Medical Specialties Commons^™

A Simulation And Small-Group Pediatric Emergency Medicine Course For Generalist Healthcare Providers: Gastrointestinal And Nutrition Emergencies, Adeola Adekunbi Kosoko, Alicia E Genisca, Nicholas A Peoples, Connor Tompkins, Ryan Sorensen, Joy Mackey

Faculty, Staff and Student Publications

Audience and type of curriculum: This is a review curriculum utilizing multiple methods of education to enhance the skills of generalist healthcare providers in low- and middle-income countries (LMICs) in the identification and stabilization of pediatric respiratory emergencies. Our audience of implementation was Belizean generalist providers (nurses and physicians).

Length of curriculum: 8-10 hours.

Introduction: Early recognition and stabilization of critical pediatric patients can improve outcomes. Compared with resource-rich systems, many low-resource settings (i.e., LMICs) rely on generalists to provide most pediatric acute care. We created a curriculum for general practitioners comprising multiple educational modules focused on identifying and stabilizing …

Interest In And Willingness To Use Prep: A Cross-Sectional Study Of Individuals With Problematic Substance Use Residing In A High Hiv Prevalence Jurisdiction, Angela M Heads, Constanza De Dios, Kaixuan An, Jin H Yoon, Robert Suchting, Adrienne Gilmore-Thomas, Joy M Schmitz

Faculty, Staff and Student Publications

Although it is an effective HIV prevention method, pre-exposure prophylaxis (PrEP) is underutilized in the Southern US. Many people who use drugs (PWUD) have increased susceptibility to HIV which could be lessened by using PrEP. Potential barriers to PrEP use include lack of awareness of PrEP, low knowledge about HIV prevention, low self-efficacy for HIV prevention, inaccurate risk perceptions, and anticipated stigma. The current study examined predisposing, enabling, and reinforcing factors that may predict interest in PrEP. The purpose of the current study was to explore factors associated with interest in and willingness to use daily oral and long acting …

A Protein Expression Atlas On Tissue Samples And Cell Lines From Cancer Patients Provides Insights Into Tumor Heterogeneity And Dependencies, Jun Li, Wei Liu, Kamalika Mojumdar, Hong Kim, Zhicheng Zhou, Zhenlin Ju, Shwetha V Kumar, Patrick Kwok-Shing Ng, Han Chen, Michael A Davies, Yiling Lu, Rehan Akbani, Gordon B Mills, Han Liang

Faculty, Staff and Student Publications

The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE) are foundational resources in cancer research, providing extensive molecular and phenotypic data. However, large-scale proteomic data across various cancer types for these cohorts remain limited. Here, we expand upon our previous work to generate high-quality protein expression data for approximately 8,000 TCGA patient samples and around 900 CCLE cell line samples, covering 447 clinically relevant proteins, using reverse-phase protein arrays. These protein expression profiles offer profound insights into intertumor heterogeneity and cancer dependency and serve as sensitive functional readouts for somatic alterations. We develop a systematic protein-centered strategy …

Tools And Recommendations For Commissioning And Quality Assurance Of Deformable Image Registration In Radiotherapy, Lando S Bosma, Mohammad Hussein, Michael G Jameson, Soban Asghar, Kristy K Brock, Jamie R Mcclelland, Sara Poeta, Johnson Yuen, Cornel Zachiu, Adam U Yeo

Faculty, Staff and Student Publications

Multiple tools are available for commissioning and quality assurance of deformable image registration (DIR), each with their own advantages and disadvantages in the context of radiotherapy. The selection of appropriate tools should depend on the DIR application with its corresponding available input, desired output, and time requirement. Discussions were hosted by the ESTRO Physics Workshop 2021 on Commissioning and Quality Assurance for DIR in Radiotherapy. A consensus was reached on what requirements are needed for commissioning and quality assurance for different applications, and what combination of tools is associated with this. For commissioning, we recommend the target registration error of …

Autonomic Dysfunction Among Adult Survivors Of Childhood Cancer In The St Jude Lifetime Cohort Study, John D Groarke, Kirsten K Ness, Rikeenkumar Dhaduk, Juan C Plana, Jean Bernard Durand, Russell V Luepker, Vijaya M Joshi, Matthew Ehrhardt, Daniel A Mulrooney, Stephanie B Dixon, Anju Nohria, Daniel M Green, Rebecca M Howell, Deo Kumar Srivastava, John L Jefferies, Leslie L Robison, Melissa M Hudson, Gregory T Armstrong

Faculty, Staff and Student Publications

Background: The burden and functional significance of autonomic dysfunction among survivors of childhood cancer is unknown.

