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Search Results: 1 - 10 of 201268 matches for " Megan N. Hall "
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Nutritional Manipulation of One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity
Megan N. Hall,Mary V. Gamble
Journal of Toxicology , 2012, DOI: 10.1155/2012/595307
Abstract: Exposure to arsenic (As) through drinking water is a substantial problem worldwide. The methylation of As, a reactive metalloid, generates monomethyl- (MMA) and dimethyl-arsenical (DMA) species. The biochemical pathway that catalyzes these reactions, one-carbon metabolism, is regulated by folate and other micronutrients. Arsenic methylation exerts a critical influence on both its urinary elimination and chemical reactivity. Mice having the As methyltransferase null genotype show reduced urinary As excretion, increased As retention, and severe systemic toxicity. The most toxic As metabolite in vitro is M M A I I I , an intermediate in the generation of D M A V , a much less toxic metabolite. These findings have raised the question of whether As methylation is a detoxification or bioactivation pathway. Results of population-based studies suggest that complete methylation of inorganic As to DMA is associated with reduced risk for As-induced health outcomes, and that nutrients involved in one-carbon metabolism, such as folate, can facilitate As methylation and elimination. 1. Introduction Arsenic (As) is a naturally occurring element commonly present in environmental sources such as air, water, and soil [1]. Through processes that are incompletely understood, As in soil can be mobilized leading to enrichment of As in groundwater. While drinking water is the most common source of exposure, other sources include As from mining and smelting, wood preservatives, pesticides, and foods irrigated and/or prepared with As-contaminated water. Current estimates suggest that roughly 140 million people in Bangladesh, India, Vietnam, Nepal, and Cambodia are drinking water with As concentrations up to 100 times the World Health Organization (WHO) and USA Environmental Protection Agency (EPA) guideline of 10?μg/L [2, 3]. Chile, Mexico, China, and Taiwan also have As in groundwater that is used for drinking. In comparison to the situation in South and East Asia, the magnitude of the problem in the USA is relatively small. Nevertheless, the US Geological Survey estimates that 42 million Americans obtain their drinking water from household wells, and roughly 15% of these wells exceed the WHO guideline, indicating that a large number of USA residents are exposed to excess As from household wells [4]. In addition, not all municipalities are yet in compliance with the EPA requirements, with up to 8% of all public water supplies exceeding 10?μg As/L. Individuals chronically exposed to As are at increased risk for various cancers, including cancers of the skin (Bowen’s disease,
Prediction of Adherence to a 9-Week Corporate Wellness Walking Program  [PDF]
Megan Flynn, Eric E. Hall
Health (Health) , 2018, DOI: 10.4236/health.2018.1012131
Abstract: The health and economic benefits of workplace wellness programs are well founded, but the favorable results only occur when employees choose to participate and adhere to these programs. The objective of this study was to use the Theory of Planned Behavior and Self-Efficacy Theory to predict whether participants adhered to a corporate wellness walking program. The sample consisted of 110 faculty and staff at a private university who enrolled in a walking program through the university’s wellness center. Participants completed surveys at the beginning of the program. The surveys measured self-reported physical activity, as well as theoretical construct of self-efficacy and those related to the Theory of Planned Behavior—attitude, social norms, perceived behavioral control and intention. Sixty percent of participants were found to meet the program’s goals. Self-reported physical activity (p = 0.036), barrier self-efficacy (p = 0.016), walking self-efficacy (p = 0.002), and intention (p < 0.001) were greater in those who met the goals than those who did not meet the goals of the program. Walking self-efficacy (p < 0.001), attitude (p < 0.001) and perceived behavioral control (p = 0.024) were all found to predict intention to walk and intention was a significant predictor of whether or not the participants met goals of the program (p = 0.022). This suggests behavioral interventions aimed at increasing participant self-efficacy and intentions could positively affect program adherence and the successfulness of a workplace wellness program.
