Medicine and Health Sciences Commons^™

Serum Concentrations Of Losartan Metabolites Correlate With Improved Physical Function In A Pilot Study Of Prefrail Older Adults, Jessica L Lee, Cissy Zhang, Reyhan Westbrook, Mariann M Gabrawy, Lolita Nidadavolu, Huanle Yang, Ruth Marx, Yuqiong Wu, Nicole M Anders, Lina Ma, Marcela-Dávalos Bichara, Min-Ji Kwak, Brian Buta, Mohammed Khadeer, Gayane Yenokyan, Jing Tian, Qian-Li Xue, Helmy M Siragy, Robert M Carey, Rafael De Cabo, Luigi Ferrucci, Ruin Moaddel, Michelle A Rudek, Anne Le, Jeremy D Walston, Peter M Abadir

Faculty, Staff and Student Publications

Losartan is an oral antihypertensive agent that is rapidly metabolized to EXP3174 (angiotensin-subtype-1-receptor blocker) and EXP3179 (peroxisome proliferator-activated receptor gamma [PPARγ] agonist), which was shown in animal studies to reduce inflammation, enhance mitochondrial energetics, and improve muscle repair and physical performance. We conducted an exploratory pilot study evaluating losartan treatment in prefrail older adults (age 70-90 years, N = 25). Participants were randomized to control (placebo) or treatment (daily oral losartan beginning at 25 mg per day and increasing every 8 weeks) for a total of 6 months. Fatigue, hyperkalemia, and hypotension were the most observed side effects of losartan …

Accelerometer-Measured Latent Physical Activity Profiles And Neurocognition Among Middle-Aged And Older Hispanic/Latino Adults In The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol)\, Priscilla M Vásquez, Wassim Tarraf, Albert Chai, Adit Doza, Daniela Sotres-Alvarez, Keith M Diaz, Zvinka Z Zlatar, Ramon A Durazo-Arvizu, Linda C Gallo, Mayra L Estrella, Elizabeth Vásquez, Kelly R Evenson, Tasneem Khambaty, Bharat Thyagarajan, Richard H Singer, Neil Schneiderman, Martha L Daviglus, Hector M González

Faculty, Staff and Student Publications

Objectives: Derive latent profiles of accelerometry-measured moderate-vigorous physical activity (MVPA) for Hispanic/Latino adults, examine associations between latent MVPA profiles and neurocognition, and describe profiles via self-reported MVPA.

Methods: Complex survey design methods were applied to cross-sectional data from 7,672 adults ages 45-74 years in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; 2008-2011). MVPA was measured via hip-worn accelerometers. Latent profile analysis was applied to derive latent MVPA profiles (minutes/day of week). Neurocognition was assessed with the Brief-Spanish English Verbal Learning Test (B-SEVLT) Sum, B-SEVLT Recall, Controlled Oral Word Association Test (word fluency), and Digit Symbol Substitution (DSS) test. All …

Feasibility And Effectiveness Of A Worksite-Weight-Loss Program For Cancer Prevention Among School-District Employees With Overweight And Obesity, Che Young Lee, Michael C Robertson, Hannah Johnston, Thuan Le, Margaret Raber, Ruth Rechis, Katherine Oestman, Alise Neff, Amber Macneish, Karen M Basen-Engquist

Faculty, Staff and Students Publications

The effects of Vibrant Lives, a 6-month worksite-weight-loss program, were examined in a cohort of school-district employees with overweight or obesity. The VL Basic (VLB) participants received materials and tailored text messages, the VL Plus (VLP) participants additionally received WIFI-enabled activity monitors and scales and participated in health challenges throughout the school year, and the VL Plus with Support (VLP + S) participants additionally received coaching support. The levels of program satisfaction and retention and changes in weight, physical activity (PA), and diet were compared across groups using Pearson chi-square tests, repeated-measure mixed models, and logistic regression. After the program, …

Assembling A Global Database Of Child Pneumonia Studies To Inform Who Pneumonia Management Algorithm: Methodology And Applications, Helena Martin, Jennifer Falconer, Emmanuel Addo-Yobo, Satinder Aneja, Luis Martinez Arroyo, Rai Asghar, Shally Awasthi, Salem Banajeh, Abdul Bari, Sudha Basnet, Ashish Bavdekar, Nita Bhandari, Shinjini Bhatnagar, Zulfiqar A Bhutta, Abdullah Brooks, Mandeep Chadha, Noel Chisaka, Monidarin Chou, Alexey W Clara, Tim Colbourn, Clare Cutland, Valérie D'Acremont, Marcela Echavarria, Angela Gentile, Brad Gessner, Christopher J Gregory, Tabish Hazir, Patricia L Hibberd, Siddhivinayak Hirve, Shubhada Hooli, Imran Iqbal, Prakash Jeena, Cissy B Kartasasmita, Carina King, Romina Libster, Rakesh Lodha, Juan M Lozano, Marilla Lucero, Norman Lufesi, William B Macleod, Shabir Ahmed Madhi, Joseph L Mathew, Irene Maulen-Radovan, Eric D Mccollum, Greta Mino, Charles Mwansambo, Mark I Neuman, Ngoc Tuong Vy Nguyen, Marta C Nunes, Pagbajabyn Nymadawa, Kerry-Ann F O'Grady, Jean-William Pape, Glaucia Paranhos-Baccala, Archana Patel, Valentina Sanchez Picot, Mala Rakoto-Andrianarivelo, Zeba Rasmussen, Vanessa Rouzier, Graciela Russomando, Raul O Ruvinsky, Salim Sadruddin, Samir K Saha, Mathuram Santosham, Sunit Singhi, Sajid Soofi, Tor A Strand, Mariam Sylla, Somsak Thamthitiwat, Donald M Thea, Claudia Turner, Philippe Vanhems, Nitya Wadhwa, Jianwei Wang, Syed Ma Zaman, Harry Campbell, Harish Nair, Shamim Ahmad Qazi, Yasir Bin Nisar, World Health Organization Pneumonia Research Partnership To Assess Who Recommendation (Prepare) Study Group

Faculty, Staff and Students Publications

BACKGROUND: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines.

