Cognitive reactivity: cultural adaptation and psychometric testing of the Persian version of the Leiden Index of Depression Sensitivity Revised (LEIDS-R) in an Iranian sample

Cognitive reactivity (CR) to the experimental induction of sad mood has been found to predict relapse in recovered depressed patients. The Leiden Index of Depression Sensitivity Revised (LEIDS-R) is a self-report measure of CR. The aim of the present study was to establish the validity and reliability of the Persian version of the LEIDS-R. The participants were recovered depressed and non-depressed Iranian individuals (n = 833). The analyses included content validation, factor analysis, construct validity, and reliability testing. Preliminary construct validation analysis confirmed that factor analysis was appropriate for the Persian version of the LEIDS-R. Factor analysis displayed similar factor loadings to the original English version. The total internal consistency of the translated version, which was assessed using Cronbach’s alpha coefficient, was equal to 0.90. The test-retest reliability of the total score was equal to that of the test-retest conducted after a two-week interval at 0.94. Content validity, face validity, and construct validity, as well as reliability analysis were all found to be satisfactory for the Persian version of the LEIDS-R. The Persian version of the LEIDS-R appears to be valid and reliable for use in future studies, and has properties comparable to the original version and to that obtained in previous studies

CYP17 blockade by abiraterone: further evidence for frequent continued hormone-dependence in castration-resistant prostate cancer

The limited prognosis of patients with castration-resistant prostate cancer (CRPC) on existing hormonal manipulation therapies calls out for the urgent need for new management strategies. The novel, orally available, small-molecule compound, abiraterone acetate, is undergoing evaluation in early clinical trials and emerging data have shown that the selective, irreversible and continuous inhibition of CYP17 is safe with durable responses in CRPC. Importantly, these efficacy data along with strong preclinical evidence indicate that a significant proportion of CRPC remains dependant on ligand-activated androgen receptor (AR) signalling. Coupled with the use of innovative biological molecular techniques, including the characterisation of circulating tumour cells and ETS gene fusion analyses, we have gained insights into the molecular basis of CRPC. We envision that a better understanding of the mechanisms underlying resistance to abiraterone acetate, as well as the development of validated predictive and intermediate endpoint biomarkers to aid both patient selection and monitor response to treatment, will improve the outcome of CRPC patients

The androgen receptor can signal through Wnt/β-Catenin in prostate cancer cells as an adaptation mechanism to castration levels of androgens

<p>Abstract</p> <p>Background</p> <p>A crucial event in Prostate Cancer progression is the conversion from a hormone-sensitive to a hormone-refractory disease state. Correlating with this transition, androgen receptor (AR) amplification and mutations are often observed in patients failing hormonal ablation therapies. β-Catenin, an essential component of the canonical Wnt signaling pathway, was shown to be a coactivator of the AR signaling in the presence of androgens. However, it is not yet clear what effect the increased levels of the AR could have on the Wnt signaling pathway in these hormone-refractory prostate cells.</p> <p>Results</p> <p>Transient transfections of several human prostate cancer cell lines with the AR and multiple components of the Wnt signaling pathway demonstrate that the AR overexpression can potentiate the transcriptional activities of Wnt/β-Catenin signaling. In addition, the simultaneous activation of the Wnt signaling pathway and overexpression of the AR promote prostate cancer cell growth and transformation at castration levels of androgens. Interestingly, the presence of physiological levels of androgen or other AR agonists inhibits these effects. These observations are consistent with the nuclear co-localization of the AR and β-Catenin shown by immunohistochemistry in human prostate cancer samples. Furthermore, chromatin immunoprecipitation assays showed that Wnt3A can recruit the AR to the promoter regions of Myc and Cyclin D1, which are well-characterized downstream targets of the Wnt signalling pathway. The same assays demonstrated that the AR and β-Catenin can be recruited to the promoter and enhancer regions of a known AR target gene PSA upon Wnt signaling. These results suggest that the AR is promoting Wnt signaling at the chromatin level.</p> <p>Conclusion</p> <p>Our findings suggest that the AR signaling through the Wnt/β-Catenin pathway should be added to the well established functional interactions between both pathways. Moreover, our data show that via this interaction the AR could promote prostate cell malignancy in a ligand-independent manner.</p

Phantom headache: pain-memory-emotion hypothesis for chronic daily headache?

