Digital Commons Network^™

Secukinumab Efficacy On Resolution Of Enthesitis In Psoriatic Arthritis: Pooled Analysis Of Two Phase 3 Studies., Laura C Coates, Johan K Wallman, Dennis Mcgonagle, Georg A Schett, Iain B Mcinnes, Philip Mease, Lawrence Rasouliyan, Erhard Quebe-Fehling, Darren L Asquith, Andreas E R Fasth, Luminita Pricop, Corine Gaillez

Articles, Abstracts, and Reports

BACKGROUND: Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies.

METHOD: Assessments of enthesitis through week 104 used the Leeds Enthesitis Index. These post hoc analyses included resolution of enthesitis count (EC = 0), median time to first resolution of enthesitis (Kaplan-Meϊer estimate), and shift analysis (as observed) of baseline EC (1, 2, or 3-6) to full resolution (FR), stable (similar or reduction …

Rapid And Sustained Response To Immune Checkpoint Inhibition In Cutaneous Squamous Cell Carcinoma After Allogenic Hematopoietic Cell Transplant For Sézary Syndrome, Karam Khaddour, Amy Musiek, Lynn A Cornelius, Farrokh Dehdashti, Peter Westervelt, Ryan Fields, George Ansstas

2010-2019 OA Pubs

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is not uncommon in association with indolent malignancies that were treated with prior radiotherapy and after allogenic bone marrow transplantation. On the other hand, cutaneous T-cell lymphoma (CTCL) is a subtype of non-Hodgkin's lymphoma which is characterized by an indolent course, with relative refractoriness to conventional chemotherapies and radiotherapy, and occasionally referred for allogeneic hematopoietic cell transplantation (allo-HCT). Recently, the use of immune checkpoint inhibitors has gained attention in the treatment of both cutaneous squamous cell carcinoma and hematological malignancies. However, many patients with hematological malignancies eventually undergo allo-HCT, raising the concern of potential …

Combination Of Pembrolizumab And Bcg Treatment After Endoscopic Ablation Of High-Risk Superficial Upper Urinary Tract Urothelial Carcinoma In Patients Not Candidates For Radical Nephroureterectomy: Protocol For Phase-Ii Study, Marcus L. Jamil, Mustafa Deebajah, Akshay Sood, Shaheen Alanee

Urology Articles

INTRODUCTION: The treatment standard for high-risk upper urinary tract urothelial carcinoma (UUTUC) is radical nephroureterectomy. However, some patients may be unfit or unwilling, and in such patients the available alternatives are suboptimal. Therapies targeting the programmed death (PD) pathway have shown promise in urothelial carcinom (UC). We designed the current study to determine the safety and efficacy of administering MK-3475 (a monoclonal antibody targeting interaction between PD-1 and its ligand) in combination with bacillus Calmette-Guerin (BCG) in high-risk non-muscle invasive UUTUC patients.

METHODS: This represents a single-centre phase-II efficacy study of MK-3475 therapy in combination with BCG for subjects, 18 …

Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito

Physiology Faculty Publications

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of …

Text-Mining Clinically Relevant Cancer Biomarkers For Curation Into The Civic Database, Jake Lever, Martin R Jones, Arpad M Danos, Kilannin Krysiak, Melika Bonakdar, Jasleen K Grewal, Luka Culibrk, Obi L Griffith, Malachi Griffith, Steven J M Jones

Open Access Publications

BACKGROUND: Precision oncology involves analysis of individual cancer samples to understand the genes and pathways involved in the development and progression of a cancer. To improve patient care, knowledge of diagnostic, prognostic, predisposing, and drug response markers is essential. Several knowledgebases have been created by different groups to collate evidence for these associations. These include the open-access Clinical Interpretation of Variants in Cancer (CIViC) knowledgebase. These databases rely on time-consuming manual curation from skilled experts who read and interpret the relevant biomedical literature.

