In-depth analysis of hyaline fibromatosis syndrome frameshift mutations at the same site reveal the necessity of personalized therapy.

Hyaline fibromatosis syndrome is an autosomal recessive disease caused by mutations in ANTXR2, a gene involved in extracellular matrix homeostasis. Sixty percent of patients carry frameshift mutations at a mutational hotspot in exon 13. We show in patient cells that these mutations lead to low ANTXR2 mRNA and undetectable protein levels. Ectopic expression of the proteins encoded by the mutated genes reveals that a two base insertion leads to the synthesis of a protein that is rapidly targeted to the ER-associated degradation pathway due to the modified structure of the cytosolic tail, which instead of being hydrophilic and highly disordered as in wild type ANTXR2, is folded and exposes hydrophobic patches. In contrast, one base insertion leads to a truncated protein that properly localizes to the plasma membrane and retains partial function. We next show that targeting the nonsense mediated mRNA decay pathway in patient cells leads to a rescue of ANTXR2 protein in patients carrying one base insertion but not in those carrying two base insertions. This study highlights the importance of in-depth analysis of the molecular consequences of specific patient mutations, which even when they occur at the same site can have drastically different consequences.

Bilateral sequential nonarteritic anterior ischemic optic neuropathy: a comparison of visual outcomes in fellow eyes using quantitative analysis of goldmann visual fields.

OBJECTIVE To better define the concordance of visual loss in patients with nonarteritic anterior ischemic optic neuropathy (NAION). METHODS The medical records of 86 patients with bilateral sequential NAION were reviewed retrospectively, and visual function was assessed using visual acuity, Goldmann visual fields, color vision, and relative afferent papillary defect. A quantitative total visual field score and score per quadrant were analyzed for each eye using the numerical Goldmann visual field scoring method. RESULTS Outcome measures were visual acuity, visual field, color vision, and relative afferent papillary defect. A statistically significant correlation was found between fellow eyes for multiple parameters, including logMAR visual acuity (P = .01), global visual field (P < .001), superior visual field (P < .001), and inferior visual field (P < .001). The mean deviation of total (P < .001) and pattern (P < .001) deviation analyses was significantly less between fellow eyes than between first and second eyes of different patients. CONCLUSIONS Visual function between fellow eyes showed a fair to moderate correlation that was statistically significant. The pattern of vision loss was also more similar in fellow eyes than between eyes of different patients. These results may help allow better prediction of visual outcome for the second eye in patients with NAION.

Lack of association between the protein tyrosine phosphatase non-receptor type 22 R263Q and R620W functional genetic variants and endogenous non-anterior uveitis.

OBJECTIVE Endogenous uveitis is a major cause of visual loss mediated by the immune system. The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes a lymphoid-specific phosphatase that plays a key role in T-cell receptor (TCR) signaling. Two independent functional missense single nucleotide polymorphisms (SNPs) located within the PTPN22 gene (R263Q and R620W) have been associated with different autoimmune disorders. We aimed to analyze for the first time the influence of these PTPN22 genetic variants on endogenous non-anterior uveitis susceptibility. METHODS We performed a case-control study of 217 patients with endogenous non-anterior uveitis and 718 healthy controls from a Spanish population. The PTPN22 polymorphisms (rs33996649 and rs2476601) were genotyped using TaqMan allelic discrimination assays. The allele, genotype, carriers, and allelic combination frequencies were compared between cases and controls with χ(2) analysis or Fisher's exact test. RESULTS Our results showed no influence of the studied SNPs in the global susceptibility analysis (rs33996649: allelic P- value=0.92, odds ratio=0.97, 95% confidence interval=0.54-1.75; rs2476601: allelic P- value=0.86, odds ratio=1.04, 95% confidence interval=0.68-1.59). Similarly, the allelic combination analysis did not provide additional information. CONCLUSIONS Our results suggest that the studied polymorphisms of the PTPN22 gene do not play an important role in the pathophysiology of endogenous non-anterior uveitis.

