COL11A1/(pro)collagen 11A1 expression is a remarkable biomarker of human invasive carcinoma-associated stromal cells and carcinoma progression.

The COL11A1 human gene codes for the α1 chain of procollagen 11A1 and mature collagen 11A1, an extracellular minor fibrillar collagen. Under regular conditions, this gene and its derived products are mainly expressed by chondrocytes and mesenchymal stem cells as well as osteoblasts. Normal epithelial cells and quiescent fibroblasts from diverse locations do not express them. Mesenchyme-derived tumors and related conditions, such as scleroderma and keloids, are positive for COL11A1/(pro)collagen 11A1 expression, as well as high-grade human gliomas/glioblastomas. This expression is almost absent in benign pathological processes such as breast hyperplasia, sclerosing adenosis, idiopathic pulmonary fibrosis, cirrhosis, pancreatitis, diverticulitis, and inflammatory bowel disease. By contrast, COL11A1/(pro)collagen 11A1 is highly expressed by activated stromal cells of the desmoplastic reaction of different human invasive carcinomas, and this expression is correlated with carcinoma aggressiveness and progression, and lymph node metastasis. COL11A1 upregulation has been shown to be associated to TGF-ß1, Wnt, and Hh signaling pathways, which are especially active in cancer-associated stromal cells. At the front of invasive carcinomas, neoplastic epithelial cells, putatively undergoing epithelial-to-mesenchymal transition, and carcinoma-derived cells with highly metastatic capabilities, can express COL11A1. Thus, in established metastases, the expression of COL11A1/(pro)collagen 11A1 could rely on both the metastatic epithelial cells and/or the accompanying activated stromal cells. COL11A1/(pro)collagen 11A1 expression is a remarkable biomarker of human carcinoma-associated stromal cells and carcinoma progression.

Predictive markers of response to neoadjuvant therapy in rectal cancer.

BACKGROUND: Neoadjuvant therapy followed by radical surgery is the standard treatment in locally advanced rectal cancer. It is important to predict the response because the treatment has side effects and is costly. The aim of this study was to establish the relationship among clinical, pathologic, and molecular biomarkers and the response to neoadjuvant therapy. METHOD: A total of 130 patients with locally advanced mid and low rectal cancer who underwent long-course radiotherapy with 5-FU based chemotherapy followed by radical surgical resection were included in the study. Clinical and pathologic data were collected. Paraffin-embedded sections obtained in diagnostic biopsies were assessed by immunohistochemical staining for molecular markers and classified using a semiquantitative method. Results were related with T-downstaging and tumor regression grade using Mandard scoring system on surgical specimens. RESULTS: Pathologic complete response was found in 19 patients (14.6%), while in another 18 (13.8%) only minor residual disease was seen in the rectal wall. T-downstaging was observed in 63 (48.5%). The average of lymph node retrieval in the surgical specimens was 9.4. Regarding predictive markers of response, there was significant correlation between the expression of B-cell lymphoma 2 (P = 0.005), ß-catenin (P = 0.03), vascular endothelial growth factor (P = 0.048) and apoptotic protease activating factor 1 (P = 0.03), tumor differentiation grade (P < 0.001), and response in the univariate analysis. T-downstaging was associated with vascular endothelial growth factor expression (P = 0.03) and tumor differentiation grade (P < 0.001). Significant parameters found in the multivariate analysis were tumor differentiation grade and Bcl-2 expression. CONCLUSIONS: Pathologic and molecular biomarkers in the diagnostic biopsies may help us predict tumor response to chemoradiation in rectal cancer patients.

Validation of COL11A1/procollagen 11A1 expression in TGF-ß1-activated immortalised human mesenchymal cells and in stromal cells of human colon adenocarcinoma.