METHODS: To aid in this curation and provide the greatest coverage for these databases, particularly CIViC, we …

Mifepristone Treatment In Four Cases Of Primary Bilateral Macronodular Adrenal Hyperplasia (Bmah)., Pejman Cohan, Honey E East, Sandi-Jo Galati, Jennifer U Mercado, Precious J Lim, Michele Lamerson, James J Smith, Anne L Peters, Kevin C J Yuen

Neurology

CONTEXT: Primary bilateral macronodular adrenal hyperplasia (BMAH) is a rare form of adrenal Cushing syndrome conventionally treated with adrenalectomy. Medical treatment is often reserved for patients not eligible for surgery. However, to date there have been few studies about the efficacy of mifepristone for the treatment of BMAH associated with hypercortisolism.

OBJECTIVE: To describe a series of patients with hypercortisolism due to BMAH treated with mifepristone from multiple medical practices.

DESIGN: We retrospectively assessed four patients treated with mifepristone for hypercortisolism due to BMAH who had either failed unilateral adrenalectomy, declined surgery, or were poor surgical candidates.

RESULTS: Mifepristone induced …

Perseverance, Faith And Stoicism: A Qualitative Study Of Medical Student Perspectives On Managing Fatigue, Taryn S Taylor, Alexandra L Raynard, Lorelei Lingard

Obstetrics & Gynaecology Publications

CONTEXT: Fatigue risk management (FRM) strategies offer a potential solution to the widespread problem of fatigued trainees in the clinical workplace. These strategies assume a shared perception that fatigue is hazardous. Despite the growing body of evidence suggesting that fatigue leads to burnout and medical errors, previous research suggests that residents perceive fatigue as a personal, surmountable burden rather than an occupational hazard. Before we can implement FRM, we need a better understanding of when and how such problematic notions of fatigue are adopted by medical trainees. Thus, we sought to explore how third-year medical students understand and manage the …

Production Of Physician Services Under Fee-For-Service And Blended Fee-For-Service: Evidence From Ontario, Canada., Nibene H Somé, Rose Anne Devlin, Nirav Mehta, Greg Zaric, Lihua Li, Salimah Shariff, Bachir Belhadji, Amardeep Thind, Amit Garg, Sisira Sarma

Epidemiology and Biostatistics Publications

We examine family physicians' responses to financial incentives for medical services in Ontario, Canada. We use administrative data covering 2003-2008, a period during which family physicians could choose between the traditional fee for service (FFS) and blended FFS known as the Family Health Group (FHG) model. Under FHG, FFS physicians are incentivized to provide comprehensive care and after-hours services. A two-stage estimation strategy teases out the impact of switching from FFS to FHG on service production. We account for the selection into FHG using a propensity score matching model, and then we use panel-data regression models to account for observed …

Healthcare Utilization Costs Of Emerging Adults With Mood And Anxiety Disorders In An Early Intervention Treatment Program Compared To A Matched Cohort, Ava A. John-Baptiste, Lihua Li, Wanrudee Isaranuwatchai, Elizabeth Osuch, Kelly K. Anderson

Epidemiology and Biostatistics Publications

AIM: The First Episode Mood and Anxiety Disorder Program (FEMAP) provides treatment to emerging adults with mood and anxiety disorders in an accessible, youth-friendly environment. We sought to investigate FEMAP's impact on the costs of care.

METHODS: We conducted a retrospective observational study of one-year health service costs using linked administrative datasets to compare emerging adults treated at FEMAP (FEMAP users) to propensity-score matched controls (non-users). Costs from the perspective of the Ontario Ministry of Health and Long-Term Care, included drug benefit claims, inpatient, physician and ambulatory care services. We used bootstrapping to perform unadjusted comparisons between FEMAP users and …

Engagement With Project Echo To Increase Medication-Assisted Treatment In Rural Primary Care, Julie Salvador, Snehal Bhatt, Rebecca Fowler, Jerrilyn Ritz, Regina James, Vanessa Jacobsohn, Heidi Rishel Brakey, Andrew L Sussman

Project ECHO Bibliography

OBJECTIVE: The purpose of this study was to understand the barriers and facilitators that affect engagement with Project ECHO (Extension for Community Healthcare Outcomes) to implement medication-assisted treatment (MAT) in primary care settings.

