Medicine and Health Sciences Commons^™

Non-Ketotic Hyperglycemia Unmasks Hemichorea - A Reply, Ezhilkugan Ganessane, Sasikumar Mahalingam, Selva Ganesan

Journal of Community Hospital Internal Medicine Perspectives

No abstract for this article type

Association Of Depression With Myocardial Infarction With Non-Obstructive Coronary Arteries: A Systematic Review, Sarim Rashid, Khawaja Usama Maqbool, Umer Hassan, Subhan Ahmed, Hamayle Saeed, Fnu Avanteeka, Syed Muhammad Jawad Zaidi, Jahanzeb Malik, Amin Mehmoodi

Journal of Community Hospital Internal Medicine Perspectives

This systematic review examined the association between depression and myocardial infarction with non-obstructive coronary arteries (MINOCA). A comprehensive literature search was conducted using electronic databases, resulting in the inclusion of six small case-control and cohort studies reported from Spain, Australia, China, and Pakistan. The studies included various study designs, such as cohort studies, case-control studies, and prospective cohort studies. The results of the systematic review indicate a significant association between depression and MINOCA. Several studies reported a higher prevalence of depression among MINOCA patients compared to those with obstructive coronary artery disease. Additionally, depression was found to be associated with …

A Rare Case Of Iga Vasculitis In An Adult Patient With Mssa Bacteremia And Prostate Abscess, Maria E Mesalles, Erinolaoluwa F Araoye, Anees Siddiqi, Adrien Janvier

Journal of Community Hospital Internal Medicine Perspectives

IgA vasculitis, previously known as Henoch Schönlein Purpura (HSP), is a disease more common in children and occurs when IgA1 immune complexes attach to the walls of small blood vessels causing inflammation. This case report is of an adult male who presented with a purpuric rash affecting both legs, microhematuria, and knee pain. Blood cultures were positive for Methicillin-sensitive Staphylococcus aureus (MSSA). Computed tomography of the pelvis revealed a prostate abscess. Skin biopsy demonstrated IgA and C3 in the dermal vessels. To our knowledge, this is the first report of IgA vasculitis associated with MSSA bacteremia due to a prostate …

Autoimmune Hepatitis: An Unusual Presentation., Ahmed Ali Aziz, Muhammad Ali Aziz, Deep Mehta, Muhammad Humayoun Rashid

Journal of Community Hospital Internal Medicine Perspectives

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that occurs in a bimodal age distribution in the second and fifth-sixth decade of life. The disease is more prevalent in females and presents with variable clinical manifestations ranging from being asymptomatic to acute liver failure. AIH is often overlooked and not worked up in elderly patients who present with liver failure. This can lead to increased morbidity and mortality in elderly patients. AIH should be considered as a differential diagnosis in patients who present with elevated transaminases regardless of age or gender as early recognition and treatment leads to improved …

Reverse Takotsubo Cardiomyopathy With Severe Dengue: Case Report From Pakistan., Warda Ajmal, Zahra Iftikhar, Asaad Akbar Khan

Journal of Community Hospital Internal Medicine Perspectives

Takotsubo Cardiomyopathy is an established transient cardiomyopathy found predominately in females with intense emotional and physical strain. It has four notable variants: Apical, Mid-Ventricular, Basal and Focal. Mid Ventricular variant is also referred to as Reverse Takotsubo Cardiomyopathy. Dengue is a viral arthopod-borne tropical disease endemic to Pakistan, with multiple reports of cardiovascular involvement. We report an atypical presentation of a 17 year old male, suffering from Dengue Fever, who presented to a tertiary care hospital with Reverse Takotsubo Cardiomyopathy.

