Digital Commons Network^™

Aberrant Structural And Functional Connectivity And Neurodevelopmental Impairment In Preterm Children, Cynthia E Rogers, Rachel E Lean, Muriah D Wheelock, Christopher D Smyser

Open Access Publications

BACKGROUND: Despite advances in antenatal and neonatal care, preterm birth remains a leading cause of neurological disabilities in children. Infants born prematurely, particularly those delivered at the earliest gestational ages, commonly demonstrate increased rates of impairment across multiple neurodevelopmental domains. Indeed, the current literature establishes that preterm birth is a leading risk factor for cerebral palsy, is associated with executive function deficits, increases risk for impaired receptive and expressive language skills, and is linked with higher rates of co-occurring attention deficit hyperactivity disorder, anxiety, and autism spectrum disorders. These same infants also demonstrate elevated rates of aberrant cerebral structural and …

Association Of Alcohol Consumption After Development Of Heart Failure With Survival Among Older Adults In The Cardiovascular Health Study, Justin S. Sadhu, Eric Novak, Kenneth J. Mukamal, Jorge R. Kizer, Bruce M. Psaty, Phyllis K. Stein, David L. Brown

Open Access Publications

Importance: More than 1 million older adults develop heart failure annually. The association of alcohol consumption with survival among these individuals after diagnosis is unknown.

Objective: To determine whether alcohol use is associated with increased survival among older adults with incident heart failure.

Design, Setting, and Participants: This prospective cohort study included 5888 community-dwelling adults aged 65 years or older who were recruited to participate in the Cardiovascular Health Study between June 12, 1989, and June 1993, from 4 US sites. Of the total participants, 393 individuals had a new diagnosis of heart failure within the first 9 years of …

A Prospective Adaptive Utility Trial To Validate Performance Of A Novel Urine Exosome Gene Expression Assay To Predict High-Grade Prostate Cancer In Patients With Prostate-Specific Antigen 2-10ng/Ml At Initial Biopsy, James Mckiernan, Michael J Donovan, Eric Margolis, Alan Partin, Ballentine Carter, Gordon Brown, Phillipp Torkler, Mikkel Noerholm, Johan Skog, Neal Shore, Gerry Andriole, Ian Thompson, Peter Carroll

Open Access Publications

BACKGROUND: Discriminating indolent from clinically significant prostate cancer (PCa) in the initial biopsy setting remains an important issue. Prospectively evaluated diagnostic assays are necessary to ensure efficacy and clinical adoption.

OBJECTIVE: Performance and utility assessment of ExoDx Prostate (IntelliScore) (EPI) urine exosome gene expression assay versus standard clinical parameters for discriminating Grade Group (GG) ≥2 PCa from GG1 PCa and benign disease on initial biopsy.

DESIGN, SETTING, AND PARTICIPANTS: A two-phase adaptive clinical utility study (NCT03031418) comparing EPI results with biopsy outcomes in men, with age ≥50 yr and prostate-specific antigen (PSA) 2-10ng/ml, scheduled for initial prostate biopsy. After EPI …

New Advances In Amblyopia Therapy Ii: Refractive Therapies, Courtney L Kraus, Susan M Culican

Open Access Publications

The treatment of anisometropic or ametropic amblyopia has traditionally enjoyed a high treatment success rate. Early initiation and consistent use of spectacle correction can completely resolve amblyopia in a majority of patients. For those with anisometropic amblyopia that fail to improve with glasses wear alone, patching or atropine penalisation can lead to equalisation of visual acuity. However, successful treatment requires full-time compliance with refractive correction and this can be a challenge for a patient population that often has one eye with good acuity without correction. Other barriers for a select population with high anisometropic or ametropic amblyopia include rejection of …

Reengineering Workflow For Curation Of Dicom Datasets, William Bennett, Kirk Smith, Quasar Jarosz, Tracy Nolan, Walter Bosch