METHODS: A 12-session weekly curriculum was delivered to participating primary care providers and clinic staff (N=24 participants from 13 clinics). Participants completed attendance logs and a qualitative interview in order to identify factors that influence engagement in the ECHO sessions and the potential integration of MAT.

RESULTS: Primary care providers and staff valued the ECHO sessions, but overall attendance was low and variable. Participants generally valued the …

Antithrombin Population Pharmacokinetics In Pediatric Ventricular Assist Device Patients, Brady S Moffett, Marc Anders, Timothy Humlicek, Marianne Galati, Jun Teruya, Iki Adachi, Sebastian Tume

Library Staff Publications

OBJECTIVES: Describe the pharmacokinetics of antithrombin in pediatric patients undergoing ventricular assist device therapy and provide dosing recommendations for antithrombin in this population.

DESIGN: A retrospective population pharmacokinetic study was designed.

SETTING: Large tertiary care children's hospital Subject inclusion criteria consisted of less than 19 years old.

PATIENTS: Subjects less than 19 years old undergoing therapy with a HeartWare ventricular assist device (HeartWare, Framingham, MA) or Berlin EXCOR ventricular assist device (Berlin GmbH, Berlin, Germany), who received a dose of antithrombin with a postdose antithrombin activity level from January 1, 2011, to June 30, 2017.

INTERVENTIONS: Population pharmacokinetic analysis and …

Hccs And Hcas In Non-Cirrhotic Patients: What You See May Not Be Enough, Christina Ling, Sameen Khalid, David Martin, Joshua Hanson, Daniel Castresana, Denis Mccarthy

Pathology Research and Scholarship

Case 1 A previously healthy 16-year-old man was initially evaluated in the emergency department for traumatic injuries following a high-impact motor vehicle accident. He was a bodybuilder who used anabolic steroids. He denied abdominal or back pain. His physical examination was signifcant for a palpable liver edge. Routine laboratory tests including liver function tests were unremarkable. A computed tomographic (CT) scan showed an unsuspected mass in the right lobe of the liver. A subsequent triple-phase magnetic resonance imaging (MRI) scan of the abdomen showed a 15.1 × 15.0 × 10.8 cm mass in the right hepatic lobe that exhibited heterogeneous …

Microwave-Assisted And One-Step Synthesis Of Peg Passivated Fluorescent Carbon Dots From Gelatin As An Efficient Nanocarrier For Methotrexate Delivery, Nasser Arsalani, Parinaz Nezhad-Mokhtari, Esmaiel Jabbari

Faculty Publications

A green and simple process for preparing the polyethylene glycol passivated fluorescent carbon dots (CDs-PEG) have been studied by a microwave pyrolysis method, using gelatin and PEG as starting materials. This method is very effective for development of carbon-based quantum dots from gelatin with high quantum yield (QY). The synthesized CDs-PEG were found to emit blue photoluminescence (PL) with a maximum QY of 34%. At the following research, we investigated the effect of the presence of PEG on PL intensity, and the result showed that CDs-PEG becomes stronger PL properties than pure CDs from gelatin. The synthesized CDs-PEG were characterized …

Phenotypic And Genotypic Characterization Of Linezolid-Resistant Enterococcus Faecium From The Usa And Pakistan, Kate E Wardenburg, Robert F Potter, Alaric W D'Souza, Tahir Hussain, Meghan A Wallace, Saadia Andleeb, Carey-Ann D Burnham, Gautam Dantas

2010-2019 OA Pubs

OBJECTIVES: Linezolid is an important therapeutic option for the treatment of infections caused by VRE. Linezolid is a synthetic antimicrobial and resistance to this antimicrobial agent remains relatively rare. As a result, data on the comparative genomics of linezolid resistance determinants in Enterococcus faecium are relatively sparse.

METHODS: To address this knowledge gap in E. faecium, we deployed phenotypic antibiotic susceptibility testing and Illumina WGS on hospital surface (environmental) and clinical isolates from the USA and Pakistan.

