Medical Specialties Commons^™

Genetic Variation Between Small Bowel And Colon-Predominant Crohn's Disease, Halee Patel, R Alan Harris, Justin H Qian, Numan Oezguen, Ashleigh Watson, Reka G Szigeti, Stanley Cho, Wenly Ruan, Savini Britto, Antone Opekun, Geoffrey Preidis, Richard Kellermayer

Faculty, Staff and Students Publications

No abstract provided.

Safety And Efficacy Of Intravenous Sotalol Following Congenital Heart Surgery, Ellis Rochelson, Maria Gutierrez, Santiago O Valdés, Katherine Lemming, Taylor S Howard, Tam Dan N Pham, Christina Y Miyake, Vicken Asadourian, Raajen Patel, Jeffrey J Kim

Faculty, Staff and Students Publications

No abstract provided.

Association Of Low Diastolic Blood Pressure With Cardiovascular Outcomes And All-Cause Mortality: A Meta-Analysis, Tariq Jamal Siddiqi, Muhammad Shariq Usman, Amna Siddiqui, Ali Salman, Nicholas Talbot, Laibah Arshad Khan, Aisha Shabbir, Michael E Hall, George E Taffet

Faculty, Staff and Students Publications

Background: Reduction of diastolic blood pressure (DBP) below 70 mmHg may decrease perfusion to the heart and worsen cardiovascular (CV) outcomes.

Aims: Explore the association between low DBP and CV outcomes.

Methods: We searched the online databases until August 2023 for studies reporting the risk of all-cause mortality (ACM) or CV outcomes in patients with low versus normal DBP (70-80mm Hg).

Results: Inclusion of 10 studies (n = 1,998,223 patients) found that a mean achieved DBP < 60 mmHg was associated with an increased risk of all-cause mortality (HR 1.48; 95 % CI [1.26-1.74]), especially in patients with pre-existing CV disease. It was also associated to a higher risk of major adverse cardiovascular events (HR 1.84; [1.28-2.65]) and myocardial infarction (HR 1.49; [1.13-1.97]). A DBP of 60-69 mmHg was associated with an increased risk of all-cause mortality (HR 1.11; [1.03-1.20]).

Conclusion: Reduction of DBP, particularly below 60 mmHg, is associated with increased risk of ACM.

Bridging The Gap: Assessing Cmv Dnaemia In Kidney Transplant Recipients With Previous Solid Organ Transplants, Goni Katz-Greenberg, Julie M Steinbrink, Krishna Shah, Jennifer S Byrns

Faculty, Staff and Students Publications

Cytomegalovirus (CMV) infection poses a significant threat to solid organ transplant (SOT) recipients and can lead to various complications and adverse outcomes. In an effort to prevent CMV infection, it is common to utilize prophylactic strategies, including antiviral medications such as valganciclovir, especially for high-risk patients. Risk factors for CMV infection in kidney transplant recipients (KTRs) include CMV mismatch between donor and recipient (i.e., donor positive, recipient negative), and intensity of immunosuppression, such as the use of T-cell depleting agents. However, little attention has been given to KTRs with a history of prior SOTs, despite their prolonged exposure to immunosuppressive …

Profile Of Caregiving Activities And Association With Physical Health Among Dementia Spousal Caregivers, Jinmyoung Cho, Laura P Sands, Alan B Stevens, Heather G Allore, Molly J Horstman

Faculty, Staff and Students Publications

Background and objectives: This study aims to identify patterns of caregiving intensity and assess associations between caregiving intensity and multidimensional physical health indicators and health behaviors among spousal caregivers of persons with Alzheimer's disease and related dementia.

Research design and methods: Using data from 152 spousal caregivers aged 65 and older, the intensity of their caregiving experience was measured as the number and frequency of health- and medical-related helping activities for their care recipient. Multidimensional health indicators included self-reported fatigue, sleep disturbance, physical functioning, pain interference, general health, and the number of chronic conditions from the electronic health records. Self-reported …

Anesthetic Management Of A Patient With Renal Cell Carcinoma-Associated Venous Thrombosis And Massive Transfusion, Gary Zhang, Ryan Palacios, Jamal Hasoon, Christopher L Robinson, Anvinh Nguyen

