Digital Commons Network^™

Cachexia, Chorea, And Pain In Chronic Nonbacterial Osteitis And Inflammatory Bowel Disease: A Case Report, Ladan Agharokh, Katherine Mamola, Andrew G Yu, Annette L Medina, Bhaskar Gurram, Julie Fuller, Jason Y Park, Weina Chen, Veena Rajaram, Matthew R Hammer, Jeff L Waugh

Faculty, Staff and Student Publications

BACKGROUND: Inflammatory bowel disease is an inflammatory disorder that primarily impacts the gastrointestinal tract, leading to malnutrition and chronic microscopic intestinal blood loss. Uncontrolled systemic inflammation can impact other parts of the body, known as extraintestinal manifestations. Up to 25% of patients with inflammatory bowel disease are reported to have these complications in their skin, joints, bones, eyes, liver, lung, and pancreas (Rogler et al. in Gastroenterology 161(4):1118-1132, 2021). Neurologic involvement as extraintestinal manifestations are less common, reported at 3-19%, including neuropathies, demyelination, and cerebrovascular events (Morís in World J Gastroenterol. 20(5):1228-1237, 2014).

CASE PRESENTATION: A 13-year-old Caucasian boy presented …

Architecture Of Androgen Receptor Pathways Amplifying Glucagon-Like Peptide-1 Insulinotropic Action In Male Pancreatic Β Cells, Weiwei Xu, M M Fahd Qadir, Daniela Nasteska, Paula Mota De Sa, Caroline M Gorvin, Manuel Blandino-Rosano, Charles R Evans, Thuong Ho, Evgeniy Potapenko, Rajakrishnan Veluthakal, Fiona B Ashford, Stavroula Bitsi, Jia Fan, Manika Bhondeley, Kejing Song, Venkata N Sure, Siva S V P Sakamuri, Lina Schiffer, Wandy Beatty, Rachael Wyatt, Daniel E Frigo, Xiaowen Liu, Prasad V Katakam, Wiebke Arlt, Jochen Buck, Lonny R Levin, Tony Hu, Jay Kolls, Charles F Burant, Alejandra Tomas, Matthew J Merrins, Debbie C Thurmond, Ernesto Bernal-Mizrachi, David J Hodson, Franck Mauvais-Jarvis

Faculty, Staff and Student Publications

Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male β cells. Testosterone cooperates with GLP-1 to enhance cAMP production at the plasma membrane and endosomes via: (1) increased mitochondrial production of CO

Architecture Of Androgen Receptor Pathways Amplifying Glucagon-Like Peptide-1 Insulinotropic Action In Male Pancreatic Β Cells, Weiwei Xu, Wandy Beatty, Et Al.

2020-Current year OA Pubs

Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male β cells. Testosterone cooperates with GLP-1 to enhance cAMP production at the plasma membrane and endosomes via: (1) increased mitochondrial production of CO

The Role Of Extracellular Heat Shock Proteins In Cardiovascular Diseases, Soumya Patnaik, Sriram Nathan, Biswajit Kar, Igor D Gregoric, Yi-Ping Li

Faculty, Staff and Student Publications

In the early 1960s, heat shock proteins (HSPs) were first identified as vital intracellular proteinaceous components that help in stress physiology and reprogram the cellular responses to enable the organism's survival. By the early 1990s, HSPs were detected in extracellular spaces and found to activate gamma-delta T-lymphocytes. Subsequent investigations identified their association with varied disease conditions, including autoimmune disorders, diabetes, cancer, hepatic, pancreatic, and renal disorders, and cachexia. In cardiology, extracellular HSPs play a definite, but still unclear, role in atherosclerosis, acute coronary syndromes, and heart failure. The possibility of HSP-targeted novel molecular therapeutics has generated much interest and hope …

