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Postoperative Bioactive Adrenomedullin Is Associated With The Onset Of Ards And Adverse Outcomes In Patients Undergoing Open Thoracoabdominal Aortic Surgery, Panagiotis Doukas, Oliver Hartmann, Jelle Frankort, Birte Arlt, Hanif Krabbe, Michael Johan Jacobs, Andreas Greiner, Jan Paul Frese, Alexander Gombert

Journal Articles

Cytokine-mediated systemic inflammation after open thoracoabdominal aortic aneurysm (TAAA) repairs plays a pivotal role in disrupting circulatory homeostasis, potentially leading to organ dysfunction. The bioactive form of adrenomedullin (bio-ADM) is a peptide hormone with immunomodulatory and vasomotor effects, making it a potential diagnostic agent in these cases. This retrospective, bicentric study, conducted between January 2019 and December 2022, recruited 36 elective open TAAA repair patients in two German centres. Serum and plasma samples were collected at multiple time points to measure bio-ADM levels. The primary objective was to evaluate the association of bio-ADM levels with the onset of acute respiratory …

Gut Microbiota, Blood Metabolites, And Left Ventricular Diastolic Dysfunction In Us Hispanics/Latinos, Kai Luo, Alkis Taryn, Eun-Hye Moon, Brandilyn A Peters, Scott D Solomon, Martha L Daviglus, Mayank M Kansal, Bharat Thyagarajan, Marc D Gellman, Jianwen Cai, Robert D Burk, Rob Knight, Robert C Kaplan, Susan Cheng, Carlos J Rodriguez, Qibin Qi, Bing Yu

Journal Articles

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is an important precursor of heart failure (HF), but little is known about its relationship with gut dysbiosis and microbial-related metabolites. By leveraging the multi-omics data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a study with population at high burden of LVDD, we aimed to characterize gut microbiota associated with LVDD and identify metabolite signatures of gut dysbiosis and incident LVDD.

RESULTS: We included up to 1996 Hispanic/Latino adults (mean age: 59.4 years; 67.1% female) with comprehensive echocardiography assessments, gut microbiome, and blood metabolome data. LVDD was defined through a composite criterion …

Case Of Human Orthohantavirus Infection, Michigan, Usa, 2021, Samuel M Goodfellow, Robert A Nofchissey, Dustin Arsnoe, Chunyan Ye, Seonghyeon Lee, Jieun Park, Won-Keun Kim, Kartik Chandran, Shannon L M Whitmer, John D Klena, Jonathan W Dyal, Trevor Shoemaker, Diana Riner, Mary Grace Stobierski, Kimberly Signs, Steven B Bradfute

Journal Articles

Orthohantaviruses cause hantavirus cardiopulmonary syndrome; most cases occur in the southwest region of the United States. We discuss a clinical case of orthohantavirus infection in a 65-year-old woman in Michigan and the phylogeographic link of partial viral fragments from the patient and rodents captured near the presumed site of infection.

Changes In Sleep Effort Mediate Insomnia Severity In Older Adults Following Online Cognitive Behavioural Therapy, Yvonne Kutzer, Lisa Whitehead, Eimear Quigley, Mandy Stanley

Research outputs 2022 to 2026

Background

To examine treatment mechanisms of digitally delivered cognitive behavioural therapy for insomnia (CBT-I), this study assessed the mediating effects of dysfunctional beliefs, hyperarousal, locus of control, self-efficacy, sleep effort, and safety behaviours on self-reported insomnia severity in older adults before and following the completion of a self-guided, online CBT-I program.

Methods

The baseline and follow-up measurements were completed by 62 older adults (55 female, 89%). This was a two-condition within-participant design. Mediation analysis using a parallel mediation model was conducted using the MEMORE macro for repeated measure designs.