Cases From A Community Hospital…Jchimp Series #2: 66-Year-Old Man With Recurrent Painful Rashes And Oral Ulcerations, Fatima Halilu, Jing Wu, Joseph Fuscaldo, Nathan Dunsmore, Zain Syed, Pauline Daley

Journal of Community Hospital Internal Medicine Perspectives

This is part of a series of case reports detailing scenarios from our community hospital. The cases are selected to feature clinical dilemmas, provide a review on what is currently known about the topic with expert perspective. A 66-year-old black man presented to the primary care clinic with his fourth episode of generalized painful rash and oral ulcerations without a diagnosis despite two emergency room (ED) visits alongside doxycycline treatment. Symptoms interfered with daily activities with skin exam notable for widespread erythematous patches and plaques. In office biopsies were obtained with final diagnosis of erythema multiforme. Etiologic workup revealed positive …

Rare Case Of Mycobacterium Avium Complex Peritonitis In A Patient With Multiple Myeloma Undergoing Peritoneal Dialysis, Sacide S. Ozgur, Nida Ansari, Dhruv Patel, Ryan Rahman, Raymond Shih

Journal of Community Hospital Internal Medicine Perspectives

Mycobacterium avium complex (MAC) infections can present as a variety of severe diseases. While it has a predilection for immunocompromised patients such as those with Human immunodeficiency virus (HIV), it can also affect immunocompetent patients as well. One of the rare yet severe diseases that MAC infections can present is MAC peritonitis. Often hard to distinguish from other causes of peritonitis, high clinical suspicion should be maintained for those who are susceptible. Here we present an 85-year-old female with a past medical history of end-stage renal disease on peritoneal dialysis who presented with nausea and vomiting. She was found to …

Reactive Arthritis After Mpox Vaccination, Indira Acharya, Lanaya Williams Smith, Chandralekha Banerjee, Lyn M. Camire, Radhika Vij

Journal of Community Hospital Internal Medicine Perspectives

Autoimmune inflammatory reaction after vaccination is a rare clinical entity. Reactive arthritis has been described after various vaccinations, but not after mpox vaccination. Here we present a case of recently diagnosed reactive arthritis after mpox vaccination that presented in the context of unrelenting fever and diarrhea complicated by migratory arthritis and anterior uveitis. We have reported this case to the Vaccine Adverse Event Reporting System (VAERS).

The Diagnostic Yield Of Endoscopic Ultrasound In Asymptomatic Patients With Unexplained Dilated Common Bile Duct, Or Double Duct Sign With Normal Transaminases A Retrospective Study From A Single Urban-Based University Endoscopy Center, Mina Fransawy Alkomos, Shaker Barham, Youssef Botros, Nader Mekheal, Ariana Tagliaferri, Alisa Farokhian, Hardikkumar M. Shah, Gabriel Melki, Yana Cavanagh, Walid Baddoura, Matthew Grossman

Journal of Community Hospital Internal Medicine Perspectives

Background Common bile duct dilatation alone or double duct sign (both CBD and dilated pancreatic duct dilatation ) and abnormal liver enzymes are highly predictive of biliary disease. This can be identified on ultrasound (US), CT scan, and/or magnetic resonance cholangiopancreatography (MRCP). Unexplained dilatation on imaging might warrant endoscopic ultrasound (EUS) to identify any occult causes. Supporting literature about the importance of using EUS in these conditions is evolving with no clear evidence-based approach to evaluate asymptomatic dilated ducts. We aim to investigate the diagnostic yield of EUS in unexplained CBD dilatation or double duct sign with normal liver enzymes. …

De-Implementation Of Fecal Occult Blood Testing In The Emergency Department And Hospital Units: A Quality Improvement Project, Adewale Ajumobi, Joline De Castro, Ammar Qureshi

Journal of Community Hospital Internal Medicine Perspectives

Background: Fecal occult blood tests (FOBT) are inappropriately used in patients with melena, hematochezia, coffee ground emesis, iron deficiency anemia, and diarrhea. The use of FOBT for reasons other than screening for colorectal cancer is considered low-value and unnecessary. Methods: Quality Improvement Project that utilized education, Best Practice Advisory (BPA) and modification of order sets in the electronic health record (EHR). The interventions were done in a sequential order based on the Plan-Do-Study-Act (PDSA) method. An annotated run chart was used to analyze the collected data. Results: Education and Best Practice Advisory within the EHR led to significant reduction in …

