SlS5H silencing reveals specific pathogen-triggered salicylic acid metabolism in tomato.

BACKGROUND: Salicylic acid (SA) is a major plant hormone that mediates the defence pathway against pathogens. SA accumulates in highly variable amounts depending on the plant-pathogen system, and several enzyme activities participate in the restoration of its levels. Gentisic acid (GA) is the product of the 5-hydroxylation of SA, which is catalysed by S5H, an enzyme activity regarded as a major player in SA homeostasis. GA accumulates at high levels in tomato plants infected by Citrus Exocortis Viroid (CEVd), and to a lesser extend upon Pseudomonas syringae DC3000 pv. tomato (Pst) infection. RESULTS: We have studied the induction of tomato SlS5H gene by different pathogens, and its expression correlates with the accumulation of GA. Transient over-expression of SlS5H in Nicotiana benthamiana confirmed that SA is processed by SlS5H in vivo. SlS5H-silenced tomato plants were generated, displaying a smaller size and early senescence, together with hypersusceptibility to the necrotrophic fungus Botrytis cinerea. In contrast, these transgenic lines exhibited an increased defence response and resistance to both CEVd and Pst infections. Alternative SA processing appears to occur for each specific pathogenic interaction to cope with SA levels. In SlS5H-silenced plants infected with CEVd, glycosylated SA was the most discriminant metabolite found. Instead, in Pst-infected transgenic plants, SA appeared to be rerouted to other phenolics such as feruloyldopamine, feruloylquinic acid, feruloylgalactarate and 2-hydroxyglutarate. CONCLUSION: Using SlS5H-silenced plants as a tool to unbalance SA levels, we have studied the re-routing of SA upon CEVd and Pst infections and found that, despite the common origin and role for SA in plant pathogenesis, there appear to be different pathogen-specific, alternate homeostasis pathways.

Prospective assessment of aneurysmal rupture risk scores in patients with subarachnoid hemorrhage: a multicentric cohort.

PURPOSE: The natural evolution of unruptured intracranial aneurysms (UIA) is indeed difficult to predict at the individual level. OBJECTIVE: In a large prospective multicentric European cohort, we aimed to evaluate whether the PHASES, UCAS, and ELPASS scores in patients with aneurysmal subarachnoid hemorrhage would have predicted a high risk of aneurysmal rupture or growth. METHODS: Academic centers treating patients with intracranial aneurysms were invited to prospectively collect de-identified data from all patients admitted at their institution for a subarachnoid hemorrhage-related to intracranial aneurysmal rupture between January 1 and March 31, 2021 through a trainee-led research collaborative network. Each responding center was provided with an electronic case record form (CRF) which collected all the elements of the PHASES, ELAPSS, and UCAS scores. RESULTS: A total of 319 patients with aneurysmal subarachnoid hemorrhage were included at 17 centers during a 3-month period. One hundred eighty-three aneurysms (57%) were less than 7 mm. The majority of aneurysms were located on the anterior communicating artery (n = 131, 41%). One hundred eighty-four patients (57%), 103 patients (32%), and 58 (18%) were classified as having a low risk of rupture or growth, according to the PHASES, UCAS, and ELAPSS scores, respectively. CONCLUSION: In a prospective study of European patients with aneurysmal subarachnoid hemorrhage, we showed that 3 common risk-assessment tools designed for patients with unruptured intracranial aneurysms would have not identified most patients to be at high or intermediate risk for rupture, questioning their use for decision-making in the setting of unruptured aneurysms.

Reward and fictive prediction error signals in ventral striatum: asymmetry between factual and counterfactual processing.

Reward prediction error, the difference between the expected and obtained reward, is known to act as a reinforcement learning neural signal. In the current study, we propose a model fitting approach that combines behavioral and neural data to fit computational models of reinforcement learning. Briefly, we penalized subject-specific fitted parameters that moved away too far from the group median, except when that deviation led to an improvement in the model's fit to neural responses. By means of a probabilistic monetary learning task and fMRI, we compared our approach with standard model fitting methods. Q-learning outperformed actor-critic at both behavioral and neural level, although the inclusion of neuroimaging data into model fitting improved the fit of actor-critic models. We observed both action-value and state-value prediction error signals in the striatum, while standard model fitting approaches failed to capture state-value signals. Finally, left ventral striatum correlated with reward prediction error while right ventral striatum with fictive prediction error, suggesting a functional hemispheric asymmetry regarding prediction-error driven learning.

