Silicone-based simulation models for peripheral nerve microsurgery

Background

There is a need for a peripheral nerve model on which surgeons-in-training can simulate the repair of nerve injuries at their own pace. Although practicing on animal models/cadavers is considered the “gold standard” of microsurgical training, the proposed model aims to provide a platform for improving the technical skills of surgical trainees prior to their practice on cadaver/animal models. In addition, this model has the potential to serve as a standardized test medium for assessing the skill sets of surgeons.

Nosocomial infections and risk factors in intensive care unit of a university hospital in Turkey

The aim of this study was to determine the types nosocomial infections (NIs) and the risk factors for NIs in the central intensive care unit (ICU) of Trakya University Hospital. The patients admitted to the ICU were observed prospectively by the unit-directed active surveillance method based on patient and the laboratory over a 9-month-period. The samples of urine, blood, sputum or tracheal aspirate were taken from the patients on the first and the third days of their hospitalization in ICU; the patients were cultured routinely. Other samples were taken and cultured if there was suspicion of an infection. Infections were considered as ICU-associated if they developed after 48 hours of hospitalization in the unit and 5 days after discharge from the unit if the patients had been sent to a different ward in the hospital. The rate of NIs in 135 patients assigned was found to be 68%. The most common infection sites were lower respiratory tract, urinary tract, bloodstream, catheter site and surgical wound. Hospitalization in ICU for more than 6 days and colonization was found to be the main risk factor for NIs. Prolonged mechanical ventilation and tracheostomy, as well as frequently changed nasogastric catheterization, were found to be risk factors for lower respiratory tract infections. For bloodstream infections, both prolonged insertion of and frequent change of arterial catheters, and for urinary tract infections, female gender, period and repeating of urinary catheterization were risk factors. A high prevalence rate of nosocomial infections was found in this study. Invasive device use and duration of use continue to greatly influence the development of nosocomial infection in ICU. Important factors to prevent nosocomial infections are to avoid long hospitalization and unnecessary device application. Control and prevention strategies based on continuing education of healthcare workers will decrease the nosocomial infections in the intensive care unit.     

Kinin B1 receptor expression and function on human brain endothelial cells

The kinin B1 receptor is an inducible receptor expressed in response to inflammatory mediators. We sought to determine whether kinin B1 receptor can be expressed on human brain endothelial cells (HBECs) in vitro and whether signaling via this receptor can regulate permeability and chemokine production properties of these cells. Multiplex RT-PCR amplification and western blot techniques were used to evaluate B1 receptor expression by HBECs. Although B1 receptor mRNA and protein could not be detected on resting HBECs, interferon-gamma induced a dose- and time-dependent up-regulation of B1 receptor mRNA and protein on HBECs. Stimulation of interferon-gamma-treated HBECs with the selective B1 agonist R-838 (Sar [D-Phe8] des Arg9-BK) induced a dose- and time-dependent increase in the production of inositol 3,4,5 tri-phosphate and nitric oxide. Permeability of the HBECs monolayer, as measured by BSA diffusion, was significantly increased by application of the B1 agonist. This biological effect of R-838 could be prevented by R-715, a B1 receptor antagonist and by L-NAME, a nitric oxide synthase blocker. R-838 also inhibited interleukin-8 release from HBECs. We demonstrate that B1 receptors can be up regulated on the surface of HBECs by molecules released during inflammatory response and that signaling via this receptor can regulate BBB permeability and chemokine production in vitro.     

PD-L1 – inhibitors in neuroendocrine neoplasia: Results from a real-life study

Immune check-point inhibitors (ICIs) have changed our view on how to treat cancer. Despite their approval in treatment of many different cancers, efficacy of immune check-point inhibitors (ICI) in neuroendocrine neoplasia is limited and poorly understood. Established treatment options of neuroendocrine tumors (NET) and neuroendocrine carcinomas (NECs) are based on surgery, tumor-targeted medical treatments, Peptide Receptor Radionuclide Therapy (PRRT), and locoregional therapies. However, in many patients these treatments lose efficacy over time, and novel therapies are urgently needed. We report on 8 patients diagnosed with neuroendocrine neoplasms (NEN) that were treated with ICI (pembrolizumab, avelumab, nivolumab plus ipilimumab) as salvage therapy. In this cohort, we observed tumor response with partial remission in 3 patients and stable disease in 1 patient. Four patients showed progressive disease. Of note, responses were observed both in PD-L1 positive and PD-L1 negative patients. Here, we discuss clinical courses of these patients in the context of available literature to highlight limitations and drawbacks currently preventing the use of ICI in routine management of patients with NEN.     

Retinal vessel diameters and their correlation with retinal nerve fiber layer thickness in patients with pseudoexfoliation syndrome

AIM: To compare retinal artery-vein diameters (RAVDs) of patients with pseudoexfoliation (PSX) syndrome with healthy controls and investigate the correlations between retinal nerve fiber layer (RNFL) thickness parameters and RAVDs. METHODS: Seventeen eyes with PSX and 17 eyes of age-matched controls were included in the study. All participants underwent routine ophthalmological examination, Humphrey visual field and RNFL examination by using Stratus OCT. Retinal images were obtained by using a retinal camera (Topcon 501X). RAVDs were measured from inferior nasal, inferior temporal, superior nasal and superior temporal arcuates by using IMAGEnet software. Superior, inferior, nasal, temporal and average RNFL thicknesses were recorded. RAVDs and RNFL parameters in groups and correlations were analyzed by Mann-Whitney U and Spearmann correlation tests. RESULTS: Only inferior quadrant and average RNFL thickness were detected thinner in the PSX group compared with control group (P=0.009, P=0.038, respectively). No statistically significant difference regarding RAVDs was found between two groups. CONCLUSION: RAVDs seems to be comparable in the PSX and control group. RNFL is thinner in the inferior quadrant in the PSX group. RNFL thickness and RAVDs show significant correlations in both groups. This correlation doesn’t seem to be specific to PSX.     

Acromegaly is associated with a distinct oral and gut microbiota

Pituitary - Our aim was to investigate the changes in the composition of oral and gut microbiota in patients with newly diagnosed acromegaly and their relationship with IGF-1 levels. Oral and fecal...     

In vitro directed differentiation of mouse embryonic stem cells into insulin-producing cells

Aims/hypothesis We recently demonstrated that insulin-producing cells derived from embryonic stem cells normalise hyperglycaemia in transplanted diabetic mice. The differentiation and selection procedure, however, was successful in less than 5% of the assays performed. Thus, to improve its effectiveness, new strategies have been developed, which increase the number of islet cells or islet progenitors. Methods Mouse embryonic stem cells transfected with a plasmid containing the Nkx6.1 promoter gene followed by a neomycin-resistance gene, were cultured with factors known to participate in endocrine pancreatic development and factors that modulate signalling pathways involved in these processes. Neomycin was used to select the Nkx6.1-positive cells, which also express insulin. The transfected cells were differentiated using several exogenous agents, followed by selection of Nkx6.1-positive cells. The resulting cells were analysed for pancreatic gene and protein expression by immunocytochemistry, RT-PCR and radioimmunoassay. Also, proliferation assays were performed, as well as transplantation to streptozotocin-induced diabetic mice.Results The protocols yielded cell cultures with approximately 20% of cells co-expressing insulin and Pdx-1. Cell trapping selection yielded an almost pure population of insulin-positive cells, which expressed the beta cell genes/proteins Pdx-1, Nkx6.1, insulin, glucokinase, GLUT-2 and Sur-1. Subsequent transplantation to streptozotocin-induced diabetic mice normalised their glycaemia during the time period of experimentation, proving the efficiency of the protocols.Conclusions/interpretation These methods were both highly efficient and very reproducible, resulting in a new strategy to obtain insulin-containing cells from stem cells with a near 100% success rate, while actively promoting the maturation of the exocytotic machinery.Abbreviations Anti-Shh antibody against sonic hedgehog - D3 undifferentiated D3 stem cell line - EB embryoid bodies - ES embryonic stem - FBS fetal bovine serum - LIF leukaemia inhibitory factor - mES mouse embryonic stem - Ngn3 neurogenin 3 - P gelatine-coated plates - Pdx-1 pancreatic duodenum homeobox 1