Public Health Commons^™

Posttranslational Modifications In Pd-L1 Turnover And Function: From Cradle To Grave, Xinfang Yu, Wei Li, Ken H Young, Yong Li

Faculty, Staff and Students Publications

Programmed death-ligand 1 (PD-L1) is one of the most classic immune checkpoint molecules. Cancer cells express PD-L1 to inhibit the activity of effector T cells' cytotoxicity through programmed death 1 (PD-1) engagement in exposure to inflammatory cytokines. PD-L1 expression levels on cancer cells might affect the clinical response to anti-PD-1/PD-L1 therapies. Hence, understanding molecular mechanisms for regulating PD-L1 expression is essential for improving the clinical response rate and efficacy of PD-1/PD-L1 blockade. Posttranslational modifications (PTMs), including phosphorylation, glycosylation, ubiquitination, and acetylation, regulate PD-L1 stability, cellular translocation, and interaction with its receptor. A coordinated positive and negative regulation via PTMs is …

Efficacy Of The Mrna-1273 Sars-Cov-2 Vaccine At Completion Of Blinded Phase, Hana M El Sahly, Lindsey R Baden, Brandon Essink, Susanne Doblecki-Lewis, Judith M Martin, Evan J Anderson, Thomas B Campbell, Jesse Clark, Lisa A Jackson, Carl J Fichtenbaum, Marcus Zervos, Bruce Rankin, Frank Eder, Gregory Feldman, Christina Kennelly, Laurie Han-Conrad, Michael Levin, Kathleen M Neuzil, Lawrence Corey, Peter Gilbert, Holly Janes, Dean Follmann, Mary Marovich, Laura Polakowski, John R Mascola, Julie E Ledgerwood, Barney S Graham, Allison August, Heather Clouting, Weiping Deng, Shu Han, Brett Leav, Deb Manzo, Rolando Pajon, Florian Schödel, Joanne E Tomassini, Honghong Zhou, Jacqueline Miller

Faculty, Staff and Students Publications

BACKGROUND: At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase. Final analyses of efficacy and safety data from the blinded phase of the trial are reported.

METHODS: We enrolled volunteers who were at high risk for Covid-19 or its complications; participants were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo, 28 days apart, at 99 centers across the United States. …

A Phase Ib Dose Escalation Trial Of Ro4929097 (A Γ-Secretase Inhibitor) In Combination With Exemestane In Patients With Er + Metastatic Breast Cancer (Mbc), Julie A. Means-Powell, Ingrid A. Mayer, Roohi Ismail-Khan, Luis Del Valle, Debra Tonetti, Vandana G. Abramson, Melinda S. Sanders, Richard M. Lush, Claudia Sorrentino, Samarpan Majumder, Lucio Miele

School of Medicine Faculty Publications

Preclinical studies: have demonstrated a complex cross-talk between Notch and estrogen signaling in ERα-positive breast cancer. Gamma-secretase inhibitors (GSIs) are investigational agents that block the cleavage and activation of Notch receptors. In animal models of endocrine-resistant breast cancer, combinations of tamoxifen and GSIs produce additive or synergistic efficacy, while decreasing the intestinal toxicity of GSIs. However, results of a clinical trial of a GSI-endocrine therapy combination in the metastatic setting have not been published to date, nor had the safety of such combinations been investigated with longer term treatment. We conducted a phase 1b dose escalation trial (NCT01149356) of GSI …

Zero Balancing: Conscious Touch And Transformation Book Review, Misty L. Rhoads

Journal of Transformative Touch

Zero Balancing: Conscious Touch and Transformation by pioneering transformative touch practitioner and teacher James McCormick is a profound and engaging textbook that teaches readers a multi-layered approach to working with the body, mind, and spirit through skilled, conscious touch.

