Brain Connectivity and Symptom Changes After Transcranial Magnetic Stimulation in Patients With Borderline Personality Disorder.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is an innovative method in the treatment of borderline personality disorder (BPD). We hypothesized that prefrontal rTMS in patients with BPD leads to improved BPD symptoms and that these effects are associated with brain connectivity changes. METHODS: Fourteen patients with BPD received 15 sessions of individually navigated prefrontal rTMS over the right dorsolateral prefrontal cortex. Clinical effects were measured by the Borderline Symptom List 23, UPPS-P, the Difficulties in Emotion Regulation Scale (DERS), the Zung Self-Rating Anxiety Scale (SAS), and the Montgomery and Åsberg Depression Rating Scale (MADRS). Effects of rTMS on brain connectivity were observed with a seed correlation analysis on resting-state fMRI and with a beta series correlation analysis on Go/No Go tasks during fMRI. Assessments were made before and immediately after the treatment. RESULTS: The assessments after rTMS showed significant reductions in two subscales of UPPS-P, and in DERS, SAS, and MADRS. The brain connectivity analysis revealed significant decreases in amygdala and insula connectivity with nodes of the posterior default mode network (pDMN; precuneus, posterior cingulate cortex, parietal lobules). Connectivity changes were observed both in the resting state and during inhibition. The decrease of amygdala-pDMN connectivity was positively correlated with reduced depression and lack of premeditation after rTMS. CONCLUSIONS: Despite the study limitations (open single-arm study in a small sample), our findings suggest a possible neural mechanism of rTMS effect in BPD, reduced amygdala connectivity with the pDMN network, which was positively associated with symptom reduction.

Efficacy and Safety of Intensive Transcranial Magnetic Stimulation.

Repetitive transcranial magnetic stimulation (rTMS) is customarily applied on a daily basis for prolonged periods of time for the treatment of psychiatric diseases. The process is demanding in terms of staff and patient time, and the onset of the effect is slow. Recently, intensive rTMS protocols have been introduced in which stimulation is applied to the same area more than once a day with a higher than standard number of pulses. This article reviews 16 articles to determine the safety and efficacy of such protocols. Intensive rTMS seems to be effective in various mental disorders. It appears to have, in general, the same adverse events as classic, long-term, daily rTMS, and it is largely well tolerated by the patients. One episode of depersonalization, one of increased suicidal thoughts, and two of induced mania were observed in the 16 studies reviewed. The advantages of intensive rTMS are in the possible acute effect of the stimulation and in the possible reduction in the time required to achieve remission in depression (and potentially other disorders). It remains uncertain whether intensive rTMS is more effective than sham stimulation or once-daily, long-term rTMS.

The influence of stevia on the flow, shear and compression behavior of sorbitol, a pharmaceutical excipient for direct compression.

Good flow and compaction properties are necessary for the manipulation of particulate material in the pharmaceutical industry. The influence of the addition of an alternative sweetener, rebaudioside A, in a concentration 0.2% w/w and 0.5% w/w on the flow, shear and compaction properties of sorbitol for direct compaction, Merisorb® 200, was investigated in this work. Rebaudioside A worsened the flow properties of sorbitol: the Hausner ratio, the compressibility index and the mass flow rate through the aperture of a model hopper. Using a Jenike shear cell revealed a significant increase in cohesion leading to the decrease of the flow function; moreover, the addition of rebaudioside A increased the total energy for compression of tablets and plasticity estimated by the force-displacement method. Finally, the tablets showed a higher tensile strength and needed longer time to disintegrate compared to the tablets made of sorbitol itself. In view of the results for the free-flowable excipient, sorbitol, the effects of stevia even for a 0.2% w/w concentration have to be carefully considered, particularly whenever used in pharmaceutical formulations of poor flow properties.

Predictors of quality of life in Czech female breast cancer survivors following treatment with special interest to coping strategies.

OBJECTIVES: This study examined the prognostic significance of breast cancer patients characteristics (coping strategies, BMI, age) and disease characteristics (stage of disease, relapse) with respect to quality of life (QoL) following treatment.Sample and settings: 120 breast cancer patients following treatment were recruited. Health-related QoL was assessed using the Czech version of FACT-B and SF-36; additionally, we used a life satisfaction questionnaire. Coping strategies were assessed using the SVF-78 method. In our sample of women, the average time from diagnosis to start of the study was 5.3 years. STATISTICAL ANALYSIS: Factors influencing QoL after treatment were analysed with univariate and multivariate linear regression. RESULTS: Overall negative strategy defined in SVF-78 (Flight tendency, Resignation and Self-accusation) was found to be associated with lower scores of most components of used QoL methods, while Resignation was found as the most negatively influencing strategy. Active problem confrontation (Situation control and Positive self-instruction) was associated with better QoL. More advanced stages and recurrence were related to a significant decrease in QoL for certain components only. CONCLUSION: Our findings suggest a significant predictive power of disease-related factors and of patients characteristics including coping strategies for QoL following treatment in Czech breast cancer survivors.Key words: breast cancer survivors - coping strategy - linear regression model - quality of life prediction - resignation.

Fractal aspects of the flow and shear behaviour of free-flowable particle size fractions of pharmaceutical directly compressible excipient sorbitol.

Flowability of powder excipients is directly influenced by their size and shape although the granulometric influence of the flow and shear behaviour of particulate matter is not studied frequently. In this work, the influence of particle size on the mass flow rate through the orifice of a conical hopper, and the cohesion and flow function was studied for four free-flowable size fractions of sorbitol for direct compression in the range of 0.080-0.400 mm. The particles were granulometricaly characterized using an optical microscopy; a boundary fractal dimension of 1.066 was estimated for regular sorbitol particles. In the particle size range studied, a non-linear relationship between the mean particle size and the mass flow rate Q10 (g/s) was detected having amaximum at the 0.245mm fraction. The best flow properties of this fraction were verified with aJenike shear tester due to the highest value of flow function and the lowest value of the cohesion. The results of this work show the importance of the right choice of the excipient particle size to achieve the best flow behaviour of particulate material.Key words: flowability size fraction sorbitol for direct compaction Jenike shear tester fractal dimension.