Use of Endoscopy in Keratoprostheses with Biological Haptics. / Endoskopieeinsatz bei Keratoprothesen mit biologischer Haptik.

INTRODUCTION: In severe ocular surface disease where penetrating keratoplasty cannot be successfully performed, implantation of a keratoprosthesis can achieve visual rehabilitation. Osteo-odonto-keratoprosthesis offers good tissue integration due to its biological haptics, resulting in a better survival rate and lower extrusion rate. Due to corneal opacity, which is often complete, assessing the potential visual acuity is challenging. Also, during implantation of a keratoprosthesis or during later intraocular revision surgery, there is a limited field of view of the peripheral retina or ciliary body region. This is due to the small size and central location of the prosthesis optics and the geometric conditions of the prosthetic haptics. These factors can complicate surgery. METHODS: Endoscopic video assistance was used in 7 eyes of 6 different patients (6 male, 2 female, mean age 66 ± 9 years). In 3 eyes the indication was for preoperative estimation of potential visual acuity during a 23 G vitrectomy. In 2 eyes it was used during implantation surgery itself, and in 2 eyes it was used during revision surgery and vitrectomy. An endoscope with semirigid optics and an image guidance system with 3,000 pixels and 70°field of view from PolyDiagnost was used, with a 23 G trocar system. RESULTS: Endoscopy was successfully applied in all eyes examined. In 1 of 3 eyes where endoscopy was performed to estimate the visual acuity potential, a keratoprosthesis was subsequently planned. In the other two eyes, the visual acuity potential was rated insufficient for future keratoprosthesis surgery. Detailed assessment of the retina and optic disc was limited to gross pathologies because of low image resolution. During implantation, it was possible to visualize correct positioning of the posterior haptic behind the host cornea. Retroprosthetic membranes could successfully be removed by endoscopy-assisted vitrectomy. CONCLUSION: Endoscopy assistance offers advantages in visualization both for determining the indication for KPro surgery, during implantation, and in the management of complications after implantation of a keratoprosthesis. Low resolution of the imaging system places limits on assessment capabilities. Although technical improvements and miniaturization may enhance its future capabilities, endoscopy in its current form is already a valuable addition in the context of keratoprosthesis surgery.

MASE: An Instrument Designed to Record Underwater Soundscape.

The study of sound in the natural environment provides interesting information for researchers and policy makers driving conservation policies in our society. The soundscape characterises the biophony, anthrophony and geophony of a particular area. The characterisation of these different sources can lead to changes in ecosystems and we need to identify these parameters in order to make the right decision in relation to the natural environment. These values could be extrapolated and potentially help different areas of ecoacoustic research. Technological advances have enabled the passive acoustic monitoring (PAM) of animal populations in their natural environment. Recordings can be made with little interference, avoiding anthropogenic effects, making it a very effective method for some species such as cetaceans and other marine species in addition to underwater noise studies. Passive acoustic monitoring can be used for population census, but also to understand the effect of human activities on animals. However, recording data over long periods of time requires large storage and processing capacity to handle all the acoustic events generated. In the case of marine environments, the installation of sensors and instruments can be costly in terms of money and maintenance effort. In addition, if they are placed offshore, a data communication problem arises with coverage and bandwidth. In this paper, we propose a low-cost instrument to monitor the soundscape of a marine area using ecoacoustic indices. The instrument is called MASE and provides three echo-acoustic indices at 10 min intervals that are available in real time, which drastically reduces the volume of data generated. It has been operating uninterruptedly for a year and a half since its deployment, except during maintenance periods. MASE has been able to operate uninterruptedly, and maintain an adequate temperature inside while preserving its structural integrity for long periods of time. This has allowed the monitoring and characterisation of the soundscape of the test area in Gando Bay, Gran Canaria Island (Spain) without the need for human intervention to access the data on the instrument itself. Thanks to its integration with an external server, this allows the long-term monitoring of the soundscape, and it is possible to observe changes in the soundscape. In addition, the instrument has made it possible to compare the period of acoustic inactivity during confinement and the return of anthropogenic acoustic activity at sea.

Implementation of a Depth from Light Field Algorithm on FPGA.

A light field is a four-dimensional function that grabs the intensity of light rays traversing an empty space at each point. The light field can be captured using devices designed specifically for this purpose and it allows one to extract depth information about the scene. Most light-field algorithms require a huge amount of processing power. Fortunately, in recent years, parallel hardware has evolved and enables such volumes of data to be processed. Field programmable gate arrays are one such option. In this paper, we propose two hardware designs that share a common construction block to compute a disparity map from light-field data. The first design employs serial data input into the hardware, while the second employs view parallel input. These designs focus on performing calculations during data read-in and producing results only a few clock cycles after read-in. Several experiments were conducted. First, the influence of using fixed-point arithmetic on accuracy was tested using synthetic light-field data. Also tests on actual light field data were performed. The performance was compared to that of a CPU, as well as an embedded processor. Our designs showed similar performance to the former and outperformed the latter. For further comparison, we also discuss the performance difference between our designs and other designs described in the literature.

