Digital Commons Network^™

Sex-Specific Epigenetic Development In The Mouse Hypothalamic Arcuate Nucleus Pinpoints Human Genomic Regions Associated With Body Mass Index, Harry Mackay, Chathura J Gunasekara, Kit-Yi Yam, Dollada Srisai, Hari Krishna Yalamanchili, Yumei Li, Rui Chen, Cristian Coarfa, Robert A Waterland

Duncan NRI Faculty and Staff Publications

Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows. Epigenetic mechanisms regulate neurodevelopment; however, little is known about their role in establishing and maintaining the brain's energy balance circuitry. We generated neuron and glia methylomes and transcriptomes from male and female mouse hypothalamic arcuate nucleus, a key site for energy balance regulation, at time points spanning the closure of an established critical window for developmental programming of obesity risk. We find that postnatal epigenetic maturation is markedly cell type and sex specific and …

Identification Of An Early Survival Prognostic Gene Signature For Localized Osteosarcoma Patients, Harry Mackay, Chathura J Gunasekara, Kit-Yi Yam, Dollada Srisai, Hari Krishna Yalamanchili, Yumei Li, Rui Chen, Cristian Coarfa, Robert A Waterland

Faculty, Staff and Students Publications

Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows. Epigenetic mechanisms regulate neurodevelopment; however, little is known about their role in establishing and maintaining the brain's energy balance circuitry. We generated neuron and glia methylomes and transcriptomes from male and female mouse hypothalamic arcuate nucleus, a key site for energy balance regulation, at time points spanning the closure of an established critical window for developmental programming of obesity risk. We find that postnatal epigenetic maturation is markedly cell type and sex specific and …

Mucus-Degrading Bacteroides Link Carbapenems To Aggravated Graft-Versus-Host Disease, Eiko Hayase, Tomo Hayase, Mohamed A Jamal, Takahiko Miyama, Chia-Chi Chang, Miriam R Ortega, Saira S Ahmed, Jennifer L Karmouch, Christopher A Sanchez, Alexandria N Brown, Rawan K El-Himri, Ivonne I Flores, Lauren K Mcdaniel, Dung Pham, Taylor Halsey, Annette C Frenk, Valerie A Chapa, Brooke E Heckel, Yimei Jin, Wen-Bin Tsai, Rishika Prasad, Lin Tan, Lucas Veillon, Nadim J Ajami, Jennifer A Wargo, Jessica Galloway-Peña, Samuel Shelburne, Roy F Chemaly, Lauren Davey, Robert W P Glowacki, Chen Liu, Gabriela Rondon, Amin M Alousi, Jeffrey J Molldrem, Richard E Champlin, Elizabeth J Shpall, Raphael H Valdivia, Eric C Martens, Philip L Lorenzi, Robert R Jenq

Faculty, Staff and Student Publications

The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well understood. In this study, we found that treatment with meropenem, a commonly used carbapenem, aggravates colonic GVHD in mice via the expansion of Bacteroides thetaiotaomicron (BT). BT has a broad ability to degrade dietary polysaccharides and host mucin glycans. BT in meropenem-treated allogeneic mice demonstrated upregulated expression of enzymes involved in the degradation of mucin glycans. These mice also had thinning of the colonic …

Vitamin C Deficiency In A Food Insecure Patient: A Rare Case Report, Gersham J. Rainone, Tatiana J. Han, Muhammed Rahim, Gregory J. Pirolli, Alina Popa, Jayaram Thimmapuram

Transformative Medicine

Introduction: Scurvy is rarely seen in developed countries and is characterized by deficiency of vitamin C, which can lead to symptoms including wound impairment, bleeding manifestations, and loss of teeth. Case Description: We present a case of a 53-year-old male with a right knee hemarthrosis after a fall. The patient also noted progressively enlarging spontaneous hematomas, denying any recent trauma except for the fall to the knee. He denied family history of bleeding and clotting disorders and endorsed aspirin use in the setting of a prior stroke. He actively resided at a local shelter with limited means of transportation for …

The Potential Role Of Selected Body Composition Phenotypes In The Interpretation Of The Exercise-Induced Components Of The Insulin-Like Growth Factor Systems, Gökhan Umutlu, Nevzat Demirci