BACKGROUND: The human COL11A1 gene has been shown to be up-regulated in stromal cells of colorectal tumours, but, so far, the immunodetection of procollagen 11A1, the primary protein product of COL11A1, has not been studied in detail in human colon adenocarcinomas. Some cancer-associated stromal cells seem to be derived from bone marrow mesenchymal cells; the expression of the COL11A1 gene and the parallel immunodetection of procollagen 11A1 have not been evaluated in these latter cells, either. METHODS: We used quantitative RT-PCR and/or immunocytochemistry to study the expression of DES/desmin, VIM/vimentin, ACTA2/αSMA (alpha smooth muscle actin) and COL11A1/procollagen 11A1 in HCT 116 human colorectal adenocarcinoma cells, in immortalised human bone marrow mesenchymal cells and in human colon adenocarcinoma-derived cultured stromal cells. The immunodetection of procollagen 11A1 was performed with the new recently described DMTX1/1E8.33 mouse monoclonal antibody. Human colon adenocarcinomas and non-malignant colon tissues were evaluated by immunohistochemistry as well. Statistical associations were sought between anti-procollagen 11A1 immunoscoring and patient clinicopathological features. RESULTS: Procollagen 11A1 was immunodetected in human bone marrow mesenchymal cells and in human colon adenocarcinoma-associated spindle-shaped stromal cells but not in colon epithelial or stromal cells of the normal colon. This immunodetection paralleled, in both kinds of cells, that of the other mesenchymal-related biomarkers studied: vimentin and alpha smooth muscle actin, but not desmin. Thus, procollagen 11A1(+) adenocarcinoma-associated stromal cells are similar to "activated myofibroblasts". In the series of human colon adenocarcinomas here studied, a high procollagen 11A1 expression was associated with nodal involvement (p = 0.05), the development of distant metastases (p = 0.017), and advanced Dukes stages (p = 0.047). CONCLUSION: The immunodetection of procollagen 11A1 in cancer-associated stromal cells could be a useful biomarker for human colon adenocarcinoma characterisation.

Synthesis of trigeneration systems: sensitivity analyses and resilience.

This paper presents sensitivity and resilience analyses for a trigeneration system designed for a hospital. The following information is utilized to formulate an integer linear programming model: (1) energy service demands of the hospital, (2) technical and economical characteristics of the potential technologies for installation, (3) prices of the available utilities interchanged, and (4) financial parameters of the project. The solution of the model, minimizing the annual total cost, provides the optimal configuration of the system (technologies installed and number of pieces of equipment) and the optimal operation mode (operational load of equipment, interchange of utilities with the environment, convenience of wasting cogenerated heat, etc.) at each temporal interval defining the demand. The broad range of technical, economic, and institutional uncertainties throughout the life cycle of energy supply systems for buildings makes it necessary to delve more deeply into the fundamental properties of resilient systems: feasibility, flexibility and robustness. The resilience of the obtained solution is tested by varying, within reasonable limits, selected parameters: energy demand, amortization and maintenance factor, natural gas price, self-consumption of electricity, and time-of-delivery feed-in tariffs.

Reproducibility analysis of the computerized tomography angiography-derived left atrial wall thickness maps.

BACKGROUND: Adapting the ablation index (AI) to the left atrial wall thickness (LAWT) derived from computed tomography angiography (CTA) allows for a personalized approach that showed to improve PVI safety and outcomes. METHODS: Three observers with different degrees of experience performed complete LAWT analysis of CTA for 30 patients and repeated the analysis for 10 of these patients. Intra- and inter-observer reproducibility of these segmentations was assessed. RESULTS: Geometric congruence of repeated reconstruction of LA endocardial surface showed that 99.4% of points in the 3D reconstructed mesh were within < 1 mm distance for the intra-observer variability and 95.1% for the inter-observer. For the LA epicardial surface, an 82.4% of points were within < 1 mm for intra-observer and a 77.7% for inter-observer. A 1.99% of points were further than 2 mm for the intra-observer and a 4.1% for the inter-observer. Colour agreement between LAWT maps showed that a 95.5% and a 92.9% intra- and inter-observer respectively presented the same colour or a change to the colour immediately above or below. The ablation index (AI), which was adapted to this LAWT colour maps to perform a personalized pulmonary vein isolation (PVI), showed an average difference in the derived AI lower than 25 units in all cases. For all analyses, the concordance increased with user-experience. CONCLUSION: Geometric congruence of LA shape was high, for both endocardial and epicardial segmentations. LAWT measurements were reproducible, increasing with user experience. This translated into a negligible impact in the target AI.