Results

Out of all the included mediator variables, only a reduction …

Dopamine, Norepinephrine And Serotonin Participate Differently In Methylphenidate Action In Concomitant Behavioral And Ventral Tegmental Area, Locus Coeruleus And Dorsal Raphe Neuronal Study In Young Rats, Cruz Reyes-Vasquez, Zachary Jones, Bin Tang, Nachum Dafny

Journal Articles

Methylphenidate (MPD), known as Ritalin, is a psychostimulant used to treat children, adults, and the elderly. MPD exerts its effects through increasing concentrations of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in the synaptic cleft. Concomitant behavioral and neuronal recording from the ventral tegmental area (VTA), locus coeruleus (LC), and from the dorsal raphe (DR) nucleus, which are the sources of DA, NE, and 5-HT to the mesocorticolimbic circuit, were investigated following acute and repetitive (chronic) saline, 0.6, 2.5, or 10.0 mg/kg MPD. Animals received daily saline or MPD administration on experimental days 1 to 6 (ED1–6), followed by a …

Iron Overload Induces Cerebral Endothelial Senescence In Aged Mice And In Primary Culture In A Sex-Dependent Manner, Brian Noh, Maria Pilar Blasco-Conesa, Syed Mushfiqur Rahman, Sheelu Monga, Rodney Ritzel, Gary Guzman, Yun-Ju Lai, Bhanu Priya Ganesh, Akihiko Urayama, Louise D Mccullough, Jose Felix Moruno-Manchon

Journal Articles

Iron imbalance in the brain negatively affects brain function. With aging, iron levels increase in the brain and contribute to brain damage and neurological disorders. Changes in the cerebral vasculature with aging may enhance iron entry into the brain parenchyma, leading to iron overload and its deleterious consequences. Endothelial senescence has emerged as an important contributor to age-related changes in the cerebral vasculature. Evidence indicates that iron overload may induce senescence in cultured cell lines. Importantly, cells derived from female human and mice generally show enhanced senescence-associated phenotype, compared with males. Thus, we hypothesize that cerebral endothelial cells (CEC) derived …

The Effect Of Dexmedetomidine On The Mini-Cog Score And High-Mobility Group Box 1 Levels In Elderly Patients With Postoperative Neurocognitive Disorders Undergoing Orthopedic Surgery, Seung Hee Yoo, Mi Jin Jue, Yu-Hee Kim, Sooyoung Cho, Won-Joong Kim, Kye-Min Kim, Jong In Han, Heeseung Lee

Journal Articles

Dexmedetomidine prevents postoperative cognitive dysfunction by inhibiting high-mobility group box 1 (HMGB1), which acts as an inflammatory marker. This study investigated the HMGB1 levels and the cognitive function using a Mini-Cog© score in elderly patients undergoing orthopedic surgery with dexmedetomidine infusion. In total, 128 patients aged ≥ 65 years were analyzed. The patients received saline in the control group and dexmedetomidine in the dexmedetomidine group until the end of surgery. Blood sampling and the Mini-Cog© test were performed before the surgery and on postoperative days 1 and 3. The primary outcomes were the effect of dexmedetomidine on the HMGB1 levels …

Nasal Iodophor Antiseptic Vs Nasal Mupirocin Antibiotic In The Setting Of Chlorhexidine Bathing To Prevent Infections In Adult Icus: A Randomized Clinical Trial, Susan S Huang, Edward J Septimus, Ken Kleinman, Lauren T Heim, Julia A Moody, Taliser R Avery, Laura Mclean, Syma Rashid, Katherine Haffenreffer, Lauren Shimelman, Whitney Staub-Juergens, Caren Spencer-Smith, Selsebil Sljivo, Ed Rosen, Russell E Poland, Micaela H Coady, Chi Hyun Lee, Eunice J Blanchard, Kimberly Reddish, Mary K Hayden, Robert A Weinstein, Brandon Carver, Kimberly Smith, Jason Hickok, Karen Lolans, Nadia Khan, S Gwynn Sturdevant, Sujan C Reddy, John A Jernigan, Kenneth E Sands, Jonathan B Perlin, Richard Platt

Journal Articles

IMPORTANCE: Universal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization.

OBJECTIVE: To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing.

DESIGN, SETTING, AND PARTICIPANTS: Two-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) …

Using Co-Creation Focus Groups To Customise A Remote Multidomain Programme Designed To Increase Dementia Literacy, Walter Wittich, Edeltraut Kröger, Gabrielle Aubin, Asma Fadhlaoui, Nicole D Anderson, Nouha Ben Gaied, Inbal Itzhak, Sylvie Belleville

Journal Articles

Objectives

To adapt the content and functionalities of Brain Health PRO, a web-based multidomain program designed to increase dementia literacy, to the context and needs of users, providers and community organisations across Québec, Canada.