Open Access Publications

Reusable, publicly available data is a pillar of open science and rapid advancement of cancer imaging research. Sharing data from completed research studies not only saves research dollars required to collect data, but also helps insure that studies are both replicable and reproducible. The Cancer Imaging Archive (TCIA) is a global shared repository for imaging data related to cancer. Insuring the consistency, scientific utility, and anonymity of data stored in TCIA is of utmost importance. As the rate of submission to TCIA has been increasing, both in volume and complexity of DICOM objects stored, the process of curation of collections …

Unilateral, 3d Arm Movement Kinematics Are Encoded In Ipsilateral Human Cortex, David T. Bundy, Nicholas Szrama, Mrinal Pahwa, Eric C. Leuthardt

Open Access Publications

There is increasing evidence that the hemisphere ipsilateral to a moving limb plays a role in planning and executing movements. However, the exact relationship between cortical activity and ipsilateral limb movements is uncertain. We sought to determine whether 3D arm movement kinematics (speed, velocity, and position) could be decoded from cortical signals recorded from the hemisphere ipsilateral to the moving limb. By having invasively monitored patients perform unilateral reaches with each arm, we also compared the encoding of contralateral and ipsilateral limb kinematics from a single cortical hemisphere. In four motor-intact human patients (three male, one female) implanted with electrocorticography …

Association Between Health Insurance Literacy And Avoidance Of Health Care Services Owing To Cost, Renuka Tipirneni, Mary C. Politi, Jeffrey T. Kullgren, Edith C. Kieffer, Susan D. Goold, Aaron M. Scherer

Open Access Publications

Importance: Navigating health insurance and health care choices requires considerable health insurance literacy. Although recommended preventive services are exempt from out-of-pocket costs under the Affordable Care Act, many people may remain unaware of this provision and its effect on their required payment. Little is known about the association between individuals' health insurance literacy and their use of preventive or nonpreventive health care services.

Objective: To assess the association between health insurance literacy and self-reported avoidance of health care services owing to cost.

Design, Setting, and Participants: In this survey study, a US national, geographically diverse, nonprobability sample of 506 US …

Dietary Protein Restriction Reduces Circulating Vldl Triglyceride Levels Via Crebh-Apoa5-Dependent And -Independent Mechanisms, J Humberto Treviño-Villarreal, Valeria Tosti, Nicola Veronese, Beatrice Bertozzi, Arnold D Bullock, Robert S Figenshau, Gerald L Andriole, Luigi Fontana, Et Al

Open Access Publications

Hypertriglyceridemia is an independent risk factor for cardiovascular disease. Dietary interventions based on protein restriction (PR) reduce circulating triglycerides (TGs), but underlying mechanisms and clinical relevance remain unclear. Here, we show that 1 week of a protein-free diet without enforced calorie restriction significantly lowered circulating TGs in both lean and diet-induced obese mice. Mechanistically, the TG-lowering effect of PR was due, in part, to changes in very low-density lipoprotein (VLDL) metabolism both in liver and peripheral tissues. In the periphery, PR stimulated VLDL-TG consumption by increasing VLDL-bound APOA5 expression and promoting VLDL-TG hydrolysis and clearance from circulation. The PR-mediated increase …

Trex1 Is Expressed By Microglia In Normal Human Brain And Increases In Regions Affected By Ischemia, Parul H Kothari, Grant R Kolar, Joanna C Jen, Rula Hajj-Ali, Paula Bertram, Robert E Schmidt, John P Atkinson

Open Access Publications

BACKGROUND: Mutations in the three-prime repair exonuclease 1 (TREX1) gene have been associated with neurological diseases, including Retinal Vasculopathy with Cerebral Leukoencephalopathy (RVCL). However, the endogenous expression of TREX1 in human brain has not been studied.

