Digital Commons Network^™

Bacterial Fecal Microbiome Composition Associated With Hiv Stage Among Rural And Peri-Urban Adults Living With Hiv In Uganda, Bożena M Morawski, Elise R Morton, Miya Yunus, Claudia Muñoz-Zanzi, Rojelio Mejia, Ran Blekhman, David R Boulware, Sarah M Lofgren

Faculty, Staff and Students Publications

Background

Gut microbiome composition in HIV-infection provides insight into HIV pathogenesis and potentially offers avenues to adjunctive HIV therapies. Although two-thirds of people living with HIV (PLHIV) are in Africa, studies of the gut microbiome PLHIV have focused on non-African populations. Additionally, social, cultural, and environmental factors influence the gut microbiome and differ substantially between African and Western and urban and rural communities. Here, we quantify the relationships between immune status and fecal microbiome composition in 175 rural Ugandan PLHIV.

Methods

In 2013, 175 Ugandan PLHIV contributed a single fecal sample as part of a cohort study of 202 participants. …

Underexplored Maternal Microbiomes: Immune, Metabolic, And Microbial Pathways Shaping Pregnancy Outcomes, Rafael Tomoya Michita, Nicole Jimenez, Melissa M Herbst-Kralovetz, Indira U Mysorekar

Faculty, Staff and Students Publications

Maternal microbial ecosystems play critical roles in shaping reproductive physiology and pregnancy outcomes. During the pre-conception and prenatal periods, these communities modulate maternal physiology by regulating immune tolerance, nutrient metabolism, and susceptibility to pregnancy complications such as preterm birth, hypertensive disorders, and gestational diabetes. While the gut microbiota has been extensively studied, the roles of cervicovaginal, urinary, respiratory, oral, and upper reproductive tract microbiomes remain less clear. In this minireview, we synthesize current knowledge on these underexplored maternal microbiomes, with an emphasis on the cervicovaginal and urinary microbiota and their interactions with the placenta and fetus. We discuss cross-niche microbial …

Hematopoietic Cell Transplantation For Wiskott-Aldrich Syndrome: A Pidtc Report, Jessie L Alexander, Blachy J Dávila Saldaña, Ruta Brazauskas, Sravya Gethika Dammalapati, Linda M Griffith, Ami J Shah, Kristin A Shimano, Hans D Ochs, Jack J Bleesing, Christen L Ebens, Malika Kapadia, Andrea Bauchat, Neena Kapoor, Joseph H Oved, Hesham Eissa, Hannah Lust, Michael D Keller, Hilary Haines, Shanmuganathan Chandrakasan, Julie-An Talano, Ahmad Rayes, Lisa Madden, Evan Shereck, Holly K Miller, Lisa Forbes Satter, Caridad Martinez, Jacob Rozmus, Jeffrey J Bednarski, Lolie C Yu, Deepakbabu Chellapandian, Victor M Aquino, Alan Knutsen, Hey Chong, Ashley Chopek, Alfred P Gillio, Avni Joshi, Hemalatha Rangarajan, Theodore B Moore, Jeffrey R Andolina, Kenneth B Desantes, Mark Vander Lugt, Susan E Prockop, David C Shyr, Kathleen E Sullivan, Suhag Parikh, Katja G Weinacht, Troy R Torgerson, Rebecca Marsh, Christopher C Dvorak, Alice Y Chan, Elie Haddad, Jennifer R Heimall, Michael A Pulsipher, Jennifer W Leiding, Donald B Kohn, Jennifer M Puck, Luigi D Notarangelo, David J Rawlings, Morton J Cowan, Aleksandra Petrovic, Sung-Yun Pai, Lauri M Burroughs

