Medicine and Health Sciences Commons^™

Atherosclerotic Cardiovascular Disease In Gulf War Veterans In Relation To Deployment Exposures, Sarah T Ahmed, Ruosha Li, Lea Steele, Peter Richardson, Kellie Sims, Rachel Quaden, Kelly M Harrington, Vijay Nambi, John M Gaziano, Robert Morgan, George L Delclos, Drew A Helmer

Faculty, Staff and Students Publications

Many 1990-1991 Gulf War Veterans (GWVs) were exposed to toxicants and environmental hazards during deployment, including oil well fire smoke, chemical/biological agents, pyridostigmine bromide (PB) pills, and pesticides. Multiple constituents of smoke are associated with increased risk for atherosclerotic cardiovascular diseases (ASCVD), and other toxic exposures have been associated with autonomic and lipid dysfunction. We used data from the Gulf War Era Cohort and Biorepository Study of veterans deployed to Gulf War in 1990-1991 (n = 942). We evaluated the association of deployment exposures (no, yes (1-6 days), (7-30 days), (31 + days), and not sure) with clinical risk factors …

A Prospective, Randomized, Controlled Clinical Trial Of High-Frequency Electromagnetic Coupling Powered Permanent Peripheral Nerve Stimulator For The Treatment Of Chronic Craniofacial Pain, Salim M Hayek, Nameer Haider, Ashwin Viswanathan, Mehul Desai, Jeffrey Rosenberg, Niek E Vanquathem

Faculty, Staff and Students Publications

than one-fifth of the US population. While various medications and conservative treatment modalities are available for this condition, many patients have refractory symptoms. These patients suffer from social impairment, reduced quality of life, and increased financial burdens.

Objective: The objective of this study was to examine the clinical outcomes of patients receiving a permanent, high-frequency electromagnetic coupling (HF-EMC) powered peripheral nerve stimulator (PNS) system for the treatment of chronic craniofacial neuropathic pain.

Study design: This study was a multicenter, randomized, controlled clinical trial conducted under an investigational device exemption (IDE).

Setting: This study was conducted in 7 clinical sites in …

Generation Of Induced Pluripotent Stem Cell Lines (Rfsci003-A, Rfsci004-A) From Monozygotic Twins Discordant For Age-Related Macular Degeneration, Naresh Rajendran, Wendy Runyon, Sam Hu, Ajeet Singh, Rinki Ratnapriya, Ritu Kumar, Karl Csaky, Srinivasa R Sripathi

Faculty, Staff and Students Publications

Age-related macular degeneration (AMD) has significant genetic component, yet monozygotic twins frequently exhibit discordance in disease status, highlighting the role of non-genetic factors. To enable comparative studies of AMD pathogenesis, we generated two induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells (PBMCs) of a monozygotic twin pair discordant for AMD. These iPSC lines offer a unique genetically matched resource to investigate molecular differences between affected and unaffected twins, as well as their responses to genetic, epigenetic, and environmental contributors to AMD development.

Steroids For Pediatric Adenotonsillectomy Pain-A Prospective Multicenter Randomized Trial, Kevin D Pereira, Wiktoria A Gocal, Anna V Borodianski, Mary E Williamson, Hengameh K Behzadpour, Sonal Saraiya, Diego A Preciado, Amal Isaiah

Faculty, Staff and Students Publications

Objective: To compare postoperative caregiver-reported pain control of two steroid regimens following pediatric adenotonsillectomy. Secondary objectives assessed differences in analgesic use, return to normal diet, caregiver calls, adverse effects, and emergency room (ER) visits.

Study design: Prospective randomized pragmatic trial.

Setting: Three academic tertiary care children's hospitals.

