Aqueous outflow imaging techniques and what they tell us about intraocular pressure regulation

Recent advances in the medical and surgical management of open-angle glaucoma have increased the number of treatment options available. Several new intraocular pressure (IOP)-lowering treatments target the conventional aqueous outflow (AO) system. However, success rates are variable and outcomes in individual patients are often difficult to predict. Variable treatment responses remain unexplained and highlight deficiencies in our current understanding of AO regulation and IOP homeostasis. Imaging is often relied upon to confirm diagnoses and monitor treatment responses in other ocular and systemic pathologies. As yet no suitable AO imaging tool has been developed to fulfil this role in glaucoma. A variety of imaging techniques have been used to study the AO tracts of humans and animals in ex vivo and in vivo eyes. In this review, results from novel imaging techniques that assess aqueous drainage through the episcleral venous system are considered and we argue these provide new insights into AO regulation. We suggest that the ability to objectively measure AO responses to interventions would be a significant clinical advance, and we have demonstrated that this can be achieved with direct visualisation of aqueous drainage. We predict that the evolution of AO imaging technology will continue to reveal critical components of AO and IOP regulation, and that personalised IOP-lowering treatment in glaucoma care may well become a reality in the near future.Subject terms: Glaucoma, Outcomes research     

Vitamin D deficiency and level of asthma control in women from North of Jordan: a case–control study

Introduction: Reduced vitamin-D levels in patients with asthma have been associated with impaired lung function, increased airway hyper-responsiveness, and reduced glucocorticoid responsiveness. Nationwide studies revealed a considerable prevalence of vitamin-D deficiency (VDD) in Jordanian women. Objective: A case–control study was conducted to determine the relationship between serum vitamin A and D levels and asthma among women in North of Jordan. Methods: Sixty-eight asthmatics, age range between 14 and 65 years and 77 healthy women, age range between 19 and 51 years, were enrolled. Asthma severity was classified using Global Initiative for Asthma (GINA) guidelines and Asthma Control Test (ACT) questionnaire. Serum vitamin-A and 25-hydroxyvitamin-D (25(OH)D3) levels were measured using high-performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods, respectively. Results: The prevalence of VDD (<15?ng/ml) was higher but not statistically significant for women with asthma compared with controls (95.6% vs. 87.0%; p?=?0.070). The severity of VDD correlated with the number of asthma medications (p?=?0.020). 25(OH)-D3 serum levels directly correlated with asthma control level using ACT score (p?=?0.012) and GINA classification (p?=?0.046). After adjusting for age, the odds of having VDD for asthmatic women were 35.9 times higher than that for women with no asthma. There was no difference in serum vitamin-A level between healthy and asthmatic women (p?=?0.214) and none had vitamin-A deficiency (<200?µg/dl). Conclusions: VDD is prevalent in women with asthma in northern Jordan. The severity of VDD correlated with poor asthma control and a need for more medications to control asthma. There was no association between vitamin-A and asthma.     

Selective inhibition of proprotein convertases represses the metastatic potential of human colorectal tumor cells

The proprotein convertases (PCs) are implicated in the activation of various precursor proteins that play an important role in tumor cell metastasis. Here, we report their involvement in the regulation of the metastatic potential of colorectal tumor cells. PC function in the human and murine colon carcinoma cell lines HT-29 and CT-26, respectively, was inhibited using siRNA targeting the PCs furin, PACE4, PC5, and PC7 or by overexpression of the general PC inhibitor alpha1-antitrypsin Portland (alpha1-PDX). We found that overexpression of alpha1-PDX and knockdown of furin expression inhibited processing of IGF-1 receptor and its subsequent activation by IGF-1 to induce IRS-1 and Akt phosphorylation, all important in colon carcinoma metastasis. These data suggest that the PC furin is a major IGF-1 receptor convertase. Expression of alpha1-PDX reduced the production of TNF-alpha and IL-1alpha by human colon carcinoma cells, and incubation of murine liver endothelial cells with conditioned media derived from these cells failed to induce tumor cell adhesion to activated murine endothelial cells, a critical step in metastatic invasion. Furthermore, colon carcinoma cells in which PC activity was inhibited by overexpression of alpha1-PDX when injected into the portal vein of mice showed a significantly reduced ability to form liver metastases. This suggests that inhibition of PCs is a potentially promising strategy for the prevention of colorectal liver metastasis.     

Open Surgical Simulation—A Review

BackgroundSurgical simulation has benefited from a surge in interest over the last decade as a result of the increasing need for a change in the traditional apprentice model of teaching surgery. However, despite the recent interest in surgical simulation as an adjunct to surgical training, most of the literature focuses on laparoscopic, endovascular, and endoscopic surgical simulation with very few studies scrutinizing open surgical simulation and its benefit to surgical trainees. The aim of this review is to summarize the current standard of available open surgical simulators and to review the literature on the benefits of open surgical simulation.Current State of Open Surgical SimulationOpen surgical simulators currently used include live animals, cadavers, bench models, virtual reality, and software-based computer simulators. In the current literature, there are 18 different studies (including 6 randomized controlled trials and 12 cohort studies) investigating the efficacy of open surgical simulation using live animal, bench, and cadaveric models in many surgical specialties including general, cardiac, trauma, vascular, urologic, and gynecologic surgery. The current open surgical simulation studies show, in general, a significant benefit of open surgical simulation in developing the surgical skills of surgical trainees. However, these studies have their limitations including a low number of participants, variable assessment standards, and a focus on short-term results often with no follow-up assessment.Future of Open Surgical SimulationThe skills needed for open surgical procedures are the essential basis that a surgical trainee needs to grasp before attempting more technical procedures such as laparoscopic procedures. In this current climate of medical practice with reduced hours of surgical exposure for trainees and where the patient’s safety and outcome is key, open surgical simulation is a promising adjunct to modern surgical training, filling the void between surgeons being trained in a technique and a surgeon achieving fluency in that open surgical procedure. Better quality research is needed into the benefits of open surgical simulation, and this would hopefully stimulate further development of simulators with more accurate and objective assessment tools.