Children's Shyness, Frontal Brain Activity, and Anxiety in the Perioperative Context.

Although preoperative anxiety affects up to 75% of children undergoing surgery each year and is associated with many adverse outcomes, we know relatively little about individual differences in how children respond to impending surgery. We examined whether patterns of anterior brain electrical activity (i.e.

Characterizing Population EEG Dynamics throughout Adulthood.

For decades, electroencephalography (EEG) has been a useful tool for investigating the neural mechanisms underlying human psychological processes. However, the amount of time needed to gather EEG data means that most laboratory studies use relatively small sample sizes. Using the Muse, a portable and wireless four-channel EEG headband, we obtained EEG recordings from 6029 subjects 18-88 years in age while they completed a category exemplar task followed by a meditation exercise.

Attentional and affective consequences of technology supported mindfulness training: a randomised, active control, efficacy trial.

Background: Mindfulness training (MT) programs represent an approach to attention training with well-validated mental health benefits. However, research supporting MT efficacy is based predominantly on weekly-meeting, facilitator-led, group-intervention formats. It is unknown whether participants might benefit from neurofeedback-assisted, technology-supported MT (N-tsMT), in which meditation is delivered individually, without the need for a facilitator, travel to a training site, or the presence of a supportive group environment.

Reprint of "Potential seminal transport of pharmaceuticals to the conceptus".

Small molecule pharmaceutical products are assumed to reach concentrations in semen similar to those in blood plasma. Exposure modeling for these small-molecule products in humans assumes a daily dose of 5mL of semen and 100% absorption from the vagina with distribution to the conceptus through the maternal systemic circulation. Monoclonal antibody drugs are present in semen at concentrations about 2% or less of those in blood, and the modeling used for small molecules will over-estimate the possibility of conceptus exposure to immunoglobulins.

Potential seminal transport of pharmaceuticals to the conceptus.

Small molecule pharmaceutical products are assumed to reach concentrations in semen similar to those in blood plasma. Exposure modeling for these small-molecule products in humans assumes a daily dose of 5mL of semen and 100% absorption from the vagina with distribution to the conceptus through the maternal systemic circulation. Monoclonal antibody drugs are present in semen at concentrations about 2% or less of those in blood, and the modeling used for small molecules will over-estimate the possibility of conceptus exposure to immunoglobulins.

Evaluation of early fetal exposure to vaginally-administered metronidazole in pregnant cynomolgus monkeys.

Given concern about potential embryo-fetal harm following seminal exposure to drugs with teratogenic potential, pharmaceutical companies use theoretical calculations to estimate seminal concentrations, maternal exposure, and distribution across the placenta to the embryo-fetal compartment for risk assessment. However, it is plausible that there are additional mechanisms whereby the conceptus is exposed. In order to determine if theoretical calculations are sufficiently conservative to predict embryo-fetal exposure from drugs in semen, pregnant cynomolgus monkeys were given a vaginal dose of metronidazole during the early fetal period and cesarean-sectioned.

An open-label study in healthy men to evaluate the risk of seminal fluid transmission of denosumab to pregnant partners.

Aims: Denosumab is a fully human monoclonal immunoglobulin G2 antibody that inhibits bone resorption and increases bone mass and strength. The present clinical study assessed serum and seminal fluid pharmacokinetics following a single denosumab dose in healthy men, and evaluated whether denosumab in seminal fluid poses any risk to a fetus in the event of unprotected sexual intercourse with a pregnant partner.

Methods: An open-label, single-dose study in 12 healthy men was conducted over a 106-day period.

Achieving across-laboratory replicability in psychophysical scaling.

It is well known that, although psychophysical scaling produces good qualitative agreement between experiments, precise quantitative agreement between experimental results, such as that routinely achieved in physics or biology, is rarely or never attained. A particularly galling example of this is the fact that power function exponents for the same psychological continuum, measured in different laboratories but ostensibly using the same scaling method, magnitude estimation, can vary by a factor of three. Constrained scaling (CS), in which observers first learn a standardized meaning for a set of numerical responses relative to a standard sensory continuum and then make magnitude judgments of other sensations using the learned response scale, has produced excellent quantitative agreement between individual observers' psychophysical functions.

Investigation of maternal and fetal exposure to an IgG2 monoclonal antibody following biweekly intravaginal administration to cynomolgus monkeys throughout pregnancy.

To assess the potential for male-mediated drug transfer to their female partner and/or developing conceptus, vaginal uptake of a monoclonal antibody (mAb) biotherapeutic was assessed in cynomolgus monkeys. A human IgG2 mAb (IgG2X; bound human and cynomolgus monkey neonatal Fc-receptor, FcRn, with similar high affinity) was administered intravaginally (IvG; 100mg/dose) to 5 pregnant cynomolgus monkeys biweekly from gestation day (gd) 21 to gd133. In all maternal samples collected before gd119, IgG2X plasma concentrations were below the limit of quantification (BLQ; <25ng/mL).

