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Background: Existing literature implies there may be gaps in post-treatment support for young people with cancer. This service evaluation explored the needs and experiences of young people when ending cancer treatment in a UK children's hospital to inform service provisions. Methods: Semi-structured interviews were conducted with nine young people, aged 13–18 years, who had finished active cancer treatment and were receiving follow-up care. The data was analysed using thematic analysis. Results: Four main themes were developed: being in the dark (i.e. limited awareness of what happens when treatment ends); separation from the hospital (i.e. the loss of valued support from staff); consequences of cancer (i.e. managing ongoing psychological and physical effects); and getting back to normal life (i.e. shifting from hospital to everyday life). Conclusions: Recommendations for improving clinical practice were made. Greater preparedness for ending treatment could be achieved by clearly setting out ongoing care arrangements, providing resource packs, having opportunities to mark the end of treatment, and offering peer support. To identify specific post-treatment needs, there should be an end of treatment multidisciplinary review and space for young people to share how they are feeling in follow-up medical appointments. [ABSTRACT FROM AUTHOR]

Excessive screen time among adolescents is discussed as a significant public health concern. Identifying adolescent longitudinal patterns of time spent on regularly-used media screens and understanding their young adulthood mental health and behavioral issue correlates may help inform strategies for improving these outcomes. This study aimed to characterize joint developmental patterns of time spent on videogames, surfing/chatting the Internet, and TV/DVDs during adolescence (at ages 11, 13, 15, 17) and their associations with mental health (i.e., depression, anxiety, suicidal ideation, and self-injury) and behavioral issues (i.e., substance use, delinquency, aggression) in early adulthood (at age 20). A parallel-process latent class growth analysis was used to model data from a diverse community-ascertained sample of youth in Zurich, Switzerland (n = 1521; 51.7% males). Results suggested that a five-class model best fitted the data: (1) low-screen use, 37.6%; (2) increasing chatting/surfing, 24.0%; (3) moderate-screen use, 18.6%; (4) early-adolescence screen use, 9.9%; and (5) increasing videogame and chatting/surfing, 9.9%. After adjusting for baseline levels of outcomes (primarily at age 11), the trajectory groups differed in their associations with adulthood outcomes of mental health and behavioral problems, indicating the importance of problematic screen usage patterns in predicting these outcomes. Future research to test the directionality of these associations will be important. These findings suggest which patterns of screen use may be a marker for later mental health and behavioral issues in different domains. [ABSTRACT FROM AUTHOR]

Growing evidence has suggested that parental mental illness and child internalizing and externalizing problems tend to co-occur and engender risk for adverse child outcomes; however, there is considerable heterogeneity in their joint developmental trajectories. This study aimed to evaluate the joint developmental trajectories of maternal and paternal psychological distress and child internalizing and externalizing problems from early childhood to middle adolescence. Given that suicide and self-harm are major public health issues in adolescence and often occur in the context of other mental health issues, we also examined the association between these joint trajectories and these outcomes in adolescence. Parallel-process latent class growth analysis was applied to 14 years of follow-up data from a large-scale, nationally representative sample of youths participating in the UK's Millennium Cohort Study (MCS; n = 12,520, 50.9% male). Results showed the best-fitting solution had four trajectory classes: (1) low symptoms, 59.0%; (2) moderate symptoms in children, 22.5%; (3) notable symptoms in fathers, 10.7%; and (4) co-occurring maternal and child symptoms, 7.8%. The trajectory groups differed in their self-harm and suicide attempts in adolescence, underscoring the possible importance of the roles of both parental distress and child problem behaviors processes in these outcomes. Future studies will be valuable to rigorously test the directionality and the respective roles of parents and children in this association. Our findings suggest the need for two-generation mental health intervention programs that are tailored based on co-developmental trajectory group membership. [ABSTRACT FROM AUTHOR]

Developing effective treatment options for negative symptoms of psychotic disorders remains a major unmet treatment need and area for further research. In a recent uncontrolled study by the main author, Metacognition Training (MCT) for negative symptoms was found to lead to fewer negative symptoms, less stigma and increased self‐rated reflective ability. As the analysis examined negative symptoms as a whole, we here performed an additional analysis on individual negative symptom items as recent research has suggested that negative symptoms are best conceptualized through a five‐factor model. It was found that the intervention led to changes specifically on sociality and blunted affect (with large effect sizes), which might reflect changes in both intrapersonal and interpersonal (meta)cognitive processes. [ABSTRACT FROM AUTHOR]

