Treatment Options for Patients With Irritable Bowel Syndrome & Comorbid Depression

• Irritable bowel syndrome & depression are common comorbidities, however there is a wide variability regarding the appropriate treatment regimens for these patients. • IBS is classified as a functional bowel disease in which patients suffer from recurrent abdominal pain or discomfort associated with alterations in bowel habits. • While the cause of IBS is multifactorial, studies have revealed that the dysfunction of the brain-gut pathways are a culprit to disease appearance and progression, as seen in the biopsychosocial model of IBS. This model proposes that abdominal symptoms secondarily impact anxiety & depression symptoms and that psychological factors influence physiologic aspects such as motor functions, sensory threshold & stress reactivity of the gut through the vagal & sympathetic afferents. • Due to the complexity of the causal mechanisms that produce symptoms of IBS with depression, there is some uncertainty regarding the best treatment regimen for these patients. • Commonly, patients are advised to increase physical activity, reduce stress & implement dietary modifications. Pharmacotherapy may be advised for some, depending on their symptoms, & may include antidepressants, antispasmodics or laxatives. • There is not a standardized method of treating IBS with comorbid depression, therefore symptom management must be performed on a patient-by-patient basis.https://commons.und.edu/pas-grad-posters/1047/thumbnail.jp

Regulation and Dynamic Behavior of the Heat Shock Transcription Factor Hsf-1 in C. Elegans

Eukaryotic cells respond to heat stress by activating the transcription factor HSF1. In addition to its role in stress response, HSF1 also functions in protein homeostasis, aging, innate immunity, and cancer. Despite prominent HSF1 involvement in processes pertinent to human health and disease, there are still gaps in our understanding of HSF1. For example, controversy exists regarding the localization of HSF1, the identity of HSF1 regulators, and the function and conservation of heat-induced HSF1 stress granules. Many of the physiological roles for HSF1 have been defined using the model organism Caenorhabditis elegans, yet little is known about how the molecular and biological properties of HSF-1 in C. elegans compare to HSF1 in other organisms, including humans. To address these questions, we generated animals expressing physiological levels of a GFP-tagged C. elegans HSF-1 protein. We studied the localization of HSF-1::GFP in vivo and observed its behavior upon heat shock in C. elegans. Furthermore, we conducted a genome-wide, RNAi-based screen for regulators of an HSF-1-dependent, heat shock-inducible transcriptional reporter. We found that in live C. elegans, HSF-1 localizes predominantly to the nucleus before and after heat shock. Following heat shock, HSF-1 redistributes into subnuclear puncta that share many characteristics with human nuclear stress granules, including rapid formation, reversibility, and colocalization with markers of active transcription. Granule formation in worms was affected by growth temperature, implying physiological regulation of this process. From our RNAi screen, we identified 44 regulators of HSF-1 target gene expression, the majority of which were positive regulators. One RNAi clone, encoding the worm homolog of the post-translational modifier SUMO, resulted in hyper-induction of the HSF-1 target after heat shock. Our findings from the screen suggest that basal repression of HSF-1 under low-temperature conditions may be very strict, and that sumoylation may be involved in downregulation of the activated heat stress response pathway. Our data also support a model of constitutively nuclear C. elegans HSF-1 and present evidence that HSF-1 nuclear stress granule formation may be an evolutionarily conserved phenomenon

The Mills Bill: An Economic Impact Study of the North Carolina State Historic Mill Rehabilitation Tax Credit

The textile, tobacco, and furniture industries in North Carolina suffered a significant loss of revenue and jobs in the 1990s. As production migrated to cheaper locations overseas, communities throughout the state faced the collateral challenge of finding new uses for hundreds of large, empty mill buildings. To encourage redevelopment of the state\u27s vacant mills, North Carolina\u27s legislature created a tax credit program that targeted mills and other similar industrial properties. This thesis quantifies the economic successes of the state\u27s mill rehabilitation tax credit. Building on equations and assumptions from Becky Holton\u27s 2008 IMPLAN software model, this economic impact study uses individual project data from the North Carolina State Historic Preservation Office, including qualified rehabilitation expenditures, to determine the level of economic development for each year of the program\u27s existence from 2006 to 2013. Significant findings include total rehabilitation expenditures, direct and indirect jobs created, direct and indirect income taxes generated, sales taxes generated, increased property taxes, eligible tax credit amounts, and the overall cost to the state of North Carolina. An analysis using a second multiplier from Donovan Rypkema of PlaceEconomics also demonstrates the indirect effects of the mill credit by estimating the economic impact, total jobs created, and household income associated with every one million dollars of investment in mill rehabilitation projects. By comparing annual results, this economic impact study demonstrates the tax credit\u27s increased efficiency and use in rehabilitating mills and revitalizing North Carolina communities. The North Carolina mill tax credit program has proved successful in finding new uses for vacant mill buildings and infusing economic energy into communities hit by loss of manufacturing jobs. While the administration of the credit creates a deduction in the state budget, the mill credit\u27s indirect economic impact on the state far exceeds the government\u27s initial investment. Although less than a third of completed mill rehabilitation projects took place outside of the state\u27s strong, urban markets, the mill credit has so far pushed 24 projects into feasibility. The future of the historic mill rehabilitation tax credit program faces renewal by the North Carolina state legislature in 2014

Female gender themes in women\u27s magazines: A content analysis testing and extending themes uncovered by Erving Goffman

This study is based on the ideas and studies of Erving Goffman (1922-1982), an influential sociologist and communications scholar (Manning, 1992). Most prior scholars, such as McLaughlin (1999) and Reichert (2003), have chosen to simply repeat and reaffirm Goffman\u27s themes, while largely ignoring that both times and society have changed. Thus, this study proposes not only to repeat Goffman\u27s methods, but also to extend and retest his findings in the modern day. A quantitative content analysis will be employed, using the following women\u27s magazines: Cosmopolitan, In Style, Allure, Glamour, and Marie Claire. The replication of this study is imperative in order to better understand modern advertising themes and to help future scholars understand and study advertisements. Although the study serves as a simple replication of a previous study conducted in the late 1970s, the findings will provide a new basis for understanding advertisements in modern times

Delayed Onset and Reduced Cognitive Deficits through Pre-Conditioning with 3-Nitropropionic Acid is Dependent on Sex and CAG Repeat Length in the R6/2 Mouse Model of Huntington's Disease.