Association Of Mutation And Expression Of The Brother Of The Regulator Of Imprinted Sites (Boris) Gene With Breast Cancer Progression, Mohammad Salman Akhtar, Naseem Akhter, Arshi Talat, Raed A. Alharbi, Abdulmajeed A. A Sindi, Faisal Klufah, Hanan E. Alyahyawi, Abdulmohsen Alruwetei, Abrar Ahmad, Mazin A. Zamzami, Svs Deo, Syed Akhtar Husain, Osama A. Badi, Mohammad Jahir Khan

Neurology Articles

INTRODUCTION: The BORIS, 11 zinc-finger transcription factors, is a member of the cancer-testis antigen (CTA) family. It is mapped to chromosome number 20q13.2 and this region is genetically linked to the early onset of breast cancer. The current study analyzed the correlation between BORIS mutations and the expression of the protein in breast cancer cases.

MATERIALS AND METHODS: A population-based study including a total of 155 breast cancer tissue samples and an equal number of normal adjacent tissues from Indian female breast cancer patients was carried out. Mutations of the BORIS gene were detected by polymerase chain reaction-single standard confirmation …

Impact Of The Covid-19 Pandemic On The Education And Procedural Volume Of Fellows In Critical Care Medicine – A Cross-Sectional Survey, Orlando Garner, Kanta Velamuri, Kristen Staggers, Andrea Barbara Braun

Faculty, Staff and Students Publications

BACKGROUND: The COVID-19 pandemic has changed the way medical education is delivered. The purpose of this study was to assess the impact of the COVID-19 pandemic on the education and procedural volume of critical care and pulmonary critical care fellows.

METHODS: We conducted a cross-sectional, internet-based, voluntary, anonymous, national survey of adult critical care fellows and academic attending physicians in critical care and pulmonary critical care fellowship programs in the United States between December 2020 and February 2021. Survey questions covered both didactic and non-didactic aspects of education and procedural volumes. Answers were ranked on a 5-point Likert scale. Survey …

The First Transcriptomic Atlas Of The Adult Lacrimal Gland Reveals Epithelial Complexity And Identifies Novel Progenitor Cells In Mice, Vanessa Delcroix, Olivier Mauduit, Hyun Soo Lee, Anastasiia Ivanova, Takeshi Umazume, Sarah M Knox, Cintia S De Paiva, Darlene A Dartt, Helen P Makarenkova

Faculty, Staff and Students Publications

The lacrimal gland (LG) secretes aqueous tears. Previous studies have provided insights into the cell lineage relationships during tissue morphogenesis. However, little is known about the cell types composing the adult LG and their progenitors. Using scRNAseq, we established the first comprehensive cell atlas of the adult mouse LG to investigate the cell hierarchy, its secretory repertoire, and the sex differences. Our analysis uncovered the complexity of the stromal landscape. Epithelium subclustering revealed myoepithelial cells, acinar subsets, and two novel acinar subpopulations: Tfrc^hi and Car6^hi cells. The ductal compartment contained Wfdc2+ multilayered ducts and an Ltf+ cluster formed …

Voluntary Wheel Running Promotes Resilience To The Behavioral Effects Of Unpredictable Chronic Mild Stress In Male And Female Mice., Elias Elias, Ariel Y Zhang, Abigail G White, Matthew J Pyle, Melissa T Manners

College of Science & Mathematics Departmental Research

Besides significant benefits to physical health, exercise promotes mental health, reduces symptoms of mental illness, and enhances psychological development. Exercise can offset the impact of chronic stress, which is a major precursor to the development of mental disorders. The effects of exercise on chronic stress-induced behaviors are contradictory in preclinical studies, primarily due to the lack of data and sex-specific investigations. We sought to evaluate the effects of exercise on chronic stress-induced behavioral changes in both male and female mice. Mice were subjected to an Unpredictable Chronic Mild Stress (UCMS) paradigm with accessibility to running wheels for 2 h daily. …

