Medicine and Health Sciences Commons^™

Simulations For Designing And Interpreting Intervention Trials In Infectious Diseases., M Elizabeth Halloran, Kari Auranen, Sarah Baird, Nicole E Basta, Steven E Bellan, +Several Additional Authors

Global Health Faculty Publications

BACKGROUND: Interventions in infectious diseases can have both direct effects on individuals who receive the intervention as well as indirect effects in the population. In addition, intervention combinations can have complex interactions at the population level, which are often difficult to adequately assess with standard study designs and analytical methods.

DISCUSSION: Herein, we urge the adoption of a new paradigm for the design and interpretation of intervention trials in infectious diseases, particularly with regard to emerging infectious diseases, one that more accurately reflects the dynamics of the transmission process. In an increasingly complex world, simulations can explicitly represent transmission dynamics, …

The Effect Of Rare Variants In Trem2 And Pld3 On Longitudinal Cognitive Function In The Wisconsin Registry For Alzheimer's Prevention, Corinne D. Engelman, Burcu F. Darst, Murat Bilgel, Eva Vasiljevic, Rebecca L. Koscik, Bruno M. Jedynak, Sterling C. Johnson

Mathematics and Statistics Faculty Publications and Presentations

Recent studies have found an association between functional variants in TREM2 and PLD3 and Alzheimer's disease (AD), but their effect on cognitive function is unknown. We examined the effect of these variants on cognitive function in 1449 participants from the Wisconsin Registry for Alzheimer's Prevention, a longitudinal study of initially asymptomatic adults, aged 36–73 years at baseline, enriched for a parental history of AD. A comprehensive cognitive test battery was performed at up to 5 visits. A factor analysis resulted in 6 cognitive factors that were standardized into z scores (∼N [0, 1]); the mean of these z scores was …

Atomistic Simulations And Network-Based Modeling Of The Hsp90-Cdc37 Chaperone Binding With Cdk4 Client Protein: A Mechanism Of Chaperoning Kinase Clients By Exploiting Weak Spots Of Intrinsically Dynamic Kinase Domains, John Czemeres, Kurt Buse, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

A fundamental role of the Hsp90 and Cdc37 chaperones in mediating conformational development and activation of diverse protein kinase clients is essential in signal transduction. There has been increasing evidence that the Hsp90-Cdc37 system executes its chaperoning duties by recognizing conformational instability of kinase clients and modulating their folding landscapes. The recent cryo-electron microscopy structure of the Hsp90-Cdc37- Cdk4 kinase complex has provided a framework for dissecting regulatory principles underlying differentiation and recruitment of protein kinase clients to the chaperone machinery. In this work, we have combined atomistic simulations with protein stability and network-based rigidity decomposition analyses to characterize dynamic …

Virtual Reality As A Training Tool To Treat Physical Inactivity In Children, Adam W. Kiefer, David Pincus, Michael J. Richardson, Gregory D. Myer

Psychology Faculty Articles and Research

Lack of adequate physical activity in children is an epidemic that can result in obesity and other poor health outcomes across the lifespan. Physical activity interventions focused on motor skill competence continue to be developed, but some interventions, such as neuromuscular training (NMT), may be limited in how early they can be implemented due to dependence on the child’s level of cognitive and perceptual-motor development. Early implementation of motor-rich activities that support motor skill development in children is critical for the development of healthy levels of physical activity that carry through into adulthood. Virtual reality (VR) training may be beneficial …

The Role Of Catalytic Residue PKA On The Hydrolysis/Transglycosylation Partition In Family 3 Β-Glucosidases, Inacrist Geronimo, Christina M. Payne, Mats Sandgren

Chemical and Materials Engineering Faculty Publications

β-Glucosidases (βgls) primarily catalyze the hydrolysis of the terminal glycosidic bond at the non-reducing end of β-glucosides, although glycosidic bond synthesis (called transglycosylation) can also occur in the presence of another acceptor. In the final reaction step, the glucose product or another substrate competes with water for transfer to the glycosyl-enzyme intermediate. The factors governing the balance between the two pathways are not fully known; however, the involvement of ionizable residues in binding and catalysis suggests that their pK_a may play a role. Through constant pH molecular dynamics simulations of a glycoside hydrolase Family 3 (GH3) βgl, we …

Long-Term Outcomes After Elective Sterilization Procedures — A Comparative Retrospective Cohort Study Of Medicaid Patients, Rachel Steward, Patricia Carney, Amy Law, Lin Xie, Yuexi Wang, Huseyin Yuce

Publications and Research

Objectives: The objectives were to compare the long-termoutcomes, including hysterectomy, chronic pelvic pain (CPP) and abnormal uterine bleeding (AUB), in women post hysteroscopic sterilization (HS) and laparoscopic tubal ligation (TL) in the Medicaid population.

