Medical Specialties Commons^™

Description Of Audiologic, Developmental, Ophthalmologic, And Neurologic Diagnoses At A Primary Care Clinic For Children In Foster Care, Jill Mcleigh, Lauren Malthaner, Melissa Reynoso, Kimberly Stone

Health Status, Outcomes, and Literacy and Healthcare Utilization

This study aimed to describe the prevalence of medically diagnosed audiologic, developmental, ophthalmologic, and neurologic conditions in a foster care primary care clinic and to identify any associations among these diagnoses and patient characteristics, placement type, and maltreatment type.

For questions about this study or others, please email [email protected]

childrens.com/fostercare

Spontaneous Coronary Artery Dissection Is Infrequent In Individuals With Heritable Thoracic Aortic Disease Despite Partially Shared Genetic Susceptibility, Regina Husman, Akiko Tanaka, S Keisin Wang, Kourosh Keyhani, Arash Keyhani

Faculty, Staff and Student Publications

Spontaneous isolated celiac artery dissection (SICAD) is a rare condition, defined as dissection of the celiac artery without aortic involvement. Because of its low prevalence, most studies have been limited to case reports and case series. We have described the case of a 44-year-old woman who had presented with symptomatic SICAD that had resulted in compromised flow to the hepatic arteries and was successfully treated with balloon angioplasty. Angioplasty alone might be effective for cases of extensive false lumen thrombosis in SICAD for immediate flow restoration to the true lumen, expediting positive remodeling.

Rising Costs Of Insulin And Effects Of Self-Management In Type 1 Diabetes, Justine Yadao

Nursing | Senior Theses

Background

Type 1 diabetes, also known as juvenile diabetes or insulin-dependent diabetes is a chronic condition where the pancreas may not be able to produce little to no insulin. This type of diabetes can be attributed to some factors such as age, family history, environmental factors or types of viruses. It is seen more often in children or adolescence but can develop in adults, averaging approximately 5-10% of the population.

Insulin is a type of hormone produced in the pancreas naturally or can be manufactured in the laboratory. People with Type 1 Diabetes need insulin from an exogenous source to …

Tceal1 Loss-Of-Function Results In An X-Linked Dominant Neurodevelopmental Syndrome And Drives The Neurological Disease Trait In Xq222 Deletions, Hadia Hijazi, Linda M Reis, Davut Pehlivan, Jonathan A Bernstein, Michael Muriello, Erin Syverson, Devon Bonner, Mehrdad A Estiar, Ziv Gan-Or, Guy A Rouleau, Ekaterina Lyulcheva, Lynn Greenhalgh, Marine Tessarech, Estelle Colin, Agnès Guichet, Dominique Bonneau, R H Van Jaarsveld, A M A Lachmeijer, Lyse Ruaud, Jonathan Levy, Anne-Claude Tabet, Rafal Ploski, Małgorzata Rydzanicz, Łukasz Kępczyński, Katarzyna Połatyńska, Yidan Li, Jawid M Fatih, Dana Marafi, Jill A Rosenfeld, Zeynep Coban-Akdemir, Weimin Bi, Richard A Gibbs, Grace M Hobson, Jill V Hunter, Claudia M B Carvalho, Jennifer E Posey, Elena V Semina, James R Lupski

Faculty, Staff and Student Publications

An Xq22.2 region upstream of PLP1 has been proposed to underly a neurological disease trait when deleted in 46,XX females. Deletion mapping revealed that heterozygous deletions encompassing the smallest region of overlap (SRO) spanning six Xq22.2 genes (BEX3, RAB40A, TCEAL4, TCEAL3, TCEAL1, and MORF4L2) associate with an early-onset neurological disease trait (EONDT) consisting of hypotonia, intellectual disability, neurobehavioral abnormalities, and dysmorphic facial features. None of the genes within the SRO have been associated with monogenic disease in OMIM. Through local and international collaborations facilitated by GeneMatcher and Matchmaker Exchange, we have identified and herein report seven de novo variants involving …