Validation of the Basic Psychological Needs in Exercise Scale in a Portuguese sample.

In line with self-determination theory (SDT: Deci & Ryan, 1985, 2002) the satisfaction of the basic psychological needs for autonomy, competence, and relatedness has been identified as an important predictor of behavior and optimal functioning in various contexts including exercise. The lack of a valid and reliable instrument to assess the extent to which these needs are fulfilled among Portuguese exercise participants limits the evaluation of causal links proposed by SDT in the Portuguese exercise context. The aim of the present study was to translate into Portuguese and validate the Basic Psychological Needs in Exercise Scale (BPNES: Vlachopoulos & Michailidou, 2006). Using data from 522 exercise participants the findings provided evidence of strong internal consistency of the translated BPNES subscales while confirmatory factor analysis supported a good fit of the correlated 3-factor model to the data. The present findings support the use of the translated into Portuguese BPNES to assess the extent of basic psychological need fulfilment among Portuguese exercise participants.

Scientists' warning against the society of waste.

The metabolism of contemporary industrialized societies, that is their energy and material flows, leads to the overconsumption and waste of natural resources, two factors often disregarded in the global ecological equation. In this Discussion article, we examine the amount of natural resources that is increasingly being consumed and wasted by humanity, and propose solutions to reverse this pattern. Since the beginning of the 20th century, societies, especially from industrialized countries, have been wasting resources in different ways. On one hand, the metabolism of industrial societies relies on non-renewable resources. On the other hand, yearly, we directly waste or mismanage around 78% of the total water withdrawn, 49% of the food produced, 31% of the energy produced, 85% of ores and 26% of non-metallic minerals extracted, respectively. As a consequence, natural resources are getting depleted and ecosystems polluted, leading to irreversible environmental changes, biological loss and social conflicts. To reduce the anthropogenic footprint in the planet, and live in harmony with other species and ourselves, we suggest to shift the current economic model based on infinite growth and reduce inequality between and within countries, following a degrowth strategy in industrialized countries. Public education to reduce superfluous consumption is also necessary. In addition, we propose a set of technological strategies to improve the management of natural resources towards circular economies that, like ecosystems, rely only upon renewable resources.

Molecular evidence to suggest the origin of a colonization: Drosophila subobscura in America.

The recent colonization of America by Drosophila subobscura represents a great opportunity for evolutionary biology studies. Knowledge of the populations from which the colonization started would provide an understanding of how genetic composition changed during adaptation to the new environment. Thus, a 793 nucleotide fragment of the Odh (Octanol dehydrogenase) gene was sequenced in 66 chromosomal lines from Barcelona (western Mediterranean) and in 66 from Mt. Parnes (Greece, eastern Mediterranean). No sequence of Odh fragment in Barcelona or Mt. Parnes was identical to any of those previously detected in America. However, an Odh sequence from Barcelona differed in only one nucleotide from another found in American populations. In both cases, the chromosomal lines presented the same inversion: O(7), and the Odh gene was located within this inversion. This evidence suggests a possible western Mediterranean origin for the colonization. Finally, the molecular and inversion data indicate that the colonization was not characterized by multiple reintroductions.

On the Use of Digital Subtraction Angiography in Stereoelectroencephalography Surgical Planning to Prevent Collisions with Vessels.

