Mental health consultations in a prison population: a descriptive study

BACKGROUND: The psychiatric morbidity among prison inmates is substantially higher than in the general population. We do, however, have insufficient knowledge about the extent of psychiatric treatment provided in our prisons. The aim of the present study was to give a comprehensive description of all non-pharmacological interventions provided by the psychiatric health services to a stratified sample of prison inmates. METHODS: Six medium/large prisons (n = 928) representing 1/3 of the Norwegian prison population and with female and preventive detention inmates over-sampled, were investigated cross-sectionally. All non-pharmacological psychiatric interventions, excluding pure correctional programs, were recorded. Those receiving interventions were investigated further and compared to the remaining prison population. RESULTS: A total of 230 of the 928 inmates (25 %) had some form of psychiatric intervention: 184 (20 %) were in individual psychotherapy, in addition 40 (4 %) received ad hoc interventions during the registration week. Group therapy was infrequent (1 %). The psychotherapies were most often of a supportive (62 %) or behavioural-cognitive (26 %) nature. Dynamic, insight-oriented psychotherapies were infrequent (8 %). Concurrent psychopharmacological treatment was prevalent (52 %). Gender and age did not correlate with psychiatric interventions, whereas prisoner category (remanded, sentenced, or preventive detention) did (p < 0.001). Most inmates had a number of defined problem areas, with substance use, depression, anxiety, and personality disorders most prevalent. Three percent of all inmates were treated for a psychotic disorder. Remand prisoners averaged 14 sessions per week per 100 inmates, while sentenced inmates and those on preventive detention averaged 22 and 25 sessions per week per 100 inmates, respectively. Five out of six psychiatric health services estimated the inmates' psychiatric therapy needs as adequately met, both overall and in the majority of individual cases. CONCLUSION: Our results pertain only to prisons with adequate primary and mental health services and effective diversion from prison of individuals with serious mental disorders. Given these important limitations, we do propose that the service estimates found may serve as a rough guideline to the minimum number of sessions a prison's psychiatric health services should be able to fulfil in order to serve the inmates psychiatric needs. The results rely on the specialist services' own estimates only. Future studies should take other important informants, including the inmates themselves, into consideration

P-glycoprotein and breast cancer resistance protein in acute myeloid leukaemia cells treated with the Aurora-B Kinase Inhibitor barasertib-hQPA

<p>Abstract</p> <p>Background</p> <p>Aurora kinases play an essential role in orchestrating chromosome alignment, segregation and cytokinesis during mitotic progression, with both aurora-A and B frequently over-expressed in a variety of human malignancies. Over-expression of the ABC drug transporter proteins P-glycoprotein (Pgp) and Breast cancer resistance protein (BCRP) is a major obstacle for chemotherapy in many tumour types with Pgp conferring particularly poor prognosis in acute myeloid leukaemia (AML). Barasertib-hQPA is a highly selective inhibitor of aurora-B kinase that has shown tumouricidal activity against a range tumour cell lines including those of leukaemic AML origin.</p> <p>Methods</p> <p>Effect of barasertib-hQPA on the pHH3 biomarker and cell viability was measured in a panel of leukaemic cell lines and 37 primary AML samples by flow cytometry. Pgp status was determined by flow cytometry and BCRP status by flow cytometry and real-time PCR.</p> <p>Results</p> <p>In this study we report the creation of the cell line OCI-AML3DNR, which over-expresses Pgp but not BCRP or multidrug resistance-associated protein (MRP), through prolonged treatment of OCI-AML3 cells with daunorubicin. We demonstrate that Pgp (OCI-AML3DNR and KG-1a) and BCRP (OCI-AML6.2) expressing AML cell lines are less sensitive to barasertib-hQPA induced pHH3 inhibition and subsequent loss of viability compared to transporter negative cell lines. We also show that barasertib-hQPA resistance in these cell lines can be reversed using known Pgp and BCRP inhibitors. We report that barasertib-hQPA is not an inhibitor of Pgp or BCRP, but by using ¹⁴[C]-barasertib-hQPA that it is effluxed by these transporters. Using phosphoHistone H3 (pHH3) as a biomarker of barasertib-hQPA responsiveness in primary AML blasts we determined that Pgp and BCRP positive primary samples were less sensitive to barasertib-hQPA induced pHH3 inhibition (p = <0.001) than samples without these transporters. However, we demonstrate that IC₅₀inhibition of pHH3 by barasertib-hQPA was achieved in 94.6% of these samples after 1 hour drug treatment, in contrast to the resistance of the cell lines.</p> <p>Conclusion</p> <p>We conclude that Pgp and BCRP status and pHH3 down-regulation in patients treated with barasertib should be monitored in order to establish whether transporter-mediated efflux is sufficient to adversely impact on the efficacy of the agent.</p

Synergistic interaction effect between job control and social support at work on general psychological distress

Purpose Little is known about the interaction between job control and social support at work on common mental disorders. To examine whether there is a synergistic interaction effect between job control and social support at work on general psychological distress and whether it differs by the level of job demands. Methods About 1,940 male and female workers from the Malmo Shoulder and Neck Study were chosen for this cross-sectional study. Job control, social support at work, and job demands were measured by the Swedish version of the Job Content Questionnaire, and general psychological distress was assessed by the General Health Questionnaire. Results A significant excessive risk increase for general psychological distress was observed when workers had both low job control and low social support at work in both men and women. The synergistic effect was stronger in women, when job demands were low (Rothman's synergy index was 2.16 vs. 1.51 when job demands were high). However, in male workers, while a strong synergistic effect between job control and social support at work was found when job demands were low (synergy index was 9.25), there was an antagonistic effect when job demands were high (synergy index was 0.52). Conclusions There was a synergistic interaction effect between job control and social support at work on general psychological distress, but the synergistic effect or its effect size differed by the level of job demands and gender. An atomic, additive approach to the risk assessment of the psychosocial work characteristics on common mental disorders could be misleading or lead to a risk underestimation

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Genome remodelling in a basal-like breast cancer metastasis and xenograft

Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour

Online repetitive transcranial magnetic stimulation during working memory in younger and older adults: A randomized within-subject comparison.

Working memory is the ability to perform mental operations on information that is stored in a flexible, limited capacity buffer. The ability to manipulate information in working memory is central to many aspects of human cognition, but also declines with healthy aging. Given the profound importance of such working memory manipulation abilities, there is a concerted effort towards developing approaches to improve them. The current study tested the capacity to enhance working memory manipulation with online repetitive transcranial magnetic stimulation in healthy young and older adults. Online high frequency (5Hz) repetitive transcranial magnetic stimulation was applied over the left dorsolateral prefrontal cortex to test the hypothesis that active repetitive transcranial magnetic stimulation would lead to significant improvements in memory recall accuracy compared to sham stimulation, and that these effects would be most pronounced in working memory manipulation conditions with the highest cognitive demand in both young and older adults. Repetitive transcranial magnetic stimulation was applied while participants were performing a delayed response alphabetization task with three individually-titrated levels of difficulty. The left dorsolateral prefrontal cortex was identified by combining electric field modeling to individualized functional magnetic resonance imaging activation maps and was targeted during the experiment using stereotactic neuronavigation with real-time robotic guidance, allowing optimal coil placement during the stimulation. As no accuracy differences were found between young and older adults, the results from both groups were collapsed. Subsequent analyses revealed that active stimulation significantly increased accuracy relative to sham stimulation, but only for the hardest condition. These results point towards further investigation of repetitive transcranial magnetic stimulation for memory enhancement focusing on high difficulty conditions as those most likely to exhibit benefits