Medicine and Health Sciences Commons^™

A Smartwatch Step-Counting App For Older Adults: Development And Evaluation Study, George Boateng, Curtis L. Petersen, David Kotz, Karen L. Fortuna, Rebecca Masutani, John A. Batsis

Dartmouth Scholarship

Background: Older adults who engage in physical activity can reduce their risk of mobility impairment and disability. Short amounts of walking can improve quality of life, physical function, and cardiovascular health. Various programs have been implemented to encourage older adults to engage in physical activity, but sustaining their motivation continues to be a challenge. Ubiquitous devices, such as mobile phones and smartwatches, coupled with machine-learning algorithms, can potentially encourage older adults to be more physically active. Current algorithms that are deployed in consumer devices (eg, Fitbit) are proprietary, often are not tailored to the movements of older adults, and have …

The Feasibility And Utility Of Harnessing Digital Health To Understand Clinical Trajectories In Medication Treatment For Opioid Use Disorder: D-Tect Study Design And Methodological Considerations, Lisa A. Marsch, Ching-Hua Chen, Sara R. Adams, Asma Asyyed, Monique B. Does, Saeed Hassanpour, Emily Hichborn, Melanie Jackson-Morris, Nicholas C. Jacobson, Heather K. Jones, David Kotz, Chantal A. Lambert-Harris, Zhiguo Li, Bethany Mcleman, Varun Mishra, Catherine Stanger, Geetha Subramaniam, Weiyi Wu, Cynthia I. Campbell

Dartmouth Scholarship

Introduction: Across the U.S., the prevalence of opioid use disorder (OUD) and the rates of opioid overdoses have risen precipitously in recent years. Several effective medications for OUD (MOUD) exist and have been shown to be life-saving. A large volume of research has identified a confluence of factors that predict attrition and continued substance use during substance use disorder treatment. However, much of this literature has examined a small set of potential moderators or mediators of outcomes in MOUD treatment and may lead to over-simplified accounts of treatment non-adherence. Digital health methodologies offer great promise for capturing intensive, longitudinal ecologically-valid …

A Weight-Loss Intervention Augmented By A Wearable Device In Rural Older Adults With Obesity: A Feasibility Study, John A. Batsis, Curtis L. Petersen, Matthew L. Clark, Summer B. Cook, Francisco Lopez-Jimenez, Rima I. Al-Nimer, Dawna Pidgeon, David Kotz, Todd A. Mackenzie, Stephen J. Bartels

Dartmouth Scholarship

Background

Older persons with obesity aged 65+ residing in rural areas have reduced access to weight management programs due to geographic isolation. The ability to integrate technology into health promotion interventions shows a potential to reach this underserved population. Methods

A 12-week pilot in 28 older rural adults with obesity (body mass index [BMI] ≥ 30 kg/m2) was conducted at a community aging center. The intervention consisted of individualized, weekly dietitian visits focusing on behavior therapy and caloric restriction with twice weekly physical therapist-led group strengthening training classes in a community-based aging center. All participants were provided a Fitbit Flex …

Feasibility And Acceptability Of A Technology-Based, Rural Weight Management Int Ervention In Older Adults With Obesity, John A. Batsis, Curtis L. Petersen, Matthew M. Clark, Summer B. Cook, David Kotz, Tyler L. Gooding, Meredith N. Roderka, Rima I. Al-Nimer, Dawna M. Pidgeon, Ann Haedrich, K. C. Wright, Christina Aquila, Todd A. Mackenzie

Dartmouth Scholarship

Background

Older adults with obesity residing in rural areas have reduced access to weight management programs. We determined the feasibility, acceptability and preliminary outcomes of an integrated technology-based health promotion intervention in rural-living, older adults using remote monitoring and synchronous video-based technology.