OBJECTIVE: Stereoelectroencephalography (SEEG) consists of the implantation of microelectrodes for the electrophysiological characterization of epileptogenic networks. To reduce a possible risk of intracranial bleeding by vessel rupture during the electrode implantation, the stereotactic trajectories must follow avascular corridors. The use of digital subtraction angiography (DSA) for vascular visualization during planning is controversial due to the additional risk related to this procedure. Here we evaluate the utility of this technique for planning when the neurosurgeon has it available together with gadolinium-enhanced T1-weighted magnetic resonance sequence (T1-Gd) and computed tomography angiography (CTA). METHODS: Twenty-two implantation plans for SEEG were initially done using T1-Gd imaging (251 trajectories). DSA was only used later during the revision process. In 6 patients CTA was available at this point as well. We quantified the position of the closest vessel to the trajectory in each of the imaging modalities. RESULTS: Two thirds of the trajectories that appeared vessel free in the T1-Gd or CTA presented vessels in their proximity, as shown by DSA. Those modifications only required small shifts of both the entry and target point, so the diagnostic aims were preserved. CONCLUSIONS: T1-Gd and CTA, despite being the most commonly used techniques for SEEG planning, frequently fail to reveal vessels that are dangerously close to the trajectories. Higher-resolution vascular imaging techniques, such as DSA, can provide the neurosurgeon with crucial information about vascular anatomy, resulting in safer plans.

SYLVIUS: A multimodal and multidisciplinary platform for epilepsy surgery.

BACKGROUND AND OBJECTIVE: We present SYLVIUS, a software platform intended to facilitate and improve the complex workflow required to diagnose and surgically treat drug-resistant epilepsies. In complex epilepsies, additional invasive information from exploration with stereoencephalography (SEEG) with deep electrodes may be needed, for which the input from different diagnostic methods and clinicians from several specialties is required to ensure diagnostic efficacy and surgical safety. We aim to provide a software platform with optimal data flow among the different stages of epilepsy surgery to provide smooth and integrated decision making. METHODS: The SYLVIUS platform provides a clinical workflow designed to ensure seamless and safe patient data sharing across specialities. It integrates tools for stereo visualization, data registration, transfer of electrode plans referred to distinct datasets, automated postoperative contact segmentation, and novel DWI tractography analysis. Nineteen cases were retrospectively evaluated to track modifications from an initial plan to obtain a final surgical plan, using SYLVIUS. RESULTS: The software was used to modify trajectories in all 19 consulted cases, which were then imported into the robotic system for the surgical intervention. When available, SYLVIUS provided extra multimodal information, which resulted in a greater number of trajectory modifications. CONCLUSIONS: The architecture presented in this paper streamlines epilepsy surgery allowing clinicians to have a digital clinical tool that allows recording of the different stages of the procedure, in a common multimodal 2D/3D setting for participation of different clinicians in defining and validating surgical plans for SEEG cases.

A new aggressive xenograft model of human colon cancer using cancer-associated fibroblasts.

BACKGROUND: Colorectal cancer is the second leading cause of cancer death. Almost half of the patients present recurrence within 5 years after the treatment of the primary tumor, the majority, with metastasis. On the other hand, in the search for new animal models that simulate metastatic cancer, it has been suggested that fibroblasts immersed in the peritumoral stroma (cancer-associated fibroblasts (CAFs)), play a relevant role in the development of cancer. The objective of this study was to identify an adequate animal model to study metastatic colon cancer and the application of new treatments. METHODS: Human CAFs and normal fibroblasts (NF) for transplant and culture were obtained from surgical fresh samples of patients with adenocarcinoma of sigmoid colon. Stromal cell purity was evaluated by morphology and immunostaining with vimentin (VIM) as a fibroblast marker and anti-proColXIα1 as a specific human CAF marker. Phenotypic characterization of cultured stromal cells was performed by co-staining with mesenchymal and epithelial cell markers. For identification in mice, human CAFs were labeled with the PKH26 red fluorescence dye. Cell line HT-29 was used as tumor cells. Transplant in the head of the pancreas of 34 SCID mice was performed in four different groups, as follows: I. 150,000 CAFS (n = 12), IIa. 1.5 million HT29 cells (n = 7), IIb. 150,000 NF+1.5 million HT29 cells (n = 5), III. 150,000 CAFS+1.5 million HT29 cells (n = 10). After euthanasia performed one month later, histological analysis was made using hematoxylin-eosin and anti-proColXIα1. A histopathological score system based on three features (tumor volume, desmoplasia and number of metastasized organs) was established to compare the tumor severity. RESULTS: The CAFs and NF cultured were proColXIα1+/VIM+, proColXIα1/alphaSMA+ and proColXIα1+/CK19+ in different proportions without differences among them, but the CAFs growth curve was significantly larger than that of the NF (p < 0.05). No tumor developed in those animals that only received CAFs. When comparing group II (a + b) vs. group III, both groups showed 100% hepatic metastases. Median hepatic nodules, tumor burden, lung metastases and severity score were bigger in group III vs group II (a + b), although without being significant, except in the case of the median tumor volume, that was significantly higher in group III (154.8 (76.9-563.2) mm3) vs group II (46.7 (3.7-239.6) mm3), p = 0.04. A correlation was observed between the size of the tumor developed in the pancreas and the metastatic tumor burden in the liver and with the severity score. CONCLUSION: Our experiments demonstrate that cultured CAFs have a higher growth than NF and that when human CAFs are associated to human tumor cells, larger tumors with liver and lung metastases are generated than if only colon cancer cells with/without NF are transplanted. This emphasizes the importance of the tumor stroma, and especially the CAFs, in the development of cancer.

