Medicine and Health Sciences Commons^™

Rev-Erbα Regulates Brain Nad+ Levels And Tauopathy Via An Nfil3-Cd38 Axis, Jiyeon Lee, Ryeonghwa Kang, Sohui Park, Ibrahim O Saliu, Minsoo Son, Jaymie R Voorhees, Julie M Dimitry, Elsa I Quillin, Brian V Lananna, Young-Ah Goo, Guoyan Zhao, Erik S Musiek, Et Al.

2020-Current year OA Pubs

Nicotinamide adenine dinucleotide (NAD

Ibrutinib Added To Standard Conditioning And As Maintenance Therapy Following Autologous Hematopoietic Stem Cell Transplantation For Relapsed Or Refractory Activated-B-Cell Type Diffuse Large B-Cell Lymphoma: Primary Analysis Of The Us Intergroup Double-Blind Randomized Phase Iii Study Alliance A051301/Bmt-Ctn 1201, Charalambos Andreadis, Brad S Kahl, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

To improve outcomes in relapsed or refractory activated B-cell type Diffuse Large B-cell Lymphoma (ABC-DLBCL), we launched a randomized phase 3 trial evaluating 2-year progression free survival (2yPFS) with the addition of ibrutinib to autologous transplant. Patients received ibrutinib 560 mg or placebo with conditioning and for 12 additional cycles. Accrual was adversely affected by implementation of the ABC classifier in this setting and the changing treatment landscape of DLBCL. In all, 39 patients on ibrutinib and 38 on placebo were evaluable. 2yPFS was 57.6% on ibrutinib versus 40.8% on placebo (

A Modification To The Brand Transfer For Claw Hand: The Four-Tailed Extensor Carpi Radialis Brevis To Lateral Band Transfer, Lauren E Wessel, Nirbhay S Jain, Ambika E Paulson, Carrie Bettlach, Mitchell A Pet, Amy M Moore

2020-Current year OA Pubs

BACKGROUND: Claw deformity is a devastating consequence of low ulnar nerve palsy, resulting in loss of finger function. Traditionally, the Brand transfer is a favored intervention but requires lengthy grafts and bulky tenorrhaphies, risking adhesions in the lumbrical canal. We present a modified Brand tendon transfer, which extends the extensor carpi radialis brevis (ECRB) into 4 tails for individual grafting into the lateral band, decreasing adhesion risk and graft length need.

METHODS: Nine consecutive patients with claw hand were examined in detail to confirm the diagnosis and appropriateness for claw-correction surgery by the senior author. All patients underwent our modified …

Distinct Roles For B Cell-Derived Ltα3 And Ltα1Β2 In Tnf-Mediated Ileitis, Emma C Erlich, Quazim A Alayo, Ayoung Kim, Jichang Han, Rachel L Mintz, Christopher G Huckstep, Heather S Ruiz, Rachael L Field, Taylor J Dunning, Leila S Saleh, Mark H Hoofnagle, Farshid Guilak, Jonathan R Brestoff, Rafael S Czepielewski, Gwendalyn J Randolph, Et Al.

2020-Current year OA Pubs

Crohn's disease pathology is modeled in TNF

Brugia Malayi And Other Filarial Parasite Species In Animals In Areas Endemic For Lymphatic Filariasis In Belitung District, Indonesia, Irina Diekmann, Taniawati Supali, Kerstin Fischer, Elisa Iskandar, Noviani Sugianto, Yossi Destani, Rahmat Alfian, Gary J. Weil, Peter U. Fischer

2020-Current year OA Pubs

BACKGROUND: Brugia malayi is the most common cause of lymphatic filariasis (LF) in Indonesia. A zoophilic ecotype that infects both humans and animals occur in Belitung District in Indonesia. The district received five annual rounds of mass drug administration (MDA) between 2006 and 2010 and passed three transmission assessment surveys (TAS) in subsequent years. However, a survey in five villages in 2021 showed a microfilaria (Mf) prevalence of 2.1% in humans. The reappearance of B. malayi infection in humans may be due to reintroduction from animal reservoirs. The goal of this study was to determine B. malayi prevalence in potential …

Predicting Acute Postsurgical Pain In The Postanesthesia Care Unit: Risk Tool Development And Internal Validation, Nicholas Papadomanolakis-Pakis, Simon Haroutounian, Johan K. Sørensen, Charlotte Runge, Lone D. Brix, Christian F Christiansen, Lone Nikolajsen

2020-Current year OA Pubs

INTRODUCTION: Moderate-to-severe acute postsurgical pain (APSP) is experienced by approximately 30% of surgical patients.

