Green-Synthesized Silver and Selenium Nanoparticles Using Berberine: A Comparative Assessment of In Vitro Anticancer Potential on Human Hepatocellular Carcinoma Cell Line (HepG2).

A well-known natural ingredient found in several medicinal plants, berberine (Ber), has been shown to have anticancer properties against a range of malignancies. The limited solubility and bioavailability of berberine can be addressed using Ber-loaded nanoparticles. In this study, we compared the in vitro cytotoxic effects of both Ber-loaded silver nanoparticles (Ber-AgNPs) and Ber-loaded selenium nanoparticles (Ber-SeNPs) in the human liver cancer cell line (HepG2) and mouse normal liver cells (BNL). The IC50 values in HepG2 for berberine, Ber-AgNPs, Ber-SeNPs, and cisplatin were 26.69, 1.16, 0.04, and 0.33 µg/mL, respectively. Our results show that Ber and its Ag and Se nanoparticles exerted a good antitumor effect against HepG2 cells by inducing apoptosis via upregulating p53, Bax, cytosolic cytochrome C levels, and caspase-3 activity, and the down-regulation of Bcl-2 levels. Similarly, incubation with Ber and both Ber-NPs (Ag and Se) led to a significant dose-dependent elevation in inflammatory markers' (TNF-α, NF-κB, and COX-2) levels compared to the control group. In addition, it led to the arrest of the G1 cell cycle by depleting the expression of cyclin D1 and CDK-2 mRNA. Furthermore, Ber and both Ber-NPs (Ag and Se) caused a significant dose-dependent increase in LDH activity in HepG2 cells. Furthermore, our findings offer evidence that Ber and its nanoparticles intensified oxidative stress in HepG2 cells. Furthermore, the migration rate of cells subjected to berberine and its nanoforms was notably decreased compared to that of control cells. It can be inferred that Ber nanoparticles exhibited superior anticancer efficacy against HepG2 compared to unprocessed Ber, perhaps due to their improved solubility and bioavailability. Furthermore, Ber-SeNPs exhibited greater efficacy than Ber-AgNPs, possibly as a result of the inherent anticancer characteristics of selenium.

Development and initial validation of a video-based peroral endoscopic myotomy assessment tool.

BACKGROUND AND AIMS: Video analysis has emerged as a potential strategy for performance assessment and improvement. We aimed to develop a video-based skill assessment tool for peroral endoscopic myotomy (POEM). METHODS: POEM was deconstructed into basic procedural components through video analysis by an expert panel. A modified Delphi approach and 2 validation exercises were conducted to refine the POEM assessment tool (POEMAT). Twelve assessors used the final POEMAT version to grade 10 videos. Fully crossed generalizability (G) studies investigated the contributions of assessors, endoscopists' performance, and technical elements to reliability. G coefficients below .5 were considered unreliable, between .5 and .7 as modestly reliable, and above .7 as indicative of satisfactory reliability. RESULTS: After task deconstruction, discussions, and the modified Delphi process, the final POEMAT comprised 9 technical elements. G analysis showed low variance for endoscopist performance (.8%-24.9%) and high interrater variability (range, 63.2%-90.1%). The G score was moderately reliable (≥.60) for "submucosal tunneling" and "myotomy" and satisfactorily reliable (≥.70) for "active hemostasis" and "mucosal closure." CONCLUSIONS: We developed and established initial content and response process validity evidence for the POEMAT. Future steps include appraisal of the tool using a wider range of POEM videos to establish and improve the discriminative validity of this tool.

Outcomes after Elective Abdominal Aortic Aneurysm Repair Have Improved Over Time in Patients on Dialysis.