Faculty, Staff and Students Publications

Wiskott-Aldrich syndrome (WAS), an X-linked disorder characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancy, can be effectively treated with allogeneic hematopoietic cell transplantation (HCT). Older age at HCT and mismatched donors are known to affect overall survival (OS). However, the influence of specific clinical manifestations or WAS variant class on OS and factors associated with event-free survival (EFS) remain incompletely defined. We analyzed outcomes of 308 patients with WAS who underwent HCT at 37 institutions of the Primary Immune Deficiency Treatment Consortium from 1990 to 2018. With a median follow-up of 5.3 years, the 5-year OS and EFS were 87.2% and …

Virtual Reality For The Management Of Postoperative Pain And Anxiety In Children And Adolescents Undergoing Nuss Repair Of Pectus Excavatum: Randomized Controlled Trial, Charlotte M. Walter, Dillon Froass, Nora Bell, Lauren Haack, Chloe Boehmer, Claudia Bruguera Torres, Rachel Spivak, Max Chou, Kristie Geisler, Keith O'Conor, Sara E. Williams, Lili Ding, Christopher D. King, Vanessa A. Olbrecht

Department of Medicine Faculty Papers

BACKGROUND: Virtual reality (VR) is a novel technology with implications for pain and sensory processing. VR may serve as a novel, scalable method to deliver clinically validated therapy for pain management as an alternative or adjunct to opioids for acute pain. Given that psychological factors and pain perception are both components of postoperative pain, it may also be beneficial to incorporate modalities that decrease anxiety, such as active relaxation and guided meditation with VR. Unfortunately, these therapies are not widely available due to multiple barriers. VR has the potential to deliver pain-reducing, psychologically based therapy to children, thereby enhancing multimodal …

A Case Of Autosomal Dominant Polycystic Kidney Disease With Multiple Bilateral Spontaneous Retroperitoneal Hemorrhages, Masato Mizuta, Tatsuya Suwabe, Yuki Oba, Akinari Sekine, Masayuki Yamanouchi, Hiroki Mizuno, Eiko Hasegawa, Takehiko Wada, Makoto Fukuda, Motoaki Miyazono, Naoki Sawa, Yoshifumi Ubara

Children’s Nutrition Research Center Staff Publications

We experienced a 45-year-old male with ADPKD who developed spontaneous retroperitoneal hemorrhages with hypertension in the right subcapsular renal space without trauma. After his condition worsened with conservative management, he was treated by renal transarterial embolization (TAE). Over the next eight years, he experienced bilateral bleeding at three different sites and underwent repeated endovascular treatment with renal TAE to stop the bleeding. After the fourth occurrence, the patient underwent hemodialysis. Although renal cysts and urinary tract bleeding occur frequently in ADPKD, retroperitoneal hemorrhage is rare; however, TAE is both effective and a good way to preserve renal function.

Penile Prosthetic Infections: What Can Be Learned From Orthopedics?, Kenneth B Mathis, Alisina Shahi

Faculty, Staff and Student Publications

No abstract provided.

Kinetic Human Movement Ontology: A Semantic Terminology Model To Symbolically Represent Physiological Movement, Muhammad Amith, Vivian Ha, Eloisa Nguyen, Yang Gong, Ahsiya Lin, Cui Tao, Licong Cui

Faculty, Staff and Student Publications

Cataloging physiological and anatomical terminologies may provide a fundamental basis for bridging the involvement of muscles, skeletal, and other essential parts in human movement, in addition to understanding their role on human morbidity. We present a general formalized ontology model that focuses on anatomical and physiological entities that are active during human movement, called the Kinetic Human Movement Ontology (KHMO). We developed a model to represent human movement that links human postures using OWL2. We used the model to assemble various open-sourced controlled terminologies involved in human movement - anatomical entities, physiological terms, etc. KHMO presents 1954 classes, 42 properties, …

Crossing The Finish Line Towards A Disease-Modifying Treatment For Angelman Syndrome, Matthew C Judson, Jason J Yi, Et Al.

