Digital Commons Network^™

Assessment Of Plasma Amyloid-Β42/40 And Cognitive Decline Among Community-Dwelling Older Adults, Kelly Virecoulon Giudici, Philipe De Souto Barreto, Sophie Guyonnet, Yan Li, Randall J. Bateman, Bruno Vellas

Open Access Publications

Importance: Plasma measurement of amyloid-β (Aβ) peptides has been associated with cognitive function, but evidence of its ability to identify cognitive decline is still scarce.

Objective: To investigate the associations between plasma Aβ42/40 and cognitive decline over time among community-dwelling older adults with subjective memory concerns.

Design, Setting, and Participants: This multicenter cohort study used data from volunteers in the 5-year study Multidomain Alzheimer Preventive Trial (MAPT). Participants were aged 70 years or older and observed for a median (interquartile range) of 3.9 (2.0-4.0) years. Recruitment of participants started in May 2008 and ended in February 2011. Follow-up ended in …

Association Between Benzodiazepine Use With Or Without Opioid Use And All-Cause Mortality In The United States, 1999-2015, Kevin Y. Xu, Sarah M. Hartz, Jacob T. Borodovsky, Laura J. Bierut, Richard A. Grucza

Open Access Publications

Importance: Although overall rates of opioid use have been plateauing, coprescriptions of benzodiazepines and opioids have increased greatly in recent years. It is unknown whether this combination is an independent risk factor for all-cause mortality as opposed to being more frequently used by persons with a baseline elevated risk of death.

Objective: To evaluate whether benzodiazepine use, with or without opioid use, is associated with increased all-cause mortality relative to the use of low-risk antidepressants.

Design, Setting, and Participants: This retrospective cohort study used a large, nationally representative US data set (the National Health and Nutrition Examination Surveys [NHANES]) from …

Association Between Intake Of Energy And Macronutrients And Memory Impairment Severity In Us Older Adults, National Health And Nutrition Examination Survey 2011-2014, Qinran Liu, Jianjun Guo, Liang Hu, Nicola Veronese, Lee Smith, Lin Yang, Chao Cao

Open Access Publications

Without a cure, dementia affects about 50 million people worldwide. Understanding the effects of dietary habits, a key lifestyle behavior, on memory impairment is critical to inform early behavioral modification to delay further memory loss and progression to dementia. We examined the associations of total energy intake and energy intake from macronutrients with memory impairment among older US adults using data from the nationally representative National Health and Nutrition Examination Survey study 2011-2014. A total of 3623 participants aged ≥60 years were analyzed. Comparing to those with low total energy intake, individuals with high intake were more likely to have …

Using The Systemic Immune-Inflammation Index (Sii) As A Mid-Treatment Marker For Survival Among Patients With Stage-Iii Locally Advanced Non-Small Cell Lung Cancer (Nsclc), Tithi Biswas, Kylie H Kang, Rohin Gawdi, David Bajor, Mitchell Machtay, Charu Jindal, Jimmy T Efird

Open Access Publications

The Systemic Immune-Inflammation Index (SII) is an important marker of immune function, defined as the product of neutrophil-to-lymphocyte ratio (NLR) and platelet count (P). Higher baseline SII levels have been associated with improved survival in various types of cancers, including lung cancer. Data were obtained from PROCLAIM, a randomized phase III trial comparing two different chemotherapy regimens pemetrexed + cisplatin (PEM) vs. etoposide + cisplatin (ETO), in combination with radiotherapy (RT) for the treatment of stage III non-squamous non-small cell lung cancer (NSCLC). We aimed to determine if SII measured at the mid-treatment window for RT (weeks 3-4) is a …

Social Jetlag And Prostate Cancer Incidence In Alberta's Tomorrow Project: A Prospective Cohort Study, Liang Hu, Andrew Harper, Emily Heer, Jessica Mcneil, Chao Cao, Yikyung Park, Kevin Martell, Geoffrey Gotto, Grace Shen-Tu, Cheryl Peters, Darren Brenner, Lin Yang