Design

Five consecutive qualitative co-creation focus group sessions 30–90 min in duration each, exploring potential barriers and facilitators to usability, accessibility, comprehensibility, participant recruitment and retention.

Setting

Virtual meetings.

Participants

A 15-member team based in Québec and Ontario, Canada, consisting of 9 researchers (including a graduate student and the project coordinator), representing occupational therapy, sensory rehabilitation, neuropsychology, psychology, health science and research methods, 3 informal caregivers …

Sexual Dimorphism In Bidirectional Sr-Mitochondria Crosstalk In Ventricular Cardiomyocytes, Richard T Clements, Radmila Terentyeva, Shanna Hamilton, Paul M L Janssen, Karim Roder, Benjamin Y Martin, Fruzsina Perger, Timothy G Schneider, Zuzana Nichtova, Anindhya S Das, Roland Veress, Beth S Lee, Do-Gyoon Kim, Gideon Koren, Matthew S Stratton, György Csordás, Federica Accornero, Andriy E Belevych, Sandor Gyorke, Dmitry Terentyev

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Calcium transfer into the mitochondrial matrix during sarcoplasmic reticulum (SR) Ca²⁺ release is essential to boost energy production in ventricular cardiomyocytes (VCMs) and match increased metabolic demand. Mitochondria from female hearts exhibit lower mito-[Ca²⁺] and produce less reactive oxygen species (ROS) compared to males, without change in respiration capacity. We hypothesized that in female VCMs, more efficient electron transport chain (ETC) organization into supercomplexes offsets the deficit in mito-Ca²⁺ accumulation, thereby reducing ROS production and stress-induced intracellular Ca²⁺ mishandling. Experiments using mitochondria-targeted biosensors confirmed lower mito-ROS and mito-[Ca²⁺] in female rat VCMs challenged …

Clinical Features And Shared Mechanisms Of Chronic Gastritis And Osteoporosis, Tao Han, Yili Zhang, Baoyu Qi, Ming Chen, Kai Sun, Xiaokuan Qin, Bowen Yang, He Yin, Aili Xu, Xu Wei, Liguo Zhu

Journal Articles

Chronic gastritis (CG) and osteoporosis (OP) are common and occult diseases in the elderly and the relationship of these two diseases have been increasingly exposed. We aimed to explore the clinical characteristics and shared mechanisms of CG patients combined with OP. In the cross-sectional study, all participants were selected from BEYOND study. The CG patients were included and classified into two groups, namely OP group and non-OP group. Univariable and multivariable logistic regression methods were used to evaluate the influencing factors. Furthermore, CG and OP-related genes were obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified …

Wellness In The Face Of Frailty Among Older Adults In First Nations Communities, Morgan Slater, Gabrielle Bruser, Roseanne Sutherland, Melissa K Andrew, Wayne Warry, Kristen M Jacklin, Jennifer D Walker

Journal Articles

OBJECTIVES: First Nations people report high levels of wellness despite high rates of chronic illness. Our goal was to understand the factors associated with wellness among First Nations adults in Ontario who were considered frail.

METHODS: Using the First Nations Regional Health Survey, we created a profile of First Nations adults (aged 45+) who were categorized as "frail" (weighted sample size = 8121). We used multivariate logistic regression to determine associations between wellness (as measured by self-reported physical, emotional, mental, and spiritual balance) and determinants of health.

RESULTS: Rates of reported wellness were high among those who were frail, ranging …

Patient With Multiple Genetically Distinct Thyroid Nodules Including Papillary Thyroid Carcinoma Harboring Novel Ywhag-Braf Fusion, Ruihe Lin, Zi-Xuan Wang, Elizabeth Cottrill, Nitika Badjatia, Stacey Gargano

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Next-generation sequencing (NGS) analysis of thyroid samples aids in risk stratification of cytologically indeterminate nodules and contributes to our understanding of molecular mechanisms in thyroid neoplasia. Several genes, including BRAF, RAS, and EIF1AX, are known to play a role in thyroid tumorigenesis. Here we report a case of papillary thyroid carcinoma (PTC) in which a single lesion harbored a novel YWHAG-BRAF fusion and EIF1AX mutation and displayed mixed morphological findings. The patient is a 74-year-old female with multiple incidentally discovered thyroid nodules, two of which were sampled by ultrasound-guided fine needle aspiration (FNA). Cytologic diagnosis for both nodules was suspicious …

