The Bereavement Guilt Scale:Development and preliminary validation

The rationale, development, and validation of the Bereavement Guilt Scale (BGS) are described in this article. The BGS was based on a theoretically developed, multidimensional conceptualization of guilt. Part 1 describes the generation of the item pool, derived from in-depth interviews, and review of the scientific literature. Part 2 details statistical analyses for further item selection (Sample 1, N = 273). Part 3 covers the psychometric properties of the emergent-BGS (Sample 2, N = 600, and Sample 3, N = 479). Confirmatory factor analysis indicated that a five-factor model fit the data best. Correlations of BGS scores with depression, anxiety, self-esteem, self-forgiveness, and mode of death were consistent with theoretical predictions, supporting the construct validity of the measure. The internal consistency and test-retest reliability were also supported. Thus, initial testing or examination suggests that the BGS is a valid tool to assess multiple components of bereavement guilt. Further psychometric testing across cultures is recommended

Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation-induced anticipatory fear in a rat mode

Background: Electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats has been shown to elicit panic-like behaviour and can be a useful tool for modelling anticipatory fear and agoraphobia. Methods: In this study, we further analysed our previous data on the effects of escitalopram (a selective serotonin reuptake inhibitor, SSRI) and buspirone (a 5-HT1A receptor partial agonist) on dlPAG-induced anticipatory fear behaviour in a rat model using freezing as a measure. We then used tyrosine hydroxylase (TH) immunohistochemistry to probe the effects on dopaminergic neurons. Results: Although acute treatment of escitalopram, but not buspirone, was effective in reducing anticipatory freezing behaviour, chronic administrations of both drugs were comparably effective. We found that the number of dopaminergic neurons in the ventral tegmental area (VTA) was lowered in both chronic buspirone and escitalopram groups. We showed a strong correlation between the number of dopaminergic neurons and freezing in the VTA. We further showed positive correlations between dopaminergic neurons in the VTA and substantia nigra pars compacta in escitalopram and buspirone groups, respectively. Limitations: Although our data strongly hint to a role of dopaminergic mechanisms in the dlPAG induced fear response, more in-depth studies with larger sample sizes are needed to understand the neuronal mechanisms underlying the interactions between serotonergic drugs and dopaminergic cell number and fear behavior. Conclusion: Chronic treatment with an SSRI and a 5-HT1A agonist decrease the number of dopaminergic neurons in the VTA. These effects seem to be associated with reduced dlPAG-induced anticipatory freezing behaviour

A decade of progress in deep brain stimulation of the subcallosal cingulate for the treatment of depression

Major depression contributes significantly to the global disability burden. Since the first clinical study of deep brain stimulation (DBS), over 446 patients with depression have now undergone this neuromodulation therapy, and 29 animal studies have investigated the efficacy of subgenual cingulate DBS for depression. In this review, we aim to provide a comprehensive overview of the progress of DBS of the subcallosal cingulate in humans and the medial prefrontal cortex, its rodent homolog. For preclinical animal studies, we discuss the various antidepressant-like behaviors induced by medial prefrontal cortex DBS and examine the possible mechanisms including neuroplasticity-dependent/independent cellular and molecular changes. Interestingly, the response rate of subcallosal cingulate Deep brain stimulation marks a milestone in the treatment of depression. DBS achieved response and remission rates of 64–76% and 37–63%, respectively, from clinical studies monitoring patients from 6–24 months. Although some studies showed its stimulation efficacy was limited, it still holds great promise as a therapy for patients with treatment-resistant depression. Overall, further research is still needed, including more credible clinical research, preclinical mechanistic studies, precise selection of patients, and customized electrical stimulation paradigms

Thermodynamic and Tunneling Density of States of the Integer Quantum Hall Critical State

We examine the long wave length limit of the self-consistent Hartree-Fock approximation irreducible static density-density response function by evaluating the charge induced by an external charge. Our results are consistent with the compressibility sum rule and inconsistent with earlier work that did not account for consistency between the exchange-local-field and the disorder potential. We conclude that the thermodynamic density of states is finite, in spite of the vanishing tunneling density of states at the critical energy of the integer quantum Hall transition.Comment: 5 pages, 4 figures, minor revisions, published versio

