Medicine and Health Sciences Commons^™

What Is The Expected Clearance Of Methotrexate? A Therapeutic Drug Monitoring Reference Guide For High-Dose Methotrexate Use In Pediatric Malignancies., Zachary L. Taylor, Tamara P. Miller, Sarah G. Board, Ethan Poweleit, Ashley Chavana, Allison Weisnicht, Austin L. Brown, Melanie B. Bernhardt, Eric S. Schafer, Maureen M. O'Brien, Sharon M. Castellino, Laura Ramsey

Manuscripts, Articles, Book Chapters and Other Papers

High-dose methotrexate dosage and infusion durations differ across treatment protocols for pediatric leukemia, lymphoma, and osteosarcoma. Supportive care interventions are dependent on a patient's elimination of methotrexate (MTX). Therefore, it is important to establish the expected MTX elimination across protocols. Using modeling and simulation of real-world data, we determined the expected MTX concentrations at common time points from the start of infusion (24, 36, 42, 48, 60, and 72 hours) and the time that each patient would reach a typical discharge threshold (0.4, 0.2, 0.15, and 0.10 µM). These data provide a reference for MTX concentrations for common pediatric protocols.

Daily Physical Activity And Cardiorespiratory Fitness In Adults With Down Syndrome With And Without Congenital Heart Disease., Julianne G. Clina, David A. White, Joseph R. Sherman, Jessica C. Danon, Daniel Forsha, Brian C. Helsel, Richard A. Washburn, Joseph E. Donnelly, Lauren T. Ptomey

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Individuals with Down syndrome (DS) typically exhibit lower cardiorespiratory fitness and reduced moderate-to-vigorous physical activity (MVPA) compared to persons without disability. Approximately 50-55 % of individuals with DS have congenital heart disease (CHD), which is associated with cardiopulmonary deficiencies and reduced MVPA participation in non-DS populations. It is unknown if CHD related comorbidities compound with DS associated deficits in physical activity and fitness.

OBJECTIVE: To compare physical activity, cardiorespiratory fitness, and cardiovascular function, of persons with DS with and without CHD.

METHODS: Baseline data were used from a 12-month randomized controlled physical activity intervention of adults with DS. Participants …

Effectiveness Of Allopurinol On Uric Acid And Pediatric Chronic Kidney Disease Severity In The Chronic Kidney Disease In Children Study., Derek K. Ng, Matthew B. Matheson, George J. Schwartz, Katherine E. Kurgansky, Bradley A. Warady, Susan L. Furth

Manuscripts, Articles, Book Chapters and Other Papers

RATIONALE & OBJECTIVE: Clinical trials have shown that serum uric acid reduction does not slow chronic kidney disease (CKD) progression in adults, but it is uncertain whether these findings apply to children.

STUDY DESIGN: An observational cohort study.

SETTING & POPULATION: The Chronic Kidney Disease in Children cohort with participants who initiated allopurinol with a comparison group matched on age, sex, uric acid, CKD diagnosis, estimated glomerular filtration rate (eGFR), and proteinuria.

EXPOSURE: Allopurinol initiation.

OUTCOMES: Uric acid, eGFR, and proteinuria before and after initiation, and longitudinal changes over time.

ANALYTICAL APPROACH: Allopurinol initiators were matched to noninitiators at a …

The Pediatric Experience Collaborative: Paving The Way In Pediatric Experience., Lauren Hamilton, Trenton House, Taylor B. Sewell, Harris Baden, Brianna Combs, Sara L. Toomey, Shehzad Saeed, Jana Rojas, Molly Warneke, Maureen Hoff, Andréa Aken'ova, Lisa Rubino, Dana Ileana Williams, Samuel P. Hanke

Manuscripts, Articles, Book Chapters and Other Papers

Positive patient experience is associated with improved patient outcomes, but efforts to improve patient experience are often underprioritized, especially with respect to pediatric care. To address this challenge, leaders at several US children's hospitals established the Pediatric Experience Collaborative (PEC) in 2016 to leverage their collaboration and scale to optimize patient, family, and provider experiences. Since then, the PEC has steadfastly incorporated the patient and family perspective in all its endeavors (e.g., installing a family member as one of the organization's co-chairs); has created both structured opportunities and unstructured opportunities for learning and connection; and has embarked on multi-institutional research …