68-Year Old Man With Progressive Weakness And Ventilator Dependent Respiratory Failure: A Case Report Of Sporadic Late Onset Nemaline Myopathy, P. Kirupaharan, Daniel Kramer, Alan Gandler, Lawrence C. Kenyon, Ross Summer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Neuromuscular pathologies must be considered when caring for patients with persistent or progressive respiratory failure. Pertinent disease states may involve skeletal muscles of respiration or associated neurologic structures including motor neurons, peripheral neurons and the neuromuscular junction. Diagnosis may require pulmonary function testing, neurophysiologic studies, imaging, and/or muscle biopsy.

Case presentation: A 68-year-old male was transferred to our intensive care unit (ICU) for management of ventilator dependent respiratory failure. Upon further historical review, he described gradually worsening gait instability and muscle weakness, which was previously attributed to vascular Parkinsonism in the setting of known cerebrovascular disease. Upon arrival to …

Effects Of The Tailored Activity Program (Tap) On Dementia-Related Symptoms, Health Events And Caregiver Wellbeing: A Randomized Controlled Trial, Laura N Gitlin, Katherine Marx, Catherine V. Piersol, Nancy A Hodgson, Jin Huang, David L Roth, Constantine Lyketsos

Department of Occupational Therapy Faculty Papers

BACKGROUND: People living with dementia (PLWD) and caregivers are adversely impacted by lack of meaningful activity leading to worse symptoms and impaired quality-of-life. There is a critical need to develop effective and well-tolerated treatments that mitigate clinical symptoms, engage PLWD and support caregiver wellbeing. We tested whether, compared to attention control, the Tailored Activity Program (TAP) reduced clinical symptoms and health-related events, and improved caregiver wellbeing, and if TAP activities were well-tolerated.

METHODS: We conducted a single-blind randomized controlled trial among 250 dyads recruited from Baltimore-Washington DC (2012-2016) with a dementia diagnosis and clinically significant agitation/aggression. Dyads were randomized to …

Long-Term Survival Of Older Patients Hospitalized For Covid-19. Do Clinical Characteristics Upon Admission Matter?, Michał Chojnicki, Agnieszka Neumann-Podczaska, Mikołaj Seostianin, Zofia Tomczak, Hamza Tariq, Jerzy Chudek, Sławomir Tobis, Iwona Mozer-Lisewska, Aleksandra Suwalska, Andrzej Tykarski, Piotr Merks, Sylwia Kropińska, Małgorzata Sobieszczańska, Frank Romanelli, Katarzyna Wieczorowska-Tobis

Pharmacy Practice and Science Faculty Publications

Older adults are particularly susceptible to COVID-19 in terms of both disease severity and risk of death. To compare clinical differences between older COVID-19 hospitalized survivors and non-survivors, we investigated variables influencing mortality in all older adults with COVID-19 hospitalized in Poznań, Poland, through the end of June 2020 (n = 322). In-hospital, post-discharge, and overall 180-day mortality were analyzed. Functional capacity prior to COVID-19 diagnosis was also documented. The mean age of subjects was 77.5 ± 10.0 years; among them, 191 were females. Ninety-five (29.5%) died during their hospitalization and an additional 30 (9.3%) during the post-discharge period …

Ten-Year Outcomes Of Uveal Melanoma Based On The Cancer Genome Atlas (Tcga) Classification In 1001 Cases., Carol L Shields, Eileen Mayro, Zeynep Bas, Philip W Dockery, Antonio Yaghy, Sara E. Lally, Arupa Ganguly, Jerry A Shields

Wills Eye Hospital Papers

Purpose: To understand the prognostic value of The Cancer Genome Atlas (TCGA) for uveal melanoma metastasis, using a simplified 4-category classification, based on tumor DNA.

Methods: A retrospective cohort study of 1001 eyes with uveal melanoma at a single center, categorized according to TCGA as Group A, B, C, or D (by fine-needle aspiration biopsy for DNA analysis), and treated with standard methods, was studied for melanoma-related metastasis at 5 and 10 years.

