Medicine and Health Sciences Commons^™

Epidemiology Of 45,616 Suspect Cases Of Hand, Foot And Mouth Disease In Chongqing, China, 2011–2015, Jian Tao, Xiao-Yan He, Yu Shi, Guohun Zhu, Shan Liu, Zhenzhen Zhang, Shi Tang, Rong Zhang, Bin Peng, Zhidai Liu, Junjie Tan, Qian Chen, Xingbin Wang, Liming Bao, Lin Zou, Penghui Zhang

Dartmouth Scholarship

Epidemiology and etiology of hand, foot, and mouth disease (HFMD) based on large sample size or evaluation of detection for more enterovirus serotypes are not well investigated in Chongqing of China. 45,616 suspect HFMD patients were prospectively enrolled among whom 21,615 were laboratory confirmed HFMD cases over a 5-year period (January 2011 to December 2015). Their epidemiological, clinical, and laboratory data were extracted and stratified by month, age, sex, disease severity, and enterovirus serotype. Subsequently 292 non-EV-A71/CV-A16 HFMD confirmed cases were randomly selected in three consecutive outbreaks to detect CV-A6 and CV-A10, using RT-PCR. Results showed that the HFMD epidemic …

Filamentous Fungal Carbon Catabolite Repression Supports Metabolic Plasticity And Stress Responses Essential For Disease Progression, Sarah R. Beattie, Kenneth Mark, Arsa Thammahong, Laure Nicolas Annick Ries, Sourabh Dhingra, Alayna Caffrey-Carr, Chao Cheng

Dartmouth Scholarship

Aspergillus fumigatus is responsible for a disproportionate number of invasive mycosis cases relative to other common filamentous fungi. While many fungal factors critical for infection establishment are known, genes essential for disease persistence and progression are ill defined. We propose that fungal factors that promote navigation of the rapidly changing nutrient and structural landscape characteristic of disease progression represent untapped clinically relevant therapeutic targets. To this end, we find that A. fumigatus requires a carbon catabolite repression (CCR) mediated genetic network to support in vivo fungal fitness and disease progression. While CCR as mediated by the transcriptional repressor CreA is …

Implementing Shared Decision Making In The Nhs: Lessons From The Magic Programme, Natalie Joseph-Williams, Amy Lloyd, Adrian Edwards, Lynne Stobbart, David Tomson, Sheila Macphail, Carole Dodd, Glyn Elwyn, Richard Thomson

Dartmouth Scholarship

No abstract provided.

Pseudomonas Aeruginosa-Derived Rhamnolipids And Other Detergents Modulate Colony Morphotype And Motility In The Burkholderia Cepacia Complex, Steve P. Bernier, Courtney Hum, Xiang Li, George A. O'Toole, Nathan A. Magarvey, Michael G. Surette

Dartmouth Scholarship

Competitive interactions mediated by released chemicals (e.g., toxins) are prominent in multispecies communities, but the effects of these chemicals at subinhibitory concentrations on susceptible bacteria are poorly understood. Although Pseudomonas aeruginosa and species of the Burkholderia cepacia complex (Bcc) can exist together as a coinfection in cystic fibrosis airways, P. aeruginosa toxins can kill Bcc species in vitro. Consequently, these bacteria become an ideal in vitro model system to study the impact of sublethal levels of toxins on the biology of typical susceptible bacteria, such as the Bcc, when exposed to P. aeruginosa toxins. Using P. aeruginosa spent medium …

Safe And Efficient Silencing With A Pol Ii, But Not A Pol Lii, Promoter Expressing An Artificial Mirna Targeting Human Huntingtin, Edith L. Pfister, Kathryn O. Chase, Huaming Sun, Lori A. Kennington, Faith Conroy, Emily Johnson, Rachael Miller, Florie Borel, Christian Mueller