Study design: This was a retrospective observational cohort analysis using data from the US Medicaid Analytic Extracts Encounters database.Women aged 18 to 49 years with at least one claimfor HS (n=3929) or TL (n=10,875) between July 1, 2009, through December 31, 2010, were included. Main outcome measures were hysterectomy, CPP or AUB in the 24 months poststerilization. Propensity score matching was used to control for patient …

Fluoroethoxy-1,4-Diphenethylpiperidine And Piperazine Derivatives: Potent And Selective Inhibitors Of [3H]Dopamine Uptake At The Vesicular Monoamine Transporter-2, Emily R. Hankosky, Shyam R. Joolakanti, Justin R. Nickell, Venumadhav Janganati, Linda P. Dwoskin, Peter A. Crooks

Pharmaceutical Sciences Faculty Publications

A small library of fluoroethoxy-1,4-diphenethyl piperidine and fluoroethoxy-1,4-diphenethyl piperazine derivatives were designed, synthesized and evaluated for their ability to inhibit [³H]dopamine (DA) uptake at the vesicular monoamine transporter-2 (VMAT2) and dopamine transporter (DAT), [³H]serotonin (5-HT) uptake at the serotonin transporter (SERT), and [³H]dofetilide binding at the human-ether-a-go-go-related gene (hERG) channel. The majority of the compounds exhibited potent inhibition of [³H]DA uptake at VMAT2, with Ki values in the nanomolar range (K_i = 0.014–0.073 μM). Compound 15d exhibited the highest affinity (K_i = 0.014 μM) at VMAT2, and had 160-, 5-, …

Long-Term Follow-Up Of Cardiac Function And Quality Of Life For Patients In Nsabp Protocol B-31/Nrg Oncology: A Randomized Trial Comparing The Safety And Efficacy Of Doxorubicin And Cyclophosphamide (Ac) Followed By Paclitaxel With Ac Followed By Paclitaxel And Trastuzumab In Patients With Node-Positive Breast Cancer With Tumors Overexpressing Human Epidermal Growth Factor Receptor 2, Patricia A. Ganz, Edward H. Romond, Reena S. Cecchini, Priya Rastogi, Charles E. Geyer Jr., Sandra M. Swain, Jong-Hyeon Jeong, Louis Fehrenbacher, Howard M. Gross, Adam M. Brufsky, Patrick J. Flynn, Tanya A. Wahl, Thomas E. Seay, James L. Wade Iii, David D. Biggs, James N. Atkins, Jonathan Polikoff, John L. Zapas, Eleftherios P. Mamounas, Norman Wolmark

Markey Cancer Center Faculty Publications

Purpose

Early cardiac toxicity is a risk associated with adjuvant chemotherapy plus trastuzumab. However, objective measures of cardiac function and health-related quality of life are lacking in long-term follow-up of patients who remain cancer free after completion of adjuvant treatment.

Patients and Methods

Patients in NSABP Protocol B-31 received anthracycline and taxane chemotherapy with or without trastuzumab for adjuvant treatment of node-positive, human epidermal growth factor receptor 2–positive early-stage breast cancer. A long-term follow-up assessment was undertaken for patients who were alive and disease free, which included measurement of left ventricular ejection fraction by multigated acquisition scan along with patient-reported …

Bayesian Prediction Intervals For Assessing P-Value Variability In Prospective Replication Studies, Olga A. Vsevolozhskaya, Gabriel Ruiz, Dmitri Zaykin

Biostatistics Faculty Publications

Increased availability of data and accessibility of computational tools in recent years have created an unprecedented upsurge of scientific studies driven by statistical analysis. Limitations inherent to statistics impose constraints on the reliability of conclusions drawn from data, so misuse of statistical methods is a growing concern. Hypothesis and significance testing, and the accompanying P-values are being scrutinized as representing the most widely applied and abused practices. One line of critique is that P-values are inherently unfit to fulfill their ostensible role as measures of credibility for scientific hypotheses. It has also been suggested that while P-values …

