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Ureases are moonlighting proteins displaying non-catalytic properties, including platelet activation, antifungal and entomotoxic effects. The structure-activity mapping of these properties is poorly developed. Proteus mirabilis urease (PMU) consists of three subunits, PmUreα, PmUreβ and PmUreγ, in an (αβγ)3 organization. In order to study the structure-activity relationships of PMU we obtained the recombinant subunits of this urease and evaluated their biological activities. The holo-urease promoted platelet aggregation, and toxicity in fungal and insect models. Similar to Jaburetox, a plant urease-derived polypeptide, PmUreβ showed the highest toxicity against yeasts and insects, and activated human platelets. PmUreγ and PmUreα presented insecticidal action upon injection. In addition, only PmUreγ and PmUreβ promote hemocytes aggregation. Bioinformatics analyses revealed gene/segment duplication and evolutionary divergence among ureases. Our findings show that PmUreβ (and probably its counterparts in other ureases) carries most of the non-enzymatic activities of these proteins.

PURPOSE. Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, excessive bleeding, and often additional symptoms. Variants in 10 different genes have been involved in HPS. However, some patients lack variants in these genes. We aimed to identify new genes involved in non-syndromic or syndromic forms of albinism. METHODS. 230 albinism patients lacking a molecular diagnosis of albinism were screened for pathogenic variants in candidate genes with known links to pigmentation or HPS pathophysiology. RESULTS. We identified two unrelated patients with distinct homozygous variants of the BLOC1S5 gene. Patients had mild oculocutaneous albinism, moderate bleeding diathesis, platelet aggregation deficit and a dramatically decreased number of platelet dense granules, all signs compatible with HPS. Functional tests performed on platelets of one patient displayed an absence of the obligate multi-subunit complex BLOC-1, showing that the mutation disrupts BLOC1S5 function and impairs BLOC-1 assembly. Expression of the patient-derived BLOC1S5 deletion in non-pigmented murine Bloc1s5(−/−) melan-mu melanocytes failed to rescue pigmentation, the assembly of a functional BLOC-1 complex, and melanosome cargo trafficking, unlike the wild-type allele. CONCLUSION. Mutation of BLOC1S5 is disease-causing, and we propose that BLOC1S5 is the gene for a new form of Hermansky-Pudlak syndrome, HPS-11.

Background Surgeries for idiopathic uveitis and juvenile idiopathic arthritis-associated uveitis in children are complex because of the high risk of inflammatory postoperative complications. There is no consensus about treatment adaptation during the perioperative period. The objectives of this study are to report the therapeutic changes made in France and to determine whether maintaining or stopping immunosuppressive therapies is associated with an increased risk of surgical site infection or an increased risk of uveitis or arthritis flare-up. Methods We conducted a retrospective cohort study between January 1, 2006 and December 31, 2018 in six large University Hospitals in France. Inclusion criteria were chronic idiopathic uveitis or chronic uveitis associated with juvenile idiopathic arthritis under immunosuppressive therapies at the time of the surgical procedure, operated before the age of 16. Data on perioperative treatments, inflammatory relapses and post-operative infections were collected. Results A total of 76 surgeries (42% cataract surgeries, 30% glaucoma surgeries and 16% posterior capsule opacification surgeries) were performed on 37 children. Adaptation protocols were different in the six hospitals. Immunosuppressive therapies were discontinued in five cases (7%) before surgery. All the children in the discontinuation group had an inflammatory relapse within 3 months after surgery compared to only 25% in the other group. There were no postoperative infections. Conclusions The results of this study show varying practices between centres. The benefit-risk balance seems to favour maintaining immunosuppressive therapies during surgery. Further studies are needed to determine the optimal perioperative treatments required to limit post-operative inflammatory relapses.