RESULTS: We found complete concordance between isolate source country and mechanism of linezolid resistance, with all the US isolates possessing a 23S rRNA …

Impact Of Project Echo Models Of Medical Tele-Education: A Systematic Review, Ryan K. Mcbain, Jessica L. Sousa, Adam J. Rose, Sangita M. Baxi, Laura J. Faherty, Caroline Taplin, Andre Chappel, Shira H. Fischer

Project ECHO Bibliography

BACKGROUND: Extension for Community Healthcare Outcomes (ECHO) and related models of medical tele-education are rapidly expanding; however, their effectiveness remains unclear. This systematic review examines the effectiveness of ECHO and ECHO-like medical tele-education models of healthcare delivery in terms of improved provider- and patient-related outcomes.

METHODS: We searched English-language studies in PubMed, Embase, and PsycINFO databases from 1 January 2007 to 1 December 2018 as well as bibliography review. Two reviewers independently screened citations for peer-reviewed publications reporting provider- and/or patient-related outcomes of technology-enabled collaborative learning models that satisfied six criteria of the ECHO framework. Reviewers then independently abstracted data, …

A Consumer Neuroscience Study Of Conscious And Subconscious Destination Preference, Thomas Zoëga Ramsøy, Noela Michael, Ian Michael

All Works

© 2019, The Author(s). In studying consumer behaviors, the inclusion of neuroscience tools and methods is improving our understanding of preference formation and choice. But such responses are mostly related to the consumption of goods and services that meet an immediate need. Tourism represents a consumer behavior that is related to a more complex decision-making process, involving a stronger relationship with a future self, and choices typically being of a higher level of involvement and of a transformational type. The aim of this study was to test whether direct emotional and cognitive responses to travel destination would be indicative of …

Incense Burning Is Associated With Human Oral Microbiota Composition, Yvonne Vallès, Claire K. Inman, Brandilyn A. Peters, Laila Abdel Wareth, Abdishakur Abdulle, Habiba Alsafar, Fatme Al Anouti, Ayesha Al Dhaheri, Divya Galani, Muna Haji, Aisha Al Hamiz, Ayesha Al Hosani, Mohammed Al Houqani, Abdulla Aljunaibi, Marina Kazim, Tomas Kirchhoff, Wael Al Mahmeed, Fatma Al Maskari, Abdullah Alnaeemi, Naima Oumeziane, Ravichandran Ramasamy, Ann Marie Schmidt, Henri Vallès, Eiman Al Zaabi, Scott Sherman, Raghib Ali, Jiyoung Ahn, Richard B. Hayes

All Works

© 2019, The Author(s). Incense burning is common worldwide and produces environmental toxicants that may influence health; however, biologic effects have been little studied. In 303 Emirati adults, we tested the hypothesis that incense use is linked to compositional changes in the oral microbiota that can be potentially significant for health. The oral microbiota was assessed by amplification of the bacterial 16S rRNA gene from mouthwash samples. Frequency of incense use was ascertained through a questionnaire and examined in relation to overall oral microbiota composition (PERMANOVA analysis), and to specific taxon abundances, by negative binomial generalized linear models. We found …

Reports Of Injury Risks And Reasons For Choice Of Sleep Environments For Infants And Toddlers, N J Scheers, Chauncey Dayton, Mary Batcher, Bradley T Thach

Open Access Publications

OBJECTIVE: Compare mothers' reports of injuries for infants and toddlers sleeping with crib-bumpers/mesh-liners/no-barriers and reasons for these sleep environment choices.

METHODS: A cross-sectional survey of mothers subscribing to a parenting magazine and using crib bumpers (n = 224), mesh liners (n = 262), and no barriers (n = 842). Analyses of four possible injuries (face-covered, climb-out/fall, slat-entrapment, hit-head) including multivariate logistic regression adjusted for missing data/demographics and Chi squared analyses of reasons for mothers' choices.

