Adipocytes Promote Endometrial Cancer Progression Through Activation of the SIRT1-HMMR Signaling Axis.

Adipocyte is a predominant component of the omental adipose tissue that influences the tumor microenvironment and increases the risk of endometrial cancer progression (EC), however, little is known about the underlying mechanism. In this study, using a co-culture model, we found that the adipocyte-EC cell interaction promoted SIRT1 signaling in vitro and in vivo xenograft mice models. Furthermore, immunostaining of SIRT1 protein showed significantly higher expression of SIRT1 in endometrial cancer patients than in normal endometria. RNA sequencing analysis revealed HMMR (hyaluronan-mediated motility receptor), an oncogene, as a downstream effector of SIRT1 in adipocyte-associated EC. Transient knockdown and chromatin immunoprecipitation assays showed that SIRT1 inhibition impedes transcription of the HMMR gene via FOXM1, and reduced expression of HMMR in co-cultured EC cells blocks AURKA activation via TPX2, leading to cell cycle arrest. This is the first study to report the positive correlation between SIRT1 and HMMR in EC patient tumors and might be used as a potential biomarker in EC. Notably, SIRT1 regulates HMMR expression in a FOXM1-dependent manner, and interfering with SIRT1 may provide a promising strategy for the management of endometrial cancer.

Impact of Elevated Serum Triglycerides on Children with Acute Recurrent or Chronic Pancreatitis from INSPPIRE-2.

OBJECTIVE: To determine if mild-moderate hypertriglyceridemia is associated with increased development of chronic pancreatitis or pancreatitis-associated complications in children with acute recurrent or chronic pancreatitis. STUDY DESIGN: Longitudinal data from the INSPPIRE-2 (INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2) cohort of children with acute recurrent or chronic pancreatitis (n=559) were analyzed. Subjects were divided into normal triglycerides (<150 mg/dL; 1.7 mmol/L), any hypertriglyceridemia (≥150 mg/dL; ≥1.7 mmol/L), mild-moderate hypertriglyceridemia (150-499 mg/dL; 1.7-5.6 mmol/L), moderate hypertriglyceridemia (500-999 mg/dL; 5.6-11.3 mmol/L), and severe hypertriglyceridemia groups (≥1,000 mg/dL; ≥11.3 mmol/L), based on highest serum triglyceride value. Laboratory, imaging, pancreatitis and hospital events, complications, and quality of life data were analyzed. RESULTS: In children with acute recurrent or chronic pancreatitis and hypertriglyceridemia, there was no increase in the number of pancreatitis attacks per person-years, nor an increase in chronic pancreatitis prevalence. However, hypertriglyceridemia severity was associated with increased pancreatic inflammation, pancreatic cysts, pain, hospital days, number of hospitalizations, intensive care, and missed school days. CONCLUSIONS: Mild-moderate hypertriglyceridemia in children with acute recurrent or chronic pancreatitis was not associated with increased pancreatitis frequency, nor increased development of chronic pancreatitis, but was associated with increased pancreatitis complications and disease burden. As a treatable condition, treatment of mild-moderate hypertriglyceridemia may be considered to reduce pancreatitis-associated complications and medical burden in children with acute recurrent or chronic pancreatitis.

Zinc: Roles in pancreatic physiology and disease.

Zinc is an essential trace element. Deficiencies are frequently seen with gastrointestinal diseases, including chronic pancreatitis, nutritional deficiency, and reduced intestinal absorption. Additionally, reduced zinc levels have been linked to cellular changes associated with acute pancreatitis such as enhanced inflammation with increased macrophage activation and production of inflammatory cytokines such as IL-1ß, impaired autophagy, and modulation of calcium homeostasis. Preliminary data suggest that zinc deficiency may lead to pancreatic injury in animal models. The purpose of this review is to explore the biologic effects of zinc deficiency that could impact pancreatic disease. MESH KEYWORDS: Malnutrition, inflammation, trace element.

