Micro-endoscopy of the human vas deferens: a feasibility study of a novel device in several ex vivo models

The aim of this study was to show limitation as well as potential of micro-endoscopy techniques as an innovative diagnostic and therapeutic approach in andrology. Two kinds of custom-made micro-endoscopes (ME) were tested in ex vivo vas deferens specimen and in post-mortem whole body. The semi-rigid ME included a micro-optic (0.9mm outer diameter [OD], 10.000 pixels, 120 degrees vision angle [VE], 3-20mm field depth [FD]) and an integrated fibre-optic light source. The flexible ME was composed of a micro-optic (OD=0.6mm, 6.000 pixels, 120 degrees VE, 3-20mm FD). The ex vivo study included retrograde investigation of the vas deferens (surgical specimen n=9, radical prostatectomy n=3). The post-mortem investigation (n=4) included the inspection of the vas deferens via both approaches. The results showed that antegrade and retrograde rigid endoscopy of the vas deferens were achieved as a diagnostic tool. The working channel enabled therapeutic use including biopsies or baskets. Using the flexible ME, the orifices of the ejaculatory ducts were identified. In vivo cadaveric retrograde cannulation of the orifices was successful. Post-mortem changes of verumontanum hindered the examinations beyond. Orifices were identified shaded behind a thin transparent membrane. Antegrade vasoscopy using flexible ME was possible up to the internal inguinal ring. Further advancement was impossible because of anatomical angle and lack adequate vision guidance. The vas deferens interior was clearly visible and was documented by pictures and movies. Altogether, the described ME techniques were feasible and effective, offering the potential of innovative diagnostic and therapeutic approaches for use in the genital tract. Several innovative indications could be expected

A hydrodynamically optimized nano-electrospray ionization source and vacuum interface

The coupling of atmospheric pressure ionization (API) sources like electrospray ionization (ESI) to vacuum based applications like mass spectrometry (MS) or ion beam deposition (IBD) is done by differential pumping, starting with a capillary or pinhole inlet. Because of its low ion transfer efficiency the inlet represents a major bottleneck for these applications. Here we present a nano-ESI vacuum interface optimized to exploit the hydrodynamic drag of the background gas for collimation and the reduction of space charge repulsion. Up to a space charge limit of 40 nA we observe 100% current transmission through a capillary with an inlet and show by MS and IBD experiments that the transmitted ion beams are well defined and free of additional contamination compared to a conventional interface. Based on computational fluid dynamics modelling and ion transport simulations, we show how the specific shape enhances the collimation of the ion cloud. Mass selected ion currents in the nanoampere range available further downstream in high vacuum open many perspectives for the efficient use of electrospray ion beam deposition (ES-IBD) as a surface coating method

A Formal Approach to Support Interoperability in Scientific Meta-workflows

Scientific workflows orchestrate the execution of complex experiments frequently using distributed computing platforms. Meta-workflows represent an emerging type of such workflows which aim to reuse existing workflows from potentially different workflow systems to achieve more complex and experimentation minimizing workflow design and testing efforts. Workflow interoperability plays a profound role in achieving this objective. This paper is focused at fostering interoperability across meta-workflows that combine workflows of different workflow systems from diverse scientific domains. This is achieved by formalizing definitions of meta-workflow and its different types to standardize their data structures used to describe workflows to be published and shared via public repositories. The paper also includes thorough formalization of two workflow interoperability approaches based on this formal description: the coarse-grained and fine-grained workflow interoperability approach. The paper presents a case study from Astrophysics which successfully demonstrates the use of the concepts of meta-workflows and workflow interoperability within a scientific simulation platform

The Potential Role of Magnetic Resonance Spectroscopy in Image-Guided Radiotherapy

Magnetic resonance spectroscopy (MRS) is a non-invasive technique to detect metabolites within the normal and tumoral tissues. The ability of MRS to diagnose areas of high metabolic activity linked to tumor cell proliferation is particularly useful for radiotherapy treatment planning because of better gross tumor volume (GTV) delineation. The GTV may be targeted with higher radiation dose, potentially improving local control without excessive irradiation to the normal adjacent tissues. Prostate cancer and glioblastoma multiforme (GBM) are two tumor models that are associated with a heterogeneous tumor distribution. Preliminary studies suggest that the integration of MRS into radiotherapy planning for these tumors is feasible and safe. Image-guided radiotherapy (IGRT) by virtue of daily tumor imaging and steep dose gradient may allow for tumor dose escalation with the simultaneous integrated boost technique (SIB) and potentially decrease the complications rates in patients with GBM and prostate cancers

Role of Porphyromonas gingivalis gingipains in multi-species biofilm formation

BackgroundPeriodontal diseases are polymicrobial diseases that cause the inflammatory destruction of the tooth-supporting (periodontal) tissues. Their initiation is attributed to the formation of subgingival biofilms that stimulate a cascade of chronic inflammatory reactions by the affected tissue. The Gram-negative anaerobes Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola are commonly found as part of the microbiota of subgingival biofilms, and they are associated with the occurrence and severity of the disease. P. gingivalis expresses several virulence factors that may support its survival, regulate its communication with other species in the biofilm, or modulate the inflammatory response of the colonized host tissue. The most prominent of these virulence factors are the gingipains, which are a set of cysteine proteinases (either Arg-specific or Lys-specific). The role of gingipains in the biofilm-forming capacity of P. gingivalis is barely investigated. Hence, this in vitro study employed a biofilm model consisting of 10 ¿subgingival¿ bacterial species, incorporating either a wild-type P. gingivalis strain or its derivative Lys-gingipain and Arg-gingipan isogenic mutants, in order to evaluate quantitative and qualitative changes in biofilm composition.ResultsFollowing 64 h of biofilm growth, the levels of all 10 species were quantified by fluorescence in situ hybridization or immunofluorescence. The wild-type and the two gingipain-deficient P. gingivalis strains exhibited similar growth in their corresponding biofilms. Among the remaining nine species, only the numbers of T. forsythia were significantly reduced, and only when the Lys-gingipain mutant was present in the biofilm. When evaluating the structure of the biofilm by confocal laser scanning microscopy, the most prominent observation was a shift in the spatial arrangement of T. denticola, in the presence of P. gingivalis Arg-gingipain mutant.ConclusionsThe gingipains of P. gingivalis may qualitatively and quantitatively affect composition of polymicrobial biofilms. The present experimental model reveals interdependency between the gingipains of P. gingivalis and T. forsythia or T. denticola

Changing climate—changing pathogens: Toxoplasma gondii in North-Western Europe

In this review, we describe the effects of global climate change for one specific pathogen: the parasite Toxoplasma gondii. It is postulated that an increase of T. gondii prevalence in humans can occur in some regions of North-Western Europe as a result of changing environmental conditions. Such a change can be predicted by using Global Climate Change models. We have elaborated such a prediction for one scenario (SRES A1) by using one specific model (CCSR/NRIES) as an example. Next to environmental factors, also anthropogenic factors may contribute to increased prevalence of T. gondii in this region. In order to counter the potential severe consequences of a potential increase resulting from the combination of climatic and anthropogenic factors, there is an urgent need for the development of a human vaccine. Until a vaccine that offers complete protection is developed, the emphasis should be on treatment optimization and prevention

Learning curves of basic laparoscopic psychomotor skills in SINERGIA VR simulator

Purpose: Surgical simulators are currently essential within any laparoscopic training program because they provide a low-stakes, reproducible and reliable environment to acquire basic skills. The purpose of this study is to determine the training learning curve based on different metrics corresponding to five tasks included in SINERGIA laparoscopic virtual reality simulator. Methods: Thirty medical students without surgical experience participated in the study. Five tasks of SINERGIA were included: Coordination, Navigation, Navigation and touch, Accurate grasping and Coordinated pulling. Each participant was trained in SINERGIA. This training consisted of eight sessions (R1–R8) of the five mentioned tasks and was carried out in two consecutive days with four sessions per day. A statistical analysis was made, and the results of R1, R4 and R8 were pair-wise compared with Wilcoxon signed-rank test. Significance is considered at P value <0.005. Results: In total, 84.38% of the metrics provided by SINERGIA and included in this study show significant differences when comparing R1 and R8. Metrics are mostly improved in the first session of training (75.00% when R1 and R4 are compared vs. 37.50% when R4 and R8 are compared). In tasks Coordination and Navigation and touch, all metrics are improved. On the other hand, Navigation just improves 60% of the analyzed metrics. Most learning curves show an improvement with better results in the fulfillment of the different tasks. Conclusions: Learning curves of metrics that assess the basic psychomotor laparoscopic skills acquired in SINERGIA virtual reality simulator show a faster learning rate during the first part of the training. Nevertheless, eight repetitions of the tasks are not enough to acquire all psychomotor skills that can be trained in SINERGIA. Therefore, and based on these results together with previous works, SINERGIA could be used as training tool with a properly designed training program

t10c12 Conjugated Linoleic Acid Suppresses HER2 Protein and Enhances Apoptosis in SKBr3 Breast Cancer Cells: Possible Role of COX2

BACKGROUND: HER2-targeted therapy with the monoclonal antibody trastuzumab (Herceptin) has improved disease-free survival for women diagnosed with HER2-positive breast cancers; however, treatment resistance and disease progression are not uncommon. Current data suggest that resistance to treatment in HER2 cancers may be a consequence of NF-kappaB overexpression and increased COX2-derived prostaglandin E2 (PGE(2)). Conjugated linoleic acid (CLA) has been shown to have anti-tumor properties and to inhibit NF-kappaB activity and COX2. METHODS: In this study, HER2-overexpressing SKBr3 breast cancer cells were treated with t10c12 CLA. Protein expression of the HER2 receptor, nuclear NF-kappaB p65, and total and phosphorylated IkappaB were examined by western blot and immunofluorescence. PGE(2) levels were determined by ELISA. Proliferation was measured by metabolism of 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), and apoptosis was measured by FITC-conjugated Annexin V staining and flow cytometry. RESULTS/CONCLUSIONS: We observed a significant decrease in HER2 protein expression on western blot following treatment with 40 and 80 microM t10c12 CLA (p<0.01 and 0.001, respectively) and loss of HER2 protein in cells using immunoflourescence that was most pronounced at 80 microM. Protein levels of nuclear NF-kappaB p65 were also significantly reduced at the 80 microM dose. This was accompanied by a significant decrease in PGE(2) levels (p = 0.05). Pretreatment with t10c12 CLA significantly enhanced TNFalpha-induced apoptosis and the anti-proliferative action of trastuzumab (p = 0.05 and 0.001, respectively). These data add to previous reports of an anti-tumor effect of t10c12 CLA and suggest an effect on the HER2 oncogene that may be through CLA mediated downregulation of COX2-derived PGE(2)