Growth factor restriction impedes progression of wound healing following cataract surgery: identification of VEGF as a putative therapeutic target

Secondary visual loss occurs in millions of patients due to a wound-healing response, known as posterior capsule opacification (PCO), following cataract surgery. An intraocular lens (IOL) is implanted into residual lens tissue, known as the capsular bag, following cataract removal. Standard IOLs allow the anterior and posterior capsules to become physically connected. This places pressure on the IOL and improves contact with the underlying posterior capsule. New open bag IOL designs separate the anterior capsule and posterior capsules and further reduce PCO incidence. It is hypothesised that this results from reduced cytokine availability due to greater irrigation of the bag. We therefore explored the role of growth factor restriction on PCO using human lens cell and tissue culture models. We demonstrate that cytokine dilution, by increasing medium volume, significantly reduced cell coverage in both closed and open capsular bag models. This coincided with reduced cell density and myofibroblast formation. A screen of 27 cytokines identified nine candidates whose expression profile correlated with growth. In particular, VEGF was found to regulate cell survival, growth and myofibroblast formation. VEGF provides a therapeutic target to further manage PCO development and will yield best results when used in conjunction with open bag IOL designs

Gross hematuria as the presentation of an inguinoscrotal hernia: a case report

<p>Abstract</p> <p>Introduction</p> <p>Several complications have been reported with inguinal hernias. Although hematuria and flank pain, either as the presentation or as a complication of inguinal hernia, are infrequent, this condition may lead to the development of obstructive uropathy, which can have diverse manifestations.</p> <p>Case presentation</p> <p>A 71-year-old Iranian man with Persian ethnicity presented with new onset episodes of gross hematuria and left-sided flank pain. A physical examination revealed a large and non-tender inguinal hernia on his left side. An initial workup included an abdominal ultrasound, an intravenous pyelogram and cystoscopy, which showed left hydronephrosis and a bulging on the left-side of his bladder wall. On further evaluation, computed tomography confirmed that his sigmoid colon was the source of the pressure effect on his bladder, resulting in hydroureteronephrosis and hematuria. No tumoral lesion was evident. Herniorrhaphy led to the resolution of his signs and symptoms.</p> <p>Conclusion</p> <p>Our case illustrates a rare presentation of inguinal hernia responsible for gross hematuria and unilateral hydronephrosis. Urologic signs and symptoms can be caused by the content of inguinal hernias. They can also present as complications of inguinal hernias.</p

Multi-institutional Evaluation of Producing and Testing a Novel 3D-Printed Laparoscopic Trainer

To create, distribute, and evaluate the efficacy of a portable, cost effective 3D-printed laparoscopic trainer for surgical skills development.Objective: To create, distribute, and evaluate the efficacy of a portable, cost-effective 3D-printed laparoscopic trainer for surgical skills development. Methods: The UCI Trainer (UCiT) laparoscopic simulator was developed via computer-aided designs (CAD), which were used to 3D-print the UCiT. Once assembled, a tablet computer with a rear-facing camera was attached for video and optics. Four institutions were sent the UCiT CAD files with a 3D-printer and instructions for UCiT assembly. For a comparison of the UCiT to a standard trainer, peg transfer and intracorporeal knot tying skills were accessed. These tasks were scored, and participants were asked to rate their experience with the trainers. Lastly, a questionnaire was given to individuals who 3D-printed and assembled the UCiT. Results: We recruited 25 urologists; none had any 3D-printing experience. The cost of printing each trainer was $26.50 USD. Each institution used the Apple iPad for optics. Six of eight participants assembled the UCiT in &lt; 45 minutes, and rated assembly as somewhat easy. On objective scoring, participants performed tasks equally well on the UCiT vs the conventional trainer. On subjective scoring, the conventional trainer provided a significantly better experience vs the UCiT; however, all reported that the UCiT was useful for surgical education. Conclusion: The UCiT is a low cost, portable training tool that is easy to assemble and use. UCiT provided a platform whereby participants performed laparoscopic tasks equal to performing the same tasks on the more expensive, nonportable standard trainer

Electroacupuncture pretreatment attenuates cerebral ischemic injury through α7 nicotinic acetylcholine receptor-mediated inhibition of high-mobility group box 1 release in rats

<p>Abstract</p> <p>Background</p> <p>We have previously reported that electroacupuncture (EA) pretreatment induced tolerance against cerebral ischemic injury, but the mechanisms underlying this effect of EA are unknown. In this study, we assessed the effect of EA pretreatment on the expression of α7 nicotinic acetylcholine receptors (α7nAChR), using the ischemia-reperfusion model of focal cerebral ischemia in rats. Further, we investigated the role of high mobility group box 1 (HMGB1) in neuroprotection mediated by the α7nAChR and EA.</p> <p>Methods</p> <p>Rats were treated with EA at the acupoint "Baihui (GV 20)" 24 h before focal cerebral ischemia which was induced for 120 min by middle cerebral artery occlusion. Neurobehavioral scores, infarction volumes, neuronal apoptosis, and HMGB1 levels were evaluated after reperfusion. The α7nAChR agonist PHA-543613 and the antagonist α-bungarotoxin (α-BGT) were used to investigate the role of the α7nAChR in mediating neuroprotective effects. The roles of the α7nAChR and HMGB1 release in neuroprotection were further tested in neuronal cultures exposed to oxygen and glucose deprivation (OGD).</p> <p>Results</p> <p>Our results showed that the expression of α7nAChR was significantly decreased after reperfusion. EA pretreatment prevented the reduction in neuronal expression of α7nAChR after reperfusion in the ischemic penumbra. Pretreatment with PHA-543613 afforded neuroprotective effects against ischemic damage. Moreover, EA pretreatment reduced infarct volume, improved neurological outcome, inhibited neuronal apoptosis and HMGB1 release following reperfusion, and the beneficial effects were attenuated by α-BGT. The HMGB1 levels in plasma and the penumbral brain tissue were correlated with the number of apoptotic neurons in the ischemic penumbra. Furthermore, OGD in cultured neurons triggered HMGB1 release into the culture medium, and this effect was efficiently suppressed by PHA-543,613. Pretreatment with α-BGT reversed the inhibitory effect of PHA-543,613 on HMGB1 release.</p> <p>Conclusion</p> <p>These data demonstrate that EA pretreatment strongly protects the brain against transient cerebral ischemic injury, and inhibits HMGB1 release through α7nAChR activation in rats. These findings suggest the novel potential for stroke interventions harnessing the anti-inflammatory effects of α7nAChR activation, through acupuncture or pharmacological strategies.</p

Role of urothelial cells in BCG immunotherapy for superficial bladder cancer

Intravesical instillation of Bacillus Calmette-Guérin (BCG) is used for the treatment of superficial bladder cancer, both to reduce the recurrence rate of bladder tumour and to diminish the risk of progression. Since its first therapeutic application in 1976, major research efforts have been directed to decipher the exact mechanism of action of the BCG-associated antitumour effect. Bacillus Calmette-Guérin causes an extensive local inflammatory reaction in the bladder wall. Of this, the massive appearance of cytokines in the urine of BCG-treated patients stands out. Activated lymphocytes and macrophages are the most likely sources of these cytokines, but at present other cellular sources such as urothelial tumour cells cannot be ruled out. Bacillus Calmette-Guérin is internalised and processed both by professional antigen-presenting cells and urothelial tumour cells, resulting in an altered gene expression of these cells that accumulates in the presentation of BCG antigens and secretion of particular cytokine

A Further Examination of the Export-Led Growth Hypothesis

This paper challenges the common view that exports generally contribute more to GDP growth than a pure change in export volume, as the export-led growth hypothesis predicts. Applying panel cointegration techniques to a production function with non-export GDP as the dependent variable, we find for a sample of 45 developing countries that: (i) exports have a positive short-run effect on non-export GDP and vice versa (short-run bidirectional causality), (ii) the long-run effect of exports on non-export output, however, is negative on average, but (iii) there are large differences in the longrun effect of exports on non-export GDP across countries. Cross-sectional regressions indicate that these cross-country differences in the long-run effect of exports on nonexport GDP are significantly negatively related to cross-country differences in primary export dependence and business and labor market regulation. In contrast, there is no significant association between the growth effect of exports and the capacity of a country to absorb new knowledge