2020-Current year OA Pubs

Recent progress in the development of genetic therapies promises that impactful treatments for single-gene neurodevelopmental disorders are imminent. But can derailed neurodevelopmental processes be mended after broken genes are replaced or otherwise restored? The results of ongoing clinical trials for Angelman syndrome will soon yield answers to this pressing question, yet the trials face significant obstacles. Here we identify insights needed to aid the quest for a disease-modifying Angelman syndrome therapy, which could serve as a roadmap for the expeditious development of genetic therapies for other single-gene neurodevelopmental disorders.

Blood And Body Fluid Exposure And Reporting Behaviors Among Healthcare Workers: A Decade-Long Comparative Study At A Tertiary Medical Center, Ziad Kaddour, Rami Abdul-Halim, Zeina Al-Khalil, Lea Al Zoghby, Raafat Alameddine, Reem Mansour, Jack El Sawda, Zeina A Kanafani

2020-Current year OA Pubs

BACKGROUND: Occupational exposure to blood and body fluids (BBFE) remains a significant risk for healthcare workers (HCWs), yet underreporting persists despite the implementation of institutional policies. This study aimed to compare BBFE prevalence, reporting practices, and HCWs' knowledge, perceptions, attitudes, and behaviors, and identify predictors of BBFE and failure to report incidents over a ten-year period at a tertiary medical center.

METHODS: Two cross-sectional surveys were conducted at the American University of Beirut Medical Center (AUBMC) in 2013-2014 and 2023-2024. In 2013-2014, all participants completed paper-based questionnaires, whereas in 2023-2024, medical students, residents, and nurses completed online surveys, and housekeeping/laundry …

Translation Of Expanded Cgg Repeats In Lrp12 Associated Oculopharyngodistal Myopathy, Chengcheng Li, Jil A Daw, Sara K Pittman, Connor J Maltby, Hidetoshi Sakurai, Peter K Todd, Conrad C Weihl

2020-Current year OA Pubs

Oculopharyngodistal myopathy (OPDM) is characterized by ptosis, ophthalmoparesis, dysphagia, and distal weakness. Myopathological features include rimmed vacuoles and intranuclear inclusions. OPDM is associated with a pathogenic CGG repeat expansions in the 5'UTR of LRP12, NOTCH2NLC, GIPC1, RILPL1 and ABCD3. Translation of the repeat in the glycine reading frame has been demonstrated for expansions in FMR1, NOTCH2NLC and GIPC1. To assess for a similar phenomenon with LRP12, we expressed normal or expanded CGG repeats in the context of the 5'UTR of LRP12, upstream of a green fluorescent protein (GFP) in the three repeat reading frames. Repeat dependent translation occurs exclusively in …

Integrating Interferon Gamma Receptor Pathways, Antigenicity, And Immune Contexture As Predictors Of Immunotherapeutic Strategies For Mucosal Melanomas, Matilde Monti, Jinglun Li, Obi Griffith, Malachi Griffith, William Vermi, Et Al.

2020-Current year OA Pubs

BACKGROUND: Mucosal melanomas (MM) arise from mucosal melanocytes at various anatomical sites. These tumors are rare, highly aggressive, and often associated with poor outcomes. Current treatments, including immune checkpoint inhibitors, show limited efficacy in advanced disease. Compared with cutaneous melanomas, there is a lack of data on the immunogenicity and interferon (IFN)-γ sensitivity of MM. In this study, we examined these features in sino-nasal melanomas (SN-MM) cell lines and clinical samples using microscopy and functional genomics.

METHODS: The immune contexture of SN-MM was analyzed by immunohistochemistry on 48 tumor biopsies. RNA sequencing and mass spectrometry-based proteomic approaches were used to …

Development Of A Sustainable Blended Food Aid Product Using Local Ingredients For Nutritionally Vulnerable Populations In Haiti, Sherlie Jean Louis Dulience, Rachel Zimmerman, Michelle Dorce, Ilana Seff, Andrea Spray Bulungu, Patricia Kohl, Carolyn Lesorogol, Bazelais Dulience, Lora Iannotti

2020-Current year OA Pubs

OBJECTIVES: This study aimed to: (1) identify optimal blended food recipe options using local flours; (2) assess behaviors, attitudes, and practices around the use of blended foods among nutritionally vulnerable groups in Haiti; and (3) evaluate the nutrient composition of prototype blended food product relative to nutrient requirements for vulnerable populations.

