Pediatrics Commons^™

Ultra-Low Extracorporeal Volume Microfluidic Leukapheresis Is Safe And Effective In A Rat Model, Mubasher Iqbal, Alexandra L Mclennan, Anton Mukhamedshin, Mai T P Dinh, Qisheng Liu, Jacob J Junco, Arvind Mohan, Poyyapakkam R Srivaths, Karen R Rabin, Thomas P Fogarty, Sean C Gifford, Sergey S Shevkoplyas, Fong W Lam

Faculty, Staff and Students Publications

Leukapheresis is a potentially life-saving therapy for children with symptomatic hyperleukocytosis. However, the standard centrifugation-based approach exposes pediatric patients to significant complications due to its large extracorporeal volume, high flow rates, and considerable platelet loss. Here, we tested whether performing cell separation with a high-throughput microfluidic technology could alleviate these limitations. In vitro, our microfluidic devices removed ~85% of large leukocytes and ~90% of spiked leukemic blasts from undiluted human whole blood, while minimizing platelet losses. Multiplexed devices connected in parallel allowed for faster, clinically relevant flow rates in vitro with no difference in leukocyte collection efficiency. When connected to …

Characterization Of Rationally Designed Crispr/Cas9-Based Dna Methyltransferases With Distinct Methyltransferase And Gene Silencing Activities In Human Cell Lines And Primary Human T Cells, Rosa Selenia Guerra-Resendez, Samantha Legoff Lydon, Alex J Ma, Guy C Bedford, Daniel R Reed, Sunghwan Kim, Erik R Terán, Tomoki Nishiguchi, Mario Escobar, Andrew R Dinardo, Isaac B Hilton

Faculty, Staff and Students Publications

Nuclease-deactivated Cas (dCas) proteins can be used to recruit epigenetic effectors, and this class of epigenetic editing technologies has revolutionized the ability to synthetically control the mammalian epigenome and transcriptome. DNA methylation is one of the most important and well-characterized epigenetic modifications in mammals, and while many different forms of dCas-based DNA methyltransferases (dCas-DNMTs) have been developed for programmable DNA methylation, these tools are frequently poorly tolerated and/or lowly expressed in mammalian cell types. Further, the use of dCas-DNMTs has largely been restricted to cell lines, which limits mechanistic insights in karyotypically normal contexts and hampers translational utility in the …

Plasma Micrornas To Select Optimal Patients For Antibody Production From Anti-Addiction Vaccines, Thomas R Kosten, Amrit Koirala, David A Nielsen, Coreen B Domingo, Ynhi T Thomas, Preethi H Gunaratne, Cristian Coarfa

Faculty, Staff and Students Publications

Background: Cocaine and illicit amphetamines (disguised as “Adderall”) are being laced with fentanyl and producing accidental and intentional fatal overdoses. Vaccines can prevent these overdoses, but 33% of humans generate insufficient anti-drug antibody (AB) levels. Plasma microRNAs (miRs) can be used to predict non-responders. We have plasma stored from 152 cocaine vaccine trial participants following three vaccinations over 9 weeks and examined miRs as potential response biomarkers. Methods: We compared 2517 miRs before anti-cocaine vaccination in participants with the highest (n = 25) to the lowest (n = 23) antibody levels. False Discovery Rates (FDRs) were applied to identify differentially …

Navigating Epstein-Barr Virus (Ebv) And Post-Transplant Lymphoproliferative Disorder (Ptld) In Pediatric Liver Transplantation: Current Knowledge And Strategies For Treatment And Surveillance, Erin Y Chen, Natasha Dilwali, Krupa R Mysore, Sara Hassan, Sara Kathryn Smith, Wikrom Karnsakul

Faculty, Staff and Students Publications

Epstein-Barr virus (EBV) is strongly associated with the development of post-transplant lymphoproliferative disorder (PTLD) in pediatric liver transplant recipients. PTLD is one of the most common malignancies following liver transplantation and is associated with significant morbidity and mortality. Factors such as EBV-serostatus mismatch and prolonged or high levels of immunosuppression impact a patient's risk of developing PTLD. While pre-transplant EBV serological screening and post-transplant monitoring of EBV-DNA levels are strongly recommended, universal guidelines for its prevention and management are lacking. Due to a lack of robust prospective studies, current clinical practices vary widely. The treatment of PTLD typically involves reducing …

Neuronal Network Activation Induced By Forniceal Deep Brain Stimulation In Mice, Bin Tang, Zhenyu Wu, Qi Wang, Jianrong Tang