Constantly Connected: What Healthcare Providers Need To Know About Vicarious Trauma In An Evolving Digitally Connected Global Community., Meghan Kanya, Patricia Davis, Gail Robertson

Manuscripts, Articles, Book Chapters and Other Papers

Easy access to streaming news and sensational headlines has transformed society's exposure to traumatic narratives. From personal stories on social media platforms to news articles about violence in communities, patients and their caregivers may not recognize their exposure as traumatic nor recognize their psychological sequalae as unhealthy. In addition, youth with trauma-related mental health symptoms are not consistently identified in pediatric primary care clinics. Due to the increase in proximity to traumatic stories, healthcare providers working with youth require additional skills designed to engage patients and families in conversations about exposure to violence via technology and symptoms of vicarious trauma. …

Psychosocial Supports For The Physical And Mental Health Of Youth With Autism And Other Neurodevelopmental Disabilities., Melissa Campbell, Elizabeth Hastings, Paige Mcardle, Darren Olsen, Kathryn Benton, Cy Nadler

Manuscripts, Articles, Book Chapters and Other Papers

One in six youth has a neurodevelopmental disability (NDD), and autism diagnostic rates continue to rise. Before and after a diagnosis, families need trusted sources of guidance to navigate co-occurring medical and psychological conditions, and to manage unique stressors including transition to adulthood. However, medical professionals from all specialty areas struggle to identify resources to support the complex psychosocial and healthcare needs of these patients and their families. This primer on psychosocial supports for youth with autism will explore the major mental and physical health stressors faced by affected youth and families, and discuss opportunities for primary care and other …

Screens Are Not The Enemy: Recommendations For Developing Healthy Digital Habits In Youth., Megan B. Bolch, Rachel Moore, Gail Robertson, Meredith J. Scafe, Libby Milkovich

Manuscripts, Articles, Book Chapters and Other Papers

With the rapid and ever-evolving growth of both digital media platforms and mental health concerns in youth, parents and practitioners are faced with the challenge of critically evaluating the effects of digital media use on youth development.1 Despite popular culture's narrow focus on the risks, research has established both positive and negative effects of youth digital media use.2,3 In contrast to interventions primarily focused on screen time limits, the goal of this article is to propose a framework for healthy digital habits rooted in a social-ecological model, called the Multisystemic Model of Digital Habits. This framework considers the intersection of …

Letter Of Concern From The Association Of Academic Chairs Of Emergency Medicine Regarding Acgme Proposed Changes., Richard J. Hamilton, Lance B. Becker, Richard E. Wolfe, D Adam Algren, Thomas Arnold, Michael Baumann, Ross P. Berkeley, Terrell S. Caffery, Chad M. Cannon, Theodore J. Corbin, Michael E. Chansky, Harinder S. Dhindsa, Charles L. Emerman, David A. Farcy, Chris Fox, Michael A. Gibbs, Christopher S. Goode, Steven Andy Godwin, Dietrich Jehle, David Johnson, Samuel M. Keim, Babak Khazaeni, Barry J. Knapp, Clint Hawthorne, John D. Hoyle, Michael Christopher Kurz, Evan Leibner, Robert Mcnamara, Robert F. Mccormack, Edward A. Michelson, Chadwick Miller, Ashley Norse, Andrew Nugent, Brian J. O'Neil, David T. Overton, Edward A. Panacek, William F. Paolo, Denis R. Pauzé, Amanda L. Perez, Ralph J. Riviello, Scott W. Rodi, Peter S. Pang, Juan A. Gonzalez Sanchez, David Seaberg, Adam Schwartz, Stephen A. Shiver, David P. Sklar, Ben C. Smith, Jeffrey R. Stowell, Marc D. Squillante, J Jeremy Thomas, Terry Vanden Hoek, Gregory A. Volturo, E Lea Walters, Thomas E. Wyatt, Donald M. Yealy

Manuscripts, Articles, Book Chapters and Other Papers

This letter, signed by over 50 academic chairs of emergency medicine, urges the ACGME to reconsider a proposed mandate requiring all emergency medicine residency programs to adopt a four-year training model. The authors argue that current three-year programs are supported by data demonstrating equivalent educational and clinical outcomes compared to four-year formats. They criticize the flawed survey methodology underpinning the proposal, note the loss of milestone-based training flexibility, and highlight the lack of added scholarly or clinical value in the fourth year. The letter also outlines negative consequences for fellowship participation, workforce development, trainee debt, and diversity. The signatories advocate …