Integrating Patient-Reported Outcomes Into Clinical Genetic Testing For Familial Hypercholesterolemia, Rachele M. Hendricks-Sturrup, Robert Block, Christine Y. Lu

Journal of Patient-Centered Research and Reviews

Patient-reported outcomes (PROs) and PRO measures (PROMs) are often used to help clinicians and researchers understand patients’ personal concerns, feelings, experiences, and perspectives following the implementation of an intervention. Notably, PROs and PROMs can inform health systems, health policy, and payers on the utility of clinical genetic testing based on each patient’s personal values, perspectives, and potential health behaviors subsequent to testing. In this topic synopsis, we discuss the underexplored role of and implications for PROs and PROMs following genetic testing for familial hypercholesterolemia (FH), an autosomal dominant genetic disorder of cholesterol metabolism that can lead to highly premature fatal …

Transmission Event Of Sars-Cov-2 Delta Variant Reveals Multiple Vaccine Breakthrough Infections, Timothy Farinholt, Harsha Doddapaneni, Xiang Qin, Vipin Menon, Qingchang Meng, Ginger Metcalf, Hsu Chao, Marie-Claude Gingras, Vasanthi Avadhanula, Paige Farinholt, Charu Agrawal, Donna M Muzny, Pedro A Piedra, Richard A Gibbs, Joseph Petrosino

Faculty, Staff and Students Publications

BACKGROUND: This study aims to identify the causative strain of SARS-CoV-2 in a cluster of vaccine breakthroughs. Vaccine breakthrough by a highly transmissible SARS-CoV-2 strain is a risk to global public health.

METHODS: Nasopharyngeal swabs from suspected vaccine breakthrough cases were tested for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) by qPCR (quantitative polymerase chain reaction) for Wuhan-Hu1 and alpha variant. Positive samples were then sequenced by Swift Normalase Amplicon Panels to determine the causal variant. GATK (genome analysis toolkit) variants were filtered with allele fraction ≥80 and min read depth 30x.

RESULTS: Viral sequencing revealed an infection cluster of …

Prevention And Screening Of Hpv Malignancies, Kristina R Dahlstrom, Andrew T Day, Erich M Sturgis

Faculty, Staff and Students Publications

It is estimated that 5% of the global cancer burden, or approximately 690,000 cancer cases annually, is attributable to human papillomavirus (HPV). Primary prevention through prophylactic vaccination is the best option for reducing the burden of HPV-related cancers. Most high-income countries (HICs) have introduced the HPV vaccine and are routinely vaccinating adolescent boys and girls. Unfortunately, although they suffer the greatest morbidity and mortality due to HPV-related cancers, many lower- and middle-income countries (LMICs) have been unable to initiate and sustain vaccination programs. Secondary prevention in the form of screening has led to substantial declines in cervical cancer incidence in …

Effects Of Hormone Replacement Therapy (Hrt) On Gene Expression In The Amyloid Processing Pathway Of Ovariectomized Rhesus Macaque Females Under An Obesogenic Diet, Megan Ball

University Honors Theses

Estrogens rapidly decline at the onset of menopause, putting women at higher risk of osteoporosis, obesity, and neurodegenerative diseases, including Alzheimer’s disease (AD). Estradiol hormone therapies (HT) have been suggested to limit these negative effects on women, with controversial findings as to their effectiveness. A study at OHSU recently found differentially expressed genes (DEGs) using RNAseq between ovariectomized/hysterectomized (OvH) old (range = 19.4–23.2 years) female rhesus macaques on HT and those on a placebo on chronic western style diet (WSD). The DEGs identified in the amyloid processing pathway of the amygdala were selected for validation using RT-qPCR because β-amyloid peptide …

Crisis Preparedness In Acute And Intensive Treatment Settings: Lessons Learned From A Year Of Covid-19, Jarrod M Leffler, Cassandra L Esposito, Elisabeth A Frazier, Michelle A Patriquin, Meredith K Reiman, Alysha D Thompson, Carl Waitz

Staff and Researcher Publications

The impact of COVID-19 changed the use and delivery of health care services, requiring an abrupt shift in treatment and staffing models 1,2. This is particularly salient in youth acute and intensive treatment services (AITS), including inpatient psychiatric hospitals (IPH), intensive outpatient programs (IOP), and partial hospitalization programs (PHP), because of challenging issues of maintaining high-quality care and a safe therapeutic milieu during increased demand for acute services,3 all while limiting transmission of COVID-19 on locked units, in close quarters, and for youths traveling back and forth to day-programs. Over the past year, AITS adapted and evolved without the ability …

Perspectives From The Society For Pediatric Research: Advice On Sustaining Science And Mentoring During Covid-19, Catherine S Forster, Suong T Nguyen, Weston T Powell, Daniel J Moore, Jacqueline Ho, Melvin B Heyman, Tara L Wenger, Fernando Gonzalez, Margaret Hostetter, Andrew Nowalk, Caroline E Rassbach, Debra Boyer, Pnina Weiss, Rebecca L Blankenburg, Jordan S Orange, Kate G Ackerman, Audrea M Burns, National Pediatric Physician-Scientist Collaborative Workgroup