RESULTS: Maternal reports of finding infants/toddlers with face covered had 3.5 times higher adjusted odds (aOR) for crib bumper versus mesh liner use. Breathing difficulties …

Temporal And Effort Cost Decision-Making In Healthy Individuals With Subclinical Psychotic Symptoms, Damiano Terenzi, Elena Mainetto, Mariapaola Barbato, Raffaella Ida Rumiati, Marilena Aiello

All Works

© 2019, The Author(s). The value people attribute to rewards is influenced both by the time and the effort required to obtain them. Impairments in these computations are described in patients with schizophrenia and appear associated with negative symptom severity. This study investigated whether deficits in temporal and effort cost computations can be observed in individuals with subclinical psychotic symptoms (PS) to determine if this dysfunction is already present in a potentially pre-psychotic period. Sixty participants, divided into three groups based on the severity of PS (high, medium and low), performed two temporal discounting tasks with food and money and …

Cognitive Decline Over Time In Patients With Systolic Heart Failure: Insights From Warcef., Tetz C Lee, Min Qian, Yutong Liu, Susan Graham, Douglas L Mann, Koki Nakanishi, John R Teerlink, Gregory Y H Lip, Ronald S. Freudenberger Md, Ralph L Sacco, Jay P Mohr, Arthur J Labovitz, Piotr Ponikowski, Dirk J Lok, Kenji Matsumoto, Conrado Estol, Stefan D Anker, Patrick M Pullicino, Richard Buchsbaum, Bruce Levin, John L P Thompson, Shunichi Homma, Marco R Di Tullio

Department of Medicine

OBJECTIVES: This study sought to characterize cognitive decline (CD) over time and its predictors in patients with systolic heart failure (HF).

BACKGROUND: Despite the high prevalence of CD and its impact on mortality, predictors of CD in HF have not been established.

METHODS: This study investigated CD in the WARCEF (Warfarin versus Aspirin in Reduced Ejection Fraction) trial, which performed yearly Mini-Mental State Examinations (MMSE) (higher scores indicate better cognitive function; e.g., normal score: 24 or higher). A longitudinal time-varying analysis was performed among pertinent covariates, including baseline MMSE and MMSE scores during follow-up, analyzed both as a continuous variable …

Results Of A Phase 1 Multicentre Investigation Of Dexmedetomidine Bolus And Infusion In Corrective Infant Cardiac Surgery, Athena F Zuppa, Susan C Nicolson, Nicole S Wilder, Juan C Ibla, Erin A Gottlieb, Kristin M Burns, Mario Stylianou, Felicia Trachtenberg, Hua Ni, Tera H Skeen, Dean B Andropoulos

Faculty, Staff and Students Publications

BACKGROUND: Dexmedetomidine (DEX) is increasingly used intraoperatively in infants undergoing cardiac surgery. This phase 1 multicentre study sought to: (i) determine the safety of DEX for cardiac surgery with cardiopulmonary bypass; (ii) determine the pharmacokinetics (PK) of DEX; (iii) create a PK model and dosing for steady-state DEX plasma levels; and (iv) validate the PK model and dosing.

METHODS: We included 122 neonates and infants (0-180 days) with D-transposition of the great arteries, ventricular septal defect, or tetralogy of Fallot. Dose escalation was used to generate NONMEM® PK modelling, and then validation was performed to achieve low (200-300 pg ml …

Standard Operating Procedure For Curation And Clinical Interpretation Of Variants In Cancer, Arpad M Danos, Kilannin Krysiak, Erica K Barnell, Adam C Coffman, Joshua F Mcmichael, Susanna Kiwala, Nicholas C Spies, Lana M Sheta, Shahil P Pema, Lynzey Kujan, Kaitlin A Clark, Amber Z Wollam, Alex H Wagner, Malachi Griffith, Obi L Griffith, Et Al