Objectives: We evaluated the prevalence, risk factors, and functional relevance of autonomic dysfunction in survivors.

Methods: We conducted a cross-sectional prospective evaluation of 1,041 adult survivors of childhood cancer treated with anthracyclines (31.1%), chest-directed radiation (13.5%), both (19.5%), or neither (35.9%), and 286 community control subjects enrolled in the SJLIFE (St Jude Lifetime Cohort Study). Four measures of autonomic dysfunction were evaluated: elevated resting heart rate, decreased heart rate reserve, decreased systolic blood pressure response to exercise, and delayed heart rate recovery. Logistic regression …

Development Of An Engineered Extracellular Vesicles-Based Vaccine Platform For Combined Delivery Of Mrna And Protein To Induce Functional Immunity, Xin Luo, Kathleen M Mcandrews, Kent A Arian, Sami J Morse, Viktoria Boeker, Shreyasee V Kumbhar, Yingying Hu, Krishnan K Mahadevan, Kaira A Church, Sriram Chitta, Nicolas T Ryujin, Janine Hensel, Jianli Dai, Dara P Dowlatshahi, Hikaru Sugimoto, Michelle L Kirtley, Valerie S Lebleu, Shabnam Shalapour, Joe H Simmons, Raghu Kalluri

Faculty, Staff and Student Publications

mRNA incorporated in lipid nanoparticles (LNPs) became a new class of vaccine modality for induction of immunity against COVID-19 and ushered in a new era in vaccine development. Here, we report a novel, easy-to-execute, and cost effective engineered extracellular vesicles (EVs)-based combined mRNA and protein vaccine platform (EVX-M+P vaccine) and explore its utility in proof-of-concept immunity studies in the settings of cancer and infectious disease. As a first example, we engineered EVs, natural nanoparticle carriers shed by all cells, to contain ovalbumin mRNA and protein (EVOvaM+P vaccine) to serve as cancer vaccine against ovalbumin-expressing melanoma tumors. EVOvaM+P administration to mice …

High Throughput And Rapid Isolation Of Extracellular Vesicles And Exosomes With Purity Using Size Exclusion Liquid Chromatography, Kshipra S Kapoor, Kristen Harris, Kent A Arian, Lihua Ma, Beatriz Schueng Zancanela, Kaira A Church, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Extracellular vesicles (EVs) have emerged as potential biomarkers for diagnosing a range of diseases without invasive procedures. Extracellular vesicles also offer advantages compared to synthetic vesicles for delivery of various drugs; however, limitations in segregating EVs from other particles and soluble proteins have led to inconsistent EV retrieval rates with low levels of purity. Here, we report a new high-yield (88.47 %) and rapid (< 20 min) EV isolation method termed size exclusion - fast protein liquid chromatography (SE-FPLC). We show SE-FPLC can effectively isolate EVs from multiple sources including EVs derived from human and mouse cells and serum samples. The results indicate that SE-FPLC can successfully remove highly abundant protein contaminants such as albumin and lipoprotein complexes, which can represent a major hurdle in large scale isolation of EVs. The high-yield nature of SE-FPLC allows for easy industrial scaling up of EV production for various clinical utilities. SE-FPLC also enables analysis of small volumes of blood for use in point-of-care diagnostics in the clinic. Collectively, SE-FPLC offers many advantages over current EV isolation methods and offers rapid clinical translation.

Oculomics Analysis In Multiple Sclerosis: Current Ophthalmic Clinical And Imaging Biomarkers, Alex Suh, Gilad Hampel, Aditya Vinjamuri, Joshua Ong, Sharif Amit Kamran, Ethan Waisberg, Phani Paladugu, Nasif Zaman, Prithul Sarker, Alireza Tavakkoli, Andrew G Lee

Faculty, Staff and Student Publications

Multiple Sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal damage. Early recognition and treatment are important for preventing or minimizing the long-term effects of the disease. Current gold standard modalities of diagnosis (e.g., CSF and MRI) are invasive and expensive in nature, warranting alternative methods of detection and screening. Oculomics, the interdisciplinary combination of ophthalmology, genetics, and bioinformatics to study the molecular basis of eye diseases, has seen rapid development through various technologies that detect structural, functional, and visual changes in the eye. Ophthalmic biomarkers (e.g., tear composition, …