Methods

A 6-month, non-randomized, non-blinded, single-arm study was conducted from October 2018 to May 2020 at a community-based aging center of adults aged ≥65 years with a body mass index (BMI) ≥30 kg/m2. Weekly dietitian visits focusing on behavior therapy and caloric restriction and twice-weekly physical therapist-led group strength, flexibility and balance training classes were delivered using video-conferencing …

Automatic Recognition, Segmentation, And Sex Assignment Of Nocturnal Asthmatic Coughs And Cough Epochs In Smartphone Audio Recordings: Observational Field Study, Filipe Barata, Peter Tinschert, Frank Rassouli, Claudia Steurer-Stey, Elgar Fleisch, Milo Puhan, Martin Brutsche, David Kotz, Tobias Kowatsch

Dartmouth Scholarship

Background: Asthma is one of the most prevalent chronic respiratory diseases. Despite increased investment in treatment, little progress has been made in the early recognition and treatment of asthma exacerbations over the last decade. Nocturnal cough monitoring may provide an opportunity to identify patients at risk for imminent exacerbations. Recently developed approaches enable smartphone-based cough monitoring. These approaches, however, have not undergone longitudinal overnight testing nor have they been specifically evaluated in the context of asthma. Also, the problem of distinguishing partner coughs from patient coughs when two or more people are sleeping in the same room using contact-free audio …

Metaanalysis Of The Relationship Between Violent Video Game Play And Physical Aggression Over Time, Anna T. Prescott, James Sargent, Jay G. Hull

Dartmouth Scholarship

To clarify and quantify the influence of video game violence (VGV) on aggressive behavior, we conducted a metaanalysis of all prospective studies to date that assessed the relation between exposure to VGV and subsequent overt physical aggression. The search strategy identified 24 studies with over 17,000 participants and time lags ranging from 3 months to 4 years. The samples comprised various nationalities and ethnicities with mean ages from 9 to 19 years. For each study we obtained the standardized regression coefficient for the prospective effect of VGV on subsequent aggression, controlling for baseline aggression. VGV was related to aggression using …

Sex-Specific Associations Of Infants’ Gut Microbiome With Arsenic Exposure In A Us Population, Anne G. Hoen, Juliette C. Madan, Zhigang Li, Modupe Coker, Sara N. Lundgren, Hilary G. Morrison, Thomas J. Palys, Brian P. Jackson, Mitchell L. Sogin, Kathryn L. Cottingham, Margaret R. Karagas

Dartmouth Scholarship

Arsenic is a ubiquitous environmental toxicant with antimicrobial properties that can be found in food and drinking water. The influence of arsenic exposure on the composition of the human microbiome in US populations remains unknown, particularly during the vulnerable infant period. We investigated the relationship between arsenic exposure and gut microbiome composition in 204 infants prospectively followed as part of the New Hampshire Birth Cohort Study. Infant urine was analyzed for total arsenic concentration using inductively coupled plasma mass spectrometry. Stool microbiome composition was determined using sequencing of the bacterial 16S rRNA gene. Infant urinary arsenic related to gut microbiome …

Prevalence Rates Of Arthritis Among Us Older Adults With Varying Degrees Of Depression: Findings From The 2011 To 2014 National Health And Nutrition Examination Survey, Jessica L. Brooks, Alexander J. Titus, Courtney A. Polenick, Nicole M. Orzechowski, Manney Carrington Reid, Todd A. Mackenzie, Stephen J. Bartels, John A. Batsis

Dartmouth Scholarship

Arthritis and depressive symptoms often interact and negatively influence one another to worsen mental and physical health outcomes. Better characterization of arthritis rates among older adults with different levels of depressive symptoms is an important step toward informing mental health professionals of the need to detect and respond to arthritis and related mental health complications. The primary objective is to determine arthritis rates among US older adults with varying degrees of depression. Using National Health and Nutrition Examination Survey 2011 to 2014 data (N = 4792), we first identified participants aged ≥50 years. Measures screened for depressive symptoms and …

Neural Responses To Naturalistic Clips Of Behaving Animals Under Two Different Task Contexts, Samuel A. Nastase, Yaroslav O. Halchenko, Andrew C. Connolly, M. Ida Gobbini, James V. Haxby

Dartmouth Scholarship

The human brain rapidly deploys semantic information during perception to facilitate our interaction with the world. These semantic representations are encoded in the activity of distributed populations of neurons (Haxby et al., 2001; McClelland and Rogers, 2003; Kriegeskorte et al., 2008b) and command widespread cortical real estate (Binder et al., 2009; Huth et al., 2012). The neural representation of a stimulus can be described as a location (i.e., response vector) in a high-dimensional neural representational space (Kriegeskorte and Kievit, 2013; Haxby et al., 2014). This resonates with behavioral and theoretical work describing mental representations of objects and actions as being …