BACKGROUND: Prior studies have demonstrated poor perioperative and long-term survival of patients with end-stage kidney disease (ESKD) on dialysis who undergo abdominal aortic aneurysm repair (AAAR). However, survival in dialysis patients overall has improved over time. We hypothesize that the contemporary rates of perioperative and long-term survival following AAAR in ESKD patients are also improving. METHODS: Data on AAAR procedures in dialysis patients were collected from the United States Renal Data System between 2008 and 2017. Endovascular (EVAR) and open AAA repair (OAR) were identified by Current Procedural Terminology codes. Patients with a functioning renal transplant, a ruptured aneurysm, and insurance other than Medicare were excluded. Demographics, comorbidities, procedural details, and long-term outcomes were collected. Standard statistical methods were used. RESULTS: We identified 3,374 patients who underwent EVAR (86%, 2,914/3,374) and OAR (14%, 460/3,374). The utilization of OAR decreased significantly from 2008 to 2017 (17.34% vs. 7.43%, P < 0.001). Kaplan-Meier survival analysis revealed no significant difference in 5-year survival between OAR and EVAR (24% vs. 17%, P = 0.1, Wilcoxon-Breslow test), but open repair was associated with increased long-term survival (Hazards ratio 0.994, confidence interval 0.990-0.999, P = 0.017) in an adjusted Cox regression model. The cohort was then divided based on the year of AAAR, group 1: 2008-2010 (1,269/3,374), group 2: 2011-2013 (1,071/3,374), and group 3: 2014-2017 (1,034/3,374). Compared to groups 1 and 2, Group 3 was less likely to have coronary artery device, peripheral vascular disease, recent pneumonia, be nonambulatory, live in a nursing facility, or undergo an OAR and more likely to be younger and dialyze through an arteriovenous fistula/arteriovenous graft at the time of AAA repair. Thirty-day postoperative mortality was significantly lower in group 3 compared to groups 1 and 2 (5.4% [56/1,034] vs. 10.3% [131/1,269]/7.3% [78/1,071], P < 0.031). One-year survival by Kaplan-Meier estimate was significantly higher in group 3 (77.7% [803/1,034]) versus groups 1 and 2 (56.7% [719/1,269], 66.9% [716/1,071], P < 0.001, log-rank test). Five-year survival was also significantly higher in group 3 (27.3%) compared to groups 1 and 2 (14.2% and 16.5%, P < 0.001, log-rank test). In a Cox regression model of long-term mortality adjusted for variables significant on a univariate testing, more recent procedure year was associated with increased survival (Hazards ratio 0.81, [0.77, 0.85], P < 0.001). CONCLUSIONS: Postoperative and long-term survival following AAA repair have increased over time in ESKD patients on dialysis. This increased survival persists after accounting for differences in patient demographics and type of procedure over time. Elective AAA repair should be considered in carefully selected good-risk patients on dialysis.

Improving nuclear morphometry imaging with real-time and low-cost line-scanning confocal microendoscope.

Fiber-optic endomicroscopy is a minimally invasive tool to probe disease progression with subcellular resolution. In this Letter, we demonstrate a low-cost and compact fluorescence microendoscope capable of line-scanning confocal imaging by synchronizing a digital light projector with a CMOS camera. We present the digital aperture design to enable real-time confocal imaging, and we implement parallel illumination to improve the optical sectioning performance. Furthermore, we show that the confocal microendoscope can enhance visualization of disease-associated features when imaging highly scattering esophageal specimens.

PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies: Rationale and Study Design for PROCEED From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer.

Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) is the first prospective, observational cohort study of chronic pancreatitis (CP) in the United States. The primary goals of PROCEED are to define disease progression, test the predictive capability of candidate biomarkers, and develop a platform to conduct translational and mechanistic studies in CP. Using objective and consensus-driven criteria, PROCEED will enroll adults at different stages of CP-controls, suspected CP, and definite CP. In addition to collecting detailed information using structured case report forms and protocol-mandated evaluations at baseline and during follow-up, PROCEED will establish a linked biorepository of blood, urine, saliva, stool, pancreatic fluid, and pancreatic tissue. Enrollment for PROCEED began in June 2017. As of July 1, 2018, nine clinical centers of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer are enrolling, and 350 subjects have completed baseline evaluation. In conclusion, PROCEED will provide the most accurate and reliable estimates to date on progression of CP. The established cohort and biorepository will facilitate numerous analyses, leading to new strategies for diagnosis, methods to monitor disease progression, and treatment of CP.