Faculty, Staff and Students Publications

A 53-year-old male with a history of multiple deep venous thromboses (DVTs) underwent a right open radical nephrectomy with inferior vena cava (IVC) thrombectomy in the context of renal cell carcinoma (RCC)-associated venous thrombosis. Imaging and renal biopsy revealed a diagnosis of RCC with non-occlusive thrombosis of the left renal vein and occlusive thrombosis of the infrarenal IVC. The major risks of concern for the procedure included thrombus embolization from surgical manipulation and massive bleeding. Intraoperatively, the patient experienced significant hemorrhage requiring massive transfusion protocol. The purpose of this case report is to emphasize the importance of multidisciplinary involvement, intraoperative …

Twenty Years Of Epithelial-Mesenchymal Transition: A State Of The Field From Temtia X, Pierre Savagner, Thomas Brabletz, Chonghui Cheng, Christine Gilles, Tian Hong, Myriam Polette, Guojun Sheng, Marc P Stemmler, Erik W Thompson

Faculty, Staff and Students Publications

This report summarizes the 10th biennial meeting of The Epithelial Mesenchymal Transition International Association (TEMTIA), that took place in Paris on November 7-10, 2022. It provides a short but comprehensive introduction to the presentations and discussions that took place during the 3-day meeting. Similarly to previous TEMTIA meetings, TEMTIA X reviewed the most recent aspects of the epithelial-mesenchymal transition (EMT), a cellular process involved during distinct stages of development but also during wound healing and fibrosis to some degree. EMT has also been associated at various levels during tumor cell progression and metastasis. The meeting emphasized the intermediate stages of …

Continuing Education And Professional Development: Unifying Opportunities For Genetic Counselors Globally, Kathleen D Valverde, Tiffiney R Hartman, Sara L Reichert, Robin L Bennett, Martha Dudek, Debra Duquette, Daniel Riconda, Nancy J Cox, Gail P Jarvik, Sarah H Elsea, Elizabeth M Mcnally, Kim C Worley, Daniel J Rader

Faculty, Staff and Students Publications

No abstract provided.

Cutting Edge Of Genetically Modified Pigs Targeting Complement Activation For Xenotransplantation, Qin Sun, Si-Yuan Song, Jiabao Ma, Danni Li, Yiping Wang, Zhengteng Yang, Yi Wang

Faculty, Staff and Students Publications

In the quest to address the critical shortage of donor organs for transplantation, xenotransplantation stands out as a promising solution, offering a more abundant supply of donor organs. Yet, its widespread clinical adoption remains hindered by significant challenges, chief among them being immunological rejection. Central to this issue is the role of the complement system, an essential component of innate immunity that frequently triggers acute and chronic rejection through hyperacute immune responses. Such responses can rapidly lead to transplant embolism, compromising the function of the transplanted organ and ultimately causing graft failure. This review delves into three key areas of …

Fam20a: A Potential Diagnostic Biomarker For Lung Squamous Cell Carcinoma, Yalin Zhang, Qin Sun, Yangbo Liang, Xian Yang, Hailian Wang, Siyuan Song, Yi Wang, Yong Feng

Faculty, Staff and Students Publications

Background: Lung squamous cell carcinoma (LUSC) ranks among the carcinomas with the highest incidence and dismal survival rates, suffering from a lack of effective therapeutic strategies. Consequently, biomarkers facilitating early diagnosis of LUSC could significantly enhance patient survival. This study aims to identify novel biomarkers for LUSC.

Methods: Utilizing the TCGA, GTEx, and CGGA databases, we focused on the gene encoding Family with Sequence Similarity 20, Member A (FAM20A) across various cancers. We then corroborated these bioinformatic predictions with clinical samples. A range of analytical tools, including Kaplan-Meier, MethSurv database, Wilcoxon rank-sum, Kruskal-Wallis tests, Gene Set Enrichment Analysis, …

Etiology Of Hospital Mortality In Children Living In Low- And Middle-Income Countries: A Systematic Review And Meta-Analysis, Teresa B Kortz, Rishi P Mediratta, Audrey M Smith, Katie R Nielsen, Asya Agulnik, Stephanie Gordon Rivera, Hailey Reeves, Nicole F O'Brien, Jan Hau Lee, Qalab Abbas, Jonah E Attebery, Tigist Bacha, Emaan G Bhutta, Carter J Biewen, Jhon Camacho-Cruz, Alvaro Coronado Muñoz, Mary L Dealmeida, Larko Domeryo Owusu, Yudy Fonseca, Shubhada Hooli, Hunter Wynkoop, Mara Leimanis-Laurens, Deogratius Nicholaus Mally, Amanda M Mccarthy, Andrew Mutekanga, Carol Pineda, Kenneth E Remy, Sara C Sanders, Erica Tabor, Adriana Teixeira Rodrigues, Justin Qi Yuee Wang, Niranjan Kissoon, Yemisi Takwoingi, Matthew O Wiens, Adnan Bhutta