The neurobiology of chronic pain, including chronic daily headache (CDH) is not completely understood. “Pain memory” hypothesis is one of the mechanisms for phantom limb pain. We reviewed the literature to delineate a relation of “pain memory” for the development of CDH. There is a direct relation of pain to memory. Patients with poor memory have less chance to develop “pain memory”, hence less possibility to develop chronic pain. Progressive memory impairment may lead to decline in headache prevalence. A similar relation of pain is also noted with emotional or psychiatric symptoms. Literature review suggests that there is marked overlap in the neural network of pain to that of memory and emotions. We speculate that pain, memory, and emotions are interrelated in triangular pattern, and each of these three is related to other two in bidirectional pattern, i.e., stimulation of one of these will stimulate other symptoms/networks and vice versa (triangular theory for chronic pain). Longstanding or recurrent noxious stimuli will strengthen this interrelation, and this may be responsible for chronicity of pain. Reduction of both chronic pain and psychological symptoms by cognitive behavioral therapy or psychological interventions further suggests a bidirectional interrelation between pain and emotion. Longitudinal studies are warranted on the prevalence of headache and other painful conditions in patients with progressive memory impairment to delineate the relation of pain to memory. Interrelation of headache to emotional symptoms should also be explored

Patterns of Childhood Trauma and Psychological Distress among Injecting Heroin Users in China

Background: Childhood trauma has been reported as a possible cause of future substance abuse in some countries. This study reports the prevalence of childhood trauma and examines its association with psychological distress among injecting drug users from mainland China. Methodology: The study was conducted in three government-operated drug rehabilitation facilities in Shanghai, China in 2007. The Early Trauma Inventory Self Report-Short Form (ETISR-SF) was used to evaluate 4 types (general, emotional, physical and sexual) and severity of childhood trauma, and the Symptom Checklist-90-Revised (SCL-90-R) to evaluate psychological distress. Principal Findings: Among 341 injecting drug users who completed the study, about 80 % reported one or more types o

Modulation of EEG spectral edge frequency during patterned pneumatic oral stimulation in preterm infants

Background—Stimulation of the nervous system plays a central role in brain development and neurodevelopmental outcome. Thalamocortical and corticocortical development is diminished in premature infants and correlated to electroencephalography (EEG) progression. The purpose of this study was to determine the effects of orocutaneous stimulation on the modulation of spectral edge frequency, fc=90% (SEF-90) derived from EEG recordings in preterm infants. Methods—Twenty two preterm infants were randomized to experimental and control conditions. Pulsed orocutaneous stimulation was presented during gavage feedings begun at around 32 weeks postmenstrual age (PMA). The SEF-90 was derived from 2-channel EEG recordings. Results—Compared to the control condition, the pulsed orocutaneous stimulation produced a significant reorganization of SEF-90 in the left (p = 0.005) and right (p \u3c 0.0001) hemispheres. Notably, the left and right hemisphere showed a reversal in the polarity of frequency shift, demonstrating hemispheric asymmetry in the frequency domain. Pulsed orocutaneous stimulation also produced a significant pattern of short term cortical adaptation and a long term neural adaptation manifest as a 0.5 Hz elevation in SEF-90 after repeated stimulation sessions. Conclusion—This is the first study to demonstrate the modulating effects of a servo-controlled oral somatosensory input on the spectral features of EEG activity in preterm infants

Modulators of Prostate Cancer Cell Proliferation and Viability Identified by Short-Hairpin RNA Library Screening

There is significant need to identify novel prostate cancer drug targets because current hormone therapies eventually fail, leading to a drug-resistant and fatal disease termed castration-resistant prostate cancer. To functionally identify genes that, when silenced, decrease prostate cancer cell proliferation or induce cell death in combination with antiandrogens, we employed an RNA interference-based short hairpin RNA barcode screen in LNCaP human prostate cancer cells. We identified and validated four candidate genes (AKT1, PSMC1, STRADA, and TTK) that impaired growth when silenced in androgen receptor positive prostate cancer cells and enhanced the antiproliferative effects of antiandrogens. Inhibition of AKT with a pharmacologic inhibitor also induced apoptosis when combined with antiandrogens, consistent with recent evidence for PI3K and AR pathway crosstalk in prostate cancer cells. Recovery of hairpins targeting a known prostate cancer pathway validates the utility of shRNA library screening in prostate cancer as a broad strategy to identify new candidate drug targets