Faculty, Staff and Students Publications

Background: The fimbria-fornix is a nerve fiber bundle that connects various structures of the limbic system in the brain and plays a key role in cognition. It has become a major target of deep brain stimulation (DBS) to treat memory impairment in both dementia patients and animal models of neurological diseases. Previously, we have reported the beneficial memory effects of chronic forniceal DBS in mouse models of intellectual disability disorders. In Rett syndrome and CDKL5 deficiency disorder models, DBS strengthens hippocampal synaptic plasticity, reduces dentate inhibitory transmission or increases adult hippocampal neurogenesis that aids memory. However, the underlying neuronal circuitry …

Acute Mecp2 Loss In Adult Mice Reveals Transcriptional And Chromatin Changes That Precede Neurological Dysfunction And Inform Pathogenesis, Sameer S Bajikar, Jian Zhou, Ryan O'Hara, Harini P Tirumala, Mark A Durham, Alexander J Trostle, Michelle Dias, Yingyao Shao, Hu Chen, Wei Wang, Hari Krishna Yalamanchili, Ying-Wooi Wan, Laura A Banaszynski, Zhandong Liu, Huda Y Zoghbi

Faculty, Staff and Students Publications

Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene cause Rett syndrome, a severe childhood neurological disorder. MeCP2 is a well-established transcriptional repressor, yet upon its loss, hundreds of genes are dysregulated in both directions. To understand what drives such dysregulation, we deleted Mecp2 in adult mice, circumventing developmental contributions and secondary pathogenesis. We performed time series transcriptional, chromatin, and phenotypic analyses of the hippocampus to determine the immediate consequences of MeCP2 loss and the cascade of pathogenesis. We find that loss of MeCP2 causes immediate and bidirectional progressive dysregulation of the transcriptome. To understand what drives gene downregulation, we …

Novel Intraoperative Applications Of Fluorescence Imaging Using Indocyanine Green In Pediatric Urology, Albert S T Lee, Ching Man Carmen Tong

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Near-infrared fluorescence imaging (NIRF) with the use of indocyanine green (ICG) has been recently adopted in pediatric urology after its well-published use in the adult population. As a powerful tool that can help delineate complex anatomy and congenital anomalies, we discuss the various applications of this imaging in minimally invasive and open surgery in pediatric urology.

RECENT FINDINGS: The most reported applications of ICG in pediatric urology are within minimally invasive surgery, particularly varicoceles, renal surgery such as nephrectomies and renal tumor excision, mimicking its use in adult urology. ICG has also been applied to reconstructive urology …

Dairy Consumption And The Colonic Mucosa-Associated Gut Microbiota In Humans-A Preliminary Investigation, Ellie Chen, Nadim J Ajami, Donna L White, Yanhong Liu, Shawn Gurwara, Kristi Hoffman, David Y Graham, Hashem B El-Serag, Joseph F Petrosino, Li Jiao

Faculty, Staff and Students Publications

Background: Dairy consumption has been associated with various health outcomes that may be mediated by changes in gut microbiota.

Methods: This cross-sectional study investigated the association between the colonic mucosa-associated gut microbiota and the self-reported intake of total dairy, milk, cheese, and yogurt. A total of 97 colonic mucosal biopsies collected from 34 polyp-free individuals were analyzed. Dairy consumption in the past year was assessed using a food frequency questionnaire. The 16S rRNA gene V4 region was amplified and sequenced. Operational taxonomic unit (OTU) classification was performed using the UPARSE and SILVA databases. OTU diversity and relative abundance were compared …