METHODS: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to …

Cardiac Neural Crest And Cardiac Regeneration, Shannon Erhardt, Jun Wang

Faculty, Staff and Student Publications

Neural crest cells (NCCs) are a vertebrate-specific, multipotent stem cell population that have the ability to migrate and differentiate into various cell populations throughout the embryo during embryogenesis. The heart is a muscular and complex organ whose primary function is to pump blood and nutrients throughout the body. Mammalian hearts, such as those of humans, lose their regenerative ability shortly after birth. However, a few vertebrate species, such as zebrafish, have the ability to self-repair/regenerate after cardiac damage. Recent research has discovered the potential functional ability and contribution of cardiac NCCs to cardiac regeneration through the use of various vertebrate …

Safety And Microbiological Activity Of Phage Therapy In Persons With Cystic Fibrosis Colonized With Pseudomonas Aeruginosa: Study Protocol For A Phase 1b/2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial, Pranita D Tamma, Maria Souli, Michael Billard, Joseph Campbell, Douglas Conrad, Damon W Ellison, Beth Evans, Scott R Evans, Kerryl E Greenwood-Quaintance, Andrey A Filippov, Holly S Geres, Toshimitsu Hamasaki, Lauren Komarow, Mikeljon P Nikolich, Thomas P Lodise, Seema U Nayak, Carmelle Norice-Tra, Robin Patel, David Pride, Janie Russell, Daria Van Tyne, Henry F Chambers, Vance G Fowlerjr, Robert T Schooley, Antibacterial Resistance Leadership Group

Faculty, Staff and Student Publications

BACKGROUND: Bacteriophages (phages) are a promising anti-infective option for human disease. Major gaps remain in understanding their potential utility.

METHODS: This is a randomized, placebo-controlled, double-blind study of a single dose of intravenous phage in approximately 72 clinically stable adult cystic fibrosis volunteers recruited from up to 20 US sites with Pseudomonas aeruginosa airway colonization. The single dose of phage consists of a mixture of four anti-pseudomonal phages. Six sentinel participants will be sequentially enrolled with dose escalation of the phage mixture by one log

DISCUSSION: This trial will investigate the activity of phages in reducing P. aeruginosa colony counts …

The Maternal And Infant Environmental Health Riskscape Study Of Perinatal Disparities In Greater Houston: Rationale, Study Design And Participant Profiles, R Jeanne Ruiz, Kristyn Grimes, Elizabeth Spurlock, Angela Stotts, Thomas F Northrup, Yolanda Villarreal, Robert Suchting, Melissa Cernuch, Liza Rivera, Raymond P Stowe, Rita H Pickler

Faculty, Staff and Student Publications

BACKGROUND: Pregnant Mexican Americans (hereafter called Latinas) and Black/African American women are at increased risk for psychological distress, contributing to preterm birth and low birthweight; acculturative stress combined with perceived stress elevates depressive symptoms in Latinas. Based on our prior research using a psychoneuroimmunology framework, we identified psychological and neuroendocrine risk factors as predictors of preterm birth in Latina women that are also identified as risk factors for Black/African American women.

METHODS/DESIGN: In this prospective, randomized controlled trial with parallel group design we will explore psychosocial, neuroendocrine, and birth outcome effects of the Mastery Lifestyle Intervention (MLI). The MLI is …

Pertussis And Influenza Immunization: Perceived Attitude And Decision Of Postpartum Patients, Nutan B Hebballi, Tayler Parker, Elisa I Garcia, Dalya M Ferguson, Susan Lesser, Kuojen Tsao, Maryam Broussard, Susan H Wootton

Faculty, Staff and Student Publications

BACKGROUND: Vaccination of pregnant patients with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccine during influenza season can reduce maternal and fetal morbidity and mortality; nevertheless, vaccination rates remain suboptimal in this patient population. To investigate the effect of a brief educational counseling session on maternal Tdap and influenza vaccination and determine factors influencing women's decision in regards to receiving Tdap and or influenza vaccine during their pregnancy.

METHODS: A face-to-face semi-structured cross-sectional survey was administered to postpartum patients on their anticipated day of discharge (June 11-August 21, 2018). A brief educational counseling session about maternal …

Interventions To Treat And Prevent Postpartum Depression: A Protocol For Systematic Review Of The Literature And Parallel Network Meta-Analyses, David Thomas Monks, Basavaraj Ankalagi, Preet Mohinder Singh, Ebony Carter, Michelle Doering, Meg Guard, Shannon Lenze

2020-Current year OA Pubs

INTRODUCTION: Postpartum depression has costly consequences for the mother, baby, and society. Numerous pharmacological and non-pharmacological interventions are available for the prevention and treatment of postpartum depression. To date, no attempt has been made to synthesize the evidence from comparisons of interventions both within and across these categories.

METHODS: We will perform a systematic review of the literature and perform network meta-analysis of interventions to (a) prevent and (b) treat postpartum depression. This review will include studies of primiparous or multiparous women during pregnancy or within 12 months of delivery of their baby that assess either interventions initiated during pregnancy …

Socioecological Predictors Of Breastfeeding Practices In Rural Eastern Ethiopia, Marina Magalhães, Amanda Ojeda, Karah Mechlowitz, Kaitlin Brittain, Jenna Daniel, Kedir Teji Roba, Jemal Yousuf Hassen, Mark J Manary, Wondwossen A Gebreyes, Arie H Havelaar, Sarah L Mckune

2020-Current year OA Pubs

BACKGROUND: Estimates by the World Health Organization indicate that over 800,000 global neonatal deaths each year are attributed to deviations from recommended best practices in infant feeding. Identifying factors promoting ideal breastfeeding practices may facilitate efforts to decrease neonatal and infant death rates and progress towards achieving the Sustainable Development Goals set for 2030. Though numerous studies have identified the benefits of breastfeeding in reducing the risk of childhood undernutrition, infection and illness, and mortality in low- and middle-income countries, no studies have explored predictors of breastfeeding practices in rural eastern Ethiopia, where undernutrition is widespread. The aim of this …

Implicating Genes, Pleiotropy, And Sexual Dimorphism At Blood Lipid Loci Through Multi-Ancestry Meta-Analysis, Stavroula Kanoni, Sarah E Graham, Yuxuan Wang, Ida Surakka, Shweta Ramdas, Xiang Zhu, Shoa L Clarke, Konain Fatima Bhatti, Sailaja Vedantam, Thomas W Winkler, Adam E Locke, Eirini Marouli, Greg J M Zajac, Kuan-Han H Wu, Ioanna Ntalla, Qin Hui, Derek Klarin, Austin T Hilliard, Zeyuan Wang, Chao Xue, Gudmar Thorleifsson, Anna Helgadottir, Daniel F Gudbjartsson, Hilma Holm, Isleifur Olafsson, Mi Yeong Hwang, Sohee Han, Masato Akiyama, Saori Sakaue, Chikashi Terao, Masahiro Kanai, Wei Zhou, Ben M Brumpton, Humaira Rasheed, Aki S Havulinna, Yogasudha Veturi, Jennifer Allen Pacheco, Elisabeth A Rosenthal, Todd Lingren, Qiping Feng, Iftikhar J Kullo, Akira Narita, Jun Takayama, Hilary C Martin, Karen A Hunt, Bhavi Trivedi, Jeffrey Haessler, Franco Giulianini, Yuki Bradford, Jason E Miller, Archie Campbell, Kuang Lin, Iona Y Millwood, Asif Rasheed, George Hindy, Jessica D Faul, Wei Zhao, David R Weir, Constance Turman, Hongyan Huang, Mariaelisa Graff, Ananyo Choudhury, Dhriti Sengupta, Anubha Mahajan, Michael R Brown, Weihua Zhang, Ketian Yu, Ellen M Schmidt, Anita Pandit, Stefan Gustafsson, Xianyong Yin, Jian'an Luan, Jing-Hua Zhao, Fumihiko Matsuda, Hye-Mi Jang, Kyungheon Yoon, Carolina Medina-Gomez, Achilleas Pitsillides, Jouke Jan Hottenga, Andrew R Wood, Yingji Ji, Zishan Gao, Simon Haworth, Noha A Yousri, Ruth E Mitchell, Jin Fang Chai, Mette Aadahl, Anne A Bjerregaard, Jie Yao, Ani Manichaikul, Chii-Min Hwu, Yi-Jen Hung, Helen R Warren, Julia Ramirez, Jette Bork-Jensen, Line L Kårhus, Anuj Goel, Maria Sabater-Lleal, Raymond Noordam, Pala Mauro, Floris Matteo, Aaron F Mcdaid, Pedro Marques-Vidal, Matthias Wielscher, Stella Trompet, Naveed Sattar, Line T Møllehave, Matthias Munz, Lingyao Zeng, Jianfeng Huang, Bin Yang, Alaitz Poveda, Azra Kurbasic, Claudia Lamina, Lukas Forer, Markus Scholz, Tessel E Galesloot, Jonathan P Bradfield, Sanni E Ruotsalainen, Ewarwick Daw, Joseph M Zmuda, Jonathan S Mitchell, Christian Fuchsberger, Henry Christensen, Jennifer A Brody, Miguel Vazquez-Moreno, Mary F Feitosa, Mary K Wojczynski, Zhe Wang, Michael H Preuss, Massimo Mangino, Paraskevi Christofidou, Niek Verweij, Jan W Benjamins, Jorgen Engmann, Noah L Tsao, Anurag Verma, Roderick C Slieker, Ken Sin Lo, Nuno R Zilhao, Phuong Le, Marcus E Kleber, Graciela E Delgado, Shaofeng Huo, Daisuke D Ikeda, Hiroyuki Iha, Jian Yang, Jun Liu, Ayşe Demirkan, Hampton L Leonard, Jonathan Marten, Mirjam Frank, Börge Schmidt, Laura J Smyth, Marisa Cañadas-Garre, Chaolong Wang, Masahiro Nakatochi, Andrew Wong, Nina Hutri-Kähönen, Xueling Sim, Rui Xia, Alicia Huerta-Chagoya, Juan Carlos Fernandez-Lopez, Valeriya Lyssenko, Suraj S Nongmaithem, Swati Bayyana, Heather M Stringham, Marguerite R Irvin, Christopher Oldmeadow, Han-Na Kim, Seungho Ryu, Paul R H J Timmers, Liubov Arbeeva, Rajkumar Dorajoo, Leslie A Lange, Gauri Prasad, Laura Lorés-Motta, Marc Pauper, Jirong Long, Xiaohui Li, Elizabeth Theusch, Fumihiko Takeuchi, Cassandra N Spracklen, Anu Loukola, Sailalitha Bollepalli, Sophie C Warner, Ya Xing Wang, Wen B Wei, Teresa Nutile, Daniela Ruggiero, Yun Ju Sung, Shufeng Chen, Fangchao Liu, Jingyun Yang, Katherine A Kentistou, Bernhard Banas, Giuseppe Giovanni Nardone, Karina Meidtner, Lawrence F Bielak, Jennifer A Smith, Prashantha Hebbar, Aliki-Eleni Farmaki, Edith Hofer, Maoxuan Lin, Maria Pina Concas, Simona Vaccargiu, Peter J Van Der Most, Niina Pitkänen, Brian E Cade, Sander W Van Der Laan, Kumaraswamy Naidu Chitrala, Stefan Weiss, Amy R Bentley, Ayo P Doumatey, Adebowale A Adeyemo, Jong Young Lee, Eva R B Petersen, Aneta A Nielsen, Hyeok Sun Choi, Maria Nethander, Sandra Freitag-Wolf, Lorraine Southam, Nigel W Rayner, Carol A Wang, Shih-Yi Lin, Jun-Sing Wang, Christian Couture, Leo-Pekka Lyytikäinen, Kjell Nikus, Gabriel Cuellar-Partida, Henrik Vestergaard, Bertha Hidalgo, Olga Giannakopoulou, Qiuyin Cai, Morgan O Obura, Jessica Van Setten, Xiaoyin Li, Jingjing Liang, Hua Tang, Natalie Terzikhan, Jae Hun Shin, Rebecca D Jackson, Alexander P Reiner, Lisa Warsinger Martin, Zhengming Chen, Liming Li, Takahisa Kawaguchi, Joachim Thiery, Joshua C Bis, Lenore J Launer, Huaixing Li, Mike A Nalls, Olli T Raitakari, Sahoko Ichihara, Sarah H Wild, Christopher P Nelson, Harry Campbell, Susanne Jäger, Toru Nabika, Fahd Al-Mulla, Harri Niinikoski, Peter S Braund, Ivana Kolcic, Peter Kovacs, Tota Giardoglou, Tomohiro Katsuya, Dominique De Kleijn, Gert J De Borst, Eung Kweon Kim, Hieab H H Adams, M Arfan Ikram, Xiaofeng Zhu, Folkert W Asselbergs, Adriaan O Kraaijeveld, Joline W J Beulens, Xiao-Ou Shu, Loukianos S Rallidis, Oluf Pedersen, Torben Hansen, Paul Mitchell, Alex W Hewitt, Mika Kähönen, Louis Pérusse, Claude Bouchard, Anke Tönjes, Yii-Der Ida Chen, Craig E Pennell, Trevor A Mori, Wolfgang Lieb, Andre Franke, Claes Ohlsson, Dan Mellström, Yoon Shin Cho, Hyejin Lee, Jian-Min Yuan, Woon-Puay Koh, Sang Youl Rhee, Jeong-Taek Woo, Iris M Heid, Klaus J Stark, Martina E Zimmermann, Henry Völzke, Georg Homuth, Michele K Evans, Alan B Zonderman, Ozren Polasek, Gerard Pasterkamp, Imo E Hoefer, Susan Redline, Katja Pahkala, Albertine J Oldehinkel, Harold Snieder, Ginevra Biino, Reinhold Schmidt, Helena Schmidt, Stefania Bandinelli, George Dedoussis, Thangavel Alphonse Thanaraj, Sharon L R Kardia, Patricia A Peyser, Norihiro Kato, Matthias B Schulze, Giorgia Girotto, Carsten A Böger, Bettina Jung, Peter K Joshi, David A Bennett, Philip L De Jager, Xiangfeng Lu, Vasiliki Mamakou, Morris Brown, Mark J Caulfield, Patricia B Munroe, Xiuqing Guo, Marina Ciullo, Jost B Jonas, Nilesh J Samani, Jaakko Kaprio, Päivi Pajukanta, Teresa Tusié-Luna, Carlos A Aguilar-Salinas, Linda S Adair, Sonny Augustin Bechayda, H Janaka De Silva, Ananda R Wickremasinghe, Ronald M Krauss, Jer-Yuarn Wu, Wei Zheng, Anneke Iden Hollander, Dwaipayan Bharadwaj, Adolfo Correa, James G Wilson, Lars Lind, Chew-Kiat Heng, Amanda E Nelson, Yvonne M Golightly, James F Wilson, Brenda Penninx, Hyung-Lae Kim, John Attia, Rodney J Scott, D C Rao, Donna K Arnett, Steven C Hunt, Mark Walker, Heikki A Koistinen, Giriraj R Chandak, Josep M Mercader, Maria C Costanzo, Dongkeun Jang, Noël P Burtt, Clicerio Gonzalez Villalpando, Lorena Orozco, Myriam Fornage, Eshyong Tai, Rob M Van Dam, Terho Lehtimäki, Nish Chaturvedi, Mitsuhiro Yokota, Jianjun Liu, Dermot F Reilly, Amy Jayne Mcknight, Frank Kee, Karl-Heinz Jöckel, Mark I Mccarthy, Colin N A Palmer, Veronique Vitart, Caroline Hayward, Eleanor Simonsick, Cornelia M Van Duijn, Zi-Bing Jin, Jia Qu, Haretsugu Hishigaki, Xu Lin, Winfried März, Vilmundur Gudnason, Jean-Claude Tardif, Guillaume Lettre, Leen M 'T Hart, Petra J M Elders, Scott M Damrauer, Meena Kumari, Mika Kivimaki, Pim Van Der Harst, Tim D Spector, Ruth J F Loos, Michael A Province, Esteban J Parra, Miguel Cruz, Bruce M Psaty, Ivan Brandslund, Peter P Pramstaller, Charles N Rotimi, Kaare Christensen, Samuli Ripatti, Elisabeth Widén, Hakon Hakonarson, Struan F A Grant, Lambertus A L M Kiemeney, Jacqueline De Graaf, Markus Loeffler, Florian Kronenberg, Dongfeng Gu, Jeanette Erdmann, Heribert Schunkert, Paul W Franks, Allan Linneberg, J Wouter Jukema, Amit V Khera, Minna Männikkö, Marjo-Riitta Jarvelin, Zoltan Kutalik, Cucca Francesco, Dennis O Mook-Kanamori, Ko Willems Van Dijk, Hugh Watkins, David P Strachan, Niels Grarup, Peter Sever, Neil Poulter, Lee-Ming Chuang, Jerome I Rotter, Thomas M Dantoft, Fredrik Karpe, Matt J Neville, Nicholas J Timpson, Ching-Yu Cheng, Tien-Yin Wong, Chiea Chuen Khor, Hengtong Li, Charumathi Sabanayagam, Annette Peters, Christian Gieger, Andrew T Hattersley, Nancy L Pedersen, Patrik K E Magnusson, Dorret I Boomsma, Allegonda H M Willemsen, Ladrienne Cupples, Joyce B J Van Meurs, Mohsen Ghanbari, Penny Gordon-Larsen, Wei Huang, Young Jin Kim, Yasuharu Tabara, Nicholas J Wareham, Claudia Langenberg, Eleftheria Zeggini, Johanna Kuusisto, Markku Laakso, Erik Ingelsson, Goncalo Abecasis, John C Chambers, Jaspal S Kooner, Paul S De Vries, Alanna C Morrison, Scott Hazelhurst, Michèle Ramsay, Kari E North, Martha Daviglus, Peter Kraft, Nicholas G Martin, John B Whitfield, Shahid Abbas, Danish Saleheen, Robin G Walters, Michael V Holmes, Corri Black, Blair H Smith, Aris Baras, Anne E Justice, Julie E Buring, Paul M Ridker, Daniel I Chasman, Charles Kooperberg, Gen Tamiya, Masayuki Yamamoto, David A Van Heel, Richard C Trembath, Wei-Qi Wei, Gail P Jarvik, Bahram Namjou, M Geoffrey Hayes, Marylyn D Ritchie, Pekka Jousilahti, Veikko Salomaa, Kristian Hveem, Bjørn Olav Åsvold, Michiaki Kubo, Yoichiro Kamatani, Yukinori Okada, Yoshinori Murakami, Bong-Jo Kim, Unnur Thorsteinsdottir, Kari Stefansson, Jifeng Zhang, Yeugene Chen, Yuk-Lam Ho, Julie A Lynch, Daniel J Rader, Philip S Tsao, Kyong-Mi Chang, Kelly Cho, Christopher J O'Donnell, John M Gaziano, Peter W F Wilson, Timothy M Frayling, Joel N Hirschhorn, Sekar Kathiresan, Karen L Mohlke, Yan V Sun, Andrew P Morris, Michael Boehnke, Christopher D Brown, Pradeep Natarajan, Panos Deloukas, Cristen J Willer, Themistocles L Assimes, Gina M Peloso

Faculty, Staff and Student Publications

BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.

RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases …

The Performance Of Plasma Amyloid Beta Measurements In Identifying Amyloid Plaques In Alzheimer's Disease: A Literature Review, Abby L Brand, Paige E Lawler, James G Bollinger, Yan Li, Suzanne E Schindler, Melody Li, Samir Lopez, Vitaliy Ovod, Akinori Nakamura, Leslie M Shaw, Henrik Zetterberg, Oskar Hansson, Randall J Bateman

2020-Current year OA Pubs

The extracellular buildup of amyloid beta (Aβ) plaques in the brain is a hallmark of Alzheimer's disease (AD). Detection of Aβ pathology is essential for AD diagnosis and for identifying and recruiting research participants for clinical trials evaluating disease-modifying therapies. Currently, AD diagnoses are usually made by clinical assessments, although detection of AD pathology with positron emission tomography (PET) scans or cerebrospinal fluid (CSF) analysis can be used by specialty clinics. These measures of Aβ aggregation, e.g. plaques, protofibrils, and oligomers, are medically invasive and often only available at specialized medical centers or not covered by medical insurance, and PET …

Sentiment Analysis Of Insomnia-Related Tweets Via A Combination Of Transformers Using Dempster-Shafer Theory: Pre- And Peri-Covid-19 Pandemic Retrospective Study, Arash Maghsoudi, Sara Nowakowski, Ritwick Agrawal, Amir Sharafkhaneh, Mark E Kunik, Aanand D Naik, Hua Xu, Javad Razjouyan

Faculty, Staff and Student Publications

BACKGROUND: The COVID-19 pandemic has imposed additional stress on population health that may result in a change of sleeping behavior.

OBJECTIVE: In this study, we hypothesized that using natural language processing to explore social media would help with assessing the mental health conditions of people experiencing insomnia after the outbreak of COVID-19.

METHODS: We designed a retrospective study that used public social media content from Twitter. We categorized insomnia-related tweets based on time, using the following two intervals: the prepandemic (January 1, 2019, to January 1, 2020) and peripandemic (January 1, 2020, to January 1, 2021) intervals. We performed a …

Covid-19 Vaccines: The Imperfect Instruments Of Vaccine Diplomacy, Peter J Hotez

Center for Medical Ethics and Health Policy Staff Publications

Although true vaccine diplomacy in the form of sharing vaccine development technologies and scientific cooperation with low- and middle-income countries has not been a dominant theme in the COVID-19 pandemic, this aspect is now taking off and generating some exciting new possibilities.

Truvari: Refined Structural Variant Comparison Preserves Allelic Diversity, Adam C English, Vipin K Menon, Richard A Gibbs, Ginger A Metcalf, Fritz J Sedlazeck

Faculty, Staff and Students Publications

The fundamental challenge of multi-sample structural variant (SV) analysis such as merging and benchmarking is identifying when two SVs are the same. Common approaches for comparing SVs were developed alongside technologies which produce ill-defined boundaries. As SV detection becomes more exact, algorithms to preserve this refined signal are needed. Here, we present Truvari-an SV comparison, annotation, and analysis toolkit-and demonstrate the effect of SV comparison choices by building population-level VCFs from 36 haplotype-resolved long-read assemblies. We observe over-merging from other SV merging approaches which cause up to a 2.2× inflation of allele frequency, relative to Truvari.

The Effect Of Zinc Supplementation On The Course Of Covid-19 – A Systematic Review And Meta-Analysis, Monika Olczak-Pruc, Lukasz Szarpak, Alla Navolokina, Jaroslaw Chmielewski, Lech Panasiuk, Raúl Juárez-Vela, Michal Pruc, Damian Swieczkowski, Ryszard Majer, Zubaid Rafique, Frank William Peacock

Faculty, Staff and Students Publications

Introduction and objective: Zinc is a trace element that plays a role in stimulating innate and acquired immunity. The aim of the study was to determine the antiviral effect of the administration of zinc in COVID-19 patients.

Material and methods: A literature search was performed in P Web of Science, PubMed, Scopus and Cochrane databases from 1 January 2020 - 22 August 2022. In addition, reference lists of the included articles and their related citations in PubMed were also reviewed for additional pertinent studies.

Results: A total of 9 eligible studies were identified. In-hospital mortality in zinc supplementation patients, and …

Anti-Cancer Mechanisms Of Action Of Therapeutic Alternating Electric Fields (Tumor Treating Fields [Ttfields]), Shadi Shams, Chirag B Patel

Faculty, Staff and Student Publications

Despite improved survival outcomes across many cancer types, the prognosis remains grim for certain solid organ cancers including glioblastoma and pancreatic cancer. Invariably in these cancers, the control achieved by time-limited interventions such as traditional surgical resection, radiation therapy, and chemotherapy is short-lived. A new form of anti-cancer therapy called therapeutic alternating electric fields (AEFs) or tumor treating fields (TTFields) has been shown, either by itself or in combination with chemotherapy, to have anti-cancer effects that translate to improved survival outcomes in patients. Although the pre-clinical and clinical data are promising, the mechanisms of TTFields are not fully elucidated. Many …

Kidney Proximal Tubule Glut2-More Than Meets The Eye, Majdoleen Ahmad, Ifat Abramovich, Bella Agranovich, Alina Nemirovski, Eyal Gottlieb, Liad Hinden, Joseph Tam

Faculty, Staff and Student Publications

Tubulopathy plays a central role in the pathophysiology of diabetic kidney disease (DKD). Under diabetic conditions, the kidney proximal tubule cells (KPTCs) are exposed to an extensive amount of nutrients, most notably glucose; these nutrients deteriorate KPTCs function and promote the development and progression of DKD. Recently, the facilitative glucose transporter 2 (GLUT2) in KPTCs has emerged as a central regulator in the pathogenesis of DKD. This has been demonstrated by identifying its specific role in enhancing glucose reabsorption and glucotoxicity, and by deciphering its effect in regulating the expression of the sodium-glucose transporter 2 (SGLT2) in KPTCs. Moreover, reduction/deletion …

Diverse Monogenic Subforms Of Human Spermatogenic Failure, Liina Nagirnaja, Wu-Lin Charng, Christina A Gurnett, Kenan R Omurtag, Et Al.

2020-Current year OA Pubs

Non-obstructive azoospermia (NOA) is the most severe form of male infertility and typically incurable. Defining the genetic basis of NOA has proven challenging, and the most advanced classification of NOA subforms is not based on genetics, but simple description of testis histology. In this study, we exome-sequenced over 1000 clinically diagnosed NOA cases and identified a plausible recessive Mendelian cause in 20%. We find further support for 21 genes in a 2-stage burden test with 2072 cases and 11,587 fertile controls. The disrupted genes are primarily on the autosomes, enriched for undescribed human "knockouts", and, for the most part, have …

Exome Array Analysis Of 9721 Ischemic Stroke Cases From The Sign Consortium, Huichun Xu, Kevin Nguyen, Brady J Gaynor, Hua Ling, Wei Zhao, Patrick F Mcardle, Timothy D O'Connor, O Colin Stine, Kathleen A Ryan, Megan Lynch, Jennifer A Smith, Jessica D Faul, Yao Hu, Jeffrey W Haessler, Myriam Fornage, Charles Kooperberg, On Behalf Of The Trans-Omics For Precision Medicine Topmed Stroke Working Group, James A Perry, Charles C Hong, John W Cole, Elizabeth Pugh, Kimberly Doheny, Sharon L R Kardia, David R Weir, Steven J Kittner, Braxton D Mitchell, Sign Consortium

Faculty, Staff and Student Publications

Recent genome wide association studies have identified 89 common genetic variants robustly associated with ischemic stroke and primarily located in non-coding regions. To evaluate the contribution of coding variants, which are mostly rare, we performed an exome array analysis on 106,101 SNPs for 9721 ischemic stroke cases from the SiGN Consortium, and 12,345 subjects with no history of stroke from the Health Retirement Study and SiGN consortium. We identified 15 coding variants significantly associated with all ischemic stroke at array-wide threshold (i.e., p < 4.7 × 10-7), including two common SNPs in ABO that have previously been associated with stroke. Twelve of the remaining 13 variants were extremely rare …

Glutamine Produces Ammonium To Tune Lysosomal Ph And Regulate Lysosomal Function, Jian Xiong, Thi Thu Trang Luu, Kartik Venkatachalam, Guangwei Du, Michael X Zhu

Faculty, Staff and Student Publications

Glutamine is one of the most abundant amino acids in the cell. In mitochondria, glutaminases 1 and 2 (GLS1/2) hydrolyze glutamine to glutamate, which serves as the precursor of multiple metabolites. Here, we show that ammonium generated during GLS1/2-mediated glutaminolysis regulates lysosomal pH and in turn lysosomal degradation. In primary human skin fibroblasts BJ cells and mouse embryonic fibroblasts, deprivation of total amino acids for 1 h increased lysosomal degradation capacity as shown by the increased turnover of lipidated microtubule-associated proteins 1A/1B light chain 3B (LC3-II), several autophagic receptors, and endocytosed DQ-BSA. Removal of glutamine but not any other amino …

Association Of Gulf War Illness With Characteristics In Deployed Vs Non-Deployed Gulf War Era Veterans In The Cooperative Studies Program 2006/Million Veteran Program 029 Cohort: A Cross-Sectional Analysis, Linh M Duong, Alice B S Nono Djotsa, Jacqueline Vahey, Lea Steele, Rachel Quaden, Kelly M Harrington, Sarah T Ahmed, Renato Polimanti, Elani Streja, John Michael Gaziano, John Concato, Hongyu Zhao, Krishnan Radhakrishnan, Elizabeth R Hauser, Drew A Helmer, Mihaela Aslan, Elizabeth J Gifford

Center for Medical Ethics and Health Policy Staff Publications

Gulf War Illness (GWI), a chronic multisymptom illness with a complex and uncertain etiology and pathophysiology, is highly prevalent among veterans deployed to the 1990-1991 GW. We examined how GWI phenotypes varied by demographic and military characteristics among GW-era veterans. Data were from the VA's Cooperative Studies Program 2006/Million Veteran Program (MVP) 029 cohort, Genomics of GWI. From June 2018 to March 2019, 109,976 MVP enrollees (out of a total of over 676,000) were contacted to participate in the 1990-1991 GW-era Survey. Of 109,976 eligible participants, 45,169 (41.1%) responded to the 2018-2019 survey, 35,902 respondents met study inclusion criteria, 13,107 …

Risk Factors For Sars-Cov-2 Transmission In Close Contacts Of Adults At High Risk Of Infection Due To Occupation: Results From The Contact Tracing Strategy Of The Covida Epidemiological Surveillance Study In Bogotá, Colombia, In 2020-2021, Andrea Ramírez Varela, Sandra Contreras-Arrieta, Guillermo Tamayo-Cabeza, Leonardo Salas Zapata, Yuldor Caballero-Díaz, Luis Jorge Hernández Florez, Andrés Patiño Benavidez, Rachid Laajaj, Fernando De La Hoz, Giancarlo Buitrago Gutierrez, Silvia Restrepo, Eduardo Behrentz

Faculty, Staff and Student Publications

OBJECTIVES: To estimate the risk factors for SARS-CoV-2 transmission in close contacts of adults at high risk of infection due to occupation, participants of the CoVIDA study, in Bogotá D.C., Colombia.

SETTING: The CoVIDA study was the largest COVID-19 intensified sentinel epidemiological surveillance study in Colombia thus far, performing over 60 000 RT-PCR tests for SARS-CoV-2 infection. The study implemented a contact tracing strategy (via telephone call) to support traditional surveillance actions performed by the local health authority.

PARTICIPANTS: Close contacts of participants from the CoVIDA study.

PRIMARY AND SECONDARY OUTCOME MEASURES: SARS-CoV-2 testing results were obtained (RT-PCR with CoVIDA …

Multiomics Characterization Of Methicillin-Resistant Staphylococcus Aureus (Mrsa) Isolates With Heterogeneous Intermediate Resistance To Vancomycin (Hvisa) In Latin America, Betsy E Castro, Rafael Rios, Lina P Carvajal, Mónica L Vargas, Mónica P Cala, Lizeth León, Blake Hanson, An Q Dinh, Oscar Ortega-Recalde, Carlos Seas, Jose M Munita, Cesar A Arias, Sandra Rincon, Jinnethe Reyes, Lorena Diaz

Faculty, Staff and Student Publications

BACKGROUND: Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) compromise the clinical efficacy of vancomycin. The hVISA isolates spontaneously produce vancomycin-intermediate Staphylococcus aureus (VISA) cells generated by diverse and intriguing mechanisms.

OBJECTIVE: To characterize the biomolecular profile of clinical hVISA applying genomic, transcriptomic and metabolomic approaches.

METHODS: 39 hVISA and 305 VSSA and their genomes were included. Core genome-based Bayesian phylogenetic reconstructions were built and alterations in predicted proteins in VISA/hVISA were interrogated. Linear discriminant analysis and a Genome-Wide Association Study were performed. Differentially expressed genes were identified in hVISA-VSSA by RNA-sequencing. The undirected profiles of metabolites were determined by liquid chromatography and …

Control Of Sars-Cov-2 Infection By Mt1-Mmp-Mediated Shedding Of Ace2, Xuanming Guo, Jianli Cao, Jian-Piao Cai, Jiayan Wu, Jiangang Huang, Pallavi Asthana, Sheung Kin Ken Wong, Zi-Wei Ye, Susma Gurung, Yijing Zhang, Sheng Wang, Zening Wang, Xin Ge, Hiu Yee Kwan, Aiping Lyu, Kui Ming Chan, Nathalie Wong, Jiandong Huang, Zhongjun Zhou, Zhao-Xiang Bian, Shuofeng Yuan, Hoi Leong Xavier Wong

Faculty, Staff and Student Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Angiotensin-converting enzyme 2 (ACE2) is an entry receptor for SARS-CoV-2. The full-length membrane form of ACE2 (memACE2) undergoes ectodomain shedding to generate a shed soluble form (solACE2) that mediates SARS-CoV-2 entry via receptor-mediated endocytosis. Currently, it is not known how the physiological regulation of ACE2 shedding contributes to the etiology of COVID-19 in vivo. The present study identifies Membrane-type 1 Matrix Metalloproteinase (MT1-MMP) as a critical host protease for solACE2-mediated SARS-CoV-2 infection. SARS-CoV-2 infection leads to increased activation of MT1-MMP that is colocalized with ACE2 in human lung …

Trem2 Dependent And Independent Functions Of Microglia In Alzheimer's Disease, Jinchao Hou, Yun Chen, Gary Grajales-Reyes, Marco Colonna

2020-Current year OA Pubs

Microglia are central players in brain innate immunity and have been the subject of extensive research in Alzheimer's disease (AD). In this review, we aim to summarize the genetic and functional discoveries that have advanced our understanding of microglia reactivity to AD pathology. Given the heightened AD risk posed by rare variants of the microglial triggering receptor expressed on myeloid cells 2 (TREM2), we will focus on the studies addressing the impact of this receptor on microglia responses to amyloid plaques, tauopathy and demyelination pathologies in mouse and human. Finally, we will discuss the implications of recent discoveries on microglia …

In Silico Activity And Admet Profiling Of Phytochemicals From Ethiopian Indigenous Aloes Using Pharmacophore Models, Lemessa Etana Bultum, Gemechu Bekele Tolossa, Gwangmin Kim, Ohhyeon Kwon, Doheon Lee

2020-Current year OA Pubs

In silico profiling is used in identification of active compounds and guide rational use of traditional medicines. Previous studies on Ethiopian indigenous aloes focused on documentation of phytochemical compositions and traditional uses. In this study, ADMET and drug-likeness properties of phytochemicals from Ethiopian indigenous aloes were evaluated, and pharmacophore-based profiling was done using Discovery Studio to predict therapeutic targets. The targets were examined using KEGG pathway, gene ontology and network analysis. Using random-walk with restart algorithm, network propagation was performed in CODA network to find diseases associated with the targets. As a result, 82 human targets were predicted and found …

Associations Between Mental Health And Hiv Status Among Sexual Minority And Heterosexual Adolescents In Nigeria, Morenike Oluwatoyin Folayan, Olakunle Oginni, Olanrewaju Ibikunle Ibigbami, Uma Philip, Nserd Ntonoba Mfam, Chinedu Mbam, Amos Ganyam, Agada A Salem, Christopher Osuji, Cory Bradley, Joanne Lusher, Nadia Adjoa Sam-Agudu

2020-Current year OA Pubs

BACKGROUND: We aimed to determine associations between the mental health status of adolescents by self-reported sexual identity; and to determine associations between the mental health status of sexual minority adolescents living with and without HIV.

METHODS: This cross-sectional study collected data from Nigerians aged 13-19 years old using an online survey. We collected information on dependent (sexual identity) and independent (presence of depressive symptoms, generalised anxiety disorder, suicidal attempt/ideation, HIV status) study variables. A multivariate regression model determined associations between the dependent and independent variables. A second multivariate regression model was developed to establish associations between HIV status among sexual …

The Role Of Er Stress In Diabetes: Exploring Pathological Mechanisms Using Wolfram Syndrome, Shuntaro Morikawa, Fumihiko Urano

2020-Current year OA Pubs

The endoplasmic reticulum (ER) is a cytosolic organelle that plays an essential role in the folding and processing of new secretory proteins, including insulin. The pathogenesis of diabetes, a group of metabolic disorders caused by dysfunctional insulin secretion (Type 1 diabetes, T1DM) or insulin sensitivity (Type 2 diabetes, T2DM), is known to involve the excess accumulation of "poorly folded proteins", namely, the induction of pathogenic ER stress in pancreatic β-cells. ER stress is known to contribute to the dysfunction of the insulin-producing pancreatic β-cells. T1DM and T2DM are multifactorial diseases, especially T2DM; both environmental and genetic factors are involved in …

Hif1a-Dependent Induction Of Alveolar Epithelial Pfkfb3 Dampens Acute Lung Injury, Christine U Vohwinkel, Nana Burns, Ethan Coit, Xiaoyi Yuan, Eszter K Vladar, Christina Sul, Eric P Schmidt, Peter Carmeliet, Kurt Stenmark, Eva S Nozik, Rubin M Tuder, Holger K Eltzschig

Faculty, Staff and Student Publications

Acute lung injury (ALI) is a severe form of lung inflammation causing acute respiratory distress syndrome in patients. ALI pathogenesis is closely linked to uncontrolled alveolar inflammation. We hypothesize that specific enzymes of the glycolytic pathway could function as key regulators of alveolar inflammation. Therefore, we screened isolated alveolar epithelia from mice exposed to ALI induced by injurious ventilation to assess their metabolic responses. These studies pointed us toward a selective role for isoform 3 of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3). Pharmacologic inhibition or genetic deletion of Pfkfb3 in alveolar epithelia (Pfkfb3loxP/loxP SPC-ER-Cre+ mice) was associated with profound increases in ALI during …