Faculty, Staff and Students Publications

In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking. The study objective was to estimate global and regional prevalence for common causes of pediatric hospital mortality and admission in LMICs. We performed a systematic review and meta-analysis to identify LMIC observational studies published January 1, 2005-February 26, 2021. Eligible studies included: a general pediatric admission population, a cause of admission or death, …

Colonic Malakoplakia In A Pediatric Renal Transplant Recipient Case Report, Kristen G Valencia Deray, Richard Kellermayer, Alexis C Gomez, Kalyani R Patel, Peace Imani, Seiji Kitagawa, Claire E Bocchini, Alvaro Orjuela

Faculty, Staff and Students Publications

Malakoplakia is a rare, chronic granulomatous disease that mainly affects the genitourinary system of immunocompromised adults. It is caused by a bactericidal deficit in macrophages and, therefore, the treatment includes antimicrobials that reach high concentrations in macrophages. To our knowledge, we present the first case of malakoplakia in a pediatric solid organ transplant recipient. Our patient is a 15-year-old male renal transplant recipient who presented with recurrent diarrhea. Blood, urine, and gastrointestinal pathogen panel testing were positive for enteroaggregative Escherichia coli. A colonoscopy revealed diffuse malakoplakia. He had a complete resolution of symptoms with trimethoprim-sulfamethoxazole therapy. Unfortunately, his malakoplakia recurred …

The Impact Of Race On Pancreatic Cancer Treatment And Survival In The Nationwide Veterans Affairs Healthcare System, Natalia Khalaf, Ann Xu, Theresa Nguyen Wenker, Jennifer R Kramer, Yan Liu, Hardeep Singh, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

OBJECTIVES: Among patients with pancreatic cancer, studies show racial disparities at multiple steps of the cancer care pathway. Access to healthcare is a frequently cited cause of these disparities. It remains unclear if racial disparities exist in an integrated, equal access public system such as the Veterans Affairs healthcare system.

METHODS: We identified all patients diagnosed with pancreatic adenocarcinoma in the national Veterans Affairs Central Cancer Registry from January 2010 to December 2018. We examined the independent association between race and 3 endpoints: stage at diagnosis, receipt of treatment, and survival while adjusting for sociodemographic factors and medical comorbidities.

RESULTS: …

Recent Trends In The Incidence Of Gastric Cancer In The United States, Kyle S Liu, Syed Ahsan Raza, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Gastric cancer (GC) incidence rates overall in the United States have declined over recent decades and are predicted to continue declining. However, there have been mixed recent findings regarding the potential stabilization of rates and potential divergent trends by age group. We used the most recent cancer data for the United States and examined trends in GC between 1992 and 2019, overall and in important subgroups of the population.

METHODS: Age-adjusted GC incidence rates and trends in adults 20 years or older were calculated using data from the Surveillance, Epidemiology, and End Results (SEER) 12 program. Secular trends were …

Gene Content, Phage Cycle Regulation Model And Prophage Inactivation Disclosed By Prophage Genomics In The Helicobacter Pylori Genome Project, Filipa F Vale, Richard J Roberts, Ichizo Kobayashi, M Constanza Camargo, Charles S Rabkin, Hpgp Research Network

Faculty, Staff and Students Publications

Prophages can have major clinical implications through their ability to change pathogenic bacterial traits. There is limited understanding of the prophage role in ecological, evolutionary, adaptive processes and pathogenicity of Helicobacter pylori, a widespread bacterium causally associated with gastric cancer. Inferring the exact prophage genomic location and completeness requires complete genomes. The international Helicobacter pylori Genome Project (HpGP) dataset comprises 1011 H. pylori complete clinical genomes enriched with epigenetic data. We thoroughly evaluated the H. pylori prophage genomic content in the HpGP dataset. We investigated population evolutionary dynamics through phylogenetic and pangenome analyses. Additionally, we identified …

The Impact Of Obesity-Associated Glycine Deficiency On The Elimination Of Endogenous And Exogenous Metabolites Via The Glycine Conjugation Pathway, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

BACKGROUND: Glycine is an integral component of the human detoxification system as it reacts with potentially toxic exogenous and endogenously produced compounds and metabolites via the glycine conjugation pathway for urinary excretion. Because individuals with obesity have reduced glycine availability, this detoxification pathway may be compromised. However, it should be restored after bariatric surgery because of increased glycine production.

