Whereas antithyroid drugs (ATD) are the preferred treatment modality for Graves’ hyperthyroidism (GH), there is still controversy about the optimal regimen for delivering ATD. To evaluate whether ‘Block and Replace’ (B + R) and ‘Titration’ (T) regimes are equivalent in terms of frequency of euthyroidism and Graves’ Orbitopathy (GO) during ATD therapy. A prospective multicentre observational cohort study of 344 patients with GH but no GO at baseline. Patients were treated with ATD for 18 months according to B + R or T regimen in line with their institution’s policy. Baseline characteristics were similar in both groups. In the treatment period between 6 and 18 months thyrotropin (TSH) slightly increased in both groups, but TSH was on average 0.59 mU/L (95% CI 0.27–0.85) lower in the B + R group at all time points (p = 0.026). Serum free thyroxine (FT4) remained stable during the same interval, with a tendency to higher values in the B + R group. The point-prevalence of euthyroidism (TSH and FT4 within their reference ranges) increased with longer duration of ATD in both groups; it was always higher in the T group than in the B + R group: 48 and 24%, respectively, at 6 months, 81 and 58% at 12 months, and 87 and 63% at 18 months (p < 0.002). There were no significant differences between the B + R and T regimens with respect to the fall in thyrotropin binding inhibiting immunoglobulins (TBII) or thyroid peroxidase antibodies (TPO-Ab). GO developed in 15.9% of all patients: 9.1 and 17.8% in B + R group and T group, respectively, (p = 0.096). GO was mild in 13% and moderate-to-severe in 2%. The prevalence of biochemical euthyroidism during treatment with antithyroid drugs is higher during T compared to B + R regimen. De novo development of GO did not differ significantly between the two regimens, although it tended to be higher in the T group. Whether one regimen is clinically more advantageous than the other remains unclear.

Nucleophosmin (NPM1) is a nucleocytoplasmic shuttling protein, mainly localized at nucleoli, that plays a number of functions in ribosome biogenesis and export, cell cycle control, and response to stress stimuli. NPM1 is the most frequently mutated gene in acute myeloid leukemia; mutations map to the C-terminal domain of the protein and cause its denaturation and aberrant cytoplasmic translocation. NPM1 C-terminal domain binds G-quadruplex regions at ribosomal DNA and at gene promoters, including the well characterized sequence from the nuclease-hypersensitive element III region of the c-MYC promoter. These activities are lost by the leukemic variant. Here we analyze the NPM1/G-quadruplex interaction, focusing on residues belonging to both the NPM1 terminal three-helix bundle and a lysine-rich unstructured tail, which has been shown to be necessary for high affinity recognition. We performed extended site-directed mutagenesis and measured binding rate constants through surface plasmon resonance analysis. These data, supported by molecular dynamics simulations, suggest that the unstructured tail plays a double role in the reaction mechanism. On the one hand, it facilitates the formation of an encounter complex through long range electrostatic interactions; on the other hand, it directly contacts the G-quadruplex scaffold through multiple and transient electrostatic interactions, significantly enlarging the contact surface.

Évaluer la prévalence des troubles visuels dans une population pédiatrique scolarisée en réseau d’éducation prioritaire en France.Le projet pilote PlanVue® a été conçu pour détecter et prendre en charge les troubles visuels des enfants scolarisés dans les réseaux d’éducation prioritaire de Nanterre, France. Au cours de cette étude pilote, 515 enfants de 4 à 13 ans ont bénéficié à l’école, entre janvier et mars 2019, d’un examen de la fonction visuelle consistant en une évaluation globale du comportement visuel, une mesure de l’acuité visuelle de chaque œil, une évaluation de la réfraction objective par photoscreening, et la recherche d’un strabisme. En cas d’examen anormal, défini par une vision altérée ou selon un algorithme établi sur les anomalies retrouvées, les enfants étaient adressés à un ophtalmologiste.Une altération de mesure de l’acuité visuelle a été retrouvée chez 20 % des élèves. Sur les 515 enfants dépistés, 22 % ont été orientés vers un ophtalmologiste. Parmi ces enfants, 13 % présentaient une amblyopie, 73 % présentaient une amétropie sphérique, 57 % présentaient un astigmatisme et 2 % présentaient un strabisme. Sur l’ensemble de la population dépistée, 12 % des enfants nécessitaient une correction optique et n’en étaient pas pourvus.Cette étude confirme la prévalence élevée des troubles réfractifs non corrigés chez les enfants d’âge scolaire. Un programme de dépistage réalisé en milieu scolaire par des professionnels paramédicaux peut permettre de réduire considérablement la proportion de troubles visuels non corrigés et leurs conséquences.To assess the prevalence of visual disturbances among school-aged children in prioritized education zones in France.The PlanVue® pilot project was designed to detect and manage visual disturbances in school-aged children in the prioritized education areas of the city of Nanterre, France. During this pilot study, a cohort of 515 children aged 4 to 13 years underwent a school vision screening between January and March 2019, consisting of an overall evaluation of the child's visual behavior, measurement of uncorrected visual acuity in each eye, objective refraction with a photoscreener and strabismus screening. If the examination was abnormal as determined by impaired vision or an algorithm based on the abnormalities found, the children were referred to an ophthalmologist.Decreased visual acuity was found in 20% of school-aged children. Out of the 515 children screened, 22% were referred to an ophthalmologist. Among these children, 13% were diagnosed with amblyopia, 73% with spherical ametropia, 57% with astigmatism and 2% with strabismus. Of the entire population screened, 12% of the children needed optical correction but had not received glasses.This study confirms the high prevalence of uncorrected refractive errors among school-age children. A screening program carried out in a school environment by paramedical professionals might make it possible to considerably reduce the rate of uncorrected visual disorders and their consequences.