Dexmedetomidine improves success of paediatric MRI sedation.

OBJECTIVE: To improve success rates of children requiring sedation for MRI. METHODS: Audits of sedation success for children attending planned MRI using three different approaches: (1) National Institute for Health and Care Excellence (NICE) guidance (chloral hydrate if <15 kg and oral midazolam if ≥15 kg), (2) Chloral hydrate for all patients, (3) Chloral hydrate±intranasal dexmedetomidine if <15 kg and intranasal dexmedetomidine alone if ≥15 kg. RESULTS: 74 patients had 85 MRI scan attempts. Overall success rates were significantly higher when using intranasal dexmedetomidine compared with following NICE guidance (81% vs 52% p=0.017). Dexmedetomidine performed better than oral midazolam for the same indication (76% vs 33% p=0.026). The side effect profile for dexmedetomidine was as reported in larger studies. CONCLUSIONS: Intranasal dexmedetomidine is an effective alternative to oral midazolam for sedation for MRI and as a rescue medication where chloral hydrate has been ineffective.

Small Hard Macular Drusen and Associations in 11- to 12-Year-Old Children in the Copenhagen Child Cohort 2000 Eye Study.

Purpose: To assess the prevalence and associations of small hard drusen in a child cohort. Methods: Cross-sectional study of 11- to 12-year-old Danish children from the population-based Copenhagen Child Cohort 2000 Eye Study. Fovea-centered, 45° color images of both eyes were graded for macular drusen (within one optic-disc-rim-to-fovea distance of the foveal center) and for extramacular drusen. Analyses tested for associations between drusen and anthropometric measures including choroidal thickness. Results: Gradable fundus images from both eyes were available for 1333 children (640 boys, 693 girls) with a mean (SD) age of 11.7 (0.40) years. One or more small hard macular drusen (diameter <63 µm) were present in 82 (6.2%) right eyes and 82 (6.2%) left eyes and in 147 (11.0%) subjects. Four children (0.30%) had 20 or more small hard macular drusen in one or both eyes. Extramacular small hard drusen were present in 10.7% of children, and 19% of children had such drusen anywhere. The odds for having one or more small hard macular drusen increased with subfoveal choroidal thickness with an odds ratio of 1.15 (95% confidence interval, 1.03-1.28; P = 0.013) per 50-µm thicker choroid, adjusted for age and sex. The association with choroidal thickness was also present for extramacular drusen. Conclusions: Having one or more small hard macular drusen was common in 11- to 12-year old children and it was associated with a thicker subfoveal choroid. Few children had many small hard drusen. There is no apparent clinical impact of small hard drusen in childhood.

USP7 deubiquitinase controls HIV-1 production by stabilizing Tat protein.

Deubiquitinases (DUBs) are key regulators of complex cellular processes. HIV-1 Tat is synthesized early after infection and is mainly responsible for enhancing viral production. Here, we report that one of the DUBs, USP7, stabilized the HIV-1 Tat protein through its deubiquitination. Treatment with either a general DUB inhibitor (PR-619) or USP7-specific inhibitor (P5091) resulted in Tat protein degradation. The USP7-specific inhibitor reduced virus production in a latently infected T-lymphocytic cell line J1.1, which produces large amounts of HIV-1 upon stimulation. A potent increase in Tat-mediated HIV-1 production was observed with USP7 in a dose-dependent manner. As expected, deletion of the USP7 gene using the CRISPR-Cas9 method reduced the Tat protein and supported less virus production. Interestingly, the levels of endogenous USP7 increased after HIV-1 infection in human T-cells (MOLT-3) and in mammalian cells transfected with HIV-1 proviral DNA. Thus, HIV-1 Tat is stabilized by the host cell deubiquitinase USP7, leading to enhanced viral production, and HIV-1 in turn up-regulates the USP7 protein level.

Phase separation of fluids in porous media: a molecular dynamics study.

We present comprehensive molecular dynamics results for phase-separation kinetics of fluids in a porous medium. This system is modeled by a symmetric Lennard-Jones fluid mixture with a quenched random field. The presence of disorder slows down domain growth from power-law to a logarithmic form. It also modifies the correlation functions and structure factors which characterize the morphology. In particular, the structure-factor tail shows a non-Porod behavior, which is the consequence of scattering from rough interfaces.

Ordering kinetics in liquid crystals with long-ranged interactions.

We present the results from comprehensive Monte Carlo (MC) simulations of ordering kinetics in d = 2 liquid crystals (LCs). Our LC system is described by the two-component Lebwohl-Lasher model with long-ranged interactions, V(r) ∼ r(-n). We find that systems with n ≥ 2 show the same dynamical behavior as the nearest-neighbor case (n = ∞). This contradicts available theoretical predictions.

Crossover in growth laws for phase-separating binary fluids: molecular dynamics simulations.

Pattern and dynamics during phase separation in a symmetrical binary (A+B) Lennard-Jones fluid are studied via molecular dynamics simulations after quenching homogeneously mixed critical (50:50) systems to temperatures below the critical one. The morphology of the domains, rich in A or B particles, is observed to be bicontinuous. The early-time growth of the average domain size is found to be consistent with the Lifshitz-Slyozov law for diffusive domain coarsening. After a characteristic time, dependent on the temperature, we find a clear crossover to an extended viscous hydrodynamic regime where the domains grow linearly with time. Pattern formation in the present system is compared with that in solid binary mixtures, as a function of temperature. Important results for the finite-size and temperature effects on the small-wave-vector behavior of the scattering function are also presented.

Aging and crossovers in phase-separating fluid mixtures.

We use state-of-the-art molecular dynamics simulations to study hydrodynamic effects on aging during kinetics of phase separation in a fluid mixture. The domain growth law shows a crossover from a diffusive regime to a viscous hydrodynamic regime. There is a corresponding crossover in the autocorrelation function from a power-law behavior to an exponential decay. While the former is consistent with theories for diffusive domain growth, the latter results as a consequence of faster advective transport in fluids for which an analytical justification has been provided.

Kinetics of phase separation in fluids: a molecular dynamics study.

We present results from extensive three-dimensional molecular dynamics (MD) simulations of phase separation kinetics in fluids. A coarse-graining procedure is used to obtain state-of-the-art MD results. We observe an extended period of temporally linear growth in the viscous hydrodynamic regime. The morphological similarity of coarsening in fluids and solids is also quantified. The velocity field is characterized by the presence of monopolelike defects, which yield a generalized Porod tail in the corresponding structure factor.