Androgen receptor footprint on the way to prostate cancer progression

The prostate gland is exquisitely sensitive to androgen receptor (AR) signaling. AR signaling is obligatory for prostate development and changes in AR levels, its ligands or shifts in AR mode of action are reflected in the physiology of the prostate. The AR is intimately linked to prostate cancer biology through the regulation of epithelial proliferation, suppression of apoptosis and the development of castration-resistant disease. Thus, AR is the primary therapeutic target in various prostate diseases such as BPH and cancer. Although some tumors lose AR expression, most retain the AR and have elevated levels and/or shifts in activity that are required for tumor progression and metastasis. New AR inhibitors currently in clinical trials with higher receptor affinity and specificity may improve prostate cancer patient outcome. Several events play an important role in initiation, primary tumor development and metastatic spread. Androgen receptor activity and promoter specificity change due to altered coregulator expression. Changes in epigenetic surveillance alter the AR cistrome. Both systemic and local inflammation increases with PCa progression affecting AR levels, activity, and requirement for ligand. Our current understanding of AR biology suggest that global androgen suppression may drive the development of castration-resistant disease and therefore the question remains: Does effective inhibition of AR activity mark the end of the road for PCa or only a sharp turn toward a different type of malignancy

Soluble CD40 ligand and prolactin levels in migraine patients during interictal period

The relationship of migraine with cardiovascular diseases has been clarified by many studies, and currently, migraine is suggested to be a systematic vasculopathy. Inflammation, thrombosis and impaired vascular reactivity are the underlying pathophysiological mechanisms of the vasculopathy. In the present study, we aimed to investigate the relationship between prolactin levels and subclinical atherosclerosis risk factors such as soluble CD40 ligand (sCD40L) and high-sensitivity CRP (hsCRP) in migraine patients during interictal period. Fifty female migraine patients and age-matched 25 female control cases were enrolled in the study. Migraine diagnosis was settled according to the ICHD-II diagnostic criteria. A questionnaire was completed about the existence of vascular risk factors. Serum samples were used to measure sCD40L, hsCRP and prolactin levels. No difference was found between the prolactin levels of the migraine patients and the controls. The sCD40L levels were significantly higher in migraine patients (p < 0.001). High-sensitivity CRP levels showed no difference between the groups. There was no correlation between prolactin, sCD40L, and hs-CRP levels in migraine patients. We consider that the migraine patients are prone to subclinical atherosclerosis, but this tendency is independent of prolactin levels

A multicenter phase III trial comparing irinotecan-gemcitabine (IG) with gemcitabine (G) monotherapy as first-line treatment in patients with locally advanced or metastatic pancreatic cancer

Our purpose was to determine the response rate and median and overall survival of gemcitabine as monotherapy versus gemcitabine plus irinotecan in advanced or metastatic pancreatic cancer. Patients with histologically or cytologically confirmed adenocarcinoma who were chemotherapy and radiotherapy naive were enrolled. Patients were centrally randomised at a one-to-one ratio to receive either gemcitabine monotherapy (900 mg m−2 on days 1, 8 and 15 every 4 weeks (arm G), or gemcitabine (days 1 and 8) plus irinotecan (300 mg m−2 on day 8) (arm IG), repeated every 3 weeks. The total number of cycles administered was 255 in the IG arm and 245 in the G arm; the median number of cycles was 3. In all, 145 patients (71 in arm IG and 74 in arm G) were enrolled; 60 and 70 patients from arms IG and G, respectively, were evaluable. A complete clinical response was achieved in three (4.3%) arm G patients; nine (15%) patients in arm IG and four (5.7%) in arm G achieved a partial response. The overall response rate was: arm IG 15% and arm G 10% (95% CI 5.96–24.04 and 95% CI 2.97–17.03, respectively; P=0.387). The median time to tumour progression was 2.8 months and 2.9 months and median survival time was 6.4 and 6.5 months for the IG and G arms, respectively. One-year survival was 24.3% for the IG arm and 21.8% for the G arm. No statistically significant difference was observed comparing gemcitabine monotherapy versus gemcitabine plus irinotecan in the treatment of advanced pancreatic cancer, with respect to overall and 1-year survival