Pseudoaneurisma de la arteria geniculada descendiente medial tras reconstrucción astroscópica del ligamento cruzado anterior

Today, reconstructive arthroscopic knee surgery of the anterior cruciate ligament is a widely used technique. In addition to the usual complications of arthroscopic techniques, the extraction of the piece must be taken into consideration, with vascular complications being the rarest and most serious of them all. We present the case of a patient who suffered an arterial pseudoaneurysm during this procedure. The management and treatment are discussed and the current bibliography reviewed.

No evidence of association between common autoimmunity STAT4 and IL23R risk polymorphisms and non-anterior uveitis.

OBJECTIVE: STAT4 and IL23R loci represent common susceptibility genetic factors in autoimmunity. We decided to investigate for the first time the possible role of different STAT4/IL23R autoimmune disease-associated polymorphisms on the susceptibility to develop non-anterior uveitis and its main clinical phenotypes. METHODS Four functional polymorphisms (rs3821236, rs7574865, rs7574070, and rs897200) located within STAT4 gene as well as three independent polymorphisms (rs7517847, rs11209026, and rs1495965) located within IL23R were genotyped using TaqMan® allelic discrimination in a total of 206 patients with non-anterior uveitis and 1553 healthy controls from Spain. RESULTS No statistically significant differences were found when allele and genotype distributions were compared between non-anterior uveitis patients and controls for any STAT4 (rs3821236: P=0.39, OR=1.12, CI 95%=0.87-1.43; rs7574865: P=0.59 OR=1.07, CI 95%=0.84-1.37; rs7574070: P=0.26, OR=0.89, CI 95%=0.72-1.10; rs897200: P=0.22, OR=0.88, CI 95%=0.71-1.08;) or IL23R polymorphisms (rs7517847: P=0.49, OR=1.08, CI 95%=0.87-1.33; rs11209026: P=0.26, OR=0.78, CI 95%=0.51-1.21; rs1495965: P=0.51, OR=0.93, CI 95%=0.76-1.15). CONCLUSION Our results do not support a relevant role, similar to that described for other autoimmune diseases, of IL23R and STAT4 polymorphisms in the non-anterior uveitis genetic predisposition. Further studies are needed to discard a possible weak effect of the studied variant.

Two functional variants of IRF5 influence the development of macular edema in patients with non-anterior uveitis.

OBJECTIVE Interferon (IFN) signaling plays a crucial role in autoimmunity. Genetic variation in interferon regulatory factor 5 (IRF5), a major regulator of the type I interferon induction, has been associated with risk of developing several autoimmune diseases. In the current study we aimed to evaluate whether three sets of correlated IRF5 genetic variants, independently associated with SLE and with different functional roles, are involved in uveitis susceptibility and its clinical subphenotypes. METHODS Three IRF5 polymorphisms, rs2004640, rs2070197 and rs10954213, representative of each group, were genotyped using TaqMan® allelic discrimination assays in a total of 263 non-anterior uveitis patients and 724 healthy controls of Spanish origin. RESULTS A clear association between two of the three analyzed genetic variants, rs2004640 and rs10954213, and the absence of macular edema was observed in the case/control analysis (P FDR =5.07E-03, OR=1.48, CI 95%=1.14-1.92 and P FDR =3.37E-03, OR=1.54, CI 95%=1.19-2.01, respectively). Consistently, the subphenotype analysis accordingly with the presence/absence of this clinical condition also reached statistical significance (rs2004640: P=0.037, OR=0.69, CI 95%=0.48-0.98; rs10954213: P=0.030, OR=0.67, CI 95%=0.47-0.96), thus suggesting that both IRF5 genetic variants are specifically associated with the lack of macular edema in uveitis patients. CONCLUSION Our results clearly showed for the first time that two functional genetic variants of IRF5 may play a role in the development of macular edema in non-anterior uveitis patients. Identifying genetic markers for macular edema could lead to the possibility of developing novel treatments or preventive therapies.

