Showing papers by "University of Vermont published in 2022"

Covid-19 pandemic impacts on essential transit riders: Findings from a U.S. Survey

Abstract: The Covid-19 pandemic has decimated public transit service across the United States and caused significant decreases in ridership. Little is known about the reasons for unevenness in pandemic-era mode shifts and the impacts of pandemic-related transit reductions on riders’ day-to-day lives. Using a national survey of U.S. transit riders (n = 500) conducted in fall 2020, this study examines changes in transit use since the pandemic began, the reasons for transit reductions, and the effects of reduced transit use and transit service on transit riders’ ability to meet their travel needs. The Covid-19 pandemic has exacerbated existing transportation burdens for those who have limited mobility options, those facing socioeconomic challenges, Hispanic or Latinx riders, and female, non-binary or genderqueer people. We close with recommendations for strengthening transit service for these groups in the long term as we recover from the pandemic.

Effects of thermal sterilization on the allergenicity of soybeans

Abstract: The study assessed the effects of industrialized sterilization (boiling and autoclaving) on proteins immunoreactivity, composition and conformation of soybeans (R251, R252 and R253). The results of indirect ELISA demonstrated that boiling and autoclaving reduced the allergenicity of soybeans by 43%–59% and 82%–83%, respectively. SDS-PAGE revealed that there was more dramatic degradation of proteins in autoclaved soybeans, compared to boiled soybeans, resulting in the destruction of epitopes. LC/MS-MS and SEM showed the changes in amounts of peptides and unique peptides (proteins screening scores ≥ 20) and micro-structure, respectively, suggesting the structural changes. Circular dichroism furtherly illustrated a greater reduction of α-helix in autoclaved soybeans, resulting in the masking of epitopes. Conformational analyses demonstrated that the effects of boiling and autoclaving on conformation also varied among treatments and soybean cultivars. Interestingly, the surface hydrophobicity was increased and decreased after boiling and autoclaving, both resulting in the masking of epitopes. In conclusion, autoclaving was an effective method to reduce the allergenicity of soybeans, resulting from dramatic proteins-degradation and reduction of α-helix. Of note, the allergenicity of raw soybeans was positively correlated with their intensity of surface hydrophobicity and total amounts of peptides and unique peptides.

Impact of dimensions of early adversity on adult health and functioning: A 2-decade, longitudinal study

Abstract: Abstract Recent neurodevelopmental and evolutionary theories offer strong theoretical rationales and some empirical evidence to support the importance of specific dimensions of early adversity. However, studies have often been limited by omission of other adversity dimensions, singular outcomes, and short follow up durations. 1,420 participants in the community, Great Smoky Mountains Study, were assessed up to eight times between age 9 and 16 for four dimensions of early adversity: Threat, Material Deprivation, Unpredictability, and Loss (as well as a Cumulative Adversity measure). Participants were followed up to four times in adulthood (ages 19, 21, 25, and 30) to measure psychiatric disorders, substance disorder, and “real-world” functioning. Every childhood adversity dimension was associated with multiple adult psychiatric, substance, or functional outcomes when tested simultaneously in a multivariable analysis that accounted for other childhood adversities. There was evidence of differential impact of dimensions of adversity exposure on proximal outcomes (e.g., material deprivation and IQ) and even on distal outcomes (e.g., threat and emotional functioning). There were similar levels of prediction between the best set of individual adversity scales and a single cumulative adversity measure when considering distal outcomes. All dimensions of childhood adversity have lasting, pleiotropic effects, on adult health and functioning, but these dimensions may act via distinct proximal pathways.