Acute-On-Chronic Liver Failure (Aclf): The ‘Kyoto Consensus’-Steps From Asia, Ashok Choudhury, Anand V Kulkarni, Vinod Arora, A S Soin, Abdul Kadir Dokmeci, Abhijeet Chowdhury, Abraham Koshy, Ajay Duseja, Ajay Kumar, Ajay Kumar Mishra, Ajay Kumar Patwa, Ajit Sood, Akash Roy, Akash Shukla, Albert Chan, Aleksander Krag, Amar Mukund, Ameet Mandot, Amit Goel, Amna Subhan Butt, Amrish Sahney, Ananta Shrestha, Andrés Cárdenas, Angelo Di Giorgio, Anil Arora, Anil Chandra Anand, Anil Dhawan, Ankur Jindal, Anoop Saraya, Anshu Srivastava, Anupam Kumar, Apichat Kaewdech, Apurva Pande, Archana Rastogi, Arun Valsan, Ashish Goel, Ashish Kumar, Ashwani K Singal, Atsushi Tanaka, Audrey Coilly, Ayaskanta Singh, Babu Lal Meena, Barath Jagadisan, Barjesh Chander Sharma, Bikrant Bihari Lal, C E Eapen, Cesar Yaghi, Chandan Kumar Kedarisetty, Chang Wook Kim, Charles Panackel, Chen Yu, Chetan R Kalal, Chhagan Bihari, Chien Hao Huang, Chitranshu Vasishtha, Christian Jansen, Christian Strassburg, Chun Yen Lin, Constantine J Karvellas, Cosmas Rinaldi Adithya Lesmana, Cyriac Abby Philips, Debbie Shawcross, Dharmesh Kapoor, Dhiraj Agrawal, Diana Alcantara Payawal, Dibya Lochan Praharaj, Dinesh Jothimani, Do Seon Song, Dong Joon Kim, Dong-Sik Kim, Duan Zhongping, Fazal Karim, Francois Durand, Gamal E Shiha, Gennaro D'Amico, George K Lau, Girish Kumar Pati, Graciela Elia Castro Narro, Guan-Huei Lee, Gupse Adali, Guru Prasad Dhakal, Gyongyi Szabo, H C Lin, Hai Li, Hari Kumar Nair, Harshad Devarbhavi, Harshvardhan Tevethia, Hasmik Ghazinian, Hemamala Ilango, Hong Ling Yu, Irsan Hasan, J Fernandez, Jacob George, Jaideep Behari, James Fung, Jasmohan Bajaj, Jaya Benjamin, Jennifer C Lai, Jidong Jia, Jin Hua Hu, Jin Jun Chen, Jin Lin Hou, Jin Mo Yang, Johannes Chang, Jonel Trebicka, Jörg C Kalf, Jose D Sollano, Joy Varghese, Juan Pablo Arab, Jun Li, K Rajender Reddy, Kaiser Raja, Kalpana Panda, Kamal Kajal, Karan Kumar, Kaushal Madan, Kemal Fariz Kalista, Kessarin Thanapirom, Khin Maung Win, Ki Tae Suk, Krishnadas Devadas, Laurentius A Lesmana, Lubna Kamani, Madhumita Premkumar, Madunil A Niriella, Mamun Al Mahtab, Man Fung Yuen, Manal Hel Sayed, Manasa Alla, Manav Wadhawan, Manoj Kumar Sharma, Manoj Sahu, Manya Prasad, Mark Dhinesh Muthiah, Martin Schulz, Meenu Bajpai, Mettu Srinivas Reddy, Michael Praktiknjo, Ming Lung Yu, Mithra Prasad, Mithun Sharma, Mohamed Elbasiony, Mohammed Eslam, Mohd Golam Azam, Mohd Rela, Moreshwar S Desai, Mukul Vij, Nadim Mahmud, Narendra Singh Choudhary, Navin Kumar Marannan, Necati Ormeci, Neeraj Saraf, Nipun Verma, Nobuaki Nakayama, Norifumi Kawada, Oidov Baatarkhuu, Omesh Goyal, Osamu Yokosuka, P N Rao, Paolo Angeli, Pathik Parikh, Patrick S Kamath, Paul J Thuluvath, Philipp Lingohr, Piyush Ranjan, Prashant Bhangui, Pravin Rathi, Puja Sakhuja, Puneet Puri, Qin Ning, R K Dhiman, Rahul Kumar, Rajan Vijayaraghavan, Rajeev Khanna, Rakhi Maiwall, Ravi Mohanka, Richard Moreau, Rino Alvani Gani, Rohit Loomba, Rohit Mehtani, Ruveena Bhavani Rajaram, S S Hamid, Sachin Palnitkar, Sadhna Lal, Sagnik Biswas, Sakkarin Chirapongsathorn, Samagra Agarwal, Sanjeev Sachdeva, Sanjiv Saigal, Santhosh E Kumar, Sargsyan Violeta, Satender Pal Singh, Satoshi Mochida, Saurabh Mukewar, Seema Alam, Seng Gee Lim, Shahinul Alam, Shalimar, Shantan Venishetty, Shikha S Sundaram, Shiran Shetty, Shobna Bhatia, Shweta A Singh, Shyam Kottilil, Simone Strasser, S M Shasthry, Soe Thiha Maung, Soek Siam Tan, Sombat Treeprasertsuk, Sonal Asthana, Steffen Manekeller, Subhash Gupta, Subrat Kumar Acharya, Sudhamshu K C, Sudhir Maharshi, Sumeet Asrani, Sunil Dadhich, Sunil Taneja, Suprabhat Giri, Surender Singh, Tao Chen, Tarana Gupta, Tatsuo Kanda, Tawesak Tanwandee, Teerha Piratvishuth, Ulrich Spengler, V G Mohan Prasad, Vandana Midha, Venera Rakhmetova, Vicente Arroyo, Vikrant Sood, Vinay Kumar Br, Vincent Wai-Sun Wong, Viniyendra Pamecha, Virendra Singh, Vishwa Mohan Dayal, Vivek A Saraswat, Wray Kim, Wasim Jafri, Wenyi Gu, Wong Yu Jun, Xiaolong Qi, Yogesh K Chawla, Yoon Jun Kim, Yu Shi, Zaigham Abbas, Guresh Kumar, Shuichiro Shiina, Lai Wei, Masao Omata, Shiv Kumar Sarin, Apasl-Aclf Research Consortium (Aarc) For Apasl-Aclf Working Party

