Supernatants derived from chemotherapy-treated cancer cell lines can modify angiogenesis

BACKGROUND: There is evidence that tumours produce substances such as cytokines and microvesicular bodies bearing bioactive molecules, which support the carcinogenic process. Furthermore, chemotherapy has also been shown to modify these exudates and in doing so, neutralise their tumourigenic influence. METHODS: In the current study, we have investigated the effect of chemotherapy agents on modifying the cytokine profile and microvesicular cargo of supernatants derived from cancer cell lines. In addition, we have explored the effect of these tumour-derived supernatants on angiogenesis, and how chemotherapy can alter the supernatants rendering them less pro-angiogenic. RESULTS: Herein, we show that supernatants contain a rich cocktail of cytokines, a number of which are potent modulators of angiogenesis. They also contain microvesicular bodies containing RNA transcripts that code for proteins involved in transcription, immune modulation and angiogenesis. These supernatants altered intracellular signalling molecules in endothelial cells and significantly enhanced their tubulogenic character; however, this was severely compromised when supernatants from tumours treated with chemotherapy was used instead. CONCLUSION: This study suggests tumour exudates and bioactive material from tumours can influence cellular functions, and that treatment with some chemotherapy can serve to negate these pro-tumourigenic processes

Role of autobiographical memory in patient response to cognitive behavioural therapies for depression: protocol of an individual patient data meta-analysis.

This is the final version. Available from the publisher via the DOI in this record.INTRODUCTION: Cognitive behavioural therapies (CBTs) are one of the most effective treatments for major depression. However, ~50% of individuals do not adequately respond to intervention and of those who do remit from a depressive episode, over 50% will experience later relapse. Identification of patient-level factors which moderate treatment response may ultimately help to identify cognitive barriers that could be targeted to improve treatment efficacy. This individual patient data meta-analysis explores one such potential moderator-the ability to retrieve specific, detailed memories of the autobiographical past-as cognitive-based therapeutic techniques draw heavily on the ability to use specific autobiographical information to challenge the dysfunctional beliefs which drive depression. METHODS AND ANALYSIS: We have formed a collaborative network which will contribute known datasets. This will be supplemented by datasets identified through literature searches in Medline, PsycInfo, Web of Science, the Cochrane Central Register of Controlled Trials and WHO trials database between December 2018 and February 2019. Inclusion criteria are delivery of a cognitive or cognitive behavioural therapy for major depression, and measurement of autobiographical memory retrieval at preintervention. Primary outcomes are depressive symptoms and clinician-rated diagnostic status at postintervention, along with autobiographical memory specificity at postintervention. Secondary outcomes will consider each of these variables at follow-up. All analyses will be completed using random-effects models employing restricted maximum likelihood estimation. Risk of bias in included studies will be measured using the Revised Cochrane Risk of Bias Tool. ETHICS AND DISSEMINATION: The findings will be published in a peer-reviewed journal. Study results will contribute to better understanding of the role of autobiographical memory in patient response to CBTs, and may help to inform personalised medicine approaches to treatment of depression. PROSPERO REGISTRATION NUMBER: CRD42018109673.Economic and Social Research Council (ESRC

Memory Category Fluency, Memory Specificity, and the Fading Affect Bias for Positive and Negative Autobiographical Events: Performance on a Good Day- Bad Day Task in Healthy and Depressed Individuals

In mentally healthy individuals, autobiographical memory is typically biased toward positive events, which may help to maintain psychological well-being. Our aim was to assess a range of important positive memory biases in the mentally healthy and explore the possibility that these biases are mitigated in those with mental health problems. We administered a novel recall paradigm that required recollection of multiple good and bad past events (the Good Day-Bad Day task) to healthy and depressed individuals. This allowed us to explore differences in memory category fluency (i.e., the ability to generate integrated sets of associated events) for positive and negative memories, along with memory specificity, and fading affect bias-a greater reduction in the intensity of memory-related affect over time for negative versus positive events. We found that healthy participants demonstrated superior category fluency for positive relative to negative events but that this effect was absent in depressed participants. Healthy participants exhibited a strong fading affect bias that was significantly mitigated, although still present, in depression. Finally, memory specificity was reduced in depression for both positive and negative memories. Findings demonstrate that the positive bias associated with mental health is maintained by multiple autobiographical memory processes and that depression is as much a function of the absence of these positive biases as it is the presence of negative biases. Results provide important guidance for developing new treatments for improving mental health.This research was supported by the UK Medical Research Council (Grant: SUAG/006/RG91365) and the UK National Institute of Health Research Cambridge Biomedical Research Centre

Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma.

BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse

Update to the effectiveness and cost-effectiveness of a mindfulness training programme in schools compared with normal school provision (MYRIAD): study protocol for a randomised controlled trial

Background: MYRIAD (My Resilience in Adolescence) is a superiority, parallel group, cluster randomised controlled trial designed to examine the effectiveness and cost-effectiveness of a mindfulness training (MT) programme, compared with normal social and emotional learning (SEL) school provision to enhance mental health, social-emotional-behavioural functioning and well-being in adolescence. The original trial protocol was published in Trials (accessible at https://doi.org/10.1186/s13063-017-1917-4). This included recruitment in two cohorts, enabling the learning from the smaller first cohort to be incorporated in the second cohort. Here we describe final amendments to the study protocol and discuss their underlying rationale. // Methods: Four major changes were introduced into the study protocol: (1) there were changes in eligibility criteria, including a clearer operational definition to assess the degree of SEL implementation in schools, and also new criteria to avoid experimental contamination; (2) the number of schools and pupils that had to be recruited was increased based on what we learned in the first cohort; (3) some changes were made to the secondary outcome measures to improve their validity and ability to measure constructs of interest and to reduce the burden on school staff; and (4) the current Coronavirus Disease 2019 (SARS-CoV-2 or COVID-19) pandemic both influences and makes it difficult to interpret the 2-year follow-up primary endpoint results, so we changed our primary endpoint to 1-year follow-up. // Discussion: These changes to the study protocol were approved by the Trial Management Group, Trial Steering Committee and Data and Ethics Monitoring Committees and improved the enrolment of participants and quality of measures. Furthermore, the change in the primary endpoint will give a more reliable answer to our primary question because it was collected prior to the COVID-19 pandemic in both cohort 1 and cohort 2. Nevertheless, the longer 2-year follow-up data will still be acquired, although this time-point will be now framed as a second major investigation to answer some new important questions presented by the combination of the pandemic and our study design

Parent and child agreement for acute stress disorder, post-traumatic stress disorder and other psychopathology in a prospective study of children and adolescents exposed to single-event trauma

Examining parent-child agreement for Acute Stress Disorder (ASD) and Post-Traumatic Stress Disorder (PTSD) in children and adolescents is essential for informing the assessment of trauma-exposed children, yet no studies have examined this relationship using appropriate statistical techniques. Parent-child agreement for these disorders was examined by structured interview in a prospective study of assault and motor vehicle accident (MVA) child survivors, assessed at 2-4 weeks and 6 months post-trauma. Children were significantly more likely to meet criteria for ASD, as well as other ASD and PTSD symptom clusters, based on their own report than on their parent's report. Parent-child agreement for ASD was poor (Cohen's κ = -.04), but fair for PTSD (Cohen's κ = .21). Agreement ranged widely for other emotional disorders (Cohen's κ = -.07-.64), with generalised anxiety disorder found to have superior parent-child agreement (when assessed by phi coefficients) relative to ASD and PTSD. The findings support the need to directly interview children and adolescents, particularly for the early screening of posttraumatic stress, and suggest that other anxiety disorders may have a clearer presentation post-trauma

Agro-materials : a bibliographic review

Facing the problems of plastic recycling and fossil resources exhaustion, the use of biomass to conceive new materials appears like a reasonable solution. Two axes of research are nowadays developed : on the one hand the synthesis of biodegradable plastics, whichever the methods may be, on the other hand the utilization of raw biopolymers, which is the object of this paper. From this perspective, the “plastic” properties of natural polymers, the caracteristics of the different classes of polymers, the use of charge in vegetable matrix and the possible means of improving the durability of these agro-materials are reviewed

Reduced specificity of autobiographical memory and depression: The role of executive control

It has been widely established that depressed mood states and clinical depression, as well as a range of other psychiatric disorders, are associated with a relative difficulty in accessing specific autobiographical information in response to emotion-related cue words on an Autobiographical Memory Test (AMT; J. M. G. Williams & K. Broadbent, 1986). In 8 studies the authors examined the extent to which this relationship is a function of impaired executive control associated with these mood states and clinical disorders. Studies 1-4 demonstrated that performance on the AMT is associated with performance on measures of executive control, independent of depressed mood. Furthermore, Study 1 showed that executive control (as measured by verbal fluency) mediated the relationship between both depressed mood and a clinical diagnosis of eating disorder and AMT performance. Using a stratified sample in Study 5, the authors confirmed the positive association between depressed mood and impaired performance on the AMT. Studies 6-8 involved experimental manipulations of the parameters of the AMT designed to further indicate that reduced executive control is to a significant extent driving the relationship between depressed mood and AMT performance. The potential role of executive control in accounting for other aspects of the AMT literature is discussed. (PsycINFO Database Record (c) 2007 APA, all rights reserved)

A SEARCH FOR RETROVIRUS INFECTION IN SYSTEMIC LUPUS-ERYTHEMATOSUS AND RHEUMATOID-ARTHRITIS

Evidence for retroviral infection in general and human immunodeficiency virus (HIV) infection in particular was sought in freshly isolated peripheral blood T cells, B cells, and monocyte-macrophages from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and also in T cell and B cell lines established from the same source. Similar cells isolated from rheumatoid synovial membrane were also examined. The strategy used for the detection of virus was cocultivation with susceptible cell lines looking for syncytia formation, reverse transcriptase production, and nucleic acid hybridisation with HIV cDNA probes. No evidence for infection was obtained