Methods: Healthy children aged 3 to 10 undergoing adenotonsillectomy were recruited and randomly assigned to receive either 0.6 mg/kg dexamethasone on postoperative day 3 or prednisolone 0.5 mg/kg days 1 to 3. Both groups continued standard weight-based regimens of acetaminophen and ibuprofen. A blinded research team member performed postoperative telephone surveys using the …

Acute Loss Of Tactile Input Leads To General Compensatory Changes In Eye-Hand Coordination During Object Manipulation, Kevin Ung, John F Magnotti, Brandon Kim, Jeffrey M Yau, Per F Nordmark

Faculty, Staff and Students Publications

Current models of motor control emphasize the critical role of sensory feedback, as demonstrated by movement coordination deficits following sensory impairment. When both vision and touch are available for object-oriented manual behaviors, they serve distinct roles; vision guides the execution of planned movements, while touch provides more direct feedback on hand-object interactions. The impact of losing somatosensory feedback on eye-hand coordination during dexterous object manipulation tasks has not been thoroughly studied. Conceivably, vision is recruited to compensate for the feedback lost when touch is abolished based on the dexterity demands of the behavior. To investigate this, we tested healthy participants …

2d Speckle Tracking Strain Echocardiography In Multisystem Inflammatory Syndrome In Children: A Multicenter Analysis From The Music Study, Francesca Sperotto, Valiantsina Kazlova, Felicia L Trachtenberg, Dongngan T Truong, Sanjeev Aggarwal, Joseph R Block, Tamara T Bradford, Sujatha Buddhe, Audrey Dionne, Andreea Dragulescu, Kanwal M Farooqi, Daniel E Forsha, Therese M Giglia, Ian F Golding, Keren Hasbani, Pei-Ni Jone, Anita Krishnan, Sean M Lang, Carol A Mcfarland, Elizabeth C Mitchell, Elias Moussi Saad, Todd T Nowlen, Ricardo H Pignatelli, Scott Pletzer, Ryan Serrano, Divya Shakti, Shubhika Srivastava, Thor Thorsson, Jodie K Votava-Smith, Hunter C Wilson, Jane W Newburger, Kevin G Friedman

Faculty, Staff and Students Publications

Background: 2D-speckle tracking echocardiography may help detect subclinical ventricular dysfunction, but data in multisystem inflammatory syndrome in children (MIS-C) are scarce. We investigated left ventricular (LV) strain parameters in MIS-C and their association with outcomes.

Methods: We performed an ambi-directional, 32-center cohort study on hospitalized patients with MIS-C (March 2020-November 2021) with at least 1 echocardiogram read by the Core Lab. Generalized estimating equation modeling was used to test associations between LV strain and a composite in-hospital adverse cardiovascular outcome (vasoactive support, arrhythmias, cardiac arrest, extracorporeal support, death, or heart transplant).

Results: Of 349 patients (median age, 8.7 years [interquartile …

A Multi-Institutional Multi-Methods Analysis Of Jeopardy Systems In Academic Hospital Medicine, Kirsten N Kangelaris, Angela Keniston, Andrew D Auerbach, Gregory Bowling, Marisha Burden, Shradha A Kulkarni, Luci K Leykum, Anne S Linker, Matthew Sakumoto, Jeffrey Schnipper, Gopi Astik

Faculty, Staff and Students Publications

Background: Hospital medicine programs use backup ("jeopardy") systems to cover unexpected staffing gaps, but little is known about their structures or optimal practices.

Objectives: To describe jeopardy structures, assess clinician perceptions, and identify potential approaches across a broad sample of hospital medicine groups.

Methods: This multi-methods study, conducted within a national hospitalist consortium, used virtual focus groups and an email survey to (1) describe the presence and structure of jeopardy systems and (2) explore features perceived as fair, equitable, and tolerable. Rapid qualitative analysis identified major themes, while descriptive methods analyzed survey data.

Results: Twenty-five individuals participated in focus groups, …

Comparative Effectiveness Of Less Vs More Frequent Hydrocortisone Dosing In Septic Shock, Alan Hao, Tianshi David Wu, Keegan Collins, Danielle Guffey, Rebecca Kessinger, Meghna Vallabh, Ali Omranian

Faculty, Staff and Students Publications

Objectives: Guidelines recommend hydrocortisone as an adjunctive treatment in septic shock, but the optimal dosing regimen is unknown. A national shortage of hydrocortisone in 2023 prompted a change in institutional practice for hydrocortisone administration from 50 mg every 6 hours to 100 mg every 12 hours in an effort to reduce waste and conserve vials, creating an opportunity to evaluate the comparative effectiveness of these two regimens. The primary efficacy outcome was time to shock resolution, and secondary outcomes evaluated in this study were mortality, renal replacement therapy (RRT), medication costs, and maximum vasopressor dose attained.

