CT treatment planning based on a simulator CT-option: comparison between calculation and measurements using TLDs in a humanoid phantom

Computer programs are widely used in radiotherapy to calculate the dose distribution in patients for different field configurations. The aim of this study was to investigate the dosimetry over the complete radiotherapy procedure. For this purpose, CT slices of a humanoid phantom (Alderson) were first taken with a simulator CT-option and the images then transferred to the treatment planning system. Irradiations were performed using linear accelerators. Measurements in the phantom were carried out with thermoluminescence dosimeters (TLD) and analysed using an automatic reader. Several common treatment configurations were investigated. Measurements within the target volume (low dose gradient) agreed with the calculation to within 3%. The differences in the penumbra region (high dose gradient) were in part much larger. This can be attributed to two factors: the uncertainties in the TLD localisation and the calculation chain. In conclusion, it can be stated that the agreement between calculations and measurements was sufficient for most clinical considerations. However, further checking is advisable in case sensitive organs lie in the vicinity of the field edge.     

Photodynamic therapy of malignant brain tumours: A complementary approach to conventional therapies

The poor outcome of primary malignant brain tumours is predominantly due to local invasion and local recurrence and their prognosis is highly dependent on the degree of resection. They have no border and, at best, a marginal zone that remains invisible to the surgeon. Photodynamic therapy (PDT) appears to be an interesting modality to fill the need for a targeted treatment that may reduce recurrence and extend survival with minimal side effects.     

One year follow-up to modular cognitive behavioral therapy for the treatment of pediatric anxiety disorders in an elementary school setting

The current study sought to evaluate the relative long-term efficacy of a modularized cognitive behavioral therapy (CBT) program for children with anxiety disorders. Twenty four children (5–12 years old) randomly assigned to modular CBT or a 3-month waitlist participated in a 1-year follow-up assessment. Independent evaluators blind to treatment condition conducted structured diagnostic interviews, and caregivers and children completed symptom checklists at pre- and post-, and 1 year follow-up assessments. Analyses revealed that 71.4% of children who received CBT demonstrated a positive treatment response 1 year following treatment, and 83.3% were free of any anxiety diagnosis at 1 year follow-up. Analyses further revealed robust effects of intervention on diagnostic outcomes, caregiver- and child-report measures of anxiety at 1 year follow-up. Results provide evidence of an ongoing advantage on anxiety-specific outcomes for this modularized school-based CBT program 1 year post-treatment.     

The visual attention span deficit in dyslexia is visual and not verbal

The visual attention (VA) span deficit hypothesis of dyslexia posits that letter string deficits are a consequence of impaired visual processing. Alternatively, some have interpreted this deficit as resulting from a visual-to-phonology code mapping impairment. This study aims to disambiguate between the two interpretations by investigating performance in a non-verbal character string visual categorization task with verbal and non-verbal stimuli. Results show that VA span ability predicts performance for the non-verbal visual processing task in normal reading children. Furthermore, VA span impaired dyslexic children are also impaired for the categorization task independently of stimuli type. This supports the hypothesis that the underlying impairment responsible for the VA span deficit is visual, not verbal.     

Stress and visceral pain: from animal models to clinical therapies

Epidemiological studies have implicated stress (psychosocial and physical) as a trigger of first onset or exacerbation of irritable bowel syndrome (IBS) symptoms of which visceral pain is an integrant landmark. A number of experimental acute or chronic exteroceptive or interoceptive stressors induce visceral hyperalgesia in rodents although recent evidence also points to stress-related visceral analgesia as established in the somatic pain field. Underlying mechanisms of stress-related visceral hypersensitivity may involve a combination of sensitization of primary afferents, central sensitization in response to input from the viscera and dysregulation of descending pathways that modulate spinal nociceptive transmission or analgesic response. Biochemical coding of stress involves the recruitment of corticotropin releasing factor (CRF) signaling pathways. Experimental studies established that activation of brain and peripheral CRF receptor subtype 1 plays a primary role in the development of stress-related delayed visceral hyperalgesia while subtype 2 activation induces analgesic response. In line with stress pathways playing a role in IBS, non-pharmacologic and pharmacologic treatment modalities aimed at reducing stress perception using a broad range of evidence-based mind-body interventions and centrally-targeted medications to reduce anxiety impact on brain patterns activated by visceral stimuli and dampen visceral pain.     

Adult-born neurons are necessary for extended contextual discrimination

New neurons are continuously produced in the adult dentate gyrus of the hippocampus. It has been shown that one of the functions of adult neurogenesis is to support spatial pattern separation, a process that transforms similar memories into nonoverlapping representations. This prompted us to investigate whether adult-born neurons are required for discriminating two contexts, i.e., for identifying a familiar environment and detect any changes introduced in it. We show that depleting adult-born neurons impairs the animal's ability to disambiguate two contexts after extensive training. These data suggest that the continuous production of new dentate neurons plays a crucial role in extracting and separating efficiently contextual representation in order to discriminate features within events.     

Multicenter Study on the Clinical Effectiveness, Pharmacokinetics, and Pharmacogenetics of Mirtazapine in Depression

ABSTRACT: Pharmacogenetic tests and therapeutic drug monitoring may considerably improve the pharmacotherapy of depression. The aim of this study was to evaluate the relationship between the efficacy of mirtazapine (MIR) and the steady-state plasma concentrations of its enantiomers and metabolites in moderately to severely depressed patients, taking their pharmacogenetic status into account. Inpatients and outpatients (n = 45; mean age, 51 years; range, 19-79 years) with major depressive episode received MIR for 8 weeks (30 mg/d on days 1-14 and 30-45 mg/d on days 15-56). Mirtazapine treatment resulted in a significant improvement in mean Hamilton Depression Rating Scale total score at the end of the study (P < 0.0001). There was no evidence for a significant plasma concentration-clinical effectiveness relationship regarding any pharmacokinetic parameter. The enantiomers of MIR and its hydroxylated (OH-MIR) and demethylated (DMIR) metabolites in plasma samples on days 14 and 56 were influenced by sex and age. Nonsmokers (n = 28) had higher mean MIR plasma levels than smokers (n = 17): S(+)-enantiomer of MIR, 9.4 (SD, 3.9) versus 6.2 (SD, 5.5) ng/mL (P = 0.005); R(-)-enantiomer of MIR, 24.4 (SD, 6.5) versus 18.5 (SD, 4.1) ng/mL (P = 0.003). Only in nonsmokers, plasma levels of S(+)-enantiomer of MIR and metabolites depended on the CYP2D6 genotype. Therefore, high CYP1A2 activity seen in smokers seems to mask the influence of the CYP2D6 genotype. In patients presenting the CYP2B6 *6/*6 genotype (n = 8), S-OH-MIR concentrations were higher those in the other patients (n = 37). Although it is not known if S-OH-MIR is associated with the therapeutic effect of MIR, the reduction of the Hamilton scores was significantly (P = 0.016) more pronounced in the CYP2B6 *6/*6-genotyped patients at the end of the study. The role of CYP2B6 in the metabolism and effectiveness of MIR should be further investigated.