A Hypomorphic Model Of Cps1 Deficiency For Investigating The Effects Of Hyperammonemia On The Developing Nervous System, Stuti Bakshi, Taryn Diep, Brandon J Willis, Rachel Reyes, Grace F Wu, Georgios Makris, Martin Poms, Isabel Day, Qin Sun, Irina Zhuravka, Lindsay Lueptow, Michelle Tang, Gareth A Cromie, Aimée M Dudley, Johannes Häberle, Gerald S Lipshutz

Faculty, Staff and Students Publications

Carbamoyl phosphate synthetase 1 (CPS1) deficiency is a rare metabolic disorder that, in neonatal onset, is typically characterized by severe life-threatening and neurologically injuring hyperammonemic episodes with high unmet patient need. Patients that retain limited enzyme activity may present later in life with less severe hyperammonemia. CPS1 drives the first step in the urea cycle, the pathway terrestrial mammals utilize to metabolize nitrogen. In order to probe the effect of hyperammonemia on the developing nervous system and explore new therapies, a murine Cps1 exon 3-4 mutant was previously generated. However, these mice die within 24 h of birth, limiting study …

Performance Of Stool Xpert Mtb/Rif Ultra For Detection Of Mycobacterium Tuberculosis Among Adults Living With Hiv: A Multicentre, Prospective Diagnostic Study, George W Kasule, Sabine Hermans, Sozinho Acacio, Alexander Kay, Joachim Kikoyo Nsubuga, Carlos Fernández-Escobar, Nosisa Shiba, Lucia Carratalá-Castro, Derrick Semugenze, Patricia Mwachan, Shilzia Munguambe, Joanna Ehrlich, Elisa Lopez-Varela, Andrew R Dinardo, Frank Cobelens, Christoph Lange, Moses Joloba, Anna M Mandalakas, Willy Ssengooba, Alberto L García-Basteiro

Faculty, Staff and Students Publications

Background: When people living with HIV develop pulmonary tuberculosis, it often manifests without detectable acid-fast bacilli on sputum microscopy. We aimed to assess the diagnostic accuracy of stool Xpert MTB/RIF Ultra (hereafter, Ultra) for Mycobacterium tuberculosis detection among adults with HIV.

Methods: This multicentre, prospective diagnostic accuracy study was done in outpatient and inpatient health centres in Eswatini, Mozambique, and Uganda. We enrolled adults aged 15 years and older with HIV with presumptive tuberculosis. We evaluated the diagnostic accuracy of stool Ultra using the simple one-step processing method against a composite microbiological reference standard (CMRS) including three WHO-recommended tuberculosis diagnostic …

High Prevalence Of Strongyloides Stercoralis In People Living With Hiv: A Critical Health Challenge In The Peruvian Amazon Basin, Silvia Otero-Rodriguez, Martin Casapia-Morales, Viviana Pinedo-Cancino, Seyer Mego-Campos, Victoria-Ysabel Villacorta-Pezo, Jorge Parráguez-De-La-Cruz, Eva H Clark, Esperanza Merino, Jose-Manuel Ramos-Rincon

Faculty, Staff and Students Publications

Introduction: Strongyloidiasis is an important but underdiagnosed soil-transmitted helminthiasis, particularly in tropical areas and some vulnerable groups.

Objectives: To assess the parasitological prevalence, seroprevalence and sociodemographic factors of Strongyloides stercoralis infection in patients living with human immunodeficiency virus (PLWH) in an endemic area.

Materials and methods: We performed a cross-sectional study of strongyloidiasis in 537 PLWH in two hospitals in Iquitos, Peru, from 20 Oct 2023 to 20 May 2024. We tested patient sera using Strongyloides IgG enzyme-linked immunosorbent assay (ELISA) and stool via the modified Baermann technique and/or charcoal fecal culture as highly sensitive parasitological techniques. We used multivariable …

Identification Of A Translatable Animal Model For Dry Eye Disease Using Comparative Analysis Of Tear Proteins Across Species, Mayelín Pérez-Perdomo, Ana González-López, Laura Ortega-Llamas, David Alba-Molina, Mario Blanco-Blanco, María Del Mar Granados, Adrián Guerrero-Moreno, Stephen Carl Pflugfelder, Christoph Ullmer, Sascha Fauser, Yolanda Jiménez-Gómez, Miguel González-Andrades

Faculty, Staff and Students Publications

Purpose: This study aimed to assess the similarity of tear proteins between experimental animals and humans to identify the most translational animal model for dry eye disease (DED).