Evaluation of the IL2/IL21, IL2RA and IL2RB genetic variants influence on the endogenous non-anterior uveitis genetic predisposition.

BACKGROUND Recently, different genetic variants located within the IL2/IL21 genetic region as well as within both IL2RA and IL2RB loci have been associated to multiple autoimmune disorders. We aimed to investigate for the first time the potential influence of the IL2/IL21, IL2RA and IL2RB most associated polymorphisms with autoimmunity on the endogenous non-anterior uveitis genetic predisposition. METHODS A total of 196 patients with endogenous non-anterior uveitis and 760 healthy controls, all of them from Caucasian population, were included in the current study. The IL2/IL21 (rs2069762, rs6822844 and rs907715), IL2RA (2104286, rs11594656 and rs12722495) and IL2RB (rs743777) genetic variants were genotyped using TaqMan® allelic discrimination assays. RESULTS A statistically significant difference was found for the rs6822844 (IL2/IL21 region) minor allele frequency in the group of uveitis patients compared with controls (P(-value)=0.02, OR=0.64 CI 95%=0.43-0.94) although the significance was lost after multiple testing correction. Furthermore, no evidence of association with uveitis was detected for the analyzed genetic variants of the IL2RA or IL2RB loci. CONCLUSION Our results indicate that analyzed IL2/IL21, IL2RA and IL2RB polymorphisms do not seem to play a significant role on the non-anterior uveitis genetic predisposition although further studies are needed in order to clear up the influence of these loci on the non-anterior uveitis susceptibility.

Historia natural de la oclusión aguda de gran arteria de la circulación cerebral anterior: serie clínica de 120 pacientes.

: Para estudiar la historia natural del ictus isquémico por oclusión de gran vaso de la circulación anterior se seleccionó una muestra prospectiva de pacientes con ictus agudo que no recibieron terapias de reperfusión en los que se confirmó una oclusión de gran vaso de la circulación anterior mediante Dúplex transcraneal. El 74% de los pacientes tuvo mal pronóstico. Los pacientes con oclusión de la a.carótida interna terminal y de la a.cerebral media proximal tuvieron peor pronóstico funcional y mayor porcentaje de mortalidad a los tres meses que los pacientes con oclusión de la a.cerebral media distal.

From Translation to Rewriting : the Interplay of Text and Image in The Fairy Tales of Charles Perrault and The Bloody Chamber and Other Stories

Abstract :This article examines the interplay of text and image in The Fairy Tales of Charles Perrault (1977), translated by Angela Carter and illustrated by Martin Ware, as a form of intersemiotic dialogue that sheds new light on Carter's work. It argues that Ware's highly original artwork based on the translation not only calls into question the association of fairy tales with children's literature (which still characterizes Carter's translation), but also captures an essential if heretofore neglected aspect of Carter's creative process, namely the dynamics between translating, illustrating and rewriting classic tales. Several elements from Ware's illustrations are indeed taken up and elaborated on in The Bloody Chamber and Other Stories (1979), the collection of "stories about fairy stories" that made Carter famous. These include visual details and strategies that she transposed to the realm of writing, giving rise to reflections on the relation between visuality and textuality.RésuméCet article considère l'interaction du texte et de l'image dans les contes de Perrault traduits par Angela Carter et illustrés par Martin Ware (The Fairy Tales of Charles Perrault, 1977) comme une forme de dialogue intersémiotique particulièrement productif. Il démontre que les illustrations originales de Ware ne mettent pas seulement en question l'assimilation des contes à la littérature de jeunesse (qui est encore la perspective adoptée par la traductrice dans ce livre), mais permettent aussi de saisir un aspect essentiel bien que jusque là ignoré du procession de création dans l'oeuvre de Carter, à savoir la dynamique qui lie la traduction, l'illustration et la réécriture des contes classiques. Plusieurs éléments des illustrations de Ware sont ainsi repris et élaborés dans The Bloody Chamber and Other Stories (1979), la collection de "stories about fairy stories" qui rendit Carter célèbre. La transposition de détails et de stratégies visuelles dans l'écriture donnent ainsi l'occasion de réflexions sur les rapports entre la visualité et la textualité.