Perspectives from healthcare professionals on the nutritional adequacy of plant-based dairy alternatives: results of a mixed methods inquiry

Abstract: Healthcare professionals are important sources of nutrition and health information for Americans. As plant-based (PB) dairy alternative products increase in popularity, concerns have been raised about their nutritional adequacy, and whether consumers understand nutritional differences to dairy. Healthcare professionals directly advise consumers on dietary choices, therefore we sought to examine their understanding and opinions of PB dairy alternatives.We analyzed comments submitted to the U.S. Food and Drug Administration (FDA) by health professionals (n = 191) in 2018-2019 in response to a request for public comment on the nutrition of PB dairy alternatives and the use of dairy terms like "milk", "cheese", and "yogurt" on their labels. Survey data from healthcare professionals (n = 417) was collected in 2020-2021. Comments and survey responses to open-ended questions were coded using template analysis and thematically analyzed. Logistic regression models examined perceptions across health professional characteristics for close-ended survey responses.Three-fourths of health professionals believe consumers are confused about the nutritional differences between dairy and PB dairy alternatives. Over half (53%) do not believe either product is nutritionally superior to the other. Many believe dairy products have higher nutrient value, but also believe PB dairy alternatives can be part of a healthful diet. Compared to other types of health professionals, dietetics professionals demonstrated a more accurate understanding of the nutritional value of both products and were more likely to believe nutrients like protein (OR 2.02; 95% CI 1.22-3.34, p = 0.006) and vitamin D (OR 2.46; 95% CI 1.48-4.09, p = 0.001) may be nutrients of concern for PB dairy alternative consumers. They were also more likely to believe consumers are confused about these products (OR 3.44; 95% CI 1.65-7.21; p = 0.001). Health professionals who submitted comments to the FDA showed stronger opinions in favor of PB dairy alternatives.Although PB dairy alternatives have nutritional value in certain diets, responses from health professionals suggest that changing their labeling to be different than dairy may reduce confusion. Improved nutrition education among health professionals may also be necessary.

Targeted RNA Sequencing of VZV-Infected Brain Vascular Adventitial Fibroblasts Indicates That Amyloid May Be Involved in VZV Vasculopathy

Abstract: Background and objectives Compared with stroke controls, patients with varicella zoster virus (VZV) vasculopathy have increased amyloid in CSF, along with increased amylin (islet amyloid polypeptide [IAPP]) and anti-VZV antibodies. Thus, we examined the gene expression profiles of VZV-infected primary human brain vascular adventitial fibroblasts (HBVAFs), one of the initial arterial cells infected in VZV vasculopathy, to determine whether they are a potential source of amyloid that can disrupt vasculature and potentiate inflammation. Methods Mock- and VZV-infected quiescent HBVAFs were harvested at 3 days postinfection. Targeted RNA sequencing of the whole-human transcriptome (BioSpyder Technologies, TempO-Seq) was conducted followed by gene set enrichment and pathway analysis. Selected pathways unique to VZV-infected cells were confirmed by enzyme-linked immunoassays, migration assays, and immunofluorescence analysis (IFA) that included antibodies against amylin and amyloid-beta, as well as amyloid staining by Thioflavin-T. Results Compared with mock, VZV-infected HBVAFs had significantly enriched gene expression pathways involved in vascular remodeling and vascular diseases; confirmatory studies showed secretion of matrix metalloproteinase-3 and -10, as well increased migration of infected cells and uninfected cells when exposed to conditioned media from VZV-infected cells. In addition, significantly enriched pathways involved in amyloid-associated diseases (diabetes mellitus, amyloidosis, and Alzheimer disease), tauopathy, and progressive neurologic disorder were identified; predicted upstream regulators included amyloid precursor protein, apolipoprotein E, microtubule-associated protein tau, presenilin 1, and IAPP. Confirmatory IFA showed that VZV-infected HBVAFs contained amyloidogenic peptides (amyloid-beta and amylin) and intracellular amyloid. Discussion Gene expression profiles and pathway enrichment analysis of VZV-infected HBVAFs, as well as phenotypic studies, reveal features of pathologic vascular remodeling (e.g., increased cell migration and changes in the extracellular matrix) that can contribute to cerebrovascular disease. Furthermore, the discovery of amyloid-associated transcriptional pathways and intracellular amyloid deposition in HBVAFs raise the possibility that VZV vasculopathy is an amyloid disease. Amyloid deposition may contribute to cell death and loss of vascular wall integrity, as well as potentiate chronic inflammation in VZV vasculopathy, with disease severity and recurrence determined by the host's ability to clear virus infection and amyloid deposition and by the coexistence of other amyloid-associated diseases (i.e., Alzheimer disease and diabetes mellitus).