Current clinical opinion on CFTR dysfunction and patient risk of pancreatitis: diagnostic and therapeutic considerations.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR)-mediated chloride and bicarbonate secretion is integral to the pancreas' ability to produce the alkaline pancreatic juice required for proper activation of enzymes for digestion. Disruption in this process increases the risk for pancreatitis. AREAS COVERED: Using original basic and clinical research, as well as clinical case reports and recent reviews indexed in PubMed, we discuss why patients with CFTR dysfunction are at risk for pancreatitis. We also discuss diagnostic modalities for assessing CFTR function, as well as new therapeutic advancements and the impact these are having on pancreatic function, pancreatitis in particular. EXPERT OPINION: CFTR-related pancreatitis occurs in the presence of monallelic or biallelic mutations and/or from toxin-mediated channel disruption. Research-based CFTR diagnostics have been expanded, yet all current methods rely on measuring CFTR chloride transport in non-pancreatic cells/tissue. Newer CFTR-directed therapies ('CFTR modulators') are both improving pancreatitis (pancreatic-sufficient CF patients) and increasing the risk for pancreatitis (previously pancreatic-insufficient CF patients). Our experiences with these drugs are enlightening us on how CFTR modulation can affect pancreatitis risk across a wide spectrum of pancreatic disease, and represents an opportunity for therapeutic relief from pancreatitis in those without CF, but who suffer from CFTR-related pancreatitis.

Neuromyelitis Optica Spectrum Disorder Manifested by Persistent Hiccups and Severe Esophagitis in an Adolescent Patient.

Patients with persistent hiccups are often referred to gastrointestinal services. Hiccups lasting greater than 48 hours are classified as persistent, while those lasting longer than 2 months are termed intractable. The etiology of hiccups is broad and can include many organ systems. Here, we present the case of an 18-year-old male patient who presented to the emergency department with an 8-day history of nausea, emesis, and intermittent hiccups. The patient was admitted to the gastroenterology service and underwent workup including esophagogastroduodenoscopy and imaging. Esophagogastroduodenoscopy revealed severe distal esophagitis. He was started on high-dose proton pump inhibitor and sucralfate. During the course of hospital admission, the patient's intermittent hiccups worsened to become constant. Several medical therapies led to little improvement. We initially felt that the esophagitis was the etiology of the patient's symptoms, however, due to ongoing symptoms unresponsive to typical therapy, we obtained a neurological consult. Brain MRI revealed a dorsal medullary lesion. Subsequent work up confirmed the diagnosis of neuromyelitis optica spectrum disorder. Neuromyelitis optica spectrum disorder is a rare, serious, sometimes fatal autoimmune condition of the central nervous system. Early diagnosis and treatment are important predictors of future relapses. Our patient was started on high-dose intravenous steroids with rapid improvement in symptoms. He was discharged home on steroids, proton pump inhibitor and close neurology and gastroenterology follow up. This case outlines the importance of consideration of neurological causes of hiccups or other centrally mediated conditions with gastrointestinal manifestations, even when a concomitant gastrointestinal condition is present.

Mammary analogue secretory carcinoma: An Indian experience of a novel entity.

AIMS: To explore clinical, histopathological and immunohistochemistry (IHC) features of mammary analogue secretory carcinoma (MASC) with systematic literature review. SETTINGS AND DESIGN: Hospital based cross-sectional study. SUBJECTS AND METHODS: The data of all cases of MASC diagnosed over a period of 1 year i.e., from July 2017 to July 2018 were retrieved. The haematoxylin and eosin (H and E) sections, and IHC sections were studied. A strict histological and recently updated criteria were applied and patients with a confirmed diagnosis of MASC were included in the study. A systematic literature review was conducted by searching the PubMed and National Centre for Biotechnology Information database. STATISTICAL ANALYSIS USED: Microsoft Excel 2010. RESULTS: The present case series is 27th in the English literature and 1stcase series describing its histopathology in the Indian literature. The mean age of presentation is 43 years. Female preponderance was found i.e., M:F ratio of 0.5. CONCLUSION: Histopathology and if necessary, followed by IHC is required for the confirmation of diagnosis of MASC. We should be aware about this recently described entity which is usually mistaken for other low grade salivary gland carcinomas like Acinic cell carcinoma (AciCC) and Mucoepidermoid carcinoma (MEC). The knowledge about its typical morphology, high degree of suspicion and IHC confirmation with both S-100 and Mammaglobin help in precise diagnosis.