Perceived Efficacy, Reduced Prescription Drug Use, And Minimal Side Effects Of Cannabis In Patients With Chronic Orthopedic Pain, Ari Greis, Eric Larsen, Conan Liu, Bryan Renslo, Anjithaa Radakrishnan, Adrianne R Wilson-Poe

Rothman Institute Papers

Introduction: Although cannabis is widely used for the treatment of chronic pain, most research relies on patient self-report and few studies have objectively quantified its efficacy and side effects. Extant inventories for measuring cannabis use were not designed to capture the medically relevant features of cannabis use, but rather were designed to detect problematic use or cannabis use disorder. Thus, we sought to capture the medically relevant features of cannabis use in a population of patients with orthopedic pain and pair these data with objective measures of pain and prescription drug use. Materials and Methods: In this prospective observational study, …

Technology-Enhanced In Vivo Exposures In Prolonged Exposure For Ptsd: A Pilot Randomized Controlled Trial, Tanya C Saraiya, Amber M Jarnecke, Alex O Rothbaum, Bethany Wangelin, Lisa M Mcteague, Ron Acierno, Delisa G Brown, Emily Bristol, Hayley Feigl, Mclain Reese, Adam R Cobb, Bill Harley, Robert J Adams, Sudie E Back

Faculty, Staff and Student Publications

In vivo exposures (IVEs) are a key component of exposure-based treatments, during which patients approach fear-provoking, yet safe, situations in "real life." This pilot study assessed the use of a wearable technology (Bio Ware) during IVEs to enhance Prolonged Exposure (PE) therapy for PTSD. Bio Ware provides a clinician dashboard with real-time physiological and subjective data for clinicians to use for virtually guided IVEs. Participants (N = 40) were randomized to a Guided group that received standard PE and virtual, clinician-guided IVEs with the Bio Ware device, or a Non-Guided group that received standard PE and used the Bio Ware …

Low-Dose Aspirin For Venous Thromboembolism Prophylaxis Is Associated With Lower Rates Of Periprosthetic Joint Infection After Total Joint Arthroplasty, Farideh Najafi, Joseph K. Kendal, Nicholas V. Peterson, Kerri-Anne Ciesielka, Camilo Restrepo, Javad Parvizi, Nicholas M. Bernthal

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Aspirin as a venous thromboembolism (VTE) prophylactic agent has been shown to have antistaphylococcal and antibiofilm roles. Optimal acetylsalicylic acid (ASA) dosage would facilitate antimicrobial effects while avoiding over-aggressive inhibition of platelet antimicrobial function. Our purpose was to determine the periprosthetic joint infection (PJI) rate after total joint arthroplasty in patients receiving low-dose ASA (81 mg twice a day), in comparison to high-dose ASA (325 mg twice a day).

METHODS: We conducted a retrospective cohort study between 2008 and 2020. Eligible patients were older than 18 years, underwent primary total joint arthroplasty, both total knee arthroplasty and total hip …

Cross-Sectional Area Of The Longus Colli And Cervical Degenerative Spondylolisthesis: A Retrospective Review Evaluating This Anatomic Consideration, Khoa Tran, Aditya Mazmudar, Taylor Paziuk, Mark J. Lambrechts, Eric Tecce, Olivia Blaber, Kamil Okroj, Brian A Karamian, Jose A Canseco, Jeffrey A Rihn, Alan Hilibrand, Christopher Kepler, Alexander R. Vaccaro, Gregory D. Schroeder