Contrasting Tick Species Behaviors: A Course-Based Undergraduate Research Experience (Cure), Sara Benham, Shovan Dutta, Rohan Maddamsetti, Clayton Wright, Alena Anderson, David T. Gauthier, Holly D. Gaff

Spora: A Journal of Biomathematics

Tick-borne diseases are on the rise throughout the world, and there is a need to better understand tick behavior in order to identify potential new interventions. Ticks have a complex life history and can survive months off-host. There is a lack of large-scale data on off-host tick behavior, which leaves a gap in understanding of tick biology outside of tick-host interactions. Introducing undergraduate students to authentic research early in their studies can help prepare them for independent inquiry in upper-level classes. To address the student needs and fill gaps in tick research, students in introductory biology courses recorded observations of …

Antibiotic-Induced Gut Dysbiosis Elicits Gut-Brain Axis Relevant Multi-Omic Signatures And Behavioral And Neuroendocrine Changes In A Nonhuman Primate Model, Shivdeep S. Hayer, Mackenzie Conrin, Jeffrey French, Andrew K. Benson, Sophie Alvarez, Kathryn Dempsey, Anne Fischer, Zahraa Wajih Alsafwani, William Gasper, Mallory J. Suhr Van Haute, Haley R. Hassenstab, Shayda Azadmanesh, Missy Briardy, Skyler Gerbers, Aliyah Jabenis, Jennifer L. Thompson, Jonathan B. Clayton

Food for Health: Publications

Emerging evidence indicates that antibiotic-induced dysbiosis can play an etiological role in the pathogenesis of neuropsychiatric disorders. However, most of this evidence comes from rodent models. The objective of this study was to evaluate if antibiotic-induced gut dysbiosis can elicit changes in gut metabolites and behavior indicative of gut-brain axis disruption in common marmosets (Callithrix jacchus) – a nonhuman primate model often used to study sociability and stress. We were able to successfully induce dysbiosis in marmosets using a custom antibiotic cocktail (vancomycin, enrofloxacin and neomycin) administered orally for 28 days. This gut dysbiosis altered gut metabolite profiles, …

Concordance In Medical Urgency Classification Of Discharge Diagnoses And Reasons For Visit, Theodoros V. Giannouchos, Benjamin Ukert, Brad Wright

APC Fund

Importance Current policies to divert emergency department (ED) visits for less medically urgent conditions to more cost-effective settings rely on retrospective adjudication of discharge diagnoses. However, patients present to the ED with concerns, making it challenging for clinicians.

Objective To characterize ED visits based on the medical urgency of the presenting reasons for visit and to explore the concordance between discharge diagnoses and reasons for visit.

Design, Setting, and Participants In this retrospective, cross-sectional study, a nationwide sample of ED visits by adults (aged ≥18 years) in the US from the 2018 and 2019 calendar years’ ED data of the …

Brain-Based Classification Of Youth With Anxiety Disorders: Transdiagnostic Examinations Within The Enigma-Anxiety Database Using Machine Learning, Willem B. Bruin, Paul Zhutovsky, Guido A. Van Wingen, Janna Marie Bas-Hoogendam, Nynke A. Groenewold, Kevin Hilbert, Anderson M. Winkler, André Zugman, Federica Agosta, Fredrik Åhs

School of Medicine Publications

Neuroanatomical findings on youth anxiety disorders are notoriously difficult to replicate, small in effect size and have limited clinical relevance. These concerns have prompted a paradigm shift toward highly powered (that is, big data) individual-level inferences, which are data driven, transdiagnostic and neurobiologically informed. Here we built and validated supervised neuroanatomical machine learning models for individual-level inferences, using a case–control design and the largest known neuroimaging database on youth anxiety disorders: the ENIGMA-Anxiety Consortium (N = 3,343; age = 10–25 years; global sites = 32). Modest, yet robust, brain-based classifications were achieved for specific anxiety disorders (panic disorder), but …

Luminescence And Excited-State Reactivity In A Heteroleptic Tricyanido Fe(Iii) Complex, Yating Ye, Pablo Garrido-Barros, Joël Wellauer, Carlos M Cruz, Rodrigue Lescouëzec, Oliver S Wenger, Juan Manuel Herrera, Juan-Ramón Jiménez