Pretargeting Of Internalizing Trastuzumab And Cetuximab With A 18f-Tetrazine Tracer In Xenograft Models, Outi Keinänen, Kimberly Fung, Jacob Pourat, Vilma Jallinoja, Delphine Vivier, Nagavara Kishore Pillarsetty, Anu J. Airaksinen, Jason S. Lewis, Brian M. Zeglis, Mirkka Sarparanta

Publications and Research

Background: Pretargeting-based approaches are being investigated for radioimmunoimaging and therapy applications to reduce the effective radiation burden to the patient. To date, only a few studies have used short-lived radioisotopes for pretargeting of antibodies, and such examples with internalizing antibodies are even rarer. Herein, we have investigated pretargeting methodology using inverse electron-demand Diels-Alder (IEDDA) for tracing two clinically relevant, internalizing monoclonal antibodies, cetuximab and trastuzumab.

Results: Bioorthogonal reaction between tetrazine and trans-cyclooctene (TCO) was used for tracing cetuximab and trastuzumab in vivo with a fluorine-18 (t½ = 109.8 min) labelled tracer. TCO-cetuximab or TCO-trastuzumab was administered 24, 48, or 72 …

Evaluating Spatial Variability In Sediment And Phosphorus Concentration-Discharge Relationships Using Bayesian Inference And Self-Organizing Maps, Kristen L. Underwood, Donna M. Rizzo, Andrew W. Schroth, Mandar M. Dewoolkar

College of Engineering and Mathematical Sciences Faculty Publications

Given the variable biogeochemical, physical, and hydrological processes driving fluvial sediment and nutrient export, the water science and management communities need data-driven methods to identify regions prone to production and transport under variable hydrometeorological conditions. We use Bayesian analysis to segment concentration-discharge linear regression models for total suspended solids (TSS) and particulate and dissolved phosphorus (PP, DP) using 22 years of monitoring data from 18 Lake Champlain watersheds. Bayesian inference was leveraged to estimate segmented regression model parameters and identify threshold position. The identified threshold positions demonstrated a considerable range below and above the median discharge—which has been used previously …

A Customized Quantitative Pcr Microrna Panel Provides A Technically Robust Context For Studying Neurodegenerative Disease Biomarkers And Indicates A High Correlation Between Cerebrospinal Fluid And Choroid Plexus Microrna Expression, Wang-Xia Wang, David W. Fardo, Gregory A. Jicha, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNA (miRNA) expression varies in association with different tissue types and in diseases. Having been found in body fluids including blood and cerebrospinal fluid (CSF), miRNAs constitute potential biomarkers. CSF miRNAs have been proposed as biomarkers for neurodegenerative diseases; however, there is a lack of consensus about the best candidate miRNA biomarkers and there has been variability in results from different research centers, perhaps due to technical factors. Here, we sought to optimize technical parameters for CSF miRNA studies. We examined different RNA isolation methods and performed miRNA expression profiling with TaqMan® miRNA Arrays. More specifically, we developed a customized …

Home Health Care Delivery Problem, Aldy Gunawan, Hoong Chuin Lau, Kun Lu

Research Collection School Of Computing and Information Systems

We address the Home Health Care Delivery Problem (HHCDP), which is concerned with staff scheduling in the home health care industry. The goal is to schedule health care providers to serve patients at their homes that maximizes the total collected preference scores from visited patients subject to several constraints, such as workload of the health care providers, time budget for each provider and so on. The complexity lies in the possibility of cancellation of patient bookings dynamically, and the generated schedule should attempt to patients’ preferred time windows. To cater to these requirements, we model the preference score as a …

A Multi-Country Assessment Of Factors Related To Smallholder Food Security In Varying Rainfall Conditions, Meredith T. Niles, Molly E. Brown

College of Agriculture and Life Sciences Faculty Publications

Given that smallholder farmers are frequently food insecure and rely significantly on rain-fed agriculture, it is critical to examine climate variability and food insecurity. We utilize data from smallholder farmer surveys from 12 countries with 30 years of rainfall data to examine how rainfall variability and household resources are correlated with food security. We find that on average, households that experienced a drier than average year are 3.81 months food insecure, while households within a normal range of rainfall were 3.67 months food insecure, and wetter than average households were 2.86 months food insecure. Reduced odds of food insecurity is …