Bivalent role of intra-platelet serotonin in liver regeneration and tumor recurrence in humans.

BACKGROUND & AIMS: Besides its critical role during liver regeneration, serotonin (5-HT) has been found to act as a mitogenic factor in several neoplastic entities. Accordingly, we aimed to evaluate whether intra-platelet 5-HT (IP5-HT) was associated with oncological outcome after liver resection and concomitantly evaluate its ability to serve as a therapeutic target to promote liver regeneration. METHODS: A total of 96 patients undergoing liver resection for malignant liver tumors were prospectively included. Optimized plasma and serum preparation were performed and IP5-HT levels were determined. Patients were followed up for postoperative liver dysfunction (LD), morbidity, disease free and overall survival (OS). RESULTS: We found increased preoperative IP5-HT levels in patients with disease recurrence at 6 and 12months (p=0.046, p=0.020, respectively). In clear contrast, patients suffering from postoperative morbidity, severe morbidity or LD had significantly reduced IP5-HT levels (p=0.011, p=0.035, p=0.003, respectively). Patients with high IP5-HT levels (>134ng/ml) suffered from an increased incidence of postoperative disease recurrence at 6 and 12months (p=0.045, p=0.006, respectively) but exhibited a reduction in morbidity, severe morbidity, and LD (p=0.006, p=0.008, p=0.005, respectively). We confirmed these results in our two largest subgroups, demonstrating that they were independent of tumor type. This bivalent effect of IP5-HT was also reflected in patients receiving selective serotonin reuptake inhibitor treatment, who displayed a reduction in disease recurrence accompanied by an increase in postoperative morbidity. Yet, both early disease recurrence and morbidity worsened OS. CONCLUSION: Herein, we present first clinical evidence for IP5-HT being associated with early disease recurrence after liver resection in humans. Thus, pharmacological intervention at the level of platelets and platelet-derived 5-HT to promote liver regeneration should be considered with caution. A careful definition of indications and timing is needed to promote liver regeneration without inducing deleterious effects. LAY SUMMARY: Preoperative intra-platelet serotonin (IP5-HT) levels seem to substantially affect patient outcomes after liver resection for liver tumors. While there is a narrow window of IP5-HT levels where liver regeneration and tumor progression is balanced, excessively high IP5-HT levels (>134ng/ml IP5-HT) lead to an increased incidence of early tumor recurrence and excessively low IP5-HT levels (<73ng/ml IP5-HT) lead to a higher rate of morbidity. Ultimately, overall survival is negatively affected by both postoperative early disease recurrence and morbidity. ClinicalTrials.gov-Identifier: NCT01700231.

Bortezomib and ixazomib protect firefly luciferase from degradation and can flaw respective reporter gene assays.

Firefly luciferase-based reporter gene assays are the most commonly used assays to investigate the transcriptional regulation of gene expression. However, direct interaction of tested compounds with the firefly luciferase leading to altered enzymatic activity may lead to misinterpretation of experimental data. When investigating the proteasome inhibitors bortezomib, carfilzomib, and ixazomib, we observed increased luminescence for bortezomib and ixazomib, but not for carfilzomib, in a pregnane-X-receptor (PXR) reporter gene assay, which was inconsistent with the mRNA expression levels of the main PXR target gene CYP3A4. To further scrutinize this phenomenon, we performed experiments with constitutively expressed firefly luciferase and demonstrated that the increase in cellular firefly luciferase activity is independent from PXR activation or CYP3A4 promoter. Using cell-free assays with recombinant firefly luciferase enzyme, we made the counterintuitive observation that firefly luciferase activity is inhibited by bortezomib and ixazomib in a reversible and competitive manner. This inhibition stabilizes the firefly luciferase enzyme against proteolytic degradation (e.g., toward trypsin), thereby increasing its half-life with subsequent enhancement of total cellular luminescence that eventually mimicked PXR-driven luciferase induction. These data show that particular compounds can strikingly interfere with firefly luciferase and once more illustrate the importance of careful interpretation of data obtained from luciferase-based assays.

Design of belief propagation based on FPGA for the multistereo CAFADIS camera.

In this paper we describe a fast, specialized hardware implementation of the belief propagation algorithm for the CAFADIS camera, a new plenoptic sensor patented by the University of La Laguna. This camera captures the lightfield of the scene and can be used to find out at which depth each pixel is in focus. The algorithm has been designed for FPGA devices using VHDL. We propose a parallel and pipeline architecture to implement the algorithm without external memory. Although the BRAM resources of the device increase considerably, we can maintain real-time restrictions by using extremely high-performance signal processing capability through parallelism and by accessing several memories simultaneously. The quantifying results with 16 bit precision have shown that performances are really close to the original Matlab programmed algorithm.

The 3-60 criteria challenge established predictors of postoperative mortality and enable timely therapeutic intervention after liver resection.

BACKGROUND: To date, definitions of liver dysfunction (LD) after hepatic resection rely on late postoperative time points. Further, the used parameters are markedly influenced by perioperative management. Thus, we aimed to establish a very early postoperative score to predict postoperative mortality. METHODS: Liver related parameters were evaluated after liver resection in a retrospective evaluation cohort of 228 colorectal cancer patients with liver metastasis (mCRC) and subsequent validation in a prospective set of 482 consecutive patients from 4 independent institutions undergoing hepatic resection was performed. RESULTS: C-reactive protein (CRP, AUC =0.739, P<0.001) and antithrombinIII-activity (ATIII, AUC =0.844, P<0.001) on the first postoperative day (POD) were found to be elevated in patients with LD. Cut-off values for CRP at 3 mg/dL and for ATIII at 60% significantly identified high-risk patients for postoperative LD and mortality (P<0.001) and thus defined the 3-60 criteria on POD1. The 3-60 criteria showed superior sensitivity and specificity compared to established criteria for LD [3-60 criteria: total positive patients: 26 patients (70% mortality detected), odds ratio (OR): 48.8; International Study Group for Liver Surgery: total positive patients: 43 (70% mortality detected), OR: 23.3; Peak7: total positive patients: 9 (30% mortality detected), OR: 27.8; 50-50: total positive patients: 9 (30% mortality detected), OR: 27.8]. These results could be validated in a multi-center analysis and ultimately the 3-60 criteria remained an independent predictor of postoperative mortality upon multivariable analysis. CONCLUSIONS: The 3-60 criteria on POD1 predict postoperative LD and mortality early after liver resection with a comparable or better accuracy than established criteria, allowing for immediate identification of high-risk patients.

Cisplatin, oxaliplatin, and carboplatin unequally inhibit in vitro mRNA translation.

DNA is considered the preferential target of platinum containing cytostatics such as cisplatin, oxaliplatin, and carboplatin. Despite profound knowledge on the interaction between platinum drugs and DNA, there is little data on the interaction with mRNA and even less on the potential differences among these antineoplastic agents to inhibit protein synthesis. We therefore established an in vitro translation system using in vitro transcribed mRNA encoding green fluorescent protein (GFP) to evaluate the effects of exposure of GFP mRNA to 0-100 µM of cisplatin, oxaliplatin, or carboplatin. We additionally investigated the interaction between these drugs and mRNA through evaluation of crossing-points during quantitative real-time polymerase chain reactions. In contrast to oxaliplatin or carboplatin, 100 µM cisplatin significantly increased crossing-points by about 3 cycles (P<0.01) and profoundly attenuated translation of GFP mRNA (P<0.05). Oxaliplatin showed a trend to reduce GFP mRNA translation, whereas carboplatin entirely failed to influence it. In conclusion, this study for the very first time documents different effects of platinum cytostatics on mRNA translation and demonstrates mRNA to be a functionally relevant target of at least cisplatin.

Telaprevir is a substrate and moderate inhibitor of P-glycoprotein, a strong inductor of ABCG2, but not an activator of PXR in vitro.

Triple therapy combining the protease inhibitor telaprevir with interferon-α and ribavirin is a promising new option for long-term treatment of hepatitis C. The interaction potential of telaprevir has not yet been fully elucidated. The in vitro potency of telaprevir to inhibit P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP, ABCG2) was assessed and its substrate characteristics for P-gp, BCRP and the multidrug resistance-associated proteins (MRPs, ABCCs) 1-3 were evaluated. The inducing properties of telaprevir on important drug-metabolising enzymes and transporters were also assessed and its ability to activate the pregnane X receptor (PXR) was investigated. Using growth inhibition assays, it was confirmed that telaprevir is a substrate of P-gp and it was demonstrated for the first time that it is not transported by BCRP and MRPs. Telaprevir only moderately inhibited P-gp in the calcein assay and did not inhibit BCRP in the pheophorbide A assay. In LS180 cells, telaprevir strongly induced mRNA expression of ABCG2 (4.3-fold at 30 µmol/L) and weakly induced ABCB11, CYP2C19 and UGT1A3. In contrast, telaprevir had no significant influence on mRNA expression of CYP3A4, UGT1A9, ABCB1, ABCC2 and SLCO1B1. In a reporter gene assay, telaprevir did not activate PXR. Thus, it appears unlikely that telaprevir induces CYP3A4 and P-gp in vivo in such a way as to provoke clinically relevant drug interactions. From the numerous perpetrator characteristics, telaprevir's inhibitor properties, especially of CYP3A4 and P-gp, appear to be the most relevant mechanism for drug interactions. The clinical relevance of the strong inducing effects on ABCG2 requires proper assessment.