Multi-Stakeholder Perspectives Regarding Preferred Modalities For Mental Health Intervention Delivered In The Orthopedic Clinic: A Qualitative Analysis, Abby L Cheng, Ashwin J Leo, Ryan P Calfee, Christopher J Dy, Melissa A Armbrecht, Joanna Abraham

2020-Current year OA Pubs

BACKGROUND: Although depressive and anxious symptoms negatively impact musculoskeletal health and orthopedic outcomes, a gap remains in identifying modalities through which mental health intervention can realistically be delivered during orthopedic care. The purpose of this study was to understand orthopedic stakeholders' perceptions regarding the feasibility, acceptability, and usability of digital, printed, and in-person intervention modalities to address mental health as part of orthopedic care.

METHODS: This single-center, qualitative study was conducted within a tertiary care orthopedic department. Semi-structured interviews were conducted between January and May 2022. Two stakeholder groups were interviewed using a purposive sampling approach until thematic saturation was …

Streptococcus Cristatus Bacteremia In A Patient With Poor Oral Hygiene: A Case Report, Camilo Guzman, Adi Zaclli, John Molinari

Internal Medicine Articles

BACKGROUND: Streptococcus cristatus is a member of the Mitis streptococcus group. Like other members of this group, it resides on mucosal surfaces of the oral cavity. However, little is known about its ability to cause disease as there are only a handful of cases in the literature. Two of these cases involved infective endocarditis with significant complications. However, these cases involved additional microbes, limiting the inferences about the pathogenicity of Streptococcus cristatus.

CASE PRESENTATION: A 59-year-old African American male with end-stage cryptogenic cirrhosis and ascites presented with fatigue and confusion. A paracentesis was negative for spontaneous bacterial peritonitis, but two …

Traf4-Mediated Nonproteolytic Ubiquitination Of Androgen Receptor Promotes Castration-Resistant Prostate Cancer, Ramesh Singh, Huan Meng, Tao Shen, Lance Edward V Lumahan, Steven Nguyen, Hong Shen, Subhamoy Dasgupta, Li Qin, Dileep Karri, Bokai Zhu, Feng Yang, Cristian Coarfa, Bert W O'Malley, Ping Yi

Faculty, Staff and Students Publications

Castration-resistant prostate cancer (CRPC) poses a major clinical challenge with the androgen receptor (AR) remaining to be a critical oncogenic player. Several lines of evidence indicate that AR induces a distinct transcriptional program after androgen deprivation in CRPCs. However, the mechanism triggering AR binding to a distinct set of genomic loci in CRPC and how it promotes CRPC development remain unclear. We demonstrate here that atypical ubiquitination of AR mediated by an E3 ubiquitin ligase TRAF4 plays an important role in this process. TRAF4 is highly expressed in CRPCs and promotes CRPC development. It mediates K27-linked ubiquitination at the C-terminal …

Traf4-Mediated Nonproteolytic Ubiquitination Of Androgen Receptor Promotes Castration-Resistant Prostate Cancer, Ramesh Singh, Huan Meng, Tao Shen, Lance Edward V Lumahan, Steven Nguyen, Hong Shen, Subhamoy Dasgupta, Li Qin, Dileep Karri, Bokai Zhu, Feng Yang, Cristian Coarfa, Bert W O'Malley, Ping Yi

Faculty, Staff and Students Publications

Castration-resistant prostate cancer (CRPC) poses a major clinical challenge with the androgen receptor (AR) remaining to be a critical oncogenic player. Several lines of evidence indicate that AR induces a distinct transcriptional program after androgen deprivation in CRPCs. However, the mechanism triggering AR binding to a distinct set of genomic loci in CRPC and how it promotes CRPC development remain unclear. We demonstrate here that atypical ubiquitination of AR mediated by an E3 ubiquitin ligase TRAF4 plays an important role in this process. TRAF4 is highly expressed in CRPCs and promotes CRPC development. It mediates K27-linked ubiquitination at the C-terminal …

