Medicine and Health Sciences Commons^™

Double-Blind Randomised Trial Of Saline Solution For Gargling And Nasal Rinsing In Sars-Cov-2 Infection, Sebastian R Espinoza, Lexton Trauffler, Amir Shamshirsaz, Alireza Shamshirsaz, Andres Espinoza, Jimmy Espinoza, Alice O'Brien

Faculty, Staff and Student Publications

Background: Previous studies have shown that hypertonic saline nasal irrigation and gargling reduced the duration of symptoms in upper respiratory infections caused by coronavirus. This study aims to investigate the effects of two saline regimens on symptoms associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Methods: Between 2020 and 2022, individuals aged 18-65 years who tested positive for SARS-CoV-2 infection via polymerase chain reaction (PCR) were randomly assigned to either low- or high-saline regimens for 14 days. The low-saline solutions contained 2.13 g of salt dissolved in eight ounces of warm water, while the high-saline solution contained six grams of …

Transition To Enteral Triazole Antifungal Therapy For Pediatric Invasive Candidiasis: Secondary Analysis Of A Multicenter Cohort Study Conducted By The Pediatric Fungal Network, Robert F T Bucayu, Craig L K Boge, Inci Yildirim, Martha Avilés-Robles, Surabhi B Vora, David M Berman, Tanvi S Sharma, Lillian Sung, Elio Castagnola, Debra L Palazzi, Lara Danziger-Isakov, Dwight E Yin, Emmanuel Roilides, Gabriela Maron, Alison C Tribble, Pere Soler-Palacin, Eduardo López-Medina, José Romero, Kiran Belani, Antonio C Arrieta, Fabianne Carlesse, Dawn Nolt, Natasha Halasa, Daniel Dulek, Sujatha Rajan, William J Muller, Monica I Ardura, Alice Pong, Blanca E Gonzalez, Christine M Salvatore, Anna R Huppler, Catherine Aftandilian, Mark J Abzug, Arunaloke Chakrabarti, Michael Green, Irja Lutsar, Elizabeth D Knackstedt, Sarah K Johnson, William J Steinbach, Brian T Fisher, Rachel L Wattier

Faculty, Staff and Students Publications

Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was successful in 66 participants who transitioned to enteral therapy.

Age-Dependent Regulation Of Axoglial Interactions And Behavior By Oligodendrocyte Ankyring, Xiaoyun Ding, Yu Wu, Anna Vainshtein, Victoria Rodriguez, Emily Ricco, James T Okoh, Yanhong Liu, Daniel C Kraushaar, Elior Peles, Matthew N Rasband

Faculty, Staff and Students Publications

The bipolar disorder (BD) risk gene ANK3 encodes the scaffolding protein AnkyrinG (AnkG). In neurons, AnkG regulates polarity and ion channel clustering at axon initial segments and nodes of Ranvier. Disruption of neuronal AnkG causes BD-like phenotypes in mice. During development, AnkG is also expressed at comparable levels in oligodendrocytes and facilitates the efficient assembly of paranodal junctions. However, the physiological roles of glial AnkG in the mature nervous system, and its contributions to BD-like phenotypes, remain unexplored. Here, we show that oligodendroglia-specific AnkG conditional knockout results in destabilization of axoglial interactions in aged but not young adult mice. In …

Patient And Parent Knowledge, Understanding, And Concerns After A New Diagnosis Of Ehlers Danlos Syndrome., Jordan T. Jones, Lora L. Black, William R. Black

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: After diagnosis of Ehlers Danlos Syndrome (EDS), it is unclear what information patients and parents need and understand about EDS. The objective of this study is to characterize patient and parent knowledge and concerns about EDS after a diagnosis of EDS is made to determine patient and parent concerns and identify barriers that cause discomfort with the diagnosis.6 METHODS: A convenience sample of patient and parent dyads were recruited after new diagnosis of EDS. Patients and parents completed questionnaires that assessed knowledge, comfort, and barriers of EDS before and after diagnosis, EDS education materials accessed, and additional clinical needs …

Carboxyl Ester Lipase Hybrid 1 (Cel-Hyb1) Haplotypes Confer Varying Risk For Chronic Pancreatitis, Gergő Berke, Xunjun K Xiao, Mark E Lowe, Et Al.

2020-Current year OA Pubs

The CEL-HYB1 hybrid allele of the carboxyl ester lipase (CEL) gene and its pseudogene (CELP) has been associated with chronic pancreatitis (CP). Recent work indicated that amino acid positions 488 and 548 in CEL-HYB1 determined pathogenicity. Haplotype Thr488-Ile548 was associated with CP while haplotypes Thr488-Thr548 and Ile488-Thr548 were benign. However, functional analysis revealed that Thr488 is the primary determinant of CEL-HYB1 misfolding and associated endoplasmic reticulum (ER) stress. To address this contradiction, we analyzed a cohort from Hungary and found significantly increased CEL-HYB1 carrier frequency in CP cases (9/319, 2.8%) versus controls (5/618, 0.8%), yielding an odds ratio of 3.6 …

Refinement Of An Algorithm To Detect And Predict Freezing Of Gait In Parkinson Disease Using Wearable Sensors, Allison M Haussler, Lauren E Tueth, David S May, Gammon M Earhart, Pietro Mazzoni

2020-Current year OA Pubs

Freezing of gait (FOG) is a debilitating symptom of Parkinson disease (PD). It is episodic and variable in nature, making assessment difficult. Wearable sensors used in conjunction with specialized algorithms, such as our group's pFOG algorithm, provide objective data to better understand this phenomenon. While these methods are effective at detecting FOG retrospectively, more work is needed. The purpose of this paper is to explore how the existing pFOG algorithm can be refined to improve the detection and prediction of FOG. To accomplish this goal, previously collected data were utilized to assess the prediction ability of the current algorithm, the …

Lack Of Association Of The Pld4 Snp Rs2841277 With Systemic Sclerosis In A European American Population, Yunqing Ma, Maureen D Mayes, Xinjian Guo, Shervin Assassi, Xiaodong Zhou

Faculty, Staff and Student Publications

This study aimed to examine whether a reported SSc-associated SNP rs2841277 in the PLD4 gene identified in an Asian population was also associated with SSc in European American (EA). The EA cohort consisting of 1005 SSc patients and 961 healthy controls was examined in this study. TaqMan genotyping assays were performed to examine the SNP. Exact P-values were obtained from 2 × 2 tables of allele counts and disease status. In contrast to the previous reports in a Japanese population, SSc patients of EA did not show an association of PLD4 rs2841277 with SSc in general (P = 0.231, OR …

Aperiodic Spectral Slope Tracks The Effects Of Brain State On Saliency Responses In The Human Auditory Cortex, Madaline Mocchi, Eleonora Bartoli, John Magnotti, Jan Willem De Gee, Brian Metzger, Bailey Pascuzzi, Raissa Mathura, Suhruthaa Pulapaka, Wayne Goodman, Sameer Sheth, Matthew J Mcginley, Kelly Bijanki

Faculty, Staff and Students Publications

Alteration of responses to salient stimuli occurs in a wide range of brain disorders and may be rooted in pathophysiological brain state dynamics. Specifically, tonic and phasic modes of activity in the reticular activating system (RAS) influence, and are influenced by, salient stimuli, respectively. The RAS influences the spectral characteristics of activity in the neocortex, shifting the balance between low- and high-frequency fluctuations. Aperiodic '1/f slope' has emerged as a promising composite measure of these brain state dynamics. However, the relationship of 1/f slope to state-dependent processes, such as saliency, is less explored, particularly intracranially in humans. Here, we record …

Cochlear Mechanics Are Preserved After Inner Ear Delivery Of Gold Nanoparticles, Dorothy W Pan, Jinkyung Kim, Patricia M Quiñones, Anthony J Ricci, Brian E Applegate, John S Oghalai

2020-Current year OA Pubs

Novel therapeutic delivery systems and delivery methods to the inner ear are necessary to treat hearing loss and inner ear disorders. However, numerous barriers exist to therapeutic delivery into the bone-encased and immune-privileged environment of the inner ear and cochlea, which makes treating inner ear disorders challenging. Nanoparticles (NPs) are a type of therapeutic delivery system that can be engineered for multiple purposes, and posterior semicircular canal (PSCC) infusion is a method to directly deposit them into the cochlea. We sought to assess PSCC infusion of gold NPs into the cochlea, including the NPs' distribution and effect on cochlear mechanics. …

Stereotactic Cardiac Radiotherapy For Refractory Ventricular Tachycardia In Structural Heart Disease Patients: A Systematic Review, Amulya Gupta, Zeeshan Sattar, Nourhan Chaaban, Sagar Ranka, Cameron Carlson, Farhad Sami, Clifford G Robinson, Phillip S Cuculich, Seth H Sheldon, Madhu Reddy, David Akhavan, Amit Noheria

2020-Current year OA Pubs

AIMS: Among patients with structural heart disease with ventricular tachycardia (VT) refractory to medical therapy and catheter ablation, cardiac stereotactic body radiotherapy (SBRT) is a paradigm-changing treatment option. This study aims to assess the efficacy of cardiac SBRT in refractory VT by comparing the rates of VT episodes, anti-tachycardia pacing (ATP) therapies, and implantable cardioverter-defibrillator (ICD) shocks post-SBRT with pre-SBRT.

METHODS AND RESULTS: We performed a comprehensive literature search and included all clinical studies reporting outcomes on cardiac SBRT for VT. Treatment efficacy was evaluated as random-effects pooled rate-ratios of VT episodes, ATP therapies and ICD shocks post-SBRT (after 6-week …

High Peripheral T Cell Diversity Is Associated With Lower Risk Of Toxicity And Superior Response To Dual Immune Checkpoint Inhibitor Therapy In Patients With Metastatic Nsclc, Mehmet Altan, Ruoxing Li, Ziyi Li, Runzhe Chen, Ajay Sheshadri, Hai T Tran, Latasha Little, Joshua Baguley, Jefferson Sinson, Natalie Vokes, Saumil Gandhi, Mara B Antonoff, Stephen G Swisher, Greg Lizee, Alexandre Reuben, John V Heymach, Jianjun Zhang

Faculty, Staff and Student Publications

INTRODUCTION: Despite significant successes, immune checkpoint blockade fails to achieve clinical responses in a significant proportion of patients, predictive markers for responses are imperfect and immune-related adverse events (irAEs) are unpredictable. We used T-cell receptor (TCR) sequencing to systematically analyze prospectively collected patient blood samples from a randomized clinical trial of dual immune checkpoint inhibitor therapy to evaluate changes in the T-cell repertoire and their association with response and irAEs.

METHODS: Patients with immunotherapy-naïve metastatic non-small cell lung cancer (NSCLC) were treated with ipilimumab and nivolumab according to trial protocol (LONESTAR, NCT03391869). Blood samples were systematically obtained at baseline (n=107), …

Lower-Intensity Cpx-351 Plus Venetoclax Induction For Adults With Newly Diagnosed Aml Unfit For Intensive Chemotherapy, Geoffrey L Uy, Vinod Pullarkat, Praneeth Baratam, Robert K Stuart, Roland B Walter, Eric S Winer, Qi Wang, Stefan Faderl, Divya Chakravarthy, Diane Menno, Ronald S Cheung, Tara L Lin

2020-Current year OA Pubs

Preclinical data suggest a rationale for combining CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine, with venetoclax, a B-cell lymphoma-2 inhibitor. This phase 1b study evaluated lower-intensity CPX-351 combined with venetoclax in adults with acute myeloid leukemia (AML) considered unfit/ineligible for intensive chemotherapy. In a dose-exploration phase using a 3+3 design, patients received stepwise dosing of CPX-351 IV on days 1 and 3 plus venetoclax 400 mg orally on days 2 to 21 per cycle to determine the recommended phase 2 dose (RP2D) for this combination. During the expansion phase, additional patients received CPX-351 plus venetoclax at the identified …

Loss Of Chop Prevents Joint Degeneration And Pain In A Mouse Model Of Pseudoachondroplasia, Jacqueline T Hecht, Alka C Veerisetty, Mohammad G Hossain, Debabrata Patra, Michele Carrer, Frankie Chiu, Dorde Relic, Paymaan Jafar-Nejad, Karen L Posey

Faculty, Staff and Student Publications

Pseudoachondroplasia (PSACH), a severe dwarfing condition characterized by impaired skeletal growth and early joint degeneration, results from mutations in cartilage oligomeric matrix protein (COMP). These mutations disrupt normal protein folding, leading to the accumulation of misfolded COMP in chondrocytes. The MT-COMP mouse is a murine model of PSACH that expresses D469del human COMP in response to doxycycline and replicates the PSACH chondrocyte and clinical pathology. The basis for the mutant-COMP pathology involves endoplasmic reticulum (ER) stress signaling through the PERK/eIF2α/CHOP pathway. C/EBP homologous protein (CHOP), in conjunction with a TNFα inflammatory process, upregulates mTORC1, hindering autophagy clearance of mutant COMP …

Digital Cognitive Behavioral Therapy Vs Education For Pain In Adults With Sickle Cell Disease, Charles R. Jonassaint, Christina M. Lalama, C. Patrick Carroll, Sherif M. Badawy, Megan E. Hamm, Jennifer N. Stinson, Chitra Lalloo, Santosh L. Saraf, Victor R. Gordeuk, Robert M. Cronin, Nirmish Shah, Sophie M. Lanzkron, Darla Liles, Julia A. O'Brien, Cassandra Trimnell, Lakiea Bailey, Raymona H. Lawrence, Leshana Saint Jean, Michael Debaun, Laura M. De Castro, Tonya M. Palermo, Kaleab Z. Abebe

Department of Medicine Faculty Papers

Despite the burden of chronic pain in sickle cell disease (SCD), nonpharmacological approaches remain limited. This multisite, randomized trial compared digital cognitive behavioral therapy (CBT) with a digital pain/SCD education program ("Education") for managing pain and related symptoms. Participants were recruited virtually from seven SCD centers and community organizations in the United States. Adults (aged ≥18 years) with SCD-related chronic pain and/or daily opioid use were assigned to receive either CBT or Education for 12 weeks. Both groups used an app with interactive chatbot lessons and received personalized health coach support. The primary outcome was the change in pain interference …

Evaluating The Impact Of A Novel Program To Address Acute Food Insecurity Among Cancer Patients, Elliott M. Sina, Michael Rowe, Gina Mancuso, Gregory Garber, W. Kevin Kelly, Amy E. Leader

Kimmel Cancer Center Faculty Papers

INTRODUCTION: Acute food insecurity (FI) significantly impacts cancer patients' health, exacerbating physical and psychological burdens. While current interventions address chronic FI, acute cases remain undermanaged. Legacy of Hope, a Philadelphia-based non-profit, addresses this gap through its Emergency Patient Support Network (EPSN), offering free bi-weekly groceries to patients facing acute FI.

MATERIALS AND METHODS: The pilot study evaluated EPSN's impact utilizing the Legacy of Hope Acute Food Insecurity (LOHAFI) survey, which was performed at baseline and two weeks post-intervention. The survey combines the Functional Assessment of Cancer Therapy-General (FACT-G7) and questions on food and financial security. Mean scores and frequencies were …

Use Of Cigarettes And E-Cigarettes, Impulsivity, And Anxiety: Influences On Suicidal Ideation Among Youth And Young Adults In Texas, Anna V Wilkinson, Baojiang Chen, Alan C Swann, David P Graham, David A Nielsen, Thomas R Kosten, Alexandra Loukas, Dale S Mantey, Bara S Bataineh, Melissa B Harrell

Faculty, Staff and Students Publications

Introduction: Cigarette use and smoking intensity increase risk of suicidal ideation. Less is known about e-cigarette use. Here we examine direct influences of cigarette versus e-cigarette use on suicidal ideation among 16- to 23-year-olds in Texas.

Aims and methods: Since 2019, the Texas Adolescent Tobacco and Marketing Surveillance Study collected data on suicidal ideation every 6 months covering the previous 2 weeks. Youths answering that they had "thoughts that you would be better off dead, or of hurting yourself" on more than 2 of 14 days were categorized as having suicidal ideation. Generalized linear mixed-effects logistic regressions examined the influence …

Phenotypic And Genetic Heterogeneity Of A Pakistani Cohort Of 15 Consanguineous Families Segregating Variants In Leber Congenital Amaurosis-Associated Genes, Zainab Akhtar, Sumaira Altaf, Yumei Li, Sana Bibi, Jamal Shah, Kiran Afshan, Meng Wang, Hafiz Muhammad Jafar Hussain, Nadeem Qureshi, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Background: Leber congenital amaurosis (LCA) is a congenital onset severe form of inherited retinal dystrophy (IRD) and a common cause of pediatric blindness. Disease-causing variants in at least 14 genes are reported to predispose LCA phenotype. LCA is inherited as an autosomal recessive disease. It can be an isolated eye disorder or as part of a syndrome, such as Senior Loken or Joubert syndrome. Sequencing studies from consanguineous populations have proven useful for novel variants identification; thus, the present study aimed to explore the genetic heterogeneity of 15 consanguineous Pakistani families, each segregating a severe IRD phenotype using targeted next …

Retrospective Derivation Of A Causal Pathway For Diabetic Ketoacidosis In Adult Patients With Type 2 Diabetes Mellitus, Jeffrey A Kline, Nicholas A Wesner, Amina T Sharif, Richard T Griffey, Phillip D Levy, Robert D Welch, George Grunberger

2020-Current year OA Pubs

BACKGROUND: Type 2 ketone-prone diabetes mellitus (T2KPDM) is thought to occur in men of African descent, with obesity who experienced prolonged hyperglycemia; the role of medication non-adherence as a contributing cause remains unstudied.

RESEARCH DESIGN AND METHODS: This was a retrospective study of unique adults (>18 years) who sought emergency care one of four hospitals in the greater Detroit area. Patients were identified on the basis of a laboratory order for a ß-hydroxybutyrate concentration. Two research coordinators abstracted 119 data fields. Patients were divided into four phenotypes: (1) no prior DM, (2) type 2 DM without prior ketosis, (3) …

Results Of The Simultaneous Combination Of Ponatinib And Blinatumomab In Philadelphia Chromosome-Positive All, Hagop Kantarjian, Nicholas J Short, Fadi G Haddad, Nitin Jain, Xuelin Huang, Guillermo Montalban-Bravo, Rashmi Kanagal-Shamanna, Tapan M Kadia, Naval Daver, Kelly Chien, Yesid Alvarado, Guillermo Garcia-Manero, Ghayas C Issa, Rebecca Garris, Cedric Nasnas, Lewis Nasr, Farhad Ravandi, Elias Jabbour

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In this analysis, we update our experience with the chemotherapy-free regimen of blinatumomab and ponatinib in 60 patients with newly diagnosed Philadelphia chromosome (Ph)-positive ALL. At a median follow-up of 24 months, the complete molecular response rate …

Survival Analysis Of Clear Cell Renal Cell Carcinoma Based On Radiomics And Deep Learning Features From Ct Images, Zhennan Lu, Sijia Wu, Dan Ni, Meng Zhou, Tao Wang, Xiaobo Zhou, Liyu Huang, Yu Yan

Faculty, Staff and Student Publications

Purpose: To create a nomogram for accurate prognosis of patients with clear cell renal cell carcinoma (ccRCC) based on computed tomography images.

Methods: Eight hundred twenty-two ccRCC patients with contrast-enhanced computed tomography images involved in this study were collected. A rectangular region of interest surrounding the tumor was used to extract quantitative radiomics and deep-learning features, which were filtered by Cox proportional hazard regression model and least absolute shrinkage and selection operator. Then the selected features formed a fusion signature, which was assessed by Cox proportional hazard regression model method, Kaplan-Meier analysis, receiver operating characteristic curves, and concordance index (C-index) …

Pediatric Providers' Views On Participating In An Hpv Vaccine Quality Improvement Intervention: A Qualitative Analysis, Edan Leshem, Sara Malone, Andrew Solsrud, Sherry Dodd, Shannon Rook, Sharon Graham, Lauren Ericson, Ruoyun Wang, Katie Plax, Jason Newland

2020-Current year OA Pubs

BACKGROUND: Human papillomavirus (HPV), a common sexually transmitted infection in the US, contributes to oropharyngeal and urogenital cancers. To improve HPV vaccine uptake, quality improvement (QI) interventions that address barriers to vaccination in primary care may help. This study aims to understand pediatric primary care providers' (PCP) perspectives on participating in an HPV QI intervention that utilized practice facilitation to improve HPV vaccine uptake in pediatric primary care clinics.

METHODS: Participants were pediatric PCPs whose clinics completed a QI intervention that utilized practice facilitation led by an outside facilitator. One PCP from each practice completed a 15-min semi-structured exit interview. …

Brain Volumes, Cognitive, And Adaptive Skills In School-Age Children With Down Syndrome, Rebecca Grzadzinski, Kelly Botteron, Natasha Marrus, Robert Mckinstry, Et Al.

2020-Current year OA Pubs

BACKGROUND: Down syndrome (DS) is the most common congenital neurodevelopmental disorder, present in about 1 in every 700 live births. Despite its prevalence, literature exploring the neurobiology underlying DS and how this neurobiology is related to behavior is limited. This study fills this gap by examining cortical volumes and behavioral correlates in school-age children with DS.

METHODS: School-age children (mean = 9.7 years ± 1.1) underwent comprehensive assessments, including cognitive and adaptive assessments, as well as an MRI scan without the use of sedation. Children with DS (n = 35) were compared to available samples of typically developing (TD; n …

Assessing Tolerability With The Functional Assessment Of Cancer Therapy Item Gp5: Psychometric Evidence From Libretto-531, A Phase 3 Trial Of Selpercatinib In Medullary Thyroid Cancer, Antoine Regnault, Laurine Bunod, Angely Loubert, Marcia S. Brose, Lisa M. Hess, Patricia Maeda, Yan Lin, Rebecca M. Speck, Adrienne M. Gilligan, Nalin Payakachat

Department of Medical Oncology Faculty Papers

BACKGROUND: This psychometric analysis generated evidence to support the use of the Functional Assessment of Cancer Therapy item GP5 (GP5) as a measure of tolerability and confirms the appropriateness of categorizing "high side-effect burden" using a rating of 3 or 4 (score ranges 0-4) in patients with advanced/metastatic RET-mutant medullary thyroid cancer (MTC).

METHODOLOGY: Blinded, pooled interim data from the safety population (n=290) enrolled in the phase 3 LIBRETTO-531 trial (NCT04211337) were used. Intraclass correlation coefficients (ICC) were calculated for test-retest reliability using data from cycles 1-2 post-baseline. Construct validity was evaluated by examining the correlations of GP5 ratings with …

Deuterated Water Labeling In Ibrutinib-Treated Patients With Cll: Leukemia Cell Kinetics Correlate With Ighv, Zap-70, And Mrd, Ekaterina Kim, Shih-Shih Chen, Mariela Sivina, Hyunsoo Hwang, Xuelin Huang, Alessandra Ferrajoli, Nitin Jain, William G Wierda, Dominik Wodarz, Nicholas Chiorazzi, Jan A Burger

Faculty, Staff and Student Publications

Deuterated (“heavy”) water labeling in patients with chronic lymphocytic leukemia (CLL) demonstrates that IGHV unmutated and ZAP-70+ patients have higher blood and tissue CLL death rates on ibrutinib therapy, resulting in lower measurable residual disease levels with long-term ibrutinib treatment. This trial was registered at www.clinicaltrials.gov as #NCT01752426.

Age-Related Tfeb Downregulation In Proximal Tubules Causes Systemic Metabolic Disorders And Occasional Apolipoprotein A4-Related Amyloidosis, Jun Nakamura, Takeshi Yamamoto, Yoshitsugu Takabatake, Tomoko Namba-Hamano, Atsushi Takahashi, Jun Matsuda, Satoshi Minami, Shinsuke Sakai, Hiroaki Yonishi, Shihomi Maeda, Sho Matsui, Hideaki Kawai, Isao Matsui, Tadashi Yamamuro, Ryuya Edahiro, Seiji Takashima, Akira Takasawa, Yukinori Okada, Tamotsu Yoshimori, Andrea Ballabio, Yoshitaka Isaka

Duncan NRI Faculty and Staff Publications

With the aging of society, the incidence of chronic kidney disease (CKD), a common cause of death, has been increasing. Transcription factor EB (TFEB), the master transcriptional regulator of the autophagy/lysosomal pathway, is regarded as a promising candidate for preventing various age-related diseases. However, whether TFEB in the proximal tubules plays a significant role in elderly patients with CKD remains unknown. First, we found that nuclear TFEB localization in proximal tubular epithelial cells (PTECs) declined with age in both mice and humans. Next, we generated PTEC-specific Tfeb-deficient mice and bred them for up to 24 months. We found that TFEB …

Transforming Growth Factor-Beta Is Increased In Sputum From Individuals With Rheumatoid Arthritis-Associated Pulmonary Fibrosis, Timothy M. Wilson, Matthew Bolt, Andrew Stahly, Joyce S. Lee, Tami J. Bang, Peter B. Sachs, Kevin D. Deane, Stephen M. Humphries, Joshua J. Solomon, M. Kristen Demoruelle

Division of Rheumatology Faculty Papers

BACKGROUND: Interstitial lung disease (ILD) develops in 5-10% of patients with RA and contributes significantly to morbidity and mortality, particularly in those with a fibrotic phenotype. Yet, biomarkers to reliably identify RA patients with underlying pulmonary fibrosis are inadequate. Herein, we used sputum to identify lung-based biomarkers that distinguish RA patients with underlying pulmonary fibrosis and may better inform underlying pathogenesis in RA-ILD.

METHODS: We included 37 RA patients with pulmonary fibrosis (RA-PF) and 30 RA patients without ILD (RA-no-ILD). Induced sputum and serum were tested for TGF-β levels by immunoassay. DNA was extracted to determine presence of the MUC5B …

Structural Variant Allelic Heterogeneity In Mecp2 Duplication Syndrome Provides Insight Into Clinical Severity And Variability Of Disease Expression, Davut Pehlivan, Marwan S Shinawi, Et Al.

2020-Current year OA Pubs

BACKGROUND: MECP2 Duplication Syndrome, also known as X-linked intellectual developmental disorder Lubs type (MRXSL; MIM: 300260), is a neurodevelopmental disorder caused by copy number gains spanning MECP2. Despite varying genomic rearrangement structures, including duplications and triplications, and a wide range of duplication sizes, no clear correlation exists between DNA rearrangement and clinical features. We had previously demonstrated that up to 38% of MRXSL families are characterized by complex genomic rearrangements (CGRs) of intermediate complexity (2 ≤ copy number variant breakpoints <  5), yet the impact of these genomic structures on regulation of gene expression and phenotypic manifestations have not been investigated.

METHODS: To study the role of the genomic rearrangement structures on an individual's clinical phenotypic variability, we employed a comprehensive …

Primary Anorectal Mammary-Like Adenocarcinoma: A Potential Diagnostic Pitfall With Conventional Colorectal Adenocarcinoma, Margaret L Axelrod, Xiuli Liu, Pooja Navale

2020-Current year OA Pubs

Anogenital mammary-like glands (AGMLGs) are present in the anogenital region that bear striking morphologic and protein-expression similarities to mammary glands in the breast. AGMLGs can give rise to both benign and malignant lesions which mimic primary breast lesions. Herein, we report two mammary-type adenocarcinomas arising from AGMLGs, including one in the previously unreported site of the rectum. Recognition of mammary-type adenocarcinoma in the rectal and anogenital regions is crucial as clinical management options may differ compared to conventional colorectal adenocarcinomas.

Utility Of Colposcopy For The Screening And Management Of Cervical Cancer In Africa: A Cross-Sectional Analysis Of Providers’ Training And Practices, Joël Fokom Domgue, Issimouha Dille, Freddy Gnangnon, Sharon Kapambwe, Celine Bouchard, Nomonde Mbatani, Elodie Gauroy, Nathalie Ledaga Ambounda, Robert Yu, Fatoumata Sidibe, Joseph Kamgno, Bangaly Traore, Pierre-Marie Tebeu, Gregory Halle-Ekane, Mohenou Isidore Diomande, Jean-Marie Dangou, Fabrice Lecuru, Isaac Adewole, Marie Plante, Partha Basu, Sanjay Shete

Faculty, Staff and Student Publications

Introduction: Cervical cancer is a public health issue in Africa with devastating socioeconomic consequences due to the lack of organized screening programs. The success of screening programs depends on the appropriate investigation and management of women who test positive for screening. Colposcopic assessment following positive screening results is a noteworthy issue in Africa. This study aimed to assess the utilization of colposcopy by providers in the region.

Methods: A cross-sectional study was conducted in 2021-2022 among healthcare providers involved in cervical cancer prevention activities in Africa. They were invited to report prior colposcopy training, whether they performed colposcopy and the …

Influenza Knowledge And Barriers To Vaccination In Immunosuppressed Patients In The Pediatric Rheumatology Clinic., Julia G. Harris, Leslie Favier, Jordan T. Jones, Maria Ibarra, Michael J. Holland, Emily Fox, Kelly Jensen, Ashley K. Sherman, Ashley M. Cooper

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Most patients with a pediatric rheumatic disease are at increased risk of influenza due to immunosuppressive medication use. Despite initial quality improvement efforts, our influenza vaccination rate plateaued at 72%, which prompted a survey of patients and families to assess provider vaccine recommendations, influenza knowledge, and barriers to influenza vaccination.

METHODS: Patients on immunosuppressive medication or their parent were eligible to complete a survey between July 2019 and January 2020. Survey questions assessed demographics, rheumatology diagnosis, immunosuppressive medication(s), influenza vaccination recommendation, patient/parent influenza knowledge, and barriers to influenza vaccination. Influenza vaccination rates for immunosuppressed patients were acquired each influenza …