Faculty, Staff and Student Publications

Harnessing sunlight via photosensitizing molecules is key for novel optical applications and solar-to-chemical energy conversion. Exploiting abundant metals such as iron is attractive but becomes challenging due to typically fast nonradiative relaxation processes. In this work, we report on the luminescence and excited-state reactivity of the heteroleptic [FeIII(pzTp)(CN)3]− complex (pzTp = tetrakis(pyrazolyl)borate), which incorporates a σ-donating trispyrazolyl chelate ligand and three monodentate σ-donating and π-accepting cyanide ligands. Contrary to the nonemissive [Fe(CN)6]3–, a broad emission band centered at 600 nm at room temperature has been recorded for the heteroleptic analogue attributed to the radiative deactivation from a 2LMCT excited state …

Outcomes Of Patients With Multiple Myeloma And 1q Gain/Amplification Receiving Autologous Hematopoietic Stem Cell Transplant: The Md Anderson Cancer Center Experience, Oren Pasvolsky, Sassine Ghanem, Denái R Milton, Mikael Rauf, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Yosra Aljawai, Hina N Khan, Partow Kebriaei, Hans C Lee, Krina K Patel, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

The prognostic impact of additional copies of chromosome 1q (1q + ) on outcomes of newly-diagnosed multiple myeloma (NDMM) patients undergoing autologous transplantation (autoSCT) is unclear. We conducted a retrospective single-center analysis of NDMM patients with 1q21 gain/amplification (3 or ≥4 copies of 1q, respectively) that received autoSCT between 2008-2018. 213 patients were included (79% 1q gain; 21% 1q amplification). The most commonly used induction regimen was bortezomib, lenalidomide, and dexamethasone (41%). At day100 post-autoSCT and at best post-transplant response, 78% and 87% of patients achieved ≥VGPR, and 38% and 50% achieved MRD-negative ≥VGPR, respectively. Median PFS and OS for …

Nuclear Phosphoproteome Reveals Prolyl Isomerase Pin1 As A Modulator Of Oncogene-Induced Senescence, Rodrigo Mohallem, Uma K. Aryal

Purdue University Libraries Open Access Publishing Fund

Mammalian cells possess intrinsic mechanisms to prevent tumorigenesis upon deleterious mutations, including oncogene-induced senescence (OIS). The molecular mechanisms underlying OIS are, however, complex and remain to be fully characterized. In this study, we analyzed the changes in the nuclear proteome and phosphoproteome of human lung fibroblast IMR90 cells during the progression of OIS induced by oncogenic RASG12V activation. We found that most of the differentially regulated phosphosites during OIS contained prolyl isomerase PIN1 target motifs, suggesting PIN1 is a key regulator of several promyelocytic leukemia nuclear body proteins, specifically regulating several proteins upon oncogenic Ras activation. We showed that PIN1 …

Regional Variability In The Prevalence Of Food Insecurity And Diet Quality Among United States Children, Jayna M Dave, Tzuan A Chen, Alexandra N Castro, Mamie White, Elizabeth A Onugha, Sloane Zimmerman, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Understanding the association between food security status (FSS) and diet quality in children is crucial. This study investigated regional variability in FSS, participation in the federal nutrition assistance program (FNAP), and diet quality among US children. National Health and Nutrition Examination Survey (NHANES) data from 2013 to 2016 were analyzed. The association between FSS, FNAP participation, and diet quality (Healthy Eating Index—HEI-2015) was assessed using multiple linear/logistic regression models. The sample included 6403 children (mean age: 7.5 years; 51% male; 33% Hispanic). Within the sample, 13% reported child food insecurity, and 30% reported household food insecurity. Additionally, 90% participated in …

Development Of Right Ventricular Electromechanical Dyssynchrony Following Surgical Repair Of Tetralogy Of Fallot In Infants., Andrew W. Mccrary, Sydney D. Collins, Zebulon Z. Spector, P Andrea Kropf, Piers C A Barker, Joseph Kisslo, Daniel Forsha