Functional Variants Identify Sex-Specific Genes And Pathways In Alzheimer’S Disease, Thomas Bourquard, Kwanghyuk Lee, Ismael Al-Ramahi, Minh Pham, Dillon Shapiro, Yashwanth Lagisetty, Shirin Soleimani, Samantha Mota, Kevin Wilhelm, Maryam Samieinasab, Young Won Kim, Eunna Huh, Jennifer Asmussen, Panagiotis Katsonis, Juan Botas, Olivier Lichtarge

Faculty, Staff and Students Publications

The incidence of Alzheimer's Disease in females is almost double that of males. To search for sex-specific gene associations, we build a machine learning approach focused on functionally impactful coding variants. This method can detect differences between sequenced cases and controls in small cohorts. In the Alzheimer's Disease Sequencing Project with mixed sexes, this approach identified genes enriched for immune response pathways. After sex-separation, genes become specifically enriched for stress-response pathways in male and cell-cycle pathways in female. These genes improve disease risk prediction in silico and modulate Drosophila neurodegeneration in vivo. Thus, a general approach for machine learning on …

Clinical Characteristics And Survival Of Pulmonary Arterial Hypertension With Or Without Interstitial Lung Disease In Systemic Sclerosis, Jessica L Fairley, Dylan Hansen, Laura Ross, Susanna Proudman, Joanne Sahhar, Gene-Siew Ngian, Jennifer Walker, Lauren V Host, Kathleen Morrisroe, Diane Apostolopoulous, Nava Ferdowsi, Michelle Wilson, Maryam Tabesh, Wendy Stevens, Mandana Nikpour

Faculty, Staff and Student Publications

Objectives

To describe the clinical phenotype and prognosis of people in the Australian Scleroderma (SSc) Cohort Study with pulmonary arterial hypertension (PAH) with or without interstitial lung disease (ILD).

Methods

Participants meeting ACR/EULAR criteria for SSc were divided into four mutually exclusive groups: those meeting criteria for PAH (PAH-only), ILD (ILD-only), concurrent PAH and ILD (PAH-ILD) or neither PAH nor ILD (SSc-only). Logistic or linear regression analyses were used for associations between clinical features, health-related quality of life (HRQoL) and physical function. Survival analysis was performed using Kaplan–Meier estimates and Cox-regression modelling.

Results

Of 1561 participants, 7% fulfilled criteria for …

Effects Of A Virtual Voice-Based Coach Delivering Problem-Solving Treatment On Emotional Distress And Brain Function: A Pilot Rct In Depression And Anxiety, Thomas Kannampallil, Et Al.

2020-Current year OA Pubs

Consumer-based voice assistants have the ability to deliver evidence-based treatment, but their therapeutic potential is largely unknown. In a pilot trial of a virtual voice-based coach, Lumen, delivering problem-solving treatment, adults with mild-to-moderate depression and/or anxiety were randomized to the Lumen intervention (n = 42) or waitlist control (n = 21). The main outcomes included changes in neural measures of emotional reactivity and cognitive control, and Hospital Anxiety and Depression Scale [HADS] symptom scores over 16 weeks. Participants were 37.8 years (SD = 12.4), 68% women, 25% Black, 24% Latino, and 11% Asian. Activation of the right dlPFC (neural region …

Immune Checkpoint B7-H3 Is A Therapeutic Vulnerability In Prostate Cancer Harboring Pten And Tp53 Deficiencies, Wei Shi, Yin Wang, Yuehui Zhao, Justin Jimin Kim, Haoyan Li, Chenling Meng, Feiyu Chen, Jie Zhang, Duncan H Mak, Vivien Van, Javier Leo, Brad St Croix, Ana Aparicio, Di Zhao