Design: Single-center, retrospective cohort …

Optimal Head-Of-Bed Positioning Before Thrombectomy In Large Vessel Occlusion Stroke: A Randomized Clinical Trial, Anne W Alexandrov, Anne J Shearin, Pitchaiah Mandava, Gabriel Torrealba-Acosta, Cheran Elangovan, Balaji Krishnaiah, Katherine Nearing, Elizabeth Robinson, Cara Guthrie-Chu, Matthew Holzmann, Bryan Fill, Dharti R Trivedi, Alicia Richardson, Sandy Middleton, Barbara B Brewer, David S Liebeskind, Nitin Goyal, James C Grotta, Andrei V Alexandrov

Faculty, Staff and Students Publications

Importance: Small studies show that 0° head positioning of patients with large vessel occlusion (LVO) stroke improves penumbral blood flow and clinical stability. Understanding whether 0° head position maintains clinical stability would allow for optimal patient positioning before thrombectomy.

Objective: To determine superiority of 0° over 30° head positioning at maintaining clinical stability in patients with LVO before thrombectomy.

Design, setting, and participants: This was a prospective randomized clinical trial with blinding to study enrollment/end points conducted from May 2018 to November 2023. There were 3 planned interim analyses, and the study was conducted at certified thrombectomy hospitals in the …

Cognitive Performance In Early Neuronal Synuclein Disease With Hyposmia But Without Motor Disability: Association With Dopamine Deficiency And Isolated Rapid Eye Movement Sleep Behavior Disorder, Daniel Weintraub, Anuprita R Nair, Ryan Kurth, Michael C Brumm, Christine Kohnen, Michele K York, Roseanne D Dobkin, Kenneth Marek, Caroline Tanner, Tanya Simuni, Andrew Siderowf, Douglas Galasko, Lana M Chahine, Christopher Coffey, Kalpana Merchant, Kathleen L Poston, Tatiana Foroud, Brit Mollenhauer, Ethan G Brown, Karl Kieburtz, Mark Frasier, Sohini Chowdhury, Roy N Alcalay, Aleksandar Videnovic, Parkinson's Progression Markers Initiative

Faculty, Staff and Students Publications

Objective: To determine the impact of dopamine deficiency and isolated rapid eye movement (REM) sleep behavior disorder (iRBD) on cognitive performance in early neuronal α-synuclein disease (NSD) with hyposmia but without motor disability.

Methods: Using Parkinson's Progression Markers Initiative baseline data, cognitive performance was assessed with a cognitive summary score (CSS) derived from robust healthy control (HC) norms. Performance was examined for participants with hyposmia in early NSD-Integrated Staging System (NSD-ISS), either stage 2A (cerebrospinal fluid α-synuclein seed amplification assay [SAA]+, dopamine transporter scan [DaTscan]-) or 2B (SAA+, DaTscan+).

Results: Participants were stage 2A (n = 101), stage 2B (N …

Cmr Findings In The Long-Term Outcomes After Multisystem Inflammatory Syndrome In Children (Music) Study, Sean M Lang, Dongngan T Truong, Andrew J Powell, Valiantsina Kazlova, Jane W Newburger, Jordan D Awerbach, Edem Binka, Tamara T Bradford, Mark Cartoski, Andrew Cheng, Michael P Dilorenzo, Audrey Dionne, Adam L Dorfman, Matthew D Elias, Olukayode Garuba, Jennifer F Gerardin, Keren Hasbani, Pei-Ni Jone, Christopher Z Lam, Nilanjana Misra, Lerraughn M Morgan, Arni Nutting, Jyoti K Patel, Joshua D Robinson, Eleanor L Schuchardt, Kristen Sexson Tejtel, Gautam K Singh, Timothy C Slesnick, Felicia Trachtenberg, Michael D Taylor, Music Study Investigators

Faculty, Staff and Students Publications

Background: Multisystem Inflammatory Syndrome in Children is characterized by high rates of acute cardiovascular involvement with rapid recovery of organ dysfunction. However, information regarding long-term sequelae is lacking. We sought to characterize the systolic function and myocardial tissue properties using cardiac magnetic resonance (CMR) imaging in a multicenter observational cohort of patients with Multisystem Inflammatory Syndrome in Children.