BACKGROUND: Impairments in energy metabolism are implicated in Huntington's disease (HD) pathogenesis. Reduced levels of the mitochondrial enzyme succinate dehydrogenase (SDH), the main element of complex II, are observed post mortem in the brains of HD patients, and energy metabolism defects have been identified in both presymptomatic and symptomatic HD patients. OBJECTIVE: Chemical preconditioning with 3-nitropropionic acid (3-NP), an irreversible inhibitor of SDH, has been shown to increase tolerance against experimental hypoxia in both heart and brain. Here we studied the effect of chronic preconditioning in the R6/2 mouse model of HD using mice carrying CAG repeat lengths of either 250 or 400 repeats. Both are transgenic fragment models, with 250CAG mice having a more rapid disease progression than 400CAG mice. METHODS: Low doses of 3-NP (24 mg/kg) were administered via the drinking water and the effect on phenotype progression and cognition function assessed. RESULTS: After 3-NP treatment there were significant improvements in all aspects of the behavioural phenotype, apart from body weight, with timing and magnitude of improvements dependent on both CAG repeat length and sex. Specifically, a delay in the deterioration of general health (as shown by delayed onset of glycosuria and increased survival) was seen in both male and female 400CAG mice and in female 250CAG mice and was consistent with improved appearance of 3-NP treated R6/2 mice. Male 250CAG mice showed improvements but these were short term, and 3-NP treatment eventually had deleterious effects on their survival rate. When cognitive performance of 250CAG mice was assessed using a two-choice discrimination touchscreen task, we found that female mice showed significant improvements. DISCUSSION: Together, our results support the idea that energy metabolism contributes to the pathogenesis of HD, and suggest that improving energy deficits might be a therapeutically useful target.CHDI Inc.This is the author accepted manuscript. The final version is available from IOS Press via http://dx.doi.org/10.3233/JHD-160189

Optimization of CRISPR-Cas9 Construct to Correct Cystic Fibrosis Mutation F508del-CFTR

Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, and 90% of CF patients possess the mutation F508del-CFTR. One potential treatment for CF patients is recombinant adeno-associated virus (rAAV) gene therapy using CRISPR-Cas9 gene-editing technology. This study focused on the design and optimization of an rAAV-CRISPR-Cas9 cassette to correct F508del-mCFTR. Five CRISPR-Cas9 constructs were constructed with different sgRNA sequences (1-5). Correction efficiency of the CRISPR-Cas9 construct with sgRNA3 was tested with a dual reporter mRFP-mCFTRF508del-eGFP plasmid in HEK 293 cells. mRFP and eGFP were detected via fluorescence microscopy two days after transfection. mRFP fluorescence indicated transfection, and eGFP fluorescence indicated successful CRISPR-Cas9 editing of F508del-mCFTR. The sgRNA3 CRISPR-Cas9 construct resulted in F508del-mCFTR gene editing, as indicated by eGFP expression in combination with mRFP expression. Future research includes optimization of transfection of the dual reporter system and CRISPR-Cas9 constructs, testing of other sgRNA CRISPR-Cas9 constructs, and development of an rAAV-CRISPR-Cas9 cassette using the most efficient sgRNA CRISPR-Cas9 construct. This cassette will be tested in F508del-CFTR mouse models and has the potential to inform human gene therapy approaches.Bachelor of Scienc

Development of a method for the simultaneous detection of Cr(iii) and Cr(vi) in exhaled breath condensate samples using μLC-ICP-MS

The method described in this study is a robust and sensitive method for the simultaneous determination of trivalent and hexavalent chromium (Cr(III) and Cr(VI)) in an exhaled breath condensate (EBC) sample and drinking water proficiency testing material sample. The method uses a hyphenated micro liquid chromatography (mLC) system coupled to inductively coupled plasma mass spectrometry (ICP-MS). The optimised method incorporates a pH adjusted EDTA complexation step to stabilise Cr(VI) and Cr(III). Separation was achieved using an anion exchange micro-sized column. The limits of quantification were 0.040 mg L-1 and 0.013 mg L-1 for Cr(III) and Cr(VI) respectively. EBC is the non-invasive collection of condensate from cooled exhaled breath during regular tidal breathing. We propose that EBC may be a suitable alternative biological matrix to give a more comprehensive picture of exposure to Cr(VI) following an inhalation exposure. This study shows that water samples and EBC samples containing Cr(III) and Cr(VI) can be stored in the fridge (~4 C) for up to 6 weeks when they have been diluted 10 fold with an EDTA solution, and that EBC samples must not be frozen after collection if the integrity of Cr(VI) is to be maintained. This study has demonstrated a practical approach to collecting EBC samples from workers potentially occupationally exposed to hexavalent chromium and that the integrity of the chromium species will be maintained prior to analysis