Social Determinants Of Health And Surgical Desirability Of Outcome Ranking In Older Veterans, Michael A Jacobs, Yubo Gao, Susanne Schmidt, Paula K Shireman, Michael Mader, Carly A Duncan, Leslie R M Hausmann, Karyn B Stitzenberg, Lillian S Kao, Mary Vaughan Sarrazin, Daniel E Hall

Faculty, Staff and Student Publications

Importance: Evaluating how social determinants of health (SDOH) influence veteran outcomes is crucial, particularly for quality improvement.

Objective: To measure associations between SDOH, care fragmentation, and surgical outcomes using a Desirability of Outcome Ranking (DOOR).

Design, setting, and participants: This was a cohort study of US veterans using data from the Veterans Affairs (VA) Surgical Quality Improvement Program (VASQIP; 2013-2019) limited to patients aged 65 years or older with inpatient stays between 2 and 30 days, merged with multiple data sources, including Medicare. Race and ethnicity data were retrieved from VASQIP, Medicare and Medicaid beneficiary summary files, the Veterans Health …

Targeting The Epidermal Growth Factor Receptor Pathway In Chemotherapy-Resistant Triple-Negative Breast Cancer: A Phase Ii Study, Clinton Yam, Miral Patel, Holly A Hill, Ryan Sun, Roland L Bassett, Elisabeth Kong, Senthil Damodaran, Kimberly B Koenig, Sausan Abouharb, Sadia Saleem, Ajit K Bisen, Rashmi K Murthy, David L Ramirez, Gaiane M Rauch, Beatriz E Adrada, Rosalind P Candelaria, Xiaoping Wang, Elizabeth A Mittendorf, Alastair M Thompson, Jason B White, Elizabeth E Ravenberg, Alyson R Clayborn, Qing-Qing Ding, Daniel J Booser, Oluchi Oke, Abenaa M Brewster, Gabriel N Hortobagyi, Nuhad K Ibrahim, Jennifer K Litton, Vicente Valero, Banu K Arun, Debu Tripathy, Jeffrey T Chang, Ken Chen, Anil Korkut, Stacy L Moulder, Lei Huo, Bora Lim, Naoto T Ueno

Faculty, Staff and Student Publications

Purpose: Epidermal growth factor receptor (EGFR) pathway activation causes chemotherapy resistance, and inhibition of the EGFR pathway sensitizes triple-negative breast cancer (TNBC) cells to chemotherapy in preclinical models. Given the high prevalence of EGFR overexpression in TNBC, we conducted a single-arm phase II study of panitumumab (anti-EGFR monoclonal antibody), carboplatin, and paclitaxel as the second phase of neoadjuvant therapy (NAT) in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02593175).

Patients and methods: Patients with early-stage, AC-resistant TNBC, defined as disease progression or ≤80% reduction in tumor volume after four cycles of AC, were eligible for this study and …

Pkmyt1 Is A Marker Of Treatment Response And A Therapeutic Target For Cdk4/6 Inhibitor-Resistance In Er+ Breast Cancer, Anran Chen, Beom-Jun Kim, Aparna Mitra, Craig T Vollert, Jonathan T Lei, Diana Fandino, Meenakshi Anurag, Matthew V Holt, Xuxu Gou, Jacob B Pilcher, Matthew P Goetz, Donald W Northfelt, Susan G Hilsenbeck, C Gary Marshall, Marc L Hyer, Robert Papp, Shou-Yun Yin, Carmine De Angelis, Rachel Schiff, Suzanne A W Fuqua, Cynthia X Ma, Charles E Foulds, Matthew J Ellis

Faculty, Staff and Students Publications

Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients with 22 ER+ breast cancer demonstrated that protein kinase, membrane-associated tyrosine/threonine one (PKMYT1), a WEE1 homolog, is estradiol (E2) regulated in E2-dependent PDXs and constitutively expressed when growth is E2-independent. In clinical samples, high PKMYT1 mRNA levels associated with resistance to both ET and CDK4/6 inhibition. The PKMYT1 inhibitor lunresertib (RP-6306) with gemcitabine selectively and synergistically reduced the viability of ET and palbociclib-resistant ER+ breast …

Discordance Between Aptt And Anti-Xa In Monitoring Heparin Anticoagulation In Mechanical Circulatory Support, Song Li, Ang Li, Jennifer A Beckman, Christopher Kim, Marian A Granich, John Mondin, Daniel E Sabath, David A Garcia, Claudius Mahr

Faculty, Staff and Students Publications

AIMS: It is unclear whether activated partial thromboplastin time (aPTT) or anti-Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti-Xa in MCS patients and identifies predictors of discordance.