OBJECTIVES: To improve early APSP management, we developed 2 pragmatic and generalizable point-of-care risk tools to preoperatively predict moderate-to-severe and severe APSP in the postanaesthesia care unit (PACU).

METHODS: This was a multicenter prospective cohort study of adult patients undergoing elective surgical procedures between May 2021 and May 2023. Candidate predictors were preidentified. Logistic regression was used to develop the models. Internal validation was conducted with bootstrap resampling. Model performance was assessed by discrimination and calibration. Decision curve analysis was conducted to evaluate clinical utility of …

Chimeric Antigen Receptor Natural Killer (Car-Nk) Cells: From Preclinical Promise To Clinical Reality In Cancer Immunotherapy, Hunter Cassidy Cochran, Kevin Ashkan Ghobadi, Armin Ghobadi

2020-Current year OA Pubs

Chimeric antigen receptor (CAR) natural killer (NK) cell therapy represents an emerging frontier in cancer immunotherapy. CAR-NK cells offer the potential for "off-the-shelf" treatments with a favorable safety profile, due in part to their innate capacity for HLA-unrestricted tumor targeting and an absence of graft-versus-host disease. Landmark clinical studies using cord blood - derived CAR-NK cells and another employing iPSC-derived CAR-NK cells have reported impressive response rates, durable remissions, and minimal toxicity. Furthermore, a growing landscape of ongoing clinical trials is exploring innovative strategies to enhance persistence, overcome solid tumor challenges, and prevent antigen escape. These advances collectively underscore the …

Irf6 Regulates Adherens Junction Proteins And Inflammatory Cytokines In Salivary Acinar Cells And Its Expression Is Elevated In Sjӧgren’S Syndrome, Vi Pham, Antonio Hernandes Chaves Neto, Julia Zheng, Mary Elmeniawi, Krishna Kumar Kookal, Muhammad F Walji, Mary C Farach-Carson, Walid D Fakhouri

Faculty, Staff and Student Publications

Objective: To investigate the mechanism of Interferon Regulatory Factor 6 (IRF6) function in regulating adherens junction proteins and inflammatory cytokines in human salivary acinar cells and Sjögren's syndrome biopsies.

Design: We used mouse model, salivary cell lines, and human salivary gland (SG) biopsies to investigate IRF6 function in SG cellular integrity and immunomodulation.

Results: In Irf6-null mice, we observed myoepithelial cell detachment from acinar cells of major SGs, and the acini were remarkably disorganized compared to wild-type littermates. At the molecular level, the acinar differentiation markers E-cadherin and MIST1 were markedly reduced in Irf6-null embryonic SG, while the proinflammatory cytokines, …