[Long term outcomes of botulinum toxin injections in infantile esotropia]. / Évaluation a long terme de l'éfficacité de la toxine botulique dans l'ésotropie precoce.

PURPOSE: To evaluate long terms outcomes of botulinum toxin in infantile esotropia by measuring the amount of microtropia 24 months after injection. Secondary purpose was to identify predictive factors of microtropia. METHODS: A retrospective, single-center study was performed at the university medical center in Bordeaux between 2001 and 2018, including all patients with infantile esotropia greater than 20 D. All patients received 5 or 7,5 IU of botulinum toxin A in each medial rectus, once or twice depending on the angle of deviation after the first injection and after wearing full optical correction at least two months. We noted the angle at 1, 6, 12 and 24 months, the occurrence of any complications and the need for later strabismus surgery. The primary endpoint was the achievement of a microtropia less than 8 diopters (D) at 24 months post-injection. We evaluated the predictive factors for microtropia with a Fischer's test. RESULTS: We included 30 patients with esotropia greater than 20 D. The mean follow-up after injection was 48 months ±30. The mean age was 16.24 months (7-29 months) with a female predominance in the population (SR=0.43). The mean pre-injection deviation was 41.25±12.17 D. The majority of patients were mildly (40%) or moderately (40%) hyperopic. At 24 months, 46.7% microtropias were obtained (95% CI: 28.9%-64.5%). The change in mean angle at 1, 6, 12 and 24 months post-injection was -8.57±25.21 D; 14.48±13.40 D; 18.38±12.07 D and 21.23±14.97 D, respectively. No factors were predictive of microtropia. Of the 30 children, 3 had transient ptosis requiring strips and 12 showed an exotropia at 1 month. All complications were self-limited and without consequences. 3 children had a second injection of botulinum toxin, which in 2/3 of the cases resulted in a long-lasting microtropia. 26.7% (n=8) of the children underwent secondary surgery. Obtaining a microtropia 24 months after injection statistically significantly reduced the need for secondary strabismus surgery: 92.9% P=0.039% CI 95% (0.002; 1.0606). CONCLUSION: Botulinum toxin appears to be a less invasive and more conservative alternative to surgery in children with infantile esotropia. In 46.7% of cases, microtropia is achieved. An improvement was noted in 90% (n=27) of the children with a reduction of half (21.23 D) of the mean post-injection angle at 24 months. When effective, it significantly reduces the need for secondary surgery.

[Cataract surgery in children with non-infectious uveitis: Review of current practices in France]. / Chirurgie de la cataracte uvéitique non infectieuse de l'enfant : bilan des pratiques actuelles en France.

PURPOSE: To evaluate the medical-surgical management of cataract surgery in children with chronic uveitis in various French pediatric ophthalmology centers. MATERIALS AND METHODS: Two-part study: first, a descriptive observational segment on the evaluation of French practices. A questionnaire was sent to the various pediatric ophthalmologists in France. A second retrospective chart review, including children with non-infectious chronic uveitis who had cataract surgery in the pediatric ophthalmology department of Bordeaux University Hospital from 2008 to 2017. RESULTS: Twenty-one ophthalmologists responded to the questionnaire. Only 23.8% systematically initiated immunosuppressive drugs (aside from corticosteroids) before surgery. A total of 88.2% prescribed oral corticosteroid treatment preoperatively. Eleven surgeons administered intravenous corticosteroid boluses during the surgery, and primary lens implantation is the most common method used in 95.2%. A total of 76.2% initiated oral steroid therapy after surgery. Postoperatively, all surgeons started local therapy with high-dose corticosteroids. At one year, 100% achieved improvement of visual acuity greater than or equal to 2 lines. On our service, 10 eyes (7 children) underwent cataract surgery. Seven were treated with systemic immunosuppressive drugs (aside from corticosteroids) and 80% of cases received oral corticosteroid therapy a few days before surgery. An intravenous corticosteroid bolus was administered preoperatively in 8 cases, and primary lens implantation was performed in 100% of cases. Postoperatively, 5 children received oral corticosteroid treatment. All were treated with local high dose steroids. At one year, the mean best-corrected visual acuity was 0.18 LogMar (0-0.7, SD: 0.25). CONCLUSION: When performed with an aggressive anti-inflammatory protocol, cataract surgery leads to a good visual outcome in selected children with chronic uveitis.

