Notes

Staff training and surgery crisis operations.
We recently described a novel missense variant [c.2090T>Gp.(Leu697Trp)] in the MYO3A gene, found in two Brazilian families with late-onset autosomal dominant nonsyndromic hearing loss (ADNSHL). Since then, with the objective of evaluating its contribution to ADNSHL in Brazil, the variant was screened in additional 101 pedigrees with probable ADNSHL without conclusive molecular diagnosis. The variant was found in three additional families, explaining 3/101 (~3%) of cases with ADNSHL in our Brazilian pedigree collection. In order to identify the origin of the variant, 21 individuals from the five families were genotyped with a high-density SNP array (~600 K SNPs- Axiom Human Origins; ThermoFisher). The identity by descent (IBD) approach revealed that many pairs of individuals from the different families have a kinship coefficient equivalent to that of second cousins, and all share a minimum haplotype of ~607 kb which includes the c.2090T>G variant suggesting it probably arose in a common ancestor. We inferred that the mutation occurred in a chromosomal segment of European ancestry and the time since the most common ancestor was estimated in 1100 years (CI = 775-1425). This variant was also reported in a Dutch family, which shares a 87,121 bp haplotype with the Brazilian samples, suggesting that Dutch colonists may have brought it to Northeastern Brazil in the 17th century. Therefore, the present study opens new avenues to investigate this variant not only in Brazilians but also in European families with ADNSHL.A major theme of addiction research has focused on the neural substrates of individual differences in the risk for addiction; however, little is known about how vulnerable populations differ from those that are relatively protected. Here, we prospectively measured dopamine (DA) neurotransmission prior to cocaine exposure to predict the onset and course of cocaine use. Using in vivo voltammetry, we first generated baseline profiles of DA release and uptake in the dorsomedial striatum (DMS) and nucleus accumbens of drug-naïve male rats prior to exposing them to cocaine using conditioned place preference (CPP) or operant self-administration. We found that the innate rate of DA uptake in the DMS strongly predicted motivation for cocaine and drug-primed reinstatement, but not CPP, responding when "price" was low, or extinction. We then assessed the impact of baseline variations in DA uptake on cocaine potency in the DMS using ex vivo voltammetry in naïve rats and in rats with DA transporter (DAT) knockdown. DA uptake in the DMS of naïve rats predicted the neurochemical response to cocaine, such that rats with innately faster rates of DA uptake demonstrated higher cocaine potency at the DAT and rats with DAT knockdown displayed reduced potency compared to controls. Together, these data demonstrate that inherent variability in DA uptake in the DMS predicts the behavioral response to cocaine, potentially by altering the apparent potency of cocaine.
Silicone personal samplers are increasingly being used to measure chemical exposures, but many of these studies do not attempt to calculate environmental concentrations.

Using measurements of silicone wristband uptake of organic chemicals from atmospheric exposure, create log K
and k
predictive models based on empirical data to help develop air equivalency calculations for both volatile and semi-volatile organic compounds.

An atmospheric vapor generator and a custom exposure chamber were used to measure the uptake of organic chemicals into silicone wristbands under simulated indoor conditions. Log K
models were evaluated using repeated k-fold cross-validation. Air equivalency was compared between best-performing models.

Log K
and log k
estimates calculated from uptake data were used to build predictive models from boiling point (BP) and other parameters (all models R
 = 0.70-0.94). The log K
models were combined with published data and refined to create comprehensive and effective predictive models (R
0.95-0.97). Final estimates of air equivalency using novel BP models correlated well over an example dataset (Spearman r = 0.984) across 5-orders of magnitude (<0.05 to >5000 ng/L).

Data from silicone samplers can be translated into air equivalent concentrations that better characterize environmental concentrations associated with personal exposures and allow direct comparisons to regulatory levels.
Data from silicone samplers can be translated into air equivalent concentrations that better characterize environmental concentrations associated with personal exposures and allow direct comparisons to regulatory levels.Transcatheter aortic valve replacement (TAVR) is a rapidly growing field. Short-term safety and efficacy of these procedures have been studied extensively. However, little is known about the safety of these devices over time. Stroke is one feared long-term complication, and an increased stroke rate could affect guidelines for treating both the aortic stenosis and choosing antithrombotic therapy after TAVR. The primary objective was to study the incidence of stroke up to 8 years after TAVR implantation, comparing it with the risk of stroke in the general population. Secondary objectives were to study risk factors for late stroke and to study outcomes after stroke. A nationwide, all-comers study of patients who underwent TAVR in Sweden 2008-2018 was performed. The study was based on data from three national registries a TAVR registry, a stroke registry, and a diagnosis registry. The main outcome was stroke incidence 30-days or more after TAVR implantation and was compared to a standardized incidence. The annual risk for stroke varied between 2.0% and 3.1% as compared to 1.5% and 1.9% in an age- and sex-matched cohort. Risk factors for developing stroke were reduced renal function, diabetes, history of stroke, age, and male sex. The 1-year mortality after stroke was 44%. L-glutamate price This study demonstrated an increased rate of stroke after TAVR, but the findings suggest that this can in part be attributed to the group's higher frequency of pre-disposing risk factors.
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