Stratifying Lung Adenocarcinoma Risk With Multi-Ancestry Polygenic Risk Scores In East Asian Never-Smokers, Batel Blechter, Xiaoyu Wang, Juncheng Dai, Christiana Karsonaki, Jianxin Shi, Kouya Shiraishi, Jiyeon Choi, Keitaro Matsuo, Tzu-Yu Chen, Rayjean J Hung, Kexin Chen, Xiao-Ou Shu, Young Tae Kim, Parichoy Pal Choudhury, Jacob Williams, Maria Teresa Landi, Dongxin Lin, Wei Zheng, Zhihua Yin, Baosen Zhou, Jiucun Wang, Wei Jie Seow, Lei Song, I-Shou Chang, Wei Hu, Li-Hsin Chien, Qiuyin Cai, Yun-Chul Hong, Hee Nam Kim, Yi-Long Wu, Maria Pik Wong, Brian Douglas Richardson, Shilan Li, Tongwu Zhang, Charles Breeze, Zhaoming Wang, Bryan A Bassig, Jin Hee Kim, Demetrius Albanes, Jason Yy Wong Sm, Min-Ho Shin, Lap Ping Chung, Yang Yang, Hong Zheng, Hongji Dai, Yasushi Yatabe, Xu-Chao Zhang, Young-Chul Kim, Neil E Caporaso, Jiang Chang, James Chung Man Ho, Yataro Daigo, Yukihide Momozawa, Yoichiro Kamatani, Masashi Kobayashi, Kenichi Okubo, Takayuki Honda, H Dean Hosgood, Hideo Kunitoh, Shun-Ichi Watanabe, Yohei Miyagi, Shingo Matsumoto, Hidehito Horinouchi, Masahiro Tsuboi, Ryuji Hamamoto, Koichi Goto, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Megumi Hara, Yuichiro Nishida, Kenji Takeuchi, Kenji Wakai, Koichi Matsuda, Yoshinori Murakami, Kimihiro Shimizu, Hiroyuki Suzuki, Motonobu Saito, Yoichi Ohtaki, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Mitchell J Machiela, Yeul Hong Kim, In-Jae Oh, Victor Ho Fun Lee, Gee-Chen Chang, Kuan-Yu Chen, Wu-Chou Su, Yuh-Min Chen, Adeline Seow, Jae Yong Park, Sun-Seog Kweon, Yu-Tang Gao, Jianjun Liu, Ann G Schwartz, Richard Houlston, Ivan P Gorlov, Xifeng Wu, Ping Yang, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, Bu-Tian Ji, H-Erich Wichmann, David C Christiani, Gad Rennert, Susanne M Arnold, Paul Brennan, James Mckay, John K Field, Michael P A Davies, Sanjay S Shete, Loïc Le Marchand, Geoffrey Liu, Angeline S Andrew, Lambertus A Kiemeney, Shan Zienolddiny-Narui, Kjell Grankvist, Angela Cox, Fiona Taylor, Jian-Min Yuan, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Hyo-Sung Jeon, Shih Sheng Jiang, Chung-Hsing Chen, Chin-Fu Hsiao, Zhibin Hu, Laura Burdett, Meredith Yeager, Amy Hutchinson, Belynda Hicks, Jia Liu, Sonja I Berndt, Wei Wu, Junwen Wang, Yuqing Li, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Chang Hyun Kang, Wen-Chang Wang, Jun Xu, Peng Guan, Wen Tan, Chong-Jen Yu, Gong Yang, Alan Dart Loon Sihoe, Yi Young Choi, In Kyu Park, Hsiao-Han Hung, Roel C H Vermeulen, Iona Cheng, Junjie Wu, Fang-Yu Tsai, John K C Chan, Jihua Li, Hsien-Chih Lin, Jie Liu, Bao Song, Norie Sawada, Taiki Yamaji, Kathleen Wyatt, Hongxia Ma, Meng Zhu, Yifan Wang, Tianchen Qi, Xuelian Li, Yangwu Ren, Ann Chao, Motoki Iwasaki, Junjie Zhu, Guoping Wu, Chih-Yi Chen, Chien-Jen Chen Scd, Pan-Chyr Yang, Victoria L Stevens, Joseph F Fraumeni, Kuang Lin, Robin G Walters, Zhengming Chen, Nilanjan Chatterjee, Olga Y Gorlova, Christopher I Amos, Hongbing Shen, Chao Agnes Hsiung, Stephen J Chanock, Nathaniel Rothman, Takashi Kohno, Qing Lan, Haoyu Zhang

Faculty, Staff and Students Publications

Background: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction.

Methods: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the …

Gender Trends In Professional Advancement Among Academic Pediatric Neurologists, Juliet K Knowles, Renée A Shellhaas, Et Al.

2020-Current year OA Pubs

No abstract provided.

Mapping The Geographic Distribution Of Dimorphic Mycoses Using A Us Commercial Insurance Database, Reid Goodman, Adriana M Rauseo, Samuel L Windham, Julio C Zuniga-Moya, William G Powderly, Andrej Spec, Patrick B Mazi

2020-Current year OA Pubs

BACKGROUND: The dimorphic mycoses (DMs) histoplasmosis, blastomycosis, and coccidioidomycosis are classically thought to be geographically restricted to specific regions of the United States. The current scientific consensus is that these geographic boundaries are expanding, but the extent of this expansion remains uncertain.

METHODS: This study is a retrospective analysis of >21 million (annually) commercially insured individuals within the United States during 2007-2016. Diagnosis of histoplasmosis, coccidioidomycosis, and blastomycosis were identified using

RESULTS: There were 37 513 histoplasmosis, 14 987 coccidioidomycosis, and 2207 blastomycosis diagnoses during 2007-2016 within 387 Metropolitan Statistical Areas. DMs were consistently diagnosed outside their historical hyperendemic regions. …

Exposure To Household Air Pollution From Biomass Cooking And Severe Pneumonia In Infants, John P Mccracken, Lindsay J Underhill, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Household air pollution from biomass cooking is considered an important risk factor for child pneumonia.

OBJECTIVE: To evaluate the longitudinal association between exposure to particulate matter with a diameter of less than or equal to 2.5 µm (PM2.5) or carbon monoxide (CO) and severe pneumonia in infants.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included infants (aged ≤12 months) whose mothers participated in a 4-country randomized clinical trial. Conducted from May 2018 to September 2021, the trial tested whether an 18-month liquefied petroleum gas stove and fuel distribution intervention reduced the incidence of severe pneumonia in offspring during infancy …

The Triglyceride-Glucose Index And Risk Of End-Stage Renal Disease Across Different Durations Of Type 2 Diabetes Mellitus: A Longitudinal Cohort Study, Mi-Sook Kim, Kyu-Na Lee, Jeongmin Lee, Jeongeun Kwak, Seung-Hwan Lee, Hyuk-Sang Kwon, Jing Hughes, Kyung-Do Han, Eun Young Lee

2020-Current year OA Pubs

BACKGRUOUND: This study investigated the association between the triglyceride-glucose (TyG) index, a marker of insulin resistance, and the risk of end-stage renal disease (ESRD) in individuals with type 2 diabetes mellitus (T2DM), focusing on variations by diabetes duration.

METHODS: We analyzed 1,219,148 Korean adults with T2DM from National Health Insurance Service data who underwent biennial health evaluations (2015 to 2016). ESRD was defined using specific procedural codes (V codes), and Cox proportional hazard models were employed to estimate hazard ratios (HRs) for ESRD across TyG index quartiles and diabetes duration categories, adjusting for various confounders.

RESULTS: Over 6,967,381 person-years of …

Targeting Rna With Small Molecules Using State-Of-The-Art Methods Provides Highly Predictive Affinities Of Riboswitch Inhibitors, Narjes Ansari, Chengwen Liu, Florent Hédin, Jérôme Hénin, Jay W Ponder, Pengyu Ren, Jean-Philip Piquemal, Louis Lagardère, Krystel El Hage

2020-Current year OA Pubs

Targeting RNA with small molecules represents a promising yet relatively unexplored avenue for the design of new drugs. Nevertheless, challenges arise from the lack of computational models and techniques able to accurately model RNA systems, and predict their binding affinities to small molecules. Here, we tackle these difficulties by developing a tailored state-of-the-art approach for absolute binding free energy calculations of RNA-binding small molecules. For this, we combine the advanced AMOEBA polarizable force field to the newly developed lambda-Adaptive Biasing Force scheme associated to refined restraints allowing for efficient sampling. To capture the free energy barrier associated to challenging RNA …

Hemodynamic Characteristics Of Dilated Ascending Aorta In Patients With Bicuspid Aortic Valve, Yu Xia, Xuehuan Zhang, Shuai Zhu, Suwei Chen, Wentao Dong, Zhuo Chen, Nan Zhang, Jiafu Ou, Junming Zhu, Duanduan Chen, Tie Zheng

2020-Current year OA Pubs

BACKGROUND: The aim of this study is to investigate the influence of aortic diameter on hemodynamic environment characteristics in patient with the bicuspid aortic valve (BAV) and dilated ascending aorta (AAo).

METHOD: In this study, an MRI of one BAV patient with 4.5 cm AAo was collected and numerical model was constructed. Based on the images, three additional anatomical models were constructed with different AAo sizes of 4.0 cm, 5.0 cm and 5.5 cm respectively, while the size and the geometry of other parts were fixed. Then hemodynamics in these four models was simulated numerically and the flow patterns and …

Using Implementation Mapping To Optimize The Impact Of Universal School Meals: A Type Iii Hybrid Implementation-Effectiveness Study Protocol, Gabriella M Mcloughlin, Angel Smith, Alex R Dopp, Resa Jones, Omar Martinez, Shiriki Kumanyika, Recai Yucel, Ross C Brownson, Jennifer Orlet Fisher

2020-Current year OA Pubs

BACKGROUND: Provision of government subsidized school meals at no charge to all students in income-eligible schools (Universal School Meals) is a critical policy approach to address food insecurity and risk for obesity in school-aged children. However, despite documented benefits, implementation challenges remain, which limit the uptake and associated impact of this provision. To ensure the longevity of this policy approach, equity-focused solutions that center the needs of those tasked with implementation and the most vulnerable Universal School Meals recipients are necessary. The aims of this study are to develop equity-focused implementation strategies and test them through a hybrid type III …

Do Complex Psychometric Analyses Really Matter? Comparing Multiple Approaches Using Individual Participant Data From Antidepressant Trials, David Byrne, Frank Doyle, Susan Brannick, Robert M Carney, Pim Cuijpers, Alexandra L Dima, Kenneth E Freedland, Suzanne Guerin, David Hevey, Bishember Kathuria, Emma Wallace, Fiona Boland

2020-Current year OA Pubs

BACKGROUND: Psychometric methods are used to remove underperforming items and reduce error in existing measures, albeit different approaches can produce different results. This study aimed to determine the implications of applying different psychometric methods for clinical trial outcomes.

METHODS: Individual participant data from 15 antidepressant treatment trials from Vivli.org were analyzed. Baseline (pretreatment) and 8-week (range 4-12 weeks) outcome data from the Montgomery-Asberg Depression Rating Scale were subjected to best-practice factor analysis (FA), item response theory (IRT), and network analysis (NA) approaches. Trial outcomes for the original summative scores and psychometric-model scores were assessed using multilevel models. Percentage differences in …

Leveraging De-Implementation Science To Promote Infection Prevention And Stewardship: A Roadmap And Practical Examples (Part Ii Of Ii), Westyn Branch-Elliman, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

De-implementation of established practices is a common challenge in infection prevention and antimicrobial stewardship and a necessary part of the life cycle of healthcare quality improvement programs. Promoting de-implementation of ineffective antimicrobial use and increasingly of low-value diagnostic testing are cornerstones of stewardship practice. Principles of de-implementation science and the interplay of implementation and de-implementation are discussed in part I of this Society for Healthcare Epidemiology of America White Paper Series.In this second part of the series, we discuss a process for applying principles of de-implementation science in infection prevention and stewardship and then review some real-world examples and case …

Molecular Dynamics Of The Host Response To Streptococcus Pneumoniae Pneumonia In Baboons, Bryan D Kraft, Et Al.

2020-Current year OA Pubs

BACKGROUND: Bacterial pneumonia remains a leading cause of morbidity and mortality worldwide despite the widespread availability of antibiotics. Novel pneumonia therapies and biomarkers are urgently needed to improve outcomes and advance personalized therapy. Using an established baboon model of S. pneumoniae pneumonia, we sought to characterize the temporal dynamics of pneumonia host responses to identify novel potential diagnostic and therapeutic molecular targets.

METHODS: We performed whole blood transcriptomics, unbiased proteomics, and peripheral cytokine measurements serially in baboons inoculated with S. pneumoniae (n = 23) or saline (n = 10) and modeled the peripheral blood host response using principal components analysis …

Microglia Regulate Gabaergic Neurogenesis In Prenatal Human Brain Through Igf1, Diankun Yu, Samhita Jain, Andi Wangzhou, Beika Zhu, Wenyuan Shao, Elena J Coley-O'Rourke, Stacy De Florencio, Jaeyeon Kim, Jennifer Ja-Yoon Choi, Mercedes F Paredes, Tomasz J Nowakowski, Eric J Huang, Xianhua Piao

2020-Current year OA Pubs

GABAergic neurons are essential cellular components of neural circuits. Their abundance and diversity have increased significantly in the human brain, contributing to the expanded cognitive capacity of humans

Spatial Multiomics Of Acute Myocardial Infarction Reveals Immune Cell Infiltration Through The Endocardium, Florian Wünnemann, Junedh M Amrute, Kory J Lavine, Et Al.

2020-Current year OA Pubs

Myocardial infarction (MI) continues to be a leading cause of death worldwide. Even though it is well established that the complex interplay between different cell types determines the overall healing response after MI, the precise changes in the tissue architecture are still poorly understood. In this study, we generated an integrative cellular map of the acute phase after murine MI using a combination of imaging-based transcriptomics (Molecular Cartography) and antibody-based highly multiplexed imaging (Sequential Immunofluorescence). This enabled us to evaluate cell type compositions and changes at subcellular resolution over time. We observed the recruitment of leukocytes to the infarcted heart …

Eliminating The Ai Digital Divide By Building Local Capacity, Freya Gulamali, Thomas M. Maddox, Philip Payne, Et Al.

2020-Current year OA Pubs

Over the past few years, health delivery organizations (HDOs) have been adopting and integrating AI tools, including clinical tools for tasks like predicting risk of inpatient mortality and operational tools for clinical documentation, scheduling and revenue cycle management, to fulfill the quintuple aim. The expertise and resources to do so is often concentrated in academic medical centers, leaving patients and providers in lower-resource settings unable to fully realize the benefits of AI tools. There is a growing divide in HDO ability to conduct AI product lifecycle management, due to a gap in resources and capabilities (e.g., technical expertise, funding, data …

Identification Of Surrogate Outcome Biomarkers In Lung Allograft Recipients With Bronchiolitis Obliterans: Implications For Randomized Controlled Trials, Derek E. Byers, Suresh Vedantham, Mary Clare Derfler, Paul Commean, Andrew Atkinson, Jeff Atkinson, Alexey Prokudin, John Mccarthy, George Despotis, Et Al.

2020-Current year OA Pubs

BACKGROUND: We developed a prospective, multicenter "registry" to evaluate the effect of extracorporeal photopheresis for lung transplant recipients who develop chronic lung allograft dysfunction (CLAD) with the bronchiolitis obliterans syndrome (BOS) phenotype (CLAD/BOS) and who are refractory to conventional standard-of-care therapy.

METHODS: Data from 258 lung transplant recipients enrolled in the Registry between April 2015 and April 2022 were included in this analysis. All recorded parameters (eg, demographics), including forced expiratory volume in 1 s (FEV

RESULTS: Mortality at 6 and 12 mo after CLAD/BOS diagnosis was 5% and 14%, whereas mortality at 6 and 12 mo after enrollment was …

Peroxisomal Metabolism Of Branched Fatty Acids Regulates Energy Homeostasis, Xuejing Liu, Anyuan He, Dongliang Lu, Donghua Hu, Min Tan, Parniyan Goodarzi, Bilal Ahmad, Brian Kleiboeker, Brian N Finck, Mohamed Zayed, Jonathan R Brestoff, Ali Javaheri, Fong-Fu Hsu, Clay F Semenkovich, Irfan J Lodhi, Et Al.

2020-Current year OA Pubs

Brown and beige adipocytes express uncoupling protein 1 (UCP1), a mitochondrial protein that dissociates respiration from ATP synthesis and promotes heat production and energy expenditure. However, UCP1

Recent Advances In The Identification And Quantification Of Xylazine And Medetomidine In Biological Specimens, Bridgit O Crews

2020-Current year OA Pubs

Xylazine is a veterinary sedative that is frequently detected in the illicit drug supply, often found mixed with illicitly manufactured fentanyl (IMF). It has been detected in the blood of overdose victims and patients who use illicit drugs. Xylazine is not approved for use in humans. It is an alpha-2-adrenergic receptor agonist that causes deep sedation that is non-responsive to naloxone, the antidote for opioid overdose. Chronic exposure to xylazine has been linked to severe wounds that can progress to amputation. Medetomidine is another related veterinary sedative that has more recently emerged as an adulterant in IMF. Medetomidine is also …

Upper And Lower Airway Microbiota Across Infancy And Childhood, Ariel J Hernandez-Leyva, Anne L Rosen, Christopher P Tomera, Elaina E Lin, Elikplim H Akaho, Allison M Blatz, William R Otto, Joey Logan, Lisa R Young, Rebecca M Harris, Samantha A Whiteside, Andrew L Kau, Audrey R Odom John

2020-Current year OA Pubs

BACKGROUND: The upper and lower respiratory tracts feature distinct environments and responses affecting microbial colonization but investigating the relationship between them is technically challenging. We aimed to identify relationships between taxa colonizing the nasopharynx and trachea across childhood.

METHODS: We employed V4 16S rRNA gene sequencing to profile nasopharyngeal swabs and tracheal aspirates collected from 172 subjects between 20 weeks and 18 years of age. These samples were collected prior to elective procedures over the course of 20 weeks in 2020 from subjects enrolled in a cross-sectional study. After extraction, sequencing, and quality control, we studied the remaining 147 of …

Family Income And Polygenic Scores Are Independently But Not Interactively Associated With Cognitive Performance Among Youth Genetically Similar To European Reference Populations, S E Paul, N M Elsayed, S M C Colbert, R Bogdan, A S Hatoum, D M Barch

2020-Current year OA Pubs

Cognitive abilities are heritable and influenced by socioeconomic status (SES). It is critical to understand the association between SES and cognition beyond genetic propensity to inform potential benefits of SES-based interventions and to determine if such associations vary across (i) cognitive domains, (ii) facets of SES, and/or (iii) genetic propensity for different aspects of cognition. We examined the contributions of neighborhood socioeconomic advantage, family income, and polygenic scores (PGS) for domains of cognition (i.e., general cognitive ability, executive function, learning and memory, fluid reasoning) in a sample of children (ages 9-10;

Mitochondrial Dysfunction And Lipid Dysregulation In Yeast Lacking Phosphatidylserine, Alaumy Joshi, Zakery N Baker, Rachel A Stanfield, Dimitris T Kalafatis, David J Pagliarini, Vishal M Gohil

2020-Current year OA Pubs

Mitochondrial membrane phospholipids impact mitochondrial structure and function by influencing the assembly and activity of membrane proteins. Although the specific roles of the three most abundant mitochondrial phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cardiolipin (CL), have been extensively studied, the precise function of less abundant phosphatidylserine (PS) is not yet determined. Here, we used genetic and nutritional manipulation to engineer a set of yeast mutants, including a mutant completely devoid of PS, to assess its role in mitochondrial bioenergetics and lipid homeostasis. To circumvent the confounding effect of downstream PS products, PE and PC, we exogenously supplied ethanolamine that allows …

Cell Autonomous Microglia Defects In A Stem Cell Model Of Frontotemporal Dementia Tau, Abhirami K Iyer, Farzaneh S Mirfakhar, Miguel Minaya, Mariana Acquarone, Rama Krishna Koppisetti, Arun Renganathan, Shih-Feng You, Emma P Danhash, Kylie J Schache, Anthony Verbeck, Grant Galasso, Scott M Lee, Guangming Huang, Katherine J Miller, Jacob Marsh, Chihiro Sato, Celeste M Karch, Et Al.

2020-Current year OA Pubs

Neuronal dysfunction has been extensively studied as a central feature of neurodegenerative tauopathies. However, across neurodegenerative diseases, there is strong evidence for active involvement of immune cells like microglia in driving disease pathophysiology. Here, we demonstrate that MAPT mRNA and tau protein are expressed in microglia in human brains and in human induced pluripotent stem cell (iPSC)-derived microglia like cells (iMGLs). Using iMGLs harboring the MAPT IVS10 + 16 mutation and isogenic controls, we demonstrate that a tau mutation is sufficient to alter microglial transcriptional states. We discovered that MAPT IVS10 + 16 microglia exhibit cytoskeletal abnormalities, stalled phagocytosis, disrupted …

Motivations, Facilitators, And Barriers Of Donation-Based Interventions In Hiv And Sexually Transmitted Infection Research: A Systematic Review, Dorian Ho, Ye Liu, Jamie Conklin, Thomas Fitzpatrick, Jiayu Wang, Suzanne Day, Takhona G Hlatshwako, Rohit Ramaswamy, Ruby Congjiang Wang, Eneyi E Kpokiri, Weiming Tang, Elvin Geng, Joseph D Tucker

2020-Current year OA Pubs

IMPORTANCE: Donation-based prosocial interventions involve someone receiving a free health service and then distributing or donating to support health services for others; examples within the HIV and sexually transmitted infection (STI) literature include secondary distribution of HIV self-tests, secondary syringe exchange, and pay it forward for STI testing. These interventions answer research and policy recommendations to incorporate prosocial behaviors into HIV/STI services.

OBJECTIVE: To describe motivations, facilitators, and barriers of donation-based interventions in HIV and STI research using data from qualitative studies.

EVIDENCE REVIEW: In this systematic review, 5 databases (PubMed, CINAHL, Embase, PsycInfo, and Scopus) and references were searched …