METHODS: Blended food recipes made from local flours were identified through matrix scoring and stakeholder consensus. Focus groups (n = 7) assessed behaviors and attitudes toward blended foods. Prototype recipes were selected based on matrix scoring, program participant feedback, and feasibility of bringing to scale. Nutrient composition of the …

Multi-Stakeholder Perspectives On Barriers To Mental Health Support For Informal Caregivers, Maria Lizette Rangel, Donaji Stelzig, Cassandra Martinez Enriquez, Hoda Badr

Department of Medical Oncology Faculty Papers

BACKGROUND: Informal caregivers experience elevated psychological distress but face substantial challenges in accessing mental health support. Prior research has focused primarily on individual or interpersonal determinants, with less attention to how organizational, community, and policy contexts shape access and contribute to inequities in service availability.

METHODS: Fifty-one stakeholders, including 17 informal caregivers, 23 community health workers (CHWs), and 11 mental health professionals, completed a demographic survey and 60-90-min semi-structured interviews in English or Spanish. Data were analyzed using thematic analysis, combining deductive coding guided by the Socioecological Model with inductive identification of emergent themes.

RESULTS: Participants identified both barriers and …

Is Male Infertility An Early Warning Of More Serious Diseases?, Dolores J. Lamb

Manuscripts, Articles, Book Chapters and Other Papers

About 12% of couples worldwide are infertile. Male factor infertility causes or is contributory to a couple's ability to conceive in approximately 50% of cases. Evidence has emerged that infertile men have poor overall health and increased morbidity and mortality, yet the causes for this are poorly understood. Although these men may appear healthy, research shows that they can harbor a wide variety of systemic diseases and illnesses that may share common links with the causes of their infertility. In fact, as semen parameters decline, their risks of several health conditions increase. In the early 1990s to the present, studies …

Brd4-Mediated Er Membrane Contact Creates Functionally Distinct Mitochondrial Subtypes, Brandon Chen, Rachel M Guerra, David J Pagliarini, Et Al.

2020-Current year OA Pubs

Inter-organellar communication is critical for cellular metabolism. One of the most abundant inter-organellar interactions occurs at the endoplasmic reticulum and mitochondria contact sites (ERMCSs). However, an understanding of the mechanisms governing ERMCS regulation and their roles in cellular metabolism is limited by a lack of tools that permit temporal induction and reversal. Through screening approaches, we identified fedratinib, an FDA-approved drug that dramatically increases ERMCS abundance by inhibiting the epigenetic modifier BRD4. Fedratinib rapidly and reversibly modulates mitochondrial and ER morphology, induces a distinct ER-mitochondria envelopment structure, and alters metabolic homeostasis. Moreover, ERMCS modulation depends on mitochondrial electron transport chain …

Immune-Mediated Necrotising Myopathy Following Semaglutide Treatment: A Contributing Factor?, Brian Lam, Eleni Tiniakou, Xinhai Robert Zhang, Shervin Assassi

Faculty, Staff and Student Publications

This report describes a female patient in her 60s with an immune-mediated necrotising myopathy (IMNM) occurring after semaglutide use. She was found to have progressive dysphagia, dysphonia, proximal muscle weakness and creatine kinase elevation over a 4-month course. Her symptoms were preceded by a single dose of semaglutide. Her work-up revealed features consistent with necrotising myopathy with inflammatory infiltrate on biopsy, and she responded to immunosuppression with corticosteroids and intravenous immunoglobulin (IVIG). She gradually improved and successfully returned to her baseline functional status while off immunosuppression for several months and with continued avoidance of glucagon-like peptide-1 (GLP-1) receptor agonists. Here, …

