Validity of model approximations for receptor-ligand kinetics in nuclear medicine

An appropriate mathematical model is required for quantitative analysis of high affinity radioligands as direct or surrogate probes to measure receptor distribution, affinity, concentration, binding potential, and endogenous or exogenous ligand occupancy levels. For studies with positron emission tomography (PET) or single photon emission computed tomography (SPECT), the receptor-ligand compartment model has been well established and widely used. This pharmacokinetic model is represented mathematically by a set of nonlinear ordinary differential equations. Variations of models for PET and SPECT account for radioactive decay differently. These are not equivalent and entail assumptions or approximations that may be not appreciated. In this study, a general form of the model is presented and compared with others with various approximations, which are valid only under specific conditions. The various approximate formulations were analytically compared to the exact model to identify the terms that were neglected in the approximate formulations. The extent to which the approximations impact the model solutions was assessed by computer simulations based on numerical solutions to each set of equations. Specifically, each model formulation was tested using three simulated injection protocols representing a typical PET experiment, a typical SPECT experiment, and an extreme experiment where both the injected activity and the specific activity were very high. No significant differences were found among the output of the three model formulations when the PET and SPECT injection protocols were tested. The only conditions that produced significant differences occurred when the specific activity and the administered activity were simultaneously very high. These conditions, however, have little practical relevance to experimentally achievable conditions due to radiation dose and specific activity of radiopharmaceuticals     

Increased methylation at an unexplored glucocorticoid responsive element within exon 1D of NR3C1 gene is related to anxious-depressive disorders and decreased hippocampal connectivity

Among the major psychiatric disorders, anxious-depressive disorders stand out as one of the more prevalent and more frequently associated with hypothalamic-pituitary-adrenal (HPA) axis abnormalities. Methylation at the exon 1_F of the glucocorticoid receptor gene NR3C1 has been associated with both early stress exposure and risk for developing a psychiatric disorder; however, other NR3C1 promoter regions have been underexplored. Exon 1_D emerges as a suggestive new target in stress-related disorders epigenetically sensitive to early adversity. After assessment of 48 monozygotic twin pairs (n=96 subjects) informative for lifetime history of anxious-depressive disorders, they were classified as concordant, discordant or healthy in function of whether both, one or neither twin in each pair had a lifetime diagnosis of anxious-depressive disorders. DNA for epigenetic analysis was extracted from peripheral blood. Exon 1_F and exon 1_D CpG-specific methylation was analysed by means of pyrosequencing technology. Functional magnetic resonance imaging was available for 54 subjects (n=27 twin pairs). Exon 1_D CpG-specific methylation within a glucocorticoid responsive element (GRE) was correlated with familial burden of anxious-depressive disorders (r=0.35, z=2.26, p=0.02). Right hippocampal connectivity was significantly associated with CpG-specific GRE methylation (β=?2.33, t=?2.85, p=0.01). Exon 1_F was uniformly hypomethylated across all subgroups of the present sample. GRE hypermethylation at exon 1_D of the NR3C1 gene in monozygotic twins concordant for anxious-depressive disorders suggests this region plays a role in increasing vulnerability to psychosocial stress, partly mediated by altered hippocampal connectivity.     

Quality of life and stability of tooth color change at three months after dental bleaching

Purpose

Intracoronary bleaching is a minimally invasive, alternative treatment that addresses aesthetic concerns related to non-vital teeth discoloration. However, to the best of our knowledge, no studies have assessed the psychosocial impacts of such procedures on patients’ aesthetic perceptions. The aim of this study was to evaluate aesthetic perceptions and the psychosocial impact of patients up to 3 months after their teeth had been bleached with hydrogen peroxide (35%) and carbamide peroxide (37%) using the walking bleach technique.

Methods

The patients were randomly divided into two groups according to the bleaching agent used: G1?=?hydrogen peroxide 35% (n?=?25) and G2?=?carbamide peroxide 37% (n?=?25). Non-vital bleaching was performed in four sessions. Color was objectively (ΔE) and subjectively (ΔSGU) evaluated. Aesthetic perception and psychosocial factors were evaluated before, 1 week and 1 month after the bleaching using the Oral Health Impact Profile (OHIP) and Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) questionnaires.

Results

The color change (ΔE) values at 1 month were G1?=?16.80?±?6.07 and G2?=?14.09?±?4.83. These values remained stable until the third month after treatment (p?>?0.05). There was a decrease in the values of OHIP-aesthetics and PIDAQ after treatment versus baseline (p?<?0.05). This status was maintained through the third month after treatment.

Conclusions

Both agents were highly effective and had a positive impact on the aesthetic perception and psychosocial impact of patients, values that also remained stable over time. Non-vital bleaching yields positive and stable impacts on aesthetic perception and psychosocial factors. ClinicalTrials.gov identifier NCT02718183.

     

ASO Visual Abstract: Repeat Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Cancers with Peritoneal Metastasis—A 30-year Institutional Experience

Annals of Surgical Oncology -     

Non-invasive high-speed blinking kinematics characterization

Graefe's Archive for Clinical and Experimental Ophthalmology - The objective of this study was to analyze the differences in blinking kinematics of spontaneous and voluntary blinks using for...     

Low-fidelity simulation improves mastery of the aseptic technique for labour epidurals: an observational study

Purpose

The objective of this study was to determine the impact of a low-fidelity simulation model on mastering the sterile technique during placement of epidural catheters.

Methods

Trainees, including residents and fellows, were given conventional teaching consisting of a lecture and a video demonstration on the appropriate sterile technique to apply during the placement of epidural catheters. The trainees were then provided with a one-on-one demonstration session using a low-fidelity Styrofoam? epidural model, followed by a series of simulation sessions. After conventional teaching and following each simulation session, the trainees were assessed on their performance until competence was achieved based on a 15-point checklist. The retention of competence was subsequently evaluated bi-weekly in clinical practice for four assessments.

Results

Twenty-one trainees participated in the study. The average score for the residents following conventional teaching was 6.0 out of 15 points on the checklist. Following the initial one-on-one hands-on demonstration, the average score increased to 10.8 (difference = 4.8, 95% confidence interval (CI): 3.3 to 6.2; P < 0.001). The average score for the fellows following conventional teaching was 7.9 out of 15 points on the checklist. Following the initial one-on-one hands-on demonstration the average score increased to 11.2 (difference = 3.3, 95% CI: 0.05 to 6.6; P = 0.047). During the retention of competence phase, scores ranged from 13-15 for both residents and fellows.

Conclusion

This study describes a comprehensive teaching model for mastering the sterile technique during epidural catheter placement. It suggests that low-fidelity simulation improves the learning process when used in addition to conventional teaching.