METHODS: We produced a rabbit polyclonal antibody (pAb) to TREX1 to characterize TREX1 by Western blotting (WB) of cell lysates from normal controls and subjects carrying an RVCL frame-shift mutation. Dual staining was performed to determine cell types expressing TREX1 in human brain tissue. TREX1 distribution in human brain was further evaluated by immunohistochemical analyses of formalin-fixed, paraffin-embedded samples from normal controls and patients …

Mouse Models Of Preterm Birth: Suggested Assessment And Reporting Guidelines, Ronald Mccarthy, Carmel Martin-Fairey, Dorothy K. Sojka, Erik D. Herzog, Emily S. Jungheim, Molly J. Stout, Justin C. Fay, Mala Mahendroo, Jeff Reese, Jennifer L. Herington, Erin J. Plosa, Elaine L. Shelton, Sarah K. England

Open Access Publications

Preterm birth affects approximately 1 out of every 10 births in the United States, leading to high rates of mortality and long-term negative health consequences. To investigate the mechanisms leading to preterm birth so as to develop prevention strategies, researchers have developed numerous mouse models of preterm birth. However, the lack of standard definitions for preterm birth in mice limits our field's ability to compare models and make inferences about preterm birth in humans. In this review, we discuss numerous mouse preterm birth models, propose guidelines for experiments and reporting, and suggest markers that can be used to assess whether …

Teenage Exercise Is Associated With Earlier Symptom Onset In Dysferlinopathy: A Retrospective Cohort Study, Ursula R Moore, Matthew Harms, Alan Pestronk, Et Al

Open Access Publications

No abstract provided.

Adapting Crowdsourced Clinical Cancer Curation In Civic To The Clingen Minimum Variant Level Data Community-Driven Standards, Arpad M Danos, Alex H Wagner, Kilannin Krysiak, Erica K Barnell, Joshua F Mcmichael, Susanna Kiwala, Adam C Coffman, Lynzey Kujan, Malachi Griffith, Obi L Griffith, Et Al

Open Access Publications

Harmonization of cancer variant representation, efficient communication, and free distribution of clinical variant-associated knowledge are central problems that arise with increased usage of clinical next-generation sequencing. The Clinical Genome Resource (ClinGen) Somatic Working Group (WG) developed a minimal variant level data (MVLD) representation of cancer variants, and has an ongoing collaboration with Clinical Interpretations of Variants in Cancer (CIViC), an open-source platform supporting crowdsourced and expert-moderated cancer variant curation. Harmonization between MVLD and CIViC variant formats was assessed by formal field-by-field analysis. Adjustments to the CIViC format were made to harmonize with MVLD and support ClinGen Somatic WG curation activities, …

Genome-Wide Association Study Of Brain Amyloid Deposition As Measured By Pittsburgh Compound-B (Pib)-Pet Imaging, Qi Yan, Jorge L Del-Aguila, Carlos Cruchaga, Et Al

Open Access Publications

Deposition of amyloid plaques in the brain is one of the two main pathological hallmarks of Alzheimer's disease (AD). Amyloid positron emission tomography (PET) is a neuroimaging tool that selectively detects in vivo amyloid deposition in the brain and is a reliable endophenotype for AD that complements cerebrospinal fluid biomarkers with regional information. We measured in vivo amyloid deposition in the brains of ~1000 subjects from three collaborative AD centers and ADNI using

Uncovering The Complex Genetics Of Human Character, Igor Zwir, Dragan M Svrakic, Sandor Rozsa, Maribel Martinez, C Robert Cloninger, Et Al

Open Access Publications

Human personality is 30-60% heritable according to twin and adoption studies. Hundreds of genetic variants are expected to influence its complex development, but few have been identified. We used a machine learning method for genome-wide association studies (GWAS) to uncover complex genotypic-phenotypic networks and environmental interactions. The Temperament and Character Inventory (TCI) measured the self-regulatory components of personality critical for health (i.e., the character traits of self-directedness, cooperativeness, and self-transcendence). In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified five …

Uncovering The Complex Genetics Of Human Temperament, Igor Zwir, Javier Arnedo, Dragan M Svrakic, Sandor Rozsa, Maribel Martinez, C Robert Cloninger, Et Al