Impact Of Prenatal Stress On Offspring Glucocorticoid Levels: A Phylogenetic Meta-Analysis Across 14 Vertebrate Species, Zaneta M. Thayer, Meredith A. Wilson, Andrew W. Kim, Adrian V. Jaeggi

Dartmouth Scholarship

Prenatal exposure to maternal stress is commonly associated with variation in Hypothalamic Pituitary Adrenal (HPA)-axis functioning in ofspring. However, the strength or consistency of this response has never been empirically evaluated across vertebrate species. Here we meta-analyzed 114 results from 39 studies across 14 vertebrate species using Bayesian phylogenetic mixed-efects models. We found a positive overall efect of prenatal stress on ofspring glucocorticoids (d’=0.43) though the 95% Highest Posterior Density Interval overlapped with 0 (−0.16–0.95). Meta-regressions of potential moderators highlighted that phylogeny and life history variables predicted relatively little variation in efect size. Experimental studies (d’=0.64) produced stronger efects than …

Closed-Loop Stimulation Of Temporal Cortex Rescues Functional Networks And Improves Memory, Yousseff Ezzyat, Paul A. Wanda, Deborah F. Levy, Allison Kadel, Ada Aka, Isaac Pedisich, Michael R. Sperling, Ashwini D. Sharan, Bradley C. Lega, Alexis Burks, Robert E. Gross, Cory S. Inman, Barbara C. Jobst, Mark A. Gorenstein

Dartmouth Scholarship

Memory failures are frustrating and often the result of ineffective encoding. One approach to improving memory outcomes is through direct modulation of brain activity with electrical stimulation. Previous efforts, however, have reported inconsistent effects when using open-loop stimulation and often target the hippocampus and medial temporal lobes. Here we use a closed-loop system to monitor and decode neural activity from direct brain recordings in humans. We apply targeted stimulation to lateral temporal cortex and report that this stimulation rescues periods of poor memory encoding. This system also improves later recall, revealing that the lateral temporal cortex is a reliable target …

Similar Neural Responses Predict Friendship, Carolyn Parkinson, Adam M. Kleinbaum, Thalia Wheatley

Dartmouth Scholarship

Human social networks are overwhelmingly homophilous: individuals tend to befriend others who are similar to them in terms of a range of physical attributes (e.g., age, gender). Do similarities among friends reflect deeper similarities in how we perceive, interpret, and respond to the world? To test whether friendship, and more generally, social network proximity, is associated with increased similarity of real-time mental responding, we used functional magnetic resonance imaging to scan subjects’ brains during free viewing of naturalistic movies. Here we show evidence for neural homophily: neural responses when viewing audiovisual movies are exceptionally similar among friends, and that similarity …

Iron Reduction Response And Demographic Differences Between Diabetics And Non-Diabetics With Cardiovascular Disease Entered To A Controlled Clinical Trial, Leo Zacharski, Galina Shamayeva, Bruce Chow

Dartmouth Scholarship

Iron-catalyzed oxygen free radical-induced oxidative stress mediates the pathogenesis of diabetes and cardiovascular disease (CVD). Diabetics (n=473) and non-diabetics (n=804) with CVD entered to a randomized trial of iron (ferritin) reduction by calibrated phlebotomy (www.clinicaltrials.gov, Identifier NCT00032357) had comparable iron measures at entry but diabetics had greater burden of CVD and comorbidities, lower hemoglobin and hematocrit levels, and higher glucose levels than non-diabetics. Entry iron measures were lower in diabetics on hypoglycemic therapy compared to diabetics untreated previously. Diabetics and non-diabetics had comparable iron measures during follow-up. Loess analysis of paired ferritin and hemoglobin, and paired ferritin and glucose levels …

Patient-Predicted Sleep Position Vs. Hst Data: A Tendency To Underestimate Supine Sleep, Adam J. Sorscher, Anthony P. Anzivino, Todd Mackenzie

Dartmouth Scholarship

Purpose The purpose of this study is to measure people’s accuracy when they estimate what proportion of their nightly sleep at home is supine vs. non-supine. Methods A series of patients referred for obstructive sleep apnea (OSA) evaluation were asked if they Bknew with confidence^ how they slept with regard to their body position. BYes^ responders were then asked to estimate what percentage of their sleep was supine vs. non-supine. This value was compared with the actual proportion of supine vs. non-supine sleep that they exhibited in a home sleep test (HST) that followed. Results We obtained data from 49 …

