVsight monitor in capturing IV infusion data compared to manual recording.

METHODS: A prospective, single-center, usability study involving patients receiving IV infusion therapy at one of the BJC's Home Infusion suites was conducted to evaluate the accuracy, performance, and acceptability of the device IVsight as a monitor for IV infusions. …

Proceedings Of The 11th Annual Deep Brain Stimulation Think Tank: Pushing The Forefront Of Neuromodulation With Functional Network Mapping, Biomarkers For Adaptive Dbs, Bioethical Dilemmas, Ai-Guided Neuromodulation, And Translational Advancements, Kara A Johnson, Nico U F Dosenbach, Evan M Gordon, Et Al.

2020-Current year OA Pubs

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and …

Lung Lymphatic Endothelial Cells Undergo Inflammatory And Prothrombotic Changes In A Model Of Chronic Obstructive Pulmonary Disease, Anjali Trivedi, Tyler M Lu, Barbara Summers, Kihwan Kim, Alexander J Rhee, Sean Houghton, Derek E Byers, Raphaël Lis, Hasina Outtz Reed

2020-Current year OA Pubs

The lymphatic vasculature regulates lung homeostasis through drainage of fluid and trafficking of immune cells and plays a key role in the response to lung injury in several disease states. We have previously shown that lymphatic dysfunction occurs early in the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke (CS) and that this is associated with increased thrombin and fibrin clots in lung lymph. However, the direct effects of CS and thrombin on lymphatic endothelial cells (LECs) in COPD are not entirely clear. Studies of the blood vasculature have shown that COPD is associated with increased thrombin …

In Vivo Measurement Of Pediatric Extracorporeal Oxygenator Insensible Losses; A Single Center Pilot Study, Tess L Suttles, John Poe, Tara M Neumayr, Ahmed S Said

2020-Current year OA Pubs

INTRODUCTION: Fluid overload on Extracorporeal Membrane Oxygenation (ECMO) is associated with worse outcomes. Previous

METHODS: Pediatric ECMO patients were approached over eleven months in the pediatric and cardiac intensive care units. The water content of the oxygenator inflow sweep gas and exhaust gas were calculated by measuring the ambient temperature and relative humidity at frequent intervals and various sweep flow.

RESULTS AND DISCUSSION: Nine subjects were enrolled, generating 431 data points. The cohort had a median age of 11 years IQR [0.83, 13], weight of 23.2 kg IQR [6.48, 44.28], and body surface area of 0.815 m

Early Detection Of Myocardial Involvement By Non-Contrast T1Ρ Mapping Of Cardiac Magnetic Resonance In Type 2 Diabetes Mellitus, Hongmin Shu, Huimin Xu, Zixiang Pan, Yan Liu, Wei Deng, Ren Zhao, Yan Sun, Zhen Wang, Jinxiu Yang, Hui Gao, Kaixuan Yao, Jie Zheng, Yongqiang Yu, Xiaohu Li

2020-Current year OA Pubs

OBJECTIVE: This study aims to determine the effectiveness of T1ρ in detecting myocardial fibrosis in type 2 diabetes mellitus (T2DM) patients by comparing with native T1 and extracellular volume (ECV) fraction.

METHODS: T2DM patients (n = 35) and healthy controls (n = 30) underwent cardiac magnetic resonance. ECV, T1ρ, native T1, and global longitudinal strain (GLS) values were assessed. Diagnostic performance was analyzed using receiver operating curves.

RESULTS: The global ECV and T1ρ of T2DM group (ECV = 32.1 ± 3.2%, T1ρ = 51.6 ± 3.8 msec) were significantly higher than those of controls (ECV = 26.2 ± 1.6%, T1ρ …

Assessing Quality Of Life In Childhood Cancer Survivors At Risk For Hearing Loss: A Comparison Of Hear-Ql And Promis Measures, Anne Spence, Allison J L'Hotta, Susan S Hayashi, Kara Felts, Emily Lafentres, Megan Jones-White, Judith E C Lieu, Allison A King, Robert J Hayashi

2020-Current year OA Pubs

BACKGROUND: Childhood cancer survivors (CCS) exposed to platinum chemotherapy are at an increased risk of developing hearing loss and reporting decreased quality of life (QOL). This study compared two QOL measures; one developed for children with hearing loss, The Hearing Environments and Refection on Quality of Life (HEAR-QL), and one validated in CCS, the Patient-Reported Outcomes Measurement Information System (PROMIS), to assess their ability to evaluate QOL deficits in this population.