Screening for retinopathy of prematurity by telemedicine in a tertiary level neonatal intensive care unit in France: Review of a six-year period.

PURPOSE: To analyze the prevalence and risk factors for retinopathy of prematurity (ROP) and severe (treatment-requiring) ROP. METHODS: A retrospective study was conducted in a level III neonatal unit in Bordeaux, France, from 2009 to 2015. Four hundred and nineteen preterm infants who were screened for ROP exclusively by RetCam were included. RESULTS: ROP of any degree was diagnosed in 27.68% of infants. Stages 1, 2, 3 and 4 ROP was found in 44%, 46%, 9% and 1% of subjects, respectively. No stage 5 ROP was observed. 28/419 infants (6.6%) were treated exclusively with laser photocoagulation. No intravitreal anti-VEGF injections or surgical treatments were performed. No infants born at>31 weeks or with BW>1110g required ROP treatment. On multivariate analysis, risk factors for ROP development were low birth weight, low gestational age at birth, high duration of invasive mechanical ventilation, shock or use of vasopressors. On multivariate analysis, risk factors for severe, treatment-requiring ROP were male gender, gestational age≤27 weeks and Apgar score at 5minutes≤7. CONCLUSION: In our 6-year series, ROP was successfully identified on screening exclusively by telemedicine, and no surgical treatment was required. This study identifies known ROP risk factors, but the Apgar score at 5minutes as a risk factor for severe ROP requires further studies in order to be confirmed.

[Evaluation of corneal biomechanical properties in glaucoma and control patients by dynamic Scheimpflug corneal imaging technology]. / Évaluation des propriétés biomécaniques de la cornée de patients glaucomateux et témoins par la technologie dynamique Scheimpflug de visualisation cornéenne.

PURPOSE: To compare corneal biomechanical properties measured with Corvis Scheimpflug technology (Corvis ST) between a group of patients with chronic open-angle glaucoma and a group of control patients. DESIGN: Prospective observational case-control study. METHODS: This study enrolled 56 right eyes of 56 patients (G1 [chronic open-angle glaucoma] n=37/G2 [control] n=19). Each patient underwent measurement of corneal biomechanical properties by dynamic Scheimpflug (Corvis ST) camera and the Ocular Response Analyser (ORA), then a measurement of intraocular pressure (IOP) by Goldmann applanation tonometry (GAT) and measurement of central corneal thickness (CCT) by optical coherence tomography during the same visit, by a single clinician. The parameters determined by Corvis ST are: Corvis IOP (IOP Corvis ST), the corneal deformation amplitude (CDA), corneal velocity, the time at highest concavity (TIME CONCAV), the lengths of applanation and their corresponding applanation time. Those studied by ORA are: compensated IOP (IOPcc), non-compensated IOL (IOPg), corneal hysteresis (CH) and corneal resistance factor (CRF). RESULTS: IOP measured on all patients by Corvis ST was positively correlated to GAT (Spearman r=0.569, P<0.001) and PIOcc (Spearman r=0.531, P<0.001). After adjusting for age effect, CCT and GAT, the CDA was significantly lower in G1 than in G2, respectively 1.10 ± 0.12 mm and 1.15 ± 0.10mm (P<0.001). The TIME CONCAV is significantly shorter in G1 than in G2, respectively 16.88 ± 0.63 ms and 17.11 ± 0.29 ms, P=0.029. CH was significantly lower in G1 (G1: 9.58 ± 1.94 than G2: 10.89 ± 2.16, P=0.026). CONCLUSIONS: This study showed differences in corneal biomechanical properties between glaucoma and control patients. The cornea of glaucoma patients appears less deformable.