Anthropometric Factors And Cutaneous Melanoma: Prospective Data From The Population-Based Janus Cohort, Jo S. Stenehjem, Marit B. Veierød, Lill Tove Nilsen, Reza Ghiasvand, Bjørn Johnsen, Tom K. Grimsrud, Ronnie Babigumira, Judy R. Rees, Trude E. Robsahm

Dartmouth Scholarship

The aim of the present study was to prospectively examine risk of cutaneous melanoma (CM) according to measured anthropometric factors, adjusted for exposure to ultraviolet radiation (UVR), in a large population-based cohort in Norway. The Janus Cohort, including 292,851 Norwegians recruited 1972–2003, was linked to the Cancer Registry of Norway and followed for CM through 2014. Cox regression was used to estimate hazard ratios (HRs) of CM with 95% confidence intervals (CIs). Restricted cubic splines were incorporated into the Cox models to assess possible non-linear relationships. All analyses were adjusted for attained age, indicators of UVR exposure, education, and smoking …

Anxiety Associated Increased Cpg Methylation In The Promoter Of Asb1: A Translational Approach Evidenced By Epidemiological And Clinical Studies And A Murine Model, Rebecca T. Emeny, Jens Baumert, Anthony S. Zannas, Sonja Kunze, Simone Wahl, Stella Iurato

Dartmouth Scholarship

Epigenetic regulation in anxiety is suggested, but evidence from large studies is needed. We conducted an epigenome-wide association study (EWAS) on anxiety in a population-based cohort and validated our finding in a clinical cohort as well as a murine model. In the KORA cohort, participants (n= 1522, age 32–72 years) were administered the Generalized Anxiety Disorder (GAD-7) instrument, whole blood DNA methylation was measured (Illumina 450K BeadChip), and circulating levels of hs-CRP and IL-18 were assessed in the association between anxiety and methylation. DNA methylation was measured using the same instrument in a study of patients with anxiety disorders recruited …

A Protocol For Prospective Studies" "5-Hydroxyvitamin D, Leptin And B Ass Index In Relation To Cutaneou Elanoma Incidence And Survival, Jo S. Stenehjem, Tom K. Grimsrud, Judy R. Rees, Linda Vos, Ronnie Babigumira, Marit B. Veierød, Trude E. Robsahm

Dartmouth Scholarship

Introduction The incidence and mortality rates of

cutaneous melanoma (CM) are increasing among fai skinned populations worldwide. Ultraviolet radiation s the principal risk factor for CM, but is also the mai source of 25-hydroxyvitamin D (25(OH)D), which has associated with reduced risk and better prognosis of cancer types. However, both low and high 25(OH)D l have been associated with increased risk of CM. Obe as measured by body mass index (BMI) is associated risk of several cancers and has also been suggested risk factor for CM, and may also be related to insuffi 25(OH)D and/or high leptin levels. Moreover, contract …

Safety And Immunogenicity Of An Inactivated Whole Cell Tuberculosis Vaccine Booster In Adults Primed With Bcg: A Randomized, Controlled Trial Of Dar-901, C. Fordham Von Reyn, Timothy Lahey, Robert D. Arbeit, Bernard Landry, Leway Kailani, Lisa Adams, Brenda Haynes, Todd Mackenzie, Wendy Wieland-Alter, Ruth Connor, Sue Tvaroha, David Hokey, Ann Ginsberg, Richard Waddell

Dartmouth Scholarship

Development of a tuberculosis vaccine to boost BCG is a major international health priority. SRL172, an inactivated whole cell booster derived from a non-tuberculous mycobacterium, is the only new vaccine against tuberculosis to have demonstrated efficacy in a Phase 3 trial. In the present study we sought to determine if a three-dose series of DAR-901 manufactured from the SRL172 master cell bank by a new, scalable method was safe and immunogenic.