METHODS AND RESULTS: aPTT and anti-Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti-Xa levels were 60-100 s and 0.3-0.7 IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning …

Challenges In Pediatric Home-Based Hospice And Palliative Care: A Case Series, Jill Ann Jarrell, Daniel H Grossoehme, Sarah Friebert, Toluwalase A Ajayi, Rachel Thienprayoon, Lisa Humphrey

Faculty, Staff and Students Publications

Pediatric home-based hospice and palliative care is a growing and important sub-field within the larger pediatric palliative care landscape. Despite research demonstrating the clinical and systemic efficacy of pediatric home-based hospice and palliative care, there remain barriers to its optimal development, implementation, and dissemination as well as best clinical practice knowledge gaps. This case series presents specific examples of ubiquitous challenges in pediatric home-based hospice and palliative care in hopes of guiding future research, education, advocacy, and program development efforts.

Global Presence And Penetrance Of, Jaroslaw Dulski, Matthew Baker, Samantha A Banks, Michael Bayat, Rose Bruffaerts, Gabriela Ortiz Cruz, Caio C Disserol, Kristen S Fisher, Jainy N Jose, Bernadette Kalman, Orhun H Kantarci, Dmytro Maltsev, Catherine Middleton, Gabriela Novotni, Dijana Plaseska-Karanfilska, Salmo Raskin, Josiane Souza, Helio A Teive, Zbigniew K Wszolek

Faculty, Staff and Students Publications

Objectives: To highlight the worldwide presence of CSF1R-related disorder (CSF1R-RD), discuss its penetrance, and provide the first haplotype analysis.

Methods: Data on patients worldwide were collected, including demographics, genotype, family history, and clinical status. For haplotype analysis, polymorphisms of short tandem repeats in 3 distinct families with CSF1R p.Ile794Thr variant were examined.

Results: Nineteen new patients were included, at a mean age of 38.7 years (ranging from 11 to 74 years), from 14 families from the Americas, Asia, Australia, and Europe, including the first from Mexico, North Macedonia, and Ukraine. Fifteen CSF1R variants were found, including 8 …

Association Of Aortic Valve Calcium With Dementia And Stroke: The Multi-Ethnic Study Of Atherosclerosis, Natalie Marrero, Kunal Jha, Timothy M Hughes, Alexander C Razavi, Jelani K Grant, Ellen Boakye, Khalil Anchouche, Omar Dzaye, Matthew J Budoff, Jerome I Rotter, Xiuqing Guo, Jie Yao, Alexis C Wood, Roger S Blumenthal, Erin D Michos, George Thanassoulis, Wendy S Post, Michael J Blaha, Chinwe Ibeh, Seamus P Whelton

Faculty, Staff and Students Publications

Background and aims: Calcific aortic valve disease is associated with increased thrombin formation, platelet activation, decreased fibrinolysis, and subclinical brain infarcts. We examined the long-term association of aortic valve calcification (AVC) with newly diagnosed dementia and incident stroke in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: AVC was measured using non-contrast cardiac CT at Visit 1. We examined AVC as a continuous (log-transformed) and categorical variable (0, 1-99, 100-299, ≥300). Newly diagnosed dementia was adjudicated using International Classification of Disease codes. Stroke was adjudicated from medical records. We calculated absolute event rates (per 1000 person-years) and multivariable adjusted Cox proportional …

Correspondence Re Essam El-Sayed Felaya Et Al, Kiyeun Nam, Dongho Lee, Seokjoon Hwang, Minsu Seo, Taeheon Lee, Yonghoon Lee, Michael Y Lee

Faculty, Staff and Students Publications

No abstract provided.