Methods: In this observational cohort study, comprising 32 centers in North America, CMR studies were analyzed by a core laboratory to assess ventricular volumetric data, tissue characterization, and coronary involvement.

Results: A total of 263 CMRs from 255 patients with Multisystem Inflammatory …

Eugenics And Polygenic Embryo Screening: Public, Clinician, And Patient Perceptions Of Conditions Versus Traits, Dorit Barlevy, Rémy A Furrer, Asha Kalapatapu, Abigail Martinez, Todd Lencz, Shai Carmi, Gabriel Lázaro-Muñoz, Stacey Pereira

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Polygenic embryo screening (PES) estimates an embryo's genetic chances of developing complex conditions (eg, cancer) and traits (eg, height). Stakeholders have raised concerns that PES promotes eugenic practices and ideology.

Methods: We surveyed a nationally representative sample of the US public on approval of screening embryos for 12 conditions and 12 traits and examined the association between disapproval and concern about eugenics. We also conducted semistructured interviews with US-based reproductive endocrinology and infertility specialists and patients undergoing in vitro fertilization on their perspectives toward PES.

Results: Among the US public (n = 1423), disapproval of screening embryos for traits …

Coenzyme Q Headgroup Intermediates Can Ameliorate A Mitochondrial Encephalopathy, Guangbin Shi, Claire Miller, Sota Kuno, Alejandro G Rey Hipolito, Salsabiel El Nagar, Giulietta M Riboldi, Megan Korn, Wyatt C Tran, Zixuan Wang, Lia Ficaro, Tao Lin, Quentin Spillier, Begoña Gamallo-Lana, Drew R Jones, Matija Snuderl, Soomin C Song, Adam C Mar, Alexandra L Joyner, Roy V Sillitoe, Robert S Banh, Michael E Pacold

Duncan NRI Faculty and Staff Publications

Decreased brain levels of coenzyme Q10 (CoQ10), an endogenously synthesized lipophilic antioxidant1,2, underpin encephalopathy in primary CoQ10 deficiencies3,4 and are associated with common neurodegenerative diseases and the ageing process5,6. CoQ10 supplementation does not increase CoQ10 pools in the brain or in other tissues. The recent discovery of the mammalian CoQ10 headgroup synthesis pathway, in which 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL) makes 4-hydroxymandelate (4-HMA) to synthesize the CoQ10 headgroup precursor 4-hydroxybenzoate (4-HB)7, offers an opportunity to pharmacologically restore CoQ10 synthesis and mechanistically treat CoQ10 deficiencies. To test whether 4-HMA …

Heightened Risk: Childhood Trauma And Anticipatory Grief Exacerbate The Impact Of Loneliness On Depressive Symptoms And Lps-Stimulated Cytokines In Dementia Caregivers, Kelly N Brice, Jensine Paoletti-Hatcher, E Lydia Wu-Chung, Vincent D Lai, Daniel L Argueta, Michelle A Chen, Itee Mahant, Bryan T Denny, Charles Green, Luis D Medina, Paul Schulz, Jennifer Stinson, Samantha K Henry, Cobi Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

Dementia spousal caregivers are at a disproportionate risk for adverse mental and physical health outcomes. Loneliness is associated with depressive symptoms and proinflammatory cytokine production among caregivers. Additionally, childhood trauma, anticipatory grief, and poor sleep quality are all associated with enhanced stress reactivity. This study used a cross-sectional design to investigate whether loneliness is associated with proinflammatory cytokine production and depressive symptoms in caregivers, and whether these relationships are strongest among caregivers who report high levels of childhood trauma, high amounts of anticipatory grief, or poor sleep quality. A sample of 111 dementia spousal caregivers provided blood samples and completed …

