Propofol Pharmacokinetics and Pharmacodynamics for Depth of Sedation in Nonventilated Infants after Major Craniofacial Surgery

Background: To support safe and effective use of propofol in nonventilated children after major surgery, a model for propofol pharmacokinetics and pharmacodynamics is described.

Methods: After craniofacial surgery, 22 of the 44 evaluated infants (aged 3-17 months) in the pediatric intensive care unit received propofol (2-4 mg [middle dot] kg-1 [middle dot] h-1) during a median of 12.5 h, based on the COMFORT-Behavior score. COMFORT-Behavior scores and Bispectral Index values were recorded simultaneously. Population pharmacokinetic and pharmacodynamic modeling was performed using NONMEM V (GloboMax LLC, Hanover, MD).

Results: In the two-compartment model, body weight (median, 8.9 kg) was a significant covariate. Typical values were Cl = 0.70 [middle dot] (BW/8.9)0.61 l/min, Vc = 18.8 l, Q = 0.35 l/min, and Vss = 146 l. In infants who received no sedative, depth of sedation was a function of baseline, postanesthesia effect (Emax model), and circadian night rhythm. In agitated infants, depth of sedation was best described by baseline, postanesthesia effect, and propofol effect (Emax model). The propofol concentration at half maximum effect was 1.76 mg/l (coefficient of variation = 47%) for the COMFORT-Behavior scale and 3.71 mg/l (coefficient of variation = 145%) for the Bispectral Index.     

Diagnostic evaluation of magnetization transfer and diffusion kurtosis imaging for prostate cancer detection in a re-biopsy population

Objective

To evaluate diffusion kurtosis imaging (DKI) and magnetisation transfer imaging (MTI) compared to standard MRI for prostate cancer assessment in a re-biopsy population.

Methods

Thirty-patients were imaged at 3 T including DKI (K_app and D_app) with b-values 150/450/800/1150/1500 s/mm² and MTI performed with and without MT saturation. Patients underwent transperineal biopsy based on prospectively defined MRI targets. Receiver-operating characteristic (ROC) analyses assessed the parameters and Wilcoxon-signed ranked test assessed relationships between metrics.

Results

Twenty patients had ≥ 1 core positive for cancer in a total of 26 MRI targets (Gleason 3+3 in 8, 3+4 in 12, ≥ 4+3 in 6): 13 peripheral (PZ) and 13 transition zone (TZ). The apparent diffusion coefficient (ADC) and D_app were significantly lower and the K_app and MT ratio (MTR) significantly higher in tumour versus benign tissue (all p ≤ 0.005); ROC values 0.767-1.000. Normal TZ had: lower ADC and D_app and higher K_app and MTR compared to normal PZ. MTR showed a moderate correlation to K_app (r = 0.570) and D_app (r = -0.537) in normal tissue but a poor correlation in tumours. No parameter separated low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease for either PZ (p = 0.414-0.825) or TZ (p = 0.148-0.825).

Conclusion

ADC, D_app, K_app and MTR all distinguished benign tissue from tumour, but none reliably differentiated low- from high-grade disease.

Key Points

? MTR was significantly higher in PZ and TZ tumours versus normal tissue ? K _app was significantly lower and D _app higher for PZ and TZ tumours ? There was no incremental value for DKI/MTI over mono-exponential ADC parameters ? No parameter could consistently differentiate low-grade (Gleason 3+3) from high-grade (≥ 3+4) disease ? Divergent MTR/DKI values in TZ tumours suggests they offer different functional information

     

The impact of a teacher-led structured physical activity session on preschoolers’ sedentary and physical activity levels

