Boerhaave syndrome is a spontaneous rupture of the esophagus. It results from a sudden increase in esophageal pressure combined with negative intrathoracic pressure as seen with severe straining or vomiting. Esophageal perforation is extremely rare with an incidence of approximately 3.1 per 1,000,000 per year with a mortality rate estimated to be 20-50%. The rare occurrence and fatal nature of an esophageal perforation makes this syndrome a difficult yet important diagnosis to consider in the clinical setting. This case presents a previously healthy 47-year-old gentleman who presented to a local emergency department with syncope, vomiting, and chest pain sequentially. He reported a 24-hour history of dark stools followed by syncope, and when he regained consciousness he had three bouts of retching and expulsion of coffee-ground vomitus. Shortly after emesis, the patient developed severe and continuous pain located in his central chest that radiated to his back. Upon arrival to the hospital he was tachycardic. Blood tests revealed metabolic acidosis, increased white blood cell count, elevated lactate, and significant anemia. The patient’s hemoglobin was 7.7 gm/dL, a significant drop from the patient’s baseline level of 14. The patient received 1 unit of packed red blood cells and was sent for imaging studies. Chest X-ray and CT imaging revealed free air in the mediastinum, and a subsequent Gastrografin esophagogram study revealed a lower esophageal perforation proximal to gastroesophageal junction. The patient was rushed to the operating room for emergency surgery. An esophagogastroduodenoscopy showed no active bleeds and confirmed a distal mucosal defect suggestive of perforation. The surgery team then performed a left thoracotomy with intercostal muscle harvest and esophageal repair, with the patient needing an additional 4 units of packed red blood cells during surgery. He tolerated the surgery well and received appropriate post-op care in the ICU. A repeat Gastrografin and barium swallow esophagogram revealed no evidence of leak, strictures, or complications from the operation. A follow up CT image of the chest, abdomen, and pelvis was performed one month after hospital discharge, and results showed complete resolution of mediastinal air without evidence of esophageal leak. This case demonstrates how a spontaneous esophageal perforation can occur in previously healthy, middle aged patients with no significant GI history or identifiable risk factors. Given this information, clinicians should consider Boerhaave Syndrome when a patient of any age presents with chest pain after an episode of emesis.

Upper gastrointestinal symptoms can be caused by many different diseases and can present themselves in many different forms and range in intensity depending on the person. In previous research, upper gastrointestinal symptoms have been correlated with stress, smoking, alcohol intake, and nonsteroidal anti-inflammatory drugs (NSAIDs), among others. The purpose of this study will be focusing on finding any association between these risk factors mention and symptoms of upper gastrointestinal disease among college students. The study will utilize an Izumo scale questionnaire for the assessment of abdominal symptoms and Quality of Life (QOL). The questionnaire was built using Survey Monkey and distributed via email to students at the University of Central Florida (UCF). The main hypothesis was that the more the student’s advancement in their college career, stress load, alcohol consumption, smoking, poor diet and a high consumption of some over the counter medication (specifically Non-Steroidal Anti Inflammatory Drugs), the more prone the students will be to present symptoms of upper gastrointestinal disease. The results were analyzed using Statistical Package for the Social Science (SPSS), and Analysis of Variance (ANOVA) were used to find any associations. The One-Way ANOVA tests showed an association between gender, ethnicity, student status, major, cigarette smoking habits, alcohol consumption, binge drinking, diet, stress, sleeping, and overall health. The results of this study present clear evidence that among college students, their demographics as well as lifestyle and school choices have significant associations to the amount of gastrointestinal symptoms they present with.

Gastroparesis (GP) is a clinical disorder recognized by measured delayed gastric emptying without mechanical obstruction, in addition to symptoms such as nausea, vomiting, chronic abdominal pain, heartburn, early satiety upon eating a regular-sized meal, and exaggerated postprandial fullness. While GP is considered a clinically rare disorder, there is much suspicion that a much larger number of patients experience GP-like symptoms without an official diagnosis. Furthermore, little work has been done to identify the causes and exacerbations of this gastrointestinal (GI) distress in the young adult population. This study's primary goal was to establish a relationship between modifiable and non-modifiable risk factors and overall GI distress at a large university campus. Utilizing an anonymous online-based survey, risk factors (Physical, psychological, and behavioral), participant demographics, levels of perceived stress, and GI symptoms were measured from 232 participants used in our analysis. Data analysis showed several significant correlations with higher GI distress: 1) being a graduate student, 2) having a higher heart rate, 3) participating in binge drinking, and 4) having higher perceived stress levels. This study is one of the first to assess multifactorial risk factors and find significant relationships within the young adult population. These results suggest that students experiencing higher levels of perceived stress may be suffering from more debilitating GI symptoms, which supports further research into methods for mediating stress amongst the student population.

The immunological mechanisms involved in virus-induced hepatitis were examined by measuring the cytotoxic capabilities and the morphological and antigenic phenotypes of leukocytes isolated from the livers of virus-infected mice. Large granular lymphocytes (LGL) of both natural killer (NK) cell and cytotoxic T lymphocyte (CTL) phenoytpes [phenotypes] accumulated in livers of mice infected with lymphocytic choriomeningitis virus (LCMV) of either the nonhepatotropic Armstrong strain (LCMV-ARM) or the hepatotropic WE strain (LCMV-WE). NK cell activity and LGL number increased 3- to 4-fold between days 1 and 5 postinfection (p.i.). These LGL were characterized as NK cells on the basis of cell surface antigens, kinetics of appearance, target cell range, and morphology. By day 7 p.i., virus-specific, H-2-restricted, Thy-1+, Lyt-2+CTL activity was present in the liver, and its appearance correlated with a second wave of LGL accumulation. Total CTL activity, leukocyte numbers, and CTL/LGL numbers were at least 5-fold higher in the livers of LCMV-WE-infected mice than in the livers of LCMV-ARM-infected mice. Mice infected with the cytopathic viruses, mouse hepatitis virus and murine cytomegalovirus, experienced greater increases in NK/LGL by day 3 p.i. than did mice either infected with LCMV or injected with poly I:C. The early and late accumulations of LGL in the virus-infected liver were associated with the appearance of two waves of LGL with blast cell morphology expressing the phenotypes of NK cells and CTL, respectively. Thus, the organ-associated accumulation, blastogenesis, and in situ proliferation of cytotoxic LGL provide a means for the localization and site-specific augmentation of a host's cell-mediated antiviral defenses. The mechanism of inhibition of virus synthesis in vivo by immune splenocytes containing virus-specific CTL was examined in mice dually infected with two different viruses and then adoptively immunized with spleen cells immune to one of the two viruses. Only the titer of the virus to which the splenocytes were immune was reduced in titer, and no nonspecific antiviral effect was seen on the titer of the 'bystander' heterologous virus. These data are consistent with an in vivo mechanism of CTL-mediated antiviral resistance involving direct cytotoxicity rather than release and dissemination of antigen-nonspecific antiviral factors, such as interferon, following recognition of appropriate viral antigen.

Asymmetric cell divisions constitute a basic foundation of animal development, providing a mechanism for placing specific cell types at defined positions in a developing organism. In a 4-cell stage embryo in Caenorhabditis elegansthe EMS cell divides asymmetrically to specify intestinal cells, which requires a polarizing signal from the neighboring P2 cell. Here we describe how the extracellular signal from P2 is transmitted from the membrane to the nucleus during asymmetric EMS cell division, and present the identification of additional components in the pathways that accomplish this signaling. P2/EMS signaling involves multiple inputs, which impinge on the Wnt, MAPK-like, and Src pathways. Transcriptional outputs downstream of these pathways depend on a homolog of β-catenin, WRM-1. Here we analyze the regulation of WRM-1, and show that the MAPK-like pathway maintains WRM-1 at the membrane, while its release and nuclear translocation depend on Wnt/Src signaling and sequential phosphorylation events by the major cell-cycle regulator CDK-1 and by the membrane-bound GSK-3 during EMS cell division. Our results provide novel mechanistic insights into how the signaling events at the cortex are coupled to the asymmetric EMS cell division through WRM-1. To identify additional regulators in the pathways governing gut specification, we performed suppressor genetic screens using temperature-sensitive alleles of the gutless mutant mom-2/Wnt, and extra-gut mutant cks-1. Five intragenic suppressors and three semi-dominant suppressors were isolated in mom-2 suppressor screens. One extragenic suppressor was mapped to the locus ifg-1, eukaryotic translation initiation factor eIF4G. From the suppressor screen using cks-1(ne549), an allele of the self-cleaving nucleopore protein npp-10 was identified as a suppressor of cks-1(ne549)and other extra-gut mutants. Taken together, these results help us better understand how the fate of intestinal cells are specified and regulated in early C. elegans embryos and broaden our knowledge of cell polarity and fate specification.

C1q TNF Related Protein 3 (CTRP3), is a cytokine that is primarily secreted from adipose tissue, which classifies it as an adipokine. Our previous research has shown that CTRP3 prevents alcoholic fatty liver disease (ALD) in male mice. However, even when accounting for confounding factors such as absolute and relative alcohol intake, females are more sensitive to the effects of consumption compared to male mice. Therefore, the goal of this project was to determine whether CTRP3 prevented ALD in female mice. Methods: Female wild type (WT) and female CTRP3 transgenic over expressing (Tg) mice were fed an ethanol containing liquid diet (5% v/v) for 6 weeks. Daily weight and food intake measurements were taken and external heat-pads were placed under a portion of the cage to facilitate thermoregulation. Hepatic steatosis was determined by total triglyceride quantification and lipid droplet quantitation in liver sections. Data were analyzed by repeated measures ANOVA, t-test, or Log-rank (Mantel-Cox) test as appropriate. Results: There was no difference between WT and Tg mice in food intake or body weight. There was no difference in survival between WT and Tg mice, however, Tg mice trended towards a reduced rate of survival compared with WT mice (78% in WT versus 44% in Tg, p=0.13). Stereological analysis indicated no difference in the percent of lipid liver volume between the two groups (WT 7.2±3.6 vs Tg 5.1±4.1%). This finding was consistent with no difference in total hepatic triglyceride accumulation observed between WT and Tg mice (12.7±4.4 vs. 13.1±6.8 mg triglycerides/gram liver protein). Conclusion: Combined these data indicate that unlike previous studies with male mice, CTRP3 is not protective against alcohol-induced hepatic steatosis in female mice. Combined, these data indicate that the adipokines such as CTRP3 contribute to physiology in a sex-specific manner.

INTRODUCTION: The diagnosis of esophageal varices in cirrhotic patients is made by the upper gastrointestinal endoscopy. Multiple non-invasive predictors have been studied for the diag-nosis of esophageal varices. The objective of this study is to testthe FIB4 index as screening of esophageal varices in patients with liver cirrhosis. MATERIALS AND METHODS: A cross-sectional analytic study was developed in four national hospital using hepatic cirrhosis patient's medi-cal files. We assessed the information using univariate and bivariate analysis, sensitivity, speci-ficity, predictive positive and negative value, the positive and negative likelihood ratio calcu-lation of the esophageal varices screening and its size. We built ROC curve for every analysis group. RESULTS: The study included 289 liver cirrhosis patients. Most of the patients were male (54.33%). 77.85% patients had esophageal varices. The distribution of varices was 19.03%, 35.99% and 22.84% for large, medium and small varices, respectively. In the FIB-4 index analysis for the presence of varices, it was found a sensitivity of 81.3%, specificity of 37.5% (AUC: 0.57). The calculation for variceal size showed a sensitivity of 81.8%, specificity of 23.9% (AUC: 0.50). In the analysis of FIB-4 index for prophylaxis groups was found a sensitivity of 81.8% and a specificity of 28.5% (AUC: 0.54). CONCLUSIONS: The FIB-4 index has no good performance in the screening for the presence of esophageal varices and its size in liver cirrhosis patients. / Revisión por pares

<p>Parasite infections around the world are a huge economic burden and decrease the quality of life for many people. Probiotic bacteria are being investigated as a possible treatment for many enteric issues due to their beneficial effects by altering the immune system. Goblet cells are the main source of mucins in the gut, and play an important role in host defense. Alterations in goblet cells and mucin have been implicated in a number of gastrointestinal (GI) diseases and infections. The aim of this study is to develop a probiotic based strategy to modulate goblet cell function in relation to host defense in enteric infection. Utilizing a murine model of parasite infection, <em>Trichuris muris</em>,<em> </em>we examined the effect of daily administration with probiotic <em>Lactobacillus reuteri</em> in different strains of mice and investigation of goblet cell alterations, immune and inflammatory responses in gut, and host defense mechanisms.</p> <p>Treatment with<strong> </strong>live <em>L. reuteri</em> significantly enhanced worm expulsion in resistant C57BL/6 mice and this was associated with significant increase in goblet cells numbers and an increase in IL-10. This lead to investigation of the probiotic effects in IL-10 knock out (KO) and Muc2 KO mice during the infection. There was no difference of worm burden or goblet cell amounts in infected IL-10 KO mice infected treated with probiotic or medium. In infected Muc2 KO mice treated with <em>L. reuteri</em>, there was an earlier increase of goblet cells, and a corresponding decrease in worm numbers. Finally, assessment of this probiotic in susceptible ARK mice revealed no alterations in worm burden, but the treatment prevented the increase in IFN-γ and IL-1β and significantly increased goblet cell numbers.</p> <p>These data demonstrate that altering the flora with probiotic <em>L. reuteri</em> treatment can modulate intestinal goblet cell biology and immune responses in gut, and promote worm expulsion, possibly through an IL-10 mediated mechanism. The increases in goblet cell numbers may also play a role in the early expulsion of the parasite. In addition to enhancing our understanding on the beneficial effect of probiotics in host defense in enteric infection, this research provides new information on gut function in the context of goblet cells and mucins.</p> / Master of Science (MSc)