OBJECTIVE: To examine the impact of obesity-associated glycine deficiency on the glycine conjugation pathway. We hypothesize that the synthesis rates of acylglycines from endogenous and exogenous sources are significantly reduced in individuals with obesity but increase after bariatric surgery.

METHODS: We …

The Tb27 Transcriptomic Model For Predicting Mycobacterium Tuberculosis Culture Conversion, Maja Reimann, Korkut Avsar, Andrew R Dinardo, Torsten Goldmann, Gunar Günther, Michael Hoelscher, Elmira Ibraim, Barbara Kalsdorf, Stefan H E Kaufmann, Niklas Köhler, Anna M Mandalakas, Florian P Maurer, Marius Müller, Dörte Nitschkowski, Ioana D Olaru, Cristina Popa, Andrea Rachow, Thierry Rolling, Helmut J F Salzer, Patricia Sanchez-Carballo, Maren Schuhmann, Dagmar Schaub, Victor Spinu, Elena Terhalle, Markus Unnewehr, Nika J Zielinski, Jan Heyckendorf, Christoph Lange

Faculty, Staff and Students Publications

RATIONALE: Treatment monitoring of tuberculosis patients is complicated by a slow growth rate of Mycobacterium tuberculosis. Recently, host RNA signatures have been used to monitor the response to tuberculosis treatment.

OBJECTIVE: Identifying and validating a whole blood-based RNA signature model to predict microbiological treatment responses in patients on tuberculosis therapy.

METHODS: Using a multi-step machine learning algorithm to identify an RNA-based algorithm to predict the remaining time to culture conversion at flexible time points during anti-tuberculosis therapy.

RESULTS: The identification cohort included 149 patients split into a training and a test cohort, to develop a multistep algorithm consisting of …

Balancing Honest Assessment And Compassion For Learners Experiencing Burnout: A Workshop And Feedback Tool For Clinical Teachers, Gal Barak, Dana Foradori, H Barrett Fromme, Linessa Zuniga, Andrea Dean

Faculty, Staff and Students Publications

INTRODUCTION: Burnout in medical trainees challenges their work effectiveness and impedes their ability to learn. Teachers in the clinical learning environment (CLE) are well situated to identify burnout and are often responsible for learner assessment.

METHODS: We developed a workshop to improve clinical teachers' identification and understanding of learner burnout while empowering them to provide constructive feedback and support. Building on best-practice feedback techniques and utilizing the Maslach Burnout Inventory (MBI) as a framework, we designed the GetINBurnOUT method to provide feedback and support for learners experiencing burnout. Applying Kern's six-step approach to curriculum development, we created and implemented a …

Development Of A Mini Pig Model Of Peanut Allergy, Akhilesh Kumar Shakya, Brittany Backus, Lazar D Nesovic, Malini Mallick, Olivia Banister, Carla M Davis, Sara Anvari, Harvinder Singh Gill

Faculty, Staff and Students Publications

INTRODUCTION: The prevalence of peanut allergies is increasing, emphasizing the need for an animal model to enhance our understanding of peanut allergy pathogenesis and to advance diagnostic tools and therapeutic interventions. While mice are frequently used as model organisms, their allergic responses do not fully mirror those observed in humans, warranting the exploration of a higher animal model. The porcine gastrointestinal system closely resembles that of humans, and exhibits allergy symptoms akin to human responses, making pigs a promising model for peanut allergy research.