Identification Of De Novo Variants From Parent-Proband Duos Via Long-Read Sequencing, Leandros Boukas, Emmanuèle C. Délot, Georgia Pitsava, Christine Lambert, Cairbre Fanslow, Primo Baybayan, Sami Belhadj, Bojan Losic, John Harting, Krista Bluske, Jonathan Lotempio, Huda B. Al-Kouatly, Rachid Karam, William J. Rowell, Changrui Xiao, Eric Vilain, Seth I. Berger

Department of Obstetrics and Gynecology Faculty Papers

While de novo variants cause many Mendelian disorders, their detection currently requires sequencing of the proband and both biological parents. This is not feasible when only one parent is available, a limitation for millions of families. Here, we develop duoNovo, which identifies de novo variants from parent-proband duos using long-read sequencing followed by haplotype reconstruction and detection of identical-by-descent haplotype blocks. We sequenced 104 trios with PacBio HiFi sequencing and applied duoNovo to each of the 208 duos constructed by masking one parent, classifying over 55 million variants according to their de novo status. We evaluated duoNovo's performance against classifications …

Proteomics Analysis Of Plasma For Risk Of Sepsis: Findings From The Atherosclerosis Risk In Communities Study, Junichi Ishigami, Xiao Hu, Pascal Schlosser, Thomas R Austin, Jingsha Chen, Bruce M Psaty, David Dowdy, Christie M Ballantyne, Morgan E Grams, Josef Coresh, James S Floyd, Kunihiro Matsushita

Faculty, Staff and Students Publications

Background: Sepsis is a life-threatening complication of infection with high mortality. A high-throughput analysis of circulating blood proteins may provide mechanistic insight and potent therapeutic targets for the prevention of sepsis.

Methods: We used multivariable Cox regression analysis to examine the association of 4955 plasma proteins, measured by SomaScan, with the risk of incident sepsis among 11 065 participants of the Atherosclerosis Risk in Communities (ARIC) Study (visit 3 in 1993 to 1995; mean age, 60.1 years, 54.4% female, 21.0% Black). Proteins (false discovery rate [FDR] of P < 0.05) discovered at visit 3 were replicated using data at visit 5 (n = 4869 in 2011 to 2013: mean age, 75.5 years) and in the Cardiovascular Health Study (CHS) (n = 3512 in 1992 to 1993; mean age, 74.5 years). Canonical pathways were identified by enrichment analyses.

Results: At ARIC visit three, 669 proteins were associated with the risk …

Bi-Allelic Variants In Nrdc Cause A Neurodevelopmental Disorder Characterized By Neonatal Lethality, Microcephaly, And Brain Abnormalities, Davut Pehlivan, Abigail Sandoval, Reza Maroofian, François Lecoquierre, Aisha M Al Shamsi, Gyu S Lee, Osman Yesilbas, Preston Taylor, Matthew B Mcdougal, Vahid Bahrambeigi, Omid Aryani, Juan Felipe Ramirez, Khalid Hama Salih, Chadi Al Alam, Heba Morsy, Haytham Hussien, Tarek Omar, Ibrahim M Abdelrazek, Anne Claire Brehin, Dana Marafi, Tugba Kalayci, Jubran Abu Rahma, Jawabreh Kassem Talbeya, Husein Dabbah, Eric Verspyck, Toktam Moosavian, Jawid M Fatih, Tadahiro Mitani, Gulsen Akay, Daniel G Calame, Anne-Marie Guerrot, Wendy K Chung, Henry Houlden, James R Lupski, Adel Shalata, Wan Hee Yoon

