Medicine and Health Sciences Commons^™

Evaluating Noninvasive Brain Stimulation To Treat Overactive Bladder In Individuals With Multiple Sclerosis: A Randomized Controlled Trial Protocol, Betsy H Salazar, Kristopher A Hoffman, John A Lincoln, Christof Karmonik, Hamida Rajab, Santosh A Helekar, Rose Khavari

Faculty, Staff and Student Publications

Background

Multiple Sclerosis (MS) is an often debilitating disease affecting the myelin sheath that encompasses neurons. It can be accompanied by a myriad of pathologies and adverse effects such as neurogenic lower urinary tract dysfunction (NLUTD). Current treatment modalities for resolving NLUTD focus mainly on alleviating symptoms while the source of the discomfort emanates from a disruption in brain to bladder neural circuitry. Here, we leverage functional magnetic resonance imaging (fMRI), repetitive transcranial magnetic stimulation (rTMS) protocols and the brains innate neural plasticity to aid in resolving overactive bladder (OAB) symptoms associated with NLUTD.

Methods

By employing an advanced neuro-navigation …

Dementia Prediction In Older Adults Using Sex-Specific Health Trajectory Clustering, Omar A Ibrahim, Muskan Garg, Sunyang Fu, Maria Vassilaki, Ronald C Petersen, Jennifer St Sauver, Sunghwan Sohn

Faculty, Staff and Student Publications

With increasing number of people living with dementia, the problem of late diagnosis significantly impacts a person's quality of life while early signs of dementia may provide useful insights to facilitate better treatment plans. With time, this progressive neurodegenerative syndrome could progress from mild cognitive impairment to dementia. A pattern of health conditions can be characterized in unsupervised manner to help predict this progress. As a significant extension to our previous work with streaming clustering model, we consider additional information for predicting dementia onset. With empirical observations, we discover the importance of examining sex and age to predict dementia onset. …

Challenges In Selecting Patient-Reported Outcome Measures For Use In A Patient-Facing Technology, Priyank Raj, Youmin Cho, Yun Jiang, Yang Gong

Faculty, Staff and Student Publications

Patient-reported outcome measures (PROMs) have been increasingly integrated into patient-facing technologies to engage and empower patients in cancer self-management at home. However, researchers and developers face several challenges in selecting the best-suited PROMs for patient-facing technologies, due to the complex nature of the disease, the multitude of PROMs with high psychometric quality, and the lack of clear standards for PROM utilization. In this paper, we have discussed these challenges, illustrated by breast cancer instruments.

Effect Of Russian Current Expert Modes On Quadriceps Muscle Torque In Healthy Adults: A Single-Blinded Randomized Controlled Trial, Ansam Hasan, Ibrahim Moustafa, Tamer Shousha

Faculty, Staff and Student Publications

BACKGROUND: Russian current (RC), a well-known neuromuscular electrical stimulation operating at 2500 Hz, has demonstrated significant strength improvement over traditional exercises due to its high tolerance and low pain provocation. Despite extensive NMES parameter research, the specific effects of expert modes, particularly ON2 and Rest, remain unexplored. This study investigates the direct effect of these expert modes on quadriceps muscle strength in healthy adults.

METHODS: This is a single-blind, randomization-controlled trial. Forty-eight healthy university students (31 females, 17 males) were assigned in two randomized experimental groups either the ON2 or Rest mode for a 15-minute electrical stimulation session. Quadriceps maximum …

Short-Term Impact Of Low-Intensity Exercise With Blood Flow Restriction On Mild Knee Osteoarthritis In Older Adults: A Pilot Study, Kang-Ho Kim, Seung-Ho Kang, Nackhwan Kim, Jaehyeong Choi, Seok Kang

Faculty, Staff and Student Publications

This pilot study aimed to investigate the immediate impact of low-intensity exercises with blood flow restriction (BFR) on older adults with knee osteoarthritis (KOA). Fifteen patients with KOA who were over 50 years old, participated and underwent low-intensity resistance knee exercises at 30% of their one-repetition maximum with BFR three times/week for two weeks. Pre- and post-exercise assessments included pain levels, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, isokinetic knee strength, lower extremity muscle volume (via leg circumference and muscle thickness), functional performance tests (timed up-and-go [TUG] and sit-to-stand [STS]), skeletal muscle index (SMI) using bioelectrical impedance analysis, …

Prenatal Cocaine Exposure And Its Influence On Pediatric Epigenetic Clocks And Epigenetic Scores In Humans, Thiago Wendt Viola, Christina Danzer, Victor Mardini, Claudia Szobot, João Henrique Chrusciel, Laura Stertz, Joy M Schmitz, Consuelo Walss-Bass, Gabriel R Fries, Rodrigo Grassi-Oliveira

Faculty, Staff and Student Publications

The investigation of the effects of prenatal cocaine exposure (PCE) on offspring has been inconsistent, with few studies investigating biological outcomes in humans. We profiled genome-wide DNA methylation (DNAm) of umbilical cord blood (UCB) from newborns with (n = 35) and without (n = 47) PCE. We used DNAm data to (1) assess pediatric epigenetic clocks at birth and (2) to estimate epigenetic scores (ES) for lifetime disorders. We generated gestational epigenetic age estimates (DNAmGA) based on Knight and Bohlin epigenetic clocks. We also investigated the association between DNAmGA and UCB serum brain-derived neurotrophic factor (BDNF) levels. Considering the large-scale …

Neural Correlates Of Automatic Emotion Regulation And Their Association With Suicidal Ideation In Adolescents During The First 90-Days Of Residential Care, Matthew Dobbertin, Karina S Blair, Joseph Aloi, Sahil Bajaj, Johannah Bashford-Largo, Avantika Mathur, Ru Zhang, Erin Carollo, Amanda Schwartz, Jaimie Elowsky, J L Ringle, Patrick Tyler, R James Blair

Faculty, Staff and Student Publications

Background: Suicide is the second leading cause of death for adolescents in the United States. However, relatively little is known about the forms of atypical neuro-cognitive function that are correlates of suicidal ideation (SI). One form of cognitive/affective function that, when dysfunctional, is associated with SI is emotion regulation. However, very little work has investigated the neural correlates of emotion dysregulation in adolescents with SI.

Methods: Participants (N = 111 aged 12-18, 32 females, 31 [27.9%] reporting SI) were recruited shortly after their arrival at a residential care facility where they had been referred for behavioral and mental health problems. …

Durvalumab Plus Carboplatin/Paclitaxel Followed By Maintenance Durvalumab With Or Without Olaparib As First-Line Treatment For Advanced Endometrial Cancer: The Phase Iii Duo-E Trial, Shannon N Westin, Kathleen Moore, Hye Sook Chon, Jung-Yun Lee, Jessica Thomes Pepin, Michael Sundborg, Ayelet Shai, Joseph De La Garza, Shin Nishio, Michael A Gold, Ke Wang, Kristi Mcintyre, Todd D Tillmanns, Stephanie V Blank, Ji-Hong Liu, Michael Mccollum, Fernando Contreras Mejia, Tadaaki Nishikawa, Kathryn Pennington, Zoltan Novak, Andreia Cristina De Melo, Jalid Sehouli, Dagmara Klasa-Mazurkiewicz, Christos Papadimitriou, Marta Gil-Martin, Birute Brasiuniene, Conor Donnelly, Paula Michelle Del Rosario, Xiaochun Liu, Els Van Nieuwenhuysen, Duo-E Investigators

Faculty, Staff and Student Publications

PURPOSE: Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease.

METHODS: This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival …

Epha2- And Hdac-Targeted Combination Therapy In Endometrial Cancer, Robiya Joseph, Santosh K Dasari, Sujanitha Umamaheswaran, Lingegowda S Mangala, Emine Bayraktar, Cristian Rodriguez-Aguayo, Yutuan Wu, Nghi Nguyen, Reid T Powell, Mary Sobieski, Yuan Liu, Mark Seungwook Kim, Sara Corvigno, Katherine Foster, Pahul Hanjra, Thanh Chung Vu, Mamur A Chowdhury, Paola Amero, Clifford Stephan, Gabriel Lopez-Berestein, Shannon N Westin, Anil K Sood

Faculty, Staff and Student Publications

Endometrial cancer is the most frequent malignant tumor of the female reproductive tract but lacks effective therapy. EphA2, a receptor tyrosine kinase, is overexpressed by various cancers including endometrial cancer and is associated with poor clinical outcomes. In preclinical models, EphA2-targeted drugs had modest efficacy. To discover potential synergistic partners for EphA2-targeted drugs, we performed a high-throughput drug screen and identified panobinostat, a histone deacetylase inhibitor, as a candidate. We hypothesized that combination therapy with an EphA2 inhibitor and panobinostat leads to synergistic cell death. Indeed, we found that the combination enhanced DNA damage, increased apoptosis, and decreased clonogenic survival …

Evaluation Of Potential Biomarkers For Lenvatinib Plus Pembrolizumab Among Patients With Advanced Endometrial Cancer: Results From Study 111/Keynote-146, Vicky Makker, Matthew H Taylor, Carol Aghajanian, Allen L Cohn, Marcia S Brose, Christopher Di Simone, Zhu Alexander Cao, Leah Suttner, Andrey Loboda, Razvan Cristescu, Petar Jelinic, Robert Orlowski, Lea Dutta, Junji Matsui, Corina E Dutcus, Yukinori Minoshima, Mark J Messing

Faculty, Staff and Student Publications

BACKGROUND: Lenvatinib plus pembrolizumab demonstrated clinically meaningful benefit in patients with previously treated advanced endometrial carcinoma in Study 111/KEYNOTE-146 (NCT02501096). In these exploratory analyses from this study, we evaluated the associations between clinical outcomes and gene expression signature scores and descriptively summarized response in biomarker subpopulations defined by tumor mutational burden (TMB) and DNA variants for individual genes of interest.

METHODS: Patients with histologically confirmed metastatic endometrial carcinoma received oral lenvatinib 20 mg once daily plus intravenous pembrolizumab 200 mg every 3 weeks for 35 cycles. Archived formalin-fixed paraffin-embedded tissue was obtained from all patients. T-cell-inflamed gene expression profile (Tcell …

Factors Affecting The Ability Of Patients With Complex Vascular Anomalies To Navigate The Healthcare System, Bryan Sisk, Sunny Lin, Anna M Kerr

2020-Current year OA Pubs

BACKGROUND: Vascular anomalies (VAs) are rare congenital disorders that can cause pain, disfigurement, coagulopathy, asymmetric growth, and disability. Patients with complex VAs experience multiple barriers to accessing expert care. It is imperative to understand which factors support these patients' ability to navigate the healthcare system.

RESULTS: We surveyed adult patients with VAs using previously validated measures, recruiting participants from five patient advocacy groups and multidisciplinary VA clinics. The primary outcome was self-reported ability to access needed medical care, using the "Navigating the Healthcare System" subscale of the Health Literacy Questionnaire. We evaluated factors associated with the ability to navigate the …

Syphilis Complicating Pregnancy And Congenital Syphilis, Irene A Stafford, Kimberly A Workowski, Laura H Bachmann

Faculty, Staff and Student Publications

No abstract provided.

Comparing Cognitive Tests And Smartphone-Based Assessment In 2 Us Community-Based Cohorts., Ileana De Anda-Duran, Preeti Sunderaraman, Edward Searls, Shirine Moukaled, Xuanyi Jin, Zachary Popp, Cody Karjadi, Phillip H Hwang, Huitong Ding, Sherral Devine, Ludy C Shih, Spencer Low, Honghuang Lin, Vijaya B Kolachalama, Lydia Bazzano, David J Libon, Rhoda Au

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Smartphone-based cognitive assessments have emerged as promising tools, bridging gaps in accessibility and reducing bias in Alzheimer disease and related dementia research. However, their congruence with traditional neuropsychological tests and usefulness in diverse cohorts remain underexplored.

METHODS AND RESULTS: A total of 406 FHS (Framingham Heart Study) and 59 BHS (Bogalusa Heart Study) participants with traditional neuropsychological tests and digital assessments using the Defense Automated Neurocognitive Assessment (DANA) smartphone protocol were included. Regression models investigated associations between DANA task digital measures and a neuropsychological global cognitive

CONCLUSIONS: Our findings demonstrate that smartphone-based cognitive assessments exhibit concurrent validity with a …

Very-Low-Density Lipoprotein Triglyceride And Free Fatty Acid Plasma Kinetics In Women With High Or Low Brown Adipose Tissue Volume And Overweight/Obesity, Maria Chondronikola, Jun Yoshino, Raja Ramaswamy, Joseph Daniel Giardina, Richard Laforest, Richard L Wahl, Bruce W Patterson, Bettina Mittendorfer, Samuel Klein

2020-Current year OA Pubs

Although a high amount of brown adipose tissue (BAT) is associated with low plasma triglyceride concentration, the mechanism responsible for this relationship in people is not clear. Here, we evaluate the interrelationships among BAT, very-low-density lipoprotein triglyceride (VLDL-TG), and free fatty acid (FFA) plasma kinetics during thermoneutrality in women with overweight/obesity who had a low (< 20 mL) or high (≥20 mL) volume of cold-activated BAT (assessed by using positron emission tomography in conjunction with 2-deoxy-2-[

Hormonal Basis Of Sex Differences In Anesthetic Sensitivity, Andrzej Z Wasilczuk, Cole Rinehart, Adeeti Aggarwal, Martha E Stone, George A Mashour, Michael S Avidan, Max B Kelz, Alex Proekt, Reccognition Study Group

2020-Current year OA Pubs

General anesthesia-a pharmacologically induced reversible state of unconsciousness-enables millions of life-saving procedures. Anesthetics induce unconsciousness in part by impinging upon sexually dimorphic and hormonally sensitive hypothalamic circuits regulating sleep and wakefulness. Thus, we hypothesized that anesthetic sensitivity should be sex-dependent and modulated by sex hormones. Using distinct behavioral measures, we show that at identical brain anesthetic concentrations, female mice are more resistant to volatile anesthetics than males. Anesthetic sensitivity is bidirectionally modulated by testosterone. Castration increases anesthetic resistance. Conversely, testosterone administration acutely increases anesthetic sensitivity. Conversion of testosterone to estradiol by aromatase is partially responsible for this effect. In contrast, …

The Respiratory Enzyme Complex Rnf Is Vital For Metabolic Adaptation And Virulence In Fusobacterium Nucleatum, Timmie A Britton, Chenggang Wu, Yi-Wei Chen, Dana Franklin, Yimin Chen, Martha I Camacho, Truc T Luong, Asis Das, Hung Ton-That

Faculty, Staff and Student Publications

The Gram-negative oral pathobiont Fusobacterium nucleatum can traverse to extra-oral sites such as placenta and colon, promoting adverse pregnancy outcomes and colorectal cancer, respectively. How this anaerobe sustains many metabolically changing environments enabling its virulence potential remains unclear. Informed by our genome-wide transposon mutagenesis, we report here that the highly conserved Rhodobacter nitrogen-fixation (Rnf) complex, encoded by the rnfCDGEAB gene cluster, is key to fusobacterial metabolic adaptation and virulence. Genetic disruption of the Rnf complex via non-polar, in-frame deletion of rnfC (ΔrnfC) abrogates polymicrobial interaction (or coaggregation) associated with adhesin RadD and biofilm formation. The defect in coaggregation …

Analysis Of Breast Cancer Mortality In The Us-1975 To 2019, Jennifer L Caswell-Jin, Liyang P Sun, Diego Munoz, Ying Lu, Yisheng Li, Hui Huang, John M Hampton, Juhee Song, Jinani Jayasekera, Clyde Schechter, Oguzhan Alagoz, Natasha K Stout, Amy Trentham-Dietz, Sandra J Lee, Xuelin Huang, Jeanne S Mandelblatt, Donald A Berry, Allison W Kurian, Sylvia K Plevritis

Faculty, Staff and Student Publications

IMPORTANCE: Breast cancer mortality in the US declined between 1975 and 2019. The association of changes in metastatic breast cancer treatment with improved breast cancer mortality is unclear.

OBJECTIVE: To simulate the relative associations of breast cancer screening, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer with improved breast cancer mortality.

DESIGN, SETTING, AND PARTICIPANTS: Using aggregated observational and clinical trial data on the dissemination and effects of screening and treatment, 4 Cancer Intervention and Surveillance Modeling Network (CISNET) models simulated US breast cancer mortality rates. Death due to breast cancer, overall and by …

Perioperative Toripalimab Plus Chemotherapy For Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial, Shun Lu, Wei Zhang, Lin Wu, Wenxiang Wang, Peng Zhang, Wentao Fang, Wenqun Xing, Qixun Chen, Lin Yang, Jiandong Mei, Lijie Tan, Xiaohong Sun, Shidong Xu, Xiaohua Hu, Guohua Yu, Dongliang Yu, Nong Yang, Yuping Chen, Jinlu Shan, Ligang Xing, Hui Tian, Xun Zhang, Ming Zhou, Haohui Fang, Guowu Wu, Yunpeng Liu, Minhua Ye, Lejie Cao, Jie Jiang, Xingya Li, Liangming Zhu, Danqing Li, Mingqiang Kang, Aihong Zhong, Keneng Chen, Nan Wu, Qian Sun, Haitao Ma, Kaican Cai, Changli Wang, Gen Lin, Kunshou Zhu, Yu Zhang, Xiaochun Zhang, Hong Hu, Wengang Zhang, Jun Chen, Zhixiong Yang, Xiaosheng Hang, Jian Hu, Yunchao Huang, Zhiye Zhang, Lumin Zhang, Liwei Zhang, Lunxu Liu, Dongmei Lin, Jie Zhang, Gang Chen, Yuan Li, Lei Zhu, Weihua Wang, Wenbo Yu, Dezhen Cao, Patricia Keegan, Sheng Yao

Faculty, Staff and Student Publications

IMPORTANCE: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown.

OBJECTIVE: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The …

Knowledge, Attitudes, And Subjective Norms Associated With Covid-19 Vaccination Among Pregnant Women In Kenya: An Online Cross-Sectional Pilot Study Using Whatsapp, Sylvia Ayieko, Walter Jaoko, Rose Okoyo Opiyo, Elkanah Omenge Orang'o, Sarah E Messiah, Kimberly Baker, Christine Markham

Faculty, Staff and Student Publications

COVID-19 vaccination during pregnancy has been recommended, but the perceptions related to uptake remain unexplored. This pilot study aimed to explore how perceptions influence COVID-19 vaccine uptake among a sample of 115 pregnant women in Kenya, recruited via WhatsApp. Data were collected using an adapted online questionnaire between May and October 2022. Logistic analyses assessed the relationship between COVID-19 vaccination uptake and the Theory of Reasoned Action (TRA) constructs: attitudes and subjective norms. COVID-19 vaccination coverage was 73%, with vaccine hesitancy estimated at 41.4% among the unvaccinated group. Most participants had completed college education and had good knowledge of COVID-19 …

Metabolomic Rewiring Promotes Endocrine Therapy Resistance In Breast Cancer, Songyeon Ahn, Jun Hyoung Park, Sandra L Grimm, Danthasinghe Waduge Badrajee Piyarathna, Tagari Samanta, Vasanta Putluri, Dereck Mezquita, Suzanne A W Fuqua, Nagireddy Putluri, Cristian Coarfa, Benny Abraham Kaipparettu

Faculty, Staff and Students Publications

Approximately one-third of endocrine-treated women with estrogen receptor-alpha positive (ER+) breast cancers (BC) are at risk of recurrence due to intrinsic or acquired resistance. Thus, it is vital to understand the mechanisms underlying endocrine therapy resistance in ER+ BC to improve patient treatment. Mitochondrial fatty acid β-oxidation (FAO) has been shown to be a major metabolic pathway in triple-negative BC (TNBC) that can activate Src signaling. Here, we found metabolic reprogramming that increases FAO in ER+ BC as a mechanism of resistance to endocrine therapy. A metabolically relevant, integrated gene signature was derived from transcriptomic, metabolomic, and lipidomic analyses in …

Impact Of Transcatheter Heart Valve Type On Outcomes Of Surgical Explantation After Failed Transcatheter Aortic Valve Replacement: The Explant-Tavr International Registry, Syed Zaid, Neal S Kleiman, Sachin S Goel, Molly I Szerlip, Michael J Mack, Mateo Marin-Cuartas, Siamak Mohammadi, Tamim M Nazif, Axel Unbehaun, Martin Andreas, Derek R Brinster, Newell B Robinson, Lin Wang, Basel Ramlawi, Lenard Conradi, Nimesh D Desai, John K Forrest, Rodrigo Bagur, Tom C Nguyen, Ron Waksman, Lionel Leroux, Eric Van Belle, Kendra J Grubb, Hasan A Ahmad, Paolo Denti, Thomas Modine, Vinayak N Bapat, Tsuyoshi Kaneko, Michael J Reardon, Gilbert H L Tang, On Behalf Of The Explant-Tavr Registry Investigators

Faculty, Staff and Students Publications

Background: There are limited data on the impact of transcatheter heart valve (THV) type on the outcomes of surgical explantation after THV failure.

Aims: We sought to determine the outcomes of transcatheter aortic valve replacement (TAVR) explantation for failed balloon-expandable valves (BEV) versus self-expanding valves (SEV).

Methods: From November 2009 to February 2022, 401 patients across 42 centres in the EXPLANT-TAVR registry underwent TAVR explantation during a separate admission from the initial TAVR. Mechanically expandable valves (N=10, 2.5%) were excluded. The outcomes of TAVR explantation were compared for 202 (51.7%) failed BEV and 189 (48.3%) failed SEV.

Results: Among 391 …

Comparative Transcriptomic Analysis Of Cerebellar Astrocytes Across Developmental Stages And Brain Regions, Wookbong Kwon, Dong-Joo Choi, Kwanha Yu, Michael R Williamson, Sanjana Murali, Yeunjung Ko, Junsung Woo, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes are the most abundant glial cell type in the central nervous system, and they play a crucial role in normal brain function. While gliogenesis and glial differentiation occur during perinatal cerebellar development, the processes that occur during early postnatal development remain obscure. In this study, we conducted transcriptomic profiling of postnatal cerebellar astrocytes at postnatal days 1, 7, 14, and 28 (P1, P7, P14, and P28), identifying temporal-specific gene signatures at each specific time point. Comparing these profiles with region-specific astrocyte differentially expressed genes (DEGs) published for the cortex, hippocampus, and olfactory bulb revealed cerebellar-specific gene signature across these …

Fecal Pharmacokinetics And Gut Microbiome Effects Of Oral Omadacycline Versus Vancomycin In Healthy Volunteers, Jinhee Jo, Chenlin Hu, Khurshida Begum, Weiqun Wang, Thanh M Le, Samantha Agyapong, Blake M Hanson, Hossaena Ayele, Chris Lancaster, M Jahangir Alam, Anne J Gonzales-Luna, Kevin W Garey

Faculty, Staff and Student Publications

BACKGROUND: Clostridioides difficile infection (CDI) is a common healthcare-associated infection with limited treatment options. Omadacycline, an aminomethylcycline tetracycline, has potent in vitro activity against C difficile and a low propensity to cause CDI in clinical trials. We aimed to assess fecal pharmacokinetics and gut microbiome effects of oral omadacycline compared to oral vancomycin in healthy adults.

METHODS: This was a phase 1, nonblinded, randomized clinical trial conducted in healthy volunteers aged 18-40 years. Subjects received a 10-day course of omadacycline or vancomycin. Stool samples were collected at baseline, daily during therapy, and at follow-up visits. Omadacycline and vancomycin stool concentrations …

Chagas Disease Diagnostic Practices At Four Major Hospital Systems In California And Texas, Emily A Kelly, Jose I Echeverri Alegre, Katherine Promer, Jesica Hayon, Roumen Iordanov, Khuzaima Rangwalla, Jerry J Zhang, Zian Fang, Cindy Huang, Cassiana E Bittencourt, Sharon Reed, Rosa M Andrade, Caryn Bern, Eva H Clark, Jeffrey D Whitman

Faculty, Staff and Students Publications

BACKGROUND: Chagas disease (CD) is a parasitic disease that affects ∼300 000 people living in the United States. CD leads to cardiac and/or gastrointestinal disease in up to 30% of untreated people. However, end-organ damage can be prevented with early diagnosis and antiparasitic therapy.

METHODS: We reviewed electronic health records of patients who underwent testing for CD at four hospital systems in California and Texas between 2016 and 2020. Descriptive analyses were performed as a needs assessment for improving CD diagnosis.

RESULTS: In total, 470 patients were tested for CD. Cardiac indications made up more than half (60%) of all …

Aging Fly Cell Atlas Identifies Exhaustive Aging Features At Cellular Resolution, Kenneth A Wilson, Sudipta Bar, Eric B Dammer, Enrique M Carrera, Brian A Hodge, Tyler A U Hilsabeck, Joanna Bons, George W Brownridge, Jennifer N Beck, Jacob Rose, Melia Granath-Panelo, Christopher S Nelson, Grace Qi, Akos A Gerencser, Jianfeng Lan, Alexandra Afenjar, Geetanjali Chawla, Rachel B Brem, Philippe M Campeau, Hugo J Bellen, Birgit Schilling, Nicholas T Seyfried, Lisa M Ellerby, Pankaj Kapahi

Faculty, Staff and Students Publications

Dietary restriction (DR) delays aging, but the mechanism remains unclear. We identified polymorphisms in mtd, the fly homolog of OXR1, which influenced lifespan and mtd expression in response to DR. Knockdown in adulthood inhibited DR-mediated lifespan extension in female flies. We found that mtd/OXR1 expression declines with age and it interacts with the retromer, which regulates trafficking of proteins and lipids. Loss of mtd/OXR1 destabilized the retromer, causing improper protein trafficking and endolysosomal defects. Overexpression of retromer genes or pharmacological restabilization with R55 rescued lifespan and neurodegeneration in mtd-deficient flies and endolysosomal defects in fibroblasts from patients with lethal loss-of-function …

Regional Variability In The Prevalence Of Food Insecurity And Diet Quality Among United States Children, Jayna M Dave, Tzuan A Chen, Alexandra N Castro, Mamie White, Elizabeth A Onugha, Sloane Zimmerman, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Understanding the association between food security status (FSS) and diet quality in children is crucial. This study investigated regional variability in FSS, participation in the federal nutrition assistance program (FNAP), and diet quality among US children. National Health and Nutrition Examination Survey (NHANES) data from 2013 to 2016 were analyzed. The association between FSS, FNAP participation, and diet quality (Healthy Eating Index—HEI-2015) was assessed using multiple linear/logistic regression models. The sample included 6403 children (mean age: 7.5 years; 51% male; 33% Hispanic). Within the sample, 13% reported child food insecurity, and 30% reported household food insecurity. Additionally, 90% participated in …

Delineating The Mechanism Of Fragility At Bcl6 Breakpoint Region Associated With Translocations In Diffuse Large B Cell Lymphoma, Vidya Gopalakrishnan, Urbi Roy, Shikha Srivastava, Khyati M Kariya, Shivangi Sharma, Saniya M Javedakar, Bibha Choudhary, Sathees C Raghavan

Faculty, Staff and Student Publications

BCL6 translocation is one of the most common chromosomal translocations in cancer and results in its enhanced expression in germinal center B cells. It involves the fusion of BCL6 with any of its twenty-six Ig and non-Ig translocation partners associated with diffuse large B cell lymphoma (DLBCL). Despite being discovered long back, the mechanism of BCL6 fragility is largely unknown. Analysis of the translocation breakpoints in 5' UTR of BCL6 reveals the clustering of most of the breakpoints around a region termed Cluster II. In silico analysis of the breakpoint cluster sequence identified sequence motifs that could potentially fold into …

Molecular And Clinical Effects Of Aromatase Inhibitor Therapy On Skeletal Muscle Function In Early-Stage Breast Cancer, Tara A Seibert, Lei Shi, Sandra Althouse, Richard Hoffman, Bryan P Schneider, Kristen A Russ, Cody A Altherr, Stuart J Warden, Theresa A Guise, Andrew R Coggan, Tarah J Ballinger

Faculty, Staff and Student Publications

We evaluated biochemical changes in skeletal muscle of women with breast cancer initiating aromatase inhibitors (AI), including oxidation of ryanodine receptor RyR1 and loss of stabilizing protein calstabin1, and detailed measures of muscle function. Fifteen postmenopausal women with stage I-III breast cancer planning to initiate AI enrolled. Quadriceps muscle biopsy, dual-energy x-ray absorptiometry, isokinetic dynamometry, Short Physical Performance Battery, grip strength, 6-min walk, patient-reported outcomes, and serologic measures of bone turnover were assessed before and after 6 months of AI. Post-AI exposure, oxidation of RyR1 significantly increased (0.23 ± 0.37 vs. 0.88 ± 0.80, p <  0.001) and RyR1-bound calstabin1 significantly decreased (1.69 ± 1.53 vs. 0.74 ± 0.85, p <  0.001), consistent with dysfunctional calcium channels in skeletal muscle. Grip strength significantly decreased at 6 months. No significant differences were seen in isokinetic dynamometry measures of muscle contractility, fatigue resistance, or muscle recovery post-AI exposure. However, there was significant correlation between oxidation of RyR1 with muscle power (r = 0.60, p = 0.02) and muscle fatigue (r = 0.57, p = 0.03). Estrogen deprivation therapy for breast cancer resulted in maladaptive changes in skeletal muscle, consistent with the biochemical signature of dysfunctional RyR1 calcium channels. Future studies will evaluate longer trajectories of muscle function change and include other high bone turnover states, such as bone metastases.

The Million Veteran Program 1990-1991 Gulf War Era Survey: An Evaluation Of Veteran Response, Characteristics, And Representativeness Of The Gulf War Era Veteran Population, Kelly M Harrington, Rachel Quaden, Lea Steele, Drew A Helmer, Elizabeth R Hauser, Sarah T Ahmed, Mihaela Aslan, Krishnan Radhakrishnan, Jacqueline Honerlaw, Xuan-Mai T Nguyen, Sumitra Muralidhar, John Concato, Kelly Cho, J Michael Gaziano, Stacey B Whitbourne, On Behalf Of The Va Million Veteran Program

Center for Medical Ethics and Health Policy Staff Publications

To address gaps in understanding the pathophysiology of Gulf War Illness (GWI), the VA Million Veteran Program (MVP) developed and implemented a survey to MVP enrollees who served in the U.S. military during the 1990–1991 Persian Gulf War (GW). Eligible Veterans were invited via mail to complete a survey assessing health conditions as well as GW-specific deployment characteristics and exposures. We evaluated the representativeness of this GW-era cohort relative to the broader population by comparing demographic, military, and health characteristics between respondents and non-respondents, as well as with all GW-era Veterans who have used Veterans Health Administration (VHA) services and …

D-Mannose Reduces Cellular Senescence And Nlrp3/Gasdermind/Il-1Β-Driven Pyroptotic Uroepithelial Cell Shedding In The Murine Bladder, Chetanchandra S Joshi, Arnold M Salazar, Caihong Wang, Marianne M Ligon, Rayvanth R Chappidi, Bisiayo E Fashemi, Paul A Felder, Amy Mora, Sandra L Grimm, Cristian Coarfa, Indira U Mysorekar

Faculty, Staff and Students Publications

Aging is a risk factor for disease via increased susceptibility to infection, decreased ability to maintain homeostasis, inefficiency in combating stress, and decreased regenerative capacity. Multiple diseases, including urinary tract infection (UTI), are more prevalent with age; however, the mechanisms underlying the impact of aging on the urinary tract mucosa and the correlation between aging and disease remain poorly understood. Here, we show that, relative to young (8-12 weeks) mice, the urothelium of aged (18-24 months) female mice accumulates large lysosomes with reduced acid phosphatase activity and decreased overall autophagic flux in the aged urothelium, indicative of compromised cellular homeostasis. …