Digital Commons Network^™

Disparities In Electronic Health Record Patient Portal Activation And Use Among People With Hematological Malignancies, Angela M Trammel, Bryan A Sisk, Mark A Fiala

2020-Current year OA Pubs

No abstract provided.

Prehospital Cricothyrotomy: A Narrative Review Of Technical, Educational, And Operational Considerations For Procedure Optimization, Aaron J Lacy, Michael J Kim, James L Li, Alexander Croft, Erin E Kane, Jason C Wagner, Philip W Walker, Christine M Brent, Jeremy J Brywczynski, Amanda C Mathews, Brit Long, Alex Koyfman, Bridgette Svancarek

2020-Current year OA Pubs

BACKGROUND: Definitive airway management is a requisite skill in the prehospital setting, most often accomplished with either an endotracheal tube or supraglottic airway. When clinicians encounter a cannot oxygenate and cannot ventilate scenario, a patient's airway still must be secured. Prehospital cricothyrotomy is a high acuity, low frequency procedure used to secure the airway through the anterior neck. Patients who require cricothyrotomy often have significant comorbid conditions and mortality, and there can be a high rate of procedural complications. The ability to perform a cricothyrotomy is within the scope of practice for many prehospital clinicians and mastery of the procedure …

Sleep Disorders Five Years After Acute Provoked Neonatal Seizures, Renée A Shellhaas, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To evaluate whether abnormal sleep is associated with adverse outcomes for children who survived acute provoked neonatal seizures, and their parents.

STUDY DESIGN: This 9-center study prospectively followed newborns with acute provoked seizures. When children reached age 5 years, parents completed the Children's Sleep Habits Questionnaire (CSHQ), the Pediatric Sleep Questionnaire-Sleep Related Breathing Disorders (PSQ-SRBD) subscale, the Vineland Adaptive Behavior Scales-3, and the Hospital Anxiety Depression Scale. Children were also assessed with the Wechsler Preschool and Primary Scale of Intelligence-IV (WPPSI-IV). Spearman correlations and multivariable analyses were used to evaluate risk factors for sleep problems.

RESULTS: The mean CSHQ …

Exploring The Differences Between Brca Mutated And Hrwild-Type High Grade Serous Ovarian Cancer: A Multiomic Analysis, Ayesha B Alvero, Sharon Wu, Alex Farrell, Seongho Kim, John J Wallbillich, Ira Winer, Robert Morris, David Spetzler, Matthew L Anderson, Alberto Puccini, Nathaniel L Jones, Thomas J Herzog, Premal H Thaker, Gil Mor, Radhika P Gogoi

2020-Current year OA Pubs

OBJECTIVE: The purpose of this study was to evaluate the transcriptomic profile of BRCA1 mutant (BRCA1mut) and BRCA2 mutant (BRCA2mut) HGSOC compared to homologous recombination wild-type (HRwt) tumors utilizing the CARIS database.

METHODS: Next-generation and Whole Transcriptome Sequencing (WTS; Caris Life Sciences, Phoenix, AZ) was performed on a total of 2745 HGSOC tumor samples. BRCA mutations were defined as variants resulting in loss-of-function of the protein and HRwt was defined as samples wildtype for aberrations in both BRCA1 and BRCA2, as well as for 28 other HR genes. HRwt group was further classified into HRwt/LOH-low (< 16 %) and HRwt/LOH-high (≥16 %). Genomic analysis consists of mutation analysis and measurements of TMB and MSI. Transcriptomic analysis included identification of Differentially expressed genes (DEGs), GSEA and immune deconvolution.

RESULTS: We identified 519 …

Detection Of Alternative Lengthening Of Telomeres Via Chromogenic In Situ Hybridization For The Prognostication Of Pannets And Other Neoplasms, Christopher M Heaphy, Ta-Chiang Liu, Dengfeng Cao, Et Al.