Open Access Publications

Experimental studies of learning suggest that human temperament may depend on the molecular mechanisms for associative conditioning, which are highly conserved in animals. The main genetic pathways for associative conditioning are known in experimental animals, but have not been identified in prior genome-wide association studies (GWAS) of human temperament. We used a data-driven machine learning method for GWAS to uncover the complex genotypic-phenotypic networks and environmental interactions related to human temperament. In a discovery sample of 2149 healthy Finns, we identified sets of single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (i.e., SNP sets) regardless of phenotype. Second, we identified …

Haptoglobin Improves Shock, Lung Injury, And Survival In Canine Pneumonia, Kenneth E. Remy, Irene Cortés-Puch, Steven B. Solomon, Junfeng Sun, Benjamin M. Pockros, Jing Feng, Juan J. Lertora, Roy R. Hantgan, Xiaohua Liu, Andreas Perlegas, H. Shaw Warren, Mark T. Gladwin, Daniel B. Kim-Shapiro, Harvey G. Klein, Charles Natanson

Open Access Publications

During the last half-century, numerous antiinflammatory agents were tested in dozens of clinical trials and have proven ineffective for treating septic shock. The observation in multiple studies that cell-free hemoglobin (CFH) levels are elevated during clinical sepsis and that the degree of increase correlates with higher mortality suggests an alternative approach. Human haptoglobin binds CFH with high affinity and, therefore, can potentially reduce iron availability and oxidative activity. CFH levels are elevated over approximately 24-48 hours in our antibiotic-treated canine model of S. aureus pneumonia that simulates the cardiovascular abnormalities of human septic shock. In this 96-hour model, resuscitative treatments, …

Impaired Monocyte Cholesterol Clearance Initiates Age-Related Retinal Degeneration And Vision Loss, Norimitsu Ban, Tae Jun Lee, Abdoulaye Sene, Mayur Choudhary, Michael Lekwuwa, Zhenyu Dong, Andrea Santeford, Jonathan B. Lin, Goldis Malek, Daniel S. Ory, Rajendra S. Apte

Open Access Publications

Advanced age-related macular degeneration (AMD), the leading cause of blindness among people over 50 years of age, is characterized by atrophic neurodegeneration or pathologic angiogenesis. Early AMD is characterized by extracellular cholesterol-rich deposits underneath the retinal pigment epithelium (RPE) called drusen or in the subretinal space called subretinal drusenoid deposits (SDD) that drive disease progression. However, mechanisms of drusen and SDD biogenesis remain poorly understood. Although human AMD is characterized by abnormalities in cholesterol homeostasis and shares phenotypic features with atherosclerosis, it is unclear whether systemic immunity or local tissue metabolism regulates this homeostasis. Here, we demonstrate that targeted deletion …

Letting Go: Conceptualizing Intervention De-Implementation In Public Health And Social Service Settings, Virginia R Mckay, Alexandra B Morshed, Ross C Brownson, Enola K Proctor, Beth Prusaczyk

Open Access Publications

The discontinuation of interventions that should be stopped, or de-implementation, has emerged as a novel line of inquiry within dissemination and implementation science. As this area grows in human services research, like public health and social work, theory is needed to help guide scientific endeavors. Given the infancy of de-implementation, this conceptual narrative provides a definition and criteria for determining if an intervention should be de-implemented. We identify three criteria for identifying interventions appropriate for de-implementation: (a) interventions that are not effective or harmful, (b) interventions that are not the most effective or efficient to provide, and (c) interventions that …

Curriculum For Neurogastroenterology And Motility Training: A Report From The Joint Anms-Esnm Task Force, C P Gyawali, Et Al