<p>Colorectal cancer leads to more than 600,000 deaths worldwide per year. An abundance of research has shown that several non-steroidal anti-inflammatory drugs (NSAIDs) can exert chemotherapeutic and chemo-preventative effects in colorectal cancer patients. It is important to note, that use of many different NSAIDs carries a significant risk for cardiovascular and gastrointestinal (GI) complications. A recently developed group of NSAIDs, which release hydrogen sulfide (H₂S), has been shown to have greatly reduced these side effects as compared to conventional NSAIDs. This is likely attributable to the ability of H₂S to increase the resistance of the GI mucosa to injury, as well as to accelerate repair of injury when it occurs. Moreover, H₂S has been shown to be a vasodilator, and therefore may offset some of the hypertensive effects of NSAIDs.</p> <p>We assessed the chemotherapeutic actions of two of these newly developed NSAIDs. ATB-346 is an H₂S-releasing derivative of naproxen and ATB-352 is an H₂S-releasing derivative of ketoprofen. These drugs were tested in the azoxymethane mouse model and in the APC^Min/+mouse model of Colorectal cancer.</p> <p>In the azoxymethane model of colorectal cancer ATB-346 caused a significant reduction in number aberrant crypt foci (ACF), which are pre-neoplastic lesions used as markers of colorectal cancer. The reduction was superior to naproxen at all doses tested. ATB-352 also caused a significant reduction in the number of ACF, however the reduction was not superior to that produced by ketoprofen. In APC^Min/+mice treated with ATB-346 for 14 days (14.5 mg/kg) we observed a complete inhibition of the formation of colonic polyps/tumours and a 97.5% reduction in total polyp score. Shorter treatment with ATB-346 also produced similar reduction in total polyp score. We found that ATB-346-treated mice had lower levels of b-catenin and cmyc without significant changes in APC or p53 levels. <strong></strong></p> <p>These results demonstrate ATB-346 can exert superior chemo-preventative effects in mice models of colon cancer while leading to no gastric or intestinal damage.</p> / Master of Science (MSc)

Syftet med denna undersökning är att ta reda på hur barns föreställning om matens väg genom kroppen skiljer sig åt. I undersökningen jämförs barn i tre- till fyra och fem- till sex årsåldern, närmare beskrivet barn födda 2010 och 2012. För att undersöka detta användes kvalitativa semistrukturerade intervjuer samt siluetter av en människokropp som barnen fick illustrera sina föreställningar på. Valet av metod gjorde det möjligt att fördjupa sig i barnens tankar och resonemang vilket är fördel när man undersöker något utifrån barns perspektiv. Resultatet i undersökningen visar att majoriteten av samtliga respondenter hade föreställningen om att maten transporteras till magen. I resultatet framgår olika beskrivningar på hur maten transporteras ned till magen men även vad som sker därefter. Resultatet visar även att femåringarna har en mer detaljerad beskrivning och bredare kunskap om matens väg genom kroppen. / The purpose of this study is to find out the difference between five- and three-years old children’s conception about the digestive system. The study was conducted by using qualitative semi-structured interviews and silhouettes of a human body so that the children could illustrate their conception on. The choice of method made it possible to immerse the children’s thoughts and reasoning which is a benefit when you base your study on children’s perspective. The results show that majority of the respondents thought that the food end up in the stomach, even though the descriptions was different. The results also show that the five- years old had more detailed description and more knowledge about the digestive system then the three-year-old children.