Faculty, Staff and Students Publications

Nardilysin (NRDC) plays a role in multiple cellular functions in diverse cellular compartments, including ectodomain shedding in the plasma membrane, as well as chaperoning a key Krebs cycle enzyme in mitochondria. We had previously reported limited clinical information from two individuals with homozygous frameshift variants in NRDC. With inclusion of previously published individuals, here we report 14 individuals (10 females, four males) from nine unrelated families carrying homozygous NRDC pathogenic variants. Common clinical features include severe to profound developmental delay/intellectual disability (12/12), microcephaly (13/13), prematurity (5/13), lethality in the first 3 years of life (9/14), seizures (7/11), joint contractures (4/8), …

Smartphone-Based Ecological Momentary Assessment Of Pain In Older Adults Undergoing Auricular Point Acupressure For Chronic Low Back Pain: Secondary Analysis Of A Randomized Controlled Trial, Nada Lukkahatai, Chitchanok Benjasirisan, Xinran Huang, Hulin Wu, Jennifer Kawi, Jingyu Zhang, Claudia M Campbell, Constance M Johnson, Paul J Christo, Johannes Thrul

Faculty, Staff and Student Publications

Background: Chronic low back pain (cLBP) is a prevalent and disabling condition in older adults. Auricular point acupressure (APA), a nonpharmacologic intervention, has shown promise in managing cLBP. However, its impact on daily symptom fluctuations remains unclear. Ecological momentary assessment (EMA), which collects real-time data, offers a method to capture these fluctuations.

Objective: This secondary analysis evaluated the effects of APA on EMA-reported pain intensity and pain interference among older adults with cLBP and examined associations among APA practice patterns, recall-based assessments, and EMA engagement.

Methods: Data were drawn from a published 3-arm randomized controlled trial of 272 adults aged …

Longitudinal Profiling Of Tumor And Immune Compartments Uncovers Patterns Of Dysregulation And Associations With Response In Multiple Myeloma, Denis J Ohlstrom, Reyka G Jayasinghe, Yizhe Song, Ravi Vij, Li Ding, Et Al.

2020-Current year OA Pubs

UNLABELLED: Multiple myeloma is a malignancy of clonally expanded plasma cells shaped by complex interactions with the immune microenvironment (IME). To investigate immune correlates of treatment response and disease progression, we conducted multi-omics profiling including CD138neg single-cell RNA sequencing of 243 bone marrow samples from 102 patients (631,226 cells) and CD138pos bulk RNA and whole-genome sequencing from 209 samples. In longitudinal analyses, interferon-γ signaling associated with markers of impaired T-cell memory after autologous stem cell transplant, whereas naïve B-cell abundance and immunoglobulin diversity correlated with improved progression-free survival (HR = 0.48; P = 2.3e-4). At disease progression, multiple myeloma cells …

Decreased Metallothionein-3 Expression In The Human Spinal Cord Is A Common Feature Of Amyotrophic Lateral Sclerosis And Multiple Sclerosis, Adam P Gunn, James B W Hilton, Soumya Mukherjee, Jeffrey R Liddell, Stephen W Mercer, Catriona A Mclean, Colin L Masters, Peter J Crouch, Blaine R Roberts

2020-Current year OA Pubs

Amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are devastating adult-onset neurological diseases with distinct pathological manifestations. Although growing evidence implicates copper dysregulation in both diseases, our understanding of this connection remains incomplete. In this study, we investigated metallothionein-3 (MT3), which is a key regulator of copper metabolism in the central nervous system (CNS), and its relationship to copper in the ALS and MS spinal cord. Using combined quantitative mass spectrometry approaches and immunohistochemical observations, we found a significant decrease in ALS and MS spinal cord MT3 levels compared to controls. This was correlated with levels of copper and MT3-copper …

Glucagon-Like Peptide-1 Receptor Agonists And Risk Of Substance Use Disorders Among Us Veterans With Type 2 Diabetes: Cohort Study, Miao Cai, Taeyoung Choi, Yan Xie, Ziyad Al-Aly

2020-Current year OA Pubs

OBJECTIVES: To investigate whether initiation of glucagon-like peptide-1 (GLP-1) receptor agonists is associated with both reduced risks of incident alcohol, cannabis, cocaine, nicotine, opioid, and other substance use disorders (SUDs) in people with no history of SUDs (protocol 1) and with reduced risk of SUD related adverse clinical outcomes among people with a pre-existing SUD (protocol 2).