Despite the global impact of substance misuse, there are inadequate levels of specialist service provision and continued difficulties with treatment engagement. Within policy and research, there is substantial consideration of the importance of these factors. However, there is little empirical evidence of the views of non-treatment-seeking substance users, who make up the majority of the substance using population. The aim of this study was to understand how these individuals make sense of their behaviour and their reasons for not accessing treatment. A constructivist grounded theory approach was used to interview eight individuals who were currently using substances and not seeking help to stop. The analysis highlighted the importance of attachment to an identity associated with substance use, and relational variables such as connectedness to others, for treatment decisions for individuals who use substances. Understanding these influences, through trauma- and attachment-informed service provision, may reduce barriers to help-seeking and improve treatment uptake. [ABSTRACT FROM AUTHOR]

Previous research has suggested that bullying victimization is associated with higher suicidal risk among young people; however, the mechanisms underlying this relation have not been well examined. The current study aimed to illuminate the developmental links between bullying victimization and suicidal ideation by examining the mediating roles of depressive symptoms, anxiety symptoms, and substance use. The study sample consisted of n = 1465 participants (51.7% male) from the normative z-proso study. Using random intercept cross-lagged panel models and three waves of longitudinal data (ages 15, 17, and 20), the hypothesized mediation effects at the within-person level were tested while partialling out between-person confounds. The results suggested that, at the within-person level, bullying victimization did not predict subsequent suicidal ideation via depressive symptoms, anxiety symptoms, or substance use. However, age 15 bullying victimization predicted within-person increases in age 17 depressive symptoms and suicidal ideation. In addition, depressive symptoms at age 15 and tobacco and cannabis use at age 17 were associated with within-person increases in bullying victimization at ages 17 and 20, respectively. The results also indicated that cannabis use and suicidal ideation were positively and reciprocally related over time. Future studies collecting data at multiple timescales are needed to understand proximal and longer-term mechanisms underlying the relation between bullying victimization and suicidality. [ABSTRACT FROM AUTHOR]

Background: Bullying, suicide, and self‐injury are significant issues among young people. Extensive research has documented bullying victimization associations with suicidal ideation and self‐injury; however, the modeling approaches used have mostly not addressed the relations between these constructs at the within‐person level, and it is these links that are critical for testing developmental theories and guiding intervention efforts. This examined the within‐person, bidirectional relations between these constructs in adolescence and emerging adulthood. Methods: Participants were from the Zurich Project on Social Development from Childhood to Adulthood (z‐proso). Random intercept cross‐lagged panel models (RI‐CLPMs) were fit to general and sexual bullying victimization and suicidal ideation data at ages 15, 17, and 20 (n = 1465), and general and sexual victimization and direct self‐injurious behavior data at ages 13, 15, 17, and 20 (n = 1482). Results: There was a positive within‐person effect of age 15 general bullying victimization on age 17 suicidal ideation (β =.10) and age 17 suicidal ideation on age 20 general bullying victimization (β =.14). Conclusions: General bullying victimization and suicidal ideation may have detrimental effects on each other over development but at different stages. [ABSTRACT FROM AUTHOR]

Neuroinflammation has been implicated in Alzheimer's disease onset and progression. Chronic neuroinflammation is initiated by amyloid-β-activated microglial cells that secrete immuno-modulatory molecules within the brain and into the vasculature. Inflammation is normally self-limiting and actively resolves by "switching off" the generation of pro-inflammatory mediators and by non-phlogistic clearance of spent cells and their debris to restore tissue homeostasis. Deficits in these anti-inflammatory/pro-resolution pathways may predispose to the development of chronic inflammation. The synthesis of endogenous lipid mediators from arachidonic acid, lipoxins via cyclooxygenase 2 and lipoxygenases, and conversion of exogenous polyunsaturated fatty acids, namely docosahexaenoic acid and eicosapentaenoic acid, to resolvins contributes to effective, timely resolution of acute inflammation. Work by Xiuzhe et al., 2020 in the Journal of Alzheimer's Disease reported that plasma level of LXA4 is related to cognitive status in ischemic stroke patients suggesting that decreased LXA4 may be a potential risk factor for post post-stroke cognitive impairment. As evident by recent clinical trials and development of drug analogues, there is recent drive to search for lipoxin analogues as therapeutics for inflammatory diseases. Understanding how bioactive lipid signaling is involved in resolution will increase our understanding of controlling inflammation and may facilitate the discovery of new classes of therapeutic pro-resolution agents for evaluation in AD prevention studies. [ABSTRACT FROM AUTHOR]