Faculty, Staff and Student Publications

Checkpoint immunotherapy has yielded meaningful responses across many cancers but has shown modest efficacy in advanced prostate cancer. B7 homolog 3 protein (B7-H3/CD276) is an immune checkpoint molecule and has emerged as a promising therapeutic target. However, much remains to be understood regarding B7-H3's role in cancer progression, predictive biomarkers for B7-H3-targeted therapy, and combinatorial strategies. Our multi-omics analyses identified B7-H3 as one of the most abundant immune checkpoints in prostate tumors containing PTEN and TP53 genetic inactivation. Here, we sought in vivo genetic evidence for, and mechanistic understanding of, the role of B7-H3 in PTEN/TP53-deficient prostate …

E-Health Literacy Scale, Patient Attitudes, Medication Adherence, And Internal Locus Of Control., Donrie J Purcell, Gesulla Cavanaugh, Kamilah Thomas-Purcell, Joshua Caballero, Drenna Waldrop, Victoria Ayala, Rosemary Davenport, Raymond L Ownby

HPD Articles

BACKGROUND: Health literacy is related to a variety of health outcomes, including disease control, health-related quality of life, and risk for death. Few studies have investigated the relation of electronic health literacy (e-health literacy) to outcomes or the mechanism by which they may be related.

METHODS: Secondary data were drawn from participants in a larger study on chronic disease self-management who were age 40 years and older, had at least one chronic health condition and a health literacy score of 8th grade or below on the validated short form of the Rapid Estimate of Adult Literacy in Medicine. Participants completed …

Phase Ib And Expansion Study Of Gemcitabine, Nab-Paclitaxel, And Ficlatuzumab In Patients With Metastatic Pancreatic Cancer, Kimberly Perez, Koushik Das, Et Al.

2020-Current year OA Pubs

BACKGROUND: In preclinical pancreatic ductal adenocarcinoma (PDAC) models, inhibition of hepatocyte growth factor (HGF) signaling using ficlatuzumab, a recombinant humanized anti-HGF antibody, and gemcitabine reduced tumor burden.

METHODS: Patients with previously untreated metastatic PDAC enrolled in a phase Ib dose escalation study with 3 + 3 design of 2 dose cohorts of ficlatuzumab 10 and 20 mg/kg administered intravenously every other week with gemcitabine 1000 mg/m2 and albumin-bound paclitaxel 125 mg/m2 given 3 weeks on and 1 week off. This was followed by an expansion phase at the maximally tolerated dose of the combination.

RESULTS: Twenty-six patients (sex, 12 male:14 …

Higher Dose Corticosteroids In Patients Admitted To Hospital With Covid-19 Who Are Hypoxic But Not Requiring Ventilatory Support (Recovery): A Randomised, Controlled, Open-Label, Platform Trial, Recovery Collaborative Group

Faculty, Staff and Student Publications

BACKGROUND: Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group.

METHODS: This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation

FINDINGS: Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen …

Higher Dose Corticosteroids In Patients Admitted To Hospital With Covid-19 Who Are Hypoxic But Not Requiring Ventilatory Support (Recovery): A Randomised, Controlled, Open-Label, Platform Trial, Recovery Collaborative Group

Faculty, Staff and Student Publications

BACKGROUND: Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group.

METHODS: This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation

FINDINGS: Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen …

Home-Based Tdcs For Apathy In Alzheimer’S Disease: A Protocol For A Randomized Double-Blinded Controlled Pilot Study, Antonio L Teixeira, Laís Bhering Martins, Thiago Macedo E Cordeiro, Lijin Jose, Robert Suchting, Holly M Holmes, Ron Acierno, Hyochol Ahn

Faculty, Staff and Student Publications

BACKGROUND: Apathy is among the most common behavioral symptoms in dementia and is consistently associated with negative outcomes in Alzheimer's disease (AD). Despite its prevalence and clinical relevance, available pharmacological and non-pharmacological strategies to treat apathy in AD have been marked, respectively, by potentially severe side effects and/or limited efficacy. Transcranial direct current stimulation (tDCS) is a relatively novel non-pharmacological method of neuromodulation with promising results. Compared to previous tDCS formats, recent technological advances have increased the portability of tDCS, which creates the potential for caregiver-administered, home use. Our study aims to evaluate the feasibility, safety, and efficacy of home-based …