METHODS: Subject eligibility were restricted to CCS exposed to platinum-based chemotherapy but who were free of known risk factors for cognitive impairment, (non-central nervous system tumor, no cranial radiation, …

Effectively Communicating With Local Policymakers: A Randomized Trial Of Policy Brief Dissemination To Address Obesity, Elizabeth A Dodson, Renee G Parks, Rebekah R Jacob, Ruopeng An, Amy A Eyler, Nathan Lee, Alexandra B Morshed, Mary C Politi, Rachel G Tabak, Yan Yan, Ross C Brownson

2020-Current year OA Pubs

INTRODUCTION: Evidence-based policies are a powerful tool for impacting health and addressing obesity. Effectively communicating evidence to policymakers is critical to ensure evidence is incorporated into policies. While all public health is local, limited knowledge exists regarding effective approaches for improving local policymakers' uptake of evidence-based policies.

METHODS: Local policymakers were randomized to view one of four versions of a policy brief (usual care, narrative, risk-framing, and narrative/risk-framing combination). They then answered a brief survey including questions about their impressions of the brief, their likelihood of using it, and how they determine legislative priorities.

RESULTS: Responses from 331 participants indicated …

Post-Traumatic Stress And Future Substance Use Outcomes: Leveraging Antecedent Factors To Stratify Risk, Henri M Garrison-Desany, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: Post-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD.

METHODS: The Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total …

Modular Horizontal Network Within Mouse Primary Visual Cortex, Andreas Burkhalter, Weiqing Ji, Andrew M Meier, Rinaldo D D'Souza

2020-Current year OA Pubs

Interactions between feedback connections from higher cortical areas and local horizontal connections within primary visual cortex (V1) were shown to play a role in contextual processing in different behavioral states. Layer 1 (L1) is an important part of the underlying network. This cell-sparse layer is a target of feedback and local inputs, and nexus for contacts onto apical dendrites of projection neurons in the layers below. Importantly, L1 is a site for coupling inputs from the outside world with internal information. To determine whether all of these circuit elements overlap in L1, we labeled the horizontal network within mouse V1 …

Membrane Potential Hyperpolarization: A Critical Factor In Acrosomal Exocytosis And Fertilization In Sperm Within The Female Reproductive Tract, Paula A Balestrini, Valeria Sulzyk, Martina Jabloñski, Liza J Schiavi-Ehrenhaus, Soledad N González, Juan J Ferreira, Matías D Gómez-Elías, Pablo Pomata, Guillermina M Luque, Dario Krapf, Patricia S Cuasnicu, Celia M Santi, Mariano G Buffone

2020-Current year OA Pubs

Hyperpolarization of the membrane potential (Em), a phenomenon regulated by SLO3 channels, stands as a central feature in sperm capacitation-a crucial process conferring upon sperm the ability to fertilize the oocyte.

The Molecular Landscape Of Sepsis Severity In Infants: Enhanced Coagulation, Innate Immunity, And T Cell Repression, Susie Shih Yin Huang, Mohammed Toufiq, Pirooz Eghtesady, Nicholas Van Panhuys, Mathieu Garand

2020-Current year OA Pubs

INTRODUCTION: Sepsis remains a major cause of mortality and morbidity in infants. In recent years, several gene marker strategies for the early identification of sepsis have been proposed but only a few have been independently validated for adult cohorts and applicability to infant sepsis remains unclear. Biomarkers to assess disease severity and risks of shock also represent an important unmet need.

METHODS: To elucidate characteristics driving sepsis in infants, we assembled a multi-transcriptomic dataset from public microarray datasets originating from five independent studies pertaining to bacterial sepsis in infant < 6-months of age (total n=335). We utilized a COmbat co-normalization strategy to enable comparative evaluation across multiple studies while preserving the relationship between cases and controls.

RESULTS: We found good concordance with only two out of seven …

Covid-19 Vaccination In Patients With Inborn Errors Of Immunity Reduces Hospitalization And Critical Care Needs Related To Covid-19: A Usidnet Report, John Mcdonnell, Alexa Michelle Altman Doss, Caroline C. Horner, Dayne H. Voelker, Et Al.

2020-Current year OA Pubs

No abstract provided.

