Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma–Past,Present, and Future

Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long‐standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5‐year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett''s esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett''s esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett''s esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett''s carcinogenesis.     

Quantification of Circulating Free DNA as a Diagnostic Marker in Gall Bladder Cancer

Gall bladder Carcinoma (GBC) is the fifth most common cancer of the digestive tract and frequently diagnosed in late stage of disease. Estimation of circulating free DNA (cfDNA) in serum has been applied as a “liquid biopsy” in several deep seated malignancies. Its value in diagnosis of gall bladder carcinoma has not been studied. The present study was designed to assess the role of cfDNA in the diagnosis of GBC and correlate levels with the TNM stage. Serum was collected from 34 patients with GBC and 39 age and sex matched controls including 22 cholecystitis and 17 healthy individuals. Serum cfDNA levels were measured through quantitative polymerase chain reaction (qPCR) by amplification of β-globin gene. Performance of the assay was calculated through the receiver operating characteristic (ROC) curve. The cfDNA level was significantly lower in healthy controls and cholecystitis (89.32 ± 59.76 ng/ml, 174.21 ± 99.93 ng/ml) compared to GBC (1245.91 ± 892.46 ng/ml, p = <0.001). The cfDNA level was significantly associated with TNM stage, lymph node involvement and jaundice (0.002, 0.027, and 0.041, respectively). Area under curve of ROC analysis for cancer group versus healthy and cholecystitis group was 1.00 and 0.983 with sensitivity of 100 %, 88.24 % and specificity of 100 % respectively. Quantitative analysis of cfDNA may distinguish cholecystitis and gall bladder carcinoma and may serve as new diagnostic, noninvasive marker adjunct to imaging for the diagnosis of GBC.     

A new approach to determine solar potential using terrestrial images

Before installing Photovoltaic (PV) panels at a place it is important to estimate the solar potential of the place. Most approaches available in literature do not consider the presence of surrounding obstructions, thus leading to wrong estimates. Light Detection and Ranging (LiDAR) data or 3D (Geographic Information System) GIS based approaches consider obstructions but prove cost-effective only at city-wide scales. This paper presents a cost-effective, accurate, and scalable approach for this purpose. The proposed approach utilizes terrestrial images of surroundings and identifies obstructions present therein. Using the azimuth and elevation angles of the principal axes of the terrestrial images the azimuth and elevation angles of each pixel in these images are determined. Using thresholding and morphological closing the terrestrial images are segmented into sky and non-sky zones. Sun is considered visible at the point of interest if it lies in the sky zone. The position of the Sun is determined using the solar position algorithm and the irradiance reaching the Earth surface is computed using the modified radiative transfer model. Finally, the total irradiance over a chosen time period at a given location is estimated by integrating the irradiances for the duration when the Sun is visible.     

Virtual reality simulation: basic concepts and use in endoscopic neurosurgery training

Introduction

Virtual reality simulation is a promising alternative to training surgical residents outside the operating room. It is also a useful aide to anatomic study, residency training, surgical rehearsal, credentialing, and recertification.

Discussion

Surgical simulation is based on a virtual reality with varying degrees of immersion and realism. Simulators provide a no-risk environment for harmless and repeatable practice. Virtual reality has three main components of simulation: graphics/volume rendering, model behavior/tissue deformation, and haptic feedback. The challenge of accurately simulating the forces and tactile sensations experienced in neurosurgery limits the sophistication of a virtual simulator. The limited haptic feedback available in minimally invasive neurosurgery makes it a favorable subject for simulation.

Conclusions

Virtual simulators with realistic graphics and force feedback have been developed for ventriculostomy, intraventricular surgery, and transsphenoidal pituitary surgery, thus allowing preoperative study of the individual anatomy and increasing the safety of the procedure. The authors also present experiences with their own virtual simulation of endoscopic third ventriculostomy.     

DNA interfaces with dimensional materials for biomedical applications

DNA interfaces with nano, micro, and macro materials have gained widespread attention for various applications. Such interfaces exhibit distinct functions and properties not only due to the unique properties of interfacing materials but also sequence- and conformation-dependent characteristics of the DNA. Therefore, DNA interfaces with diverse dimensional materials have advanced our understanding of the interaction mechanisms and the properties of such interfaces. The unique interfacial properties of such novel materials have applications in nanotechnology, biophysics, cell biology, biosensing, and bioelectronics. The field is growing rapidly with the frequent emergence of new interfaces carrying remarkable interfacial character. In this review article, we have classified the DNA interfaces into 0D, 1D, 2D, and 3D categories based on the types of dimensional materials. We review the key efforts made in the last five years and focus on types of interfaces, interfacing mechanisms, and their state-of-the-art applications. This review will draw a general interest because of the diversity in the DNA materials science but also the unique applications that will play a cutting-edge role in biomedical and biosensing research.

DNA interfaces with 0–3 dimensional materials through physisorption and chemisorption mechanisms acquire unique interfacial character for novel biomedical applications.     

Isolation of exfoliated colonic epithelial cells, a novel, non-invasive approach to the study of cellular markers.