Transcatheter Mitral Repair for Functional Mitral Regurgitation According to Left Ventricular Function: A Real-Life Propensity-Score Matched Study.

BACKGROUND: Transcatheter mitral valve repair (TMVR) could improve survival in functional mitral regurgitation (FMR), but it is necessary to consider the influence of left ventricular ejection fraction (LVEF). Therefore, we compare the outcomes after TMVR with Mitraclip® between two groups according to LVEF. METHODS: In an observational registry study, we compared the outcomes in patients with FMR who underwent TMVR with and without LVEF <30%. The primary endpoint was the combined one-year all-cause mortality and unplanned hospital readmissions due to HF. The secondary end-points were New York Heart Association (NYHA) functional class and mitral regurgitation (MR) severity. Propensity-score matching was used to create two groups with the same baseline characteristics, except for baseline LVEF. RESULTS: Among 535 FMR eligible patients, 144 patients with LVEF <30% (group 1) and 144 with LVEF >30% (group 2) had similar propensity scores and were included in the analyses. The primary study endpoint was significantlly higher in group 1 (33.3% vs. 9.4%, p = 0.002). There was a maintained improvement in secondary endpoints without significant differences among groups. CONCLUSION: FMR patients with LVEF <30% treated with MitraClip® had higher mortality and readmissions than patients with LVEF ≥30% treated with the same device. However, both groups improved the NYHA functional class and MR severity.

Evolution of Chilean colonizing populations of Drosophila subobscura: lethal genes and chromosomal arrangements.

Knowledge of the frequency, distribution, and fate of lethal genes in chromosomal inversions helps to illuminate the evolution of recently founded populations. We analyze the relationship between lethal genes and inversions in two colonizing populations of D. subobscura in Chile. In the ancestral Palearctic populations of this species, lethal genes seem distributed at random on chromosomes. But in colonizing American populations, some lethal genes are associated with specific chromosomal arrangements. Some of these associated lethals were detected only during the first stages of the colonization (O( 3+4+2 )), and never thereafter, whereas others have persisted (O( 3+4+7 ) and O(5)). However, most lethal genes in American populations have been observed only once: they have arisen by novel mutation and soon disappear. Finally, recombination between different inversions has been observed in America. However, the persistence of lethal genes associated with the heterotic inversions O( 3+4+7 ) and O(5) could indicate that recombination inside these inversions is rare.

Scar Characterization to Predict Life-Threatening Arrhythmic Events and Sudden Cardiac Death in Patients With Cardiac Resynchronization Therapy: The GAUDI-CRT Study.