Sex-Biased Immunological Processes Drive Hidradenitis Suppurativa, Kelly Z. Young, Peter Dimitrion, Li Zhou, Indra Adrianto, Qing-Sheng Mi

Dermatology Articles

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that can manifest with abscesses, sinus tracts, and scarring in the intertriginous areas of the body. HS is characterized by immune dysregulation, featuring elevated levels of myeloid cells, T helper (Th) cells, and pro-inflammatory cytokines, particularly those involved in Th1- and Th17-mediated immunity. In most epidemiological studies, HS shows a strong female sex bias, with reported female-to-male ratios estimated at roughly 3:1, suggesting that sex-related factors contribute to HS pathophysiology. In this article, we review the role of intrinsic and extrinsic factors that contribute to immunological differences between the sexes and …

The Correlation Between Traumatic Brain Injury And Incarceration Among Adult Males In The United States, Shadi Shams

Rowan-Virtua Research Day

The United States has one of the largest growing prison populations in the world. A large amount of social and economic resources go towards the cost and maintenance of correctional facilities each year. Additionally, the current correctional programs are insufficient in assisting inmates with getting back to society; especially those with traumatic brain injury (TBI) who often remain undiagnosed and are usually treated unfairly in the prison system instead of receiving the appropriate help. Prior scholarly work has shown that patients in the post-TBI stage are more likely to enter the judicial system. In the recent population-based cohort study, the …

Srsf1 Haploinsufficiency Is Responsible For A Syndromic Developmental Disorder Associated With Intellectual Disability, Elke Bogaert, Aurore Garde, Thierry Gautier, Kathleen Rooney, Yannis Duffourd, Pontus Leblanc, Emma Van Reempts, Frederic Tran Mau-Them, Ingrid M Wentzensen, Kit Sing Au, Kate Richardson, Hope Northrup, Vincent Gatinois, David Geneviève, Raymond J Louie, Michael J Lyons, Lone Walentin Laulund, Charlotte Brasch-Andersen, Trine Maxel Juul, Fatima El It, Nathalie Marle, Patrick Callier, Raissa Relator, Sadegheh Haghshenas, Haley Mcconkey, Jennifer Kerkhof, Claudia Cesario, Antonio Novelli, Nicola Brunetti-Pierri, Michele Pinelli, Perrine Pennamen, Sophie Naudion, Marine Legendre, Cécile Courdier, Aurelien Trimouille, Martine Doco Fenzy, Lynn Pais, Alison Yeung, Kimberly Nugent, Elizabeth R Roeder, Tadahiro Mitani, Jennifer E Posey, Daniel Calame, Hagith Yonath, Jill A Rosenfeld, Luciana Musante, Flavio Faletra, Francesca Montanari, Giovanna Sartor, Alessandra Vancini, Marco Seri, Claude Besmond, Karine Poirier, Laurence Hubert, Dimitri Hemelsoet, Arnold Munnich, James R Lupski, Christophe Philippe, Christel Thauvin-Robinet, Laurence Faivre, Bekim Sadikovic, Jérôme Govin, Bart Dermaut, Antonio Vitobello

Faculty, Staff and Students Publications

SRSF1 (also known as ASF/SF2) is a non-small nuclear ribonucleoprotein (non-snRNP) that belongs to the arginine/serine (R/S) domain family. It recognizes and binds to mRNA, regulating both constitutive and alternative splicing. The complete loss of this proto-oncogene in mice is embryonically lethal. Through international data sharing, we identified 17 individuals (10 females and 7 males) with a neurodevelopmental disorder (NDD) with heterozygous germline SRSF1 variants, mostly de novo, including three frameshift variants, three nonsense variants, seven missense variants, and two microdeletions within region 17q22 encompassing SRSF1. Only in one family, the de novo origin could not be established. All individuals …

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 …

Associations Between Cannabis Use, Polygenic Liability For Schizophrenia, And Cannabis-Related Experiences In A Sample Of Cannabis Users, Emma C Johnson, Sarah M C Colbert, Paul W Jeffries, Rebecca Tillman, Nicole R Karcher, Elliot C Nelson, Arpana Agrawal, Et Al.