Results: Of 1001 eyes with uveal melanoma, the TCGA categories included Group A (n = 486, 49%), B (n = 141, 14%), C (n = 260, 26%), …

Point-Of-Care Lung Ultrasound For Covid-19: Findings And Prognostic Implications From 105 Consecutive Patients, Kosuke Yasukawa, Taro Minami, David R Boulware, Ayako Shimada, Ernest A Fischer

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: The prognostic value of point-of-care lung ultrasound has not been evaluated in a large cohort of patients with COVID-19 admitted to general medicine ward in the United States. The aim of this study was to describe lung ultrasound findings and their prognostic value in patients with COVID-19 admitted to internal medicine ward.

Method: This prospective observational study consecutively enrolled 105 hospitalized participants with COVID-19 at 2 tertiary care centers. Ultrasound was performed in 12 lung zones within 24 hours of admission. Findings were assessed relative to 4 outcomes: intensive care unit (ICU) need, need for intensive respiratory support, length …

Evaluation Of Ambulance Calls For Patients Over 65 Years Of Age In İzmir, Turkey: A Twoyear Retrospective Analysis, Ahu Pakdemi̇rli̇, Başak Bayram, Erkan Güvenç, Hülya Elli̇dokuz

Turkish Journal of Medical Sciences

Background/aim: Analysis of interventions for special patient groups is important for the planning of health services, especially emergency medical services. In this study, we aimed to evaluate emergency medical service (EMS) interventions for the elderly and determine the decisive factors affecting transfer to the hospital of EMS team over 2 years (2017 and 2018) in İzmir. Materials and methods: Records of 112 emergency calls that were made between 2017 and 2018 followed up with interventions for patients aged 65 years and older were obtained from the 112 system. The reasons for the calls, outcomes, possible diagnoses of the patients, differences …

Diagnostic Value Of Procalcitonin And C Reactive Protein For Infection And Sepsis Inelderly Patients, Çi̇ler Zi̇nci̇rci̇oğlu, Kazim Rollas, Işil Güldoğan, Aykut Saritaş, Hüseyi̇n Özkarakaş, Gürsel Ersan, Ni̇met Şenoğlu

Turkish Journal of Medical Sciences

Background/aim: Biomarkers are useful for diagnosing infection and sepsis in adults, but data are limited in elderly patients. Furthermore, clinical symptoms of infection in elderly patients are usually atypical or unclear. We aimed to assess the usefulness of PCT, CRP, and WBC in distinguishing elderly patients infected with sepsis from infected without sepsis and those with no-infection. We also aimed to find a cut-off value for diagnosing sepsis and infection without sepsis in elderly critically ill patients. Materials and methods: In this single-center and prospective observational study, patients older than 65 years were enrolled. Serum levels of PCT, CRP, and …

The Poststroke Peripheral Immune Response Is Differentially Regulated By Leukemia Inhibitory Factor In Aged Male And Female Rodents, Stephanie M. Davis, Lisa A. Collier, Sarah J. Messmer, Keith R. Pennypacker

Neurology Faculty Publications

Background. The goal of this study was to determine whether leukemia inhibitory factor (LIF) promotes anti-inflammatory activity after stroke in a sex-dependent manner. Methods. Aged (18-month-old) Sprague-Dawley rats of both sexes underwent sham surgery or permanent middle cerebral artery occlusion (MCAO). Animals received three doses of intravenous LIF (125 μg/kg) or PBS at 6, 24, and 48 h before euthanization at 72 h. Spleen weights were measured immediately following euthanization. Western blot was used to measure protein levels of CCL8, CD11b, CXCL9, CXCL10, IL-12 p40, IL-3, and the LIF receptor (LIFR) in spleen tissue. ELISA was used …

Elucidation Of The Mechanisms By Which Anesthetics Induce Blood-Brain Barrier Breakdown And Delirium In The Elderly, George A. Godsey Ii

Graduate School of Biomedical Sciences Theses and Dissertations

Delirium is a highly prevalent neuropsychiatric or neurocognitive disorder that presents a major problem to modern healthcare. Patients suffering from delirium normally have a worse prognosis, prolonged hospital stay, increased hospital cost, long-term cognitive impairment, and higher mortality rates. Many factors can predispose one to develop delirium, which makes treating this disorder a daunting task. Unfortunately, delirium is the most common psychiatric syndrome found in the hospital setting. In fact, a form of delirium known as postoperative delirium (POD) is one of the most common postoperative complications faced by elderly patients undergoing surgery.