Diffusion Of Digital Breast Tomosynthesis Among Women In Primary Care: Associations With Insurance Type, Cheryl R. Clark, Tor Tosteson, Anna Tosteson, Tracy Onega, Julie Weiss, Kimberly A. Harris, Jennifer S. Haas

Dartmouth Scholarship

Digital breast tomosynthesis (DBT) has shown potential to improve breast cancer screening and diagnosis compared to digital mammography (DM). The FDA approved DBT use in conjunction with conventional DM in 2011, but coverage was approved by CMS recently in 2015. Given changes in coverage policies, it is important to monitor diffusion of DBT by insurance type. This study examined DBT trends and estimated associations with insurance type. From June 2011 to September 2014, DBT use in 22 primary care centers in the Dartmouth -Brigham and Women's Hospital Population-based Research Optimizing Screening through Personalized Regimens research center (PROSPR) was examined among …

Optimal Nutrition For Endurance Exercise: A Systematic Review, Sarah E. Andrus Ms, Bruce W. Andrus Md Ms

Dartmouth Scholarship

Introduction

As fatigue in endurance events correlates with depletion of muscle glycogen, the traditional approach to nutritional support has been carbohydrate loading. However, there has been recent interest in improving athletic endurance performance by novel diets in the days to weeks prior to endurance events, the pre-event meal, and during exercise.

Methods

We searched PubMed and SCOPUS for randomized trials published from 1992-2017 with a primary endpoint of endurance performance. We identified 407 citations which were examined against our inclusion criteria of randomization or crossover allocation to diet and for which a primary outcome was endurance performance.

Results

Twenty full …

The E2f4 Prognostic Signature Predicts Pathological Response To Neoadjuvant Chemotherapy In Breast Cancer Patients, Kenneth M. K. Mark, Frederick S. Varn, Matthew H. Ung, Feng Qian, Chao Cheng

Dartmouth Scholarship

Neoadjuvant chemotherapy is a key component of breast cancer treatment regimens and pathologic complete response to this therapy varies among patients. This is presumably due to differences in the molecular mechanisms that underlie each tumor’s disease pathology. Developing genomic clinical assays that accurately categorize responders from non-responders can provide patients with the most effective therapy for their individual disease. We applied our previously developed E2F4 genomic signature to predict neoadjuvant chemotherapy response in breast cancer. E2F4 individual regulatory activity scores were calculated for 1129 patient samples across 5 independent breast cancer neoadjuvant chemotherapy datasets. Accuracy of the E2F4 signature in …

Optimization Of Fluorescent Imaging In The Operating Room Through Pulsed Acquisition And Gating To Ambient Background Cycling, Kristian J. Sexton, Yan Zhao, Scott C. Davis, Shudong Jiang, Brian Pogue

Dartmouth Scholarship

The design of fluorescence imaging instruments for surgical guidance is rapidly evolving, and a key issue is to efficiently capture signals with high ambient room lighting. Here, we introduce a novel time-gated approach to fluorescence imaging synchronizing acquisition to the 120 Hz light of the room, with pulsed LED excitation and gated ICCD detection. It is shown that under bright ambient room light this technique allows for the detection of physiologically relevant nanomolar fluorophore concentrations, and in particular reduces the light fluctuations present from the room lights, making low concentration measurements more reliable. This is particularly relevant for the light …

Ferritin And Percent Transferrin Saturation Levels Predict Type 2 Diabetes Risk And Cardiovascular Disease Outcomes, Leo R. Zacharski, Galina Shamayeva, Bruce K. Chow, Ralph G. Depalma

Dartmouth Scholarship

Introduction: Type 2 diabetes (T2D) and cardiovascular disease (CVD) risk associate withferritin and percent transferrin saturation (%TS) levels. However, increased risk has been observed at levels considered within the “normal range” for these markers.

Objective: To define normative ferritin and %TS levels associated with T2D and CVD risk.

Methods: Six-monthly ferritin, %TS and hemoglobin levels from 1,277 iron reduction clinical trial participants with CVD (peripheral arterial disease, 37% diabetic) permitted pair-wise analysis using Loess Locally Weighted Smoothing plots. Curves showed continuous quantitative ferritin, hemoglobin (reflecting physiologic iron requirements), and %TS (reflecting iron transport and sequestration) levels over a wide range …

Do The Disc Degeneration And Osteophyte Contribute To The Curve Rigidity Of Degenerative Scoliosis?, Feng Zhu, Hongda Bao, Peng Yan, Shunan Liu, Mike Bao

Dartmouth Scholarship

The factors associated with lateral curve flexibility in degenerative scoliosis have not been well documented. Disc degeneration could result in significant change in stiffness and range of motion in lateral bending films. The osteophytes could be commonly observed in degenerative spine but the relationship between osteophyte formation and curve flexibility remains controversial. The aim of the current study is to clarify if the disc degeneration and osteophyte formation were both associated with curve flexibility of degenerative scoliosis.