Dartmouth Scholarship

Huntington's disease is a devastating, incurable neurodegenerative disease affecting up to 12 per 100,000 patients worldwide. The disease is caused by a mutation in the Huntingtin (Htt) gene. There is interest in reducing mutant Huntingtin by targeting it at the mRNA level, but the maximum tolerable dose and long-term effects of such a treatment are unknown. Using a self-complementary AAV9 vector, we delivered a mir-155-based artificial miRNA under the control of the chicken β-actin or human U6 promoter. In mouse brain, the artificial miRNA reduced the human huntingtin mRNA by 50%. The U6, but not the CβA promoter, produced the …

Genetic Variants Of Ptpn2 Are Associated With Lung Cancer Risk: A Re-Analysis Of Eight Gwass In The Tricl-Ilcco Consortium, Yun Feng, Yanru Wang, Hongliang Liu, Zhensheng Liu, Coleman Mills, Younghun Han, Rayjean J. Hung, Yonathan Brhane, John Mcclaughlin, Paul Brennan

Dartmouth Scholarship

The T-cell protein tyrosine phosphatase (TCPTP) pathway consists of signaling events mediated by TCPTP. Mutations and genetic variants of some genes in the TCPTP pathway are associated with lung cancer risk and survival. In the present study, we first investigated associations of 5,162 single nucleotide polymorphisms (SNPs) in 43 genes of this TCPTP pathway with lung cancer risk by using summary data of six published genome-wide association studies (GWAS) of 12,160 cases and 16,838 controls. We identified 11 independent SNPs in eight genes after correction for multiple comparisons by a false discovery rate < 0.20. Then, we performed in silico functional analyses for these 11 SNPs by eQTL analysis, two of which, PTPN2 SNPs rs2847297 and rs2847282, were chosen as tagSNPs. We further included two additional GWAS datasets of Harvard University (984 cases and 970 controls) and deCODE (1,319 cases and 26,380 controls), and the overall effects of these two SNPs among all eight GWAS studies remained significant (OR = 0.95, 95% CI = 0.92–0.98, and P = 0.004 for rs2847297; OR = 0.95, 95% CI = 0.92–0.99, and P = 0.009 for rs2847282). In conclusion, the PTPN2 rs2847297 and rs2847282 may be potential susceptible loci for lung cancer risk.

Production Of Putative Enhanced Oral Cholera Vaccine Strains That Express Toxin-Coregulated Pilus, Caitlyn A. Hauke, Ronald K. Taylor

Dartmouth Scholarship

The use of whole cell killed (WCK) oral cholera vaccines is an important strategy for cholera prevention in endemic areas. To overcome current vaccine limitations, we engineered strains of V. cholerae to be non-toxigenic and to express the protective protein colonization factor, toxin-coregulated pilus (TCP), under scale-up conditions potentially amenable to vaccine production. Two V. cholerae clinical strains were selected and their cholera toxin genes deleted. The tcp operon was placed under control of a rhamnose-inducible promoter. Production and stability of TCP were assessed under various conditions. The strains lack detectable cholera toxin production. The addition of 0.1% …

Tenofovir Inhibits Wound Healing Of Epithelial Cells And Fibroblasts From The Upper And Lower Human Female Reproductive Tract, Marta Rodriguez-Garcia, Mickey V. Patel, Zheng Shen, Jack Bodwell, Richard M. Rossol, Charles R. Wira

Dartmouth Scholarship

Disruption of the epithelium in the female reproductive tract (FRT) is hypothesized to increase HIV infection risk by interfering with barrier protection and facilitating HIV-target cell recruitment. Here we determined whether Tenofovir (TFV), used vaginally in HIV prevention trials, and Tenofovir alafenamide (TAF), an improved prodrug of TFV, interfere with wound healing in the human FRT. TFV treatment of primary epithelial cells and fibroblasts from the endometrium (EM), endocervix (CX) and ectocervix (ECX) significantly delayed wound closure. Reestablishment of tight junctions was compromised in EM and CX epithelial cells even after wound closure occurred. In contrast, TAF had no inhibitory …

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 …

Cis-Eqtl-Based Trans-Ethnic Meta-Analysis Reveals Novel Genes Associated With Breast Cancer Risk, Joshua Hoffman, Rebecca Graff, Nima Emami, Caroline Tai, Michael Passarelli

Dartmouth Scholarship

Breast cancer is the most common solid organ malignancy and the most frequent cause of cancer death among women worldwide. Previous research has yielded insights into its genetic etiology, but there remains a gap in the understanding of genetic factors that contribute to risk, and particularly in the biological mechanisms by which genetic variation modulates risk. The National Cancer Institute's "Up for a Challenge" (U4C) competition provided an opportunity to further elucidate the genetic basis of the disease. Our group leveraged the seven datasets made available by the U4C organizers and data from the publicly available UK Biobank cohort to …

Cxcr3+ Monocytes/Macrophages Are Required For Establishment Of Pulmonary Metastases, Kiah L. Butler, Eleanor Clancy-Thompson, David W. Mullins

Dartmouth Scholarship

We present a new foundational role for CXCR3 + monocytes/macrophages in the process of tumor engraftment in the lung. CXCR3 is associated with monocytic and lymphocytic infiltration of inflamed or tumor-bearing lung. Although the requirement for tumor-expressed CXCR3 in metastatic engraftment has been demonstrated, the role of monocyte-expressed CXCR3 had not been appreciated. In a murine model of metastatic-like melanoma, engraftment was coordinate with CXCR3 + monocyte/macrophage accumulation in the lungs and was sensitive to pharmacologic inhibition of CXCR3 signaling. Tumor engraftment to lung was impaired in CXCR3 − / − mice, and transient reconstitution with circulating CXCR3-replete monocytes was …

Use Of The 9-Item Shared Decision Making Questionnaire (Sdm-Q-9 And Sdm-Q-Doc) In Intervention Studies—A Systematic Review, Hanna Doherr, Eva Christalle, Levente Kriston, Martin Härter, Isabel Scholl

Dartmouth Scholarship

Background:

The Shared Decision Making Questionnaire (SDM-Q-9 and SDM-Q-Doc) is a 9-item measure of the decisional process in medical encounters from both patients’ and physicians’ perspectives. It has good acceptance, feasibility, and reliability. This systematic review aimed to 1) evaluate the use of the SDM-Q-9 and SDM-Q-Doc in intervention studies on shared decision making (SDM) in clinical settings, 2) describe how the SDM-Q-9 and SDM-Q-Doc performed regarding sensitivity to change, and 3) assess the methodological quality of studies and study protocols that use the measure.

Methods:

We conducted a systematic review of studies published between 2010 and October 2015 that …

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.

Mitogen-Activated Protein Kinase Phosphatase-3 (Mkp-3) In The Surgical Wound Is Necessary For The Resolution Of Postoperative Pain In Mice, Sladjana Skopelja-Gardner, Madhurima Saha, Perla Abigail Alvarado-Vazquez, Brenna S. Liponis, Elena Martinez, E Alfonso Romero-Sandoval

Dartmouth Scholarship

Mitogen-activated protein kinase (MAPK) phosphatase-3 (MKP-3) and its substrates (extracellular signal-regulated kinase [ERK] and p38) play an important role in pathophysiological mechanisms of acute postoperative and chronic neuropathic pain in the spinal cord. This study aimed to understand the role of MKP-3 and its target MAPKs at the site of surgical incision in nociceptive behavior. Wild-type (WT) and MKP-3 knockout (KO) mice underwent unilateral plantar hind paw incision. Mechanical allodynia was assessed by using von Frey filaments. Peripheral ERK-1/2 and p38 phosphorylation were measured by Western blot. Cell infiltration was determined using hematoxylin and eosin histological staining. Peripheral phosphorylated ERK-1/2 …

A Novel Multi-Network Approach Reveals Tissue-Specific Cellular Modulators Of Fibrosis In Systemic Sclerosis, Jaclyn N. Taroni, Casey S. Greene, Viktor Martyanov, Tammara A. Wood

Dartmouth Scholarship

Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology.We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast …

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, …

Lactate Dehydrogenase In Toxoplasma Gondii Controls Virulence, Bradyzoite Differentiation, And Chronic Infection, Abdelbaset E. Abdelbaset, Barbara A. Fox, Mohamed H. Karram, Mahmoud R. Abd Ellah, David J. Bzik, Makoto Igarashi

Dartmouth Scholarship

In the asexual stages, Toxoplasma gondii stage converts between acute phase rapidly replicating tachyzoites and chronic phase slowly dividing bradyzoites. Correspondingly, T. gondii differentially expresses two distinct genes and isoforms of the lactate dehydrogenase enzyme, expressing LDH1 exclusively in the tachyzoite stage and LDH2 preferentially in the bradyzoite stage. LDH catalyzes the interconversion of pyruvate and lactate in anaerobic growth conditions and is utilized for energy supply, however, the precise role of LDH1 and LDH2 in parasite biology in the asexual stages is still unclear. Here, we investigated the biological role of LDH1 and LDH2 in the asexual stages, …

Pseudomonas Aeruginosa Alginate Overproduction Promotes Coexistence With Staphylococcus Aureus In A Model Of Cystic Fibrosis Respiratory Infection, Dominique H. Limoli, Gregory B. Whitfield, Tomoe Kitao, Melissa L. Ivey, Michael R. Davis, Nora Grahl, Deborah A. Hogan, Laurence G. Rahme, P. Lynne Howell, George A. O'Toole, Joanna B. Goldberg

Dartmouth Scholarship

While complex intra- and interspecies microbial community dynamics are apparent during chronic infections and likely alter patient health outcomes, our understanding of these interactions is currently limited. For example, Pseudomonas aeruginosa and Staphylococcus aureus are often found to coinfect the lungs of patients with cystic fibrosis (CF), yet these organisms compete under laboratory conditions. Recent observations that coinfection correlates with decreased health outcomes necessitate we develop a greater understanding of these interbacterial interactions. In this study, we tested the hypothesis that P. aeruginosa and/or S. aureus adopts phenotypes that allow coexistence during infection. We compared competitive interactions of P. aeruginosa …

Greater Dyspnea Is Associated With Lower Health-Related Quality Of Life Among European Patients With Copd, Jean-Bernard Gruenberger, Jeffrey Vietri, Dorothy Keininger, Donald Mahler

Dartmouth Scholarship

OBJECTIVE:

Dyspnea is a defining symptom in the classification and treatment of chronic obstructive pulmonary disease (COPD). However, the degree of variation in burden among symptomatic COPD patients and the possible correlates of burden remain unclear. This study was conducted to characterize patients in Europe currently being treated for COPD according to the level of dyspnea in terms of sociodemographics, health-related quality of life, work productivity impairment, and health care resource use assessed by patient reports.

METHODS:

Data were derived from the 5-EU 2013 National Health and Wellness Survey (N=62,000). Respondents aged ≥40 years who reported currently using a prescription …

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 …

Gene-Set Meta-Analysis Of Lung Cancer Identifies Pathway Related To Systemic Lupus Erythematosus, Albert Rosenberger, Melanie Sohns, Stefanie Friedrichs, Rayjean J. Hung, Gord Fehringer, John Mclaughlin, Christopher I. Amos, Paul Brennan, Angela Risch, Irene Bruske, Neil E. Caporaso, Maria Teresa Landi, David C. Christiani, Yongyue Wei, Heike Bickeboller

Dartmouth Scholarship

Introduction: Gene-set analysis (GSA) is an approach using the results of single-marker genome-wide association studies when investigating pathways as a whole with respect to the genetic basis of a disease. Methods: We performed a meta-analysis of seven GSAs for lung cancer, applying the method META- GSA. Overall, the information taken from 11,365 cases and 22,505 controls from within the TRICL/ILCCO consortia was used to investigate a total of 234 pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results: META-GSA reveals the systemic lupus erythematosus KEGG pathway hsa05322 , driven by the gene region 6p21-22, as also …