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: In adolescents and adults with tetralogy of Fallot (TOF), right ventricle (RV) electromechanical dyssynchrony (EMD) due to right bundle branch block (RBBB) is associated with reduced exercise capacity and RV dysfunction. While the development of RBBB following surgical repair of tetralogy of Fallot (rTOF) is a frequent sequela, it is not known whether EMD is present in every patient immediately following rTOF. The specific timing of the onset of RBBB following rTOF therefore provides an opportunity to assess whether acute RBBB is associated with the simultaneous acquisition of EMD.

METHODS: Transthoracic echocardiography with speckle tracking analysis for RV global …

Age And Sex Disparities In Blood Pressure Control And Therapeutic Inertia: Impact Of A Quality Improvement Program, Olivia Myers, Talar Markossian, Beatrice Probst, Grant Hiura, Katherine Habicht, Brent Egan, Holly Kramer

Parkinson School of Health Sciences and Public Health

Objective

Methods

Delineating The Mechanism Of Fragility At Bcl6 Breakpoint Region Associated With Translocations In Diffuse Large B Cell Lymphoma, Vidya Gopalakrishnan, Urbi Roy, Shikha Srivastava, Khyati M Kariya, Shivangi Sharma, Saniya M Javedakar, Bibha Choudhary, Sathees C Raghavan

Faculty, Staff and Student Publications

BCL6 translocation is one of the most common chromosomal translocations in cancer and results in its enhanced expression in germinal center B cells. It involves the fusion of BCL6 with any of its twenty-six Ig and non-Ig translocation partners associated with diffuse large B cell lymphoma (DLBCL). Despite being discovered long back, the mechanism of BCL6 fragility is largely unknown. Analysis of the translocation breakpoints in 5' UTR of BCL6 reveals the clustering of most of the breakpoints around a region termed Cluster II. In silico analysis of the breakpoint cluster sequence identified sequence motifs that could potentially fold into …

Molecular And Clinical Effects Of Aromatase Inhibitor Therapy On Skeletal Muscle Function In Early-Stage Breast Cancer, Tara A Seibert, Lei Shi, Sandra Althouse, Richard Hoffman, Bryan P Schneider, Kristen A Russ, Cody A Altherr, Stuart J Warden, Theresa A Guise, Andrew R Coggan, Tarah J Ballinger

Faculty, Staff and Student Publications

We evaluated biochemical changes in skeletal muscle of women with breast cancer initiating aromatase inhibitors (AI), including oxidation of ryanodine receptor RyR1 and loss of stabilizing protein calstabin1, and detailed measures of muscle function. Fifteen postmenopausal women with stage I-III breast cancer planning to initiate AI enrolled. Quadriceps muscle biopsy, dual-energy x-ray absorptiometry, isokinetic dynamometry, Short Physical Performance Battery, grip strength, 6-min walk, patient-reported outcomes, and serologic measures of bone turnover were assessed before and after 6 months of AI. Post-AI exposure, oxidation of RyR1 significantly increased (0.23 ± 0.37 vs. 0.88 ± 0.80, p <  0.001) and RyR1-bound calstabin1 significantly decreased (1.69 ± 1.53 vs. 0.74 ± 0.85, p <  0.001), consistent with dysfunctional calcium channels in skeletal muscle. Grip strength significantly decreased at 6 months. No significant differences were seen in isokinetic dynamometry measures of muscle contractility, fatigue resistance, or muscle recovery post-AI exposure. However, there was significant correlation between oxidation of RyR1 with muscle power (r = 0.60, p = 0.02) and muscle fatigue (r = 0.57, p = 0.03). Estrogen deprivation therapy for breast cancer resulted in maladaptive changes in skeletal muscle, consistent with the biochemical signature of dysfunctional RyR1 calcium channels. Future studies will evaluate longer trajectories of muscle function change and include other high bone turnover states, such as bone metastases.