A New Class Of Inhibitors Of The Arac Family Virulence Regulator Vibrio Cholerae Toxt, Anne K. Woodbrey, Evans O. Onyango, Maria Pellegrini, Gabriela Kovacikova, Ronald Taylor, Gordon Gribble, F. Jon Kull

Dartmouth Scholarship

Vibrio cholerae is responsible for the diarrheal disease cholera that infects millions of people worldwide. While vaccines protecting against cholera exist, and oral rehydration therapy is an effective treatment method, the disease will remain a global health threat until long-term solutions such as improved sanitation and access to clean water become widely available. Because of this, there is a pressing need for potent therapeutics that can either mitigate cholera symptoms, or act prophylactically to prevent the virulent effects of a cholera infection. Here we report the design, synthesis, and characterization of a set of compounds that bind and inhibit ToxT, …

Neurologic Correlates Of Gait Abnormalities In Cerebral Palsy: Implications For Treatment, Joanne Zhou, Erin E. Butler, Jessica Rose

Dartmouth Scholarship

Cerebral palsy (CP) is the most common movement disorder in children. A diagnosis of CP is often made based on abnormal muscle tone or posture, a delay in reaching motor milestones, or the presence of gait abnormalities in young children. Neuroimaging of high-risk neonates and of children diagnosed with CP have identified patterns of neurologic injury associated with CP, however, the neural underpinnings of common gait abnormalities remain largely uncharacterized. Here, we review the nature of the brain injury in CP, as well as the neuromuscular deficits and subsequent gait abnormalities common among children with CP. We first discuss brain …

Associations Between Genetic Variants In Mrna Splicing-Related Genes And Risk Of Lung Cancer: A Pathway-Based Analysis From Published Gwass, Yongchu Pan, Hongliang Liu, Yanru Wang, Xiaozheng Kang, Kouros Owzar, Younghun Han

Dartmouth Scholarship

mRNA splicing is an important mechanism to regulate mRNA expression. Abnormal regulation of thisprocess may lead to lung cancer. Here, we investigated the associations of 11,966 single-nucleotide polymorphisms (SNPs) in 206 mRNA splicing-related genes with lung cancer risk by using the summarydata from six published genome-wide association studies (GWASs) of Transdisciplinary Research in Cancerof the Lung (TRICL) (12,160 cases and 16,838 controls) and another two lung cancer GWASs of Harvard University (984 cases and 970 controls) and deCODE (1,319 cases and 26,380 controls). We found that a total of 12 significant SNPs with false discovery rate (FDR) ≤0.05 were mapped …

Polyp Resection - Controversial Practices And Unanswered Questions, Daniel Von Renteln, Heiko Pohl

Dartmouth Scholarship

Detection and complete removal of precancerous neoplastic polyps are central to effective colorectal cancer screening. The prevalence of neoplastic polyps in the screening population in the United States is likely 450%. However, most persons with neoplastic polyps are never destined to develop cancer, and do not benefit for finding and removing polyps, and may only be harmed by the procedure. Further 70–80% of polyps are diminutive (≤5 mm) and such polyps almost never contain cancer. Given the questionable benefit, the high-cost and the potential risk changing our approach to the management of diminutive polyps is currently debated. Deemphasizing diminutive polyps …

Transactivation Of The Estrogen Receptor Promoter By Brca1, William B. Archey, Bradley A. Arrick

Dartmouth Scholarship

Background: Absence of the estrogen receptor-α (ER) is perhaps the most distinctive pathological feature of breast cancers arising in women who inherit a mutation in BRCA1. Two hypotheses, not necessarily mutually exclusive, exist in the literature that describe mechanisms of ER transcriptional repression in breast cancer. One hypothesis suggests that methylation of cytosine–guanine dinucleotides (CpGs) primarily mediates repression, while the other maintains that transcriptional control is mediated by certain positive and negative promoter elements.

Methods: To determine if wild type BRCA1 could induce activity of the ER promoter, we performed a series of tran- sient transfections with ER promoter segments …

Potent Single-Domain Antibodies That Arrest Respiratory Syncytial Virus Fusion Protein In Its Prefusion State, Iebe Rossey, Morgan Gilman, Stephanie Kabeche, Koen Sedeyn, Daniel Wrapp

Dartmouth Scholarship

Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs …