Gastroesophageal reflux disease (GERD) is commonly seen in patients with chronic kidney disease (CKD), although data on the relationship between these conditions are still limited. We aimed to explore whether CKD is related to a higher prevalence of GERD and its complications. National Inpatient Sample data were used in this retrospective analysis, including 7,159,694 patients. Patients who had a diagnosis of GERD with and without CKD were compared with patients without GERD. Complications associated with GERD that were analyzed included Barrett’s esophagus and esophageal stricture. Risk factors of GERD were used for variable adjustment analysis. Different stages of CKD were evaluated in patients with and without GERD. Bivariate analyses were performed using the chi-squared test or Fisher exact test (2-tailed) for categorical variables as appropriate to assess the difference. There were significantly different demographic characteristics between GERD patients with and without CKD regarding age, sex, race, and other co-mobilities. Interestingly, a greater prevalence of GERD was seen in CKD patients (23.5%) compared to non-CKD patients (14.8%), and this increased prevalence was consistently seen in all CKD stages. CKD patients also had 1.70 higher odds of risk of having GERD compared with non-CKD after adjustment. The association between different stages of CKD and GERD showed a similar trend. Interestingly, patients with early-stage CKD were found to have a higher prevalence and odds of risk of esophageal stricture and Barrett’s esophagus than non-CKD patients. CKD is associated with a high prevalence of GERD and its complications.

Background and Objective: Presenting chronic obstructive pulmonary disease (COPD) patients frequently report concurrent symptoms of gastroesophageal reflux disease (GERD). Few studies have shown a correlation between GERD and COPD. We aimed to examine the correlation between GERD and COPD as well as secondary related reflux complications, such as esophageal stricture, esophageal cancer, and Barrett’s esophagus. Methods: This population-based analysis included 7,159,694 patients. Patients diagnosed with GERD with and without COPD were compared to those without GERD. The enrollment of COPD included centrilobular and panlobular emphysema and chronic bronchitis. Risk factors of COPD or GERD were used for adjustment. Bivariate analyses were performed using the chi-squared test or Fisher exact test (2-tailed) for categorical variables as appropriate to assess the differences in the groups. Results: Our results showed that COPD patients had a significantly higher incidence of GERD compared to those without COPD (27.8% vs. 14.1%, p < 0.01). After adjustment of demographics and risk factors, COPD patients had a 1.407 times higher risk of developing non-erosive esophagitis (p < 0.01), 1.165 higher risk of erosive esophagitis (p < 0.01), 1.399 times higher risk of esophageal stricture (p < 0.01), 1.354 times higher risk of Barrett’s esophagus without dysplasia (p < 0.01), 1.327 times higher risk of Barrett’s esophagus with dysplasia, as well as 1.235 times higher risk of esophageal cancer than those without COPD. Conclusions: Based on the evidence from this study, there are sufficient data to provide convincing evidence of an association between COPD and GERD and its secondary reflux-related complications.

Patients with obstructive sleep apnea (OSA) commonly report gastroesophageal reflux disease (GERD) symptoms, and limited data suggest a relationship between OSA and GERD-related complications. To investigate this association, we performed a population-based analysis using National Inpatient Sample (NIS) data for 7,159,694 patients. After adjusting for risk factors, OSA patients had a significantly higher incidence of GERD (32.3%) compared to those without OSA (15.0%, p < 0.01). OSA patients also had a higher risk of developing GERD-related complications, including non-erosive esophagitis, erosive esophagitis, esophageal stricture, and Barrett’s esophagus with and without dysplasia. Therefore, our results emphasize the importance of early detection and management of GERD and its complications in patients with OSA, particularly those with additional risk factors such as obesity and smoking.

This study aimed to investigate the relationship between chronic kidney disease (CKD) and different gastric diseases by conducting a population-based retrospective analysis using National Inpatient Sample (NIS) data. A total of 7,159,694 patients diagnosed with gastric diseases with or without CKD were included, and the diagnoses of gastritis, gastric polyps, peptic ulcer disease (PUD), and Helicobacter pylori infection were based on ICD-10-CM codes. The study found a higher prevalence of gastritis and gastric polyps in patients with CKD compared to patients without CKD, especially in the late stages of CKD. After adjustment, patients with CKD also had a higher risk of developing these gastric diseases than patients without CKD. However, there was no significant association between all stages of CKD and PUD or Helicobacter pylori infection. These results underscored the importance of monitoring gastric health in patients with CKD.

Photoreceptor cells are specialized neurons optimized for the capture of light and the signal transduction to downstream cells that provides vision. Proper photoreceptor cell function depends heavily on efficient regulation of protein-protein interactions both during development and in the adult retina. Despite years of research on photoreceptor development and protein trafficking, the components vital to these processes are poorly understood. Interestingly, there are a number of small GTPases, which act as molecular switches, that are believed to play a role in regulating such interactions throughout the process of ciliogenesis, OS formation and protein trafficking. However, research into the role of these proteins in photoreceptor cells is in its infancy. Moreover, there are a growing number of discoveries linking small GTPases with photoreceptor mediated disease, such as ARL6, ARL2, ARL3, and RAB28. In this work I characterize the role of the small GTPases, ARL2 and ARL3, in the regulation of photoreceptor cell protein trafficking and OS development. In order to study these proteins in vivo, we utilized site-direct mutagenesis and transgenesis to create multiple animal models. Through these models, we have discovered that ARL2 and ARL3 serve different primary functions in vivo despite their high sequence similarity and sharing a number of binding partners. In Chapter 1 of this dissertation, we discuss the potential mechanisms and key players of photoreceptor cell ciliary development and protein trafficking. In Chapter 2, data is presented from the first animal model we generated expressing dominant active ARL3-Q71L. We further propose a mechanistic model for the role of ARL3 in prenylated protein trafficking in photoreceptor cells in which it acts to displace lipid modified cargo at the cilium. Chapter 3 focuses on data obtained from our dominant active ARL2-Q70L transgenic animal model. Here we discuss the potential role for ARL2 in ciliogenesis and OS formation in photoreceptor cells highlighting the novel observation that proper ARL2 function is necessary for cilia localization and axonemal extension. Finally, in Chapter 4 we discuss the data obtained during my dissertation and strategies to fill the gaps in knowledge that remain concerning the role of these small GTPases in photoreceptor cells. This work provides a strong foundation for the mechanisms of ARL2 and ARL3 action in photoreceptor cells. Complete elucidation of the components involved in photoreceptor protein trafficking and OS formation will provide the data necessary to generate novel therapeutics targeting the pathways underlying photoreceptor mediated blinding disease.

Background: Although heartburn and reflux are frequently reported in ulcerative colitis [UC], the correlation between UC and gastroesophageal reflux disease [GERD], and its complications, esophageal stricture and Barrett’s esophagus [BE], is not well understood. This study aims to examine the prevalence and associated risk of GERD and its complications within the UC population. Methods: We analyzed the National Inpatient Sample (NIS) dataset, consisting of 7,159,694 patients, comparing GERD patients with and without UC to those without GERD. We assessed the degree of colonic involvement in UC and the occurrence of esophageal complications. Bivariate analyses were conducted using the chi-squared test or Fisher exact test (two-tailed). Results: A higher prevalence of GERD (23.0% vs. 16.5%) and GERD phenotypes, such as non-erosive reflux disease (NERD) (22.3% vs. 16%) and erosive esophagitis (EE) (1.2% vs. 0.6%), was found in UC patients (p < 0.01), including pancolitis, proctitis, proctosigmoiditis, left-sided colitis, and indetermined UC (with undefined colonic involvement). UC patients were more likely to develop GERD (1.421), NERD (1.407), and EE (1.681) (p < 0.01). A higher prevalence of esophageal stricture (16.9 vs. 11.4 per 10,000 patients) and BE without dysplasia (94.5 vs. 39.3 per 10,000 patients) was found in UC (p < 0.05). The odds of developing BE without dysplasia were higher (1.892) in patients with UC (p < 0.01), including ulcerative pancolitis, proctitis, and indeterminate UC (OR of 1.657, 3.328, and 1.996, respectively) (p < 0.05). Conclusions: Our study demonstrates an increased risk of developing GERD and its complications in UC. This highlights the importance of vigilant monitoring and early intervention to minimize associated GERD-related risks in patients with UC.