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Purpose The objective of this study was to analyze the nycthemeral variations in blood pressure (BP) in individuals who presented with non-arteritic anterior ischemic optic neuropathy (NAION).Methods BP was recorded for 24 h (ambulatory blood pressure monitoring, ABPM) in 65 patients with acute NAION. Three definitions of nighttime periods were used: definition 1, 1 a.m.–6 a.m.; definition 2, 10 p.m.–7 a.m.; and definition 3, 10 p.m.–8 a.m. For each of these definitions, patients were classified according to the value of nocturnal reduction in BP into dippers (10–20%), mild dippers (0–10%), reverse dippers (< 0%), and extreme dippers (> 20%).Results The proportions of dippers, mild dippers, reverse dippers, and extreme dippers varied significantly depending on the definition chosen. We found the highest number of patients with extreme dipping (23%) when using the strictest definition of nighttime period (definition 1, 1 a.m.–6 a.m.), as compared with 6.2% and 1.5% for the other definitions, respectively. Overall, 13 of 33 patients without known systemic hypertension (39%) were diagnosed with hypertension after ABPM. No risk factor for NAION was associated with the extreme-dipping profile. Finally, the prevalence of systemic hypertension was high (69%).Conclusion In our population of patients who had an episode of NAION, the proportion of extreme dippers was higher than that usually found in the literature. However, extreme dipping is not a frequent feature of patients with NAION as compared to patients with systemic hypertension. ABPM is recommended for all patients with NAION and unknown history of systemic hypertension.

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Purpose: Assess the prevalence and evolution of PHOMS in optic neuritis. Methods: We analysed the medical files of 126 patients included in the OCTON cohort. Patients’ medical files, digital retinal images and OCT examinations were reviewed, searching for optic nerve head oedema and PHOMS at the initial presentation and during the follow-up. Results: We included 102 patients in the final analysis. Twenty-nine (29) eyes had optic nerve head oedema at the initial presentation. PHOMS were found to be present in 8 eyes affected with optic neuritis. All cases of PHOMS were associated with optic nerve head oedema. All the PHOMS decreased in size and disappeared with the improvement of the oedema. Discussion: Our results show that PHOMS is not a common sign of optic neuritis. We didn’t observe any case of PHOMS in the absence of optic nerve head oedema in eyes with optic neuritis. PHOMS seem to be a rare sign of optic neuritis associated to optic nerve head oedema, and they tend to disappear with the improvement of the optic nerve head oedema. We suggest that the presence of PHOMS in optic neuritis eyes with no optic nerve oedema should be a considered warning sign.

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La diplopía binocular es la consecuencia de una afectación del sistema oculomotor. El proceso diagnóstico ante este síntoma se basa en la anamnesis y la exploración precisa del paciente, que se completan con una evaluación que depende de los datos de esta exploración inicial y en el que las pruebas de imagen ocupan un lugar casi sistemático. Las parálisis oculomotoras son la principal causa de diplopía binocular. Sus etiologías son múltiples y en ellas predominan los traumatismos, las afectaciones vasculares y la patología tumoral. Existen cuatro urgencias absolutas que se deben buscar sistemáticamente. La ruptura aneurismática debe sospechare ante cualquier parálisis del nervio III, sobre todo en presencia de dolor y de midriasis homolateral, la arteritis de células gigantes en cualquier paciente mayor de 50 años, la miastenia generalizada en caso de fluctuaciones o de signos neurológicos asociados, así como la apoplejía hipofisaria en caso de afectación de varios nervios oculomotores, a menudo dolorosa y asociada a una disminución de la agudeza visual. Aparte del tratamiento etiológico propio, es importante impedir que los pacientes vean doble.

The role of Human pegivirus (HPgV) in patients with encephalitis has been recently questioned. We present cases of 4 patients with similar clinical, biological, and radiological characteristics, including a past history of transplantation with long-term immunosuppression and a progressive course of severe and predominantly myelitis, associated in 3 cases with optic neuropathy causing blindness. Extensive workup was negative but analysis of the CSF by use of pan-microorganism DNA- and RNA-based shotgun metagenomics was positive for HPgV. This case series further supports the hypothesis of HPgV CNS infection and highlights the utility of metagenomic next-generation sequencing of CSF in immunocompromised patients.

La neuropathie optique héréditaire de Leber (NOHL) est une maladie mitochondriale rare responsable de de cécité par atteinte bilatérale de la vision centrale. Elle touche préférentiellement les hommes jeunes mais peut survenir à tout âge et chez une femme. Son diagnostic est suspecté sur les antécédents familiaux et le tableau clinique initial, et repose sur la mise en évidence de la mutation génétique. Le bilan initial doit comporter une évaluation de la structure et de la fonction visuelle. Son pronostic visuel est sévère, mais dépend de la mutation causale. La prise en charge doit comporter un conseil génétique, une proposition thérapeutique et prise en charge du handicap visuel.

Les objets connectés (OC) proposant la collecte de données sur l’activité physique et sportive sont de plus en plus performants, accessibles et présents notamment en course à pied. Dans le même temps la question des usages des OC, des effets (empouvoirement v/s altération du rapport à l’activité) apparait. Cet article propose de se centrer sur les raisons qui poussent les coureuses à utiliser ou non des dispositifs numériques, décrire les modalités d’usage ainsi que la manière dont les coureuses à pied connectées composent avec, et rendre compte de ce que ces dispositifs leur font. Le terrain a été abordé à partir d’une méthode de recherche mixte combinant approches qualitatives et quantitatives. Les résultats rendent compte des usages (ou non-usages) spécifiques que font les coureuses à pied de leurs objets connectés, mais aussi des spécificités de cet usage en fonction de leur profil de coureuses et de leurs formes de pratique.

Occipital lobe seizure are underrepresented in epilepsy surgery cases series. This may reflect the fear for post-surgical functional deficits but also the doubt about the ability of anatomo-electro-clinical correlations to localize precisely the epileptogenic zone in occipital lobe seizure.

Background/objectives: REALITY is an international observational retrospective registry of LHON patients evaluating the visual course and outcome in Leber hereditary optic neuropathy (LHON). Subjects/methods: Demographics and visual function data were collected from medical charts of LHON patients with visual loss. The study was conducted in 11 study centres in the United States of America and Europe. The collection period extended from the presymptomatic stage to at least more than one year after onset of vision loss (chronic stage). A Locally Weighted Scatterplot Smoothing (LOWESS) local regression model was used to analyse the evolution of best-corrected visual acuity (BCVA) over time. Results: 44 LHON patients were included; 27 (61%) carried the m.11778G>A ND4mutation, 8 (18%) carried the m.3460G>A ND1mutation, and 9 (20%) carried the m.14484T>C ND6mutation. Fourteen (32%) patients were under 18 years old at onset of vision loss and 5 (11%) were below the age of 12. The average duration of follow-up was 32.5 months after onset of symptoms. At the last observed measure, mean BCVA was 1.46 LogMAR in ND4patients, 1.52 LogMAR in ND1patients, and 0.97 LogMAR in ND6patients. The worst visual outcomes were reported in ND4patients aged at least 15 years old at onset, with a mean BCVA of 1.55 LogMAR and no tendency for spontaneous recovery. The LOESS modelling curve depicted a severe and permanent deterioration of BCVA. Conclusions: Amongst LHON patients with the three primary mtDNA mutations, adult patients with the m.11778G>A ND4mutation had the worst visual outcomes, consistent with prior reports.

This study investigates the association between giant cell arteritis and paracentral acute middle maculopathy. Our study reveals that isolated findings of paracentral acute middle maculopathy can be the only indication of giant cell arteritis.

Mutations in MLC1cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare form of leukodystrophy characterized by macrocephaly, epilepsy, spasticity, and slow mental deterioration. Genetic studies of MLC are lacking from many parts of the world, especially in Sub-Saharan Africa. Genomic DNA was extracted for 67 leukodystrophic patients from 43 Sudanese families. Mutations were screened using the NGS panel testing 139 leukodystrophies and leukoencephalopathies causing genes (NextSeq500 Illumina). Five homozygous MLC1variants were discovered in seven patients from five distinct families, including three consanguineous families from the same region of Sudan. Three variants were missense (c.971 T > G, p.Ile324Ser; c.344 T > C, p.Phe115Ser; and c.881 C > T, p.Pro294Leu), one duplication (c.831_838dupATATCTGT, p.Ser280Tyrfs*8), and one synonymous/splicing-site mutation (c.762 C > T, p.Ser254). The segregation pattern was consistent with autosomal recessive inheritance. The clinical presentation and brain MRI of the seven affected patients were consistent with the diagnosis of MLC1. Due to the high frequency of distinct MLC1mutations found in our leukodystrophic Sudanese families, we analyzed the coding sequence of MLC1gene in 124 individuals from the Sudanese genome project in comparison with the 1000-genome project. We found that Sudan has the highest proportion of deleterious variants in MLC1gene compared with other populations from the 1000-genome project.

In March 2020, the sudden rise in the number of SARS-CoV-2 infections in France led the government to impose a strict lockdown during which all non-urgent medical consultations were postponed. From March 17 to May 10, 2020, private medical practices were closed, and telemedicine was encouraged. The consequences on ophthalmic care were dramatic, with over 90% of scheduled consultations canceled. The goal of this study was to describe consultations during the 2-month strict lockdown in Paris and to analyze its impact on the visual outcomes of patients consulting in the ophthalmology emergency department (OED).

Background. The authors measured pharmacokinetic parameters before, during, and after immunotherapy by continuous intrapleural infusion of recombinant interleukin-2 (rIL-2) and correlated the resulting data with clinical effects in nine patients with malignant pleural effusion. Methods. The underlying disease was malignant mesothelioma in five patients and adenocarcinoma in four patients. Continuous intrapleural infusion of rIL-2 was performed for 5 days at 21 X [10 sup.6] IU/[m.sup.2] /day. Maximum tolerated dose previously was determined to be 24 X [10 sup.6] IU/[m sup.2] /day in a Phase I study. Peak levels, the areas under the concentration curve (AUC), and drug half-lives were measured in pleural fluid and plasma samples collected at 0 (baseline), 12, 24, 48, 72, 96, and 120 hours during infusion and at 2, 6, 8, 32, 44, 56, 80, and 120 hours after the end of infusion. Results. High and prolonged intracavitary drug levels were achieved in all but two patients, with a statistically significant correlation between peak values and AUC. Four patients achieved objective responses according to World Health Organization criteria. Neither of the patients with undetectable RIL-2 levels had response to therapy. Serum RIL-2 levels were low regardless intrapleural levels. Mean AUC was lower in the plasma than in the pleural fluid. Conclusions. This study demonstrates that continuous intrapleural infusion of RIL-2 is an active method of treatment for malignant pleural effusion. The low serum levels associated with this method greatly improve tolerance. The results also indicate that the concentration and duration of intrapleural rIL-2 levels may depend on the extent of pleural invasion. Additional study is needed to confirm this finding. Cancer 1994; 73:308-13.

IMPORTANCE: The coronavirus disease 2019 (COVID-19) pandemic has made alcohol-based hand sanitizers (ABHS) widely available in public places. This may warrant determining whether cases of unintentional ocular exposure are increasing, especially in children. OBJECTIVE: To describe the epidemiologic trend of pediatric eye exposures to ABHS and to report the severity of the ocular lesions. DESIGN, SETTING, AND PARTICIPANTS: Retrospective case series conducted from April 1, 2020, to August 24, 2020. Cases were retrieved from the national database of the French Poison Control Centers (PCC) and from a pediatric ophthalmology referral hospital in Paris, France. Cases of ocular exposure to chemical agents in children younger than 18 years during the study period were reviewed. Cases of ABHS exposure were included. EXPOSURES: The following data were collected: age, sex, circumstances of exposure, symptoms, size of the epithelial defect at first examination, time between the incident and re-epithelialization, and medical and/or surgical management. MAIN OUTCOMES AND MEASURES: Comparison of the number of eye exposures to ABHS in children between April to August 2020 and April to August 2019. RESULTS: Between April 1 and August 24, 2020, there were 7 times more pediatric cases of ABHS eye exposures reported in the PCC database compared with the same period in 2019 (9.9% of pediatric eye exposures in 2020 vs 1.3% in 2019; difference, 8.6%; 95% CI, 7.4-9.9; P &lt; .001). The number of cases occurring in public places increased in 2020 (from 16.4% in May to 52.4% in August). Similarly, admissions to the eye hospital for ABHS exposure increased at the same period (16 children in 2020 including 10 boys; mean [SD] age, 3.5 [1.4] years vs 1 boy aged 16 months in 2019). Eight of them presented with a corneal and/or conjunctival ulcer, involving more than 50% of the corneal surface for 6 of them. Two cases required amniotic membrane transplant. CONCLUSIONS AND RELEVANCE: These data support the likelihood of an increasing number of unintentional ocular exposures to ABHS in the pediatric population. To maintain good public compliance with hand disinfection, these findings support that health authorities should ensure the safe use of these devices and warn the parents and caregivers about their potential danger for children.

Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity1–4. Sparse taxon sampling has previously been proposed to confound phylogenetic inference5, and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families—including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species.

Complex architectures like 3D gold dendritic nanostructures were synthesized by an in situtemplated growth method using a thin film of a block copolymer [polystyrene-b-poly(4-vinylpyridine)] deposited onto silicon substrates. The overall study has demonstrated the strong link between the morphology, size, and distribution of the structures and the synthetic physicochemical parameters, such as pH, reaction temperature, concentration, and nature of reactants. A nonequilibirum state of the medium has been required to create a fractal growth of the gold structures onto a prepatterned gold-seeded surface and has led to a better control of the structures’ surface coverage rate. Those as-prepared nanodendrites have also exhibited high electrocatalytic activity toward a significant enhancement factor, as well as important sensitivity, thanks to tip effects. The electrochemical experiment results have demonstrated efficient adsorption and quantification of very low traces of specific molecules like glutathione or hexadecanethiol.

La pollution atmosphérique est reconnue comme un facteur de risque cardiovasculaire. Les biomarqueurs MPO, TIMP-1 et vWF sont liés à l'augmentation du risque cardio-vasculaire. L'objectif de notre travail est d’étudier l'association entre la pollution, nos trois biomarqueurs et le profil métabolique et inflammatoire.

Tyrosine kinase inhibitors efficacy in central nervous system (CNS) disease remains uncertain. Ponatinib was studied for CNS distribution in 16 patients with Philadelphia-positive acute lymphoblastic leukemia. Cerebrospinal fluid concentrations fell below the 40 nM threshold, suggesting suboptimal CNS exposure.

La neuropathie optique héréditaire de Leber (NOHL) est une maladie mitochondriale responsable de cécité par atteinte bilatérale des nerfs optiques. La thérapie génique vise à réduire l’impact de la progression de la NOHL après le déclenchement de la maladie.

Le diagnostic de névrite optique (NOI), ou inflammation du nerf optique repose sur la clinique : d’abords marquée par une baisse visuelle rapidement progressive, associée à des douleurs oculaires accentuées par les mouvements des yeux ; on peut également retrouver la notion d’anomalie des couleurs et ou des contrastes. Ici les neuropathies inflammatoires sont associées aux anti-corps anti MOG. Les MOG, sont des glycoprotéines oligodendrocytaires, impliquée dans la production de la myéline, ils sont identifiés depuis près de trois décennies associées à des NOI démyélinisantes. Les premières séries ont été rapportée chez les enfants au décours de manifestations neurologiques démyélinisantes, en particulier lors d’ADEM (encéphalomyélite démyélinisante aiguë) ou de sclérose en plaque (SEP ou MS)[1]. Les anti MOG sont associées aux neuropathies dans la cadre phénotypique du spectre de la neuro-myélite optique (NMO) ; Et les anticorps anti-Aquaporine 4 (AQP4) sont forcément négatifs. Ainsi les anti-MOG pourraient expliquer jusqu’à 30 % des formes de névrites optiques séronégatives, leurs présences représente alors une aide diagnostique significative pour le clinicien, en particulier lors d’un premier épisode neurologique [1]. Les premières courtes séries publiées mettaient en évidence chez des populations AQP4-/MOG+ une atteinte ophtalmologique au premier plan avec un bon pronostic de récupération [1]. La connaissance de ces antigènes est importante, elle ne permettrait pas seulement la compréhension de la physiopathologie mais aussi la stratification des patients en terme de pronostic et de réponse au traitement [2]. Ainsi le diagnostic précoce de NOI anti MOG positif doit mettre en route un traitement initial agressif et plus ou moins un traitement de fond pour éviter les récidives. Le rôle de l’ophtalmologiste reste primordial, car en première ligne dans les atteintes purement oculaire.

The article presents a musical critique of Franz Josef Haydn's organ concertos, harpsichord and piano. It mentions that the autograph manuscript of the Concerto, Hob. XVIII: 1 indicates an orchestra of two clarini (trumpets or horns), two oboes, and strings. It mentions that the concertos for organ in C major other than Hob. XVIII: 1, and having circulated under Haydn's name, number not two but three: Hob. XVIII: 5, 8, and 10.

The spectrum of Myelin Oligodendrocytes Glycoprotein (MOG) antibody disease constitutes a recently described challenging entity, referring to a relatively new spectrum of autoimmune disorders with antibodies against MOG predominantly involving the optic nerve and spinal cord. The purpose of this article is to describe MRI features of MOG-AD involvement in the optic nerves, spinal cord and the brain of adults.

IMPORTANCE: Intravitreal gene therapy is regarded as generally safe with limited mild adverse events, but its systemic effects remain to be investigated. OBJECTIVE: To examine the association between immune response and intraocular inflammation after ocular gene therapy with recombinant adeno-associated virus 2 carrying the ND4 gene (rAAV2/2-ND4). DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of an open-label, dose-escalation phase 1/2 randomized clinical trial of rAAV2/2-ND4 included data from February 13, 2014 (first patient visit), to March 30, 2017 (last patient visit at week 96), the first 2 years after injection. Patients older than 15 years with diagnosed ND4 Leber hereditary optic neuropathy (LHON) and visual acuity of at least counting fingers were enrolled in 1 of 5 cohorts. Four dose cohorts of 3 patients each were treated sequentially. An extension cohort of 3 patients received the dose of 9 × 1010 viral genomes per eye. INTERVENTIONS: Patients received increasing doses of rAAV2/2-ND4 (9 × 109, 3 × 1010, 9 × 1010, and 1.8 × 1011 viral genomes per eye) as a single unilateral intravitreal injection. Patients were monitored for 96 weeks after injection; ocular examinations were performed regularly, and blood samples were collected for immunologic testing. MAIN OUTCOMES AND MEASURES: A composite ocular inflammation score (OIS) was calculated based on grades of anterior chamber cells and flare, vitreous cells, and haze according to the Standardization of Uveitis Nomenclature. The systemic immune response was quantified by enzyme-linked immunospot (cellular immune response), enzyme-linked immunosorbent assay (IgG titers), and luciferase assay (neutralizing antibody [NAb] titers). RESULTS: The present analysis included 15 patients (mean [SD] age, 47.9 [17.2] years; 13 men and 2 women) enrolled in the 5 cohorts of the clinical trial. Thirteen patients experienced intraocular inflammation after rAAV2/2-ND4 administration. Mild anterior chamber inflammation and vitritis were reported at all doses, and all cases were responsive to treatment. A maximum OIS of 9.5 was observed in a patient with history of idiopathic uveitis. Overall, OIS was not associated with the viral dose administered. No NAbs against AAV2 were detected in aqueous humor before treatment. Two patients tested positive for cellular immune response against AAV2 at baseline and after treatment. Humoral immune response was not apparently associated with the dose administered or with the immune status of patients at baseline. No association was found between OISs and serum NAb titers. CONCLUSIONS AND RELEVANCE: In this study, intravitreal administration of rAAV2/2-ND4 in patients with LHON was safe and well tolerated. Further investigations may shed light into the local immune response to rAAV2/2-ND4 as a potential explanation for the observed intraocular inflammation.

Les neuropathies optiques héréditaires de Leber (NOHL) entrainent une baisse d’acuité visuelle rapide et sévère. Raxone®(Idébénone, Santhéra) est le seul médicament à disposer d’une AMM européenne dans le traitement de cette neuropathie optique. Selon l’avis d’une réunion de consensus international, il peut être proposé au cours des premiers mois après l’installation de cette neuropathie optique.

Inflammatory Bowel Diseases (IBD) are chronic inflammatory conditions of the intestinal tract. IBD are believed to result from an inappropriate immune response against the intestinal flora in genetically predisposed patients. The precise etiology of these diseases is not fully understood, therefore treatments rely on the dampening of symptoms, essentially inflammation, rather than on the cure of the disease. Despite the availability of biologics, such as anti-TNF antibodies, some patients remain in therapeutic failure and new treatments are thus needed. The multiligand receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor implicated in inflammatory reactions and immune system activation. Here, we investigated the role of RAGE in intestinal inflammation and its potential as a therapeutic target in IBD. We showed that RAGE was upregulated in inflamed tissues from IBD patients compared to controls. Rage−/−mice were less susceptible to intestinal and colonic inflammation development than WT mice. WT mice treated with the RAGE-specific inhibitor FPS-ZM1 experienced less severe enteritis and colitis. We demonstrated that RAGE could induce intestinal inflammation by promoting oxidative stress and endothelial activation which were diminished by FPS-ZM1 treatment. Our results revealed the RAGE signaling pathway as a promising therapeutic target for IBD patients.