Department of Orthopaedic Surgery Faculty Papers

Background: Limited literature is available to define the impact of the longus colli muscle, a deep flexor of the spine, on cervical spine stability despite its close proximity to the vertebrae. Aims and Objectives: The purpose of this study was to determine if longus colli cross-sectional area (CSA) is associated with the severity preoperative cervical degenerative spondylolisthesis. Materials and Methods: Patients undergoing elective anterior cervical discectomy and fusion (ACDF) for cervical spondylolisthesis between 2010-2021 were retrospectively identified. Longus colli cross-sectional areas (CSA) were measured from preoperative MRI images at the C5 level. Preoperative spondylolisthesis measurements were recorded with cervical radiographs. …

A National Multi-Institutional Analysis Of Predictors Of Surgical Site Complications And Unplanned Reoperation After Paramedian Forehead Flap Reconstruction, Garrett Ni, Rohan Brebion, Pablo A. Baltodano, Michael C. Coronado, Nicholas Elmer, Theresa K. Webster, Huaqing Zhao, Xiaoning Lu, Sthefano Araya, Sameer Patel

Student Papers, Posters & Projects

Background: Although postoperative complications of paramedian forehead flap (PMFF) are generally low, surgical site complications and unplanned reoperation can still occur. Recent literature suggests infection to be the most common complication following PMFF reconstruction. This study sought to determine the patient and preoperative factors associated with surgical site complications and unplanned reoperations at a national level.

Methods: Patients who underwent PMFF reconstruction from the ACS-NSQIP 2007 - 2019 database were analyzed to determine composite surgical site morbidity and unplanned return to the operating room. Patient and operative factors were also analyzed to assess independent risk factors for surgical site morbidity …

Barriers And Facilitators In Implementing Multiplatform Remote Patient Monitoring Of Heart Failure Patients In Clinical Settings, Zachary Andrew Reilly

All Theses

Remote patient monitoring (RPM), which provides continuous monitoring of vital signs, has become increasingly utilized in patients with heart failure (HF). As this condition impacts more than 26 million Americans each year, it is important to determine the barriers and facilitators of RPM to both improve patient care and help medical professionals make more informed medical decisions. To determine these barriers and facilitators, our research team partnered with Prisma Health-Upstate to interview healthcare professionals working at Carolina Cardiology Consultants--Greenville, which uses multiple RPM systems to monitor heart failure patients.

The twelve interviews conducted support that healthcare professionals would benefit from …

Intensivist -Driven Ventilator Management Shortens Duration Of Mechanical Ventilation In Coronary Artery Bypass Graft Surgery Patients, Yonatan Dollin, Brian Elliott, Ronald J. Markert, Angela Morman, Matthew Koroscil

Internal Medicine Faculty Publications

Background Prolonged mechanical ventilation in post Coronary Artery Bypass Graft Surgery (CABG) is associated with deleterious effects including, increased ICU and hospital length of stay (LOS), infectious complications, and mortality. Standardized ventilator weaning protocols and the utilization of critical care physicians in post CABG patient care vary substantially among institutions. The purpose of this study was to evaluate if intensivist consultation in conjunction with a multidisciplinary, standardized ventilator weaning protocol improves outcomes in CABG patients. Materials and Methods We performed a single-center, retrospective, before-after cohort analysis at Miami Valley Hospital in Dayton, OH, a 970-bed community hospital. Patients were divided …

An Unexpected Case Of Non-Uremic Calciphylaxis In A Patient With Multiple Risk Factors, Shannon Nugent, Fred Karaisz, Maisa Elbadawi, Andrew Touati, Neda Nikbakht, Jason B. Lee, Hasan Arif

Division of Internal Medicine Faculty Papers & Presentations

A 58-year-old woman with a history of morbid obesity, asthma, and prior warfarin use presented to the hospital with shortness of breath and a three-month history of painful, ulcerated ulcers with retiform purpura of her bilateral distal extremities. A punch biopsy specimen demonstrated focal necrosis and hyalinization of the adipose tissue with subtle arteriolar calcium deposition, findings consistent with calciphylaxis. We discuss the presentation of non-uremic calciphylaxis and review the risk factors, pathophysiology, and interdisciplinary management approach of this rare disease.