Methods: Eleven species were selected for a structural and physicochemical comparison of healthy human tear fluid proteins involved in DED. Amino acid sequences were compared using BLAST. Protein primary structure, isoelectric point (pI) and grand average of hydropathicity (GRAVY) were determined using ExPASy and compared with humans.

Results: Among non-primate mammals, the cat (69.7 %) and pig (68.7 %) showed the highest protein sequence similarity to humans. The ruminants and cat showed …

The State Of The Science Of Natural Family Planning: A Report From Nfp Scientists’ Meeting Held In Orlando, Fl, September 4, 2024, Michael D. Manhart, Richard J. Fehring

College of Nursing Faculty Research and Publications

A one-day meeting was held as a pre-conference to the Catholic Medical Association Annual Educational event in 2024. A panel of eighteen physicians, scientists, and researchers involved in NFP work was convened to review the available evidence in four topical areas: (i) evidence for effectiveness of NFP methods to postpone and achieve pregnancy, (ii) evidence for effectiveness in the postpartum and perimenopause transition periods, (iii) evaluate the current state of technology in NFP (specifically app and quantitative hormone monitoring), and (iv) evidence examining the impact of NFP on marital relations. In each topical area, the panel worked to reach a …

Emergence Of Cellular Nematic Order Is A Conserved Feature Of Gastrulation In Animal Embryos, Xin Li, Robert J Huebner, Margot L K Williams, Jessica Sawyer, Mark Peifer, John B Wallingford, D Thirumalai

Faculty, Staff and Students Publications

Cells undergo dramatic morphological changes during embryogenesis, yet how these changes affect the formation of ordered tissues remains elusive. Here, we show that a phase transition leading to the formation of a nematic liquid crystal state during gastrulation in the development of embryos of fish, frogs, and fruit flies occurs by a common mechanism despite substantial differences between these evolutionarily distant animals. Importantly, nematic order forms early before any discernible changes in the shapes of cells. All three species exhibit similar propagation of the nematic phase, reminiscent of nucleation and growth mechanisms. The spatial correlations in the nematic phase in …

Against The Phrase "Aggressive Care", Trevor M Bibler

Center for Medical Ethics and Health Policy Staff Publications

Language is the primary technology clinical ethicists use as they offer guidance about norms. Like any other piece of technology, to use the technology well requires attention, intention, skill, and knowledge. Word choice becomes a matter of professional practice. The Brief Report offers clinical ethicists several reasons for rejecting the phrase "aggressive care." Instead, ethicists should consider replacing "aggressive care" with the adjacent concept of a "recovery-focused path." The virtues of this neologism include: the opportunity to set aside the emotion of "aggression," the phrase's accuracy when capturing the intention of the patient or their representative, and an unappreciated rhetorical …

Enzyme-Independent Functions Of Hdac3 In The Adult Hear, Sichong Qian, Chen Zhang, Wenbo Li, Shiyang Song, Guanqiao Lin, Zixiu Cheng, Wenjun Zhou, Huiqi Yin, Yueli Wang, Haiyang Li, Ying H Shen, Zheng Sun

Center on Aging Staff Publications

The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes …

Metabolic Clearance Rate Of Insulin Across The Glucose Tolerance Spectrum By Race And Ethnicity In Youth With Obesity, Wonhee Cho, Fida Bacha, Hala Tfayli, Sojung Lee, Sara F Michaliszyn, Joon Young Kim, Silva Arslanian

Children’s Nutrition Research Center Staff Publications

Objective: Despite β-cell failure in youth with dysglycemia (i.e., impaired glucose tolerance [IGT] and type 2 diabetes), fasting insulin (FI) concentrations are elevated. Herein, we examined the following: 1) metabolic clearance rate of insulin (MCRI) in youth with obesity and normal glucose tolerance (NGT) versus those with IGT versus those with type 2 diabetes; 2) racial and ethnic differences in insulin dynamics; and 3) metabolic/adiposity correlates of MCRI.

Methods: A total of 206 youth underwent assessment of fasting glucose, FI, MCRI and peripheral insulin sensitivity (PIS), first-phase insulin secretion, disposition index, body composition, and abdominal adiposity.