2020-Current year OA Pubs

BACKGROUND AND HYPOTHESIS: Risk for cannabis use and schizophrenia is influenced in part by genetic factors, and there is evidence that genetic risk for schizophrenia is associated with subclinical psychotic-like experiences (PLEs). Few studies to date have examined whether genetic risk for schizophrenia is associated with cannabis-related PLEs.

STUDY DESIGN: We tested whether measures of cannabis involvement and polygenic risk scores (PRS) for schizophrenia were associated with self-reported cannabis-related experiences in a sample ascertained for alcohol use disorders (AUDs), the Collaborative Study on the Genetics of Alcoholism (COGA). We analyzed 4832 subjects (3128 of European ancestry and 1704 of African …

3-Year Outcomes After Transcatheter Or Surgical Aortic Valve Replacement In Low-Risk Patients With Aortic Stenosis., John K Forrest, G Michael Deeb, Steven J Yakubov, Hemal Gada, Mubashir A Mumtaz, Basel Ramlawi, Tanvir Bajwa, Paul S Teirstein, Michael Defrain, Murali Muppala, Bruce J Rutkin, Atul Chawla, Bart Jenson, Stanley J Chetcuti, Robert C Stoler, Marie-France Poulin, Kamal Khabbaz, Melissa Levack, Kashish Goel, Didier Tchétché, Ka Yan Lam, Pim A L Tonino, Saki Ito, Jae K Oh, Jian Huang, Jeffrey J Popma, Neal Kleiman, Michael J Reardon

Heart and Vascular Articles

BACKGROUND: Randomized data comparing outcomes of transcatheter aortic valve replacement (TAVR) with surgery in low-surgical risk patients at time points beyond 2 years is limited. This presents an unknown for physicians striving to educate patients as part of a shared decision-making process.

OBJECTIVES: The authors evaluated 3-year clinical and echocardiographic outcomes from the Evolut Low Risk trial.

METHODS: Low-risk patients were randomized to TAVR with a self-expanding, supra-annular valve or surgery. The primary endpoint of all-cause mortality or disabling stroke and several secondary endpoints were assessed at 3 years.

RESULTS: There were 1,414 attempted implantations (730 TAVR; 684 surgery). Patients …

Association Of Mitochondrial Dna Copy Number With Brain Mri Markers And Cognitive Function: A Meta-Analysis Of Community-Based Cohorts, Yuankai Zhang, Xue Liu, Kerri L Wiggins, Nuzulul Kurniansyah, Xiuqing Guo, Amanda L Rodrigue, Wei Zhao, Lisa R Yanek, Scott M Ratliff, Achilleas Pitsillides, Juan Sebastian Aguirre Patiño, Tamar Sofer, Dan E Arking, Thomas R Austin, Alexa S Beiser, John Blangero, Eric Boerwinkle, Jan Bressler, Joanne E Curran, Lifang Hou, Timothy M Hughes, Sharon L R Kardia, Lenore J Launer, Daniel Levy, Thomas H Mosley, Ilya M Nasrallah, Stephen S Rich, Jerome I Rotter, Sudha Seshadri, Wassim Tarraf, Kevin A González, Vasan Ramachandran, Kristine Yaffe, Paul A Nyquist, Bruce M Psaty, Charles S Decarli, Jennifer A Smith, David C Glahn, Hector M González, Joshua C Bis, Myriam Fornage, Susan R Heckbert, Annette L Fitzpatrick, Chunyu Liu, Claudia L Satizabal

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Previous studies suggest that lower mitochondrial DNA (mtDNA) copy number (CN) is associated with neurodegenerative diseases. However, whether mtDNA CN in whole blood is related to endophenotypes of Alzheimer disease (AD) and AD-related dementia (AD/ADRD) needs further investigation. We assessed the association of mtDNA CN with cognitive function and MRI measures in community-based samples of middle-aged to older adults.