Mathematical model insights into arsenic detoxification
Sean D Lawley, Molly Cinderella, Megan N Hall, Mary V Gamble, H Frederik Nijhout, Michael C Reed
Theoretical Biology and Medical Modelling , 2011, DOI: 10.1186/1742-4682-8-31
Abstract: We develop a whole body mathematical model of arsenic metabolism including arsenic absorption, storage, methylation, and excretion. The parameters for arsenic methylation in the liver were taken from the biochemical literature. The transport parameters between compartments are largely unknown, so we adjust them so that the model accurately predicts the urine excretion rates of time for the iAs, MMAs, and DMAs in single dose experiments on human subjects.We test the model by showing that, with no changes in parameters, it predicts accurately the time courses of urinary excretion in mutiple dose experiments conducted on human subjects. Our main purpose is to use the model to study and interpret the data on the effects of folate supplementation on arsenic methylation and excretion in clinical trials in Bangladesh. Folate supplementation of folate-deficient individuals resulted in a 14% decrease in arsenicals in the blood. This is confirmed by the model and the model predicts that arsenicals in the liver will decrease by 19% and arsenicals in other body stores by 26% in these same individuals. In addition, the model predicts that arsenic methyltransferase has been upregulated by a factor of two in this population. Finally, we also show that a modification of the model gives excellent fits to the data on arsenic metabolism in human cultured hepatocytes.The analysis of the Bangladesh data using the model suggests that folate supplementation may be more effective at reducing whole body arsenic than previously expected. There is almost no data on the upregulation of arsenic methyltransferase in populations chronically exposed to arsenic. Our model predicts upregulation by a factor of two in the Bangladesh population studied. This prediction should be verified since it could have important public health consequences both for treatment strategies and for setting appropriate limits on arsenic in drinking water. Our model has compartments for the binding of arsenicals to protei
Influence of Prenatal Arsenic Exposure and Newborn Sex on Global Methylation of Cord Blood DNA
J. Richard Pilsner, Megan N. Hall, Xinhua Liu, Vesna Ilievski, Vesna Slavkovich, Diane Levy, Pam Factor-Litvak, Mahammad Yunus, Mahfuzar Rahman, Joseph H. Graziano, Mary V. Gamble
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0037147
Abstract: Background An emerging body of evidence indicates that early-life arsenic (As) exposure may influence the trajectory of health outcomes later in life. However, the mechanisms underlying these observations are unknown. Objective The objective of this study was to investigate the influence of prenatal As exposure on global methylation of cord blood DNA in a study of mother/newborn pairs in Matlab, Bangladesh. Design Maternal and cord blood DNA were available from a convenience sample of 101 mother/newborn pairs. Measures of As exposure included maternal urinary As (uAs), maternal blood As (mbAs) and cord blood As (cbAs). Several measures of global DNA methylation were assessed, including the [3H]-methyl-incorporation assay and three Pyrosequencing assays: Alu, LINE-1 and LUMA. Results In the total sample, increasing quartiles of maternal uAs were associated with an increase in covariate-adjusted means of newborn global DNA methylation as measured by the [3H]-methyl-incorporation assay (quartile 1 (Q1) and Q2 vs. Q4; p = 0.06 and 0.04, respectively). Sex-specific linear regression analyses, while not reaching significance level of 0.05, indicated that the associations between As exposures and Alu, LINE-1 and LUMA were positive among male newborns (N = 58) but negative among female newborns (N = 43); tests for sex differences were borderline significant for the association of cbAs and mbAs with Alu (p = 0.05 and 0.09, respectively) and for the association between maternal uAs and LINE-1 (p = 0.07). Sex-specific correlations between maternal urinary creatinine and newborn methyl-incorporation, Alu and LINE-1 were also evident (p<0.05). Conclusions These results suggest that prenatal As exposure is associated with global DNA methylation in cord blood DNA, possibly in a sex-specific manner. Arsenic-induced epigenetic modifications in utero may potentially influence disease outcomes later in life. Additional studies are needed to confirm these findings and to examine the persistence of DNA methylation marks over time.