Genomic Signature Of Adaptive Divergence Despite Strong Nonadaptive Forces On Edaphic Islands: A Case Study Of Primulina Juliae, Jing Wang, Chao Feng, Tenglong Jiao, Eric Bishop Von Wettberg, Ming Kang

College of Agriculture and Life Sciences Faculty Publications

Both genetic drift and divergent selection are expected to be strong evolutionary forces driving population differentiation on edaphic habitat islands. However, the relative contribution of genetic drift and divergent selection to population divergence has rarely been tested simultaneously. In this study, restriction-site associated DNA-based population genomic analyses were applied to assess the relative importance of drift and divergent selection on population divergence of Primulina juliae, an edaphic specialist fromsouthern China. All populations were found with low standing genetic variation, small effective population size (NE), and signatures of bottlenecks. Populations with the lowest genetic variation were most genetically differentiated from other …

Reliability Of An Observational Method Used To Assess Tennis Serve Mechanics In A Group Of Novice Raters, Natalie L. Myers, W. Ben Kibler, Gilson J. Capilouto, Philip M. Westgate, Tony English, Timothy L. Uhl

Physical Therapy Faculty Publications

Background: Previous research has developed an observational tennis serve analysis (OTSA) tool to assess serve mechanics. The OTSA has displayed substantial agreement between the two health care professionals that developed the tool; however, it is currently unknown if the OTSA is reliable when administered by novice users.

Purpose: The purpose of this investigation was to determine if reliability for the OTSA could be established in novice users via an interactive classroom training session.

Methods: Eight observers underwent a classroom instructional training protocol highlighting the OTSA. Following training, observers participated in two different rating sessions approximately a week apart. Each observer …

A Cluster Analysis Of Challenging Behaviors In Autism Spectrum Disorder, Elizabeth Stevens, Abigail Atchison, Laura Stevens, Esther Hong, Doreen Granpeesheh, Dennis Dixon, Erik J. Linstead

Mathematics, Physics, and Computer Science Faculty Articles and Research

We apply cluster analysis to a sample of 2,116 children with Autism Spectrum Disorder in order to identify patterns of challenging behaviors observed in home and centerbased clinical settings. The largest study of this type to date, and the first to employ machine learning, our results indicate that while the presence of multiple challenging behaviors is common, in most cases a dominant behavior emerges. Furthermore, the trend is also observed when we train our cluster models on the male and female samples separately. This work provides a basis for future studies to understand the relationship of challenging behavior profiles to …

Disease Gene Classification With Metagraph Representations, Sezin Kircali Ata, Yuan Fang, Min Wu, Xiao-Li Li, Xiaokui Xiao

Research Collection School Of Computing and Information Systems

Protein-protein interaction (PPI) networks play an important role in studying the functional roles of proteins, including their association with diseases. However, protein interaction networks are not sufficient without the support of additional biological knowledge for proteins such as their molecular functions and biological processes. To complement and enrich PPI networks, we propose to exploit biological properties of individual proteins. More specifically, we integrate keywords describing protein properties into the PPI network, and construct a novel PPI-Keywords (PPIK) network consisting of both proteins and keywords as two different types of nodes. As disease proteins tend to have a similar topological characteristics …

An Analysis Of Operant Conditioning And Its Relationship With Video Game Addiction, Daniel Vu

ART 108: Introduction to Games Studies

A report published by the Entertainment Software Association revealed that in 2015, 155 million Americans play video games with an average of two gamers in each game-playing household (Entertainment Software Association, “Essential Facts about the Computer and Video Game Industry”). With this massive popularity that has sprung alongside video games, the question must be asked: how are video games affecting today's people? With the current way some video games are structured, the video game rewards players for achieving certain accomplishments. For example, competitive video games reward players who achieve victories by giving them a higher ranking or other games display …

Challenges In Characterizing The Environmental Fate And Effects Of Carbon Nanotubes And Inorganic Nanomaterials In Aquatic Systems, Peter Laux, Christian Riebeling, Andy M. Booth, Joseph D. Brain, Josephine Brunner, Cristina Cerrillo, Otto Creutzenberg, Irina Estrela-Lopis, Thomas Gebel, Gunnar Johanson, Harald Jungnickel, Heiko Kock, Jutta Tentschert, Ahmed Tlili, Andreas Schäffer, Adriënne J. A. M. Sips, Robert A. Yokel, Andreas Luch