ObjectivesThe purpose of this observational study was to examine differences in preschoolers’ sedentary time and physical activity (PA) participation between preschool-attending weekdays with and without a teacher-led structured PA session.DesignA sample of 200 preschoolers (5.3 ± 0.4 y; 113 boys) from 26 preschools in Flanders, Belgium were included in data analysis.MethodsParticipants wore a GT1M ActiGraph accelerometer on one preschool-attending weekday with and on one preschool-attending weekday without the provision of a teacher-led structured PA session. Preschoolers’ sedentary time, light PA, and moderate-to-vigorous physical activity (MVPA) during the time in preschool (08:00–16:00 h) and after preschool (16:00–20:00 h) were estimated. To assess differences in the outcome measures between both days, multi-level linear regression models were conducted.ResultsDuring the time at preschool, lower sedentary levels (β = 13.0 min; SE = 1.6; p < 0.001) and higher light PA (β = 2.9 min; SE = 0.7 p < 0.001) and MVPA levels (β = 10.1 min; SE = 1.1; p < 0.001) were prevalent on days with a structured PA session compared to days without a structured PA session in both boys and girls. After preschool, no differences were found between both days in sedentary time (β = 0.7; SE = 1.4; p > 0.05), light PA (β = 0.3; SE = 0.5; p > 0.05), and MVPA (β = 0.3; SE = 0.9; p > 0.05).ConclusionsThe results demonstrate that no compensatory changes were found after preschool for the structured PA session during the preschool hours. Therefore, a teacher-led structured PA session integrated in the preschool curriculum is a promising mean to decrease sedentary time and to increase PA in preschool-aged boys and girls.     

A randomized study of the effect of carbonated water prior to myocardial SPECT

Objective

In myocardial perfusion single-photon emission computed tomography (SPECT), abdominal activity often interferes with the evaluation of perfusion in the inferior wall, especially after pharmacological stress. In this randomized study, we examined the effect of carbonated water intake versus still water intake on the quality of images obtained during myocardial perfusion images (MPI) studies.

Methods

A total of 467 MIBI studies were randomized into a carbonated water group and a water group. The presence of intestinal activity adjacent to the inferior wall was evaluated by two observers. Furthermore, a semi-quantitative analysis was performed in the adenosine subgroup, using a count ratio of the inferior myocardial wall and adjacent abdominal activity.

Results

The need for repeated SPECT in the adenosine studies was 5.3 % in the carbonated water group versus 19.4 % in the still water group (p = 0.019). The inferior wall-to-abdomen count ratio was significantly higher in the carbonated water group compared to the still water group (2.11 ± 1.00 vs. 1.72 ± 0.73, p < 0.001). The effect of carbonated water during rest and after exercise was not significant.

Conclusions

This randomized study showed that carbonated water significantly reduced the interference of extra-cardiac activity in adenosine SPECT MPI.     

Lack of lithium-like behavioral and molecular effects in IMPA2 knockout mice.

Lithium is a potent mood-stabilizing medication in bipolar disorder. Despite 50 years of clinical use, the mechanism of action is unknown. Multiple effects have been attributed to lithium including the uncompetitive inhibition of inositol monophosphatase (IMPase). IMPA2, one of the genes that encode IMPase, is located in a region with linkage to bipolar disorder. Owing to the role of IMPase in cell signaling and the possibility that this enzyme is a target for mood-stabilizing drugs, we generated IMPA2(-/-) mice. Possible involvement of IMPase in complex behaviors related to affective disorders was assessed by monitoring the behavior of the IMPA2(-/-) mice in the forced swim test, the tail suspension test (TST), the elevated zero-maze and open field test. It has been described that chronically lithium-treated mice exhibit reduced immobility time in the forced swim test and decreased exploratory behavior. We found increased rearing of IMPA2(-/-) mice in the open field, suggesting an increased exploratory behavior. Although immobility time of IMPA2(-/-) female but not male mice in the forced swim test was reduced, no difference was found between male and female IMPA2(-/-) and IMPA2(+/+) mice in the TST and overall there was no clear effect of the deletion of IMPA2 on depression-like behavior. Frontal cortex IMPase activity and inositol levels in the IMPA2(-/-) mice did not differ from IMPA2(+/+) mice, but kidney inositol levels were reduced. In conclusion, phenotypic characterization of the IMPA2(-/-) mouse indicates that deleting IMPA2 does not mimic the effects of lithium treatment.     

The application of a social cognition model in explaining fruit intake in Austrian, Norwegian and Spanish schoolchildren using structural equation modelling

Background  

The aim of this paper was to test the goodness of fit of the Attitude – Social influence – self-Efficacy (ASE) model in explaining schoolchildren's intentions to eat fruit and their actual fruit intake in Austria, Norway and Spain; to assess how well the model could explain the observed variance in intention to eat fruit and in reported fruit intake and to investigate whether the same model would fit data from all three countries.     