Significance: Antibacterial defense invokes the innate immune system as a first responder, with neutrophils phagocytozing and forming neutrophil extracellular traps around pathogens in a reactive oxygen species (ROS)-dependent manner. Increased NOX2 activity and mitochondrial ROS production in phagocytic, antigen-presenting cells (APCs) affect local cytokine secretion and proteolysis of antigens for presentation to T cells at the immune synapse. Uncontrolled oxidative post-translational modifications to surface and cytoplasmic proteins in APCs during aging can impair innate immunity. Recent Advances: NOX2 plays a role in the maturation of dendritic cells, but paradoxically NOX2 activity has also been shown to promote viral pathogenicity. Accumulating evidence suggests that a reducing environment is essential to inhibit pathogen proliferation, facilitate antigenic processing in the endosomal lumen, and enable an effective immune synapse between APCs and T cells. This suggests that the kinetics and location of ROS production and reducing potential are important for effective innate immunity. Critical Issues: During aging, innate immune cells are less well able to phagocytoze, kill bacteria/viruses, and process proteins into antigenic peptides—three key steps that are necessary for developing a specific targeted response to protect against future exposure. Aberrant control of ROS production and impaired Nrf2-dependent reducing potential may contribute to age-associated immune decline. Future Directions: Local changes in redox potential may be achieved through adjuvant formulations to improve innate immunity. Further work is needed to understand the timing of delivery for redox modulators to facilitate innate immune cell recruitment, survival, antigen processing and presentation activity without disrupting essential ROS-dependent bacterial killing. [ABSTRACT FROM AUTHOR]

Impaired fertility is one potential late effect of cancer, with 15% of adolescents and young adults with cancer (AYAC) at a high risk. Guidelines state that fertility advice should be available at diagnosis; however, research shows that this is not routinely provided. This can negatively affect patients' emotional well-being, mental health, and satisfaction with care. This review aimed to synthesize and critically evaluate studies investigating professionals' experiences of discussing fertility issues with AYAC patients and to understand the barriers and facilitating factors to having these conversations with this specific age group. Peer-reviewed qualitative and quantitative studies were identified by systematically searching eight databases. Fifteen articles reporting from 14 studies were included in the review. Participants reported patient, parent, professional, and institutional factors that influenced fertility discussions. The most commonly reported barriers were the lack of patient educational materials and staff training. Participants were more likely to discuss fertility with patients who were male; had less severe disease; and raised the issue of fertility themselves. The findings suggest that professionals' own values and opinions influence the likelihood of fertility being discussed, with implications for guidance and training. Further, institutional barriers lead to a lack of consistent provision for patients both nationally and internationally. A paucity of research looking solely at AYA populations was noted. A need for research comparing the experiences of different professional groups and exploring the extent to which reported barriers impact on fertility discussions was highlighted. There is also a need for higher-quality qualitative research adopting stronger methodology. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to explore the relationship between affective disturbances and aberrant salience in the context of childhood trauma, attachment, and mentalization in an analogue study. Methods: Using a cross‐sectional design, an online community sample completed self‐report measures of key variables. Structural equation modelling was used to test childhood trauma's influence on aberrant salience via a set of intermediate risk factors (depression, negative schizotypy, and insecure attachment). These intermediate risk factors were assumed to lead to the proximal risk factors of aberrant salience (i.e., disorganized schizotypy and disorganized attachment) depending on the vulnerability of mentalizing capacity to elevated stress. Results: The sample (N = 1263) was 78% female and aged between 18 and 35 years. The tested models closely fitted the observed data, revealing significant pathways from childhood trauma to aberrant salience via the hypothesized pathways. The direct effect of childhood trauma on aberrant salience was significant. Conclusion: Findings suggest that the pathway to aberrant salience may be characterized by disorganization of self‐state and intersubjectivity as a function of diminishment in mentalizing ability. This may relate to changes in attachment organization and socio‐cognitive capacity, which could constitute possible risk factors signalling development of aberrant salience. [ABSTRACT FROM AUTHOR]