METHODS: In this study we compared two allergen sensitization protocols involving either topical allergen application after …

Levofloxacin Prophylaxis For Pediatric Leukemia Patients: Monitoring Of Outcomes For Sustained Benefit And Consequences, Andrea L Davis, Alexandra M Stevens, Julienne Brackett, Lucila Marquez, Catherine E Foster, Adriana Sarmiento Clemente, Hannah E Sauer, Grant T Stimes, Judith R Campbell

Faculty, Staff and Students Publications

Levofloxacin prophylaxis reduces bloodstream infections in neutropenic patients with acute myeloid leukemia or relapsed acute lymphoblastic leukemia. A retrospective, longitudinal cohort study compares incidence of bacteremia, multidrug-resistant organisms (MDRO), and Clostridioides difficile (CDI) between time periods of levofloxacin prophylaxis implementation. Benefits were sustained without increasing MDRO or CDI.

Population-Based Screening Strategies For Biliary Atresia In The Newborn: A Systematic Review And Meta-Analysis, Srirupa Hari Gopal, Rema Zebda, Arvind Mohan, Kristin Borovsky, Yemisi Takwoingi, Katie Scandrett, Mohan Pammi

Faculty, Staff and Students Publications

BACKGROUND: Newborn screening for biliary atresia (BA) may facilitate earlier diagnosis and intervention for improved clinical outcomes.

METHODS: We systematically reviewed the accuracy of population-based screening strategies for BA in the newborn using PRISMA-DTA guidelines. We included cohort or cross-sectional studies. The screening (index) tests included stool color card (SCC) and direct/conjugated bilirubin (DB/CB) and the reference standard was intraoperative cholangiogram. Meta-analysis was performed using random-effects logistic regression models.

RESULTS: We included 15 studies (1,816,722 participants) that assessed 5 different population-based screening strategies. QUADAS-2 assessment revealed high risk of bias for patient selection in one study and uncertain risks for …

Researching Covid To Enhance Recovery (Recover) Pediatric Study Protocol: Rationale, Objectives And Design, Rachel S Gross, Tanayott Thaweethai, Erika B Rosenzweig, James Chan, Lori B Chibnik, Mine S Cicek, Amy J Elliott, Valerie J Flaherman, Andrea S Foulkes, Margot Gage Witvliet, Richard Gallagher, Maria Laura Gennaro, Terry L Jernigan, Elizabeth W Karlson, Stuart D Katz, Patricia A Kinser, Lawrence C Kleinman, Michelle F Lamendola-Essel, Joshua D Milner, Sindhu Mohandas, Praveen C Mudumbi, Jane W Newburger, Kyung E Rhee, Amy L Salisbury, Jessica N Snowden, Cheryl R Stein, Melissa S Stockwell, Kelan G Tantisira, Moriah E Thomason, Dongngan T Truong, David Warburton, John C Wood, Shifa Ahmed, Almary Akerlundh, Akram N Alshawabkeh, Brett R Anderson, Judy L Aschner, Andrew M Atz, Robin L Aupperle, Fiona C Baker, Venkataraman Balaraman, Dithi Banerjee, Deanna M Barch, Arielle Baskin-Sommers, Sultana Bhuiyan, Marie-Abele C Bind, Amanda L Bogie, Tamara Bradford, Natalie C Buchbinder, Elliott Bueler, Hülya Bükülmez, B J Casey, Linda Chang, Maryanne Chrisant, Duncan B Clark, Rebecca G Clifton, Katharine N Clouser, Lesley Cottrell, Kelly Cowan, Viren D'Sa, Mirella Dapretto, Soham Dasgupta, Walter Dehority, Audrey Dionne, Kirsten B Dummer, Matthew D Elias, Shari Esquenazi-Karonika, Danielle N Evans, E Vincent S Faustino, Alexander G Fiks, Daniel Forsha, John J Foxe, Naomi P Friedman, Greta Fry, Sunanda Gaur, Dylan G Gee, Kevin M Gray, Stephanie Handler, Ashraf S Harahsheh, Keren Hasbani, Andrew C Heath, Camden Hebson, Mary M Heitzeg, Christina M Hester, Sophia Hill, Laura Hobart-Porter, Travis K F Hong, Carol R Horowitz, Daniel S Hsia, Matthew Huentelman, Kathy D Hummel, Katherine Irby, Joanna Jacobus, Vanessa L Jacoby, Pei-Ni Jone, David C Kaelber, Tyler J Kasmarcak, Matthew J Kluko, Jessica S Kosut, Angela R Laird, Jeremy Landeo-Gutierrez, Sean M Lang, Christine L Larson, Peter Paul C Lim, Krista M Lisdahl, Brian W Mccrindle, Russell J Mcculloh, Kimberly Mchugh, Alan L Mendelsohn, Torri D Metz, Julie Miller, Elizabeth C Mitchell, Lerraughn M Morgan, Eva M Müller-Oehring, Erica R Nahin, Michael C Neale, Manette Ness-Cochinwala, Sheila M Nolan, Carlos R Oliveira, Onyekachukwu Osakwe, Matthew E Oster, R Mark Payne, Michael A Portman, Hengameh Raissy, Isabelle G Randall, Suchitra Rao, Harrison T Reeder, Johana M Rosas, Mark W Russell, Arash A Sabati, Yamuna Sanil, Alice I Sato, Michael S Schechter, Rangaraj Selvarangan, S Kristen Sexson Tejtel, Divya Shakti, Kavita Sharma, Lindsay M Squeglia, Shubika Srivastava, Michelle D Stevenson, Jacqueline Szmuszkovicz, Maria M Talavera-Barber, Ronald J Teufel, Deepika Thacker, Felicia Trachtenberg, Mmekom M Udosen, Megan R Warner, Sara E Watson, Alan Werzberger, Jordan C Weyer, Marion J Wood, H Shonna Yin, William T Zempsky, Emily Zimmerman, Benard P Dreyer, Recover-Pediatric Consortium