OBJECTIVES: The aim of this study was to analyze whether scar characterization could improve the risk stratification for life-threatening ventricular arrhythmias and sudden cardiac death (SCD). BACKGROUND: Among patients with a cardiac resynchronization therapy (CRT) indication, appropriate defibrillator (CRT-D) therapy rates are low. METHODS: Primary prevention patients with a class I indication for CRT were prospectively enrolled and assigned to CRT-D or CRT pacemaker according to physician's criteria. Pre-procedure contrast-enhanced cardiac magnetic resonance was obtained and analyzed to identify scar presence or absence, quantify the amount of core and border zone (BZ), and depict BZ distribution. The presence, mass, and characteristics of BZ channels in the scar were recorded. The primary endpoint was appropriate defibrillator therapy or SCD. RESULTS: 217 patients (39.6% ischemic) were included. During a median follow-up of 35.5 months (12 to 62 months), the primary endpoint occurred in 25 patients (11.5%) and did not occur in patients without myocardial scar. Among patients with scar (n = 125, 57.6%), those with implantable cardioverter-defibrillator (ICD) therapies or SCD exhibited greater scar mass (38.7 ± 34.2 g vs. 17.9 ± 17.2 g; p < 0.001), scar heterogeneity (BZ mass/scar mass ratio) (49.5 ± 13.0 vs. 40.1 ± 21.7; p = 0.044), and BZ channel mass (3.6 ± 3.0 g vs. 1.8 ± 3.4 g; p = 0.018). BZ mass (hazard ratio: 1.06 [95% confidence interval: 1.04 to 1.08]; p < 0.001) and BZ channel mass (hazard ratio: 1.21 [95% confidence interval: 1.10 to 1.32]; p < 0.001) were the strongest predictors of the primary endpoint. An algorithm based on scar mass and the absence of BZ channels identified 148 patients (68.2%) without ICD therapy/SCD during follow-up with a 100% negative predictive value. CONCLUSIONS: The presence, extension, heterogeneity, and qualitative distribution of BZ tissue of myocardial scar independently predict appropriate ICD therapies and SCD in CRT patients.

Contouring in 2D while viewing stereoscopic 3D volumes.

The ability to manually specify contours in a volumetric data is often required in situations when automatic algorithms are unable to accurately extract the desire volume. Conventionally, the contours are drawn over a slice, working on plane-by-plane basis usually constrained to orthogonal planes. In defining the contour on a 2D image, the user faces the problem of loosing 3D context (does the tissue belong to inside the contour or outside?). This requires the constant back and forth movement from a plane view where the interaction takes place (usually with the mouse) to the 3D volumetric view that provides the contextual information. We present an interactive environment that allows for efficient contouring while providing contextual 3D information to the user.

Temperature-related genetic changes in laboratory populations of Drosophila subobscura: evidence against simple climatic-based explanations for latitudinal clines.

Parallel latitudinal clines to the long-standing ones in the original Palearctic populations have independently evolved at different rates for chromosomal polymorphism and body size in South and North American populations of Drosophila subobscura since colonization around 25 years ago. This strongly suggests that (micro) evolutionary changes are largely predictable, but the underlying mechanisms are unknown. The putative role of temperature per se was investigated by using three sets of populations at each of three temperatures (13 degrees , 18 degrees , and 22 degrees C) spanning much of the tolerable range for this species. We found a lower chromosomal diversity at the warmest temperature; a quick and consistent shift in gene arrangement frequencies in response to temperature; an evolutionary decrease in wing size, mediated by both cell area and cell number, at 18 degrees C; no relationship between wing size and those inversions involved in latitudinal clines; and a shortening of the basal length of longitudinal vein IV relative to its total length with increasing standard dose. The trends for chromosomal polymorphism and body size were generally inconsistent from simple climatic-based explanations of worldwide latitudinal patterns. The findings are discussed in the light of available information on D. subobscura and results from earlier thermal selection experiments with various Drosophila species.

The effects of antiglaucoma and systemic medications on ocular blood flow.

Based on the body of evidence implicating ocular blood flow disturbances in the pathogenesis of glaucoma, there is great interest in the investigation of the effects of antiglaucoma drugs and systemic medications on the various ocular vascular beds. The primary aim of this article was to review the current data available on the effects of antiglaucoma drugs and systemic medications on ocular blood flow. We performed a literature search in November 2002, which consisted of a textword search in MEDLINE for the years 1968-2002. The results of this review suggest that there is a severe lack of well-designed long-term studies investigating the effects of antiglaucoma and systemic medications on ocular blood flow in glaucomatous patients. However, among the 136 articles dealing with the effect of antiglaucoma drugs on ocular blood flow, only 36 (26.5%) investigated the effects of medications on glaucoma patients. Among these 36 articles, only 3 (8.3%) were long-term studies, and only 16 (44.4%) were double-masked, randomized, prospective trials. Among the 33 articles describing the effects of systemic medications on ocular blood flow, only 11 (33.3%) investigated glaucoma patients, of which only one (9.1%) was a double-masked, randomized, prospective trial. Based on this preliminary data, we would intimate that few antiglaucoma medications have the potential to directly improve ocular blood flow. Unoprostone appears to have a reproducible antiendothelin-1 effect, betaxolol may exert a calcium-channel blocker action, apraclonidine consistently leads to anterior segment vasoconstriction, and carbonic anhydrase inhibitors seem to accelerate the retinal circulation. Longitudinal, prospective, randomized trials are needed to investigate the effects of vasoactive substances with no hypotensive effect on the progression of glaucoma.

The impact of ocular blood flow in glaucoma.

Two principal theories for the pathogenesis of glaucomatous optic neuropathy (GON) have been described--a mechanical and a vascular theory. Both have been defended by various research groups over the past 150 years. According to the mechanical theory, increased intraocular pressure (IOP) causes stretching of the laminar beams and damage to retinal ganglion cell axons. The vascular theory of glaucoma considers GON as a consequence of insufficient blood supply due to either increased IOP or other risk factors reducing ocular blood flow (OBF). A number of conditions such as congenital glaucoma, angle-closure glaucoma or secondary glaucomas clearly show that increased IOP is sufficient to lead to GON. However, a number of observations such as the existence of normal-tension glaucoma cannot be satisfactorily explained by a pressure theory alone. Indeed, the vast majority of published studies dealing with blood flow report a reduced ocular perfusion in glaucoma patients compared with normal subjects. The fact that the reduction of OBF often precedes the damage and blood flow can also be reduced in other parts of the body of glaucoma patients, indicate that the hemodynamic alterations may at least partially be primary. The major cause of this reduction is not atherosclerosis, but rather a vascular dysregulation, leading to both low perfusion pressure and insufficient autoregulation. This in turn may lead to unstable ocular perfusion and thereby to ischemia and reperfusion damage. This review discusses the potential role of OBF in glaucoma and how a disturbance of OBF could increase the optic nerve's sensitivity to IOP.

Computation of the change in length of a braided device when deployed in realistic vessel models.

PURPOSE: An important issue in the deployment of braided stents, such as flow diverters, is the change in length, also known as foreshortening, underwent by the device when is released from the catheter into a blood vessel. The position of the distal end is controlled by the interventionist, but knowing a priori the position of the proximal end of the device is not trivial. In this work, we assess and validate a novel computer method to predict the length that a braided stent will adopt inside a silicon model of an anatomically accurate vessel. METHODS: Three-dimensional rotational angiography images of aneurysmatic patients were used to generate surface models of the vessels (3D meshes) and then create accurate silicon models from them. A braided stent was deployed into each silicon model to measure its length. The same stents deployed on the silicon models were virtually deployed on the 3D meshes using the method being evaluated. RESULTS: The method was applied to five stent placements on three different silicon models. The length adopted by the real braided device in the silicon models varies between 15 and 30% from the stent length specified by the manufacturer. The final length predicted by the method was within the estimated error of the measured real stent length. CONCLUSIONS: The method provides, in a few seconds, the length of a braided stent deployed inside a vessel, showing an accurate estimation of the final length for the cases studied. This technique could provide useful information for planning the intervention and improve endovascular treatment of intracranial aneurysms in the future.