Impairment-Based Multidisciplinary Rehabilitation Management In Multiple Sclerosis In Pakistan, Sarah Razaq, Fahim Anwar, Wasim Wali

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Perceptions Of Orthopaedic Medicine Students And Their Supervisors About Practice-Based Learning: An Exploratory Qualitative Study, Muhamed Nsubuga, Robert Opoka, Moses Galukande, Ian G. Munabi, Aloysius . Mubuuke, Sarah Kiguli

Paediatrics and Child Health, East Africa

Background: Practice-based learning is crucial in forming appropriate strategies for improving learning among the medical students that support the country’s understaffed health sector. Unsatisfactory learning consequently results in poor performance of students and poor quality of health care workforce in the long run. Exploring the perceptions about the current practice-based learning system and how to improve is thus vital. This study set out to explore the perceptions of Orthopaedic medicine students and their supervisors about practice-based learning at a tertiary training hospital.

Methods: This was an exploratory phenomenological qualitative study that involved in-depth interviews among 10 Orthopedic students during their …

Who Leads The Emergency Department Debrief?, Allison D. Lane, Ethan Bryce, Marcy R. Milbrandt, Lisa R. Stoneking

Journal of Wellness

No abstract provided.

Effectiveness Of Non-Invasive Respiratory Support Strategies In Patients With Covid-19: A Systematic Review And Meta Analysis, Vinesh Kumar, Umair Arshad Malik, Reshman Kumari, Berkha Berkha, Vijay Kumar, Manoj Kumar, Simran Simran, Suman Suman, Bushra Nasim

Medical College Documents

Background: The effectiveness of non-invasive respiratory strategies, namely CPAP and HFNO, in reducing the risk of mortality and tracheal intubation in patients with severe COVID-19 is not well established.
Methods: A thorough literature search was conducted across 3 electronic databases (Medline, EMBASE and Cochrane Central) from inception through July 2022. Randomized controlled trials (RCTs) and observational studies assessing the impact of CPAP or HFNO on clinical outcomes in patients infected with COVID-19 were considered for inclusion. End-points included all-cause mortality and risk of tracheal intubation. Evaluations were reported as risk ratios (RRs) with 95% confidence intervals (CI) and analysis was …

The Relationship Between Anti-Müllerian Hormone, Body Mass Index And Weight Loss: A Review Of The Literature, Jacqueline Kloos, Rachel Weinerman

Student Scholarship

Anti-Müllerian hormone (AMH) is commonly used as a proxy for ovarian reserve due to its secretion by antral follicles. It is considered a metric for prediction of ovarian response to certain assisted reproduction therapies. As obesity has a negative impact on fertility, it is important to establish whether obesity-induced hormonal changes influence AMH levels, if and how weight loss affects AMH, and if that influence represents altered reproductive function. The aim of this study was to review the existing literature on the effects of body mass index and weight loss on AMH levels. A PubMed literature keyword search with relevant …

Facilitators And Inhibitors To First Adult Care Visits In The Transition From Paediatric To Adult Orientated Inflammatory Bowel Disease Healthcare, Joanna Rea

Theses

Background: Inflammatory bowel disease (IBD) can be a very debilitating disease and it is found to be more extensive in children with rapid early progression (Van Limbergen et al., 2008). As adolescents, these children transition from paediatric to adult oriented care. The first adult care visits are a pivotal phase of a successful transition process, where adolescents potentially begin to actively take control of their disease. The aim of this study is to explore the inhibitors and facilitators to first adult care visits in the transition process from paediatric to adult oriented IBD healthcare.