Baltic Journal of Health and Physical Activity

Introduction: Increased adiposity leads to impaired physiologic growth hormone secretion and low and high body mass index (BMI) values increase health risks. However, BMI only measures results in variations in fat-free mass (FFM), fat-free mass index (FFMI), normalized fat-free mass index (NFMI), and body fat mass (BFM). This study evaluated the insulin-like growth factor system responses to the given exercise and their interaction with the changes in BMI, FFM, FFMI, and NFFMI in healthy male participants. Material and methods: A randomized controlled trial with a parallel groups study design was used. Thirty healthy male participants (age: 21.33 ±1.24 years) were …

Salivary Molecules As Indicators Of Hydration Status, José Meléndez-Gallardo Dr., Mariana Figueroa, Gonzalo Butti, Mauro Iriart, María Lucía Stefanelli

Baltic Journal of Health and Physical Activity

Introduction: Maintaining an appropriate level of hydration is essential to health, especially when doing physical exercise. Thus, the importance of monitoring the before, during and after exercise status. Therefore, knowing and studying the changes and indicators that may provide reliable information on fluctuations in a simple, quick manner, via non-invasive sampling techniques becomes essential. Material and Methods: The data analyzed and processed (α-amylase, K⁺, Cl^-, cortisol, total protein, and osmolality concentration in saliva) in this study are available on the free access research platform for complex physiological signals (https://physionet.org/content/qde/1.0.0/). Ten male subjects voluntarily took part in …

Body Composition And Psychophysical Well-Being Of Women Practicing Yoga, Aneta Omelan, Justyna Wiśniewska, Robert Podstawski

Baltic Journal of Health and Physical Activity

Introduction: This study characterized yoga as a form of free-time physical activity by analyzing and evaluating the body composition of women who regularly practice yoga, and by describing the effect of yoga on their psychophysical health. Material and Methods: The study involved 94 women: 56 yoga practitioners and 38 Zumba participants. The subjects were surveyed with a questionnaire to elicit information about their socioeconomic status. Body composition was determined by bioelectrical impedance analysis. Differences were assessed with two-tailed chi-square tests and Student’s t-tests. Results: The vast majority of the participants (89%) felt a positive influence of yoga on their mental …

Relationship Between Lower Limb Power Output, Sprint And Change Of Direction Performance In Soccer Players., Monika Papla, Agata Latocha, Wojciech Grzyb, Artur Gołaś

Baltic Journal of Health and Physical Activity

Introduction: Although soccer matches require players to perform repetitive power-related abilities, the impact of lower-body strength and power asymmetry on sprint and change of direction (COD) performance receives little attention. Therefore, this study aimed to establish the relationship between lower limb power, sprint, and change of direction (COD) performance. In addition, the relationship between lower limb power asymmetry and the above mentioned running tests was determined. Material and Methods: Twenty-four male soccer players from First Polish League (age = 24.8 ±8.2 years, body mass = 77.4 ±16.9kg, body height=179.5 ±14.5cm, soccer training experience = 10 ± 1.5years) took part in …

Association Of Hypomagnesemia And Liver Injury, Role Of Gut-Barrier Dysfunction And Inflammation: Efficacy Of Abstinence, And 2-Week Medical Management In Alcohol Use Disorder Patients., Evan J. Winrich, Khushboo S. Gala, Abhas Rajhans, Christian D. Rios-Perez, Amor J. Royer, Zarlakhta Zamani, Ranganathan Parthasarathy, Luis S. Marsano-Obando, Ashutosh J. Barve, Melanie L. Schwandt, Vatsalya Vatsalya

Faculty and Staff Scholarship

(1) We investigated the involvement of serum magnesium level in early alcoholic liver disease (ALD), gut barrier dysfunction, and inflammation in alcohol use disorder (AUD) patients; and lastly, the efficacy of 2-week abstinence and medical management to alleviate hypomagnesemia. (2) Forty-eight heavy drinking AUD patients (34 males (M)/14 females (F)) participated in this study. Patients were grouped by serum alanine aminotransferase (ALT) level (a marker of liver injury) as group 1 (Group 1 (Gr.1); ALT ≤ 40 U/L, 7M/8F, without any indication of early-stage ALD) and group 2 (Group 2 (Gr.2); ALT > 40 U/L, 27M/6F or early-stage ALD). These patients …

