Baffling perforation of the colon

Idiopathic perforation of the colon is extremely unusual and unexpected, with a very limited number of published reports. The condition’s definition depends on the absence of any detectable pathology in the bowel wall that could be responsible for the perforation. A 62-year-old male patient presented with acute thrombosis of the brachial artery. This was successfully treated with an open thrombectomy and systemic anticoagulation, with rapid resolution of the symptoms. During the hospital stay the patient had regular bowel movements and no abdominal complaints. Suddenly he complained of acute abdominal pain. Physical examination and emergency CT scan of the abdomen were consistent with generalized peritonitis. Emergency laparotomy revealed two perforations of the mid-sigmoid colon, each measuring 1.5 x 1.5 cm, an

The secret recipe : to leadership and career pathway success in dietetics

Advisors: LaVerne Gyant.Committee members: Sheila Barrett; Jane Rheineck.Includes bibliographical references.Includes illustrations.This dissertation focused on leaders within the dietetics profession and allowed their "voice" to be heard related to their specific personal and lived experiences throughout their own career pathways. A total of twenty participants (eighteen women and two men) were selected for this qualitative research study. I completed twenty in-depth face-to-face and phone interviews, which each lasted approximately 90 minutes. Narrative inquiry analysis was used to identify some of the key themes that emerged from the findings. A total of five key themes emerged as they related to participants' career pathway and leadership development. Mentoring was one theme that emerged; the participants shared how family, education, and professional colleagues influenced their career pathway development. A second theme was career pathways, which focused on traditional and non-traditional pathways toward becoming a Registered Dietitian Nutritionist (RDN) and how certain issues/events caused career pathway shifts to occur. The third theme related to specific successes and barriers faced by these participants in their family, educational, and professional lives and how these impacted their own career pathway development. The fourth theme related to personality styles. I used participants' self-reported assessments and my own personal interpretation to identify how certain distinct traits emerged and related to the types of career pathways they chose. The last theme focused on participants' personal journey to leadership, the successes and challenges they faced, styles of leadership, and words of wisdom for future leaders. There exist many leaders within the dietetics profession, but their voices have not been conveyed in the professional research literature. Due to the ever-changing landscape of the allied healthcare professions, the field of nutrition as a whole needs to focus on gaining a better understanding about leadership. These findings can provide some key insights into areas where future development and leadership training should be focused in order to create empowered nutrition professionals who are relevant and can make an impact on our society's future nutrition, health, and well-being.Ed.D. (Doctor of Education

Start Early and See Inflammatory; Late, Nothing Save RAVE: How to Appreciate Radiation Proctitis as a Continuum

Background and Aims: It has been recently proposed to change the nomenclature of “chronic radiation proctitis” (CRP) to “radiation-associated vascular ectasia” on the basis that signs of inflammation are rarely observed. We herein present data supporting the idea that inflammation is a critical step that initiates the process that culminates in the characteristic changes of CRP. Methods: In support of inflammation in the pathogenesis of CRP, we review the pertinent literature and publish our new results, including the role of amifostine treatment and proinflammatory factors (p38 MAP kinase, VEGF, and CEACAM1). Results: Immunohistochemistry from anterior rectal wall biopsies obtained in a prospective pilot study demonstrates that expression of VEGF and the downstream vascular effector CEACAM1 were elevated before radiotherapy and declined with time. We also show that MAP Kinase p38 expression usually precede the radiation. Fibrosis scores increase from baseline at 9 and 18 months, while vascular scores decrease at 18 months. Conclusion: The proposed new nomenclature should be held in obeyance until more supportive data are presented. Possibly, the best way to view CRP is as a continuum that may take one of three forms, inflammation-predominant, vasculopathy-predominant, or mixed

In the SARS-CoV-2 Pandora Pandemic: Can the Stance of Premorbid Intestinal Innate Immune System as Measured by Fecal Adnab-9 Binding of p87:Blood Ferritin, Yielding the FERAD Ratio, Predict COVID-19 Susceptibility and Survival in a Prospective Population Database?

SARS-CoV-2 severity predictions are feasible, though individual susceptibility is not. The latter prediction allows for planning vaccination strategies and the quarantine of vulnerable targets. Ironically, the innate immune response (InImS) is both an antiviral defense and the potential cause of adverse immune outcomes. The competition for iron has been recognized between both the immune system and invading pathogens and expressed in a ratio of ferritin divided by p87 (as defined by the Adnab-9 ELISA stool-binding optical density, minus the background), known as the FERAD ratio. Associations with the FERAD ratio may allow predictive modeling for the susceptibility and severity of disease. We evaluated other potential COVID-19 biomarkers prospectively. Patients with PCR+ COVID-19 tests (Group 1; n = 28) were compared to three other groups. In Group 2 (n = 36), and 13 patients displayed COVID-19-like symptoms but had negative PCR or negative antibody tests. Group 3 (n = 90) had no symptoms and were negative when routinely PCR-tested before medical procedures. Group 4 (n = 2129) comprised a pool of patients who had stool tests and symptoms, but their COVID-19 diagnoses were unknown; therefore, they were chosen to represent the general population. Twenty percent of the Group 4 patients (n = 432) had sufficient data to calculate their FERAD ratios, which were inversely correlated with the risk of COVID-19 in the future. In a case report of a neonate, we studied three biomarkers implicated in COVID-19, including p87, Src (cellular-p60-sarcoma antigen), and Abl (ABL-proto-oncogene 2). The InImS of the first two were positively correlated. An inverse correlation was found between ferritin and lysozyme in serum (p < 0.05), suggesting that iron could have impaired an important innate immune system anti-viral effector and could partially explain future COVID-19 susceptibility