The Relationship Between Adverse Childhood Experiences, Symptom Severity, Negative Thinking, Comorbidity, And Treatment Response In Youth With Obsessive-Compulsive Disorder, Mariana Vazquez, Amanda Palo, Mckenzie Schuyler, Brent J Small, Joseph F Mcguire, Sabine Wilhelm, Wayne K Goodman, Daniel Geller, Eric A Storch

Faculty, Staff and Students Publications

Although youth and adults with obsessive-compulsive disorder (OCD) endorse elevated incidence of exposure to traumatic life events during childhood, the existing literature on adverse childhood experiences (ACEs) and OCD is mixed and studies focusing on pediatric OCD are limited. The present study examines the relationship between ACEs and OCD onset, symptom severity, negative cognitive patterns, comorbidity, and cognitive-behavioral therapy (CBT) response in 142 children and adolescents with OCD. ACEs were ascertained from parent reports. Most parents reported child exposure to ACEs. Out of the parents who reported ACEs, 50% reported ACE exposure prior to OCD diagnosis and 50% reported ACE …

Inhaled Corticosteroids Attenuate The Association Of Fine Particulate Matter And Acute Asthma Events, Kristen A Staggers, Paula Sierra, Drew A Helmer, Charles Minard, Meredith C Mccormack, Tianshi David Wu

Faculty, Staff and Students Publications

No abstract provided.

Distinct Landscape And Clinical Implications Of Therapy-Related Clonal Hematopoiesis, Koichi Takahashi, Daisuke Nakada, Margaret Goodell

Faculty, Staff and Student Publications

Therapy-related clonal hematopoiesis (t-CH) is defined as clonal hematopoiesis detected in individuals previously treated with chemotherapy and/or radiation therapy. With the increased use of genetic analysis in oncological care, the detection of t-CH among cancer patients is becoming increasingly common. t-CH arises through the selective bottleneck imposed by chemotherapies and potentially through direct mutagenesis from chemotherapies, resulting in a distinct mutational landscape enriched with mutations in DNA damage-response pathway genes such as TP53, PPM1D, and CHEK2. Emerging evidence sheds light on the mechanisms of t-CH development and potential strategies to mitigate its emergence. Due to its unique characteristics that predominantly …

Human Embryonic Genetic Mosaicism And Its Effects On Development And Disease, Sarah M Waldvogel, Jennifer E Posey, Margaret A Goodell

Center on Aging Staff Publications

Nearly every mammalian cell division is accompanied by a mutational event that becomes fixed in a daughter cell. When carried forward to additional cell progeny, a clone of variant cells can emerge. As a result, mammals are complex mosaics of clones that are genetically distinct from one another. Recent high-throughput sequencing studies have revealed that mosaicism is common, clone sizes often increase with age and specific variants can affect tissue function and disease development. Variants that are acquired during early embryogenesis are shared by multiple cell types and can affect numerous tissues. Within tissues, variant clones compete, which can result …

A Method For Rapid And Reliable Quantification Of Vegf-Cell Binding Activity, Prabuddha Waduge, Avinash Kaur, Wei Li

Faculty, Staff and Students Publications

Vascular endothelial growth factor (VEGF) is a pleiotropic growth factor that binds a broad spectrum of cell types and regulates diverse cellular processes, including angiogenesis, growth and survival. However, it is technically difficult to quantify VEGF-cell binding activity because of reversible nature of ligand-receptor interactions. Here we used T7 bacteriophage display to quantify and compare binding activity of three human VEGF-A (hVEGF) isoforms, including hVEGF111, 165 and 206. All three isoforms bound equally well to immobilized aflibercept, a decoy VEGF receptor. hVEGF111-Phage exhibited minimal binding to immobilized heparan sulfate, whereas hVEGF206-Phage and hVEGF165-Phage had the highest and intermediate binding to …

Design And Cohort Characteristics Of Track, A Prospective Study Of Hyperkalaemia Management Decision-Making, Judith Hsia, Nitin Shivappa, Ameet Bakhai, Jordi Bover, Javed Butler, Pietro Manuel Ferraro, Linda Fried, Markus P Schneider, Navdeep Tangri, Wolfgang C Winkelmayer, Meredith Bishop, Hungta Chen, Anna-Karin Sundin, Marc P Bonaca

Faculty, Staff and Students Publications

BACKGROUND: Guideline-recommended hyperkalaemia management includes dietary potassium (K

METHODS: This study enrolled participants within 21 days of an episode of hyperkalaemia in four European countries (UK, Spain, Germany, Italy) and the USA. During the 12-month follow up, data collected will include participant and healthcare provider characteristics (specialty and practice setting), hyperkalaemia treatment objectives and strategies, rationale for management decisions and indicators of response and patient-reported perceptions of their hyperkalaemia treatment.

RESULTS: The enrolled cohort includes 1330 participants, mean age 68 years, of whom 31% were women. At baseline, 6% reported heart failure, 55% chronic kidney disease, 29% both and 9% …

Dna Methylation-Derived Immune Cell Proportions And Cancer Risk In Black Participants, Christopher S Semancik, Naisi Zhao, Devin C Koestler, Eric Boerwinkle, Jan Bressler, Rachel J Buchsbaum, Karl T Kelsey, Elizabeth A Platz, Dominique S Michaud

Faculty, Staff and Student Publications

Prior cohort studies assessing cancer risk based on immune cell subtype profiles have predominantly focused on White populations. This limitation obscures vital insights into how cancer risk varies across race. Immune cell subtype proportions were estimated using deconvolution based on leukocyte DNA methylation markers from blood samples collected at baseline on participants without cancer in the Atherosclerosis Risk in Communities Study. During a mean of 17.5 years of follow-up, 668 incident cancers were diagnosed in 2,467 Black participants. Cox proportional hazards regression was used to examine immune cell subtype proportions and overall cancer incidence and site-specific incidence (lung, breast, and …

Tau Is Required For Glial Lipid Droplet Formation And Resistance To Neuronal Oxidative Stress, Lindsey D Goodman, Isha Ralhan, Xin Li, Shenzhao Lu, Matthew J Moulton, Ye-Jin Park, Pinghan Zhao, Oguz Kanca, Ziyaneh S Ghaderpour Taleghani, Julie Jacquemyn, Joshua M Shulman, Kanae Ando, Kai Sun, Maria S Ioannou, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

The accumulation of reactive oxygen species (ROS) is a common feature of tauopathies, defined by Tau accumulations in neurons and glia. High ROS in neurons causes lipid production and the export of toxic peroxidated lipids (LPOs). Glia uptake these LPOs and incorporate them into lipid droplets (LDs) for storage and catabolism. We found that overexpressing Tau in glia disrupts LDs in flies and rat neuron-astrocyte co-cultures, sensitizing the glia to toxic, neuronal LPOs. Using a new fly tau loss-of-function allele and RNA-mediated interference, we found that endogenous Tau is required for glial LD formation and protection against neuronal LPOs. Similarly, …

Cerebellar Deep Brain Stimulation As A Dual-Function Therapeutic For Restoring Movement And Sleep In Dystonic Mice, Luis E Salazar Leon, Linda H Kim, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Dystonia arises with cerebellar dysfunction, which plays a key role in the emergence of multiple pathophysiological deficits that range from abnormal movements and postures to disrupted sleep. Current therapeutic interventions typically do not simultaneously address both the motor and non-motor symptoms of dystonia, underscoring the necessity for a multi-functional therapeutic strategy. Deep brain stimulation (DBS) is effectively used to reduce motor symptoms in dystonia, with existing parallel evidence arguing for its potential to correct sleep disturbances. However, the simultaneous efficacy of DBS for improving sleep and motor dysfunction, specifically by targeting the cerebellum, remains underexplored. Here, we test the effect …

Piezo Ion Channels: Force Sensors Of The Interoceptive Nervous System, Yasmeen M F Hamed, Britya Ghosh, Kara L Marshall

Duncan NRI Faculty and Staff Publications

Many organs are designed to move: the heart pumps each second, the gastrointestinal tract squeezes and churns to digest food, and we contract and relax skeletal muscles to move our bodies. Sensory neurons of the peripheral nervous system detect signals from bodily tissues, including the forces generated by these movements, to control physiology. The processing of these internal signals is called interoception, but this is a broad term that includes a wide variety of both chemical and mechanical sensory processes. Mechanical senses are understudied, but rapid progress has been made in the last decade, thanks in part to the discovery …

Meta-Analysis Comparing Oral Anticoagulant Monotherapy Versus Dual Antithrombotic Therapy In Patients With Atrial Fibrillation And Stable Coronary Artery Disease, Mushood Ahmed, Areeba Ahsan, Aimen Shafiq, Raheel Ahmed, Mahboob Alam, Pierre Sabouret, Jamal S Rana, Gregg C Fonarow

Faculty, Staff and Students Publications

BACKGROUND: Oral anticoagulants (OACs) are routinely used for the management of atrial fibrillation (AF) while antiplatelet agents are used in coronary artery disease (CAD). However, data regarding the comparative clinical outcomes of OAC monotherapy versus dual antithrombotic therapy (anticoagulant plus antiplatelet agent) in patients with AF and stable CAD are limited.