Open Access Publications

We investigated the association of social jetlag (misalignment between the internal clock and socially required timing of activities) and prostate cancer incidence in a prospective cohort in Alberta, Canada. Data were collected from 7455 cancer-free men aged 35-69 years enrolled in Alberta's Tomorrow Project (ATP) from 2001-2007. In the 2008 survey, participants reported usual bed- and wake-times on weekdays and weekend days. Social jetlag was defined as the absolute difference in waking time between weekday and weekend days, and was categorized into three groups: 0-<1 h (from 0 to anything smaller than 1), 1-<2 h (from 1 to anything smaller than 2), and 2+ h. ATP facilitated data linkage with the Alberta Cancer Registry in June 2018 to determine incident prostate cancer cases (

Histone H3.3 Beyond Cancer: Germline Mutations In Histone 3 Family 3a And 3b Cause A Previously Unidentified Neurodegenerative Disorder In 46 Patients, Laura Bryant, Marcia C Willing, Linda Manwaring, Et Al

Open Access Publications

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (

Adolescent Alcohol, Nuts, And Fiber: Combined Effects On Benign Breast Disease Risk In Young Women, Catherine S. Berkey, Rulla M. Tamimi, Walter C. Willett, Bernard Rosner, Martha Hickey, Adetunji T. Toriola, A. Lindsay Frazier, Graham A. Colditz

Open Access Publications

No abstract provided.

Decreased Adipose Tissue Oxygenation Associates With Insulin Resistance In Individuals With Obesity, Vincenza Cifarelli, Scott C Beeman, Gordon I Smith, Jun Yoshino, Darya Morozov, Joseph W Beals, Brandon D Kayser, Jeramie D Watrous, Mohit Jain, Bruce W Patterson, Samuel Klein

Open Access Publications

BACKGROUNDData from studies conducted in rodent models have shown that decreased adipose tissue (AT) oxygenation is involved in the pathogenesis of obesity-induced insulin resistance. Here, we evaluated the potential influence of AT oxygenation on AT biology and insulin sensitivity in people.METHODSWe evaluated subcutaneous AT oxygen partial pressure (pO2); liver and whole-body insulin sensitivity; AT expression of genes and pathways involved in inflammation, fibrosis, and branched-chain amino acid (BCAA) catabolism; systemic markers of inflammation; and plasma BCAA concentrations, in 3 groups of participants that were rigorously stratified by adiposity and insulin sensitivity: metabolically healthy lean (MHL; n = 11), metabolically healthy …

From Stigma To Validation: A Qualitative Assessment Of A Novel National Program To Improve Retention Of Physician-Scientists With Caregiving Responsibilities, Rochelle D. Jones, Victoria J. Fraser, Et Al.

Open Access Publications

No abstract provided.

Endothelial Cell Cd36 Deficiency Prevents Normal Angiogenesis And Vascular Repair, Lara Bou Khzam, Ni-Huiping Son, Adam E Mullick, Nada A Abumrad, Ira J Goldberg

Open Access Publications

Endothelial cells (ECs) maintain vascular integrity and mediate vascular repair and angiogenesis, by which new blood vessels are formed from pre-existing blood vessels. Hyperglycemia has been shown to increase EC angiogenic potential. However, few studies have investigated effects of fatty acids (FAs) on EC angiogenesis. Cluster of differentiation 36 (CD36) is a FA transporter expressed by ECs, but its role in EC proliferation, migration, and angiogenesis is unknown. We sought to determine if circulating FAs regulate angiogenic function in a CD36-dependent manner. CD36-dependent effects of FAs on EC proliferation and migration of mouse heart ECs (MHECs) and lung ECs (MLECs) …

Roles Of The Vagina And The Vaginal Microbiota In Urinary Tract Infection: Evidence From Clinical Correlations And Experimental Models, Amanda L Lewis, Nicole M Gilbert

Open Access Publications

Mounting evidence indicates that the vagina can harbor uropathogenic bacteria. Here, we consider three roles played by the vagina and its bacterial inhabitants in urinary tract infection (UTI) and urinary health. First, the vagina can serve as a reservoir for

Lipin-1 Contributes To Il-4 Mediated Macrophage Polarization, Sunitha Chandran, Robert M Schilke, Cassidy M R Blackburn, Aila Yurochko, Rusella Mirza, Rona S Scott, Brian N Finck, Matthew D Woolard

Open Access Publications

Macrophage responses contribute to a diverse array of pathologies ranging from infectious disease to sterile inflammation. Polarization of macrophages determines their cellular function within biological processes. Lipin-1 is a phosphatidic acid phosphatase in which its enzymatic activity contributes to macrophage pro-inflammatory responses. Lipin-1 also possesses transcriptional co-regulator activity and whether this activity is required for macrophage polarization is unknown. Using mice that lack only lipin-1 enzymatic activity or both enzymatic and transcriptional coregulator activities from myeloid cells, we investigated the contribution of lipin-1 transcriptional co-regulator function toward macrophage wound healing polarization. Macrophages lacking both lipin-1 activities did not elicit IL-4 …

The Role Of Ct-Quantified Body Composition On Longitudinal Health-Related Quality Of Life In Colorectal Cancer Patients: The Colocare Study, Biljana Gigic, Graham A Colditz, Adetunji T Toriola, Et Al

Open Access Publications

BACKGROUND: Obesity, defined by body mass index (BMI), measured at colorectal cancer (CRC) diagnosis has been associated with postoperative complications and survival outcomes. However, BMI does not allow for a differentiation between fat and muscle mass. Computed tomography (CT)-defined body composition more accurately reflects different types of tissue and their associations with health-related quality of life (HRQoL) during the first year of disease, but this has not been investigated yet. We studied the role of visceral and subcutaneous fat area (VFA and SFA) and skeletal muscle mass (SMM) on longitudinally assessed HRQoL in CRC patients.

METHODS: A total of 138 …

Maternal Activation Of The Egfr Prevents Translocation Of Gut-Residing Pathogenic Escherichia Coli In A Model Of Late-Onset Neonatal Sepsis, Kathryn A. Knoop, Paige E. Coughlin, Alexandria N. Floyd, I. Malick Ndao, Carla Hall-Moore, Nurmohammad Shaikh, Andrew J. Gasparrini, Brigida Rusconi, Marilyn Escobedo, Misty Good, Barbara B. Warner, Phillip I. Tarr, Rodney D. Newberry

Open Access Publications

No abstract provided.

Use Of The Theory Of Planned Behavior Framework To Understand Breastfeeding Decision-Making Among Mothers Of Preterm Infants, Margaret G. Parker, Sunah S. Hwang, Emma S. Forbes, Bryanne N. Colvin, Kyria R. Brown, Eve R. Colson

Open Access Publications

No abstract provided.

Characterization Of A High-Resolution Breath Acetone Meter For Ketosis Monitoring, Donald J Suntrup Iii, Timothy V Ratto, Matt Ratto, James P Mccarter

Open Access Publications

Background: The ketone bodies beta-hydroxybutyrate (BHB) and acetone are endogenous products of fatty acid metabolism. Although ketone levels can be monitored by measuring either blood BHB or breath acetone, determining the precise correlation between these two measurement methods has been challenging. The purpose of this study is to characterize the performance of a novel portable breath acetone meter (PBAM) developed by Readout, Inc., to compare single versus multiple daily ketone measurements, and to compare breath acetone (BrAce) and blood BHB measurements.

Methods: We conducted a 14-day prospective observational cohort study of 21 subjects attempting to follow either a low-carbohydrate/ketogenic or …

Diet-Induced Metabolic Dysregulation In Female Mice Causes Osteopenia In Adult Offspring, Yu Shi, Jessica L. Saben, Guangxu He, Kelle H. Moley, Fanxin Long

Open Access Publications

Bone mass and quality in humans are controlled by numerous genetic and environmental factors that are not fully understood. Increasing evidence has indicated that maternal metabolic dysregulation impairs multiple physiological processes in the adult offspring, but a similar effect on bone health is yet to be established. Here, we have analyzed the bones of first-generation offspring from murine dams that present metabolic syndrome due to a high-fat and high-sugar (HF/HS) diet. Micro-CT analyses show that the long bones of HF/HS offspring possess lower cortical bone mass and weaker mechanical strength than normal, even though the trabecular bone is not affected. …

Quantitative Definition Of Neurobehavior, Vision, Hearing And Brain Volumes In Macaques Congenitally Exposed To Zika Virus, Michelle R. Koenig, Kevin Noguchi, Et Al.

Open Access Publications

Congenital Zika virus (ZIKV) exposure results in a spectrum of disease ranging from severe birth defects to delayed onset neurodevelopmental deficits. ZIKV-related neuropathogenesis, predictors of birth defects, and neurodevelopmental deficits are not well defined in people. Here we assess the methodological and statistical feasibility of a congenital ZIKV exposure macaque model for identifying infant neurobehavior and brain abnormalities that may underlie neurodevelopmental deficits. We inoculated five pregnant macaques with ZIKV and mock-inoculated one macaque in the first trimester. Following birth, growth, ocular structure/function, brain structure, hearing, histopathology, and neurobehavior were quantitatively assessed during the first week of life. We identified …

Comparison Of The Ekblom-Bak Submaximal Test To A Maximal Test In A Cohort Of Healthy Younger And Older Adults In The United States, Stephanie A Schultz, Jennifer Byers, Tammie L S Benzinger, Dominic Reeds, Andrei G Vlassenko, W Todd Cade, Manu S Goyal

Open Access Publications

Cardiorespiratory fitness (CRF) is routinely investigated in diverse populations, including in older adults of varying physical activity levels. Commonly performed maximal exercise testing protocols might be contraindicated and/or inadequate for older individuals who have physical or cognitive impairment. Moreover, early termination of an attempted maximal exercise test could result in underestimation of CRF in this population. The goal of the current study was to compare CRF estimates using the Ekblom-Bak (EB) submaximal exercise test - previously validated in a cohort of Scandinavian adults - versus a subsequent maximal exercise test in a diverse, Midwestern United States cohort. Fifteen generally healthy …

New Imaging Tools To Measure Nephron Number In Vivo: Opportunities For Developmental Nephrology, K M Bennett, E J Baldelomar, D Morozov, R L Chevalier, J R Charlton

Open Access Publications

The mammalian kidney is a complex organ, requiring the concerted function of up to millions of nephrons. The number of nephrons is constant after nephrogenesis during development, and nephron loss over a life span can lead to susceptibility to acute or chronic kidney disease. New technologies are under development to count individual nephrons in the kidney in vivo. This review outlines these technologies and highlights their relevance to studies of human renal development and disease.

Landscape Of Somatic Single Nucleotide Variants And Indels In Colorectal Cancer And Impact On Survival, Syed H. Zaidi, Yin Cao, Et Al.

Open Access Publications

No abstract provided.

Top Ten Tips Palliative Care Clinicians Should Know About Amyotrophic Lateral Sclerosis, Elyse A. Everett, Elizabeth Pedowitz, Samuel Maiser, Joss Cohen, Jessica Besbris, Ambereen K. Mehta, Luqi Chi, Christopher A. Jones

Open Access Publications

No abstract provided.

Assessing The Relationship Between District And State Policies And School Nutrition Promotion-Related Practices In The United States, Gabriella M Mcloughlin, Lindsey Turner, Julien Leider, Elizabeth Piekarz-Porter, Jamie F Chriqui

Open Access Publications

School environments are an optimal setting to promote healthy student diets, yet it is unclear what role state and district policies play in shaping school contexts. This study examined how state and district policies are associated with school-reported practices for promoting student participation in school lunch programs. School nutrition manager data were obtained from the School Nutrition and Meal Cost Study's (SNMCS) sample of 1210 schools in 46 states and the District of Columbia (DC) during school year 2014-2015. Relevant state laws and district policies were compiled and coded. Multivariable logistic and Poisson regressions, controlling for school characteristics, examined the …

Exposure To Covid-19 Patients Increases Physician Trainee Stress And Burnout, Thomas G. Kannampallil, Charles W. Goss, Bradley A. Evanoff, Jaime R. Strickland, Rebecca P. Mcalister, Jennifer Duncan

Open Access Publications

The coronavirus disease 2019 (COVID-19) pandemic has put considerable physical and emotional strain on frontline healthcare workers. Among frontline healthcare workers, physician trainees represent a unique group-functioning simultaneously as both learners and caregivers and experiencing considerable challenges during the pandemic. However, we have a limited understanding regarding the emotional effects and vulnerability experienced by trainees during the pandemic. We investigated the effects of trainee exposure to patients being tested for COVID-19 on their depression, anxiety, stress, burnout and professional fulfillment. All physician trainees at an academic medical center (n = 1375) were invited to participate in an online survey. We …