Methods: An exploratory, descriptive, qualitative approach …

A Substring Replacement Approach For Identifying Missing Is-A Relations In Snomed Ct, Xubing Hao, Rashmie Abeysinghe, Jay Shi, Licong Cui

Faculty, Staff and Student Publications

Biomedical ontologies provide formalized information and knowledge in the biomedical domain. Over the years, biomedical ontologies have played an important role in facilitating biomedical research and applications. Common quality issues of biomedical ontologies include inconsistent naming of concepts, redundant concepts, redundant relations, incomplete/incorrect concept definitions, and incomplete/incorrect class hierarchies. In this work, we focus on addressing the incompleteness of the class hierarchy in SNOMED CT. We develop a substring replacement approach, leveraging concepts’ lexical features and existing IS-A relations to identify potential missing IS-A relations in SNOMED CT. To evaluate the effectiveness of our approach, we performed both automated and …

Single Low-Dose Targeted Bevacizumab Infusion In Adult Patients With Steroid-Refractory Radiation Necrosis Of The Brain: A Phase Ii Open-Label Prospective Clinical Trial, Shervin R. Dashti, Robert J. Kadner, Bradley S. Folley, Jason P. Sheehan, Dong Y. Han, Richard J. Kryscio, Mary B. Carter, Lisa B. E. Shields, Brian M. Plato, Renato V. La Rocca, Aaron C. Spalding, Tom L. Yao, Justin F. Fraser

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVE There is an unmet need for safe and rapidly effective therapies for refractory brain radiation necrosis (RN). The aim of this prospective single-arm phase II trial was to evaluate the safety and efficacy of a single low-dose targeted bevacizumab infusion after blood-brain barrier disruption (BBBD) in adult patients with steroid-refractory brain RN.

METHODS Ten adults with steroid-refractory, imaging-confirmed brain RN were enrolled between November 2016 and January 2018 and followed for 12 months after treatment. Bevacizumab 2.5 mg/kg was administered as a one-time targeted intra-arterial infusion immediately after BBBD. Primary outcomes included safety and > 25% decrease in lesion volume. …

Impact Of The 2016 American College Of Surgeons Guideline Revision On Overlapping Lumbar Fusion Cases At A Large Academic Medical Center, Ali S. Farooqi, Austin J. Borja, Rashad Jabarkheel, Gregory Glauser, Krista Strouz, Scott Mcclintock, Neil R. Malhotra

Mathematics Faculty Publications

OBJECTIVE: The American College of Surgeons (ACS) u pdated its guidelines on overlapping surgery in 2016. The objective was to examine differences in postoperative outcomes after overlapping surgery either pre-ACS guide-line revision or post-guideline revision, in a coarsened exact matching sample. -METHODS: A total of 3327 consecutive adult patients u ndergoing single-level posterior lumbar fusion from 2013 to 2019 were retrospectively analyzed. Patients were separated into a pre-ACS guideline revision cohort (surgery before April 2016) or a post-guideline revision cohort (surgery after October 2016) for comparison. The primary outcomes were proportion of cases performed with any degree of overlap, and …

Perioperative Chanage In Cervical Lordosis And Health-Related Quality-Of-Life Outcomes, Jose A Canseco, Brian A Karamian, Parthik D Patel, Michael Markowitz, Joseph K Lee, Mark F Kurd, D Greg Anderson, Jeffrey A Rihn, Alan S Hilibrand, Christopher K Kepler, Alexander R Vaccaro, Gregory D Schroeder

Rothman Institute Papers

BACKGROUND: Surgeons have scrutinized spinal alignment and its impact on improving clinical outcomes following anterior cervical discectomy and fusion (ACDF). The primary analysis of this study examines the relationship between change in perioperative cervical lordosis (CL) and health-related quality-of-life (HRQOL) outcomes after ACDF. Secondary analysis evaluates the effects of fusion construct length on outcomes in patients grouped by preoperative cervical alignment.