Effect Of Al2o3 On Nanostructure And Ion Transport Properties Of Pva/Peg/Ssa Polymer Electrolyte Membrane, Hamdy F M Mohamed, Esam E Abdel-Hady, Mostafa M Y Abdel-Moneim, Mohamed A M Bakr, Mohamed A M Soliman, Mahmoud G H Shehata, Mahmoud A T Ismail

Faculty, Staff and Student Publications

Polymer electrolyte membrane (PEM) fuel cells have the potential to reduce our energy consumption, pollutant emissions, and dependence on fossil fuels. To achieve a wide range of commercial PEMs, many efforts have been made to create novel polymer-based materials that can transport protons under anhydrous conditions. In this study, cross-linked poly(vinyl) alcohol (PVA)/poly(ethylene) glycol (PEG) membranes with varying alumina (Al2O3) content were synthesized using the solvent solution method. Wide-angle X-ray diffraction (XRD), water uptake, ion exchange capacity (IEC), and proton conductivity were then used to characterize the membranes. XRD results showed that the concentration of Al2O3 affected the degree of …

Study Protocol For An Adapted Personal Project Analysis To Measure Vertical Inter-Goal Relations On Physical Activity And Diet, Sara Kassas, Catherine Culot, Geert Crombez, Annique Smeding, Christophe Leys, Debbe Thompson, Ann Desmet

Children’s Nutrition Research Center Staff Publications

Background: The promotion of multiple healthy lifestyles has been implemented as part of public health efforts to prevent and reduce the burden of non-communicable diseases. However, these interventions have shown a heterogeneity in their effectiveness. The pursuit of multiple daily goals may influence overall progress in achieving health goals. Horizontal inter-goal relations can be conflicting (due to time constraints) or facilitating (due to goal compatibility) and impact progress towards goal achievement. Personal values also play an important role in health promotion. Personal values direct attention towards accomplishing a higher-level goal through goal setting. Identifying the conflicting or facilitating relationships between …

Glycemia Reduction In Type 2 Diabetes - Glycemic Outcomes, David M Nathan, John M Lachin, Ashok Balasubramanyam, Henry B Burch, John B Buse, Nicole M Butera, Robert M Cohen, Jill P Crandall, Steven E Kahn, Heidi Krause-Steinrauf, Mary E Larkin, Neda Rasouli, Margaret Tiktin, Deborah J Wexler, Naji Younes

Faculty, Staff and Students Publications

BACKGROUND: The comparative effectiveness of glucose-lowering medications for use with metformin to maintain target glycated hemoglobin levels in persons with type 2 diabetes is uncertain.

METHODS: In this trial involving participants with type 2 diabetes of less than 10 years' duration who were receiving metformin and had glycated hemoglobin levels of 6.8 to 8.5%, we compared the effectiveness of four commonly used glucose-lowering medications. We randomly assigned participants to receive insulin glargine U-100 (hereafter, glargine), the sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or sitagliptin, a dipeptidyl peptidase 4 inhibitor. The primary metabolic outcome was a glycated hemoglobin level, …

External Validation Of A Prediction Model For Estimating Fat Mass In Children And Adolescents In 19 Countries: Individual Participant Data Meta-Analysis, Mohammed T Hudda, Jonathan C K Wells, Linda S Adair, Jose R A Alvero-Cruz, Maxine N Ashby-Thompson, Martha N Ballesteros-Vásquez, Jesus Barrera-Exposito, Benjamin Caballero, Elvis A Carnero, Geoff J Cleghorn, Peter S W Davies, Malgorzata Desmond, Delan Devakumar, Dympna Gallagher, Elvia V Guerrero-Alcocer, Ferdinand Haschke, Mary Horlick, Houda Ben Jemaa, Ashraful I Khan, Amani Mankai, Makama A Monyeki, Hilde L Nashandi, Luis Ortiz-Hernandez, Guy Plasqui, Felipe F Reichert, Alma E Robles-Sardin, Elaine Rush, Roman J Shypailo, Jakub G Sobiecki, Gill A Ten Hoor, Jesús Valdés, V Pujitha Wickramasinghe, William W Wong, Richard D Riley, Christopher G Owen, Peter H Whincup, Claire M Nightingale

Children’s Nutrition Research Center Staff Publications

Objective: To evaluate the performance of a UK based prediction model for estimating fat-free mass (and indirectly fat mass) in children and adolescents in non-UK settings.