DESIGN: Emulation of eight parallel, new user, active comparator target trials using electronic health records: seven trials for each incident SUD outcome (protocol 1) and one trial for adverse outcomes in people with pre-existing SUD (protocol 2).

SETTING: US Department of Veterans Affairs. …

Sickle Cell Visualization In Vivo In Humans: Microvascular Occlusion Formation And Hemorheological Indices, Marisa M Morakis, Luojie Huang, Gregory N. Mckay, Sophie Lanzkron, Lydia H. Pecker, Nicholas J. Durr

Cardeza Foundation for Hematologic Research

Vaso-occlusion is a signature pathology of sickle cell disease (SCD). However, the lack of in vivo methods to observe individual blood cell dynamics in humans limits our understanding of occlusion formation mechanisms. We present a novel in vivo, noninvasive, label-free, and high-resolution imaging technique to study blood flow and sickled cell behavior in affected individuals. We used oblique back-illumination microscopy (OBM) to capture videos of 91.0 ± 42.3 sublingual capillaries in each of 10 participants with SCD before and after red cell transfusions and compared the measurements to 10 unaffected controls. With direct observation of blood cell activity, we identified …

Medial Pulvinar Nucleus As A Causal Hub For Heteromodal Naming, Oscar Woolnough, Tessy Thomas, Kathryn M Snyder, Ellery Wheeler, Jay Gavvala, Nitin Tandon

Faculty, Staff and Student Publications

Our ability to retrieve the names of objects in our environment is a fundamental aspect of everyday life. This process requires a complex, dynamic network of cortical and subcortical interactions. While the cortical constituents of this network have been extensively studied with intracranial recordings, the subcortical nodes of the naming network are unclear. We probed the role of the left medial pulvinar nucleus in naming with direct intracranial recordings and stimulation in eight humans (three male, five female) as they named objects using pictures and auditory and written descriptions. We found a spectrotemporal signature of naming in the left medial …

Modulating Alternative Splicing Of Mecp2 Is A Potential Therapeutic Strategy For Rett Syndrome, Harini P Tirumala, Li Wang, Yan Li, Sameer S Bajikar, Ashley G Anderson, Wei Wang, Alexander J Trostle, Mahla Zahabiyon, Aleksandar Bajic, Jean J Kim, Hu Chen, Zhandong Liu, Huda Y Zoghbi

Faculty, Staff and Students Publications

Rett syndrome (RTT) is a neurological disorder caused by loss-of-function mutations in methyl CpG binding protein 2 (MECP2), a transcriptional regulator essential for maintenance of normal neuronal function. The current FDA-approved treatment for RTT, Trofinetide, mildly alleviates some symptoms. In contrast, re-introducing MeCP2 or increasing its amount through transgenesis in mouse RTT models improves most neurological phenotypes and enhances survival. Here, we devised a therapeutic strategy to moderately increase MeCP2 protein by modulating the alternative splicing of MECP2 to switch the less efficiently translated e2 to the more efficiently translated e1 isoform. We deleted Mecp2 exon 2 (unique …

Proteomic Profiling Of Pulmonary Function And Cardiovascular Disease Risk In The Atherosclerosis Risk In Communities Study, Yura Lee, Astrid M Manuel, Ngoc Quynh H Nguyen, Christine Ladd-Acosta, Alanna C Morrison, Kari E North, Eric Boerwinkle, Amil M Shah, Zhongming Zhao, Stephanie J London, Bing Yu

Faculty, Staff and Student Publications

Background: Pulmonary function is linked to cardiovascular disease risk; however, the underlying mechanisms remain unclear. We aimed to identify protein biomarkers associated with pulmonary function and examine their impact on incident chronic obstructive pulmonary disease, coronary heart disease, heart failure, and all-cause mortality.