Faculty, Staff and Students Publications

The COVID-19 pandemic will leave an indelible mark on the careers of current medical trainees. Given the disruptions to medical education, economic impact on institutions, and the uncertainties around future job prospects, trainees are facing unprecedented challenges. This situation is especially concerning for futures of pediatric physician-scientist trainees, where concerns regarding maintaining the pipeline were well documented prior to the emergence of COVID-19. In this Perspectives article, we leverage the unique expertise of our workgroup to address concerns of physician-scientist trainees and to provide suggestions on how to navigate career trajectories in the post-COVID-19 era. We identified and addressed four …

Atomistic Simulations And In Silico Mutational Profiling Of Protein Stability And Binding In The Sars-Cov-2 Spike Protein Complexes With Nanobodies: Molecular Determinants Of Mutational Escape Mechanisms, Gennady M. Verkhivker, Steve Agajanian, Deniz Yasar Oztas, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Structure-functional studies have recently revealed a spectrum of diverse high-affinity nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this study, we combine atomistic simulations with the ensemble-based mutational profiling of binding for the SARS-CoV-2 S-RBD complexes with a wide range of nanobodies to identify dynamic and binding affinity fingerprints and characterize the energetic determinants of nanobody-escaping mutations. Using an in silico mutational profiling approach for probing the protein stability and binding, we examine dynamics and energetics of the SARS-CoV-2 complexes with single nanobodies Nb6 and Nb20, VHH E, a pair combination VHH E + …

Associations Between Air Pollution Exposure And Empirically Derived Profiles Of Cognitive Performance In Older Women, Andrew J. Petkus, Diana Younan, Xinhui Wang, Daniel P. Beavers, Mark A. Espeland, Margaret Gatz, Tara Gruenewald, Joel D. Kaufman, Helena C. Chui, Joshua Millstein, Stephen R. Rapp, Joann E. Manson, Susan M. Resnick, Gregory A. Wellenius, Eric A. Whitsel, Keith Widaman, Jiu-Chiuan Chen

Psychology Faculty Articles and Research

Background:Elucidating associations between exposures to ambient air pollutants and profiles of cognitive performance may provide insight into neurotoxic effects on the aging brain. Objective:We examined associations between empirically derived profiles of cognitive performance and residential concentrations of particulate matter of aerodynamic diameter < 2.5 (PM2.5) and nitrogen dioxide (NO2) in older women. Method:Women (N = 2,142) from the Women’s Health Initiative Study of Cognitive Aging completed a neuropsychological assessment measuring attention, visuospatial, language, and episodic memory abilities. Average yearly concentrations of PM2.5 and NO2 were estimated at the participant’s addresses for the 3 years prior to the assessment. Latent profile structural equation models identified subgroups of women exhibiting similar profiles across tests. Multinomial regressions examined associations between exposures and latent profile classification, controlling for covariates. Result:Five latent profiles were identified: low performance across multiple domains (poor multi-domain; n = 282;13%), relatively poor verbal episodic memory (poor memory; n = 216; 10%), average performance across all domains (average multi-domain; n = 974; 45%), superior memory (n = 381; 18%), and superior attention (n = 332; 15%). Using women with average cognitive ability as the referent, higher PM2.5 (per interquartile range [IQR] = 3.64μg/m3) was associated with greater odds of being classified in the poor memory (OR = 1.29; 95% Confidence Interval [CI] = 1.10–1.52) or superior attention (OR = 1.30; 95% CI = 1.10–1.53) profiles. NO2 (per IQR = 9.86 ppb) was associated with higher odds of being classified in the poor memory (OR = 1.38; 95% CI = 1.17–1.63) and lower odds of being classified with superior memory (OR = 0.81; 95% CI = 0.67–0.97). Conclusion:Exposure to PM2.5 and NO2 are associated with patterns of cognitive performance characterized by worse verbal episodic memory relative to performance in other domains.