Design: Individual participant data meta-analysis.

Setting: 19 countries.

Participants: 5693 children and adolescents (49.7% boys) aged 4 to 15 years with complete data on the predictors included in the UK based model (weight, height, age, sex, and ethnicity) and on the independently assessed outcome measure (fat-free mass determined by deuterium dilution assessment).

Main outcome measures: The outcome of the UK based prediction model was natural log transformed fat-free mass (lnFFM). Predictive performance statistics of …

The Age-Dependent Immune Response To Ischemic Stroke, Marissa M Shams-White, Ashley H Tjaden, Sharon L Edelstein, Sarah Bassiouni, Lisa L Kahle, Catherine Kim, Xavier Pi-Sunyer, Karla A Temple, Elizabeth M Venditti, Jill Reedy, Brandy M Heckman-Stoddard

Faculty, Staff and Student Publications

BACKGROUND: The 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) 3rd expert report highlights up-to-date Cancer Prevention Recommendations that may reduce burdens of many chronic diseases, including diabetes. This study examined if following a lifestyle that aligns with the recommendations - assessed via the 2018 WCRF/AICR Score - was associated with lower risk of type 2 diabetes in high-risk adults participating in the Diabetes Prevention Program Outcomes Study (DPPOS).

METHODS: The Diabetes Prevention Program (DPP) randomized adults at high risk for diabetes to receive a lifestyle intervention (ILS), metformin (MET) or a placebo (PLB) (mean: 3.2 years), with …

Fibrodysplasia Ossificans Progressiva And Pregnancy: A Case Series And Review Of The Literature, Alexandra D Forrest, Danielle M Vuncannon, Jane E Ellis, Zvi Grunwald, Frederick S Kaplan

Department of Anesthesiology Faculty Papers

Objective: To evaluate maternal and fetal outcomes in pregnant patients with fibrodysplasia ossificans progressiva (FOP; OMIM#135100), an ultrarare genetic disorder characterized by progressive heterotopic ossification of soft tissues and cumulative disability.

Methods: This is a retrospective case series of three patients with FOP who were admitted to Grady Memorial Hospital in Atlanta, Georgia, from to February 2011 to July 2021.

Results: Three women delivered preterm infants at our institution. These cases posed unique anesthetic and obstetric technical challenges, particularly when securing the airway and performing cesarean delivery. Importantly, each patient received perioperative glucocorticoids for prevention of further heterotopic ossification.

Conclusion: …

Serologic Versus Molecular Testing For Screening For Hepatitis C Virus Infection In Patients With Hematologic Malignancies, Harrys A Torres, Georgios Angelidakis, Ying Jiang, Minas Economides, Khalis Mustafayev, Marcel Yibirin, Robert Orlowski, Richard Champlin, Srdan Verstovsek, Issam Raad

Faculty, Staff and Student Publications

Testing for antibody against hepatitis C virus (anti-HCV) is a low-cost diagnostic method worldwide; however, an optimal screening test for HCV in patients with cancer has not been established. We sought to identify an appropriate screening test for HCV infection in patients with hematologic malignancies and/or hematopoietic cell transplants (HCT). Patients in our center were simultaneously screened using serological (anti-HCV) and molecular (HCV RNA) assays (February 2019-November 2019). In total, 214 patients were enrolled in this study. Three patients (1.4%) were positive for anti-HCV, and 2 (0.9%) were positive for HCV RNA. The overall percentage agreement was 99.5% (95% CI: …

Dietary Risk Factors And Eating Behaviors In Peripheral Arterial Disease (Pad), Andrea Leonardo Cecchini, Federico Biscetti, Maria Margherita Rando, Elisabetta Nardella, Giovanni Pecorini, Luis H. Eraso, Paul J. Dimuzio, Antonio Gasbarrini, Massimo Massetti, Andrea Flex