Placental transfer of a fully human IgG2 monoclonal antibody in the cynomolgus monkey, rat, and rabbit: a comparative assessment from during organogenesis to late gestation.

Understanding species differences in the placental transfer of monoclonal antibodies is important to inform species selection for nonclinical safety assessment, interpret embryo-fetal changes observed in these studies, and extrapolate their human relevance. Data presented here for a fully human immunoglobulin G2 monoclonal antibody (IgG2X) revealed that, during organogenesis, in both the cynomolgus monkey (gestation day 35 [gd35]) and the rat (gd10) the extent of IgG2X placental transfer (approximately 0.5% maternal plasma concentration, MPC) was similar to the limited published human data for endogenous IgG.

Placental transfer of Fc-containing biopharmaceuticals across species, an industry survey analysis.

Background: Understanding species differences in placental transfer of Fc-containing biopharmaceuticals (particularly monoclonal antibodies) will improve human risk extrapolation from nonclinical embryo-fetal development toxicity data.

Methods: Maternal and fetal concentration data from 10, 15, 8, and 34 Fc-containing biopharmaceuticals in the rabbit, rat, mouse, and cynomolgus monkey, respectively, from an industry survey were analyzed for trends in placental transfer.

Results And Conclusions: Embryonic (before the end of organogenesis) exposure was assessed in one molecule each in rabbit, rat, and mouse, but detectable levels were present only in rodents.

Assessment of menstrual cycle length in cynomolgus monkeys as a female fertility endpoint of a biopharmaceutical in a 6 month toxicity study.

According to ICH S6(R1), mating studies are not practical for assessing effects on female fertility of biopharmaceuticals that are pharmacologically active only in non-human primates (NHPs). Instead, fertility should be assessed by evaluating histopathology and organ weights of the reproductive tract in studies of at least 3 months dosing duration using sexually mature NHPs. An assessment of the menstrual cycle in females can be included if there is cause for concern based on pharmacological mode of action or relevant findings in previous studies.

Residual inhibition functions overlap tinnitus spectra and the region of auditory threshold shift.

Animals exposed to noise trauma show augmented synchronous neural activity in tonotopically reorganized primary auditory cortex consequent on hearing loss. Diminished intracortical inhibition in the reorganized region appears to enable synchronous network activity that develops when deafferented neurons begin to respond to input via their lateral connections. In humans with tinnitus accompanied by hearing loss, this process may generate a phantom sound that is perceived in accordance with the location of the affected neurons in the cortical place map.

Residual inhibition functions in relation to tinnitus spectra and auditory threshold shift.

Conclusions: Psychoacoustic functions relating the depth and duration of tinnitus suppression ('residual inhibition') to the center frequency of band-passed noise masking sounds appear to span the region of hearing loss, as do psychoacoustic measurements of the tinnitus spectrum. The results (1) suggest that cortical map reorganization induced by hearing loss is not the principal source of the tinnitus sensation and (2) provide a necessary baseline for optimizing residual inhibition in individual cases.

Objective: To measure residual inhibition functions and tinnitus spectra using sounds spanning the region of hearing loss.

Confirmation of uterotrophic activity of 3-(4-methylbenzylidine)camphor in the immature rat.

In this study we found that the ultraviolet sunscreen component 3-(4-methylbenzylidine)camphor (4MBC) is uterotrophic in immature rats when administered by either subcutaneous injection or oral gavage. These data confirm earlier reports of uterotrophic activity for this agent when administered to immature rats in the diet or by whole-body immersion; however, they are in contrast to negative unpublished immature rat uterotrophic assay results. Data also indicate that 4MBC binds to isolated rat uterine estrogen receptors and shows activity in a human estrogen receptor yeast transactivation assay; however, we considered both of these effects equivocal.

Loss of the Nrf2 transcription factor causes a marked reduction in constitutive and inducible expression of the glutathione S-transferase Gsta1, Gsta2, Gstm1, Gstm2, Gstm3 and Gstm4 genes in the livers of male and female mice.

Mice that lack the Nrf2 basic-region leucine-zipper transcription factor are more sensitive than wild-type (WT) animals to the cytotoxic and genotoxic effects of foreign chemicals and oxidants. To determine the basis for the decrease in tolerance of the Nrf2 homozygous null mice to xenobiotics, enzyme assay, Western blotting and gene-specific real-time PCR (TaqMan) have been used to examine the extent to which hepatic expression of GSH-dependent enzymes is influenced by the transcription factor. The amounts of protein and mRNA for class Alpha, Mu and Pi glutathione S-transferases were compared between WT and Nrf2 knockout (KO) mice of both sexes under both constitutive and inducible conditions.