Open Access Publications

Manually curated variant knowledgebases and their associated knowledge models are serving an increasingly important role in distributing and interpreting variants in cancer. These knowledgebases vary in their level of public accessibility, and the complexity of the models used to capture clinical knowledge. CIViC (Clinical Interpretation of Variants in Cancer - www.civicdb.org) is a fully open, free-to-use cancer variant interpretation knowledgebase that incorporates highly detailed curation of evidence obtained from peer-reviewed publications and meeting abstracts, and currently holds over 6300 Evidence Items for over 2300 variants derived from over 400 genes. CIViC has seen increased adoption by, and also undertaken collaboration …

Mutations In Lamb2 Are Associated With Albuminuria And Optic Nerve Hypoplasia With Hypopituitarism, Mona Tahoun, Jennifer C Chandler, Emma Ashton, Scott Haston, Athia Hannan, Ji Soo Kim, Felipe D'Arco, D Bockenhauer, G Anderson, Meei-Hua Lin, Salah Marzouk, Marwa H Saied, Jeffrey H Miner, Mehul T Dattani, Aoife M Waters

Open Access Publications

CONTEXT: Mutations in LAMB2, encoding the basement membrane protein, laminin β2, are associated with an autosomal recessive disorder characterized by congenital nephrotic syndrome, ocular abnormalities, and neurodevelopmental delay (Pierson syndrome).

CASE DESCRIPTION: This report describes a 12-year-old boy with short stature, visual impairment, and developmental delay who presented with macroscopic hematuria and albuminuria. He had isolated growth hormone deficiency, optic nerve hypoplasia, and a small anterior pituitary with corpus callosum dysgenesis on his cranial magnetic resonance imaging, thereby supporting a diagnosis of optic nerve hypoplasia syndrome. Renal histopathology revealed focal segmental glomerulosclerosis. Using next-generation sequencing on a targeted gene panel …

Factors Affecting Acceptance Of At-Birth Point Of Care Hiv Testing Among Providers And Parents In Kenya: A Qualitative Study., Catherine Wexler, May Maloba, Melinda Brown, Natabhona Mabachi, Kathy Goggin, Brad Gautney, Beryne Odeny, Sarah Finocchario-Kessler

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: At-birth and point-of-care (POC) HIV testing are emerging strategies to streamline infant HIV diagnosis and expedite ART initiation for HIV-positive infants. The purpose of this qualitative study was to evaluate factors influencing the provision and acceptance of at-birth POC testing among both HIV care providers and parents of HIV-exposed infants in Kenya.

METHODS: We conducted semi-structured interviews with 26 HIV care providers and 35 parents of HIV-exposed infants (including 23 mothers, 6 fathers, and 3 mother-father pairs) at four study hospitals prior to POC implementation. An overview of best available evidence related to POC was presented to participants prior …

Three Genetic-Environmental Networks For Human Personality, Igor Zwir, Coral Del-Val, Dragan M Svrakic, Nigel Lester, Sandor Rozsa, Maribel Martinez, Daniel Mamah, C Charles Gu, C Robert Cloninger, Et Al

Open Access Publications

Phylogenetic, developmental, and brain-imaging studies suggest that human personality is the integrated expression of three major systems of learning and memory that regulate (1) associative conditioning, (2) intentionality, and (3) self-awareness. We have uncovered largely disjoint sets of genes regulating these dissociable learning processes in different clusters of people with (1) unregulated temperament profiles (i.e., associatively conditioned habits and emotional reactivity), (2) organized character profiles (i.e., intentional self-control of emotional conflicts and goals), and (3) creative character profiles (i.e., self-aware appraisal of values and theories), respectively. However, little is known about how these temperament and character components of personality are …

Metabolism Of Non-Enzymatically Derived Oxysterols: Clues From Sterol Metabolic Disorders, William J Griffiths, Eylan Yutuc, Jonas Abdel-Khalik, Peter J Crick, Thomas Hearn, Alison Dickson, Brian W Bigger, Teresa Hoi-Yee Wu, Anu Goenka, Arunabha Ghosh, Simon A. Jones, Douglas F Covey, Daniel S Ory, Yuqin Wang