Validation Of An Electronic Trigger To Measure Missed Diagnosis Of Stroke In Emergency Departments, Viralkumar Vaghani, Li Wei, Umair Mushtaq, Dean F Sittig, Andrea Bradford, Hardeep Singh

Faculty, Staff and Students Publications

OBJECTIVE: Diagnostic errors are major contributors to preventable patient harm. We validated the use of an electronic health record (EHR)-based trigger (e-trigger) to measure missed opportunities in stroke diagnosis in emergency departments (EDs).

METHODS: Using two frameworks, the Safer Dx Trigger Tools Framework and the Symptom-disease Pair Analysis of Diagnostic Error Framework, we applied a symptom-disease pair-based e-trigger to identify patients hospitalized for stroke who, in the preceding 30 days, were discharged from the ED with benign headache or dizziness diagnoses. The algorithm was applied to Veteran Affairs National Corporate Data Warehouse on patients seen between 1/1/2016 and 12/31/2017. Trained …

Deviating From The Zero Balancing Protocol, John Hamwee

Journal of Transformative Touch

When is it appropriate to deviate from the Zero Balancing protocol? John Hamwee shares when there are exceptions to the rule and the times it makes more sense to deviate from the protocol than to observe it.

Ankyrin-Dependent Na+ Channel Clustering Prevents Neuromuscular Synapse Fatigue, Chuansheng Zhang, Abhijeet Joshi, Yanhong Liu, Ozlem Sert, Seth G Haddix, Lindsay H Teliska, Anne Rasband, George G Rodney, Matthew N Rasband

Faculty, Staff and Students Publications

Skeletal muscle contraction depends on activation of clustered acetylcholine receptors (AchRs) and muscle-specific Na+ channels (Nav1.4). Some Nav1.4 channels are highly enriched at the neuromuscular junction (NMJ) and their clustering is thought to be essential for effective muscle excitation. However, this has not been experimentally tested, and how NMJ Na+ channels are clustered is unknown. Here, using muscle-specific AnkyrinR, AnkyrinB, and AnkyrinG single, double, and triple-conditional knockout mice we show that Nav1.4 channels fail to cluster only after deletion of all three ankyrins. Remarkably, ankyrin-deficient muscles have normal NMJ morphology, AchR clustering, sarcolemmal levels of Nav1.4, and muscle force, and …

Dna-Encoded Chemistry Technology Yields Expedient Access To Sars-Cov-2m Pro Inhibitors, Srinivas Chamakuri, Shuo Lu, Melek Nihan Ucisik, Kurt M Bohren, Ying-Chu Chen, Huang-Chi Du, John C Faver, Ravikumar Jimmidi, Feng Li, Jian-Yuan Li, Pranavanand Nyshadham, Stephen S Palmer, Jeroen Pollet, Xuan Qin, Shannon E Ronca, Banumathi Sankaran, Kiran L Sharma, Zhi Tan, Leroy Versteeg, Zhifeng Yu, Martin M Matzuk, Timothy Palzkill, Damian W Young

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed more than 4 million humans globally, but there is no bona fide Food and Drug Administration–approved drug-like molecule to impede the COVID-19 pandemic. The sluggish pace of traditional therapeutic discovery is poorly suited to producing targeted treatments against rapidly evolving viruses. Here, we used an affinity-based screen of 4 billion DNA-encoded molecules en masse to identify a potent class of virus-specific inhibitors of the SARS-CoV-2 main protease (Mpro) without extensive and time-consuming medicinal chemistry. CDD-1714, the initial three-building-block screening hit (molecular weight [MW] = 542.5 g/mol), was a potent inhibitor (inhibition …

Theoretical Mediators Of Diabetes Risk And Quality Of Life Following A Diabetes Prevention Program For Latino Youth With Obesity, Erica G Soltero, Stephanie L Ayers, Marvyn A Avalos, Armando Peña, Allison N Williams, Micah L Olson, Yolanda P Konopken, Felipe G Castro, Kimberly J Arcoleo, Colleen S Keller, Donald L Patrick, Justin Jager, Gabriel Q Shaibi

Children’s Nutrition Research Center Staff Publications

Purpose: This study tested self-efficacy and social support for activity and dietary changes as mediators of changes in type 2 diabetes related outcomes following a lifestyle intervention among Latino youth.

Setting and intervention: Latino adolescents (14-16 years) with obesity (BMI% = 98.1 ± 1.4) were randomized to a 3-month intervention (n = 67) that fostered self-efficacy and social support through weekly, family-centered sessions or a comparison condition (n = 69).

