Investigating the Role of 17-Beta Estradiol in the Regulation of the Unfolded Protein Response (UPR) in Pancreatic Beta Cells.

Diabetes mellitus is clinically defined by chronic hyperglycemia. Sex differences in the presentation and outcome of diabetes exist with premenopausal women having a reduced risk of developing diabetes, relative to men, or women after menopause. Accumulating evidence shows a protective role of estrogens, specifically 17-beta estradiol, in the maintenance of pancreatic beta cell health; however, the mechanisms underlying this protection are still unknown. To elucidate these potential mechanisms, we used a pancreatic beta cell line (BTC6) and a mouse model of hyperglycemia-induced atherosclerosis, the ApoE-/-:Ins2+/Akita mouse, exhibiting sexual dimorphism in glucose regulation. In this study we hypothesize that 17-beta estradiol protects pancreatic beta cells by modulating the unfolded protein response (UPR) in response to endoplasmic reticulum (ER) stress. We observed that ovariectomized female and male ApoE-/-:Ins2+/Akita mice show significantly increased expression of apoptotic UPR markers. Sham operated female and ovariectomized female ApoE-/-:Ins2+/Akita mice supplemented with exogenous 17-beta estradiol increased the expression of adaptive UPR markers compared to non-supplemented ovariectomized female ApoE-/-:Ins2+/Akita mice. These findings were consistent to what was observed in cultured BTC6 cells, suggesting that 17-beta estradiol may protect pancreatic beta cells by repressing the apoptotic UPR and enhancing the adaptive UPR activation in response to pancreatic ER stress.

Investigating the protective effects of estrogen on ß-cell health and the progression of hyperglycemia-induced atherosclerosis.

Sex differences in the prevalence and development of diabetes and associated cardiometabolic complications are well established. The objective of this study was to analyze the effects of estrogen on the maintenance of ß-cell health/function and atherosclerosis progression, using a mouse model of hyperglycemia-induced atherosclerosis, the ApoE-/-:Ins2+/Akita mouse. ApoE-/-:Ins2+/Akita mice exhibit sexual dimorphism in the control of blood glucose levels. Male ApoE-/-:Ins2+/Akita mice are chronically hyperglycemic due to a significant reduction in pancreatic ß-cell mass. Female mice are only transiently hyperglycemic, maintain ß-cell mass, and blood glucose levels normalize at 35 ± 1 days of age. To determine the effects of estrogen on pancreatic ß-cell health and function, ovariectomies and estrogen supplementation experiments were performed, and pancreatic health and atherosclerosis were assessed at various time points. Ovariectomized ApoE-/-:Ins2+/Akita mice developed chronic hyperglycemia with significantly reduced ß-cell mass. To determine whether the observed effects on ovariectomized ApoE-/-:Ins2+/Akita mice were due to a lack of estrogens, slow-releasing estradiol pellets were inserted subcutaneously. Ovariectomized ApoE-/-:Ins2+/Akita mice treated with exogenous estradiol showed normalized blood glucose levels and maintained ß-cell mass. Exogenous estradiol significantly reduced atherosclerosis in both ovariectomized female and male ApoE-/-:Ins2+/Akita mice relative to controls. Together, these findings suggest that estradiol confers significant protection to pancreatic ß-cell health and can directly and indirectly slow the progression of atherosclerosis.NEW & NOTEWORTHY This study examines the effect(s) of estrogen on ß cell and cardiometabolic health/function in a novel mouse model of hyperglycemia-induced atherosclerosis (ApoE-/-:Ins2+/Akita). Using a combination of estrogen deprivation (ovariectomy) and supplementation strategies, we quantify effects on glucose homeostasis and atherogenesis. Our results clearly show a protective role for estrogen on pancreatic ß-cell health and function and glucose homeostasis. Furthermore, estrogen supplementation dramatically reduces atherosclerosis progression in both male and female mice.

Thirty-Day Readmissions After Upper and Lower Gastrointestinal Hemorrhage: A National Perspective in the United States.

BACKGROUND: Upper gastrointestinal hemorrhage (UGIH) and lower gastrointestinal hemorrhage (LGIH) are 2 of the most common reasons for hospital admissions across the United States. The 30-day readmission after index admission poses a major burden on the health care infrastructure, and thus, it is important to assess the causes of 30-day readmission for patients with UGIH and LGIH. METHODS: The study cohort was derived from the 2013 National Readmission Database. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) Volume 3 diagnosis codes were utilized to identify UGIH and LGIH patients from this data set. Patients who were readmitted to the hospital within 30 days within the same calendar year were further analyzed. Categorical variables and continuous variables were assessed by the χ test and the student t test, respectively. The independent predictors of unplanned 30-day readmissions were recognized by multivariate logistic regression, adjusting for stratified cluster design of National Readmission Database. SAS 9.4 (SAS Institute Inc., Cary, NC) was used for data analysis. RESULTS: The number of index admissions identified from the National Readmission Data 2013 were 82,290 for UGIH and 133,114 for LGIH. All-cause 30-day readmission rate for UGIH versus LGIH was 14.6% (readmitted N=12,046; 56.64% age 65 y and above) versus 14.4% (readmitted N=19,128; 70.21% age 65 y and above and 49.61% men). Gastrointestinal causes were most common (33.9% vs. 39.6%), followed by cardiac (13.3% vs. 15.3%), infectious (10.4% vs. 9.1%), and respiratory causes (7.8% vs. 7.1%) for 30-day readmission for UGIH and LGIH. Significant predictors of increased 30-day readmission (odds ratio, 95% confidence interval, P-value) included metastatic disease (2.15, 1.75-2.64, P<0.001), discharge against medical advice (1.85, 1.55-2.22, P<0.001), and length of stay >3 days (1.50, 1.38-1.63, P<0.001). Predictors for 30-day readmission for LGIH included metastatic disease (1.75, 1.48-2.06, P<0.001), liver disease (1.59, 1.49-1.71, P<0.001), and drug abuse (1.38, 1.21-1.58, P<0.001). CONCLUSIONS: Most common reason for UGIH and LGIH readmission was related to gastrointestinal disease, followed by cardiac, infectious, and respiratory etiologies. By addressing these etiologies for readmission, it may be possible to reduce adverse outcomes.