Effects of Starting a Gastroenterology Fellowship Training Program on Quality Measures of Colonoscopy.

OBJECTIVES: Adenoma detection rate (ADR) is the most established indicator of the quality of screening colonoscopy. The effect of gastroenterology (GI) fellows on the quality of screening colonoscopies has been evaluated previously; however, the effect of starting a new GI fellowship program on the quality of screening colonoscopies has not been studied. The aim of our study was to assess the effects of starting a GI fellowship program and the participation of fellows in screening colonoscopies on ADR and other measures of quality. METHODS: This was a retrospective, cross-sectional study of all screening colonoscopies performed 20 months before and 20 months after starting the GI fellowship at our medical center (November 2010-February 2014). Colonoscopy procedure notes and pathology records were reviewed for each patient. Data from the two periods were compared using either the Fisher exact test or the two-sample t test. RESULTS: A total of 2127 complete colonoscopies were included in the analysis. The mean age of patients was 58.8 ± 6.6 years. Of the 2127 colonoscopies, GI fellows were involved in 385 (18%), whereas 1742 (82%) were performed solely by GI attendings (attending physicians). Multivariate analysis using relative risk (RR) of regression was done. The after starting the GI fellowship period was significantly associated with an increase in ADR (RR 1.19, 95% confidence interval 1.10-1.30, P < 0.001) and advanced adenoma detection rate (RR 1.17, 95% confidence interval 1.00-1.38, P < 0.001) compared with the before starting the GI fellowship period. In the after starting the GI fellowship period, the polyp detection rate and ADR for colonoscopies performed by the attending physicians with the fellows were significantly higher than colonoscopies performed solely by the same attendings (58.4% vs 44.5%, P = 0.001, 42.0% vs 32.9%, P = 0.017, respectively). CONCLUSIONS: Starting a GI fellowship program significantly increased the polyp detection rate, ADR, and advanced ADR.

A Secure Region-Based Geographic Routing Protocol (SRBGR) for Wireless Sensor Networks.

Due to the lack of dependency for routing initiation and an inadequate allocated sextant on responding messages, the secure geographic routing protocols for Wireless Sensor Networks (WSNs) have attracted considerable attention. However, the existing protocols are more likely to drop packets when legitimate nodes fail to respond to the routing initiation messages while attackers in the allocated sextant manage to respond. Furthermore, these protocols are designed with inefficient collection window and inadequate verification criteria which may lead to a high number of attacker selections. To prevent the failure to find an appropriate relay node and undesirable packet retransmission, this paper presents Secure Region-Based Geographic Routing Protocol (SRBGR) to increase the probability of selecting the appropriate relay node. By extending the allocated sextant and applying different message contention priorities more legitimate nodes can be admitted in the routing process. Moreover, the paper also proposed the bound collection window for a sufficient collection time and verification cost for both attacker identification and isolation. Extensive simulation experiments have been performed to evaluate the performance of the proposed protocol in comparison with other existing protocols. The results demonstrate that SRBGR increases network performance in terms of the packet delivery ratio and isolates attacks such as Sybil and Black hole.

Federal funding for endoscopic research in the United States: 2003-2008.

OBJECTIVES: Endoscopic research is underfunded compared with other areas of research. In 2003 we evaluated trends in National Institutes of Health (NIH) funding for endoscopic research from 1972 through 2002. Here, we update those trends for 2003-2008. METHODS: We calculated the number of federally funded endoscopic research grants and classified them as primary or secondary. Endoscopy funding was compared with other funding for the same period. RESULTS: From 2003 through 2008, the NIH funded 76 primary and 114 secondary endoscopy grants. R01 grants accounted for 25% of these. Colorectal cancer research and imaging and advanced optical technology received most of the grants. More primary endoscopic grants were funded than Helicobacter pylori research grants or cardiac catheterization grants. The number of funded endoscopic grants was not different between the periods 1972-2002 and 2003-2008. CONCLUSIONS: Endoscopic research remains underfunded compared with other areas of research.