Isotherms, Kinetics And Thermodynamic Mechanism Of Methylene Blue Dye Adsorption On Synthesized Activated Carbon, Atef El Jery, Heba Saed Kariem Alawamleh, Mustafa Humam Sami, Hussein Abdullah Abbas, Saad Sh Sammen, Amimul Ahsan, M A Imteaz, Abdallah Shanableh, Md Shafiquzzaman, Haitham Osman, Nadhir Al-Ansari

Faculty, Staff and Student Publications

The treatment of methylene blue (MB) dye wastewater through the adsorption process has been a subject of extensive research. However, a comprehensive understanding of the thermodynamic aspects of dye solution adsorption is lacking. Previous studies have primarily focused on enhancing the adsorption capacity of methylene blue dye. This study aimed to develop an environmentally friendly and cost-effective method for treating methylene blue dye wastewater and to gain insights into the thermodynamics and kinetics of the adsorption process for optimization. An adsorbent with selective methylene blue dye adsorption capabilities was synthesized using rice straw as the precursor. Experimental studies were conducted …

The Effects Of Physical Activity On Experimental Models Of Vascular Dementia; A Systematic Review And Meta-Analysis, Ifechukwude J. Biose, Wesley H. Chastain, Rebecca J. Solch-Ottaiano, Viktoriya S. Grayson, Hanyun Wang, Somdeb Banerjee, Gregory J. Bix

School of Medicine Faculty Publications

Background; Physical activity is associated with improved brain health and cognition in humans. However, the validity, range, and quality of evidence for the beneficial outcomes linked to exercise in experimental models of vascular dementia (VaD) have not been evaluated. We performed a systematic review and meta-analysis of studies that assessed the effect of exercise intervention on models of VaD to provide an unbiased and comprehensive determination of the cognitive function and brain morphology benefits of exercise. Summary; A systematic search in three databases as well as study design characteristics and experimental data extraction were completed in December 2021. We investigated …

Precision Microbial Intervention Improves Social Behavior But Not Autism Severity: A Pilot Double-Blind Randomized Placebo-Controlled Trial, Luigi Mazzone, Sean W Dooling, Elisabetta Volpe, Mirko Uljarević, Jillian L Waters, Andrea Sabatini, Lucrezia Arturi, Roberta Abate, Assia Riccioni, Martina Siracusano, Marcela Pereira, Lars Engstrand, Fernanda Cristofori, Domenico Adduce, Ruggiero Francavilla, Mauro Costa-Mattioli, Antonio Y Hardan

Faculty, Staff and Students Publications

Autism spectrum disorder (ASD) is characterized by the presence of restricted/repetitive behaviors and social communication deficits. Because effective treatments for ASD remain elusive, novel therapeutic strategies are necessary. Preclinical studies show that L. reuteri selectively reversed social deficits in several models for ASD. Here, in a double-blind, randomized, placebo-controlled trial, we tested the effect of L. reuteri (a product containing a combination of strains ATCC-PTA-6475 and DSM-17938) in children with ASD. The treatment does not alter overall autism severity, restricted/repetitive behaviors, the microbiome composition, or the immune profile. However, L. reuteri combination yields significant improvements in social functioning that generalized …

Neuroactive Steroid Effects On Autophagy In A Human Embryonic Kidney 293 (Hek) Cell Model, Sofia V Salvatore, Ma Xenia G Ilagan, Hongjin Shu, Peter M Lambert, Ann Benz, Mingxing Qian, Douglas F Covey, Charles F Zorumski, Steven Mennerick

2020-Current year OA Pubs

Neuropsychiatric and neurodegenerative disorders are correlated with cellular stress. Macroautophagy (autophagy) may represent an important protective pathway to maintain cellular homeostasis and functionality, as it targets cytoplasmic components to lysosomes for degradation and recycling. Given recent evidence that some novel psychiatric treatments, such as the neuroactive steroid (NAS) allopregnanolone (AlloP, brexanolone), may induce autophagy, we stably transfected human embryonic kidney 293 (HEK) cells with a ratiometric fluorescent probe to assay NAS effects on autophagy. We hypothesized that NAS may modulate autophagy in part by the ability of uncharged NAS to readily permeate membranes. Microscopy revealed a weak effect of AlloP …

The Chromatin Landscape Of Healthy And Injured Cell Types In The Human Kidney, Debora L Gisch, Jeannine Basta, Reetika Ghag, Charles Lu, Lisa Stout, Bo Zhang, Amanda Knoten, Shamim Mollah, Sanjay Jain, Michael Rauchman, Et Al.