Aim: Compared with adult onset psychosis, adolescent psychosis has been associated with poorer outcomes in terms of social and cognitive functioning and negative symptoms. Young people experiencing first episode psychosis have developmental needs that frequently pre‐date and are compounded by psychosis onset (a previous study). There is a lack of published studies of adolescent onset psychosis and further information is needed so that developmentally appropriate interventions can be developed. We report an observational naturalistic cohort study of an adolescent specific service, the Early Psychosis Support service (EPSS). Method: We examined baseline demographic and clinical variables, treatments outcomes and predictors of outcome for this population. Results: The mean age of our sample was 16.3 years. Median duration of untreated illness (DUI) was 88 weeks, and median duration of untreated psychosis (DUP) was 16 weeks. We found significant improvements in positive symptoms, negative symptoms, disorganization, excitement, emotional distress and depression from 0 to 12 months. We found that baseline positive symptoms and DUI significantly predicted positive symptoms at 12 months and only negative symptoms at baseline predicted 12‐month negative symptoms. Conclusion: Our finding that specialist early intervention for adolescents experiencing psychosis is effective suggests that such treatment should be routinely offered in line with existing clinical guidelines. Our finding that DUI is predictive of poorer outcome at 12 months suggests that even earlier intervention from a specialist team may further improve treatment outcomes. [ABSTRACT FROM AUTHOR]

We describe the introduction of the Power Threat Meaning Framework (PTMF) to our teaching on critical and community psychology with particular reference to formulation, and critically consider the implementation of this teaching. [ABSTRACT FROM AUTHOR]

Abstract Reactive oxygen species (ROS) are created in cells during oxidative phosphorylation by the respiratory chain in the mitochondria or by the family of NADPH oxidase (NOX) complexes. The first discovered and most studied of these complexes, NOX2, mediates the oxidative burst in phagocytes. ROS generated by NOX2 are dreadful weapons: while being essential to kill ingested pathogens they can also cause degenerative changes on tissue if production and release are not balanced by sufficient detoxification. In the last fifteen years evidence has been accumulating that ROS are also integral signaling molecules and are important for regulating autoimmunity and immune-mediated inflammatory diseases. It seems that an accurate redox balance is necessary to sustain an immune state that both prevents the development of overt autoimmunity (the bright side of ROS) and minimizes collateral tissue damage (the dark side of ROS). Herein, we review studies from rodent models of arthritis, lupus, and neurodegenerative diseases that show that low NOX2-derived ROS production is linked to disease and elaborate on the underlying cellular and molecular mechanisms and the translation of these results to disease in humans. Highlights • ROS are created during oxidative phosphorylation and by NADPH oxidase complexes. • ROS-induced signaling regulates immune reactions and can prevent autoimmunity. • Prolonged and uncontrolled ROS production can cause collateral tissue damage. • Temporally and spatial balance of ROS levels is essential to sustain homeostasis. [ABSTRACT FROM AUTHOR]

Apoptosis is a key event in the control of inflammation. However, for this to be successful, dying cells must efficiently and effectively communicate their presence to phagocytes to ensure timely removal of dying cells. Here, we consider apoptotic cell-derived extracellular vesicles and the role of contained lipids and lipid mediators in ensuring effective control of inflammation. We discuss key outstanding issues in the study of cell death and cell communication, and introduce the concept of the 'active extracellular vesicle' as a metabolically active and potentially changing intercellular communicator. [ABSTRACT FROM AUTHOR]

Background To present clinical outcome data of the Adolescent Mentalization-based Integrative Treatment ( AMBIT)-trained NHS Lothian Tier 4 child and adolescent mental health service in the context of service utilization and engagement. Method Data were obtained for a 2-year period that included details of all face-to-face contacts between young people and clinicians along with routinely collected clinical outcomes data relating to anxiety, depression, symptoms of psychosis and quality of life. Results Improvements were observed in quality of life, symptoms and distress across the course of the intervention. Overall attendance rates were high (80%). Relative to those who were better engaged, the less well-engaged group received the same number of appointments but spent longer in the service (χ2(1) = 5.26, p = .022), had more professionals involved in their care (χ2(1) = 4.91, p = .027) and showed a nonsignificant trend to more inpatient admissions. Later engagement was not associated with distress or symptoms at entry into the service with the exception of negative symptoms in the Early Psychosis Support Service cohort. Age and two quality of life factors were associated with later engagement (p < .05). Conclusions Our AMBIT-trained Tier 4 CAMH service demonstrates change over the course of intervention consistent with the service model's theoretical expectations. Engagement with the service may be associated more with factors related to social circumstance and functioning than with key symptoms and distress. Less well-engaged young people utilize increased service resource. AMBIT's mentalizing focus may improve service provision for young people who are poorly engaged with mental health services. [ABSTRACT FROM AUTHOR]

In this paper we use Transformative Learning Theory as a lens for making sense of teachers’ learning from study visits to the Global South. Transformative Learning theory is made up of two main elements: the form of transformations and the processes that support transformations. ‘Life changing’ experiences as expressed by study visit participants have been interpreted as transformational, but questions about who and what are transformed, and whether this is at the expense of the ‘Other’, are rarely addressed. Drawing on data from a project investigating study visits for UK teachers to Gambia and Southern India, we analyse theformthat changes take and discuss whether these can be seen as transformational. We argue that without an explicit focus on relational forms of knowledge about culture and identity, self and other, the potential for transformations in how we relate to, and learn from, each other in postcolonial contexts is severely diminished. [ABSTRACT FROM PUBLISHER]