Recruiting A Prospective Community Cohort To Study Alzheimer's Disease And Structural And Social Determinants Of Health Among Adults Racialized As Black: The Arches Cohort, Alexis I B Walker, Jean-Francois Trani, Christian F Banks, Samantha A Murphy, Wenqing Zha, Monique M Williams, Gregory S Day, Yiqi Zhu, Beau M Ances, Carl V Hill, Darrell L Hudson, Ganesh M Babulal

2020-Current year OA Pubs

INTRODUCTION: This ongoing, prospective study examines the effectiveness of methods used to successfully recruit and retain 238 Black older adults in a longitudinal, observational Alzheimer's disease (AD) study.

METHODS: Recruitment strategies included traditional media, established research registries, speaking engagements, community events, and snowball sampling. Participants were asked to complete an annual office testing session, blood-based biomarker collection, optional one-time magnetic resonance imaging (MRI) scan, and community workshop.

RESULTS: Within the first 22 months of active recruitment, 629 individuals expressed interest in participating, and 238 enrolled in the ongoing study. Of the recruitment methods used, snowball sampling, community events, and speaking …

Cognitive And Functional Performance And Plasma Biomarkers Of Early Alzheimer's Disease In Down Syndrome, Emily K Schworer, Beau M Ances, Et Al.

2020-Current year OA Pubs

INTRODUCTION: People with Down syndrome (DS) have a 75% to 90% lifetime risk of Alzheimer's disease (AD). AD pathology begins a decade or more prior to onset of clinical AD dementia in people with DS. It is not clear if plasma biomarkers of AD pathology are correlated with early cognitive and functional impairments in DS, and if these biomarkers could be used to track the early stages of AD in DS or to inform inclusion criteria for clinical AD treatment trials.

METHODS: This large cross-sectional cohort study investigated the associations between plasma biomarkers of amyloid beta (Aβ)42/40, total tau, and …

Impahct: A Randomized Phase 2b/3 Study Of Inhaled Imatinib For Pulmonary Arterial Hypertension, Hunter Gillies, Murali M Chakinala, Benjamin T Dake, Jeremy P Feldman, Marius M Hoeper, Marc Humbert, Zhi-Cheng Jing, Jonathan Langley, Vallerie V Mclaughlin, Ralph W Niven, Stephan Rosenkranz, Xiaosha Zhang, Nicholas S Hill

2020-Current year OA Pubs

AV-101 (imatinib) powder for inhalation, an investigational dry powder inhaled formulation of imatinib designed to target the underlying pathobiology of pulmonary arterial hypertension, was generally well tolerated in healthy adults in a phase 1 single and multiple ascending dose study.

Classification Of Ipsc-Derived Cultures Using Convolutional Neural Networks To Identify Single Differentiated Neurons For Isolation Or Measurement, Purva Patel, Lina K. Mohammad Ali, Uma Kaushik, Malllory Wright, Kaylee Green, Jason E. Waligorski, Colin L. Kremitzki, Graham W. Bachman, Serena N. Elia, William J. Buchser

2020-Current year OA Pubs

No abstract provided.

Hippocampal Volumes In Uk Biobank Are Associated With Apoe Only In Older Adults, Ariya Chaloemtoem, Vera Thornton, Yoonhoo Chang, Andrey P Anokhin, Michaël E Belloy, Janine Bijsterbosch, Brian A Gordon, Sarah M Hartz, Laura J Bierut

2020-Current year OA Pubs

INTRODUCTION: The hippocampus atrophies with age and is implicated in neurodegenerative disorders including Alzheimer's disease (AD). We examined the interplay between age and apolipoprotein E (

METHODS: Using neuroimaging data from 37,463 UK Biobank participants, we applied linear regression to quantify the association of age and

RESULTS: Total hippocampal volume declined with age, with significant differences by

DISCUSSION: The association of

HIGHLIGHTS: Apolipoprotein E (

Clinical, Laboratory, And Orbital Imaging Features Of Giant Cell Arteritis In Comparison To Non-Arteritic Anterior Ischemic Optic Neuropath: A Single Center Case Series, Rami W Eldaya, Yi-Hsien Yeh, Leanne Stunkel, Matthew S Parsons, Gregory P Van Stavern

2020-Current year OA Pubs

BACKGROUND: Giant cell arteritis (GCA) is the most common vasculitis in patients older than 50 years and is considered a "do not miss" diagnosis. However, it remains a diagnostic challenge given overlapping clinical syndromes such as non-arteritic anterior ischemic optic neuropathy (NAION) and poorly explored imaging findings.

MATERIALS AND METHODS: In this retrospective study between the time period of January 2013 and December 2021, a total of 13 consecutive patients with a pathological diagnosis of GCA and 8 patients with clinical diagnosis of NAION were isolated. Demographic and clinical data for each patient were collected, including pertinent laboratory data. Pertinent …

Surviving Septic Patients Endotyped With A Functional Assay Demonstrate Active Immune Responses, Adam D Price, Andrew H Walton, Sydney Miles, Richard S Hotchkiss, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Sepsis is a complex clinical syndrome characterized by a heterogenous host immune response. Historically, static protein and transcriptomic metrics have been employed to describe the underlying biology. Here, we tested the hypothesis that

METHODS: This prospective, observational study of patient samples collected from the SPIES consortium included patients at five health systems enrolled over 17 months, with 46 healthy control patients, 68 ICU patients without sepsis, and 107 ICU patients with sepsis. Whole blood was collected on day 1, 4, and 7 of ICU admission. Outcomes included in-hospital and 180-day mortality and non-favorable discharge disposition defined by skilled nursing …

The Role Of Mek Inhibition In Pediatric Low-Grade Gliomas, Shehryar R Sheikh, Laura J Klesse, Ross Mangum, Ashley Bui, Benjamin I Siegel, Mohamed S Abdelbaki, Neha J Patel

2020-Current year OA Pubs

Pediatric low-grade gliomas (pLGGs) are the most common brain tumors in children. Many patients with unresectable tumors experience recurrence or long-term sequelae from standard chemotherapeutics. This mini-review explores the emerging role of MEK inhibitors in the management of pLGGs, highlighting their potential to transform current treatment paradigms. We review the molecular basis for therapeutic MEK inhibition in the context of pLGG, provide an evidence base for the use of the major MEK inhibitors currently available in the market for pLGG, and review the challenges in the use of MEKi inhibitors in this population.

Perspectives Of Traditional Herbal Medicines In Treating Retinitis Pigmentosa, Shihui Liu, Toshihiko Matsuo, Chie Matsuo, Takumi Abe, Jinghua Chen, Chi Sun, Qing Zhao

2020-Current year OA Pubs

Medicinal plants, also known as herbs, have been discovered and utilized in traditional medical practice since prehistoric times. Medicinal plants have been proven rich in thousands of natural products that hold great potential for the development of new drugs. Previously, we reviewed the types of Chinese traditional medicines that a Tang Dynasty monk Jianzhen (Japanese: Ganjin) brought to Japan from China in 742. This article aims to review the origin of Kampo (Japanese traditional medicine), and to present the overview of neurodegenerative diseases and retinitis pigmentosa as well as medicinal plants in some depth. Through the study of medical history …

Reinforcement Learning In Motor Skill Acquisition: Using The Reward Positivity To Understand The Mechanisms Underlying Short- And Long-Term Behavior Adaptation, Mariane F B Bacelar, Keith R Lohse, Juliana O Parma, Matthew W Miller

2020-Current year OA Pubs

INTRODUCTION: According to reinforcement learning, humans adjust their behavior based on the difference between actual and anticipated outcomes (i.e., prediction error) with the main goal of maximizing rewards through their actions. Despite offering a strong theoretical framework to understand how we acquire motor skills, very few studies have investigated reinforcement learning predictions and its underlying mechanisms in motor skill acquisition.

METHODS: In the present study, we explored a 134-person dataset consisting of learners' feedback-evoked brain activity (reward positivity; RewP) and motor accuracy during the practice phase and delayed retention test to investigate whether these variables interacted according to reinforcement learning …

Best Practices In Robotic Magnetic Navigation-Guided Catheter Ablation Of Cardiac Arrhythmias, A Position Paper Of The Society For Cardiac Robotic Navigation, Anna M E Noten, Daniel H Cooper, Et Al.

2020-Current year OA Pubs

PREAMBLE: Robotic magnetic navigation (RMN)-guided catheter ablation (CA) technology has been used for the treatment of cardiac arrhythmias for almost 20 years. Various studies reported that RMN allows for high catheter stability, improved lesion formation and a superior safety profile. So far, no guidelines or recommendations on RMN-guided CA have been published.