Results: In type 2 …

Mechanisms Of Change In Exposure Therapy For Anxiety And Related Disorders: A Research Agenda, Kristen Benito, Andre Pittig, Jonathan Abramowitz, Joanna J Arch, Denise Chavira, Rianne De Kleine, Alessandro S De Nadai, Dirk Hermans, Stefan G Hofmann, Jürgen Hoyer, Jonathan D Huppert, Katharina Kircanski, Peter M Mcevoy, Heidi Meyer, Marie-H Monfils, Santiago Papini, Winfried Rief, David Rosenfield, Eric A Storch, Michael J Telch, Michael W Otto, Jasper A J Smits

Faculty, Staff and Students Publications

Anxiety and related disorders are a significant public health burden with rising prevalence in the wake of the COVID-19 pandemic. As demand for effective anxiety treatment increases, so too does the need for strategies to bolster treatment outcomes. Research on the mechanisms of exposure therapy, the frontline behavioral treatment, will be critically important for optimizing clinical outcomes. We outline an initial agenda for future research on the mechanisms of change of exposure therapy, developed in collaboration with a large international team of researchers through the Exposure Therapy Consortium (ETC). Key questions and recommendations for future research focus on five priority …

C-Terminal Frameshift Variants In Gpkow Are Associated With A Multisystemic X-Linked Disorder, Jung-Wan Mok, Laura Mackay, Maria Blazo, Elizabeth Mizerik, Jozef Gecz, Renee Carroll, Mathilde Nizon, Sophie Rondeau, Madeleine Joubert, Silvestre Cuinat, Wallid Deb, Fernanda Valle Sirias, Monika Weisz-Hubshman, Shamika Ketkar, Urszula Polak, Alyssa A Tran, Debra Kearney, Neil A Hanchard, Oguz Kanca, Michael F Wangler, Hugo J Bellen, Brendan H Lee, Shinya Yamamoto, Keren Machol

Duncan NRI Faculty and Staff Publications

Purpose: GPKOW, a gene on the X-chromosome, encodes a nuclear RNA-binding protein important in messenger RNA (mRNA) processing as a spliceosome subunit. This work aims to establish GPKOW as a disease-associated gene.

Methods: We describe 3 males from 2 unrelated families with hemizygous frameshift variants affecting the last exon of GPKOW p.(Arg441SerfsTer30) and p.(Ser444GlufsTer28). The effect of p.(Ser444GlufsTer28) on gene expression was evaluated in patient's fibroblasts. In vivo studies in Drosophila melanogaster targeting the sole GPKOW fly ortholog, CG10324 (Gpkow) were performed.

Results: Clinical presentations included intrauterine growth restriction, microcephaly/microencephaly, and eye, brain, skin, and skeletal abnormalities. Heterozygote females presented …

Integrative Analysis Reveals The Prognostic Effects Of Epigenetic Regulators In Bladder Cancer, Venugopalareddy Mekala, Yupei Lin, Xiang Wang, Naail Chowdhury, Jianrong Li, Chao Cheng

Faculty, Staff and Students Publications

Background: Epigenetic regulatory genes (epiRG) are pivotal in the epigenetic regulation of the human genome, primarily through DNA and histone modifications. These genes are frequently mutated in human cancers, particularly bladder cancer (BC). However, the functional impact of epiRG mutations on patient outcomes remains poorly understood.

Methods: In this study, we developed gene signatures for the most frequent genomic aberrations of epiRG using The Cancer Genome Atlas Bladder Carcinoma (TCGA-BLCA) dataset and validated these signatures with independent tumor expression profiles for prognostic relevance. Furthermore, we evaluated the role of these signature scores in the immune system within the tumor microenvironment …

A Survey Study Of Roadblocks In Translational Science, Fasiha Kanwal, Christopher I Amos, Katherine H Sippel, Claudia Neuhauser, Ariel Harrison, Mary E Dickinson, Charles Minard, Bettina M Beech

Faculty, Staff and Students Publications

Clinical and translational science needs to address roadblocks to the translational processes. We conducted a survey at two institutions, a private medical school and a large public university, to understand the frequency and distribution of barriers and roadblocks to research. We reviewed the literature to compile a pool of barriers and roadblocks and convened a panel of relevant stakeholders to develop a 20-item questionnaire. Survey respondents were asked to select and prioritize the five leading clinical and translational roadblocks, provide information regarding their academic degrees and rank/position, complete open-ended items regarding their areas of research, and optionally add additional remarks …