Active recall strategies associated with academic achievement in young adults: A systematic review.

BACKGROUND: Effective learning strategies are crucial to the development of academic skills and information retention, especially in post secondary education where increasingly complex subjects are explored. Active recall-based strategies have been identified as particularly effective for long-term learning. This systematic review investigates the effectiveness of various active recall-based learning strategies for improving academic performance and self-efficacy in higher education students. METHODS: A systematic review of peer-reviewed articles was conducted with a priori criteria by searching PubMed, ScienceDirect, JSTOR, PsycInfo, and Web of Science databases. Search results were screened/extracted and reconciled by two independent authors with the use of a piloted screening tool. Included studies were assessed for quality and risk of bias using the GRADE Quality Assessment Tool for Quantitative Studies. Three overarching study strategies were extracted for further investigation including flashcards, practice testing or retrieval practice, and concept mapping. Within each category, three additional unique search strings were searched, screened, and extracted. A qualitative analysis of the studies was provided. RESULTS: Among the appraised articles, flashcards were found to be popular and correlated with higher GPA and test scores. Self-testing, retrieval practice, and concept mapping were also effective but under-utilized. Concept mapping was found to boost student confidence. CONCLUSION: Active recall strategies exhibit promise for effective learning and additional research in these developing field can support academic pursuits.

Thyroid Metastasis to the Colon.

Approximately 1% of colorectal cancers can be attributed to metastatic neoplasms originating from other primary sources typically the lung, ovary, breast, prostate, kidney, or skin. Metastasis to the colon from the thyroid however is exceedingly rare. We present a 76-year-old man with a history of papillary thyroid carcinoma WHO presented with colon polyps consistent with carcinoma from his papillary thyroid carcinoma. The findings in this report suggest prompt colorectal cancer screening after thyroid cancer diagnosis and regular screening thereafter.

Large Unilateral Adrenal Mass with Surrounding Brown Fat: A Case Report.

Pheochromocytomas are rare tumors derived from chromaffin cells located in the adrenal and extra adrenal tissues. Pheochromocytomas are diagnosed biochemically and localized using different imaging modalities. The definitive management is surgical resection. Brown adipose tissues are normally present during fetal development, with regression over time. Brown adipose tissues are thermogenic and usually located in the neck, mediastinum, and retroperitoneum. Here, we report a case of a unilateral pheochromocytoma surrounded by brown fat. The abnormal stimulation of brown fat noted on positive emission tomography scan (PET) resolved after the pheochromocytoma was resected.

A Giant Adrenal Mass in a Super Obese Patient.

Giant pheochromocytomas (Pheo) are rare entities requiring clinical suspicion coupled with strategic diagnostic evaluation to confirm the diagnosis. The majority of cases are discovered incidentally. The diagnosis consists of biochemical evaluation and imaging study to localize the mass. Pathological examination confirms the diagnosis. The female patient in this case report presented with chest pain, palpitation of three weeks duration and was found on evaluation to have an abdominal mass concerning for pheochromocytoma. She was treated with surgical resection. The pheo measured 20.5 x 18 x 10 cm and weighed 2,582 grams. Pathological examination confirmed the diagnosis of pheochromocytoma.

Type 2 autoimmune pancreatitis: case report of a 9-year-old female and a review of the literature.

We report a case of autoimmune pancreatitis in a 9-year-old female who presented with persistent epigastric pain for 3 weeks. Magnetic resonance cholangiopancreatography (MRCP) showed both intrahepatic and extrahepatic biliary ductal dilatation. The common bile duct, along with the pancreatic duct, was noted to be dilated. Labs showed normal IgG and IgG4 levels and negative for autoimmune antibodies. Endoscopic ultrasound revealed the pancreatic head to be enlarged and surrounded by hypoechoic and lobulated lymph nodes. Biopsy of the pancreatic head showed chronic mildly active inflammation with fibrosis, acinar atrophy, and lymphocytic infiltrate. A diagnosis of autoimmune pancreatitis (AIP) was made, and she was treated with prednisone. The patient's symptoms improved quickly, and follow-up MRCP showed resolution of inflammatory changes and intrahepatic and pancreatic ductal dilatation.

Orthokeratinized odontogenic cyst of the mandible: A rare case report with a systematic review.

Orthokeratinized odontogenic cyst (OOC) is an odontogenic cyst was initially termed as the uncommon orthokeratinized type of odontogenic keratocyst by the World Health Organization. It usually occurs in mandible. Various studies have shown that OOC has typical characteristic clinicopathologic features when compared to other developmental odontogenic lesions such as dentigerous cyst and the keratocystic odontogenic tumor (KCOT). Rare recurrence was noted after surgical removal of the lesion. The purpose of this article is to present a case of OOC arising in the posterior mandible and emphasize on differentiating it from the KCOT and dentigerous cyst.