Methods: Data from White and Black Americans in the Atherosclerosis Risk in Communities study (visit 2: N=11 354, mean age=57 years; visit 5: N=3517, mean age=75 years), a prospective cohort, were analyzed. Linear regression assessed associations between protein levels and pulmonary function measures, including forced expiratory volume in 1 second and forced vital capacity. The impact of …

Association Between Functional Status And Cardiac Function In Chronic Heart Failure: Insights From The C-Mic Ii Trial., Marat Fudim, Tamara Kovacevic-Preradovic, Marija Zdravkovic, Sasko Jovev, Nermir Granov, Tanja Popov, Igor Rudez, Petar Vukovic, Velibor Ristic, Annette Holtdirk, Muhammad Shahzeb Khan, Faouzi Kallel, Miodrag Peric, Javed Butler, Stefan D. Anker, Dragana Kosevic, J. Eduardo Rame

Department of Medicine Faculty Papers

INTRODUCTION: Relationship between changes in cardiac function, functional capacity, and patient-reported health status in heart failure (HF) remains incompletely defined, which may help inform endpoint selection and clarify how distinct clinical domains reflect treatment response.

METHODS: This post hoc analysis of the randomized cardiac microcurrent (C-MIC) II trial, which evaluated the efficacy and safety of C-MIC therapy in patients with chronic HF with reduced ejection fraction on optimal guideline-directed medical therapy, included 65 ambulatory patients with non-ischaemic dilated cardiomyopathy, New York Heart Association (NYHA) Class III-IV symptoms, and baseline left ventricular ejection fraction (LVEF) 25-35%. Correlations between changes in Kansas …

Sex-Related Differences In Clinical Profile, Management, And Outcomes Of Patients With Type A And B Acute Aortic Dissection: Observations From Irad, Elizabeth Jackson, Andreina Carbone, Sherene Shalhub, Chih-Wen Pai, Marek Ehrlich, Toru Suzuki, G Chad Hughes, Anil Bhan, Rumi Faizer, Antonio Cittadini, Alan Braverman, Eric Isselbacher, Kim Eagle, Christoph Nienaber, Eduardo Bossone

2020-Current year OA Pubs

BACKGROUND: Available data about sex differences in patients with acute aortic dissection (AAD) are scant and conflicting. The aim of this study is to assess sex-related differences in clinical characteristics, presentation, diagnostic findings, management, and outcomes among patients with type A (TA-AAD) and type B AAD (TB-AAD).

METHODS: Data about 11 586 patients enrolled in the IRAD (International Registry of Acute Aortic Dissection) from 1996 to 2022, were analyzed; 7819 (67.5%) experienced TA-AAD and 3867 (33.0%) TB-AAD. Men and women were compared with regard to diagnosis, treatment, and in-hospital and long-term survival.

RESULTS: One third of patients were women (TA-AAD, …

Post-Traumatic Stress Disorder And Risk Of All-Cause And Cause-Specific Mortality: A Nationwide Population And Sibling-Controlled Cohort Study In Taiwan, Chih-Wei Hsu, Yang-Chieh Brian Chen, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Aims: Post-traumatic stress disorder (PTSD) may shorten life expectancy, but evidence for Asian populations and cause-specific mortality remains limited. The aim of this study is to investigate the association between PTSD and mortality risk in an Asian population.

Methods: We used Taiwan's National Health Insurance Research Database (2000-2022) to assemble a cohort of 28,777 individuals with incident PTSD and 115,108 age- and sex-matched unexposed individuals, plus a sibling cohort of 13,305 affected patients and 22,030 unaffected siblings. Cox models estimated adjusted hazard ratios (AHRs) for all-cause, unnatural-cause (suicide and accidents) and natural-cause mortality, with progressive adjustment for sociodemographic factors, comorbidity …