Faculty, Staff and Students Publications

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the …

Advance: A Biomedical Informatics Approach To Investigate Acute Kidney Injury In Infants, Jennifer A Rumpel, Sofia Perazzo, Jonathan Bona, Andrew M South, Matthew W Harer, Daniel Liu, Michelle C Starr, Mona Khattab, Rachel Han, Cara Slagle, Eileen Ciccia, Tasnim Najaf, Matthew Gillen, Mimily Harsono, Arwa Nada, Kiran Dwarakanath, Semsa Gogcu, Tahagod Mohamed, Christine Stoops, Elizabeth Bonachea, Mary Revenis, Jessica Roberts, Robert Michael Lenzini, Anne Debuyserie, Catherine Joseph, Karna Murthy, Patricio Ray, Mario Schootman, Corey Nagel

Faculty, Staff and Students Publications

Background: Acute kidney injury (AKI) occurs in up to half of infants admitted to the neonatal intensive care unit (NICU) and is associated with increased risks of death and more days of mechanical ventilation, hospitalization, and vasopressor drug support. Our objective was to build a granular relational database to study the impact that AKI has on infants admitted to Level-IV NICUs.

Methods: A relational database was created by linking data from the Children's Hospitals Neonatal Database with AKI-focused data from electronic health records from 9 centers.

Results: The current cohort consists of 24,870 infants with a median (IQR) gestational age …

Hes V20 Outperforms Galad For Detection Of Hcc: A Phase 3 Biomarker Study In The United States, Hashem B El-Serag, Qingchun Jin, Nabihah Tayob, Emad Salem, Michelle Luster, Abeer Alsarraj, Saira Khaderi, Amit G Singal, Jorge A Marrero, Sumeet K Asrani, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: The original hepatocellular carcinoma early detection screening (HES) score, which combines alpha-fetoprotein (AFP) with age, alanine aminotransferase, and platelets, has better performance than AFP alone for early HCC detection. We have developed HES V2.0 by adding AFP-L3 and des-gamma-carboxy prothrombin to the score and compared its performance to GALAD and ASAP scores among patients with cirrhosis.

APPROACH AND RESULTS: We conducted a prospective-specimen collection, retrospective-blinded-evaluation phase 3 biomarker cohort study in patients with cirrhosis enrolled in imaging and AFP surveillance. True-positive rate (TPR)/sensitivity and false-positive rate for any or early HCC were calculated for GALAD, ASAP, and …

Pediatric Participation In Biobanking Related To Inflammatory Bowel Diseases, Jennifer Saccente Thompson, Sahna Reddy, Alison Shaw, Antone R Opekun, Richard Kellermayer

Faculty, Staff and Students Publications

No abstract provided.

Comprehensive Assessment Reveals Numerous Clinical And Neurophysiological Differences Between Mecp2-Allelic Disorders, Davut Pehlivan, Chengjun Huang, Holly K Harris, Christine Coquery, Aditya Mahat, Mirjana Maletic-Savatic, Laurence Mignon, Sukru Aras, Daniel G Glaze, Charles S Layne, Leonardo Sahelijo, Huda Y Zoghbi, Matthew J Mcginley, Bernhard Suter

Faculty, Staff and Students Publications

OBJECTIVE: Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) result from under- and overexpression of MECP2, respectively. Preclinical studies using genetic-based treatment showed robust phenotype recovery for both MDS and RTT. However, there is a risk of converting MDS to RTT, or vice versa, if accurate MeCP2 levels are not achieved. The aim of this study was to identify biomarkers distinguishing RTT from MDS.

MATERIALS AND METHODS: We prospectively enrolled 11 MDS and 6 male RTT like (MRL) individuals for a panel of clinical and neurophysiological assessments over two visits, 8-10 months apart.

RESULTS: We identified numerous clinical and physiological …

Prospective Analysis Of Liver Stiffness Measurement By Vibration Controlled Transient Elastography As A Predictor Of Outcomes In Biliary Atresia, Jean P Molleston, Nathan P Goodrich, Wen Ye, Daniel H Leung, Ronald J Sokol, Benjamin L Shneider, Children Force Outcomes Working Group

Faculty, Staff and Students Publications

No abstract provided.

Diagnostic Performance Of Contrast-Enhanced Ultrasound In Traumatic Solid Organ Injuries In Children: A Systematic Review And Meta-Analysis, Payam Jannatdoust, Parya Valizadeh, Amir Hassankhani, Melika Amoukhteh, Delaram J Ghadimi, Mahsa Heidari-Foroozan, Paniz Sabeghi, Paniz Adli, Jennifer H Johnston, Pauravi S Vasavada, Ali Gholamrezanezhad

Faculty, Staff and Student Publications

Background: Blunt abdominal trauma (BAT) is a significant contributor to pediatric mortality, often causing liver and spleen injuries. Contrast-enhanced computed tomography (CT), the gold standard for diagnosing solid organ injury, poses radiation risks to children. Contrast-enhanced ultrasound (CEUS) may be a promising alternative imaging modality.

Objectives: To evaluate the diagnostic utility of CEUS for detecting solid organ injuries following BAT in the pediatric population.

Methods: A systematic review and meta-analysis were conducted through a thorough literature search in PubMed, Scopus, Web of Science, and Embase databases up to October 1, 2023. Diagnostic accuracy metrics were aggregated using a bivariate model, …

American Cochlear Implant Alliance Position Statement On Newborn Congenital Cytomegalovirus Screening, Megan Honor Pesch, Kevin David Brown, Amy L Birath, Gail J Demmler-Harrison, Cailtin Sapp, Anne Morgan Selleck, Alex D Sweeney

Faculty, Staff and Students Publications

It is estimated that 1 in every 200 US newborns has congenital cytomegalovirus (cCMV). Delayed identification of cCMV in newborns precludes timely intervention to mitigate sequelae of the infection such as hearing loss and other neurological complications. Newborn testing for cCMV enables appropriate diagnosis and intervention by multidisciplinary teams to properly manage the immediate sequelae of cCMV, avoid unnecessary additional testing that can result from delayed diagnosis, and monitor for future complications. It is the position of the American Cochlear Implant Alliance, the National CMV Foundation, and the American Academy of Otolaryngology-Head and Neck Surgery that universal newborn cCMV screening …

Parasite-Microbiota Interactions: A Pathway To Innovative Interventions For Chagas Disease, Leishmaniasis, And Ascariasis, Juan David Ramírez, Sergio Castañeda, Jill Weatherhead, Cristina Poveda

Faculty, Staff and Students Publications

Parasitic infections are a major global health challenge, driven in part by complex interactions between parasites, host microbiota, and immune responses. Recent advances in microbiome research highlight the critical role of microbiota in influencing disease outcomes and treatment effectiveness. This review examines how changes in the microbiota impact parasite transmission, disease progression, and responses to treatment, focusing on key parasitic diseases such as Chagas disease, leishmaniasis, and ascariasis. The microbiota can either exacerbate or mitigate disease severity, depending on its composition, providing critical insights for novel therapeutic strategies. Emerging approaches discussed include the use of targeted probiotics, prebiotics, and microbiota-modulating …

Sudden Cardiac Death Associated With Fatty Liver Disease, Jonathan Vo, Thien T T T Truyen, Audrey Uy-Evanado, Arayik Sargsyan, Harpriya Chugh, Christopher Young, Sean Hurst, Christina Y Miyake, Kyndaron Reinier, Sumeet S Chugh

Faculty, Staff and Students Publications

BACKGROUND: Fatty liver disease or steatotic liver disease (SLD) affects 25% of the global population and has been associated with heart disease. However, there is a lack of postmortem studies in the context of sudden cardiac death (SCD).

OBJECTIVES: To investigate the relationship between SLD and SCD.

METHODS: A post-mortem case-case study was conducted in victims of SCD from an ongoing community-based study in Southern California (Ventura, CA, 2015-2023). Diagnosis of SLD was determined from post-mortem liver histopathology reports. For each patient, demographic variables, laboratory values, and presence of co-morbidities were ascertained from medical records and were compared between patients …

Hybrid Versus Vaccine Immunity Of Mrna-1273 Among People Living With Hiv In East And Southern Africa: A Prospective Cohort Analysis From The Multicentre Covpn 3008 (Ubuntu) Study, Nigel Garrett, Asa Tapley, Aaron Hudson, Sufia Dadabhai, Bo Zhang, Nyaradzo M Mgodi, Jessica Andriesen, Azwidihwi Takalani, Leigh H Fisher, Jia Jin Kee, Craig A Magaret, Manuel Villaran, John Hural, Erica Andersen-Nissen, Guido Ferarri, Maurine D Miner, Bert Le Roux, Eduan Wilkinson, Richard Lessells, Tulio De Oliveira, Jackline Odhiambo, Parth Shah, Laura Polakowski, Margaret Yacovone, Taraz Samandari, Zvavahera Chirenje, Peter James Elyanu, Joseph Makhema, Ethel Kamuti, Harriet Nuwagaba-Biribonwoha, Sharlaa Badal-Faesen, William Brumskine, Soritha Coetzer, Rodney Dawson, Sinead Delany-Moretlwe, Andreas Henri Diacon, Samantha Fry, Katherine Margaret Gill, Zaheer Ahmed Ebrahim Hoosain, Mina C Hosseinipour, Mubiana Inambao, Craig Innes, Steve Innes, Dishiki Kalonji, Margaret Kasaro, Priya Kassim, Noel Kayange, William Kilembe, Fatima Laher, Moelo Malahleha, Vongane Louisa Maluleke, Grace Mboya, Kirsten Mcharry, Essack Mitha, Kathryn Mngadi, Pamela Mda, Tumelo Moloantoa, Cissy Kityo Mutuluuza, Nivashnee Naicker, Vimla Naicker, Anusha Nana, Annet Nanvubya, Maphoshane Nchabeleng, Walter Otieno, Elsje Louise Potgieter, Disebo Potloane, Zelda Punt, Jamil Said, Yashna Singh, Mohammed Siddique Tayob, Yacoob Vahed, Deo Ogema Wabwire, M Juliana Mcelrath, James G Kublin, Linda-Gail Bekker, Peter B Gilbert, Lawrence Corey, Glenda E Gray, Yunda Huang, Philip Kotze, Covpn 3008 Ubuntu Study Team

Faculty, Staff and Students Publications

BACKGROUND: With limited access to mRNA COVID-19 vaccines in lower income countries, and people living with HIV (PLWH) largely excluded from clinical trials, Part A of the multicentre CoVPN 3008 (Ubuntu) study aimed to assess the safety of mRNA-1273, the relative effectiveness of hybrid versus vaccine immunity, and SARS-CoV-2 viral persistence among PLWH in East and Southern Africa during the omicron outbreak.

METHODS: Previously unvaccinated adults with HIV and/or other comorbidities associated with severe COVID-19 received either one (hybrid immunity) or two (vaccine immunity) 100-mcg doses of ancestral strain mRNA-1273 in the first month, depending on baseline evidence of prior …

Management Of Children With Food Allergies By Allergists In The United States, Aikaterini Anagnostou, Matthew Greenhawt, Jay A Lieberman, Christina E Ciaccio, Sayantani B Sindher, Blaine Creasy, Katherine Baran, Sachin Gupta, Anna Nowak-Wegrzyn

Faculty, Staff and Students Publications

BACKGROUND: Management of patients with food allergies is complex, especially in cases of patients with multiple and potentially severe food allergies. Although international guidelines exist for food allergy management, the role of the allergist in the decision-making process is key.

OBJECTIVE: Our aim was to investigate the management patterns and educational needs of practicing allergists treating patients with food allergies.

METHODS: An online survey was e-mailed to United States-based practicing allergists (N = 2833) in November-December 2021. The allergists were screened for managing 1 or more patients (including ≥25% pediatric patients) with food allergies per month. The allergists responded to …

Effectiveness Of The Primary Bacillus Calmette-Guérin Vaccine Against The Risk Of Mycobacterium Tuberculosis Infection And Tuberculosis Disease: A Meta-Analysis Of Individual Participant Data, Puck T Pelzer, Logan Stuck, Leonardo Martinez, Alexandra S Richards, Carlos Acuña-Villaorduña, Naomi E Aronson, Maryline Bonnet, Anna C Carvalho, Pei-Chun Chan, Li-Min Huang, Chi-Tai Fang, Gavin Churchyard, Helena Del Corral-Londoño, Manjula Datta, Marcos A Espinal, Katherine Fielding, Andrew J Fiore-Gartland, Alberto Garcia-Basteiro, Willem Hanekom, Mark Hatherill, Phillip C Hill, Helena Huerga, Edward C Jones-López, Afranio Kritski, Anna M Mandalakas, Punam Mangtani, Eduardo Martins Netto, Harriet Mayanja, Rufaida Mazahir, Megan Murray, Molebogeng Rangaka, Thomas Scriba, Jitendra Singh, Sarman Singh, Catherine M Stein, Johan Vekemans, Lilly M Verhagen, Julian A Villalba, Anne Wajja, Basilea Watson, Richard G White, Frank G J Cobelens

Faculty, Staff and Students Publications

Background: Tuberculosis vaccine trials using disease as the primary endpoint are large, time consuming, and expensive. An earlier immunological measure of the protection against disease would accelerate tuberculosis vaccine development. We aimed to assess whether the effectiveness of the Bacillus Calmette-Guérin (BCG) vaccine for prevention of Mycobacterium tuberculosis infection was consistent with that for prevention of tuberculosis disease.

Methods: We conducted an individual participant data (IPD) meta-analysis on experimental and observational longitudinal studies before April 6, 2018, identified through systematic reviews, known to us through expert knowledge in the field, reporting on BCG vaccination status, M tuberculosis infection test (QuantiFERON …

The Adiponectin-Pparγ Axis In Hepatic Stellate Cells Regulates Liver Fibrosis, Shangang Zhao, Qingzhang Zhu, Wang-Hsin Lee, Jan-Bernd Funcke, Zhuzhen Zhang, May-Yun Wang, Qian Lin, Bianca Field, Xue-Nan Sun, Guannan Li, Mbolle Ekane, Toshiharu Onodera, Na Li, Yi Zhu, Christine M Kusminski, Terry D Hinds, Philipp E Scherer

Faculty, Staff and Students Publications

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear. We recently generated a transgenic mouse line (Lrat-rtTA) that expresses the doxycycline-responsive transcriptional activator rtTA under the control of the HSC-specific lecithin retinol acyltransferase (Lrat) promoter, which enables us to specifically and inducibly overexpress or eliminate genes in these cells. The inducible elimination of HSCs protects mice from methionine/choline-deficient (MCD) diet-induced liver fibrosis, confirming their causal involvement in fibrosis development. We generated …

Sex-Specific Astrocyte Regulation Of Spinal Motor Circuits By Nkx61, Navish A Bosquez Huerta, Zhung-Fu Lee, Eun-Ah Christine Song, Junsung Woo, Yi-Ting Cheng, Debosmita Sardar, Ozlem Sert, Ehson Maleki, Kwanha Yu, Ekin Su Akdemir, Kaitlyn Sanchez, Juyeon Jo, Matthew N Rasband, Hyun Kyoung Lee, Akdes Serin Harmanci, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes exhibit diverse cellular and molecular properties across the central nervous system (CNS). Recent studies identified region-specific transcription factors (TF) that oversee these diverse properties; how sex differences intersect with region-specific transcriptional programs to regulate astrocyte function is unknown. Here, we show that the TF Nkx6.1 is specifically expressed in ventral astrocytes of the spinal cord and that its deletion results in sex-specific effects on astrocyte morphology. Astrocytes from males exhibit enhanced morphological complexity, accompanied by increased motor function and cholinergic synapses. In contrast, female astrocytes exhibit reduced complexity and no changes in motor function. Mechanistically, we found that Nkx6.1 …

A Randomized, Placebo-Controlled, Cross-Over Trial Of Ketamine In Rett Syndrome, Kathleen Campbell, Jeffrey L Neul, David N Lieberman, Elizabeth Berry-Kravis, Tim A Benke, Cary Fu, Alan Percy, Bernhard Suter, David Morris, Randall L Carpenter, Eric D Marsh, Jana Von Hehn

Faculty, Staff and Students Publications

BACKGROUND: Preclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy.

DESIGN: This was a sequentially initiated, dose-escalating cohort, placebo-controlled, double blind, randomized sequence, cross-over study of oral ketamine in 6-12-year-old girls with RTT to evaluate short-term safety and tolerability and explore efficacy.

METHODS: Participants were randomized to either five days treatment with oral ketamine or matched placebo, followed by a nine-day wash-out period and then crossed-over to the opposite …

Management And Outcome Of Invasive Clindamycin-Resistant Mrsa Community-Associated Infections In Children, Amanda E Macias, Grant Stimes, Sheldon L Kaplan, Jesus G Vallejo, Kristina G Hulten, J Chase Mcneil

Faculty, Staff and Students Publications

Background: Clindamycin resistance among community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) complicates the management of a challenging infection. Little data exist to guide clinicians in the management of invasive clindamycin-resistant CA-MRSA infections in children and studies using oral regimens such as trimethoprim-sulfamethoxazole (TMP-SMX) and linezolid for treatment of these infections are limited. We sought to reevaluate antibiotic management among invasive CA-MRSA at a tertiary children’s hospital.

Methods: Cases of invasive clindamycin-resistant MRSA infections in children were identified through an ongoing S. aureus surveillance study. Eligible cases were those occurring in otherwise healthy children from 2011–2021. Medical records were reviewed.

Results: Thirty-four subjects …

Resurgence Of Pediatric Mycoplasma Pneumoniae Infections In Southeast Texas, November 2023-June 2024, Margaret Taylor Danner, Heather Colvin Binns, Khanh Nguyen, Coreen Johnson, Jim Dunn, Denver Niles, Diana K Nguyen

Faculty, Staff and Students Publications

We conducted a retrospective review of children tested for Mycoplasma pneumoniae from January 1, 2020 to June 30, 2024. M. pneumoniae polymerase chain reaction positivity increased starting in November 2023, peaking at 18.3% in June 2024. During the resurgence, children with laboratory-confirmed infection often had severe respiratory disease or extrapulmonary manifestations.

Congenital Rickets, Melissa Intriago

Mako: NSU Undergraduate Student Journal

No abstract provided.

Synesis As A Framework To Enable Safety Interventions In Complex Healthcare Environments, Aarti Bavare, Tiffany Wrenn, Anne Lam, Jamie Cargill, Lauren Salinas, Itode Idowu, Asma Razavi, Venessa Lynn Pinto, Eric Williams

Faculty, Staff and Students Publications

BACKGROUND: Despite wide adoption in the healthcare of safety event report (SER) systems, there is a paucity of unified structures for prompt analysis and action while retaining reporter confidentiality. We used a synesis framework to change siloed reviews of safety reports to a comprehensive appraisal of quality, safety, productivity and reliability to facilitate interventions.

METHODS: After a needs assessment survey, we launched serial plan-do-study-act cycles to (1) enhance teams' ability to access SERs, (2) facilitate regular multidisciplinary review of SERs to identify actionable opportunities, (3) allocate action priority using failure mode and effects analysis, and (4) launch actions and summarise …

Sex Differences In Response To Diet Enriched With Glutathione Precursors In The Aging Heart, Aude Angelini, Grecia Garcia Marquez, Anna Malovannaya, Marta L Fiorotto, Alexander Saltzman, Antrix Jain, Joann Trial, George E Taffet, Katarzyna A Cieslik

Faculty, Staff and Students Publications

Common features of the aging heart are dysregulated metabolism, inflammation, and fibrosis. Elevated oxidative stress is another hallmark of cardiac aging that can exacerbate each of these conditions. We hypothesize that by increasing natural antioxidant levels (glutathione), we will improve cardiac function. Twenty-one-month-old mice were fed glycine and N-acetyl cysteine (GlyNAC; glutathione precursors)-supplemented or control diets for 12 weeks. Heart function was monitored longitudinally, and the exercise performance was determined at the end of the study. We found that the GlyNAC diet was beneficial for old male but not old female mice, leading to an increase of Ndufb8 expression (a …

Dna Methylation Profile In Buffy Coat Identifies Methylation Differences Between Cirrhosis With And Without Hepatocellular Carcinoma, Hyeyeun Lim, Hashem B El-Serag, Michelle Luster, Megan L Grove, Jinyoung Byun, Yuri Jung, Younghun Han, Eric Boerwinkle, Christopher I Amos, Aaron P Thrift

Faculty, Staff and Students Publications

Background/Objectives: Cirrhosis is the precursor to most cases of hepatocellular carcinoma (HCC). Understanding the mechanisms leading to the transition from cirrhosis to HCC and identifying key biomarkers is crucial to developing effective screening strategies and reducing HCC-related mortality. DNA methylation is associated with gene inactivation and plays an important role in physiological and pathological processes; however, its role in cirrhosis progression to HCC is unknown.

Methods: We performed genome-wide DNA methylation profiling using Illumina Infinium MethylationEPI BeadChip in pre-diagnostic samples from 22 cirrhosis patients who subsequently developed HCC and 22 cirrhosis patients who remained HCC-free during an average 4-year follow-up. …