Open Access Publications

Although neurogastroenterology and motility (NGM) disorders are some of the most frequent disorders encountered by practicing gastroenterologists, a structured competency-based training curriculum developed by NGM experts is lacking. The American Neurogastroenterology and Motility Society (ANMS) and the European Society of Neurogastroenterology and Motility (ESNM) jointly evaluated the components of NGM training in North America and Europe. Eleven training domains were identified within NGM, consisting of functional gastrointestinal disorders, visceral hypersensitivity and pain pathways, motor disorders within anatomic areas (esophagus, stomach, small bowel and colon, anorectum), mucosal disorders (gastro-esophageal reflux disease, other mucosal disorders), consequences of systemic disease, consequences of therapy …

Cardiovascular Consequences Of Katp Overactivity In Cantu Syndrome, Yan Huang, Conor Mcclenaghan, Theresa M Harter, Kristina Hinman, Carmen M Halabi, Scot J Matkovich, Haixia Zhang, G Schuyler Brown, Robert P Mecham, Sarah K England, Attila Kovacs, Maria S Remedi, Colin G Nichols

Open Access Publications

Cantu syndrome (CS) is characterized by multiple vascular and cardiac abnormalities including vascular dilation and tortuosity, systemic hypotension, and cardiomegaly. The disorder is caused by gain-of-function (GOF) mutations in genes encoding pore-forming (Kir6.1, KCNJ8) and accessory (SUR2, ABCC9) ATP-sensitive potassium (KATP) channel subunits. However, there is little understanding of the link between molecular dysfunction and the complex pathophysiology observed, and there is no known treatment, in large part due to the lack of appropriate preclinical disease models in which to test therapies. Notably, expression of Kir6.1 and SUR2 does not fully overlap, and the relative contribution of KATP GOF in …

Soluble Inflammatory Mediators Induce Transcriptional Re-Organization That Is Independent Of Dna Methylation Changes In Cultured Human Chorionic Villous Trophoblasts., Kaiyu Jiang, Laiping Wong, Yanmin Chen, Xiaoyun Xing, Daofeng Li, Ting Wang, James N Jarvis

Open Access Publications

The studies proposed here were undertaken to test the hypothesis that, under specific circumstances (e.g., a strong enough inflammatory stimulus), genes that are repressed at the maternal-fetal interface via DNA methylation might be de-methylated, allowing either a maternal immune response to the semi-allogenic fetus or the onset of early labor. Chorionic trophoblasts (CT) were isolated from fetal membranes, followed by incubation with medium from LPS-activated PBMC or resting PBMC medium for 2 h. RNA and DNA were isolated from the cells for RNA-seq and DNA methylation studies. Two hrs after being exposed to conditioned medium from LPS-activated PBMC, CT showed …

Site-1 Protease Deficiency Causes Human Skeletal Dysplasia Due To Defective Inter-Organelle Protein Trafficking, Yuji Kondo, Debabrata Patra, Et Al

Open Access Publications

Site-1 protease (S1P), encoded by MBTPS1, is a serine protease in the Golgi. S1P regulates lipogenesis, endoplasmic reticulum (ER) function, and lysosome biogenesis in mice and in cultured cells. However, how S1P differentially regulates these diverse functions in humans has been unclear. In addition, no human disease with S1P deficiency has been identified. Here, we report a pediatric patient with an amorphic and a severely hypomorphic mutation in MBTPS1. The unique combination of these mutations results in a frequency of functional MBTPS1 transcripts of approximately 1%, a finding that is associated with skeletal dysplasia and elevated blood lysosomal enzymes. We …

Human Fibroblast And Stem Cell Resource From The Dominantly Inherited Alzheimer Network, Celeste M Karch, Damián Hernández, Jen-Chyong Wang, Jacob Marsh, Alex W Hewitt, Simon Hsu, Joanne Norton, Denise Levitch, Tamara Donahue, Wendy Sigurdson, Bernardino Ghetti, Martin Farlow, Jasmeer Chhatwal, Sarah Berman, Carlos Cruchaga, John C Morris, Randall J Bateman, Dominantly Inherited Alzheimer Network (Dian), Alice Pébay, Alison M Goate

Open Access Publications

BACKGROUND: Mutations in amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) cause autosomal dominant forms of Alzheimer disease (ADAD). More than 280 pathogenic mutations have been reported in APP, PSEN1, and PSEN2. However, understanding of the basic biological mechanisms that drive the disease are limited. The Dominantly Inherited Alzheimer Network (DIAN) is an international observational study of APP, PSEN1, and PSEN2 mutation carriers with the goal of determining the sequence of changes in presymptomatic mutation carriers who are destined to develop Alzheimer disease.