Department of Surgery Faculty Papers

Dietary risk factors play a fundamental role in the prevention and progression of atherosclerosis and PAD (Peripheral Arterial Disease). The impact of nutrition, however, defined as the process of taking in food and using it for growth, metabolism and repair, remains undefined with regard to PAD. This article describes the interplay between nutrition and the development/progression of PAD. We reviewed 688 articles, including key articles, narrative and systematic reviews, meta-analyses and clinical studies. We analyzed the interaction between nutrition and PAD predictors, and subsequently created four descriptive tables to summarize the relationship between PAD, dietary risk factors and outcomes. We …

Mochi: A Comprehensive Cross-Platform Tool For Amplicon-Based Microbiota Analysis, Jun-Jie Zheng, Po-Wen Wang, Tzu-Wen Huang, Yao-Jong Yang, Hua-Sheng Chiu, Pavel Sumazin, Ting-Wen Chen

Children’s Nutrition Research Center Staff Publications

Motivation: Microbiota analyses have important implications for health and science. These analyses make use of 16S/18S rRNA gene sequencing to identify taxa and predict species diversity. However, most available tools for analyzing microbiota data require adept programming skills and in-depth statistical knowledge for proper implementation. While long-read amplicon sequencing can lead to more accurate taxa predictions and is quickly becoming more common, practitioners have no easily accessible tools with which to perform their analyses.

Results: We present MOCHI, a GUI tool for microbiota amplicon sequencing analysis. MOCHI preprocesses sequences, assigns taxonomy, identifies different abundant species and predicts species diversity and …

Clinical Activity Of Checkpoint Inhibitors In Angiosarcoma: A Retrospective Cohort Study, Vinod Ravi, Aparna Subramaniam, Jing Zheng, Behrang Amini, Van A Trinh, Jocelyn Joseph, Robert G Mennel, Andrew J Bishop, Erich M Sturgis, Ryan P Goepfert, Sudha Yalamanchili, Gilberto Botello, Bettzy Stephen, Sarina A Piha-Paul, Anisha B Patel, Alexander J Lazar, Anthony P Conley, Robert S Benjamin, Shreyaskumar R Patel, Phillip A Futreal, Neeta Somaiah, Aung Naing

Faculty, Staff and Student Publications

Background: Systemic treatments for angiosarcoma remains an area of unmet clinical need. The authors conducted this retrospective study to assess the clinical activity of checkpoint inhibitors in patients with angiosarcoma. The primary objective was to assess the objective response rate, and the secondary objective was to assess the progression-free and overall survival durations and disease control rate.

Methods: Patient data were obtained using The University of Texas MD Anderson Cancer Center Tumor Registry database. The final study population was refined to only include patients who had undergone pembrolizumab monotherapy. The objective response rate was evaluated using RECIST/irRECIST version 1.1. Progression-free …

How Did The Dietary Habits Of Patients With Chronic Medical Conditions Change During Covid-19?, Sahil K. Patel, Adarsh Gupta

Rowan-Virtua School of Osteopathic Medicine Departmental Research

CONTEXT: Previous studies have examined the changes in the dietary habits of general populations during the COVID-19 pandemic but have not focused on specific populations such as those with chronic medical conditions (CMCs). Prior to major vaccination efforts, 96.1% of deaths were attributed to patients with preexisting CMCs, thus it is important to examine how this population has endured changes.

OBJECTIVES: The purpose of this study was to identify differences in dietary habits, lifestyle habits, and food attitudes between those with CMCs compared to the populations without chronic medical conditions (non-CMCs) since the beginning of the COVID-19 pandemic.

METHODS: An …

Transmembrane Helices Mediate The Formation Of A Stable Ternary Complex Of B5r, Cyt B5, And Scd1, Jiemin Shen, Gang Wu, Ah-Lim Tsai, Ming Zhou

Faculty, Staff and Students Publications

Mammalian cytochrome b5 (cyt b5) and cytochrome b5 reductase (b5R) are electron carrier proteins for membrane-embedded oxidoreductases. Both b5R and cyt b5 have a cytosolic domain and a single transmembrane (TM) helix. The cytosolic domains of b5R and cyt b5 contain cofactors required for electron transfer, but it is not clear if the TM helix has function beyond being an anchor to the membrane. Here we show that b5R and cyt b5 form a stable binary complex, and so do cyt b5 and stearoyl-CoA desaturase-1 (SCD1). We also show that b5R, cyt b5 and SCD1 form a stable ternary complex. …