Faculty, Staff and Students Publications

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of …

Understanding The Role Of Ampa Receptors In Autism: Insights From Circuit And Synapse Dysfunction, Andres Jimenez-Gomez, Megan X Nguyen, Jason S Gill

Faculty, Staff and Students Publications

Autism spectrum disorders represent a diverse etiological spectrum that converge on a syndrome characterized by discrepant deficits in developmental domains often highlighted by concerns in socialization, sensory integration, and autonomic functioning. Importantly, the incidence and prevalence of autism spectrum disorders have seen sharp increases since the syndrome was first described in the 1940s. The wide etiological spectrum and rising number of individuals being diagnosed with the condition lend urgency to capturing a more nuanced understanding of the pathogenic mechanisms underlying the autism spectrum disorders. The current review seeks to understand how the disruption of AMPA receptor (AMPAr)-mediated neurotransmission in the …

Mecp2-Related Disorders While Gene-Based Therapies Are On The Horizon, Katherine Allison, Mirjana Maletic-Savatic, Davut Pehlivan

Faculty, Staff and Students Publications

The emergence of new genetic tools has led to the discovery of the genetic bases of many intellectual and developmental disabilities. This creates exciting opportunities for research and treatment development, and a few genetic disorders (e.g., spinal muscular atrophy) have recently been treated with gene-based therapies. MECP2 is found on the X chromosome and regulates the transcription of thousands of genes. Loss of MECP2 gene product leads to Rett Syndrome, a disease found primarily in females, and is characterized by developmental regression, motor dysfunction, midline hand stereotypies, autonomic nervous system dysfunction, epilepsy, scoliosis, and autistic-like behavior. Duplication of MECP2 causes …

Branched-Chain Amino Acid Accumulation Fuels The Senescence-Associated Secretory Phenotype, Yaosi Liang, Christopher Pan, Tao Yin, Lu Wang, Xia Gao, Ergang Wang, Holly Quang, De Huang, Lianmei Tan, Kun Xiang, Yu Wang, Peter B Alexander, Qi-Jing Li, Tso-Pang Yao, Zhao Zhang, Xiao-Fan Wang

Faculty, Staff and Students Publications

The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine play critical roles in protein synthesis and energy metabolism. Despite their widespread use as nutritional supplements, BCAAs' full effects on mammalian physiology remain uncertain due to the complexities of BCAA metabolic regulation. Here a novel mechanism linking intrinsic alterations in BCAA metabolism is identified to cellular senescence and the senescence-associated secretory phenotype (SASP), both of which contribute to organismal aging and inflammation-related diseases. Altered BCAA metabolism driving the SASP is mediated by robust activation of the BCAA transporters Solute Carrier Family 6 Members 14 and 15 as well as downregulation …

Citrulline And Adi-Peg20 Reduce Inflammation In A Juvenile Porcine Model Of Acute Endotoxemia, Caitlin Vonderohe, Barbara Stoll, Inka Didelija, Trung Nguyen, Mahmoud Mohammad, Yava Jones-Hall, Miguel A Cruz, Juan Marini, Douglas Burrin

Faculty, Staff and Students Publications

BACKGROUND: Arginine is a conditionally essential amino acid that is depleted in critically ill or surgical patients. In pediatric and adult patients, sepsis results in an arginine-deficient state, and the depletion of plasma arginine is associated with greater mortality. However, direct supplementation of arginine can result in the excessive production of nitric oxide (NO), which can contribute to the hypotension and macrovascular hypo-reactivity observed in septic shock. Pegylated arginine deiminase (ADI-PEG20, pegargiminase) reduces plasma arginine and generates citrulline that can be transported intracellularly to generate local arginine and NO, without resulting in hypotension, while maintaining microvascular patency. The objective of …

Polygenic Scores And Mendelian Randomization Identify Plasma Proteins Causally Implicated In Alzheimer’S Disease, Davis B Cammann, Yimei Lu, Jerome I Rotter, Alexis C Wood, Jingchun Chen

Faculty, Staff and Students Publications

BACKGROUND: An increasing body of evidence suggests that neuroinflammation is one of the key drivers of late-onset Alzheimer's disease (LOAD) pathology. Due to the increased permeability of the blood-brain barrier (BBB) in older adults, peripheral plasma proteins can infiltrate the central nervous system (CNS) and drive neuroinflammation through interactions with neurons and glial cells. Because these inflammatory factors are heritable, a greater understanding of their genetic relationship with LOAD could identify new biomarkers that contribute to LOAD pathology or offer protection against it.

METHODS: We used a genome-wide association study (GWAS) of 90 different plasma proteins (

RESULTS: We identified …

Critical Dialogue And Capacity-Building Projects Reduced Alcohol And Substance Use In A Randomized Clinical Trial Among Formerly Incarcerated Men, Liliane Cambraia Windsor, Ellen Benoit, Carol Lee, Alexis Jemal, Kari Kugler, Douglas C Smith, Rogério M Pinto, Salma Musaad

Faculty, Staff and Students Publications

Background:

Rates of alcohol and/or substance use (ASU) among residents of predominantly Black and marginalized communities are similar to ASU rates in White communities. Yet ASU has worse consequences in predominantly Black and marginalized communities (e.g., higher incarceration).

Objective:

We randomized participants to one of 16 intervention conditions using a 2⁴ full factorial design to optimize a multilevel intervention reducing ASU among 602 formerly incarcerated men with substance-use-disorders (SUD). Candidate intervention components included (1) critical dialogue (CD; six weekly 2-hour-long group sessions vs. no CD sessions), (2) Quality of Life Wheel (QLW; six weekly 1-hour-long group sessions vs. no …

Call The Experts: Identifying Stakeholders In The Long-Term Care Of Youth With Hypospadias, Vinaya P Bhatia, Kristin Ebert, Shannon Cannon, Walid A Farhat, Heidi W Brown, Jane Mahoney, Marisa E Hilliard, Kristina L Penniston

Faculty, Staff and Students Publications

Long-term follow-up for individuals with hypospadias remains a critical area of need, yet evidence-based guidelines for such follow-up are lacking, and the role of involvement of relevant experts is not yet established. Using our hypospadias-specific health-related quality of life conceptual framework and a subsequent qualitative study of prepubertal males and parents of males with hypospadias, we identified potential priorities for long-term follow-up of youth with hypospadias. Using thematic codes from our patient and parent interviews, we searched PubMed for relevant articles and identified the specialties represented by all the authors of these articles. Our search strategy revealed consistent expertise across …

International Society For Pediatric And Adolescent Diabetes Clinical Practice Consensus Guidelines 2024: Diabetes Technologies - Insulin Delivery, Torben Biester, Cari Berget, Charlotte Boughton, Laura Cudizio, Laya Ekhlaspour, Marisa E Hilliard, Leenatha Reddy, Suzanne Sap Ngo Um, Melissa Schoelwer, Jennifer L Sherr, Klemen Dovc

Faculty, Staff and Students Publications

The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This chapter builds on the 2022 ISPAD guidelines, and summarizes recent advances in the technology behind insulin administration, with special emphasis on insulin pump therapy, especially on glucose-responsive integrated technology that is feasible with the use of automated insulin delivery (AID) systems in children and adolescents. The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive …