RSRC1 loss-of-function variants cause mild to moderate autosomal recessive intellectual disability.

We present the results of computation of cohomology for some Lie (super)algebras of Hamiltonian vector fields and related algebras. At present, the full cohomology rings for these algebras are not known even for the low dimensional vector fields. The partial ``experimental'' results may give some hints for solution of the whole problem. The computations have been carried out with the help of recently written program in C language. Some of the presented results are new.Comment: 11 pages, LaTeX, uses the Springer file lncse.cl

Fast versus gradual adaptation of soft monthly contact lenses in neophyte wearers

AIM: To determine if a gradual adaptation period is necessary for neophytes when fitted with modern hydrogel or silicone hydrogel reusable disposable contact lenses. METHOD: Across four sites, 74 neophytes (18-28 years) were randomly assigned to a reusable lens cleaned nightly with Opti-Free® Puremoist® multi-purpose contact lens solution: Proclear® (hydrogel) or Biofinity® (silicone hydrogel) and an adaptation schedule: fast (10 h wear from the first day) or gradual (4 h on the first day, increasing their wear time by 2 h on each subsequent day until they had reached 10 h). Masked investigators graded ocular surface physiology and non-invasive tear breakup time (NIBUT) and a range of comfort, vision and lens handling subjective ratings (0-100 visual analogue scales) were recorded at the baseline visit and after 10 h of lens wear, 4-6 days and 12-14 days after lens fitting. Subjective scores were also repeated after 7 days. RESULTS: There was no difference (p > 0.05) in ocular surface physiology or NIBUT between fast and gradual adaptation groups at any time point in either lens type with the exception of increased corneal staining (p = 0.019) in the silicone hydrogel fast adaptation group after 4-6 days, but was similar by 12-14 days. Subjective scores were also similar across the visits and lens types with the exception of 'lens awareness' (p = 0.019) which was less in the gradual versus the fast adaptation silicone hydrogel lens group at 12-14 days. CONCLUSION: There seems to be no clinical benefit for recommending a gradual adaptation period in new wearers fitted with modern soft reusable disposable contact lenses. The findings of this work add to a growing body of evidence suggesting that such advice is unnecessary in regular soft contact lens wear, which has important ramifications for the initial clinical management of these patients

Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease

We investigated the genetic, phenotypic, and interferon status of 46 patients from 37 families with neurological disease due to mutations in ADAR1. The clinicoradiological phenotype encompassed a spectrum of Aicardi-Goutières syndrome, isolated bilateral striatal necrosis, spastic paraparesis with normal neuroimaging, a progressive spastic dystonic motor disorder, and adult-onset psychological difficulties with intracranial calcification. Homozygous missense mutations were recorded in five families. We observed a p.Pro193Ala variant in the heterozygous state in 22 of 23 families with compound heterozygous mutations. We also ascertained 11 cases from nine families with a p.Gly1007Arg dominant-negative mutation, which occurred de novo in four patients, and was inherited in three families in association with marked phenotypic variability. In 50 of 52 samples from 34 patients, we identified a marked upregulation of type I interferon-stimulated gene transcripts in peripheral blood, with a median interferon score of 16.99 (interquartile range [IQR]: 10.64-25.71) compared with controls (median: 0.93, IQR: 0.57-1.30). Thus, mutations in ADAR1 are associated with a variety of clinically distinct neurological phenotypes presenting from early infancy to adulthood, inherited either as an autosomal recessive or dominant trait. Testing for an interferon signature in blood represents a useful biomarker in this context