POD is a major problem in modern …

Precision Medicine And Actionable Alterations In Lung Cancer: A Single Institution Experience, Isa Mambetsariev, Yingyu Wang, Chen Chen, Sorena Nadaf, Rebecca Pharaon, Jeremy Fricke, Idoroenyi Amanam, Arya Amini, Andrea Bild, Peiguo Chu, Loretta Erhunmwunsee, Jae Kim, Janet Munu, Raju Pillai, Dan Raz, Sagus Sampath, Lalit Vora, Fang Qiu, Lynette M. Smith, Surinder K. Batra, Erminia Massarelli, Marianna Koczywas, Karen Reckamp, Ravi Salgia

Journal Articles: Biochemistry & Molecular Biology

OBJECTIVES: Oncology has become more reliant on new testing methods and a greater use of electronic medical records, which provide a plethora of information available to physicians and researchers. However, to take advantage of vital clinical and research data for precision medicine, we must initially make an effort to create an infrastructure for the collection, storage, and utilization of this information with uniquely designed disease-specific registries that could support the collection of a large number of patients.

MATERIALS AND METHODS: In this study, we perform an in-depth analysis of a series of lung adenocarcinoma patients (n = 415) with genomic …

Psychometric Evaluation Of The Persian Version Of The Doloplus-2 (P-Doloplus-2) Scale In Elderly With Dementia, Mohammad Zare, Zahra Tagharrobi, Khadijeh Sharifi, Zahra Sooki, Javad Abolhasani

Turkish Journal of Medical Sciences

Background/aim: A scale for behavioural pain assessment is useful for the detection and determination of pain in the elderly with dementia. This study aimed to translate and evaluate the psychometric properties of Doloplus-2 in the elderly with dementia in Iran. Materials and methods: In this methodological study, after translation and evaluating the face and content validity of Doloplus-2, 100 elderly people were selected by the convenience sampling method in Kashan, 2018-2019. Exploratory factor analysis, convergent validity, and known-groups comparison were applied to determine construct validity. Reliability was also assessed through internal consistency, equivalence, and stability methods were used. The ceiling …

Chronic Obstructive Pulmonary Disease: Thoracic Ct Texture Analysis And Machine Learning To Predict Pulmonary Ventilation, Andrew Westcott, Dante P I Capaldi, David G Mccormack, Aaron D Ward, Aaron Fenster, Grace Parraga

Medical Biophysics Publications

Background Fixed airflow limitation and ventilation heterogeneity are common in chronic obstructive pulmonary disease (COPD). Conventional noncontrast CT provides airway and parenchymal measurements but cannot be used to directly determine lung function. Purpose To develop, train, and test a CT texture analysis and machine-learning algorithm to predict lung ventilation heterogeneity in participants with COPD. Materials and Methods In this prospective study (

The Effects Of Long-Term Benzodiazepine Use And Withdrawal In The Elderly, Lydia Suchecki, Hannah Granger, Jamie Kellner, Mary Ellen Hethcox

Pharmacy and Wellness Review

Benzodiazepines remain a commonly prescribed medication in the United States, and the high usage of this drug class is especially a concern in the elderly population for several reasons. First, elderly patients metabolize drugs differently, leading to varying responses. Age-related changes also have a significant impact on the effects of benzodiazepines. Second, elderly patients are more likely to be taking multiple centrally-acting drugs, which can further exacerbate negative effects. In regard to long-term benzodiazepine use, elderly patients experience an increased risk of cognitive impairment, motor vehicle accidents, decline in physical performance, falls and subsequent fractures, and sleep disturbances. Withdrawal is …

Rheumatoid Arthritis-Relevant Dna Methylation Changes Identified In Acpa-Positive Asymptomatic Individuals Using Methylome Capture Sequencing., Xiaojian Shao, Marie Hudson, Ines Colmegna, Celia M T Greenwood, Marvin J. Fritzler, Philip Awadalla, T Pastinen, Sasha Bernatsky

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To compare DNA methylation in subjects positive vs negative for anti-citrullinated protein antibodies (ACPA), a key serological marker of rheumatoid arthritis (RA) risk.