<i>Helicobacter pylori</i> Status May Differentiate Two Distinct Pathways of Gastric Adenocarcinoma Carcinogenesis

Background: We evaluated the phenotype of sporadic gastric cancer based on HP status and binding of a tumor risk marker monoclonal, Adnab-9. Methods: We compared a familial GC kindred with an extremely aggressive phenotype to HP-positive (HP+) and -negative (HP−) sporadic gastric adenocarcinoma (GC) patients in the same community to determine if similar phenotypes exist. This might facilitate gene discovery to understand the pathogenesis of aggressive GC phenotypes, particularly with publications implicating immune-related gene-based signatures, and the development of techniques to gauge the stance of the innate immune system (InImS), such as the FERAD ratio (blood ferritin:fecal Adnab-9 binding OD-background binding). Resection specimens for the sporadic and familial group were stained for HP and examined for intestinal metaplasia (IM) and immunostaining for Adnab-9. Familial kindred specimens were also tested for the E-cadherin mutation and APC (adenomatous polyposis coli). Survival was evaluated. Results: Of 40 GC patients, 25% were HP+ with a greater proportion of intestinal metaplasia (IM) and gastric atrophy than the HP− group. The proband of the familial GC kindred, a 32-year-old mother with fatal GC, was survived by 13-year-old identical twins. Twin #1 was HP− with IM and Twin #2 was HP+. Both twins subsequently died of GC within two years. The twins did not have APC or E-cadherin mutations. The mean overall survival in the HP+ sporadic GC group was 2.47 ± 2.58 years and was 0.57 ± 0.60 years in the HP− group (p = 0.01). Survival in the kindred was 0.22 ± 0.24 years. Adnab-9 labeling was positive in fixed tissues of 50% of non-familial GC patients and in gastric tissue extract from Twin #2. The FERAD ratio was determined separately in six prospectively followed patient groups (n = 458) and was significantly lower in the gastric cancer patients (n = 10) and patients with stomach conditions predisposing them to GC (n = 214), compared to controls (n = 234 patients at increased risk for colorectal cancer but without cancer), suggesting a failure of the InImS. Conclusion: The HP+ sporadic GC group appears to proceed through a sequence of HP infection, IM and atrophy before cancer supervenes, and the HP− phenotype appear to omit this sequence. The familial cases may represent a subset with both features, but the natural history strongly resembles that of the HP− group. Two different paths of carcinogenesis may exist locally for sporadic GC. The InImS may also be implicated in prognosis. Identifying these patients will allow for treatment stratification and early diagnosis to improve GC survival

Identification and testing of novel CARP-1 functional mimetic compounds as inhibitors of non-small cell lung and triple negative breast cancers

The triple negative breast cancer (TNBCs) and non-small cell lung cancers (NSCLCs) often acquire mutations that contribute to failure of drugs in clinic and poor prognosis, thus presenting an urgent need to develop new and improved therapeutic modalities. Here we report that CARP-1 functional mimetic (CFMs) compounds 4 and 5, and 4.6, a structurally related analog of CFM-4, are potent inhibitors of TNBC and NSCLC cells in vitro. Cell growth suppression by CFM-4 and -4.6 involved interaction and elevated expression of CARP-1/CCAR1 and Death Effector Domain (DED) containing DNA binding (DEDD)2 proteins. Apoptosis by these compounds also involved activation of pro-apoptotic stress-activated kinases p38 and JNK1/2, cleavage of PARP and loss of mitotic cyclin B1. Both the CFMs inhibited abilities of NSCLC and TNBC cells to migrate, invade, and form colonies in suspension, while disrupting tubule formation by the human umbilical vein endothelial cells (HUVECs). Nano-lipid formulation of CFM-4 (CFM-4 NLF) enhanced its serum bioavailability when compared with the free CFM-4. Oral administration of CFM-4 NLF reduced weights and volume of the xenografted tumors derived from A549 NSCLC and MDA-MB-231 TNBC cells. Although no gross tissue or histological toxicities were noticed, the immuno-histochemical analysis revealed increased CARP-1 and DNA fragmentation in tumors of the CFM-4 NLF-treated animals. In conclusion, while stimulation of pro-apoptotic CARP-1 and DEDD2 expression and their binding underscore a novel mechanism of apoptosis transduction by CFM compounds, our proof-of-concept xenograft studies demonstrate therapeutic potential of CFM-4 for TNBC and NSCLC