RESULTS: We generated a library of 98 dermal fibroblast lines from 42 ADAD families …

Plasticity Of Differentiated Cells In Wound Repair And Tumorigenesis, Part I: Stomach And Pancreas, Joseph Burclaff, Jason C Mills

Open Access Publications

For the last century or so, the mature, differentiated cells throughout the body have been regarded as largely inert with respect to their regenerative potential, yet recent research shows that they can become progenitor-like and re-enter the cell cycle. Indeed, we recently proposed that mature cells can become regenerative via a conserved set of molecular mechanisms ('paligenosis'), suggesting that a program for regeneration exists alongside programs for death (apoptosis) and division (mitosis). In two Reviews describing how emerging concepts of cellular plasticity are changing how the field views regeneration and tumorigenesis, we present the commonalities in the molecular and cellular …

Discovery And Validation Of Autosomal Dominant Alzheimer's Disease Mutations, Simon Hsu, Brian A Gordon, Russ Hornbeck, Joanne B Norton, Denise Levitch, Adia Louden, Ellen Ziegemeier, Robert Laforce, Jasmeer Chhatwal, Gregory S Day, Eric Mcdade, John C Morris, Anne M Fagan, Tammie L S Benzinger, Alison M Goate, Carlos Cruchaga, Randall J Bateman, Dominantly Inherited Alzheimer Network (Dian), Celeste M Karch

Open Access Publications

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease that is clinically characterized by progressive cognitive decline. Mutations in amyloid-β precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the pathogenic cause of autosomal dominant AD (ADAD). However, polymorphisms also exist within these genes.

METHODS: In order to distinguish polymorphisms from pathogenic mutations, the DIAN Expanded Registry has implemented an algorithm for determining ADAD pathogenicity using available information from multiple domains, including genetic, bioinformatic, clinical, imaging, and biofluid measures and in vitro analyses.

RESULTS: We propose that PSEN1 M84V, PSEN1 A396T, PSEN2 R284G, and APP T719N are likely pathogenic …

Hepatic Tristetraprolin Promotes Insulin Resistance Through Rna Destabilization Of Fgf21, Konrad T. Sawicki, Hsiang-Chun Chang, Jason S. Shapiro, Marina Bayeva, Adam De Jesus, Brian N. Finck, Jason A. Wertheim, Perry J. Blackshear, Hossein Ardehali

Open Access Publications

The role of posttranscriptional metabolic gene regulatory programs in diabetes is not well understood. Here, we show that the RNA-binding protein tristetraprolin (TTP) is reduced in the livers of diabetic mice and humans and is transcriptionally induced in response to insulin treatment in murine livers in vitro and in vivo. Liver-specific Ttp-KO (lsTtp-KO) mice challenged with high-fat diet (HFD) have improved glucose tolerance and peripheral insulin sensitivity compared with littermate controls. Analysis of secreted hepatic factors demonstrated that fibroblast growth factor 21 (FGF21) is posttranscriptionally repressed by TTP. Consistent with increased FGF21, lsTtp-KO mice fed HFD have increased brown fat …

Association Of Inferior Vena Cava Filter Placement For Venous Thromboembolic Disease And A Contraindication To Anticoagulation With 30-Day Mortality, Tyson E. Turner, Mohammed J. Saeed, Eric Novak, David L. Brown

Open Access Publications

Importance: Despite the absence of data from randomized clinical trials, professional societies recommend inferior vena cava (IVC) filters for patients with venous thromboembolic disease (VTE) and a contraindication to anticoagulation therapy. Prior observational studies of IVC filters have suggested a mortality benefit associated with IVC filter insertion but have often failed to adjust for immortal time bias, which is the time before IVC filter insertion, during which death can only occur in the control group.