Synthesis and biological evaluation of cycloalkylidene carboxylic acids as novel effectors of Ras/Raf interaction

The protooncogenes Ras and Raf play important roles in signal transduction pathways regulated by mitogen-activated protein kinases. Mutations of Ras that arrest the protein in its active state are frequently implicated in tumor formation. We used Ras and Raf proteins in the yeast two-hybrid system to search for natural or synthesized substances capable of modulating Ras/Raf interaction by specifically binding to one of the interacting partners. We found that cycloalkylidene carboxylic acids enhanced Ras/Raf interaction by acting on the cysteine-rich domain of Raf. Several analogues of the active substance 2-cyclohexylidene propanoic acid were synthesized and the importance of the semicyclic double bond in the stabilization of Ras/Raf interaction was demonstrated. Variation of the size and the substituents of the cyclic system as well as the length of the carboxylic acid resulted in enhanced Ras/Raf interaction.     

Computational flow modeling in hollow-fiber dialyzers

A three-dimensional finite volume model of the blood-dialysate interface over the complete length of the dialyzer was developed. Different equations govern dialyzer flow and pressure distribution (Navier-Stokes) and radial transport (Darcy). Blood was modeled as a non-Newtonian fluid with a viscosity varying in radial and axial direction determined by the local hematocrit, the diameter of the capillaries, and the local shear rate. The dialysate flow was assumed to be an incompressible, isothermal laminar Newtonian flow with a constant viscosity. The permeability characteristics of the membrane were calculated from laboratory tests for forward and backfiltration. The oncotic pressure induced by the plasma proteins was implemented as well as the reduction of the overall permeability caused by the adhesion of proteins to the membrane. From the calculated pressure distribution, the impact of flow, hematocrit, and capillary dimensions on the presence and localization of backfiltration can be investigated.     

Female genital mutilation: knowledge, attitudes and practices of Flemish gynaecologists.

ObJECTIVE: To assess the knowledge, attitudes and practices with regard to female genital mutilation (FGM) among gynaecologists in Flanders, Belgium. METHODS: A questionnaire-based survey was sent to 724 Flemish gynaecologists and trainees. RESULTS: Three-hundred-and-thirty-four questionnaires were returned. The survey revealed gaps in the knowledge of FGM and the provision of care by Flemish gynaecologists to women who had been mutilated. It also appeared that FGM was not properly addressed in the basic and specialized medical training in Flanders, that little was known about codes of conduct issued by the hospitals when these were not lacking altogether, and that knowledge about legislation concerning FGM was deficient. There was much confusion whether re-infibulation is authorized, and what its legal status is. Some respondents considered cosmetic vaginal surgery as a form of FGM and many were in favour of the medicalization of FGM. Gynaecologists were most commonly confronted with complaints related to sexual problems caused by FGM. Finally, the study also showed that only about a third of the gynaecologists were discouraging women from having their daughters excised. CONCLUSION: There is a need for a thorough discussion among all those concerned of the ethical and legal aspects of re-infibulation, medicalization of FGM and cosmetic vaginal surgery.     

Identity development, coping, and adjustment in emerging adults with a chronic illness: the sample case of type 1 diabetes

PURPOSE: The present study focused on identity development in emerging adults (aged 18-30 years) with type 1 diabetes. The three study aims were to examine the following: (1) whether identity development was affected by having diabetes, as compared with development in a nondiabetic sample; (2) how identity development was related to depressive symptoms, coping with diabetes, and diabetes-related problems in the diabetic sample; and (3) whether the pathways from identity development to problems with diabetes and depressive symptoms were mediated through coping strategies in the diabetic sample. METHODS: A total of 194 emerging adults with type 1 diabetes and 344 nondiabetic emerging adults participated. RESULTS: First, using analyses of variance, some mean identity differences between the diabetic and comparison samples were found, with emerging adults with diabetes scoring lower on proactive identity exploration. Using cluster analysis, we found that the same identity types or statuses emerged in both the diabetic and nondiabetic samples. Second, in emerging adults with diabetes, these identity statuses were differentially related to diabetes-related problems, depressive symptoms, and illness coping, with the identity statuses representing a strong sense of identity being accompanied by less diabetes-related problems and depressive symptoms and more adequate coping strategies. Third, using structural equation modeling, the pathways from a strong sense of identity to diabetes-related problems and depressive symptoms were mediated through adaptive and maladaptive coping. CONCLUSIONS: Clinicians should be sensitive to the normative task of identity development in emerging adults with diabetes because identity development can function as a resource in coping with and adjusting to diabetes.