Open Access Publications

Cholestane-3β,5α,6β-triol (3β,5α,6β-triol) is formed from cholestan-5,6-epoxide (5,6-EC) in a reaction catalysed by cholesterol epoxide hydrolase, following formation of 5,6-EC through free radical oxidation of cholesterol. 7-Oxocholesterol (7-OC) and 7β-hydroxycholesterol (7β-HC) can also be formed by free radical oxidation of cholesterol. Here we investigate how 3β,5α,6β-triol, 7-OC and 7β-HC are metabolised to bile acids. We show, by monitoring oxysterol metabolites in plasma samples rich in 3β,5α,6β-triol, 7-OC and 7β-HC, that these three oxysterols fall into novel branches of the acidic pathway of bile acid biosynthesis becoming (25R)26-hydroxylated then carboxylated, 24-hydroxylated and side-chain shortened to give the final products 3β,5α,6β-trihydroxycholanoic, 3β-hydroxy-7-oxochol-5-enoic and …

Gut Microbiota: From The Forgotten Organ To A Potential Key Player In The Pathology Of Alzheimer's Disease, Dong-Oh Seo, David M Holtzman

Open Access Publications

More than 300 years ago, Antony van Leewenhoeck first described observing single-celled microorganisms, which he termed "animalcules," examining his saliva under a microscope. Although the idea of the coexistence of microorganisms in our body is not new, we have only recently been able to investigate their ecological relationship to our body, with the development of high-throughput molecular techniques. The diverse microorganism communities residing in our guts are established and maintained by complex interactions among microorganisms and their host. Notably, their alteration has been implicated in influencing various diseases including neurological diseases. Alzheimer's disease (AD) is the most common cause of …

The Community Structure Of Functional Brain Networks Exhibits Scale-Specific Patterns Of Inter- And Intra-Subject Variability, Richard F Betzel, Maxwell A Bertolero, Evan M Gordon, Caterina Gratton, Nico U F Dosenbach, Danielle S Bassett

2010-2019 OA Pubs

The network organization of the human brain varies across individuals, changes with development and aging, and differs in disease. Discovering the major dimensions along which this variability is displayed remains a central goal of both neuroscience and clinical medicine. Such efforts can be usefully framed within the context of the brain's modular network organization, which can be assessed quantitatively using computational techniques and extended for the purposes of multi-scale analysis, dimensionality reduction, and biomarker generation. Although the concept of modularity and its utility in describing brain network organization is clear, principled methods for comparing multi-scale communities across individuals and time …

Associations Of Race And Ethnicity With Risk Of Developing Invasive Breast Cancer After Lobular Carcinoma In Situ, Vanessa Dania, Ying Liu, Foluso Ademuyiwa, Jason D Weber, Graham A Colditz

Open Access Publications

BACKGROUND: Lobular carcinoma in situ (LCIS) of the breast is a risk factor of developing invasive breast cancer. We evaluated the racial differences in the risks of subsequent invasive breast cancer following LCIS.

METHODS: We utilized data from the Surveillance, Epidemiology, and End Results registries to identify 18,835 women diagnosed with LCIS from 1990 to 2015. Cox proportional hazards regression was used to estimate race/ethnicity-associated hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of subsequent invasive breast cancer.

RESULTS: During a median follow-up of 90 months, 1567 patients developed invasive breast cancer. The 10-year incidence was 7.9% for Asians, …

Pharmacological Interventions For Painful Sickle Cell Vaso-Occlusive Crises In Adults., Tess E. Cooper, Ian R. Hambleton, Samir K. Ballas, Brydee A. Johnston, Philip J. Wiffen

Cardeza Foundation for Hematologic Research

BACKGROUND: Sickle cell disease (SCD) is a group of inherited disorders of haemoglobin (Hb) structure in a person who has inherited two mutant globin genes (one from each parent), at least one of which is always the sickle mutation. It is estimated that between 5% and 7% of the world's population are carriers of the mutant Hb gene, and SCD is the most commonly inherited blood disorder. SCD is characterized by distorted sickle-shaped red blood cells. Manifestations of the disease are attributed to either haemolysis (premature red cell destruction) or vaso-occlusion (obstruction of blood flow, the most common manifestation). Shortened …