Objective: To determine the association of IVC filter placement with 30-day mortality after adjustment for immortal time bias.

Design, Setting, and Participants: This comparative effectiveness, …

Epigenomics And Metabolomics Reveal The Mechanism Of The Apoa2-Saturated Fat Intake Interaction Affecting Obesity, Chao-Qiang Lai, Caren E Smith, Laurence D Parnell, Yu-Chi Lee, Dolores Corella, Paul Hopkins, Bertha A Hidalgo, Stella Aslibekyan, Michael A Province, Devin Absher, Donna K Arnett, Katherine L Tucker, Jose M Ordovas

Open Access Publications

Background: The putative functional variant -265T>C (rs5082) within the APOA2 promoter has shown consistent interactions with saturated fatty acid (SFA) intake to influence the risk of obesity.

Objective: The aim of this study was to implement an integrative approach to characterize the molecular basis of this interaction.

Design: We conducted an epigenome-wide scan on 80 participants carrying either the rs5082 CC or TT genotypes and consuming either a low-SFA (<22 g/d) or high-SFA diet (≥22 g/d), matched for age, sex, BMI, and diabetes status in the Boston Puerto Rican Health Study (BPRHS). We then validated the findings in selected participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study (n = 379) and the Framingham Heart Study (FHS) (n = 243). Transcription and metabolomics analyses were conducted to determine the relation between epigenetic status, APOA2 mRNA expression, and blood metabolites.

Results: In the BPRHS, we identified methylation site cg04436964 as exhibiting significant differences between CC and TT participants consuming a high-SFA diet, but not among those consuming low-SFA. Similar …

Longitudinal Decreases In Multiple Cerebrospinal Fluid Biomarkers Of Neuronal Injury In Symptomatic Late Onset Alzheimer's Disease, Courtney L Sutphen, Lena Mccue, Elizabeth M Herries, Chengjie Xiong, Jack H Ladenson, David M Holtzman, Anne M Fagan, Adni

Open Access Publications

INTRODUCTION: Individuals in early stages of Alzheimer's disease are a targeted population for secondary prevention trials aimed at preserving normal cognition. Understanding within-person biomarker(s) change over time is critical for trial enrollment and design.

METHODS: Longitudinal cerebrospinal fluid samples from the Alzheimer's Disease Neuroimaging Initiative were assayed for novel markers of neuronal/synaptic injury (visinin-like protein 1, Ng, and SNAP-25) and neuroinflammation (YKL-40) and compared with β amyloid 42, tau, and phospho-tau181. General linear mixed models were used to compare within-person rates of change in three clinical groups (cognitively normal, mild cognitive impairment, and Alzheimer's disease) further defined by β amyloid …

Decreasing Recurrent Bowel Obstructions, Improving Quality Of Life With Physiotherapy: Controlled Study, Amanda D Rice, Kimberley Patterson, Evette D Reed, Belinda F Wurn, Kristen Robles, Bernhard Klingenberg, Leonard B Weinstock, Janey S. A. Pratt, C. Richard King Iii, Lawrence J Wurn

Open Access Publications

AIM: To compare (1) quality of life and (2) rate of recurrent small bowel obstructions (SBO) for patients treated with novel manual physiotherapy

METHODS: One hundred and three subjects (age 19-89) with a history of recurrent adhesive SBO were treated with a manual physiotherapy called the Clear Passage Approach (CPA) which focused on decreasing adhesive crosslinking in abdominopelvic viscera. Pre- and post-therapy data measured recurring obstructions and quality of life, using a validated test sent 90 d after therapy. Results were compared to 136 untreated control subjects who underwent the same measurements for subjects who did not receive any therapy, …