METHODS: With banked serum from a random subset (N = 3600) of a large general population cohort, we identified ACPA-positive samples and compared them to age- and sex-matched ACPA-negative controls. We used a custom-designed methylome panel to conduct targeted bisulfite sequencing of 5 million CpGs located in regulatory or hypomethylated regions of DNA from whole blood (red blood cell lysed). Using binomial regression models, we investigated the differentially methylated regions (DMRs) between ACPA-positive vs ACPA-negative subjects. …

Ucp1 Expression-Associated Gene Signatures Of Human Epicardial Adipose Tissue., Kanta Chechi, Jinchu Vijay, Pierre Voisine, Patrick Mathieu, Yohan Bossé, Andre Tchernof, Elin Grundberg, Denis Richard

Manuscripts, Articles, Book Chapters and Other Papers

Multiple reports of uncoupling protein 1 (UCP1) expression have established its presence in human epicardial adipose tissue (eAT). Its functional relevance to eAT, however, remains largely unknown. In a recent study, we reported that adrenergic stimulation of eAT was associated with downregulation of secreted proteins involved in oxidative stress-related and immune-related pathways. Here, we explored the UCP1-associated features of human eAT using next-generation deep sequencing. Paired biopsies of eAT, mediastinal adipose tissue (mAT), and subcutaneous adipose tissue (sAT) obtained from cardiac surgery patients, with specific criteria of high and low expression of UCP1 in eAT, were subjected to RNA sequencing. …

H3k27m Induces Defective Chromatin Spread Of Prc2-Mediated Repressive H3k27me2/Me3 And Is Essential For Glioma Tumorigenesis., Ashot S. Harutyunyan, Brian Krug, Haifen Chen, Simon Papillon-Cavanagh, Michele Zeinieh, Nicolas De Jay, Shriya Deshmukh, Carol C L Chen, Jad Belle, Leonie G. Mikael, Dylan M. Marchione, Rui Li, Hamid Nikbakht, Bo Hu, Gael Cagnone, Warren A. Cheung, Abdulshakour Mohammadnia, Denise Bechet, Damien Faury, Melissa K. Mcconechy, Manav Pathania, Siddhant U. Jain, Benjamin Ellezam, Alexander G. Weil, Alexandre Montpetit, Paolo Salomoni, Tomi Pastinen, Chao Lu, Peter W. Lewis, Benjamin A. Garcia, Claudia L. Kleinman, Nada Jabado, Jacek Majewski

Manuscripts, Articles, Book Chapters and Other Papers

Lys-27-Met mutations in histone 3 genes (H3K27M) characterize a subgroup of deadly gliomas and decrease genome-wide H3K27 trimethylation. Here we use primary H3K27M tumor lines and isogenic CRISPR-edited controls to assess H3K27M effects in vitro and in vivo. We find that whereas H3K27me3 and H3K27me2 are normally deposited by PRC2 across broad regions, their deposition is severely reduced in H3.3K27M cells. H3K27me3 is unable to spread from large unmethylated CpG islands, while H3K27me2 can be deposited outside these PRC2 high-affinity sites but to levels corresponding to H3K27me3 deposition in wild-type cells. Our findings indicate that PRC2 recruitment and propagation on …

Dissecting Features Of Epigenetic Variants Underlying Cardiometabolic Risk Using Full-Resolution Epigenome Profiling In Regulatory Elements., Fiona Allum, Åsa K. Hedman, Xiaojian Shao, Warren A. Cheung, Jinchu Vijay, Frédéric Guénard, Tony Kwan, Marie-Michelle Simon, Bing Ge, Cristiano Moura, Elodie Boulier, Lars Rönnblom, Sasha Bernatsky, Mark Lathrop, Mark I. Mccarthy, Panos Deloukas, André Tchernof, T Pastinen, Marie-Claude Vohl, Elin Grundberg

Manuscripts, Articles, Book Chapters and Other Papers

Sparse profiling of CpG methylation in blood by microarrays has identified epigenetic links to common diseases. Here we apply methylC-capture sequencing (MCC-Seq) in a clinical population of ~200 adipose tissue and matched blood samples (Ntotal~400), providing high-resolution methylation profiling (>1.3 M CpGs) at regulatory elements. We link methylation to cardiometabolic risk through associations to circulating plasma lipid levels and identify lipid-associated CpGs with unique localization patterns in regulatory elements. We show distinct features of tissue-specific versus tissue-independent lipid-linked regulatory regions by contrasting with parallel assessments in ~800 independent adipose tissue and blood samples from the general population. We follow-up …