Impact of β-glucan on the Fecal Water Genotoxicity of Polypectomized Patients

The aim of the study was to determine the effect of β-glucan on the cytotoxicity and genotoxicity of polypectomized patient's fecal water (FW). Polypectomized volunteers (n = 69) were randomly assigned to consume bread with or without β-glucan, for 3 months. FW was collected at the beginning (t = 0), the 30th and 90th day and 2 wk after the intervention. Cytotoxicity and genotoxicity were estimated on Caco-2 cells, using trypan blue exclusion test and comet assay, respectively. Gastrointestinal symptoms were recorded and subjects kept a 3-day food diary at baseline and after completion. Trypan blue exclusion test revealed cell survival of approximately 87% after incubation with FW. The FW samples showed 49% genotoxicity at the baseline. Genotoxicity in the intervention group decreased during the trial reaching statistical significance on the 90th day compared to control. An increase was noticed 2 wk after the trial, but it still remained significantly lower compared to control. Group-specific analysis for β-glucan also revealed significant decrease in the genotoxicity on the 90th day compared to baseline. β-glucan ingestion in polypectomized patients significantly decreased the genotoxicity of their FW. Our findings suggest that β-glucan consumption could possibly provide protection against colon cancer development.     

Validation of PATHFx 2.0: An open-source tool for estimating survival in patients undergoing pathologic fracture fixation

Treatment decisions in patients with metastatic bone disease rely on accurate survival estimation. We developed the original PATHFx models using expensive, proprietary software and now seek to provide a more cost-effective solution. Using open-source machine learning software to create PATHFx version 2.0, we asked whether PATHFx 2.0 could be created using open-source methods and externally validated in two unique patient populations. The training set of a well-characterized, database records of 189 patients and the bnlearn package within R Version 3.5.1 (R Foundation for Statistical Computing), was used to establish a series of Bayesian belief network models designed to predict survival at 1, 3, 6, 12, 18, and 24 months. Each was externally validated in both a Scandinavian (n = 815 patients) and a Japanese (n = 261 patients) data set. Brier scores and receiver operating characteristic curves to assessed discriminatory ability. Decision curve analysis (DCA) evaluated whether models should be used clinically. DCA showed that the model should be used clinically at all time points in the Scandinavian data set. For the 1-month time point, DCA of the Japanese data set suggested to expect better outcomes assuming all patients will survive greater than 1 month. Brier scores for each curve demonstrate that the models are accurate at each time point. Statement of Clinical Significance: we successfully transitioned to PATHFx 2.0 using open-source software and externally validated it in two unique patient populations, which can be used as a cost-effective option to guide surgical decisions in patients with metastatic bone disease.     

Demonstration of a modelling-based multi-criteria decision analysis procedure for prioritisation of occupational risks from manufactured nanomaterials

Several tools to facilitate the risk assessment and management of manufactured nanomaterials (MN) have been developed. Most of them require input data on physicochemical properties, toxicity and scenario-specific exposure information. However, such data are yet not readily available, and tools that can handle data gaps in a structured way to ensure transparent risk analysis for industrial and regulatory decision making are needed. This paper proposes such a quantitative risk prioritisation tool, based on a multi-criteria decision analysis algorithm, which combines advanced exposure and dose-response modelling to calculate margins of exposure (MoE) for a number of MN in order to rank their occupational risks. We demonstrated the tool in a number of workplace exposure scenarios (ES) involving the production and handling of nanoscale titanium dioxide, zinc oxide (ZnO), silver and multi-walled carbon nanotubes. The results of this application demonstrated that bag/bin filling, manual un/loading and dumping of large amounts of dry powders led to high emissions, which resulted in high risk associated with these ES. The ZnO MN revealed considerable hazard potential in vivo, which significantly influenced the risk prioritisation results. In order to study how variations in the input data affect our results, we performed probabilistic Monte Carlo sensitivity/uncertainty analysis, which demonstrated that the performance of the proposed model is stable against changes in the exposure and hazard input variables.     

Current and emerging osteoporosis pharmacotherapy for women: state of the art therapies for preventing bone loss

Introduction: Pharmacological options to address the imbalance between bone resorption and accrual in osteoporosis include anti-resorptive and osteoanabolic agents. Unique biologic pathways such as the Wnt/β-catenin pathway have been targeted in the quest for new emerging therapeutic strategies.

Areas covered: This review provides an overview of existing pharmacotherapy for osteoporosis in women and explore state-of–the-art and emerging therapies to prevent bone loss, with an emphasis on the mechanism of action, indications and side effects.

Expert opinion: Bisphosphonates appear to be a reliable and cost-effective option, whereas denosumab has introduced a simpler dosing regimen and may achieve a linear increase in bone mineral density (BMD) with no plateau being observed, along with continuous anti-fracture efficacy. Abaloparatide, a parathyroid-hormone-related peptide (PTHrP)-analogue, approved by the FDA in April 2017, constitutes the first new anabolic osteoporosis drug in the US for nearly 15 years and has also proven its anti-fracture efficacy. Romosozumab, a sclerostin inhibitor, which induces bone formation and suppresses bone resorption, has also been developed and shown a significant reduction in fracture incidence; however, concerns have arisen with regard to increased cardiovascular risk.     

Immunohistochemical and molecular analysis of PI3K/AKT/mTOR pathway in esophageal carcinoma

Among the numerous signaling pathways involved in tumorigenesis, PI3K‐AKT‐mTOR is a key one that regulates diverse cellular functions. However, its prognostic value in esophageal carcinoma remains unclear. In our study, we examined the immunohistochemical expression of phosphorylated (p‐) AKT, mTOR, p70S6K and 4E‐BP1 along with the mutational status of PIK3CA and AKT1 genes by High Resolution Melting Analysis and Pyrosequencing in 44 esophageal carcinomas. The results were correlated with the clinicopathological characteristics of the patients in an effort to define their possible prognostic significance. Total p‐mTOR cytoplasmic expression, assessed in 10 random areas, was positively correlated with tumor stage (Kruskal–Wallis ANOVA, I/II vs III/IV, p = 0.0500). Μoreover, maximum p‐mTOR cytoplasmic immunoexpression, estimated in hot spot areas, was positively associated with tumor grade (Mann–Whitney U test, I/II vs III, p = 0.0565). Interestingly, p‐4E‐BP1 immunoreactivity was negatively correlated with tumor histological grade (Mann–Whitney U test, I/II vs III, p = 0.0427). No mutation was observed in exons 9 and 20 of PIK3CA gene and in exon 4 of AKT1 gene. In conclusion, our findings depict the presence of activated PI3K/AKT/mTOR pathway in esophageal cancer bringing forward p‐mTOR and p‐4E‐BP1 for their potential role in esophageal carcinogenesis. Additional studies are warranted to validate our findings.     

Six Cases of Prenatal and Neonatal Torsion of the Spermatic Cord

Torsions of the spermatic cord occurring from the intrauterine period to the end of the first year of life are termed perinatal. These are divided into prenatal and postnatal torsions, depending on their occurrence in the intrauterine or postuterine period. From January 1984 to January 1996, 6 cases were identified at our institution, involving 4 prenatal and 2 postnatal extravaginal torsions of the spermatic cord. These cases are reviewed with regard to optimal therapeutic approaches for the treatment of both the affected gonad as well as the contralateral one, and whether the event occurred prenatally or postnatally. The authors also propose several clinical indications useful for obstetricians, pediatricians, urologists and nurses.