Hyper-Methylated Loci Persisting From Sessile Serrated Polyps To Serrated Cancers, Angeline S. Andrew, John A. Baron, Lynn F. Butterfly, Arief A. Suriawinata, Gregory J. Tsongalis, Christina M. Robinson, Christopher I. Amos

Dartmouth Scholarship

Although serrated polyps were historically considered to pose little risk, it is now understood that progression down the serrated pathway could account for as many as 15%–35% of colorectal cancers. The sessile serrated adenoma/polyp (SSA/P) is the most prevalent pre-invasive serrated lesion. Our objective was to identify the CpG loci that are persistently hyper-methylated during serrated carcinogenesis, from the early SSA/P lesion through the later cancer phases of neoplasia development. We queried the loci hyper-methylated in serrated cancers within our rightsided SSA/Ps from the New Hampshire Colonoscopy Registry, using the Illumina Infinium Human Methylation 450 k panel to comprehensively assess …

Dueling Biological And Social Contagions, Feng Fu, Nicholas A. Christakis, James H. Fowler

Dartmouth Scholarship

Numerous models explore how a wide variety of biological and social phenomena spread in social networks. However, these models implicitly assume that the spread of one phenomenon is not affected by the spread of another. Here, we develop a model of “dueling contagions”, with a particular illustration of a situation where one is biological (influenza) and the other is social (flu vaccination). We apply the model to unique time series data collected during the 2009 H1N1 epidemic that includes information about vaccination, flu, and face-to-face social networks. The results show that well- connected individuals are more likely to get vaccinated, …

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 …

Boosting Of Hiv Envelope Cd4 Binding Site Antibodies With Long Variable Heavy Third Complementarity Determining Region In The Randomized Double Blind Rv305 Hiv-1 Vaccine Trial, David Easterhoff, M. Anthony Moody, Daniela Fera, Hao Cheng, Margaret Ackerman

Dartmouth Scholarship

The canary pox vector and gp120 vaccine (ALVAC-HIV and AIDSVAX B/E gp120) in the RV144 HIV-1 vaccine trial conferred an estimated 31% vaccine efficacy. Although the vaccine Env AE.A244 gp120 is antigenic for the unmutated common ancestor of V1V2 broadly neutralizing antibody (bnAbs), no plasma bnAb activity was induced. The RV305 (NCT01435135) HIV-1 clinical trial was a placebo-controlled randomized double-blinded study that assessed the safety and efficacy of vaccine boosting on B cell repertoires. HIV-1- uninfected RV144 vaccine recipients were reimmunized 6–8 years later with AIDSVAX B/E gp120 alone, ALVAC-HIV alone, or a combination of ALVAC-HIV and AIDSVAX B/E gp120 …

Evaluating Collaborate In A Clinical Setting: Analysis Of Mode Effects On Scores, Response Rates And Costs Of Data Collection, Paul J. Barr, Rachel C. Forcino, Rachel Thompson, Elissa M. Ozanne, Roger Arend, Molly Ganger Castaldo, A. James O'Malley, Glyn Elwyn

Dartmouth Scholarship

Shared decision-making (SDM) has become a policy priority, yet its implementation is not routinely assessed. To address this gap we tested the delivery of CollaboRATE, a 3-item patient reported experience measure of SDM, via multiple survey modes.To assess CollaboRATE response rates and respondent characteristics across different modes of administration, impact of mode and patient characteristics on SDM performance and cost of administration per response in a real-world primary care practice.Observational study design, with repeated assessment of SDM performance using CollaboRATE in a primary care clinic over 15 months of data collection. Different modes of administration were introduced sequentially including paper, …

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 …

Neighborhood Environment And Falls Among Community-Dwelling Older Adults, Emily Nicklett, Matthew Lohman, Matthew Smith

Dartmouth Scholarship

Falls present a major challenge to active aging, but the relationship between neighborhood factors and falls is poorly understood. This study examined the relationship between fall events and neighborhood factors, including neighborhood social cohesion (sense of belonging, trust, friendliness, and helpfulness) and physical environment (vandalism/graffiti, rubbish, vacant/deserted houses, and perceived safety walking home at night).