2020-Current year OA Pubs

Molecular studies have shown alternative lengthening to telomeres (ALT) to be an important prognostic biomarker of shorter relapse-free survival (RFS) for patients with pancreatic neuroendocrine tumors (PanNETs) and other neoplasms. However, the preferred method of detecting ALT in tissue is by fluorescence in situ hybridization (FISH), which has several clinical limitations. These issues necessitate the creation of a chromogenic ALT assay that can be easily implemented into routine practice. A chromogenic in situ hybridization (CISH) assay was developed using genetically modified osteosarcoma cell lines, 20 normal pancreata, 20 ALT-positive PanNETs, and 20 ALT-negative PanNETs. Thereafter, it was validated on a …

Cropland Associated With Risk Of Parkinson's Disease In The Northern Great Plains, Brittany Krzyzanowski, Kassu M Beyene, Susan Searles Nielsen, Jordan A Killion, Brad A Racette

2020-Current year OA Pubs

INTRODUCTION: We sought to identify regional associations between cropland density and crop types and PD in the U.S.

METHODS: We conducted a population-based study of 21,639,190 Medicare beneficiaries, 89,790 with incident PD in 2009. We used county-level geographic weighted regression (GWR) to identify region(s) of the U.S. where the association between PD RR and cropland density was strongest. In a broad region identified by GWR in which cropland density was associated with PD, we performed logistic regression using individual-level beneficiary data (2733 cases and 805,984 non-cases) with high-resolution cropland density data. We adjusted for age, sex, race, smoking, healthcare utilization, …

Combining Radioembolization And Immune Checkpoint Inhibitors For The Treatment Of Hepatocellular Carcinoma: The Quest For Synergy, Christopher D Malone, Suryansh Bajaj, Aiwu He, Kabir Mody, Ryan M Hickey, Ammar Sarwar, Sunil Krishnan, Tushar C Patel, Beau B Toskich

2020-Current year OA Pubs

Hepatocellular carcinoma is a leading and increasing contributor to cancer-related death worldwide. Recent advancements in both liver-directed therapies in the form of yttrium-90 (

Relationships Between Brain Glucose Metabolism Patterns And Impaired Glycemic Status: A Systematic Review Of Fdg-Pet Studies With A Focus On Alzheimer's Disease, Setareh Soltani, Mahsa Dolatshahi, Sara Soltani, Kian Khazaei, Maryam Rahmani, Cyrus A Raji

2020-Current year OA Pubs

It is well-established that individuals with type 2 diabetes have an increased risk of developing cognitive impairment and Alzheimer's disease (AD). However, it is not fully determined how insulin resistance and type 2 diabetes are related to AD-related brain glucose metabolism abnormalities. For this aim, we performed a systematic review of the studies investigating the association between cerebral glucose metabolism and glycemic status, including diabetes, insulin resistance, or hyperglycemia. Medline, Embase, and Cochrane databases were searched (till February 2, 2025). All English full-text papers studying 18F-FDG-PET that investigated the association between cerebral FDG uptake or cerebral metabolism rate and glycemic …

Rapid Development Of An Online Tracker To Communicate The Human Impact Of Abruptly Halting Pepfar Support, Brooke E Nichols, Elvin H Geng, Eric Moakley, Andrew N Phillips, Jeffrey W Imai-Eaton, John Stover, Edinah Mudimu, Anna Grimsrud

2020-Current year OA Pubs

No abstract provided.

Vitamin K Deficiency Bleeding In Children With Cholestatic Liver Disease: A Systematic Review And Meta-Analysis, Anusak Sakwit, Pongpak Pongphitcha, Patcharee Komvilaisak, Masayuki Ochiai, Daijiro Takahashi, Shutaro Suga, Ampaiwan Chuansumrit, Marisol Betensky, Stephen P Pereira, Amber Afzal, C Heleen Van Ommen, Neil Goldenberg, Sasivimol Rattanasiri, Nongnuch Sirachainan

2020-Current year OA Pubs

Vitamin K deficiency (VKD) in cholestatic liver disease affects up to 23% of pediatric patients. While several vitamin K (VK) prophylaxis regimens have been proposed, optimal therapeutic strategies remain undefined. The study aimed to identify the most effective VK prophylaxis for children with cholestatic liver disease. We conducted a systematic review of articles focusing on studies of children aged < 18 years with cholestatic liver disease who reported outcomes of either VKD or vitamin K deficiency bleeding (VKDB) after VK prophylaxis. The articles were sourced from PubMed, Scopus, and Embase. A meta-analysis was performed to determine the prevalence of VKD and the efficacy of each prophylactic protocol in preventing VKD/VKDB. The study was registered on PROSPERO (CRD 42021270048). Of the 889 articles, 37 were selected (2 comparative studies, 6 noncomparative studies, and 29 case reports/series). The results from the comparative studies indicated a lower incidence of VKD in the parenteral than that in the oral VK. The meta-analysis of the noncomparative studies showed the prevalence of VKD in high prothrombin induced by vitamin K absence-II group was 56% (95% CI, 45%-68%;

Spatial Histomorphometry Reveals That Local Peripheral Nerves Modulate But Are Not Required For Skeletal Adaptation To Applied Load In Mice, Alec T Beeve, Mohamed G Hassan, Anna Li, Nicole Migotsky, Matthew J Silva, Erica L Scheller

2020-Current year OA Pubs

Mechanical loading is required for bone health and results in skeletal adaptation to optimize strength. Local nerve axons, particularly within the periosteum, may respond to load-induced biomechanical and biochemical cues. However, their role in the bone anabolic response remains controversial. We hypothesized that spatial alignment of periosteal nerves with sites of load-induced bone formation would clarify this relationship. To achieve this, we developed RadialQuant, a custom tool for spatial histomorphometry. Tibiae of control and neurectomized (sciatic/femoral nerve cut) pan-neuronal Baf53b-tdTomato reporter mice were loaded for 5 days. Bone formation and periosteal nerve axon density were then quantified simultaneously in non-decalcified …

Spatial Proteomics Of Onchocerca Volvulus With Pleomorphic Neoplasms Shows Local And Systemic Dysregulation Of Protein Expression, Lucia S. Di Maggio, Kerstin Fischer, Bruce A. Rosa, Devyn Yates, Byoung-Kyu Cho, Jessica Lukowski, Antonia Zamacona Calderon, Minsoo Son, Young Ah Goo, Nicholas O. Opoku, Gary J. Weil, Makedonka Mitreva, Peter U. Fischer

2020-Current year OA Pubs

Onchocerca volvulus is the agent of onchocerciasis (river blindness) and targeted by WHO for elimination though mass drug administration with ivermectin. A small percentage of adult female worms develop pleomorphic neoplasms (PN) which occur more frequently after ivermectin treatment. Worms with PN have a lower life expectancy and improved understanding of proteins expressed in PN and their impact on different tissues could help elucidate the mechanisms of macrofilaricidal activity of ivermectin. Within paraffin embedded nodules removed after ivermectin treatment, we detected 24 (5.6%) O. volvulus females with PN. To assess the protein inventory of the PN and identify proteins potentially …

Transcranial Vibration Stimulation At 40 Hz Induced Neural Activity And Promoted The Coupling Of Global Brain Activity And Cerebrospinal Fluid Flow, Linghan Kong, Wei Jin, Yue Jiang, Fuhua Yan, Jun Liu, Eric C Leuthardt, Guang-Zhong Yang, Yuan Feng

2020-Current year OA Pubs

BACKGROUND: Neuroscience advances have highlighted the potential of non-invasive brain stimulation in influencing cognitive and emotional processes. Conventional stimulation methods such as electrical, magnetic, and ultrasound have been studied intensively, but little is known about the mechanical stimulation.

OBJECTIVE: To investigate the effects of 40 Hz transcranial vibration stimulation (TVS) on human brain activity, specifically focusing on changes in the Amplitude of Low-Frequency Fluctuation (ALFF), fractional ALFF (fALFF) and Regional Homogeneity (ReHo) as measures of spontaneous brain activity. Additionally, this study investigates alterations in the global blood-oxygen-level-dependent (gBOLD) signal and cerebrospinal fluid (CSF) inflow coupling, which serve as indicators of …

Effect Of Midwife-Led Pelvic Floor Muscle Training On Prolapse Symptoms And Quality Of Life In Women With Pelvic Organ Prolapse In Ethiopia: A Cluster-Randomized Controlled Trial, Melese Siyoum, Rahel Nardos, Biniyam Sirak, Theresa Spitznagle, Wondwosen Teklesilasie, Ayalew Astatkie

2020-Current year OA Pubs

BACKGROUND: Pelvic organ prolapse (POP) is a common condition that can significantly impact a woman's quality of life. Pelvic floor muscle training (PFMT) is recommended as a first-line conservative treatment for prolapse, but evidence on its effectiveness from low-resource settings is limited. This study aimed to assess the effect of midwife-led PFMT on prolapse symptoms and health-related quality of life (HRQoL) among women with mild-to-moderate POP in Ethiopia.

METHODS AND FINDINGS: A community-based, parallel-groups, two-arm cluster-randomized controlled trial was conducted in Dale and Wonsho districts of Sidama Region, Ethiopia. Women with symptomatic POP stages I-III were randomized by cluster to …

Treatment Of Non-Hodgkin Lymphoma With Point-Of-Care Manufactured Car T Cells: A Dual Institution, Phase 1 Trial, Armin Ghobadi, Linda Eissenberg, John Dipersio, Et Al.

2020-Current year OA Pubs

BACKGROUND: Point-of-care manufacture of chimeric antigen receptor (CAR)-T cells can significantly reduce the time from apheresis to infusion. We conducted a dual-institution phase I trial aimed evaluating the safety and feasibility of this manufacturing model.

METHODS: CASE 2417 was a phase I clinical trial. Adults with relapsed or refractory CD19 positive non-Hodgkin lymphoma (R/R NHL) treated with ≥2 prior systemic therapies were eligible. MB-CART-19 is an anti-CD19 CAR T-cell product manufactured using the CliniMACS Prodigy device with 4-1BB and CD3ζ costimulatory domains. Lymphodepletion included fludarabine 25 mg/m

FINDINGS: Thirty-one patients were enrolled between July 2018 and January 2021. Twenty-four (77%) …

Inhibition Of Soluble Epoxide Hydrolase Reduces Inflammation And Myocardial Injury In Arrhythmogenic Cardiomyopathy, Dipak Panigrahy, Vinay Penna, Kory Lavine, Et Al.

2020-Current year OA Pubs

We analyzed the role of pro- and anti-inflammatory eicosanoids in the pathogenesis of arrhythmogenic cardiomyopathy (ACM). Lipidomics revealed reduced levels of anti-inflammatory oxylipins in plasma and increased levels of pro-inflammatory eicosanoids in hearts of Dsg2

Rest And Rinse: Sleeping Rhythms Drive Brain Detox, Leon C D Smyth, Benjamin A Plog, Jonathan Kipnis

2020-Current year OA Pubs

Sleep is a major driver of waste clearance from the brain, but the mechanisms underpinning brain cleansing during sleep, which are also important for immunological functions, are poorly understood. Recent mouse work by Hauglund et al. shows how oscillatory surges in norepinephrine (NE) during sleep drive vascular pulsation and cerebrospinal fluid (CSF) movement to cleanse the brain.

The Current State Of Outcome Measurements After Peripheral Nerve Injury: A Systematic Review, Abigail G Carey-Ewend, Jake H Goldfarb, Zachary D Randall, David M Brogan, Christopher J Dy

2020-Current year OA Pubs

PURPOSE: The manner in which outcomes are reported after peripheral nerve injury (PNI) varies tremendously and often centers on surgeon-manual muscle testing. The purpose of our systematic review was to quantify the use of outcome measures after PNI in the contemporary literature (published in 2008 and beyond) and to evaluate which domains of recovery are assessed most frequently.

METHODS: With the assistance of a medical librarian, we performed a systematic review of the literature published in or after 2008 (to represent the last 15 years) for patients with upper-extremity PNI. We excluded articles with < 5 participants, minors, brachial plexus or digital nerve injuries, compressive neuropathies, or < 6 months of follow-up. Data were extracted to identify which outcome measures were used in each study, categorizing the outcome measures under the domains of motor, sensory, function, and pain.

RESULTS: Of the 4 outcome domains …

The Single-Cell Immune Profile Throughout Gestation And Its Potential Value For Identifying Women At Risk For Spontaneous Preterm Birth, Dorien Feyaerts, Maïgane Diop, Jose Galaz, Jakob F Einhaus, Petra C Arck, Anke Diemert, Virginia D Winn, Mana Parast, Cynthia Gyamfi-Bannerman, Jelmer R Prins, Nardhy Gomez-Lopez, Ina A Stelzer

2020-Current year OA Pubs

Precisely timed immune adaptations, observed in the maternal circulation, underpin the notion of an immune clock of human pregnancy that supports its successful progression and completion at delivery. This immune clock is divided into three immunological phases, with the first phase starting at the time of conception and implantation, shifting into the second phase that supports homeostasis and tolerance throughout pregnancy, and culminating in the last phase of labor and parturition. Disruptions of this immune clock are reported in pregnancy complications such as spontaneous preterm birth. However, our understanding of the immune clock preceding spontaneous preterm birth remains scattered. In …

Endothelial Cell Piezo1 Promotes Vascular Smooth Muscle Cell Differentiation On Large Arteries, Javier Abello, Ying Yin, Yonghui Zhao, Josh Maurer, Jihui Lee, Cherokee Bodell, Jahmiera Richee, Zarek Burton, Megan E Goeckel, Michelle Lin, Carmen M Halabi, Rajan Sah, Amber N Stratman, Et Al.

2020-Current year OA Pubs

Vascular stabilization is a mechanosensitive process, in part driven by blood flow. Here, we demonstrate the involvement of the mechanosensitive ion channel, Piezo1, in promoting arterial accumulation of vascular smooth muscle cells (vSMCs) during zebrafish development. Using a series of small molecule antagonists or agonists to temporally regulate Piezo1 activity, we identified a role for the Piezo1 channel in regulating klf2a, a blood flow responsive transcription factor, expression levels and altered targeting of vSMCs between arteries and veins. Increasing Piezo1 activity suppressed klf2a and increased vSMC association with the cardinal vein, while inhibition of Piezo1 activity increased klf2a levels and …

Acute Hyperglycemia Induces Podocyte Apoptosis By Monocyte Tnf-Α Release, A Process Attenuated By Vitamin D And Glp-1 Receptor Agonists, Rong M Zhang, Jisu Oh, Burton M Wice, Adriana Dusso, Carlos Bernal-Mizrachi

2020-Current year OA Pubs

Targeting optimal glycemic control based on hemoglobin A1c (A1c) values reduces but does not abolish the onset of diabetic kidney disease and its progression to chronic kidney disease (CKD). This suggests that factors other than the average glucose contribute to the residual risk. Vitamin D deficiency and frequent episodes of acute hyperglycemia (AH) are associated with the onset of albuminuria and CKD progression in diabetes. This study aimed to determine if moderate levels of AH harm podocytes directly or promote a pro-inflammatory monocyte/macrophage phenotype that leads to podocyte apoptosis, and whether vitamin D deficiency accelerates these processes. We found that …

Sacubitril/Valsartan Attenuates Inflammation And Myocardial Fibrosis In Takotsubo-Like Cardiomyopathy, Jiangying Kuang, Zhiyi Jia, Tou Kun Chong, Jian Chen, Kan Liu, Xin Wang, Zhaohua Li, Jing Zhang, Yanru Kong, Lin Deng, Martin Cadieras, Yuanyuan Sun, Rong Sun, Qinghua Lu, Yusheng Liu

2020-Current year OA Pubs

BACKGROUND: Takotsubo syndrome (TTS) primarily manifests as a cardiomyopathy induced by physical or emotional stress, remains a poorly understood condition with no established treatments. In this study, we investigated the potential of sacubitril/valsartan (sac/val) to increase the survival of TTS patients and reduce inflammation and myocardial fibrosis in experimental models.

AIM: This study aimed to evaluate whether sac/val could improve survival rates in TTS patients, mitigate cardiac remodeling in vivo, and explore its anti-inflammatory and antifibrotic mechanisms in vitro.

METHODS: Clinical cases from the Chinese Takotsubo syndrome (ChiTTS) registry were analyzed to assess patient survival rates. In addition, we used …

Genetically Engineered Brain Organoids Recapitulate Spatial And Developmental States Of Glioblastoma Progression, Matthew Ishahak, Rowland H Han, Devi Annamalai, Timothy Woodiwiss, Colin Mccornack, Ryan T Cleary, Patrick A Desouza, Xuan Qu, Sonika Dahiya, Albert H Kim, Jeffrey R Millman

2020-Current year OA Pubs

Glioblastoma (GBM) is an aggressive form of brain cancer that is highly resistant to therapy due to significant intra-tumoral heterogeneity. The lack of robust in vitro models to study early tumor progression has hindered the development of effective therapies. Here, this study develops engineered GBM organoids (eGBOs) harboring GBM subtype-specific oncogenic mutations to investigate the underlying transcriptional regulation of tumor progression. Single-cell and spatial transcriptomic analyses revealed that these mutations disrupt normal neurodevelopment gene regulatory networks resulting in changes in cellular composition and spatial organization. Upon xenotransplantation into immunodeficient mice, eGBOs form tumors that recapitulate the transcriptional and spatial landscape …

Norovirus Co-Opts Ninj1 For Selective Protein Secretion, Jaewon Song, Wandy L Beatty, Anthony Orvedahl, Et Al.

2020-Current year OA Pubs

Plasma membrane rupture by Ninjurin-1 (NINJ1) executes programmed cell death, releasing large cellular damage-associated molecular patterns (DAMPs). However, the regulation and selectivity of NINJ1-mediated DAMP release remain unexplored. Here, we uncover that murine norovirus (MNoV) strategically co-opts NINJ1 to selectively release the intracellular viral protein NS1, while NINJ1-mediated plasma membrane rupture simultaneously bulk-releases various cellular DAMPs. Host caspase-3 cleaves the precursor NS1/2, leading to NS1 secretion via an unconventional pathway. An unbiased CRISPR screen identifies NINJ1 as an essential factor for NS1 secretion. During infection, NINJ1 is recruited to the viral replication site, where it oligomerizes and forms speckled bodies, …

Myelin-Reactive Cd8+ T Cells Influence Conventional Dendritic Cell Subsets Towards A Mature And Regulatory Phenotype In Experimental Autoimmune Encephalomyelitis, Mohit Upadhye, Connor R Wilhelm, Kai J Rogers, Chakrapani Vemulawada, Nicholas Borcherding, Alexander W Boyden, Kevin L Legge, Nitin J Karandikar

2020-Current year OA Pubs

Multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system, is modeled in mice as experimental autoimmune encephalomyelitis (EAE). While CD4

Successful Treatment Of Pediatric Patient With Dravet Syndrome With Cenobamate: Case Report, Oleg V Lobanov, Mary Bertrand

2020-Current year OA Pubs

Dravet syndrome, also known as severe myoclonic epilepsy of infancy, is an epileptic encephalopathy characterized by severe epilepsy accompanied by impaired psychomotor and neurologic development. Onset is in the first year of life in apparently healthy infants. Seizures in Dravet syndrome are highly pharmacoresistant, and the SUDEP mortality rate is high. Here, we present the first case of the successful use of cenobamate in a pediatric patient (9-year-old female) with Dravet syndrome and pharmacoresistant epilepsy despite the prior use and failure of typical medications for Dravet syndrome, including fenfluramine, valproate, and clobazam, among others. At 6-month follow-up, the frequency of …

Accelerating Earlier Access To Anti-Tnf-Α Agents With Biosimilar Medicines In The Management Of Inflammatory Bowel Disease, Gionata Fiorino, Ashwin Ananthakrishnan, Russell D Cohen, Raymond K Cross, Parakkal Deepak, Francis A Farraye, Jonas Halfvarson, A Hillary Steinhart

2020-Current year OA Pubs

Data indicate that earlier initiation of anti-tumor necrosis factor alpha (anti-TNF-α) biologic medicines may prevent progression to irreversible bowel damage and improve outcomes for patients with inflammatory bowel disease (IBD), particularly Crohn's disease. However, the high cost of such therapies may restrict access and prevent timely treatment of IBD. Biosimilar anti-TNF-α medicines may represent a valuable opportunity for cost savings and optimized patient outcomes by improving access to advanced therapies and allowing earlier anti-TNF-α treatment initiation. Biosimilar anti-TNF-α medicines have been shown to offer consistent therapeutic outcomes to their reference medicines, yet despite entering the IBD treatment armamentarium over 10 …

Developing Evaluation Metrics To Measure The Us National Institute Of Health Plans To Enhance Diverse Perspectives: A Protocol For A Consensus-Based Study, Yulia A Levites Strekalova, Sanjay Jain, Pinaki Sarder

2020-Current year OA Pubs

INTRODUCTION: The diversity of participating investigators representing diverse disciplines, career stages, stakeholder groups, regions and types of institutions is essential for the success of large-scale research programmes. In 2021, the National Institutes of Health introduced a requirement for some of its large grants to include a separate section that describes the project's plan for enhancing diverse perspectives (PEDPs). Our project aims to develop consensus-based PEDP evaluation metrics and instruments that can be systematically and sustainably collected across the projects.

METHODS AND ANALYSIS: Evaluation work is organised into three objectives. First, shared knowledge about PEDP infrastructures, activities and outcomes will be …

Atp-Sensitive Potassium Channels Alter Glycolytic Flux To Modulate Cortical Activity And Sleep, Nicholas J Constantino, Caitlin M Carroll, Holden C Williams, Hemendra J Vekaria, Carla M Yuede, Kai Saito, Patrick W Sheehan, J Andy Snipes, Marcus E Raichle, Erik S Musiek, Patrick G Sullivan, Josh M Morganti, Lance A Johnson, Shannon L Macauley

2020-Current year OA Pubs

Metabolism plays a key role in the maintenance of sleep/wake states. Brain lactate fluctuations are a biomarker of sleep/wake transitions, where increased interstitial fluid (ISF) lactate levels are associated with wakefulness and decreased ISF lactate is required for sleep. ATP-sensitive potassium (K

Epidemiology And Genetic Determination Of Measures Of Peripheral Vascular Health In The Long Life Family Study, Deidra R Fricke, Ryan K Cvejkus, Emma Barinas-Mitchell, Mary F Feitosa, Joanne M Murabito, Sandeep Acharya, Michael R Brent, E Warwick Daw, Ryan L Minster, Joseph M Zmuda, Allison L Kuipers

2020-Current year OA Pubs

Peripheral artery disease (PAD) is a major contributor to morbidity in older adults. We aimed to determine genetic and non-genetic determinants of PAD and ankle-brachial index (ABI) in the Long Life Family Study (LLFS). 3006 individuals had ABI assessment, including 1090 probands (mean age 89), 1554 offspring (mean age 60) and 362 spousal controls (mean age 61). Outcomes include minimum of right and left ABIs and PAD (ABI <0.9). Stepwise regression determined independent significant non-genetic correlates of ABI and PAD. Genomewide association and linkage analyses were adjusted for age, sex, study center, significant principal components, and independent predictors. All analyses accounted for familial relatedness. Median ABI was 1.16 and 7.4% had PAD (18.2% probands, 1.0% offspring, 1.9% controls). Correlates of PAD and lower ABI included age, SBP, and creatinine (ABI only); BMI (ABI only), HDL (ABI only) and DBP (PAD only); and antihypertensive use, current smoking, female sex (ABI only), and high school noncompletion (ABI only). Genomewide linkage identified 1 region (15q12-q13) and association identified 3 single nucleotide polymorphisms (rs780213, rs12512857, rs79644420) of interest. In these families, PAD prevalence was low compared to other studies of older adults. We identified four genomic sites that may harbor variants associated with protection from PAD.