Major and Minor Group Rhinoviruses Elicit Differential Signaling and Cytokine Responses as a Function of Receptor-Mediated Signal Transduction
Bryce A. Schuler, Michael T. Schreiber, LuYuan Li, Michal Mokry, Megan L. Kingdon, Dana N. Raugi, Cosonya Smith, Chelsea Hameister, Vincent R. Racaniello, David J. Hall
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0093897
Abstract: Major- and minor-group human rhinoviruses (HRV) enter their host by binding to the cell surface molecules ICAM-1 and LDL-R, respectively, which are present on both macrophages and epithelial cells. Although epithelial cells are the primary site of productive HRV infection, previous studies have implicated macrophages in establishing the cytokine dysregulation that occurs during rhinovirus-induced asthma exacerbations. Analysis of the transcriptome of primary human macrophages exposed to major- and minor-group HRV demonstrated differential gene expression. Alterations in gene expression were traced to differential mitochondrial activity and signaling pathway activation between two rhinovirus serotypes, HRV16 (major-group) and HRV1A (minor-group), upon initial HRV binding. Variances in phosphorylation of kinases (p38, JNK, ERK5) and transcription factors (ATF-2, CREB, CEBP-alpha) were observed between the major- and minor-group HRV treatments. Differential activation of signaling pathways led to changes in the production of the asthma-relevant cytokines CCL20, CCL2, and IL-10. This is the first report of genetically similar viruses eliciting dissimilar cytokine release, transcription factor phosphorylation, and MAPK activation from macrophages, suggesting that receptor use is a mechanism for establishing the inflammatory microenvironment in the human airway upon exposure to rhinovirus.
Prolotherapy Injections for Diastasis Recti: A Case Report  [PDF]
Megan N. Strauchman, Mark W. Morningstar
Case Reports in Clinical Medicine (CRCM) , 2016, DOI: 10.4236/crcm.2016.59052
Abstract: This case report detailed the history and treatment of a female postpartum patient with diastasis recti. Treatment for this patient included the use of prolotherapy, an injection-based therapy using dextrose as the active compound. The solution used during the course of therapy was composed of 6 mL of 50% dextrose, 3 mL of 1% lidocaine, and 1 mL of methylcobalamin (1000 mcg/mL). Injections were administered every 2 weeks for a total of 7 prolotherapy sessions. Following the series of prolotherapy injections, there was a marked closure observed in the diastasis, decreasing from 2.7 cm to 0.5 cm. The patient did not report any side effects, and no complications were observed or recorded. This appears to be the first case report documenting an improvement in abdominal diastasis recti following a course of prolotherapy. Within the limitations of the study design, further research is recommended to evaluate prolotherapy for diastasis recti in postpartum patients.
Urinary and Dietary Analysis of 18,470 Bangladeshis Reveal a Correlation of Rice Consumption with Arsenic Exposure and Toxicity
Stephanie Melkonian, Maria Argos, Megan N. Hall, Yu Chen, Faruque Parvez, Brandon Pierce, Hongyuan Cao, Briseis Aschebrook-Kilfoy, Alauddin Ahmed, Tariqul Islam, Vesna Slavcovich, Mary Gamble, Parvez I. Haris, Joseph H. Graziano, Habibul Ahsan
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0080691
Abstract: Background We utilized data from the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh, to evaluate the association of steamed rice consumption with urinary total arsenic concentration and arsenical skin lesions in the overall study cohort (N=18,470) and in a subset with available urinary arsenic metabolite data (N=4,517). Methods General linear models with standardized beta coefficients were used to estimate associations between steamed rice consumption and urinary total arsenic concentration and urinary arsenic metabolites. Logistic regression models were used to estimate prevalence odds ratios (ORs) and their 95% confidence intervals (CIs) for the associations between rice intake and prevalent skin lesions at baseline. Discrete time hazard models were used to estimate discrete time (HRs) ratios and their 95% CIs for the associations between rice intake and incident skin lesions. Results Steamed rice consumption was positively associated with creatinine-adjusted urinary total arsenic (β=0.041, 95% CI: 0.032-0.051) and urinary total arsenic with statistical adjustment for creatinine in the model (β=0.043, 95% CI: 0.032-0.053). Additionally, we observed a significant trend in skin lesion prevalence (P-trend=0.007) and a moderate trend in skin lesion incidence (P-trend=0.07) associated with increased intake of steamed rice. Conclusions This study suggests that rice intake may be a source of arsenic exposure beyond drinking water.
Early Lens Ablation Causes Dramatic Long-Term Effects on the Shape of Bones in the Craniofacial Skeleton of Astyanax mexicanus
Megan Dufton, Brian K. Hall, Tamara A. Franz-Odendaal
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0050308
Abstract: The Mexican tetra, Astyanax mexicanus, exists as two morphs of a single species, a sighted surface morph and a blind cavefish. In addition to eye regression, cavefish have an increased number of taste buds, maxillary teeth and have an altered craniofacial skeleton compared to the sighted morph. We investigated the effect the lens has on the development of the surrounding skeleton, by ablating the lens at different time points during ontogeny. This unique long-term study sheds light on how early embryonic manipulations on the eye can affect the shape of the adult skull more than a year later, and the developmental window during which time these effects occur. The effects of lens ablation were analyzed by whole-mount bone staining, immunohistochemisty and landmark based morphometric analyzes. Our results indicate that lens ablation has the greatest impact on the skeleton when it is ablated at one day post fertilisation (dpf) compared to at four dpf. Morphometric analyzes indicate that there is a statistically significant difference in the shape of the supraorbital bone and suborbital bones four through six. These bones expand into the eye orbit exhibiting plasticity in their shape. Interestingly, the number of caudal teeth on the lower jaw is also affected by lens ablation. In contrast, the shape of the calvariae, the length of the mandible, and the number of mandibular taste buds are unaltered by lens removal. We demonstrate the plasticity of some craniofacial elements and the stability of others in the skull. Furthermore, this study highlights interactions present between sensory systems during early development and sheds light on the cavefish phenotype.
Changes in Urinary Bone Resorption Marker after Taking a Combination Nutrient Formula in Adults with Scoliosis: A Retrospective, Open-Label, Case-Controlled Series  [PDF]
Mark W. Morningstar, Megan N. Strauchman, Gretchen Fleischmann
Open Journal of Internal Medicine (OJIM) , 2016, DOI: 10.4236/ojim.2016.61002
Abstract: Background: Scoliosis is a common condition in adult patients, and often causes chronic back pain compared to non-scoliosis. It has also been identified that bone mineral density is very often compromised in patients with scoliosis, even occurring in adolescence. At this time, no study has looked at how bone mineral density and scoliosis incidence or severity may be connected with specific regard to treatment. This study presents data on the outcomes of a scoliosis-specific exercise therapy and its ability to correct scoliotic curvatures in adult patients alone and in combination with bone mineral density supplementation. Methods: The charts of 14 total patients were retrospectively selected based upon specific inclusion criteria. Outcome assessments included the radiographic Cobb angle of the primary curvature, as well as laboratory measures of urinary deoxypyridinoline cross links. These results were compared against 12 patients who did not take the bone density supplement during or after their exercise-based treatment. Results: Patients taking the bone density supplement achieved the same level of Cobb angle reduction as compared to the control group. However, they additionally achieved a significant reduction in urinary deoxypyridinoline cross links as compared to the control group at 6 months. Conclusion: Patients taking a multi-ingredient bone density supplement daily for 6 months after completing a scoliosis-specific exercise program reported statistically significant improvements in urinary deoxypyridinoline cross links as compared to controls. It is unknown if or how bone density loss may contribute to the onset or progression of scoliosis. Long-term follow-up of these patients will be ongoing to assess bone mineral density status and Cobb angle changes longitudinally.
The Effects of Juvenile Stress on Anxiety, Cognitive Bias and Decision Making in Adulthood: A Rat Model
Nichola M. Brydges, Lynsey Hall, Rachael Nicolson, Megan C. Holmes, Jeremy Hall
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048143
Abstract: Stress experienced in childhood is associated with an increased risk of developing psychiatric disorders in adulthood. These disorders are particularly characterized by disturbances to emotional and cognitive processes, which are not currently fully modeled in animals. Assays of cognitive bias have recently been used with animals to give an indication of their emotional/cognitive state. We used a cognitive bias test, alongside a traditional measure of anxiety (elevated plus maze), to investigate the effects of juvenile stress (JS) on adulthood behaviour using a rodent model. During the cognitive bias test, animals were trained to discriminate between two reward bowls based on a stimulus (rough/smooth sandpaper) encountered before they reached the bowls. One stimulus (e.g. rough) was associated with a lower value reward than the other (e.g. smooth). Once rats were trained, their cognitive bias was explored through the presentation of an ambiguous stimulus (intermediate grade sandpaper): a rat was classed as optimistic if it chose the bowl ordinarily associated with the high value reward. JS animals were lighter than controls, exhibited increased anxiety-like behaviour in the elevated plus maze and were more optimistic in the cognitive bias test. This increased optimism may represent an optimal foraging strategy for these underweight animals. JS animals were also faster than controls to make a decision when presented with an ambiguous stimulus, suggesting altered decision making. These results demonstrate that stress in the juvenile phase can increase anxiety-like behaviour and alter cognitive bias and decision making in adulthood in a rat model.
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