Measures: Primary outcomes included insulin sensitivity and weight specific quality of life. Mediators included self-efficacy, friend, and family social support for health behaviors. Data was collected at baseline, 3-months, 6-months, …

Challenges In Feeding Children Posed By The Covid-19 Pandemic: A Systematic Review Of Changes In Dietary Intake Combined With A Dietitian's Perspective, Heather Campbell, Alexis C Wood

Children’s Nutrition Research Center Staff Publications

Purpose of review: To examine the evidence that the dietary quality of children changed between the period preceding the COVID-19 pandemic and the first year during the pandemic.

Recent findings: A systematic review of the evidence for dietary changes occurring as a result of the pandemic-related restrictions, in Part I of this article, yielded 38 original research articles. These articles had conflicting results, some describing improvements in overall quality and some describing deteriorations. As a whole the studies were characterized by a low study quality, and children were poorly represented. Taken together, these studies do not provide enough evidence to …

Exome Sequence Association Study Of Levels And Longitudinal Change Of Cardiovascular Risk Factor Phenotypes In European Americans And African Americans From The Atherosclerosis Risk In Communities Study, Elena V Feofanova, Elise Lim, Han Chen, Minjae Lee, Ching-Ti Liu, L Adrienne Cupples, Eric Boerwinkle

Faculty, Staff and Student Publications

Cardiovascular disease (CVD) is responsible for 31% of all deaths worldwide. Among CVD risk factors are age, race, increased systolic blood pressure (BP), and dyslipidemia. Both BP and blood lipids levels change with age, with a dose-dependent relationship between the cumulative exposure to hyperlipidemia and the risk of CVD. We performed an exome sequence association study using longitudinal data with up to 7805 European Americans (EAs) and 3171 African Americans (AAs) from the Atherosclerosis Risk in Communities (ARIC) study. We assessed associations of common (minor allele frequency > 5%) nonsynonymous and splice-site variants and gene-based sets of rare variants with levels …

Genetic Testing Reveals Germline Mutations Among Patients Undergoing Surgery For Colorectal Carcinoma In A Community Hospital Setting, Alex R. Jones, Dana Greer Rn, Bsn, Ocn, Karin L. Cole Md

Journal of Maine Medical Center

Introduction: Defined germline mutations contribute to 5% to 10% of cases of colorectal carcinoma (CRC). While protocols for universal tumor screening have been adopted to detect mismatch repair (MMR) protein deficiency, widespread multigene panel testing has not been achieved. Barriers to implementing testing protocols may occur in community settings.

Methods: A total of 160 patients presenting for surgical management of CRC between 2011 and 2020 were considered for retrospective analysis in a single-surgeon, single-institution, community-based cohort. The rate of multigene panel testing and prevalence of germline mutations were calculated, and patient characteristics were assessed.

Results: A total of 32/160 (20%) …

Apobec Mutagenesis Is Concordant Between Tumor And Viral Genomes In Hpv-Positive Head And Neck Squamous Cell Carcinoma, Daniel L. Faden, Krystle A. Lang Kuhs, Maoxuan Lin, Adam Langenbucher, Maisa Pinheiro, Meredith Yeager, Michael Cullen, Joseph F. Boland, Mia Steinberg, Sara Bass, James S. Lewis, Michael S. Lawrence, Robert L. Ferris, Lisa Mirabello

Epidemiology and Environmental Health Faculty Publications

APOBEC is a mutagenic source in human papillomavirus (HPV)-mediated malignancies, including HPV+ oropharyngeal squamous cell carcinoma (HPV + OPSCC), and in HPV genomes. It is unknown why APOBEC mutations predominate in HPV + OPSCC, or if the APOBEC-induced mutations observed in both human cancers and HPV genomes are directly linked. We performed sequencing of host somatic exomes, transcriptomes, and HPV16 genomes from 79 HPV + OPSCC samples, quantifying APOBEC mutational burden and activity in both host and virus. APOBEC was the dominant mutational signature in somatic exomes. In viral genomes, there was a mean of five (range 0–29) mutations per …

Use Of Telehealth In Home-Based End-Of-Life Care For Children In Rural Regions, Meaghann S. Weaver

Theses & Dissertations

A national shortage in pediatric-trained providers results in certain geographies, primarily rural, where children with special needs are not able to access home-based care at their end-of-life. Advances in technology have made the use of telemedicine a potential modality for palliative care subspecialty clinicians to provide clinical care and support for adult-trained hospice teams. This dissertation utilizes four approaches to consider telehealth as an unexplored opportunity in care delivery: (1) a systematic review of telehealth measures and instruments to select the Technology Acceptance Model as a validated metric of telehealth acceptance uniquely now applied to pediatric care; (b) a pilot …

Polyploid Giant Cancer Cells And Ovarian Cancer: New Insights Into Mitotic Regulators And Polyploidy†, Joanne S Richards, Nicholes R Candelaria, Rainer B Lanz

Faculty, Staff and Students Publications

Current first-line treatment of patients with high-grade serous ovarian cancer (HGSOC) involves the use of cytotoxic drugs that frequently lead to recurrent tumors exhibiting increased resistance to the drugs and poor patient survival. Strong evidence is accumulating to show that HGSOC tumors and cell lines contain a subset of cells called polyploidy giant cancer cells (PGCCs) that act as stem-like, self-renewing cells. These PGCCs appear to play a key role in tumor progression by generating drug-resistant progeny produced, in part, as a consequence of utilizing a modified form of mitosis known as endoreplication. Thus, developing drugs to target PGCCs and …

Gestational Weight Gain In 4 Low- And Middle-Income Countries And Associations With Birth Outcomes: A Secondary Analysis Of The Women First Trial., Melissa S Bauserman, Carla M Bann, K Michael Hambidge, Ana L Garces, Lester Figueroa, Jamie L Westcott, Jackie K Patterson, Elizabeth M Mcclure, Vanessa R Thorsten, Sumera Ali Aziz, Sarah Saleem, Robert L Goldenberg, Richard Derman, Veena Herekar, Manjunath Somannavar, Marion W Koso-Thomas, Adrien L Lokangaka, Antoinette K Tshefu, Nancy F Krebs, Carl L Bose, Shivaprasad Goudar, Sangappa Dhaded, Bhalchandra Kodkany, Omrana Pasha, Abhik Das, Menachem Miodovnik, N K Raju Tonse

Global Health Articles

BACKGROUND: Adequate gestational weight gain (GWG) is essential for healthy fetal growth. However, in low- and middle-income countries, where malnutrition is prevalent, little information is available about GWG and how it might be modified by nutritional status and interventions.

OBJECTIVE: We describe GWG and its associations with fetal growth and birth outcomes. We also examined the extent to which prepregnancy BMI, and preconception and early weight gain modify GWG, and its effects on fetal growth.

METHODS: This was a secondary analysis of the Women First Trial, including 2331 women within the Democratic Republic of Congo (DRC), Guatemala, India, and Pakistan, …

Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants In The Chrebp (Carbohydrate Responsive Element Binding Protein) Locus And Hdl-C (High-Density Lipoprotein Cholesterol) And Triglyceride Concentrations, Danielle E Haslam, Gina M Peloso, Melanie Guirette, Fumiaki Imamura, Traci M Bartz, Achilleas N Pitsillides, Carol A Wang, Ruifang Li-Gao, Jason M Westra, Niina Pitkänen, Kristin L Young, Mariaelisa Graff, Alexis C Wood, Kim V E Braun, Jian'an Luan, Mika Kähönen, Jessica C Kiefte-De Jong, Mohsen Ghanbari, Nathan Tintle, Rozenn N Lemaitre, Dennis O Mook-Kanamori, Kari North, Mika Helminen, Yasmin Mossavar-Rahmani, Linda Snetselaar, Lisa W Martin, Jorma S Viikari, Wendy H Oddy, Craig E Pennell, Frits R Rosendall, M Arfan Ikram, Andre G Uitterlinden, Bruce M Psaty, Dariush Mozaffarian, Jerome I Rotter, Kent D Taylor, Terho Lehtimäki, Olli T Raitakari, Kara A Livingston, Trudy Voortman, Nita G Forouhi, Nick J Wareham, Renée De Mutsert, Steven S Rich, Joann E Manson, Samia Mora, Paul M Ridker, Jordi Merino, James B Meigs, Hassan S Dashti, Daniel I Chasman, Alice H Lichtenstein, Caren E Smith, Josée Dupuis, Mark A Herman, Nicola M Mckeown