Identificació de subjectes a partir de l'anàlisi de dades multimodals RGB-Depth

En aquest treball s'explora el camp de la identificació facial de subjectes utilitzant tècniques d'anàlisi multimodal. Això és utilitzant imatges RGB i imatges de profunditat (3D) amb l'objecte de validar les diverses tècniques emprades en el reconeixement facial i aprofundir en sistemes que incorporen informació tridimensional als algorismes de detecció i identificació facial.

Contribution de la biomicroscopie ultrasonore au traitement conservateur des mélanomes de l'uvée antérieure [Contribution of ultrasound biomicroscopy to conservative treatment of anterior uveal melanoma]

BACKGROUND: Ultrasound Biomicroscopy (UBM) is a new ophthalmological imaging technique essentially designed for the study of the anterior eye segment. Over the last 10 months, we've evaluated its contribution to the conservative treatment of anterior uveal melanoma's by means of accelerated proton beam irradiation. MATERIAL: Using UBM, we have examined 55 cases of uveal melanoma's, whose anterior border was situated at 6 mm or less from the limbus and that were consequently treated by proton beam irradiation. RESULTS: The presumed tumoral origin was the ciliary body's pars plicata in 13 cases and the pars plana or the choroid in 42 cases, 17 of which presented a tumoral invasion of the pars plicata. A pars plana detachment anterior to or surrounding the anterior tumoral border, was present in 22 cases. The height of the tumor could only be measured by UBM if it was less than 2.5 mm. Information gathered using UBM have contributed to an improvement of the therapy plan in 32 cases. CONCLUSION: Because of the strong attenuation of the high frequency ultrasound signal, UBM can only be used for the examination of intra-ocular structures situated in direct neighbourhood to the global wall. Despite this technical limitation, ist contribution to the planning of the conservative treatment of anterior uveal melanoma's by proton beam irradiation has appeared to be considerable.

Differences Between Posterior and Anterior Acute Ischaemic Circulation Strokes in 1449 Consecutive Patients

Background: The current data comparing posterior and anterior circulation strokes with regards to clinical, etiological, radiological and outcome factors are conflicting. We searched for distinguishing features between both territories in 1'449 consecutive acute ischemic stroke patients. Methods: All consecutive patients with acute ischemic stroke admitted to a single stroke unit from January 2003 to July 2008 were included in a prospective registry. Territory of acute stroke was determined by a combination of neuroimaging (MRI and / CT / CTP) and clinical symptoms and signs. Patients with uncertain localisation and patients with simultaneous strokes in the anterior and posterior circulation were excluded from this analysis. Results: Of a total of 1728 patients, 466 (17.0%) had had posterior, 983 (56.8%) anterior, 136 (7.9%) unknown territory, and 43 (2.5%) simultaneous posterior and anterior territory stroke. Of 39 variables that were compared, 29 differed significantly in univariate analysis, including less dependency (OR_0.50) and mortality (OR_0.56) at 3 months in posterior stroke. In multivariate analysis (see table), male gender, lacunar mechanism, arterial dissection and endovascular recanalisation were more frequent in posterior stroke, and admission NIHSS and IV-thrombolysis rate were lower. Significant acute arterial pathology (_50% stenosis) was less frequently found on acute imaging in posterior stroke (OR_0.33). Of 633 patients with significant arterial pathology, it was more frequently present intracranially in posterior (OR_1.62) and extracranially in anterior stroke (OR _ 0.87). In 610 patients where recanalisation was assessed at 24 hours, intracranial (OR_0.26), extracranial (OR_0.25) and overall recanalisation (OR_0.34) was less frequent in the posterior circulation. Conclusions: Acute posterior strokes are less severe and recover better, despite lower IV thrombolysis and recanalisation rates. They are more frequently due to lacunes and dissections and have less arterial pathology burden then anterior circulation strokes.