Human prostate sphere-forming cells represent a subset of basal epithelial cells capable of glandular regeneration in vivo.

BackgroundProstate stem/progenitor cells function in glandular development and maintenance. They may be targets for tumor initiation, so characterization of these cells may have therapeutic implications. Cells from dissociated tissues that form spheres in vitro often represent stem/progenitor cells. A subset of human prostate cells that form prostaspheres were evaluated for self-renewal and tissue regeneration capability in the present study.MethodsProstaspheres were generated from 59 prostatectomy specimens. Lineage marker expression and TMPRSS-ERG status was determined via immunohistochemistry and fluorescence in situ hybridization (FISH). Subpopulations of prostate epithelial cells were isolated by cell sorting and interrogated for sphere-forming activity. Tissue regeneration potential was assessed by combining sphere-forming cells with rat urogenital sinus mesenchyme (rUGSM) subcutaneously in immunocompromised mice.ResultsProstate tissue specimens were heterogeneous, containing both benign and malignant (Gleason 3-5) glands. TMPRSS-ERG fusion was found in approximately 70% of cancers examined. Prostaspheres developed from single cells at a variable rate (0.5-4%) and could be serially passaged. A basal phenotype (CD44+CD49f+CK5+p63+CK8-AR-PSA-) was observed among sphere-forming cells. Subpopulations of prostate cells expressing tumor-associated calcium signal transducer 2 (Trop2), CD44, and CD49f preferentially formed spheres. In vivo implantation of sphere-forming cells and rUGSM regenerated tubular structures containing discreet basal and luminal layers. The TMPRSS-ERG fusion was absent in prostaspheres derived from fusion-positive tumor tissue, suggesting a survival/growth advantage of benign prostate epithelial cells.ConclusionHuman prostate sphere-forming cells self-renew, have tissue regeneration capability, and represent a subpopulation of basal cells

Two-dimensional turbulence in magnetised plasmas

In an inhomogeneous magnetised plasma the transport of energy and particles perpendicular to the magnetic field is in general mainly caused by quasi two-dimensional turbulent fluid mixing. The physics of turbulence and structure formation is of ubiquitous importance to every magnetically confined laboratory plasma for experimental or industrial application. Specifically, high temperature plasmas for fusion energy research are also dominated by the properties of this turbulent transport. Self-organisation of turbulent vortices to mesoscopic structures like zonal flows is related to the formation of transport barriers that can significantly enhance the confinement of a fusion plasma. This subject of great importance in research is rarely touched on in introductory plasma physics or continuum dynamics courses. Here a brief tutorial on 2D fluid and plasma turbulence is presented as an introduction to the field, appropriate for inclusion in undergraduate and graduate courses.Comment: This is an author-created, un-copyedited version of an article published in European Journal of Physics. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The definitive publisher authenticated version is available online at doi: 10.1088/0143-0807/29/5/00

An affinity matured minibody for PET imaging of prostate stem cell antigen (PSCA)-expressing tumors

PurposeProstate stem cell antigen (PSCA), a cell surface glycoprotein expressed in normal human prostate and bladder, is over-expressed in the majority of localized prostate cancer and most bone metastases. We have previously shown that the hu1G8 minibody, a humanized anti-PSCA antibody fragment (single-chain Fv-C(H)3 dimer, 80 kDa), can localize specifically and image PSCA-expressing xenografts at 21 h post-injection. However, the humanization and antibody fragment reformatting decreased its apparent affinity. Here, we sought to evaluate PET imaging contrast with affinity matured minibodies.MethodsYeast scFv display, involving four rounds of selection, was used to generate the three affinity matured antibody fragments (A2, A11, and C5) that were reformatted into minibodies. These three affinity matured anti-PSCA minibodies were characterized in vitro, and following radiolabeling with (124)I were evaluated in vivo for microPET imaging of PSCA-expressing tumors.ResultsThe A2, A11, and C5 minibody variants all demonstrated improved affinity compared to the parental (P) minibody and were ranked as follows: A2 > A11 > C5 > P. The (124)I-labeled A11 minibody demonstrated higher immunoreactivity than the parental minibody and also achieved the best microPET imaging contrast in two xenograft models, LAPC-9 (prostate cancer) and Capan-1 (pancreatic cancer), when evaluated in vivo.ConclusionOf the affinity variant minibodies tested, the A11 minibody that ranked second in affinity was selected as the best immunoPET tracer to image PSCA-expressing xenografts. This candidate is currently under development for evaluation in a pilot clinical imaging study

Relationships of Mental Disorders and Weight Status in the Korean Adult Population

The purpose of this study was to evaluate the associations between weight status and mental disorders, including depressive disorder, anxiety disorder and alcohol use disorder. A total of nationally representative 6,510 subjects aged 18-64 yr was interviewed in face-to-face household survey. Response rate was 81.7%. Mental disorders were diagnosed using the Korean version of the Composite International Diagnostic Interview (K-CIDI). The subjects reported their heights and weights. After adjusting for age and gender, the lifetime diagnosis of depressive disorder had a significant association with only the underweight group (odds ratio [OR], 1.68, 95% confidence interval [CI], 1.19-2.38). The association between underweight and depressive disorder was the strongest for subjects with a high education level (OR, 1.75, 95% CI, 1.2-2.56), subjects with a married/cohabiting status (OR, 1.94, 95% CI, 1.17-3.22) and smokers (OR, 2.58, 95% CI, 1.33-4.98). There was no significant association between obesity and depressive disorder in Korea. But there was a significant association between the underweight group and depressive disorder. The relationship between obesity and mental disorder in a Korean population was different from that in a Western population. These results suggest that the differences of traditional cultures and races might have an important effect on the associations between the weight status and mental disorders

Psychological approaches to understanding and promoting recovery in psychosis and bipolar disorder:a mixed-methods approach

BackgroundRecovery in mental health is a relatively new concept, but it is becoming more accepted that people can recover from psychosis. Recovery-orientated services are recommended for adult mental health, but with little evidence base to support this. ObjectivesTo facilitate understanding and promotion of recovery in psychosis and bipolar disorder (BD), in a manner that is empowering and acceptable to service users. MethodThere were six linked projects using qualitative and quantitative methodologies: (1) developing and piloting a service user-defined measure of recovery; (2) a Delphi study to determine levels of consensus around the concept of recovery; (3) examination of the psychological factors associated with recovery and how these fluctuate over time; (4) development and evaluation of cognitive–behavioural approaches to guided self-help including a patient preference trial (PPT); (5) development and evaluation of cognitive–behavioural therapy (CBT) for understanding and preventing suicide in psychosis including a randomised controlled trial (RCT); and (6) development and evaluation of a cognitive–behavioural approach to recovery in recent onset BD, including a RCT of recovery-focused cognitive–behavioural therapy (RfCBT). Service user involvement was central to the programme. ResultsMeasurement of service user-defined recovery from psychosis (using the Subjective Experience of Psychosis Scale) and BD (using the Bipolar Recovery Questionnaire) was shown to be feasible and valid. The consensus study revealed a high level of agreement among service users for defining recovery, factors that help or hinder recovery and items which demonstrate recovery. Negative emotions, self-esteem and hope predicted recovery judgements, both cross-sectionally and longitudinally, whereas positive symptoms had an indirect effect. In the PPT, 89 participants entered the study, three were randomised, 57 were retained in the trial until 15-month follow-up (64%). At follow-up there was no overall treatment effect on the primary outcome (Questionnaire about the Process of Recovery total; p = 0.82). In the suicide prevention RCT, 49 were randomised and 35 were retained at 6-month follow-up (71%). There were significant improvements in suicidal ideation [Adult Suicidal Ideation Questionnaire; treatment effect = –12.3, 95% confidence interval (CI) –24.3 to –0.14], Suicide Probability Scale (SPS; treatment effect = –7.0, 95% CI –15.5 to 0) and hopelessness (subscale of the SPS; treatment effect = –3.8, 95% CI –7.3 to –0.5) at follow-up. In the RCT for BD, 67 participants were randomised and 45 were retained at the 12-month follow-up (67%). Recovery score significantly improved in comparison with treatment as usual (TAU) at follow-up (310.87, 95% CI 75.00 to 546.74). At 15-month follow-up, 32 participants had experienced a relapse of either depression or mania (20 TAU vs. 12 RfCBT). The difference in time to recurrence was significant (estimated hazard ratio 0.38, 95% CI 0.18 to 0.78; p < 0.006). ConclusionsThis research programme has improved our understanding of recovery in psychosis and BD. Key findings indicate that measurement of recovery is feasible and valid. It would be feasible to scale up the RCTs to assess effectiveness of our therapeutic approaches in larger full trials, and two of the studies (CBT for suicide prevention in psychosis and recovery in BD) found significant benefits on their primary outcomes despite limited statistical power, suggesting definitive trials are warranted. FundingThe National Institute for Health Research Programme Grants for Applied Research programme