Faculty, Staff and Students Publications

BACKGROUND: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the

METHODS: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near

RESULTS: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers …

Post-Acute Sequelae Of Covid-19 (Pasc): Association With Inflammation And Autoimmunity, Raghava S. Ambadapoodi, Fnu Deepti, Javaria Anwer Mbbs, Rafael Fernandez-Botran

The University of Louisville Journal of Respiratory Infections

It has become increasingly evident that a high percentage of patients that recover from acute COVID-19 infection continue to suffer from a variety of persistent symptoms even months after viral clearance, the most common ones being fatigue, dyspnea, anosmia, dysgeusia, cognitive dysfunction, and psychological problems, including anxiety and depression. This syndrome, known as Post-acute sequelae of COVID-19 (PASC), can severely affect the life quality and represents an important health care concern. The exact causes for the symptoms observed in patients with PASC remain to be adequately characterized, but are likely to be associated with multiple factors, including residual disease and/or …

Triple Negative Breast Cancer In An Appalachian Region: Exponential Tumor Grade Increase With Age Of Diagnosis, Gina Sizemore, Toni Marie Rudisill

Journal of Appalachian Health

Introduction: Triple negative breast cancer is an aggressive breast cancer with decreased five-year survival, increased risk for recurrence, and higher risk for metastases. Unlike other breast cancers, it has no targeted treatment and has heterogeneous genetics which make classification and treatment difficult.

Purpose: The purpose of our research was to compare triple negative breast cancer to non-triple negative breast cancer to identify key epidemiologic factors that might lead to improved basic science directives for biomarkers, treatments, and classification.

Methods: The state cancer registry was used to provide the first West Virginia state-wide population evaluation of triple negative breast cancer.

Results: …

Covid-19 Deliveries: Maternal Features And Neonatal Outcomes, Viviana Zlochiver, Blair Tilkens, Ana Cristina Perez Moreno, Fatima Aziz, M. Fuad Jan

Journal of Patient-Centered Research and Reviews

Integrated, data-driven criteria are necessary to evaluate delivery outcomes in pregnancies affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the ongoing COVID-19 pandemic. This study analyzed maternal demographics, clinical characteristics, treatments, and delivery outcomes of 85 ethnically diverse, adult pregnant women who tested positive for SARS-CoV-2 at the time of delivery. Median maternal and gestational ages were 27 years (interquartile range [IQR]: 23–31) and 39 weeks (IQR: 37.3–40.0), respectively. Of the 85 SARS-CoV-2–positive participants, 67 (79%) had no COVID-19 symptoms at the time of routine COVID-19 admission testing, 14 (16%) reported mild COVID-19 symptoms, and 4 (5%) presented …

Reducing Covid-19 Quarantine With Sars-Cov-2 Testing: A Simulation Study, Bo Peng, Wen Zhou, Rowland W Pettit, Patrick Yu, Peter G Matos, Alexander L Greninger, Julie Mccashin, Christopher I Amos

Faculty, Staff and Students Publications

OBJECTIVE: To evaluate the effectiveness of SARS-CoV-2 testing on shortening the duration of quarantines for COVID-19 and to identify the most effective choices of testing schedules.

DESIGN: We performed extensive simulations to evaluate the performance of quarantine strategies when one or more SARS-CoV-2 tests were administered during the quarantine. Simulations were based on statistical models for the transmissibility and viral loads of SARS-CoV-2 infections and the sensitivities of available testing methods. Sensitivity analyses were performed to evaluate the impact of perturbations in model assumptions on the outcomes of optimal strategies.

RESULTS: We found that SARS-CoV-2 testing can effectively reduce the …

Baricitinib In The Treatment Of A Critical Patient With Covid-19 Pneumonia: A Case Report, Nishant Patel, Dylan Goldsmith, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

A 72-year-old male presented to the emergency department with a chief complaint of diarrhea after having tested positive for COVID-19 two days prior. He initially had minimal respiratory complaints, but was eventually transferred to the intensive care unit for acute hypoxic respiratory failure. In addition to dexamethasone, remdesivir, and antibiotics, the patient was treated with baricitinib, a Janus kinase inhibitor that was recently granted emergency use authorization by the Food and Drug Administration for treatment of hospitalized patients with COVID-19. He had an extensive and complicated hospital course and had to be placed on mechanical ventilation, ultimately undergoing tracheostomy. After …