Role Of Hla-I Structural Variants And The Polyreactive Antibodies They Generate In Immune Homeostasis, Mepur H Ravindranath, Fatiha El Hilali, Carly J Amato-Menker, Hajar El Hilali, Senthamil R Selvan, Edward J Filippone

Department of Medicine Faculty Papers

Cell-surface HLA-I molecules consisting of β2-microglobulin (β2m) associated heavy chains (HCs), referred to as Face-1, primarily present peptides to CD8+ T-cells. HCs consist of three α-domains, with selected amino acid sequences shared by all alleles of all six isoforms. The cell-surface HLA undergoes changes upon activation by pathological conditions with the expression of β2m-free HCs (Face-2) resulting in exposure of β2m-masked sequences shared by almost all alleles and the generation of HLA-polyreactive antibodies (Abs) against them. Face-2 may homodimerize or heterodimerize with the same (Face-3) or different alleles (Face-4) preventing exposure of shared epitopes. Non-allo immunized males naturally carry HLA-polyreactive …

Role Of Sympathetic Pathway In Light-Phase Time-Restricted Feeding-Induced Blood Pressure Circadian Rhythm Alteration, Tianfei Hou, Aaron Chacon, Wen Su, Yuriko Katsumata, Zhenheng Guo, Ming Gong

Sanders-Brown Center on Aging Faculty Publications

Disruption of blood pressure (BP) circadian rhythm, independent of hypertension, is emerging as an index for future target organ damage and is associated with a higher risk of cardiovascular events. Previous studies showed that changing food availability time alters BP rhythm in several mammalian species. However, the underlying mechanisms remain largely unknown. To address this, the current study specifically investigates (1) the relationship between rhythms of food intake and BP in wild-type mice; (2) effects of light-phase time-restricted feeding (TRF, food only available during light-phase) on BP circadian rhythm in wild-type and diabetic db/db mice; (3) the roles of the …

Design, Development, And Testing Of Best4baby, An Mhealth Technology To Support Exclusive Breastfeeding In India: Pilot Study., Tony Ma, Katie Chang, Amal Alyusuf, Elina Bajracharya, Yukiko Washio, Patricia J Kelly, Roopa M Bellad, Niranjana S Mahantashetti, Umesh Charantimath, Vanessa Short, Parth Lalakia, Frances J. Jaeger, Shivaprasad Goudar, Richard Derman

Department of Pediatrics Faculty Papers

Background: Exclusive breastfeeding (EBF) at 6 months of age in most low- and middle-income countries, including India, is surprisingly low. There is a relative lack of mobile health apps that specifically focus on leveraging the use of peer counselors (PCs) to support mothers as a means of increasing EBF practices in low- and middle-income countries.

Objective: This study aimed to design, develop, and test the usability of Breastfeeding Education Support Tool for Baby (BEST4Baby), a mobile health app specifically designed to support PCs in providing in-home breastfeeding counseling support to mothers in rural India on optimal breastfeeding practices.

Methods: A …

Turning Nonselective Inhibitors Of Type I Protein Arginine Methyltransferases Into Potent And Selective Inhibitors Of Protein Arginine Methyltransferase 4 Through A Deconstruction-Reconstruction And Fragment-Growing Approach, Giulia Iannelli, Ciro Milite, Nils Marechal, Vincent Cura, Luc Bonnefond, Nathalie Troffer-Charlier, Alessandra Feoli, Donatella Rescigno, Yalong Wang, Alessandra Cipriano, Monica Viviano, Mark T Bedford, Jean Cavarelli, Sabrina Castellano, Gianluca Sbardella

Faculty, Staff and Student Publications

Protein arginine methyltransferases (PRMTs) are important therapeutic targets, playing a crucial role in the regulation of many cellular processes and being linked to many diseases. Yet, there is still much to be understood regarding their functions and the biological pathways in which they are involved, as well as on the structural requirements that could drive the development of selective modulators of PRMT activity. Here we report a deconstruction-reconstruction approach that, starting from a series of type I PRMT inhibitors previously identified by us, allowed for the identification of potent and selective inhibitors of PRMT4, which regardless of the low cell …