Cryoem Structure Of The Slfn14 Endoribonuclease Reveals Insight Into Rna Binding And Cleavage, Justin Van Riper, Arleth O Martinez-Claros, Lie Wang, Hannah E Schneiderman, Sweta Maheshwari, Monica C Pillon

Faculty, Staff and Students Publications

The SLFN14 endoribonuclease is a post-transcriptional regulator that targets the ribosome and its associated RNA substrates for codon-bias translational repression. SLFN14 nuclease activity is linked to antiviral defense and platelet function. Despite its prominent role in gene regulation, the molecular signals regulating SLFN14 substrate recognition and catalytic activation remain unclear. SLFN14 dysregulation is linked to human diseases, including ribosomopathies and inherited thrombocytopenia, thus underscoring the importance of establishing the signals coordinating its RNA processing activity. Here, we reconstitute active full-length human SLFN14 and report a high-resolution cryoEM reconstruction of the SLFN14•RNA complex. The structure reveals a medallion-like architecture that shares …

Diagnostic Accuracy Of Screening Tools For Depression And Anxiety In Cervical Dystonia, Davide Martino, Mehrafarin Ramezani, Steven Bellows, Brian D Berman, Florence Ching-Fen Chang, Jeanne Feuerstein, Victor Fung, Gamze Kilic Berkmen, Irene A Malaty, Claire Maciver, Scott A Norris, Kathryn J Peall, Joel S Perlmutter, Sarah Pirio Richardson, Laura J Wright, Zahra Goodarzi, Hyder A Jinnah

Faculty, Staff and Students Publications

Introduction: Despite their high prevalence and impact, depression and anxiety are not routinely screened for, and accuracy of screening procedures is unknown in adult-onset dystonia. We evaluated accuracy parameters of selected self-rated scales for depression and anxiety in patients with idiopathic cervical dystonia (CD).

Methods: Two-hundred-and-ten patients with idiopathic CD were recruited from 10 movement disorders centers from the US, Canada, Australia, and UK. At the end of each botulinum toxin cycle, participants were administered the Adult Standard Mini-International Neuropsychiatric Interview (MINI) as reference standard for depression and anxiety. Participants completed 8 self-administered index instruments (2 for depression, 2 for …

Beyond The Bone: A Misdiagnosis Of Paget’S Disease Reveals Polyostotic Mazabraud Syndrome, Michael Higham, Stephanie Campbell, Amanda Killeen

School of Podiatric Medicine Publications

Introduction: Mazabraud Syndrome is a rare benign condition characterized by polyostotic fibrous dysplasia and intramuscular myxomas. Due to its overlapping radiographic features, it is frequently misdiagnosed. We present a case where Mazabraud Syndrome was misdiagnosed as Paget’s disease for nearly 6 decades.

Case Presentation: A 59-year-old woman presented to the podiatry clinic with complaints of numbness and sharp pain of the left foot while in stance. Her surgical history is positive for numerous lower extremity myxomas excised over her lifetime, beginning in adolescence, and now with non-mobile soft tissue mass at the porta pedis of the left foot for 1 …

Covid-19-Associated Pulmonary Aspergillosis In Mechanically Ventilated Patients At 7 Us Hospitals: Epidemiology And Estimated Likelihood Of Invasive Pulmonary Aspergillosis-Results Of The Prospective Msg-017 Study, M Hong Nguyen, Sixto M Leal, Luis Ostrosky-Zeichner, Andrej Spec, George R Thompson, Thomas F Patterson, John Baddley, Rachel Mcmullen, Drashti Shah, Cornelius J Clancy, Gerald Mcgwin, Peter G Pappas

2020-Current year OA Pubs

BACKGROUND: There is no prospective, US multicenter study of COVID-19-associated pulmonary aspergillosis (CAPA). CAPA definitions do not differentiate invasive aspergillosis (IPA) from colonization. Validity of single mycologic test results is unclear.

