Endocrinology of equine metabolic pathophysiology

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.Title from title screen of research.pdf file (viewed on July 31, 2007)Vita.Thesis (Ph. D.) University of Missouri-Columbia 2006.Obesity in horses is associated with a number of maladies including insulin resistance and laminitis; therefore studies investigating the metabolic physiology of equine were done. In our first study, we characterized the profiles of leptin, insulin-like growth factor-1, and thyroid stimulating hormone in mares and foals in the peri-parturient period. The highest concentration of all hormones was found in the first milk sample, which is in agreement with other equine research. This study also provided the first data on leptin concentrations in the neonatal foal. In our second study, we examined the link between leptin and adrenocorticoid hormones by administering the mineralocorticoid receptor antagonist spironolactone to pony mares. We found no change in cortisol or leptin concentrations between treatments, but did see a trend for increased aldosterone concentrations in the blood of spironolactone treated ponies over time. Further work is necessary to elucidate the relationship between leptin and adrenocorticoids in equine. In our third study, we investigated the effects lipoic acid supplementation on blood glucose and insulin responses, as well as leptin concentrations in pony mares. We found no differences between treatments for blood glucose or leptin concentrations during a glucose tolerance test; however there was a trend for decreased insulin concentrations. These results suggest that lipoic acid may improve insulin effectiveness and warrant further investigation into the potential benefits of lipoic acid supplementation in the management of insulin resistance in equine.Includes bibliographical reference

Prognostic impact of Claudin 18.2 in gastric and esophageal adenocarcinomas

Introduction: The tight junction molecule Claudin 18.2 is selectively expressed in healthy and malignant gastric epithelial tissue and is a promising therapy target for high Claudin 18.2 expressing adenocarcinomas of the esophagogastric junction and stomach (AEG/S). Methods: This study analyzed the prevalence, characteristics and prognostic impact of Claudin 18.2 expression in primary tumor, lymph node and distant metastasis in a large Caucasian AGE/S cohort with 414 patients. Results: Claudin 18.2 was highly expressed in 17.1% of primary tumors, 26.7% of lymph node metastasis and 16.7% of distant metastasis. High Claudin 18.2 expression in lymph node metastasis and primary tumors correlated significantly (p < 0.001). High expression of Claudin 18.2 was neither associated with histomorphogical subtype, or tumor state, nor with overall survival. Conclusion: In Caucasian AEG/S patients, 17.1% appeared to be eligible for an anti-Claudin 18.2 therapy. Claudin 18.2 expression itself has no impact on prognosis and is not related to any tumor subtype

Unifying candidate gene and GWAS Approaches in Asthma.

The first genome wide association study (GWAS) for childhood asthma identified a novel major susceptibility locus on chromosome 17q21 harboring the ORMDL3 gene, but the role of previous asthma candidate genes was not specifically analyzed in this GWAS. We systematically identified 89 SNPs in 14 candidate genes previously associated with asthma in >3 independent study populations. We re-genotyped 39 SNPs in these genes not covered by GWAS performed in 703 asthmatics and 658 reference children. Genotyping data were compared to imputation data derived from Illumina HumanHap300 chip genotyping. Results were combined to analyze 566 SNPs covering all 14 candidate gene loci. Genotyped polymorphisms in ADAM33, GSTP1 and VDR showed effects with p-values <0.0035 (corrected for multiple testing). Combining genotyping and imputation, polymorphisms in DPP10, EDN1, IL12B, IL13, IL4, IL4R and TNF showed associations at a significance level between p = 0.05 and p = 0.0035. These data indicate that (a) GWAS coverage is insufficient for many asthma candidate genes, (b) imputation based on these data is reliable but incomplete, and (c) SNPs in three previously identified asthma candidate genes replicate in our GWAS population with significance after correction for multiple testing in 14 genes

College student reactions to health warning labels: Sociodemographic and psychosocial factors related to perceived effectiveness of different approaches

Objective. To examine factors associated with perceiving different types of pictorial cigarette health warning labels as most effective in motivating smokers to quit or preventing smoking initiation among college students. Method. We administered an online survey to 24,055 students attending six Southeast colleges in Fall, 2010. We obtained complete data for the current analysis from 2600. Results. Current smoking prevalence was 23.5%. The largest majority (78.6%) consistently rated gruesome images as most effective, 19.5% rated testimonial images as most effective, and only a small proportion rated either standard (1.6%) or human suffering images (0.3%) as most effective. Subsequent analyses focused on differences between those endorsing gruesome images or testimonials as most effective. Factors related to ranking testimonials versus gruesome images as most effective included being female (p\u3c0.01), White (p\u3c0.01), and nonsmokers (p=0.04), lower perceived smoking prevalence (p\u3c0.01), and greater receptivity to laws/restrictions around smoking (p\u3c0.01) and tobacco marketing (p=0.01). Among smokers, factors related to ranking testimonials as most effective versus gruesome images included being female (p=0.03), being White (p=0.03), higher autonomous motivation (p=0.03), and greater extrinsic self-efficacy (p=0.02). Conclusions. Understanding factors related to perceived effectiveness of different pictorial warnings among subpopulations should inform health warning labels released by the FDA

Atopic dermatitis and food sensitization in South African toddlers: Role of fiber and gut microbiota

The pathogenesis of atopic dermatitis (AD) is complex and related to allergic responses and defects in skin barrier function. In common with many atopic diseases, the prevalence of AD has been increasing across the world.1 One of the theories for this increase is increased hygiene and urbanization-related changes in the environment, which can affect the human microbiome.2 Previous studies have found associations between the composition of the early gut microbiome and development of atopic conditions, including AD.3 Although the rate of atopic conditions, including AD and food allergy, is increasing on all continents, the prevalence of these diseases is still lower in African countries.1 This is especially interesting because individuals of African origin who live in Western countries, such as African Americans, are at a higher risk for severe AD.4 This variation places Africa in a special position; studying African populations is necessary not only to find ways to prevent increases of allergy conditions in African countries but also to provide important clues to the causes of this global increasing of allergic conditions. Young children who have developed AD in African communities with a low incidence of atopic disease might be the transitional group. In the current study, we have, for the first time to our knowledge, analyzed the fecal microbiota composition of a group of young black African children aged 12 to 36 months old with and without AD living in the same community in Cape Town, South Africa. Our primary goal was to examine whether toddlers with AD and control toddlers from Cape Town have different microbiomes in terms of bacterial richness and diversity. We also aimed to investigate the differences in the relative abundance for different operational taxonomic units between these 2 groups. In our subgroup analyses, we further tested the effect of multiple environmental factors on the gut microbiome in these children

TAB2 deletions and variants cause a highly recognisable syndrome with mitral valve disease, cardiomyopathy, short stature and hypermobility

Deletions that include the gene TAB2 and TAB2 loss-of-function variants have previously been associated with congenital heart defects and cardiomyopathy. However, other features, including short stature, facial dysmorphisms, connective tissue abnormalities and a variable degree of developmental delay, have only been mentioned occasionally in literature and thus far not linked to TAB2. In a large-scale, social media-based chromosome 6 study, we observed a shared phenotype in patients with a 6q25.1 deletion that includes TAB2. To confirm if this phenotype is caused by haploinsufficiency of TAB2 and to delineate a TAB2-related phenotype, we subsequently sequenced TAB2 in patients with matching phenotypes and recruited patients with pathogenic TAB2 variants detected by exome sequencing. This identified 11 patients with a deletion containing TAB2 (size 1.68-14.31 Mb) and 14 patients from six families with novel truncating TAB2 variants. Twenty (80%) patients had cardiac disease, often mitral valve defects and/or cardiomyopathy, 18 (72%) had short stature and 18 (72%) had hypermobility. Twenty patients (80%) had facial features suggestive for Noonan syndrome. No substantial phenotypic differences were noted between patients with deletions and those with intragenic variants. We then compared our patients to 45 patients from the literature. All literature patients had cardiac diseases, but syndromic features were reported infrequently. Our study shows that the phenotype in 6q25.1 deletions is caused by haploinsufficiency of TAB2 and that TAB2 is associated not just with cardiac disease, but also with a distinct phenotype, with features overlapping with Noonan syndrome. We propose the name "TAB2-related syndrome"

Effects of CO 2 and nutrient availability on mineral weathering in controlled tree growth experiments

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94968/1/gbc911.pd