PURPOSE: The aim of this consensus paper was to summarize knowledge and provide recommendations on management of arrhythmias using RMN-guided CA as treatment of atrial fibrillation (AF) and ventricular arrhythmias (VA).

METHODOLOGY: An expert writing group, performed a detailed review of available literature, and drawing on their own …

Simplified Methods For Variance Estimation In Microbiome Abundance Count Data Analysis, Yiming Shi, Lili Liu, Jun Chen, Kristine M Wylie, Todd N Wylie, Molly J Stout, Chan Wang, Haixiang Zhang, Ya-Chen T Shih, Xiaoyi Xu, Ai Zhang, Sung Hee Park, Hongmei Jiang, Lei Liu

2020-Current year OA Pubs

The complex nature of microbiome data has made the differential abundance analysis challenging. Microbiome abundance counts are often skewed to the right and heteroscedastic (also known as overdispersion), potentially leading to incorrect inferences if not properly addressed. In this paper, we propose a simple yet effective framework to tackle the challenges by integrating Poisson (log-linear) regression with standard error estimation through the Bootstrap method and Sandwich robust estimation. Such standard error estimates are accurate and yield satisfactory inference even if the distributional assumption or the variance structure is incorrect. Our approach is validated through extensive simulation studies, demonstrating its effectiveness …

Centering Intersectional Breast Cancer Screening Experiences Among Black, Latina, And White Women: A Qualitative Analysis, Sienna Ruiz, Kamilah Abdur-Rashid, Rachel L Mintz, Maggie Britton, Ana A Baumann, Graham A Colditz, Ashley J Housten

2020-Current year OA Pubs

OBJECTIVE: Mammography screening guidelines in the United States highlight the importance of informing and involving women when making their breast cancer screening decisions. However, the complexity of interpreting and applying these population-level guidelines can contribute to patient burden. Patient-centered communication strategies can alleviate patient burden, but few consider perspectives from racially and ethnically marginalized populations. We examine diverse women's perspectives on screening to characterize patient-centered experiences.

METHODS: We conducted 28 focus groups with 134 non-Latina Black (

RESULTS: We identified three themes: (1) personal relationships with primary care providers, (2) potential impacts of cancer on families, and (3) interactions with …

The Risks Of Unconcern: Low Sensitivity To Threat Can Have Unfortunate Consequences, Stephen L Ristvedt

2020-Current year OA Pubs

Each one of us is confronted with warnings of danger or threats to wellbeing in our everyday life, whether in the form of certain road signs, Public Service Announcements, ominous changes in bodily functioning, or cautionary tales heard from family or friends. There is great inter-individual variation in how people respond to such threats, with some people habitually tending to ignore or dismiss them, often to their peril. The first purpose of the present paper is to review several studies showing that individuals-most often men-who score very low on measures of trait anxiety are more likely to engage in behaviors …

Protein Quality Malnutrition, Mark J Manary, Donna R Wegner, Kenneth Maleta

2020-Current year OA Pubs

Protein quality refers to the evaluation of a food or a diet based on its amino acid composition, protein digestibility, and protein bioavailability. When these parameters are specified, either through direct measurement or estimation, the amino acids provided by the diet are compared to those required by a healthy individual, and based on this comparison, an adequacy ratio or score is assigned. Two widely used protein quality scoring systems are the protein digestibility-corrected amino acid score (PDCAAS) and the digestible indispensable amino acid score (DIAAS), neither of which account for the dietary source of the protein. In malnourished children, metabolic …

Awareness, Use, Motivations And Methods Of Accessing Genetic Testing In 2022 In The United States, Sukh Makhnoon, Minjae Lee, Tanushree Prasad, Alexa Badalamenti, Tami Gurley, Erika A Waters, Celette Sugg Skinner

2020-Current year OA Pubs

INTRODUCTION: Awareness, access, and use of clinical and direct-to-consumer (DTC) genetic tests has increased in recent years with documented disparities in these services. We provide updated data on test awareness and use, and report novel data on motivations and methods for accessing genetic tests.

METHODS: Nationally representative data from the 2022 Health Information National Trends Survey (HINTS 6) were used to assess awareness and use of ancestry, personal trait, specific disease, and carrier testing by sociodemographic characteristics, examine reasons for undergoing tests, and methods of accessing them.

RESULTS: Overall, 81.4% of respondents were aware and 40.0% had undergone testing. Only …