METHODS: We performed a prospective 7-center US study of mechanically ventilated adults with COVID-19 (April 2021-May 2022). Mycoses Study Group (MSGERC) CAPA criteria include host and clinical factors, imaging and test results (histopathology; bronchoalveolar lavage [BAL] culture and/or BAL or serum galactomannan-immunoassay). Proven, putative, and unlikely IPA were defined by clinical criteria. CAPA-unlikely IPA criteria included survival or negative autopsy following no/limited antifungal treatment. IPA likelihood was estimated using …

Sexually Dimorphic Impact Of Prenatal Hyperandrogenism On Offspring Growth Trajectory In Sheep, Eylem Topaktas, Joseph Ciarelli, Stephanie Domke, Brooke Pallas, Adel Ghnenis, Mansi Agarwal, Charles Goss, Kevin Cho, Leah P Shriver, Gary J Patti, Vasantha Padmanabhan, Arpita Kalla Vyas

2020-Current year OA Pubs

In a translationally relevant ovine model of gestational hyperandrogenism we have previously reported cardiometabolic disruption in female offspring (males were not extensively studied). We hypothesized that gestational hyperandrogenism would lead to sex-specific disruption in offspring's growth, cytokine and metabolic milieu, potential mediators of cardiometabolic disease (CMD). 100 mg Testosterone propionate (T) or vehicle (C) was administered intramuscularly twice weekly between gestational days (GD) 30-90. Two cohorts of offspring were generated, including both males and females. Fetal weight and systemic metabolomics were analyzed in the fetal cohort (GD120). Growth trajectory, systemic cytokines, and metabolomics were analyzed in the postnatal cohort. Data …

Distinct Patterns Of Weight Gain, Age, And Subcortical Microstructure In Early Adolescence, Shana Adise, Zhaolong Adrian Li, Jonatan Ottino-González, Filip Morys, Peter A Chiarelli, Tamara Hershey

2020-Current year OA Pubs

IMPORTANCE: Associations between childhood obesity and brain microstructural differences have been observed. It remains unknown whether these associations are driven by sex-specific excessive weight gain. Restriction spectrum imaging characterizes brain tissue microstructural health via water diffusion, where the restricted normalized isotropic (RNI) compartment assesses neuronal and glial cellularity, which may reflect neuroinflammation, synaptic pruning, or both.

OBJECTIVE: To identify associations among RNI scaling factor values, normal neurodevelopment, and weight gain during early adolescence.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the Adolescent Brain Cognitive Development (ABCD) Study, a 10-year, ongoing, multisite longitudinal cohort study conducted among youths …

Utility Of The Us Preventive Services Task Force For Preeclampsia Risk Assessment And Aspirin Prophylaxis, Thomas F Mcelrath, Antonina I Frolova, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The US Preventive Services Task Force (USPSTF) guidelines on preeclampsia risk assessment and aspirin prophylaxis (AP) have not been evaluated for clinical utility.

OBJECTIVE: To evaluate which characteristics in the USPSTF guidelines identify risk status and the association of preeclampsia risk with AP recommendations.

DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study enrolled from July 2020 to March 2023 with data analysis performed from October to December 2024. Enrollment occurred at 11 centers throughout the US or via direct-to-participant recruitment. Pregnant participants aged 18 years or older with a singleton pregnancy less than 22 weeks' gestation were selected via …

Molecular Mechanisms Of Inverse Agonism Via Κ-Opioid Receptor-G Protein Complexes, Aaliyah S Tyson, Saif Khan, Zenia Motiwala, Gye Won Han, Zixin Zhang, Mohsen Ranjbar, Daniel Styrpejko, Nokomis Ramos-Gonzalez, Stone Woo, Kelly Villers, Delainey Landaker, Terry Kenakin, Ryan Shenvi, Susruta Majumdar, Cornelius Gati

2020-Current year OA Pubs

Opioid receptors, a subfamily of G protein-coupled receptors (GPCRs), are key therapeutic targets. In the canonical GPCR activation model, agonist binding is required for receptor-G protein complex formation, while antagonists prevent G protein coupling. However, many GPCRs exhibit basal activity, allowing G protein association without an agonist. The pharmacological impact of agonist-free receptor-G protein complexes is poorly understood. Here we present biochemical evidence that certain κ-opioid receptor (KOR) inverse agonists can act via KOR-G

Mayo Normative Studies: Regression-Based Normative Data For Remote Self-Administration Of The Stricker Learning Span, Symbols Test, And Mayo Test Drive Screening Battery Composite And Validation In Individuals With Mild Cognitive Impairment And Dementia, Nikki H Stricker, Jason Hassenstab, Et Al.

2020-Current year OA Pubs

No abstract provided.