Pharmaceutical Sciences Faculty Publications

The current lack of commonly used protocols for dispersion, characterization, and aquatic toxicity testing of nanomaterials (NMs) has resulted in inconsistent results, which make meaningful comparisons difficult. The need for standardized sample preparation procedures that allow the reproducible generation of relevant test conditions remains a key challenge for studies of the environmental fate and aquatic toxicity of NMs. Together with the further development of optimized and cost-effective analytical techniques for physicochemical characterization that depend on reproducible sample preparation, such methods have the potential to overcome the current uncertainties with regard to NM dispersion properties, effective dose, and particle dissolution. In …

In Place: November 27, 2017, Place

PLACE Historical Documents

In PLACE is a newsletter designed to keep the Linfield College community apprised of information related to PLACE activities, as well as ways to bring the program into classes. Included in this issue:

• Spotlight On: "What's the Big Idea"
• Upcoming Events
• PLACE in the News

Clinical Evaluation Of The Cepheid Xpert® Tv Assay For Detection Of Trichomonas Vaginalis With Prospectively Collected Female And Male Specimens., Jane R Schwebke, C A Gaydos, T Davis, J Marrazzo, D Furgerson, S N Taylor, B Smith, L H Bachmann, R Ackerman, T Spurrell, D Ferris, C A Burnham, H Reno, J Lebed, D Eisenberg, P Kerndt, S Philip, J Jordan, N Quigley

Epidemiology Faculty Publications

Trichomoniasis is the most prevalent curable sexually transmitted disease (STD). It has been associated with preterm birth and acquisition/transmission of HIV. Recently, nucleic acid amplification tests (NAAT) have been FDA-cleared in the United States for detection of Trichomonas vaginalis (TV) in specimens from both women and men. This current study reports the results of a multicenter study recently conducted using the Xpert TV Assay to test specimens from both men and women. On-demand results were available in as little as 40 minutes for positive specimens. A total of 1867 women and 4791 men were eligible for inclusion in the analysis. …

Reducing Symptom Distress In Patients With Advanced Cancer Using An E-Alert System For Caregivers: Pooled Analysis Of Two Randomized Clinical Trials, David H. Gustafson, Lori L. Dubenske, Amy K. Atwood, Ming-Yuan Chih, Roberta A. Johnson, Fiona Mctavish, Andrew Quanbeck, Roger L. Brown, James F. Cleary, Dhavan Shah

Health and Clinical Sciences Faculty Publications

Background: Symptom distress in patients toward the end of life can change rapidly. Family caregivers have the potential to help patients manage those symptoms, as well as their own stress, if they are equipped with the proper resources. Electronic health (eHealth) systems may be able to provide those resources. Very sick patients may not be able to use such systems themselves to report their symptoms but family caregivers could.

Objective: The aim of this paper was to assess the effects on cancer patient symptom distress of an eHealth system that alerts clinicians to significant changes in the patient’s symptoms, as …

Evaluating And Improving The Effectiveness Of Vehicle Inspection And Maintenance Programs: A Cost-Benefit Analysis Framework, Ying Li

ETSU Faculty Works

Motor vehicle inspection and maintenance (I/M) programs are designed to identify high-emitting vehicles and mitigate their impacts on air quality and climate. I/M programs have been traditionally ranked superior among various vehicle emission control measures by the results of cost-benefit analysis, based on the assumption that these programs will achieve the targeted emission reduction outcomes. However, the actual effects of I/M programs may be greatly uncertain and when this uncertainty is taken into account, these programs may become suboptimal. This study develops a new a cost-benefit analysis framework that links various program design consideration, such as program participation rate, identification …

Effects Of Global Warming On Work-Rest Routines For Crop Workers In Appalachia, Ken Silver, Ying Li, Emmanuel Odame, Yuqiang Zhang

ETSU Faculty Works

Background: Workers in outdoor occupations are expected to be at high risk of increased morbidity and mortality, and diminished productivity, as a result of global warming in the 21st century. A previous modelling study of geographic variations in heat-related mortality risk in projected U.S. populations mid-century showed the states of Tennessee, Kentucky and North Carolina to be highly vulnerable. Methods: Under both the RCP4.5 and RCP8.5 emissions scenarios of IPCC AR5, we evaluate the effect of future warming on estimated Wet Bulb Globe Thermometer (WBGT) temperatures using model-simulated future climate variables that were dynamically downscaled by a regional meteorology model …