Walking Interventions And Cognitive Health In Older Adults: A Systematic Review Of Randomized Controlled Trials, Jongwon Lee, Delia West, Christine Pellegrini, Jingkai Wei, Sara Wilcox, Jean Neils-Strunjas, A Caroline Rudisill, Daniela B Friedman, David X Marquez, Jenna Dzwierzynski, Joyce Balls-Berry, Rachelle Gajadhar, Chih-Hsiang Yang

2020-Current year OA Pubs

ObjectiveThis systematic review summarizes the effectiveness and the dose of walking interventions on specific cognition domains in older adults, including executive function, memory, attention, processing speed, and global cognition.Data sourcePublished randomized controlled trials in PubMed, Embase, and Web of Science until 10 May 2023.Study Inclusion and Exclusion CriteriaStudies include older adults without Alzheimer's or related dementias, involving a walking intervention and performance-based neuropsychological assessments for executive function, memory, processing speed, attention, or global cognition.Data ExtractionTwo independent research assistants reviewed 8424 studies and included 17 studies.Data SynthesisParticipant demographics, intervention features (type, intensity, time, frequency, duration, format, and context), cognitive assessment tools, …

Inflammatory Pain In Mice Induces Light Cycle-Dependent Effects On Sleep Architecture, Dominika J Burek, Khairunisa Mohamad Ibrahim, Andrew G Hall, Ashish Sharma, Jessica A Cucinello-Ragland, Erik S Musiek, Jose A Morón, William A Carlezon Jr

2020-Current year OA Pubs

Pain syndromes include physical, sensory, emotional, and cognitive symptoms such as disability, negative affect, feelings of stress, and fatigue. Experimental induction of long-term inflammatory pain in rodents by hindpaw injection of complete Freund's adjuvant (CFA) produces anhedonia and dysregulated naturalistic behaviors, similar to the effects of unregulated stress. We examined whether these similarities extend to changes in sleep and rhythms, such as those induced by chronic social defeat stress, using actigraphy and wireless EEG in mice. Comparisons were made between groups that received injections at the onset of the light or dark phase. We found that CFA-induced inflammatory pain alters …

Dual-Vector Raavrh8 Gene Therapy For Gm2 Gangliosidosis: A Phase 1/2 Trial, Florian Eichler, Xuntian Jiang, Et Al.

2020-Current year OA Pubs

The dual rAAVrh8-HEXA and rAAVrh8-HEXB vector can restore central nervous system hexosaminidase (Hex) enzyme activity, decrease GM2 levels in cerebrospinal fluid and rescue phenotypic consequences of GM2 gangliosidosis, Tay-Sachs and Sandhoff diseases in animal models following simultaneous bi-thalamic (BiT) injections. Following up on an n = 2 expanded access trial, we initiated a phase 1/2, single-dose, dose-escalation of combined BiT, intra-cisterna magna and intrathecal infusion in children with Tay-Sachs and Sandhoff diseases (six infantile, three juvenile). The BiT injection volume and vector dose were doubled between four cohorts, with the lowest dose matching the earlier expanded access trial. Cerebrospinal fluid …

Bacterial Vaginosis Toxins Impair Sperm Capacitation And Fertilization, Shweta Bhagwat, Leila Asadi, Ronald Mccarthy, Juan Ferreira, Ping Li, Ethan Li, Sariela Spivak, Ariana Gaydon, Vaka Reddy, Christy Armstrong, Sydney R Morrill, Hillary Zhou, Amanda L Lewis, Warren G Lewis, Celia M Santi

2020-Current year OA Pubs

STUDY QUESTION: What effect do toxins produced by bacterial vaginosis (BV) bacteria have on sperm function?

SUMMARY ANSWER: BV toxins dysregulate sperm capacitation and intracellular calcium homeostasis, and impair the ability of sperm to fertilize oocytes.

WHAT IS KNOWN ALREADY: In BV, which is linked to infertility, overgrowth of Prevotella and Gardnerella in the vagina is accompanied by elevated concentrations of the toxins lipopolysaccharide (LPS) and vaginolysin (VLY).