METHODS: A retrospective cohort study was performed on an institutional database including patients who underwent 1- to 3-level ACDF. C2-C7 CL was measured preoperatively and at final follow-up. For primary analysis, patients were classified based on their perioperative cervical …

Ten Year Real World Experience With Ultrafiltration For The Management Of Acute Decompensated Heart Failure, Donald C. Haas, Maureen Hummel, Patricia Barrella, Waqas Ullah, Misung Yi, Robert Watson

Abington Jefferson Health Papers

Background: Randomized controlled trials (RCT) of ultrafiltration (UF) have demonstrated conflicting results regarding its efficacy and safety.

Objective: We reviewed 10 years of data for adjustable UF during heart failure hospitalizations in a real world cohort.

Methods: We performed a retrospective, single center analysis of 335 consecutive patients treated with adjustable rate UF using the CHF Solutions Aquadex Flex Flo System from 2009 to 2019.

Results: Compared to previous RCTs investigating UF, our cohort was older, with worse renal impairment and more antecedent HF hospitalizations in the year preceding therapy. Mean fluid removal with UF was 14.6 l. Mean weight …

Characterizing Treatment Resistance In Muscle Invasive Bladder Cancer Using The Chicken Egg Chorioallantoic Membrane Patient-Derived Xenograft Model, Hugo Villanueva, Gabrielle A Wells, Malachi T Miller, Mariana Villanueva, Ravi Pathak, Patricia Castro, Michael M Ittmann, Andrew G Sikora, Seth P Lerner

Faculty, Staff and Student Publications

BACKGROUND: Non-metastatic muscle invasive urothelial bladder cancer (MIBC) has a poor prognosis and standard of care (SOC) includes neoadjuvant cisplatin-based chemotherapy (NAC) combined with cystectomy. Patients receiving NAC have at best

METHODS: We optimized engraftment conditions for primary MIBC tumors using the CAM-PDX model and tested concordance between cisplatin-based chemotherapy response of patients to matching PDX tumors using tumor growth coupled with immunohistochemistry markers of proliferation and apoptosis. We also tested select kinase inhibitor response on chemotherapy-resistant bladder cancers on the CAM-PDX using tumor growth measurements and immuno-detection of proliferation marker, Ki-67.

RESULTS: Our results show primary, NAC-resistant, MIBC tumors …

A Minimal Role For Synonymous Variation In Human Disease, Ryan S Dhindsa, Quanli Wang, Dimitrios Vitsios, Oliver S Burren, Fengyuan Hu, James E Dicarlo, Leonid Kruglyak, Daniel G Macarthur, Matthew E Hurles, Slavé Petrovski

Duncan NRI Faculty and Staff Publications

Synonymous mutations change the DNA sequence of a gene without affecting the amino acid sequence of the encoded protein. Although some synonymous mutations can affect RNA splicing, translational efficiency, and mRNA stability, studies in human genetics, mutagenesis screens, and other experiments and evolutionary analyses have repeatedly shown that most synonymous variants are neutral or only weakly deleterious, with some notable exceptions. Based on a recent study in yeast, there have been claims that synonymous mutations could be as important as nonsynonymous mutations in causing disease, assuming the yeast findings hold up and translate to humans. Here, we argue that there …

Neurobehavioral Deficits And A Progressive Ictogenesis In The Tetrodotoxin Model Of Epileptic Spasms, John T Le, Carlos J Ballester-Rosado, James D Frost, John W Swann

Duncan NRI Faculty and Staff Publications

Objective: Our goal was to determine whether animals with a history of epileptic spasms have learning and memory deficits. We also used continuous (24/7) long-term electroencephalographic (EEG) recordings to evaluate the evolution of epileptiform activity in the same animals over time.

Methods: Object recognition memory and object location memory tests were undertaken, as well as a matching to place water maze test that evaluated working memory. A retrospective analysis was undertaken of long-term video/EEG recordings from rats with epileptic spasms. The frequency and duration of the ictal events of spasms were quantified.