METHODS: We included dementia-free participants from 9 diverse community-based cohorts with whole-genome sequencing in the Trans-Omics for Precision Medicine (TOPMed) program. Circulating mtDNA CN was estimated as twice the ratio of the average coverage of mtDNA to nuclear …

Variability And Magnitude Of Brain Glutamate Levels In Schizophrenia: A Meta And Mega-Analysis., Kate Merritt, Robert A Mccutcheon, André Aleman, Sarah Ashley, Katherine Beck, Wolfgang Block, Oswald J N Bloemen, Faith Borgan, Christiana Boules, Juan R Bustillo, Aristides A Capizzano, Jennifer M Coughlin, Anthony David, Camilo De La Fuente-Sandoval, Arsime Demjaha, Kara Dempster, Kim Q Do, Fei Du, Peter Falkai, Beata Galińska-Skok, Jürgen Gallinat, Charles Gasparovic, Cedric E Ginestet, Naoki Goto, Ariel Graff-Guerrero, Beng-Choon Ho, Oliver Howes, Sameer Jauhar, Peter Jeon, Tadafumi Kato, Charles A Kaufmann, Lawrence S Kegeles, Matcheri S Keshavan, Sang-Young Kim, Bridget King, Hiroshi Kunugi, J Lauriello, Pablo León-Ortiz, Edith Liemburg, Meghan E Mcilwain, Gemma Modinos, Elias Mouchlianitis, Jun Nakamura, Igor Nenadic, Dost Öngür, Miho Ota, Lena Palaniyappan, Christos Pantelis, Tulsi Patel, Eric Plitman, Sotirios Posporelis, Scot E Purdon, Jürgen R Reichenbach, Perry F Renshaw, Francisco Reyes-Madrigal, Bruce R Russell, Akira Sawa, Martin Schaefer, Dikoma C Shungu, Stefan Smesny, Jeffrey A Stanley, James Stone, Agata Szulc, Reggie Taylor, Katharine N Thakkar, Jean Theberge, Philip G Tibbo, Thérèse Van Amelsvoort, Jerzy Walecki, Peter C Williamson, Stephen J Wood, Lijing Xin, Hidenori Yamasue, Philip Mcguire, Alice Egerton

Department of Medicine Publications

Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan's unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on …

Heterogeneity Of Treatment Effects Of Hydrocortisone By Risk Of Bronchopulmonary Dysplasia Or Death Among Extremely Preterm Infants In The National Institute Of Child Health And Human Development Neonatal Research Network Trial: A Secondary Analysis Of A Randomized Clinical Trial, Samuel J. Gentle, Matthew A. Rysavy, Lei Li, Matthew M. Laughon, Ravi M. Patel, Erik A. Jensen, Susan Hintz, Namasivayam Ambalavanan, Waldemar A. Carlo, Kristi Watterberg, National Institute Of Child Health And Human Development Neonatal Research Network

Pediatrics Research and Scholarship

IMPORTANCE: Extremely preterm infants who develop bronchopulmonary dysplasia (BPD) are at a higher risk for adverse pulmonary and neurodevelopmental outcomes. In the National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) Hydrocortisone Trial, hydrocortisone neither reduced rates of BPD or death nor increased rates of neurodevelopmental impairment (NDI) or death.

OBJECTIVE: To determine whether estimated risk for grades 2 to 3 BPD or death is associated with the effect of hydrocortisone on the composite outcomes of (1) grades 2 to 3 BPD or death and (2) moderate or severe NDI or death.

DESIGN, SETTING, AND PARTICIPANTS: …