A Phase Ii Study Of Glembatumumab Vedotin For Metastatic Uveal Melanoma, Merve Hasanov, Matthew J Rioth, Kari Kendra, Leonel Hernandez-Aya, Richard W Joseph, Stephen Williamson, Sunandana Chandra, Keisuke Shirai, Christopher D Turner, Karl Lewis, Elizabeth Crowley, Jeffrey Moscow, Brett Carter, Sapna Patel

Open Access Publications

Glembatumumab vedotin (CDX-011, GV) is a fully human Immunoglobulin G2 monoclonal antibody directed against glycoprotein NMB coupled via a peptide linker to monomethyl auristatin E (MMAE), a potent cytotoxic microtubule inhibitor. This phase II study evaluated the overall response rate and safety of GV, glycoprotein NMB (GPNMB) expression, and survival in patients with metastatic uveal melanoma. Eligible patients with metastatic uveal melanoma who had not previously been treated with chemotherapy received GV 1.9 mg/kg every three weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included GPNMB expression, progression-free survival (PFS), overall survival (OS), and toxicity analysis. …

Cancer In Youth Living With Hiv (Ylwhiv): A Narrative Review Of The Access To Oncological Services Among Ylwhiv And The Role Of Economic Strengthening In Child Health, Ruth G N Katumba, Ozge Sensoy Bahar, Kimberly J Johnson, Fred M Ssewamala

Open Access Publications

Youth Living with HIV/AIDS (YLWHIV) have a higher risk of developing immunodeficiency related illnesses including certain cancers than their general population counterparts of the same age. This narrative review of current available literature describes factors associated with pediatric access to oncological services, and the role economic strengthening could play in improving health outcomes for this vulnerable population. Findings suggest that both HIV-infected and -uninfected children living in low and middle-income countries struggle with access and adherence to cancer treatment and care. Cost of treatment is a major barrier to access and adherence. Asset-building savings programs may increase financial security and …

Obesity Is A Risk Factor For Acute Promyelocytic Leukemia: Evidence From Population And Cross-Sectional Studies And Correlation With Flt3 Mutations And Polyunsaturated Fatty Acid Metabolism, Luca Mazzarella, Timothy J. Ley, Et Al.

Open Access Publications

No abstract provided.

Macrophage Secretion Of Mir-106b-5p Causes Renin-Dependent Hypertension, J. Oh, S. J. Matkovich, A. E. Riek, S. M. Bindom, J. S. Shao, R.D. Head, R. A. Barve, M. S. Sands, G. Carmeliet, P. Osei-Owusu, R.H. Knutsen, H. Zhang, K. J. Blumer, C. G. Nichols, R. P. Mecham, Á Baldán, B. A. Benitez, M. L. Sequeira-Lopez, R. A. Gomez, C. Bernal-Mizrachi

Open Access Publications

No abstract provided.

Lactate-Protechypoglycemia (Lph), Matthew L Goodwin, L Bruce Gladden, Maarten W N Nijsten

Open Access Publications

Here, we provide an overview of the concept of a lactate-protected hypoglycemia ("LPH"), originally proposed as lowering glucose while simultaneously increasing lactate concentration as a method by which tumors might be targeted. Central to this hypothesis is that lactate can act as a critical salvage fuel for the central nervous system, allowing for wide perturbations in whole body and central nervous system glucose concentrations. Further, many tumors exhibit "the Warburg" effect, consuming glucose and producing and exporting lactate despite adequate oxygenation. While some recent data have provided evidence for a "reverse-Warburg," where some tumors may preferentially consume lactate, many of …

Impact Of Functional Status On Outcomes Of Simultaneous Pancreas-Kidney Transplantation: Risks And Opportunities For Patient Benefit, Krista L. Lentine, Tarek Alhamad, Wisit Cheungpasitporn, Jane C. Tan, Su-Hsin Chang, Matthew Cooper, Darshana M. Dadhania, David A. Axelrod, Mark A. Schnitzler, Rosemary Ouseph, Franco H. Cabeza Rivera, Bertram L. Kasiske, Kenneth J. Woodside, Ronald F. Parsons

Open Access Publications

No abstract provided.