Epithelioid sarcoma of paratesticular region: A case report of an unusual case.

Primary tumors of the paratesticular region are rare, with sarcomas constituting a major proportion, particularly in the old age. The paratesticular region consists of mesothelial, various epithelial, and mesenchymal cells and may therefore give rise to a variety of tumors. Epithelioid sarcoma usually occurs at the distal extremities of young adults. The proximal-type variant is characterized by a more aggressive course and resistance to treatment. We herein report a case of 32 years male with scrotal swelling diagnosed as proximal-type epithelioid sarcoma of paratesticular region after histopathological examination and immunohistochemistry. To the best of our knowledge, this is only the second case of proximal epithelioid sarcoma of paratesticular region in the English literature. As these tumors are rare, it has been difficult to establish their optimal treatment. Also, these can be easily misdiagnosed as other epithelioid lesions.

Increasing the perceptual salience of relationships in parallel coordinate plots.

We present three extensions to parallel coordinates that increase the perceptual salience of relationships between axes in multivariate data sets: (1) luminance modulation maintains the ability to preattentively detect patterns in the presence of overplotting, (2) adding a one-vs.-all variable display highlights relationships between one variable and all others, and (3) adding a scatter plot within the parallel-coordinates display preattentively highlights clusters and spatial layouts without strongly interfering with the parallel-coordinates display. These techniques can be combined with one another and with existing extensions to parallel coordinates, and two of them generalize beyond cases with known-important axes. We applied these techniques to two real-world data sets (relativistic heavy-ion collision hydrodynamics and weather observations with statistical principal component analysis) as well as the popular car data set. We present relationships discovered in the data sets using these methods.

Exploring Ensemble Visualization.

An ensemble is a collection of related datasets. Each dataset, or member, of an ensemble is normally large, multidimensional, and spatio-temporal. Ensembles are used extensively by scientists and mathematicians, for example, by executing a simulation repeatedly with slightly different input parameters and saving the results in an ensemble to see how parameter choices affect the simulation. To draw inferences from an ensemble, scientists need to compare data both within and between ensemble members. We propose two techniques to support ensemble exploration and comparison: a pairwise sequential animation method that visualizes locally neighboring members simultaneously, and a screen door tinting method that visualizes subsets of members using screen space subdivision. We demonstrate the capabilities of both techniques, first using synthetic data, then with simulation data of heavy ion collisions in high-energy physics. Results show that both techniques are capable of supporting meaningful comparisons of ensemble data.

Comparative Visualization of Ensembles Using Ensemble Surface Slicing.

By definition, an ensemble is a set of surfaces or volumes derived from a series of simulations or experiments. Sometimes the series is run with different initial conditions for one parameter to determine parameter sensitivity. The understanding and identification of visual similarities and differences among the shapes of members of an ensemble is an acute and growing challenge for researchers across the physical sciences. More specifically, the task of gaining spatial understanding and identifying similarities and differences between multiple complex geometric data sets simultaneously has proved challenging. This paper proposes a comparison and visualization technique to support the visual study of parameter sensitivity. We present a novel single-image view and sampling technique which we call Ensemble Surface Slicing (ESS). ESS produces a single image that is useful for determining differences and similarities between surfaces simultaneously from several data sets. We demonstrate the usefulness of ESS on two real-world data sets from our collaborators.