2020-Current year OA Pubs

There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. Comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measure dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We establish a spatially-anchored epigenomic atlas to define the kidney's active, …

Genome-Wide Study Investigating Effector Genes And Polygenic Prediction For Kidney Function In Persons With Ancestry From Africa And The Americas, Odessica Hughes, Amy R Bentley, Charles E Breeze, Francois Aguet, Xiaoguang Xu, Girish Nadkarni, Quan Sun, Bridget M Lin, Thomas Gilliland, Mariah C Meyer, Jiawen Du, Laura M Raffield, Holly Kramer, Robert W Morton, Mateus H Gouveia, Elizabeth G Atkinson, Adan Valladares-Salgado, Niels Wacher-Rodarte, Nicole D Dueker, Xiuqing Guo, Yang Hai, Adebowale Adeyemo, Lyle G Best, Jianwen Cai, Guanjie Chen, Michael Chong, Ayo Doumatey, James Eales, Mark O Goodarzi, Eli Ipp, Marguerite Ryan Irvin, Minzhi Jiang, Alana C Jones, Charles Kooperberg, Jose E Krieger, Ethan M Lange, Matthew B Lanktree, James P Lash, Paulo A Lotufo, Ruth J F Loos, Vy Thi Ha My, Jesús Peralta-Romero, Lihong Qi, Leslie J Raffel, Stephen S Rich, Erik J Rodriquez, Eduardo Tarazona-Santos, Kent D Taylor, Jason G Umans, Jia Wen, Bessie A Young, Zhi Yu, Ying Zhang, Yii-Der Ida Chen, Tanja Rundek, Jerome I Rotter, Miguel Cruz, Myriam Fornage, Maria Fernanda Lima-Costa, Alexandre C Pereira, Guillaume Paré, Pradeep Natarajan, Shelley A Cole, April P Carson, Leslie A Lange, Yun Li, Eliseo J Perez-Stable, Ron Do, Fadi J Charchar, Maciej Tomaszewski, Josyf C Mychaleckyj, Charles Rotimi, Andrew P Morris, Nora Franceschini

Faculty, Staff and Students Publications

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10−8), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all.

Smaller Total And Subregional Cerebellar Volumes In Posttraumatic Stress Disorder: A Mega-Analysis By The Enigma-Pgc Ptsd Workgroup, Ashley A. Huggins, Evan M. Gordon, Et Al.

2020-Current year OA Pubs

No abstract provided.

A Structurally Precise Mechanism Links An Epilepsy-Associated Kcnc2 Potassium Channel Mutation To Interneuron Dysfunction, Jerome Clatot, Christopher B. Currin, Qiansheng Liang, Tanadet Pipatpolkai, Shavonne L. Massey, Ingo Helbig, Lucie Delemotte, Tim P. Vogels, Manuel Covarrubias, Ethan M. Goldberg

Farber Institute for Neuroscience Staff Papers and Presentations

De novo heterozygous variants in KCNC2 encoding the voltage-gated potassium (K+) channel subunit Kv3.2 are a recently described cause of developmental and epileptic encephalopathy (DEE). A de novo variant in KCNC2 c.374G > A (p.Cys125Tyr) was identified via exome sequencing in a patient with DEE. Relative to wild-type Kv3.2, Kv3.2-p.Cys125Tyr induces K+ currents exhibiting a large hyperpolarizing shift in the voltage dependence of activation, accelerated activation, and delayed deactivation consistent with a relative stabilization of the open conformation, along with increased current density. Leveraging the cryogenic electron microscopy (cryo-EM) structure of Kv3.1, molecular dynamic simulations suggest that a strong π-π stacking …