METHODS: A comprehensive search of major databases including PubMed/MEDLINE, Cochrane Library, and Embase was performed from inception to September 1, 2024 to identify randomized control trials (RCTs) that compared OAC monotherapy with dual antithrombotic therapy in patients with AF and stable CAD. The risk ratios (RRs) were estimated with …

Update On Recommendations For Surveillance For Children With Predisposition To Hematopoietic Malignancy, Luke D Maese, Marcin W Wlodarski, Sun Young Kim, Alison A Bertuch, Gaelle Bougeard, Vivian Y Chang, Lucy A Godley, Payal P Khincha, Roland P Kuiper, Harry Lesmana, Rose B Mcgee, Lisa J Mcreynolds, Julia Meade, Sharon E Plon, Sharon A Savage, Sarah R Scollon, Hamish S Scott, Michael F Walsh, Kim E Nichols, Christopher C Porter

Center for Medical Ethics and Health Policy Staff Publications

Children harboring certain germline gene variants have an increased risk of developing myelodysplastic syndrome (MDS) and other hematopoietic malignancies (HM), such as leukemias and lymphomas. Recent studies have identified an expanding number of these predisposition genes, with variants most prevalent in children with MDS but also found in children with other HM. For some hematopoietic malignancy predispositions (HMP), specifically those with a high risk of MDS, early intervention through hematopoietic stem cell transplantation can favorably impact overall survival, providing a rationale for rigorous surveillance. A multidisciplinary panel of experts at the 2023 AACR Childhood Cancer Predisposition Workshop reviewed the latest …

A Mouse Model For Conditional Expression Of Activated Β-Catenin In Epidermal Keratinocytes, Vineet K Maurya, Yan Ying, John P Lydon

Faculty, Staff and Students Publications

We report the generation and characterization of the K5: CAT bigenic mouse in which the constitutively activated form of β-catenin (ΔN89 β-catenin) is conditionally expressed in cytokeratin-5 (K5) positive epidermal keratinocytes. Following short-term doxycycline intake during the telogen resting phase, the adult K5: CAT bigenic develops enlarged pilosebaceous units that expand deep into the dermis, an expansion usually observed during the anagen growth phase. Prolonged doxycycline treatment results in significant thickening and folding of the K5: CAT epidermis. During this persistent induction period, there is clear evidence of increased keratinocyte proliferation, particularly in the epidermal basal cell layer and the …

Psychological Distress Among Ethnically Diverse Participants From Eastern And Southern Africa, Kester B B Tindi, Allan Kalungi, Eugene Kinyanda, Bizu Gelaye, Alicia R Martin, Ronald Galiwango, Wilber Ssembajjwe, Fred Kirumira, Adele Pretorius, Anne Stevenson, Charles R J C Newton, Dan J Stein, Elizabeth G Atkinson, Emanuel K Mwesiga, Joseph Kyebuzibwa, Lori B Chibnik, Lukoye Atwoli, Mark Baker, Melkam Alemayehu, Rehema M Mwende, Rocky E Stroud, Solomon Teferra, Stella Gichuru, Symon M Kariuki, Zukiswa Zingela, Moffat Nyirenda, Segun Fatumo, Dickens H Akena

Faculty, Staff and Students Publications

IMPORTANCE: Psychological distress is characterized by anxiety and depressive symptoms. Although prior research has investigated the occurrence and factors associated with psychological distress in low- and middle-income countries, including those in Africa, these studies' findings are not very generalizable and have focused on different kinds of population groups.

OBJECTIVE: To investigate the prevalence and characteristics (sociodemographic, psychosocial, and clinical) associated with psychological distress among African participants.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study analyzed data of participants in the Neuropsychiatric Genetics in African Populations-Psychosis (NeuroGAP-Psychosis) study, which recruited from general outpatient clinics in Eastern (Uganda, Kenya, and Ethiopia) and Southern …