Bio-inspired green light crosslinked alginate-heparin hydrogels support HUVEC tube formation.

Abstract: Alginate is a polysaccharide which forms hydrogels via ionic and/or covalent crosslinking. The goal was to develop a material with suitable, physiologically relevant mechanical properties and biological impact for use in wound treatment. To determine if the novel material can initiate tube formation on its own, without the dependance on the addition of growth factors, heparin and/or arginyl-glycyl-aspartic acid (RGD) was covalently conjugated onto the alginate backbone. Herein, cell adhesion motifs and bioactive functional groups were incorporated covalently within alginate hydrogels to study the: 1) impact of crosslinked heparin on tubular network formation, 2) impact of RGD conjugation, and the 3) biological effect of vascular endothelial growth factor (VEGF) loading on cellular response. We investigated the structure-properties-function relationship and determined the viscoelastic and burst properties of the hydrogels most applicable for use as a healing cell and tissue adhesive material. Methacrylation of alginate and heparin hydroxyl groups respectively enabled free-radical covalent inter- and intra-molecular photo-crosslinking when exposed to visible green light in the presence of photo-initiators; the shear moduli indicate mechanical properties comparable to clinical standards. RGD was conjugated via carbodiimide chemistry at the alginate carboxyl groups. The adhesive and mechanical properties of alginate and alginate-heparin hydrogels were determined via burst pressure testing and rheology. Higher burst pressure and material failure at rupture imply physical tissue adhesion, advantageous for a tissue sealant healing material. After hydrogel formation, human umbilical vein endothelial cells (HUVECs) were seeded onto the alginate-based hydrogels; cytotoxicity, total protein content, and tubular network formation were assessed. Burst pressure results indicate that the cell responsive hydrogels adhere to collagen substrates and exhibit increased strength under high pressures. Furthermore, the results show that the green light crosslinked alginate-heparin maintained cell adhesion and promoted tubular formation.

Personalized pacing for diastolic dysfunction and heart failure with preserved ejection fraction: Design and rationale for the myPACE randomized controlled trial

Abstract: Patients with pacemakers and heart failure with preserved ejection fraction (HFpEF) or isolated diastolic dysfunction (DD) may benefit from a higher backup heart rate (HR) setting compared with the standard setting of 60 bpm.The purpose of this study was to assess the effects of a personalized backup HR setting (myPACE group) compared with 60 bpm (control group).In this prospective, blinded, randomized controlled study, pacemaker patients with DD or HFpEF and atrial pacing with intrinsic ventricular conduction or conduction system or biventricular pacing are randomized to the myPACE group or control group for 1 year. The primary outcome is the change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores. Secondary endpoints include changes in N-terminal pro-brain natriuretic peptide levels, physical and emotional MLHFQ subscores, and pacemaker-detected atrial arrhythmia burden, patient activity levels, and thoracic impedance; hospitalization for heart failure, atrial fibrillation, cerebrovascular accident, or myocardial infarction; and loop diuretic or antiarrhythmic medication initiation or up-titration. A sample size of 118 subjects is expected to allow detection of a 5-point change in MLHFQ score in an intention-to-treat analysis and allow initial assessment of clinical outcomes and subgroup analyses.Enrollment began in July 2019. As of November 2020, 107 subjects have been enrolled. It is projected that the 1-year follow-up will be completed by December 2021.Atrial pacing with intrinsic ventricular conduction or advanced ventricular pacing at a higher, personalized backup HR may be a therapeutic target for patients with isolated DD or HFpEF. The myPACE trial is designed to test this hypothesis.

Therapeutic ketosis decreases methacholine hyperresponsiveness in mouse models of inherent obese asthma

Abstract: Obese asthmatics tend to have severe, poorly controlled disease and exhibit methacholine hyperresponsiveness manifesting in proximal airway narrowing and distal lung tissue collapsibility. Substantial weight loss in obese asthmatics or in mouse models of the condition decreases methacholine hyperresponsiveness. Ketone bodies are rapidly elevated during weight loss, coinciding with or preceding relief from asthma-related comorbidities. As ketone bodies may exert numerous potentially therapeutic effects, augmenting their systemic concentrations is being targeted for the treatment of several conditions. Circulating ketone body levels can be increased by feeding a ketogenic diet or by providing a ketone ester dietary supplement, which we hypothesized would exert protective effects in mouse models of inherent obese asthma. Weight loss induced by feeding a low-fat diet to mice previously fed a high-fat diet was preceded by increased urine and blood levels of the ketone body β-hydroxybutyrate (BHB). Feeding a ketogenic diet for 3 wk to high-fat diet-fed obese mice or genetically obese db/db mice increased BHB concentrations and decreased methacholine hyperresponsiveness without substantially decreasing body weight. Acute ketone ester administration decreased methacholine responsiveness of normal mice, and dietary ketone ester supplementation of high-fat diet-fed mice decreased methacholine hyperresponsiveness. Ketone ester supplementation also transiently induced an "antiobesogenic" gut microbiome with a decreased Fermicutes/Bacteroidetes ratio. Dietary interventions to increase systemic BHB concentrations could provide symptom relief for obese asthmatics without the need for the substantial weight loss required of patients to elicit benefits to their asthma through bariatric surgery or other diet or lifestyle alterations.

High Dimensional Multi-omics Reveals Unique Characteristics of Early Plasma Administration in Polytrauma Patients with TBI

Abstract: Objectives: The authors sought to identify causal factors that explain the selective benefit of prehospital administration of thawed plasma (TP) in traumatic brain injury (TBI) patients using mediation analysis of a multiomic database. Background: The Prehospital Air Medical Plasma (PAMPer) Trial showed that patients with TBI and a pronounced systemic response to injury [defined as endotype 2 (E2)], have a survival benefit from prehospital administration of TP. An interrogation of high dimensional proteomics, lipidomics and metabolomics previously demonstrated unique patterns in circulating biomarkers in patients receiving prehospital TP, suggesting that a deeper analysis could reveal causal features specific to TBI patients. Methods: A novel proteomic database (SomaLogic Inc., aptamer-based assay, 7K platform) was generated using admission blood samples from a subset of patients (n=149) from the PAMPer Trial. This proteomic dataset was combined with previously reported metabolomic and lipidomic datasets from these same patients. A 2-step analysis was performed to identify factors that promote survival in E2-TBI patients who had received early TP. First, features were selected using both linear and multivariate-latent-factor regression analyses. Then, the selected features were entered into the causal mediation analysis. Results: Causal mediation analysis of observable features identified 16 proteins and 41 lipids with a high proportion of mediated effect (>50%) to explain the survival benefit of early TP in E2-TBI patients. The multivariate latent-factor regression analyses also uncovered 5 latent clusters of features with a proportion effect >30%, many in common with the observable features. Among the observable and latent features were protease inhibitors known to inhibit activated protein C and block fibrinolysis (SERPINA5 and CPB2), a clotting factor (factor XI), as well as proteins involved in lipid transport and metabolism (APOE3 and sPLA(2)-XIIA). Conclusions: These findings suggest that severely injured patients with TBI process exogenous plasma differently than those without TBI. The beneficial effects of early TP in E2-TBI patients may be the result of improved blood clotting and the effect of brain protective factors independent of coagulation.

Craving among individuals with stimulant use disorder in residential social model-based treatment – Can exercise help?

Abstract: In a randomized controlled 8-week trial, we examined the efficacy of aerobic and resistance exercise in reducing craving for methamphetamine (MA) among individuals with MA-use disorder during residential treatment.Individuals with MA use disorder (138) who were newly enrolled in residential treatment volunteered for random assignment to either an 8-week exercise intervention (EX) or health education control (HE), with both conditions meeting 3 times weekly; 3 dropped out of the trial, bringing the analysis sample to 135. The majority of participants were male (80%), and 48% were Latino/Hispanic. The mean age of the sample was 31.7 (SD = 6.9) years. Using multivariate mixed models, differences between conditions were examined in: (1) craving for MA, measured by self-reported ratings on a Visual Analog Scale over the 8-week trial and, (2) MA use, measured by self-report and urine drug screens at baseline and 30 and 60 days after discharge from the 8-week study.Results revealed significantly lower craving scores among the participants in the EX group than those in the HE group over the 8-week trial (median daily craving score for EX = 13.5, for HE = 21.8; p = .009). In addition, participants with less craving during treatment had significantly lower rates of MA use after discharge than participants with high craving measured at 30-days (p = .004) and 60-days post-discharge (p < .001).Results support the utility of incorporating a structured exercise program for individuals with MA-use disorder to reduce craving and improve MA-use outcomes.

The pathogenic R5L mutation disrupts formation of Tau complexes on the microtubule by altering local N-terminal structure

Abstract: The microtubule-associated protein (MAP) Tau is an intrinsically disordered protein (IDP) primarily expressed in axons, where it functions to regulate microtubule dynamics, modulate motor protein motility, and participate in signaling cascades. Tau misregulation and point mutations are linked to neurodegenerative diseases, including progressive supranuclear palsy (PSP), Pick's disease, and Alzheimer's disease. Many disease-associated mutations in Tau occur in the C-terminal microtubule-binding domain of the protein. Effects of C-terminal mutations in Tau have led to the widely accepted disease-state theory that missense mutations in Tau reduce microtubule-binding affinity or increase Tau propensity to aggregate. Here, we investigate the effect of an N-terminal arginine to leucine mutation at position 5 in Tau (R5L), associated with PSP, on Tau-microtubule interactions using an in vitro reconstituted system. Contrary to the canonical disease-state theory, we determine that the R5L mutation does not reduce Tau affinity for the microtubule using total internal reflection fluorescence microscopy. Rather, the R5L mutation decreases the ability of Tau to form larger-order complexes, or Tau patches, at high concentrations of Tau. Using NMR, we show that the R5L mutation results in a local structural change that reduces interactions of the projection domain in the presence of microtubules. Altogether, these results challenge both the current paradigm of how mutations in Tau lead to disease and the role of the projection domain in modulating Tau behavior on the microtubule surface.

Untaming/untameable tongues: methodological openings and critical strategies for tracing raciality

Abstract: Race theories generate method-making and onto-epistemological connections central to inquiry. In this article, the authors share a conversation that created methodological openings about what constitutes ‘racially just’ in this particular moment of qualitative research. Is the call for ‘racially just’ a form of disruption or rupture? Is it a logic of inclusion, or a logic of obliteration? While the racial character of knowledge systems has become more explicit, it is important to consider how the analytics of raciality, a social scientific apparatus that produces racial subjugation, is already configured and entangled within sociopolitical systems. Following the work of Denise Ferreira da Silva, the authors argue that attention to raciality requires a different set of critical strategies for troubling ‘racially just’ approaches in the name of racial justice, asking more of themselves, of each other, and of their collective aims to unsettle colonial and racial logics within and outside of higher education institutions. The potential for transforming research practises and the teaching of research methods, by building on radical women of colour feminisms, are also discussed.