Human stool is a heterogeneous mixture of non-digestible food residues, bacteria, cells exfoliated from the gastrointestinal mucosa and other secretory products. We have demonstrated that fresh human stools dispersed in a buffered saline solution can be fractionated over Percoll/BSA gradients to yield 9 discrete bands of cells in the density range of rho 1.033 to 1.139 and which could be further purified over Histopaque 1077. Enzyme-linked immunoassays (ELISA) for colon-specific antigen (CSA) and cytokeratins (CK) were positive. Western blot analysis showed the presence of 3 cytokeratin bands in the 40-kDa to 60-kDa range suggestive of cytokeratins 8, 18, and 19. Fluorescence flow-cytometric analysis of these cells using antibodies against CSA, CK, the blood-group antigens, carcinoembryonic antigen (CEA), non-mucus-secreting columnar-epithelium-specific MAb PR1A3, and to mucus-secreting colonic-epithelium-specific MAb PR5D5 showed varying degrees of reactivity. Expression of the blood-group phenotype suggests that cells from the proximal half of the colon had survived the transit, since in the adult expression of this marker is limited to cells from the proximal region of the colon. In this report we demonstrate the feasibility of studying, non-invasively, cell-specific markers on exfoliated cells isolated from stools. The evidence strongly suggests that almost all the cells are of colonic origin.     

Cellular repair of oxidatively induced DNA base lesions is defective in prostate cancer cell lines, PC-3 and DU-145

Mutagenic oxidative DNA base damage increases with age in prostatic tissue. Various factors may influence this increase including: increased production of reactive oxygen species, increased susceptibility to oxidative stress, alterations in detoxifying enzyme levels or defects in DNA repair. Using liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry, we show increased levels of oxidative DNA base lesions, 8-hydroxyguanine (8-oxoG), 8-hydroxyadenine (8-oxoA) and 5-hydroxycytosine (5OHC) over the baseline in PC-3 and DU-145 prostate cancer cells following exposure to ionizing radiation and a repair period. Nuclear extracts from PC-3 and DU-145 prostate cancer cell lines are defective in the incision of 8-oxoG, 5OHC and thymine glycol (TG) relative to the non-malignant prostate cell line. Consistent with reduced expression of OGG1 2a, incision of 8-oxoG is reduced in PC-3 and DU-145 mitochondrial extracts. We also show a correlation between severely defective incision of TG and 5OHC and reduced levels of NTH1 in PC-3 mitochondria. The antioxidant enzymes, glutathione peroxidase (GPx), catalase and superoxide dismutases (SOD1, SOD2), have altered expression patterns in these cancer cell lines. Genetic analysis of the OGG1 gene reveals that both PC-3 and DU-145 cell lines harbor polymorphisms associated with a higher susceptibility to certain cancers. These data suggest that the malignant phenotype in PC-3 and DU-145 cell lines may be associated with defects in base excision repair and alterations in expression of antioxidant enzymes.     

Differential response of A 68930 and sulpiride in stress-induced gastric ulcers in rats

Dopamine is linked to gastrointestinal functions. However, its exact nature in stress-induced gastric pathology is still not clear. In the present study, an attempt has been made to identify the effects of dopamine in stress-induced gastric ulcers, and concurrent alterations in various ulcer-influencing factors such as plasma corticosterone levels, gastric mucosal PGE₂ content and proton pump activity. The dopamine D₁ receptor agonist (A 68930) and antagonist (SCH 23390), and D₂ receptor agonist (quinpirole) and antagonist (sulpiride) were used to evaluate their effects on acute stress (single immobilization for 150 min) and chronic unpredictable stress (two different types of stressors for 7 days) induced gastric ulcers in rats. Acute and chronic unpredictable stress significantly increased the gastric ulcer severity, adrenal hypertrophy and corticosterone levels, while gastric mucosal dopamine levels were decreased. Pretreatment of sulpiride (60 mg/kg) significantly reverted the acute stress-induced alterations, while A 68930 (0.25 mg/kg) significantly restored the acute and chronic unpredictable stress-induced alterations. In contrast, administration of SCH 23390 (0.1-0.5 mg/kg) and quinpirole (0.1-0.5 mg/kg) failed to alter acute stress-induced alterations. Further, A 68930 and sulpiride showed different response on proton pump inhibition under in-vitro condition. A 68930 (10-50 μg/ml) inhibited the gastric H⁺ K⁺-ATPase activity comparable to positive control omeprazole, while sulpiride (10-50 μg/ml) had no effect. A 68930 also normalized the decreased gastric PGE2 content observed during chronic unpredictable stress. The histopathological evaluation of gastric mucosal tissue supported the observations regarding the gastroprotective effect of sulpiride during acute stress and of A 68930 during both acute and chronic unpredictable stress conditions. Our results provide important insights into the mechanism of dopamine-regulated pathways, which cause an overall pathophysiology of gastric stress ulcers and implicating the importance of D₁ agonist in ulcer protection. Thus, current study highlights the need to evaluate anti-stress and anti-ulcer agents in terms of their ability to modulate dopaminergic transmissions.