Epistemic and social scripts in computer-supported collaborative learning

Collaborative learning in computer-supported learning environments typically means that learners work on tasks together, discussing their individual perspectives via text-based media or videoconferencing, and consequently acquire knowledge. Collaborative learning, however, is often sub-optimal with respect to how learners work on the concepts that are supposed to be learned and how learners interact with each other. One possibility to improve collaborative learning environments is to conceptualize epistemic scripts, which specify how learners work on a given task, and social scripts, which structure how learners interact with each other. In this contribution, two studies will be reported that investigated the effects of epistemic and social scripts in a text-based computer-supported learning environment and in a videoconferencing learning environment in order to foster the individual acquisition of knowledge. In each study the factors ‘epistemic script’ and ‘social script’ have been independently varied in a 2×2-factorial design. 182 university students of Educational Science participated in these two studies. Results of both studies show that social scripts can be substantially beneficial with respect to the individual acquisition of knowledge, whereas epistemic scripts apparently do not to lead to the expected effects

Comprehensive lung injury pathology induced by mTOR inhibitors

Molecular Targets in Oncology[Abstract] Interstitial lung disease is a rare side effect of temsirolimus treatment in renal cancer patients. Pulmonary fibrosis is characterised by the accumulation of extracellular matrix collagen, fibroblast proliferation and migration, and loss of alveolar gas exchange units. Previous studies of pulmonary fibrosis have mainly focused on the fibro-proliferative process in the lungs. However, the molecular mechanism by which sirolimus promotes lung fibrosis remains elusive. Here, we propose an overall cascade hypothesis of interstitial lung diseases that represents a common, partly underlying synergism among them as well as the lung pathogenesis side effects of mammalian target of rapamycin inhibitors

Long-term outcomes of young, node-negative, chemotherapy-naïve, triple-negative breast cancer patients according to BRCA1 status

Background Due to the abundant usage of chemotherapy in young triple-negative breast cancer (TNBC) patients, the unbiased prognostic value of BRCA1-related biomarkers in this population remains unclear. In addition, whether BRCA1-related biomarkers modify the well-established prognostic value of stromal tumor-infiltrating lymphocytes (sTILs) is unknown. This study aimed to compare the outcomes of young, node-negative, chemotherapy-na & iuml;ve TNBC patients according to BRCA1 status, taking sTILs into account. Methods We included 485 Dutch women diagnosed with node-negative TNBC under age 40 between 1989 and 2000. During this period, these women were considered low-risk and did not receive chemotherapy. BRCA1 status, including pathogenic germline BRCA1 mutation (gBRCA1m), somatic BRCA1 mutation (sBRCA1m), and tumor BRCA1 promoter methylation (BRCA1-PM), was assessed using DNA from formalin-fixed paraffin-embedded tissue. sTILs were assessed according to the international guideline. Patients' outcomes were compared using Cox regression and competing risk models. Results Among the 399 patients with BRCA1 status, 26.3% had a gBRCA1m, 5.3% had a sBRCA1m, 36.6% had tumor BRCA1-PM, and 31.8% had BRCA1-non-altered tumors. Compared to BRCA1-non-alteration, gBRCA1m was associated with worse overall survival (OS) from the fourth year after diagnosis (adjusted HR, 2.11; 95% CI, 1.18-3.75), and this association attenuated after adjustment for second primary tumors. Every 10% sTIL increment was associated with 16% higher OS (adjusted HR, 0.84; 95% CI, 0.78-0.90) in gBRCA1m, sBRCA1m, or BRCA1-non-altered patients and 31% higher OS in tumor BRCA1-PM patients. Among the 66 patients with tumor BRCA1-PM and >= 50% sTILs, we observed excellent 15-year OS (97.0%; 95% CI, 92.9-100%). Conversely, among the 61 patients with gBRCA1m and < 50% sTILs, we observed poor 15-year OS (50.8%; 95% CI, 39.7-65.0%). Furthermore, gBRCA1m was associated with higher (adjusted subdistribution HR, 4.04; 95% CI, 2.29-7.13) and tumor BRCA1-PM with lower (adjusted subdistribution HR, 0.42; 95% CI, 0.19-0.95) incidence of second primary tumors, compared to BRCA1-non-alteration. Conclusions Although both gBRCA1m and tumor BRCA1-PM alter BRCA1 gene transcription, they are associated with different outcomes in young, node-negative, chemotherapy-na & iuml;ve TNBC patients. By combining sTILs and BRCA1 status for risk classification, we were able to identify potential subgroups in this population to intensify and optimize adjuvant treatment.Hereditary cancer genetic