The Complete Chloroplast Genome Of Primulina And Two Novel Strategies For Development Of High Polymorphic Loci For Population Genetic And Phylogenetic Studies, Chao Feng, Meizhen Xu, Chen Feng, Eric J.B. Von Wettberg, Ming Kang

College of Agriculture and Life Sciences Faculty Publications

Background: Primulina Hance is an emerging model for studying evolutionary divergence, adaptation and speciation of the karst flora. However, phylogenetic relationships within the genus have not been resolved due to low variation detected in the cpDNA regions. Chloroplast genomes can provide important information for phylogenetic and population genetic studies. Recent advances in next-generation sequencing (NGS) techniques greatly facilitate sequencing whole chloroplast genomes for multiple individuals. Consequently, novel strategies for development of highly polymorphic loci for population genetic and phylogenetic studies based on NGS data are needed. Methods: For development of high polymorphic loci for population genetic and phylogenetic studies, two …

In Place: November 6, 2017, Place

PLACE Historical Documents

In PLACE is a newsletter designed to keep the Linfield College community apprised of information related to PLACE activities, as well as ways to bring the program into classes. Included in this issue:

• Spotlight On: PLACE Sponsored Events
• Upcoming Events
• PLACE in the News

Ensemble-Based Modeling And Rigidity Decomposition Of Allosteric Interaction Networks And Communication Pathways In Cyclin-Dependent Kinases: Differentiating Kinase Clients Of The Hsp90-Cdc37 Chaperone, Gabrielle Stetz, Amanda Tse, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The overarching goal of delineating molecular principles underlying differentiation of protein kinase clients and chaperone-based modulation of kinase activity is fundamental to understanding activity of many oncogenic kinases that require chaperoning of Hsp70 and Hsp90 systems to attain a functionally competent active form. Despite structural similarities and common activation mechanisms shared by cyclin-dependent kinase (CDK) proteins, members of this family can exhibit vastly different chaperone preferences. The molecular determinants underlying chaperone dependencies of protein kinases are not fully understood as structurally similar kinases may often elicit distinct regulatory responses to the chaperone. The regulatory divergences observed for members of CDK …

Organic Solvent Exposure And Depressive Symptoms Among Licensed Pesticide Applicators In The Agricultural Health Study, Miriam Siegel, Sarah E. Starks, Wayne T. Sanderson, Freya Kamel, Jane A. Hoppin, Fred Gerr

Epidemiology and Environmental Health Faculty Publications

Purpose

Although organic solvents are often used in agricultural operations, neurotoxic effects of solvent exposure have not been extensively studied among farmers. The current analysis examined associations between questionnaire-based metrics of organic solvent exposure and depressive symptoms among farmers.

Methods

Results from 692 male Agricultural Health Study participants were analyzed. Solvent type and exposure duration were assessed by questionnaire. An “ever-use” variable and years of use categories were constructed for exposure to gasoline, paint/lacquer thinner, petroleum distillates, and any solvent. Depressive symptoms were ascertained with the Center for Epidemiologic Studies Depression Scale (CES-D); scores were analyzed separately as continuous (0–60) …

Combustion-Derived Nanoparticles, The Neuroenteric System, Cervical Vagus, Hyperphosphorylated Alpha Synuclein And Tau In Young Mexico City Residents, Lilian Calderón-Garcidueñas, Rafael Reynoso-Robles, Beatriz Pérez-Guillé, Partha S. Mukherjee, Angélica Gónzalez-Maciel

Mathematics Faculty Publications and Presentations

Mexico City (MC) young residents are exposed to high levels of fine particulate matter (PM_2.5), have high frontal concentrations of combustion-derived nanoparticles (CDNPs), accumulation of hyperphosphorylated aggregated α-synuclein (α-Syn) and early Parkinson's disease (PD). Swallowed CDNPs have easy access to epithelium and submucosa, damaging gastrointestinal (GI) barrier integrity and accessing the enteric nervous system (ENS). This study is focused on the ENS, vagus nerves and GI barrier in young MC v clean air controls. Electron microscopy of epithelial, endothelial and neural cells and immunoreactivity of stomach and vagus to phosphorylated ɑ-synuclein Ser129 and Hyperphosphorylated-Tau (Htau) …