Fighting For Recovery On Multiple Fronts: The Past, Present, And Future Of Clinical Trials For Spinal Cord Injury, Valerie A Dietz, Nolan Roberts, Katelyn Knox, Sherilynne Moore, Michael Pitonak, Chris Barr, Jesus Centeno, Scott Leininger, Kent C New, Peter Nowell, Matthew Rodreick, Cedric G Geoffroy, Argyrios Stampas, Jennifer N Dulin

Faculty, Staff and Student Publications

Through many decades of preclinical research, great progress has been achieved in understanding the complex nature of spinal cord injury (SCI). Preclinical research efforts have guided and shaped clinical trials, which are growing in number by the year. Currently, 1,149 clinical trials focused on improving outcomes after SCI are registered in the U.S. National Library of Medicine at ClinicalTrials.gov. We conducted a systematic analysis of these SCI clinical trials, using publicly accessible data downloaded from ClinicalTrials.gov. After extracting all available data for these trials, we categorized each trial according to the types of interventions being tested and the types of …

Review: Management Of Midshaft Clavicle Fractures In Adolescents , Matthew B. Holloway

Longitudinal Scholar's Project

Clavicle fractures are common injuries that occur across all age ranges, but are largely seen in young, active males. The majority of these fractures (70-80%) occur in the midshaft of the clavicle. The purpose of this review was to compare non-operative treatment to operative treatment of midclavicular fractures and determine whether treatment for adolescent clavicle fractures more closely aligns with pediatric or adult management. Adolescent clavicle fractures are increasingly treated with open reduction and internal fixation, especially in the 15 to 19 age group. Nevertheless, there remains a lack of high-level studies comparing outcomes of operative and conservative treatment specifically …

Xpert Mtb/Rif Ultra Assay For Tuberculosis Disease And Rifampicin Resistance In Children, Alexander W Kay, Tara Ness, Sabine E Verkuijl, Kerri Viney, Annemieke Brands, Tiziana Masini, Lucia González Fernández, Michael Eisenhut, Anne K Detjen, Anna M Mandalakas, Karen R Steingart, Yemisi Takwoingi

Faculty, Staff and Students Publications

BACKGROUND: Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects Mycobacterium tuberculosis complex and rifampicin resistance. We previously published a Cochrane Review 'Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for tuberculosis disease and rifampicin resistance in children'. The current review updates evidence on the diagnostic accuracy of Xpert Ultra in children presumed to have tuberculosis disease. Parts of this review update informed the 2022 WHO updated guidance on management of …

Rolling Stones: An Instructive Case Of Neonatal Cholestasis, Paige Killelea, Shruti Sakhuja, Jose Hernandez, M John Hicks, Sanjiv Harpavat

Faculty, Staff and Students Publications

BACKGROUND: Jaundice within the first 1-2 weeks of a neonate's life will generally self-resolve; however, if it lasts longer than this time frame it warrants further work up. Direct or conjugated hyperbilirubinemia can suggest neonatal cholestasis, which in turn reflects marked reduction in bile secretion and flow. The differential diagnosis for neonatal cholestasis is broad. Neonatal choledocholithiasis is a rare cause of neonatal cholestasis, but should be considered on the differential diagnosis for patients presenting with elevated conjugated bilirubin.

CASE PRESENTATION: We describe an infant who presented with neonatal cholestasis. He subsequently underwent work up for biliary atresia, as this …

Bone Health Management In The Continuum Of Prostate Cancer Disease, Ettickan Boopathi, Ruth Birbe, Sunday A. Shoyele, Robert B. Den, Thangavel Chellappagounder

Department of Medicine Faculty Papers

Prostate cancer (PCa) is the second-leading cause of cancer-related deaths in men. PCa cells require androgen receptor (AR) signaling for their growth and survival. Androgen deprivation therapy (ADT) is the preferred treatment for patients with locally advanced and metastatic PCa disease. Despite their initial response to androgen blockade, most patients eventually will develop metastatic castration-resistant prostate cancer (mCRPC). Bone metastases are common in men with mCRPC, occurring in 30% of patients within 2 years of castration resistance and in >90% of patients over the course of the disease. Patients with mCRPC-induced bone metastasis develop lesions throughout their skeleton; the 5-year …