STUDY DESIGN, SIZE, DURATION: This was a laboratory study in which human semen samples were collected from consenting healthy donors with normal semen parameters. Mouse sperm samples were obtained from the caudal …

Acad10 And Acad11 Enable Mammalian 4-Hydroxy Acid Lipid Catabolism, Edrees H Rashan, Abigail K Bartlett, Jingying Zhang, Andrew J Smith, Zakery N Baker, Patrick Forny, Peng Yuan, David J Pagliarini, Et Al.

2020-Current year OA Pubs

Fatty acid β-oxidation is a central catabolic pathway with broad health implications. However, various fatty acids, including 4-hydroxy acids (4-HAs), are largely incompatible with β-oxidation machinery before being modified. Here we reveal that two atypical acyl-CoA dehydrogenases, ACAD10 and ACAD11, drive 4-HA catabolism in mice. Unlike other ACADs, ACAD10 and ACAD11 feature kinase domains that phosphorylate the 4-hydroxy position as a requisite step in converting 4-hydroxyacyl-CoAs into conventional 2-enoyl-CoAs. Through cryo-electron microscopy and molecular modeling, we identified an atypical dehydrogenase binding pocket capable of accommodating this phosphorylated intermediate. We further show that ACAD10 is mitochondrial and necessary for catabolizing shorter-chain …

Variation In Recommended Treatment Strategies Among American Surgeons For Actual Adult Traumatic Brachial Plexus Injury Cases, Michele N Christy, Christopher J Dy, R Glenn Gaston, Bryan J Loeffler, Mihir J Desai, Steve K Lee, Harvey Chim, Jeffrey B Friedrich, Sameer K Puri, Jason H Ko, Planet Study Group

2020-Current year OA Pubs

PURPOSE: The surgical management of adult traumatic brachial plexus injuries (BPI) is challenging, with no consensus on optimal strategies. This study aimed to gather preferred reconstructive strategies from BPI surgeons for actual cases from a multicenter cohort to identify areas of agreement.

METHODS: Four case files (history, physical examination, and imaging and electrodiagnostic testing results) were distributed to eight self-designated Level IV expert BPI surgeons in the United States. Each surgeon independently reviewed the cases and provided a preferred reconstructive plan via free text response.

RESULTS: For a pan-plexus case after blunt trauma (67 years old; 3 months from injury): …

Machine Learning Feasibility In Cochlear Implant Speech Perception Outcomes-Moving Beyond Single Biomarkers For Cochlear Implant Performance Prediction, Matthew A. Shew, Cole Pavelchek, Andrew Michelson, Amanda Ortmann, Shannon Lefler, Amit Walia, Nedim Durakovic, Alisa Phillips, Ayna Rejepova, Jacques A. Herzog, Phillip Payne, Jay F. Piccirillo, Craig A. Buchman

2020-Current year OA Pubs

OBJECTIVES: Machine learning (ML) is an emerging discipline centered around complex pattern matching and large data-based prediction modeling and can improve precision medicine healthcare. Cochlear implants (CI) are highly effective, however, outcomes vary widely, and accurately predicting speech perception performance outcomes between patients remains a challenge. This study aims to evaluate the ability of ML to predict speech perception performance among CI recipients at 6-month post-implantation using only preoperative variables on one of the largest CI datasets to date, with an emphasis placed on identification of poor performers.

DESIGN: All patients enrolled in the national CI outcome tracking database, HERMES, …

Neutrophils Drive Vascular Occlusion, Tumour Necrosis And Metastasis, Jose M Adrover, Xiao Han, Lijuan Sun, Takeo Fujii, Nicole Sivetz, Juliane Daßler-Plenker, Clary Evans, Jessica Peters, Xue-Yan He, Courtney D Cannon, Won Jin Ho, George Raptis, R Scott Powers, Mikala Egeblad

2020-Current year OA Pubs

Tumour necrosis is associated with poor prognosis in cancer

Assessing Stages Of Objective Memory Impairment And Neuroimaging As Risk Factors Of Incident Cognitive Impairment, Kellen K Petersen, Ali Ezzati, Bhargav T Nallapu, Richard B Lipton, Reisa A Sperling, Kathryn V Papp, Dorene M Rentz, Keith A Johnson, Ellen Grober

2020-Current year OA Pubs

OBJECTIVE: The Stages of Objective Memory Impairment (SOMI) system, based on the Free and Cued Selective Reminding Test (FCSRT), is a potential marker of subtle cognitive impairment in cognitively normal persons defined by a Clinical Dementia Rating (CDR) = 0. We investigated SOMI's ability to predict incident cognitive impairment (CDR >0) in combination with demographic features and neuroimaging biomarkers.

METHODS: Cognitively unimpaired participants (CDR = 0) from the Harvard Aging Brain Study had baseline FCSRT scores, MRI, FDG-PET, and PiB-PET as well as follow-up CDRs for 5 years. Cox proportional hazards models with correction for multiple testing assessed the predictive …

Predictors Of Perceived Hiv Stigma Among People Who Inject Drugs In The United States, Itunu Sokale, Paige Wermuth, Johnny Wilkerson, Folefac Atem, Salma Khuwaja, Catherine Troisi

Faculty, Staff and Student Publications

Background: HIV stigma is a huge impediment to ending the HIV epidemic. To develop effective HIV interventions, we must determine factors associated with HIV stigma, particularly among high-risk groups like people who inject drugs (PWID). We aimed to identify predictors of perceived HIV stigma (PHS) among a sample of PWID from 23 U.S. cities.

Methods: We analyzed the 2018 National HIV Behavioral Surveillance data on PWID aged ≥ 18 years. PHS was assessed using a validated survey that measured four PHS constructs: perceived unfriendliness, perceived discrimination, perceived punishment, and perceived support. We created a composite PHS index score by summing …

Zika In Infants And Pregnancy (Zip) Study: Results From A Prospective International Cohort Study Of Prenatal Zika Virus Infection And Adverse Fetal And Infant Outcomes, Jill Farnell Lebov, Martha Nason, Kristen B Stolka, Ricardo Ximenes, Marisa M Mussi-Pinhata, Jack Moye, Carmen D Zorrilla, Carmen M Velez Vega, José F Cordero, Deolinda M F Scalabrin, Albert I Ko, Maria Elisabeth Lopes Moreira, Luiz Augusto Galvão, William Britt, Ernesto T A Marques, Angel Balmaseda, Eva Harris, Juan F Arias, Stacey Schultz-Cherry, Ana Lucía Garces, Nancy F Krebs, Theresa J Ochoa, César Augusto Ugarte-Gil, Elizabeth Fogleman, Erin Gabriel, Michael Welton, Carmen M Irizarry, Silvia Biason De Moura Negrini, Conrado Milani Coutinho, Demócrito De Barros Miranda-Filho, Ulisses Ramos Montarroyos, Marli Tenorio Cordeiro, Anna Gajewski, Jorge E Osorio, Lester Figueroa

Faculty, Staff and Student Publications

Background: Before Zika virus (ZIKV) infections were observed in the Americas, an association between ZIKV and microcephaly or other congenital malformations was not well documented. Initial reports suggested strong associations between ZIKV and congenital malformations, but plausible estimates of causal effects from prospective studies with adequate sample size and covariate data were few.

Methods: From 2016-2018, the Zika in Infants and Pregnancy (ZIP) study enrolled pregnant people before 18 weeks gestation or with confirmed symptomatic ZIKV in a prospective cohort across 10 sites in South and Central America, and in Puerto Rico. Pregnancies were followed monthly through delivery and 6 …

Drug-Drug Interaction Between Dolutegravir And Artemether-Lumefantrine In Hiv And Malaria Mono- And Co-Infections: A Pharmacogenetic Analysis From Ghana, Nicholas Ekow Thomford, Tracy Kellermann, Joel Adu Twum, John Anyimadu, Charné Dixon, Dennis Sappor, Dee Blackhurst, Prince Amoah Barnie, Oksana Ryabinina, Samuel Badu Nyarko, Robert Peter Biney, Martins Ekor, George B Kyei

2020-Current year OA Pubs

BACKGROUND: Human Immunodeficiency Virus and malaria are significant public health challenges in sub-Saharan Africa, contributing substantially to morbidity and mortality in the region. The trajectory of HIV and malaria mono- and coinfections may be different with presentations of drug-drug and disease-disease interactions. Current medications of artemether-lumefantrine and dolutegravir (DTG) -based anti-retroviral therapy which are the preferred drugs are metabolised by CYP2B6, CYP3A4/5 and UGTs which are polymorphic and may contribute to drug disposition and clinical outcomes. This study investigated the pharmacogenetic effects of co-administration of arthemeter-lumfantrine and DTG in HIV-malaria mono and coinfection.

METHODS: Malaria and HIV mono- and coinfected …

Risk Of Major Depression In Partners Of People With Alzheimer's Disease: A National Cohort Study, Casey Crump, Jingkai Wei, Barbara G Vickrey, Alexis C Edwards, Paul E Schulz, Weiva Sieh, Jan Sundquist, Kristina Sundquist

Faculty, Staff and Student Publications

Background: Alzheimer's disease (AD) may cause significant psychosocial distress not only in the patient but also their partner. However, long-term risks of major depression in partners of AD patients are largely unknown.

Methods: A national cohort study was conducted of all 145 289 partners of people diagnosed with all-cause dementia, including 57 113 partners of people diagnosed with AD, in Sweden during 1998-2017, and 1 300 561 population-based controls. Cox regression was used to compute hazard ratios (HRs) for subsequent risk of major depression identified from nationwide outpatient and inpatient diagnoses through 2018, adjusting for sociodemographic factors and prior mental …

Hiv-1 Controllers Possess A Unique Cd8+ T Cell Activation Phenotype And Loss Of Control Is Associated With Increased Expression Of Exhaustion Markers, Amber D. Jones, Zachary Capriotti, Erin Santos, Angel Lin, Rachel Van Duyne, Stephen Smith, Zachary Klase

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

BACKGROUND: HIV-1 controllers are a rare population of individuals that exhibit spontaneous control of HIV-1 infection without antiretroviral therapy. Understanding the mechanisms by which HIV-1 controllers maintain and eventually lose this ability would be highly valuable in HIV-1 cure or vaccine research. Previous work revealed the ability of CD8+ T cells isolated from HIV-1 controllers to suppress HIV-1 replication in matched CD4+ T cells and PBMCs ex vivo and suggested the loss of control may be tied to CD8+ T cell exhaustion.

RESULTS: We explored whether CD8+ T cell exhaustion plays a role in the maintenance and loss of control …

Dna Double-Stranded Breaks, A Hallmark Of Aging, Defined At The Nucleotide Resolution, Are Increased And Associated With Transcription In The Cardiac Myocytes In Lmna-Cardiomyopathy, Benjamin Cathcart, Sirisha M Cheedipudi, Leila Rouhi, Zhongming Zhao, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

Aims: An intrinsic feature of gene transcription is the formation of DNA superhelices near the transcription bubble, which are resolved upon induction of transient double-stranded breaks (DSBs) by topoisomerases. Unrepaired DSBs are pathogenic as they lead to cell cycle arrest, senescence, inflammation, and organ dysfunction. We posit that DSBs would be more prevalent at the genomic sites that are associated with gene expression. The objectives were to identify and characterize genome-wide DSBs at the nucleotide resolution and determine the association of DSBs with transcription in cardiac myocytes.

Methods and results: We identified the genome-wide DSBs in ∼1 million cardiac myocytes …

Low-Level Pm2.5 Exposure And Mortality In The Medicare Cohort: The Role Of Native American Beneficiaries, Judy Wendt Hess, Wenyaw Chan

Faculty, Staff and Student Publications

Fine particulate matter (PM2.5) has been associated with mortality at low concentrations, with higher per-unit risk at lower exposure levels, and no threshold of effect. We examined characteristics of Medicare decedents living in zip codes at the lowest end of the U.S. PM2.5 exposure distribution to determine whether there is a demographic, health or exposure profile of beneficiaries for whom even low PM2.5 exposure is associated with increased mortality. The study included 2,773,647 decedent cases and 27,736,470 non-decedent controls, matched on decile of long-term PM2.5 exposure from among 36 million Medicare fee-for-service beneficiaries enrolled 2015–2016. Outcomes of the study included …