Results: Rats with a history of epileptic spasms …

Use Of Fenoldopam In Children With Congenital Heart Disease To Decrease Fluid Balance: A Retrospective, Descriptive Study And Insights Into Predictors Of Decreased Fluid Balance, Jacqueline Rausa, Rohit S Loomba, Vincent Dorsey, Priya Chandra, Jamie S Penk, Saul Flores, Enrique G Villarreal, Stuart L Goldstein

Faculty, Staff and Students Publications

This retrospective study aimed to determine if fenoldopam is associated with a decrease in fluid balance and to define the factors that may promote this in children with a history of congenital heart disease at the cardiac intensive care unit (CICU). Patients cared from January 2014 to December 2018 in the CICU were reviewed, and those on fenoldopam infusion were identified. Patient cohort data included demographics, clinical information, laboratory results, hemodynamic and urine output measurements, and information regarding fenoldopam infusion were compared between those with and without decrease in fluid balance. Forty-six patients were identified. Patients received a starting dose …

Luspatercept In Low-Risk Myelodysplastic Syndrome: A Real-World Single Institution Case Series, Shamis Khan, Sara Taveras Alam, Rosa Torres Ramos, John Etumbani Mbue, Effrosyni Apostolidou, Gustavo A Rivero, Sarvari Venkata Yellapragada

Faculty, Staff and Student Publications

No abstract provided.

Single-Cell Crispr Immune Screens Reveal Immunological Roles Of Tumor Intrinsic Factors, Jiakai Hou, Shaoheng Liang, Chunyu Xu, Yanjun Wei, Yunfei Wang, Yukun Tan, Nidhi Sahni, Daniel J Mcgrail, Chantale Bernatchez, Michael Davies, Yumei Li, Rui Chen, S Stephen Yi, Yiwen Chen, Cassian Yee, Ken Chen, Weiyi Peng

Faculty, Staff and Student Publications

Genetic screens are widely exploited to develop novel therapeutic approaches for cancer treatment. With recent advances in single-cell technology, single-cell CRISPR screen (scCRISPR) platforms provide opportunities for target validation and mechanistic studies in a high-throughput manner. Here, we aim to establish scCRISPR platforms which are suitable for immune-related screens involving multiple cell types. We integrated two scCRISPR platforms, namely Perturb-seq and CROP-seq, with both in vitro and in vivo immune screens. By leveraging previously generated resources, we optimized experimental conditions and data analysis pipelines to achieve better consistency between results from high-throughput and individual validations. Furthermore, we evaluated the performance …

Human Loss-Of-Function Variants In The Serotonin 2c Receptor Associated With Obesity And Maladaptive Behavior, Yang He, Bas Brouwers, Hesong Liu, Hailan Liu, Katherine Lawler, Edson Mendes De Oliveira, Dong-Kee Lee, Yongjie Yang, Aaron R Cox, Julia M Keogh, Elana Henning, Rebecca Bounds, Aliki Perdikari, Vikram Ayinampudi, Chunmei Wang, Meng Yu, Longlong Tu, Nan Zhang, Na Yin, Junying Han, Nikolas A Scarcelli, Zili Yan, Kristine M Conde, Camille Potts, Jonathan C Bean, Mengjie Wang, Sean M Hartig, Lan Liao, Jianming Xu, Inês Barroso, Jacek Mokrosinski, Yong Xu, I Sadaf Farooqi

Children’s Nutrition Research Center Staff Publications

Serotonin reuptake inhibitors and receptor agonists are used to treat obesity, anxiety and depression. Here we studied the role of the serotonin 2C receptor (5-HT2CR) in weight regulation and behavior. Using exome sequencing of 2,548 people with severe obesity and 1,117 control individuals without obesity, we identified 13 rare variants in the gene encoding 5-HT2CR (HTR2C) in 19 unrelated people (3 males and 16 females). Eleven variants caused a loss of function in HEK293 cells. All people who carried variants had hyperphagia and some degree of maladaptive behavior. Knock-in male mice harboring a human loss-of-function HTR2C variant developed …