Infection by Proteus mirabilis causes urinary stones and catheter incrustation due to ammonia formed by urease (PMU), one of its virulence factors. Non-enzymatic properties, such as pro-inflammatory and neurotoxic activities, were previously reported for distinct ureases, including that of the gastric pathogen Helicobacter pylori. Here, PMU was assayed on isolated cells to evaluate its non-enzymatic properties. Purified PMU (nanomolar range) was tested in human (platelets, HEK293 and SH-SY5Y) cells, and in murine microglia (BV-2). PMU promoted platelet aggregation. It did not affect cellular viability and no ammonia was detected in the cultures’ supernatants. PMU-treated HEK293 cells acquired a pro-inflammatory phenotype, producing reactive oxygen species (ROS) and cytokines IL-1β and TNF-α. SH-SY5Y cells stimulated with PMU showed high levels of intracellular Ca2+ and ROS production, but unlike BV-2 cells, SH-SY5Y did not synthesize TNF-α and IL-1β. Texas Red-labeled PMU was found in the cytoplasm and in the nucleus of all cell types. Bioinformatic analysis revealed two bipartite nuclear localization sequences in PMU. We have shown that PMU, besides urinary stone formation, can potentially contribute in other ways to pathogenesis. Our data suggest that PMU triggers pro-inflammatory effects and may affect cells beyond the renal system, indicating a possible role in extra-urinary diseases.

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 centerin 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. (c) 2021 Elsevier Masson SAS. All rights reserved.; Objectif: Évaluer l’efficacité à long terme de la toxine botulique dans le traitement de l’ésotropie précoce grâce au pourcentage de microtropie à 24 mois post-injection. L’objectif secondaire était de rechercher les facteurs prédictifs à l’obtention de cette microtropie. Méthodes: Nous avons réalisé une étude rétrospective, monocentrique au Centre Hospitalier universitaire (CHU) de Bordeaux entre 2001 et 2018 en incluant tous les patients ayant une ésotropie précoce. Ces patients ont reçu une injection bilatérale de 5 ou 7,5 unités de toxine botulique à une ou deux reprises en fonction de l’angle après la première injection et port de la correction optique totale. L’ensemble des caractéristiques sociodémographiques et ophtalmologiques ont été recueillis en préopératoire. Nous avons noté l’angle à 1,6,12 et 24 mois ; l’apparition de complications ainsi que la nécessité d’une chirurgie de strabisme à distance. Le critère de jugement principal était l’obtention d’une microtropie inférieure à 8 dioptries (D) à 24 mois post-injection. Nous avons évalué les facteurs prédictifs de la microtropie par un test de Fischer. Résultats: Nous avons inclus 30 patients ayant une ésotropie supérieure à 20 D avec un délai moyen de suivi post-injection de 48 mois ± 30. L’âge moyen était de 16,24 mois (7–29 mois) avec une prédominance féminine dans la population (sex ratio SR = 0,43). L’angle moyen pré-injection était de 41,25 ± 12,17 D. Il y avait une majorité d’hypermétropes légers (40 %) et modérés (40 %). À 24 mois, on obtenait 46,7 % de microtropies (intervalle de confiance : IC 95 % : 28,9 %–64,5 %). L’évolution de l’angle moyen à 1,6,12 et 24 mois post-injection était respectivement de −8,57 ± 25,21 D ; 14,48 ± 13,40 D ; 18,38 ± 12,07 D et 21,23 ± 14,97 D. Aucun facteur n’était prédictif de l’obtention d’une microtropie. Parmi les 30 enfants, 3 ont eu des ptôsis transitoires nécessitant la pose de strips et 12 ont présenté une exotropie à 1 mois. Toutes les complications étaient spontanément résolutives et sans conséquences. 3 enfants ont eu une seconde injection de toxine botulique permettant dans 2/3 des cas l’obtention d’une microtropie durable. 26,7 % (n = 8) des enfants ont été opérés secondairement ; l’obtention d’une microtropie à 24 mois diminuait de façon statistiquement significative les chirurgies secondaires du strabisme : p = 0,039 % IC 95 % (0,002 ; 1,0606). Conclusion: La toxine botulique semble être une alternative moins invasive et plus conservatrice que la chirurgie chez les enfants présentant une ésotropie précoce. Elle permet l’obtention d’une microtropie dans 46,7 % des cas. On notait une amélioration chez 90 % (n = 27) des enfants avec une réduction de la moitié (21,23 D) de l’angle moyen post-injection à 24 mois. Lorsqu’elle est efficace elle réduit significativement les chirurgies secondaires.

Hermansky-Pudlak syndrome (HPS) is a rare form of syndromic oculocutaneous albinism caused by disorders in lysosome-related organelles. Ten genes are associated with different forms of HPS. HPS type 9 (HPS-9) is caused by biallelic variants of BLOC1S6. To date, only three patients with HPS-9 have been reported. We described one patient presenting with ocular features of albinism. Genetic analysis revealed two compound heterozygous variants in the BLOC1S6 gene. Extended hematological studies confirmed the platelet storage pool disease with absence of dense granules and abnormal platelet aggregation. By reviewing the previous published cases we confirm the phenotype of HPS-9 patients. This patient is the only one described with dextrocardia and abnormal psychomotor development.

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) do not have a stable 3D structure but still have important biological activities. Jaburetox is a recombinant peptide derived from the jack bean (Canavalia ensiformis) urease and presents entomotoxic and antimicrobial actions. The structure of Jaburetox was elucidated using nuclear magnetic resonance which reveals it is an IDP with small amounts of secondary structure. Different approaches have demonstrated that Jaburetox acquires certain folding upon interaction with lipid membranes, a characteristic commonly found in other IDPs and usually important for their biological functions. Soyuretox, a recombinant peptide derived from the soybean (Glycine max) ubiquitous urease and homologous to Jaburetox, was also characterized for its biological activities and structural properties. Soyuretox is also an IDP, presenting more secondary structure in comparison with Jaburetox and similar entomotoxic and fungitoxic effects. Moreover, Soyuretox was found to be nontoxic to zebra fish, while Jaburetox was innocuous to mice and rats. This profile of toxicity affecting detrimental species without damaging mammals or the environment qualified them to be used in biotechnological applications. Both peptides were employed to develop transgenic crops and these plants were active against insects and nematodes, unveiling their immense potentiality for field applications. Fil: Grahl, Matheus V. Coste. Pontificia Universidade Católica do Rio Grande do Sul; Brasil Fil: Lopes, Fernanda Cortez. Universidade Federal do Rio Grande do Sul; Brasil Fil: Martinelli, Anne H. Souza. Universidade Federal do Rio Grande do Sul; Brasil Fil: Carlini, Célia Regina R. S.. Pontificia Universidade Católica do Rio Grande do Sul; Brasil Fil: Fruttero, Leonardo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina

Background: Pregnant women are susceptible to the novel coronavirus (SARS-CoV-2) and the consequences on the fetus are still uncertain. Here, we present a case of a pregnant woman with subclinical hypothyroidism and PAI-1 4G/5G mutation who was infected with SARS-CoV-2 at the end of the third trimester of pregnancy. Methods: nested PCR were performed to detect the virus, followed by ssDNA sequencing. Results: transplacental transmission of SARS-CoV-2 can cause placental inflammation, ischemia and neonatal viremia, with complications such as preterm labor and damage to the placental barrier in patients with PAI-1 4G/5G mutation. Conclusion: we show the possibility of transplacental transmission of SARS-CoV-2 infection during the last weeks of pregnancy.

Jaburetox is a recombinant peptide derived from one of the Canavalia ensiformis urease isoforms. This peptide induces several toxic effects on insects of different orders, including interference on muscle contractility in cockroaches, modulation of UDP-N-acetylglucosamine pyrophosphorylase (UAP) and nitric oxide synthase (NOS) activities in the central nervous system of triatomines, as well as activation of the immune system in Rhodnius prolixus. When injected, the peptide is lethal for R. prolixus and Triatoma infestans. Here, we evaluated Jaburetox toxicity to Nauphoeta cinerea cockroaches, exploring the effects on the central nervous system through the activities of UAP, NOS, acid phosphatases (ACP), and acetylcholinesterase (AChE). The results indicated that N. cinerea is not susceptible to the lethal effect of the peptide. Moreover, both in vivo and in vitro treatments with Jaburetox inhibited NOS activity, without modifying the protein levels. No alterations on ACP activity were observed. In addition, the enzyme activity of UAP only had its activity affected at 18 hr after injection. The peptide increased the AChE activity, suggesting a mechanism involved in overcoming the toxic effects. In conclusion, our findings indicate that Jaburetox affects the nitrinergic signaling as well as the AChE and UAP activities and establishes N. cinerea as a Jaburetox-resistant model for future comparative studies.

Phylogenetic analysis has demonstrated that the etiologic agent of the 2020 pandemic outbreak is a betacoronavirus named SARS-CoV-2. For public health interventions, a diagnostic test with high sensitivity and specificity is required. The gold standard protocol for diagnosis by the Word Health Organization (WHO) is RT-PCR. To detect low viral loads and perform large-scale screening, a low-cost diagnostic test is necessary. Here, we developed a cost-effective test capable of detecting SARS-CoV-2. We validated an auxiliary protocol for molecular diagnosis with the SYBR Green RT-PCR methodology to successfully screen negative cases of SARS-CoV-2. Our results revealed a set of primers with high specificity and no homology with other viruses from the Coronovideae family or human respiratory tract pathogenic viruses, presenting with complementarity only for rhinoviruses/enteroviruses and Legionella spp. Optimization of the annealing temperature and polymerization time led to a high specificity in the PCR products. We have developed a more affordable and swift methodology for negative SARS-CoV-2 screening. This methodology can be applied on a large scale to soften panic and economic burden through guidance for isolation strategies.

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.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.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).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.

Jaburetox is a recombinant peptide derived from a Canavalia ensiformis urease that presents toxic effects uponseveral species of insects, phytopathogenic fungi and yeasts of medical importance. So far, no toxicity of Jaburetoxto mammals has been shown. Previous reports have identified biochemical targets of this toxic peptide ininsect models, although its mechanism of action is not completely understood. In this work, we aimed to characterizethe effects of Jaburetox in hemolymphatic insect cells. For this purpose, the model insect and Chagas´disease vector Rhodnius prolixus was used. In vivo and in vitro experiments indicated that Jaburetox interacts witha subset of hemocytes and it can be found in various subcellular compartments. In insects injected with Jaburetoxthere was an increase in the gene expression of the enzymes UDP-N-acetylglucosamine pyrophosphorylase(UAP), chitin synthase and nitric oxide synthase (NOS). Nevertheless, the expression of NOS protein, the enzymeactivities of UAP and acid phosphatase (a possible link between UAP and NOS) as well as the phosphorylationstate of proteins remained unchanged upon the in vivo Jaburetox treatment. Nitric oxide (NO) imaging using fluorescentprobes showed that Jaburetox augmented NO production in the hemocyte aggregates when comparedto controls. Even though Jaburetox activated the hemocytes, as demonstrated by wheat germ agglutinin bindingassays, the peptide did not lead to an increase of their phagocytic behavior. Taken together, these findingscontribute to our understanding of toxic effects of Jaburetox, a peptide with biotechnological applications and aprospective tool for rational insect control. Fil: Moyetta, Natalia Rita. Pontificia Universidade Católica do Rio Grande do Sul; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Broll, Valquiria. Universidade Federal do Rio Grande do Sul; Brasil Fil: Perin, Ana Paula A.. Universidade Federal do Rio Grande do Sul; Brasil Fil: Uberti, Augusto F.. Universidade Federal do Rio Grande do Sul; Brasil Fil: Coste Grahl, Matheus V.. Pontificia Universidade Católica do Rio Grande do Sul; Brasil Fil: Staniscuaski, Fernanda. Universidade Federal do Rio Grande do Sul; Brasil Fil: Carlini, Célia Regina R S. Pontificia Universidade Católica do Rio Grande do Sul; Brasil Fil: Fruttero, Leonardo Luis. Pontificia Universidade Católica do Rio Grande do Sul; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina

The communication between the digestive tract and the brain is an important aspect to the regulation and maintenance of its functionality. This communication is made by a network of signals that the brain sends to the gastrointestinal tract and vice-versa through the gut-brain axis. These signals can be direct or indirect, direct is a signal sent by the pathogen to the brain, while indirect is a signal originated from the alterations that the pathogen triggers.

Extracellular traps (ETs) are extracellular nucleic acids associated with cytoplasmic proteins that may aid in the capture and killing of pathogens. To date, only a few insects were shown to display this kind of immune response. Jaburetox, a peptide derived from jack bean urease, showed toxic effects in Rhodnius prolixus, affecting its immune response. The present study aims to evaluate the role of extracellular nucleic acids in R. prolixus' immune response, using Jaburetox as a model entomotoxin. The insects were treated with extracellular nucleic acids and/or Jaburetox, and the cellular and humoral responses were assessed. We also evaluated the release of extracellular nucleic acids induced by toxins, and performed immunocompetence assays using pathogenic bacteria. Our results demonstrated that extracellular nucleic acids can modulate the insect immune responses, either alone or associated with the toxin. Although RNA and DNA induced a cellular immune response, only DNA was able to neutralize the Jaburetox-induced aggregation of hemocytes. Likewise, the activation of the humoral response was different for RNA and DNA. Nevertheless, it was observed that both, extracellular DNA and RNA, immunocompensated the Jaburetox effects on insect defenses upon the challenge of a pathogenic bacterium. The toxin was not able to alter cellular viability, in spite of inducing an increase in the reactive species of oxygen formation. In conclusion, we have demonstrated a protective role for extracellular nucleic acids in R. prolixus´ immune response to toxins and pathogenic bacteria.

Resume Objectif Evaluer la prise en charge medicochirurgicale de la cataracte uveitique chez l’enfant dans differents centres d’ophtalmologie pediatriques francais. Methode Etude en deux parties : une premiere partie observationnelle descriptive sur l’evaluation des pratiques francaises. Un questionnaire a ete envoye aux differents ophtalmologistes pediatres en France. Une seconde partie retrospective, menee dans le service d’ophtalmologie pediatrique du CHU de Bordeaux de 2008 a 2017 incluant les enfants atteints d’uveites chroniques non infectieuses operes de la cataracte. Resultats Vingt-et-un ophtalmologistes ont repondu au questionnaire. Seulement 23,8 % instauraient un traitement immunosuppresseur en systematique (corticoides exclus) avant l’intervention. Au total, 88,2 % prescrivaient une corticotherapie en preoperatoire. Onze ophtalmologistes realisaient un bolus de cortisone en peroperatoire et 95,2 % implantaient en premiere intention. Au total, 76,2 % instauraient une corticotherapie apres la chirurgie. En postoperatoire, tous debutaient un traitement local par des corticoides a forte dose. A un an, 100 % obtenaient une amelioration superieure ou egale a 2 lignes d’acuite visuelle. Concernant notre service, 10 yeux (7 enfants) ont ete operes de la cataracte. Sept etaient sous immunosuppresseurs (corticoides exclus) et 80 % des cas ont recu une corticotherapie orale quelques jours avant la chirurgie. Un bolus de cortisone a ete effectue en peroperatoire dans 8 cas et une implantation primaire a ete realisee dans 100 % des cas. En postoperatoire, 5 enfants ont recu des corticoides per os. Tous ont beneficie d’un traitement local par forte dose de cortisone. A un an, la moyenne de la meilleure acuite visuelle corrigee etait de 0,18 LogMar (0–0,7 ; SD : 0,25). Conclusion Encadree par un protocole anti-inflammatoire agressif, la chirurgie de la cataracte chez les enfants atteints d’uveites chroniques donne de bons resultats.

To evaluate the medical-surgical management of cataract surgery in children with chronic uveitis in various French pediatric ophthalmology centers.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.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).When performed with an aggressive anti-inflammatory protocol, cataract surgery leads to a good visual outcome in selected children with chronic uveitis.

Resume Introduction Comparer les proprietes biomecaniques de la cornee mesurees par la technologie Scheimpflug Corvis (Corvis ST) entre un groupe de patients atteints d’un glaucome chronique a angle ouvert et un groupe de patients temoins. Materiels et methodes Etude prospective monocentrique comparative cas-temoins portant sur 56 yeux droits de 56 patients (G1 [glaucome chronique a angle ouvert] n = 37/G2 [temoins] n = 19). Chaque patient a beneficie d’une mesure des proprietes biomecaniques de la cornee par camera dynamique Scheimpflug (Corvis ST) et par l’Ocular Response Analyser (ORA) puis d’une mesure de pression intraoculaire (PIO) par tonometrie a aplanation de Goldmann, et de mesure de la pachymetrie (CCT) par tomographie a coherence optique au cours de la meme visite, par un seul operateur. Les parametres etudies par le Corvis sont la PIO (PIO Corvis ST), l’amplitude de deformation corneenne (AMPLI DEFO), la velocite corneenne, le temps de plus haute concavite (TEMPS CONCAV), les longueurs d’aplanation et leurs delais d’obtention. Ceux etudies par l’ORA sont la PIO compensee par les proprietes biomecaniques (PIOcc), la PIO non compensee (PIOg), l’hysterese corneenne (CH) et le coefficient de resistance corneenne (CRF). Resultats La PIO mesuree sur l’ensemble de la population par Corvis ST etait positivement correlee a la PIO Goldmann (coefficient de Spearman r = 0,569, p Conclusion Les patients glaucomateux presentent des proprietes biomecaniques modifiees par rapport aux patients temoins avec une cornee apparaissant moins deformable.

Albinism is a rare genetic disease, comprising syndromic and non-syndromic forms. We assessed clinical and genetic characteristics in a prospective evaluation of 64 patients (33 children and 31 adults) seen at a specialized day hospital. Causative genetic mutations were found in TYR (23/64, 35.9%), OCA2 (19/64, 29.7%), TYRP1 (1/64, 1.6%), SLC45A2 (12/64, 18.7%), C10orf11 (1/64, 1.6%), HPS1 (3/64, 4.7%), HPS5 (1/64, 1.5%), HPS6 (1/64, 1.6%) and GPR143 (2/64, 3.1%). Causative mutations remained undetermined for one patient (1.6%). Heterogeneity for hair and skin phenotype was noted across and within the different genotypes. Skin and hair hypopigmentation did not correlate with visual impairment. The diagnosis of unrecognized syndromic forms and of cases of ocular albinism in this prospective and comprehensive series of patients with albinism in a European setting is remarkable. Photoprotection was overall good but not optimal.

Summary 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. Resume Objectif Analyser la prevalence et les facteurs de risques de retinopathie du premature (ROP) et de ROP severe (necessitant un traitement). Methodes Une etude retrospective a ete menee dans une maternite de niveau 3 a Bordeaux, de 2009 a 2015. Quatre cent dix-neuf nourrissons prematures dont la ROP a ete depistee exclusivement avec la RetCam ont ete inclus. Resultats Une ROP a ete retrouvee chez 27,68 % des nourrissons. Une ROP de stades 1, 2, 3 et 4 a ete retrouvee dans 44 %, 46 %, 9 % et 1 % des sujets, respectivement. Il n’y avait pas de ROP de stade 5. Au total, 6,6 % des nourrissons (28/419) ont ete traites par photocoagulation laser exclusive. Aucune injection intra-vitreenne d’anti-VEGF ou de traitement chirurgical n’ont ete realises. Aucun nourrisson dont le terme etait>31SA ou de poids de naissance>1110g n’a necessite de traitement. En analyse multivariee, les facteurs de risques de developper une ROP etaient un faible poids de naissance, un faible âge gestationnel a la naissance, la duree de ventilation mecanique invasive et un etat de choc ou l’utilisation d’amines vasopressives. En analyse multivariee, les facteurs de risques de ROP severe etaient le sexe masculin, le terme≤27SA et le score d’Apgar a 5minutes≤7. Conclusion Dans notre serie sur 6 ans, la ROP a ete depistee avec succes par telemedecine exclusive et aucun traitement chirurgical n’a ete necessaire. Cette etude retrouve les facteurs de risques connus de ROP mais le score d’Apgar a 5minutes comme facteur de risque de ROP severe necessite des etudes ulterieures avant d’etre confirme.

Although the entomotoxicity of plant ureases has been reported almost 20 years ago, their insecticidal mechanism of action is still not well understood. Jaburetox is a recombinant peptide derived from one of the isoforms of Canavalia ensiformis (Jack Bean) urease that presents biotechnological interest since it is toxic to insects of different orders. Previous studies of our group using the Chagas disease vector and model insect Rhodnius prolixus showed that the treatment with Jack Bean Urease (JBU) led to hemocyte aggregation and hemolymph darkening, among other effects. In this work, we employed cell biology and biochemical approaches to investigate whether Jaburetox would induce not only cellular but also humoral immune responses in this species. Results: The findings indicated that nanomolar doses of Jaburetox triggered cation-dependent, in vitro aggregation of hemocytes of fifth-instar nymphs and adults. The use of specific eicosanoid synthesis inhibitors revealed that the cellular immune response required cyclooxygenase products since indomethacin prevented the Jaburetox-dependent aggregation whereas baicalein and esculetin (inhibitors of the lipoxygenases pathway) did not. Cultured hemocytes incubated with Jaburetox for 24 h showed cytoskeleton disorganization, chromatin condensation and were positive for activated caspase 3, an apoptosis marker, although their phagocytic activity remained unchanged. Finally, in vivo treatments by injection of Jaburetox induced both a cellular response, as observed by hemocyte aggregation, and a humoral response, as seen by the increase of spontaneous phenoloxidase activity, a key enzyme involved in melanization and defense. On the other hand, the humoral response elicited by Jaburetox injections did not lead to an increment of antibacterial or lysozyme activities. Jaburetox injections also impaired the clearance of the pathogenic bacteria Staphylococcus aureus from the hemolymph leading to increased mortality, indicating a possible immunosuppression induced by treatment with the peptide. Conclusions: In our experimental conditions and as part of its toxic action, Jaburetox activates some responses of the immune system of R. prolixus both in vivo and in vitro, although this induction does not protect the insects against posterior bacterial infections. Taken together, these findings contribute to the general knowledge of insect immunity and shed light on Jaburetox's mechanism of action. Fil: Fruttero, Leonardo Luis. Pontificia Universidade Católica do Rio Grande do Sul; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Moyetta, Natalia Rita. Pontificia Universidade Católica do Rio Grande do Sul; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Uberti, Augusto F.. Pontificia Universidade Católica do Rio Grande do Sul; Brasil Fil: Grahl, Matheus V. Coste. Pontificia Universidade Católica do Rio Grande do Sul; Brasil Fil: Lopes, Fernanda C.. Pontificia Universidade Católica do Rio Grande do Sul; Brasil Fil: Broll, Valquiria. Universidade Federal do Rio Grande do Sul; Brasil Fil: Feder, Denise. Universidade Federal Fluminense; Brasil Fil: Carlini, Celia R.. Pontificia Universidade Católica do Rio Grande do Sul; Brasil

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.Prospective observational case-control study.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).IOP measured on all patients by Corvis ST was positively correlated to GAT (Spearman r=0.569, P0.001) and PIOcc (Spearman r=0.531, P0.001). 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 (P0.001). 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).This study showed differences in corneal biomechanical properties between glaucoma and control patients. The cornea of glaucoma patients appears less deformable.

Visceral leishmaniasis is endemic around Mediterranean and is considered by certain authors as an opportunist disease. We report on the case of a 7-year-old girl treated by anti-TNF for an idiopathic juvenile arthritis which has presented a visceral leishmaniasis. Four years later, she presented a pseudotumoral-like recurrence located in a nasal mucous membrane. Leishmania infantum is classically responsible for visceral leishmaniasis but pure mucocutaneous leishmaniasis has been described. It is, for our knowledge, the first observation of a recurrence of visceral leishmaniasis in a mucocutaneous location. Atypical leishmaniasis in the endemic zones can appear in immunodepressed patients and must be evoked when in doubt.

For the selection of polymer-based materials to be used in radiation environments, radiation tests have been performed at the European Organization for Particle Physics Research (CERN) for several decades. According to the recommendations of the IEC Standard 544, mechanical tests are carried out, and the radiation degradation is measured after accelerated irradiations. It is well known that during long-term exposures, oxygen and moisture are allowed to diffuse in the materials and hence to induce more severe degradation; this phenomenon is known as the `dose-rate effect'. During machine shut-downs, samples of rigid and flexible polymeric insulators (magnet-coil resins and cable insulations) have been taken out and tested after several years of exposure in the Super Proton Synchrotron (SPS) and in the Large Electron-Position Collider (LEP). The mechanical test results are compared to the ones after the accelerated qualification tests, and to the ones of a study conducted in 1991 to estimate the lifetime of cables in the radiation environment of LEP 200. They confirm that thermoplastics are more sensitive to long-term irradiations than the thermosetting resins and the composites, but that the dose-rate effect cannot be neglected in the latter.