The oxidoreductase Trx-1 (thioredoxin 1) is highly conserved and found intra- and extra-cellularly in mammalian systems. There is increasing interest in its capacity to regulate immune function based on observations of altered distribution and expression during ageing and disease. We have investigated previously whether extracellular T-cell or peripheral blood mononuclear cell Trx-1 levels serve as a robust marker of ageing. In a preliminary study of healthy older adults compared with younger adults, we showed that therewas a significant, butweak, relationshipwith age. Interestingly, patientswith rheumatoid arthritis and cancer have been described by others to secrete or express greater surface Trx-1 than predicted. It is interesting to speculate whether a decline in Trx-1 during ageing protects against such conditions, but correspondingly increases risk of disease associated with Trx-1 depletion such as cardiovascular disease. These hypotheses are being explored in the MARK-AGE study, and preliminary findings confirm an inverse correlation of surface Trx-1 with age. We review recent concepts around the role of Trx-1 and its partners in T-cell function on the cell surface and as an extracellular regulator of redox state in a secreted form. Further studies on the redox state and binding partners of surface and secreted Trx-1 in larger patient datasets are needed to improve our understanding of why Trx-1 is important for lifespan and immune function. [ABSTRACT FROM AUTHOR]

Despite improvements in interventional and pharmacological therapy of atherosclerotic disease, it is still the leading cause of death in the developed world. Hence, there is a need for further development of effective therapeutic approaches. This requires better understanding of the molecular mechanisms and pathophysiology of the disease. Atherosclerosis has long been identified as having an inflammatory component contributing to its pathogenesis, whereas the available therapy primarily targets hyperlipidemia and prevention of thrombosis. Notwithstanding a pleotropic anti-inflammatory effect to some therapies, such as acetyl salicylic acid and the statins, none of the currently approved medicines for management of either stable or complicated atherosclerosis has inflammation as a primary target. Monocytes, as representatives of the innate immune system, play a major role in the initiation, propagation, and progression of atherosclerosis from a stable to an unstable state. Experimental data support a role of monocytes in acute coronary syndromes and in outcome post-infarction; however, limited research has been done in humans. Analysis of expression of various cell surface receptors allows characterization of the different monocyte subsets phenotypically, whereas downstream assessment of inflammatory pathways provides an insight into their activity. In this review we discuss the functional role of monocytes and their different subpopulations in atherosclerosis, acute coronary syndromes, cardiac healing, and recovery with an aim of critical evaluation of potential future therapeutic targets in atherosclerosis and its complications. We will also discuss technical difficulties of delineating different monocyte subpopulations, understanding their differentiation potential and function. [Copyright &y& Elsevier]

This paper critically analyses the neo‐liberal discourse informing global education policy and practice. We use postcolonial theory to deconstruct the contexts for global educational partnerships, highlighting how issues of power and representation are central to their development and the learning that takes place within them. Teacher development through North—South study visits is one way of challenging teachers' worldviews, but these are not always effective. We argue that study visit courses, where learning is facilitated by differently knowledgeable others, have the potential to be more effective, but only if the courses are underpinned by postcolonial theory and informed by socio‐cultural pedagogy. [ABSTRACT FROM AUTHOR]

Abstract: This paper reports two experiments to determine the contribution of the suppressing eye to the generation of saccadic eye movements in constant strabismus. Eye movements were recorded using a Skalar infra-red recorder. Experiment 1 tested six participants with constant strabismus, pathological suppression and no clinically demonstrable binocular single vision (BSV). We explored the effect of visual distractors presented monocularly (to either the fixing eye or the strabismic eye) and binocularly, on saccade latency and accuracy. Saccade latency significantly increased when distractors were presented to the strabismic eye compared to the no distractor condition. In all participants the effect on latency, with distractors presented to the strabismic eye, was maximum when distractors were presented towards the location of the anatomical fovea. Saccade accuracy was reduced with ipsilateral distractors to the target when presented binocularly or monocularly to the fixing eye but not affected by distractors presented to the strabismic eye. Experiment 2 investigated fast disconjugate saccade adaptations in six participants with constant strabismus, pathological suppression and no clinically demonstrable BSV and for comparison 8 with normal bifoveal BSV. Saccade disconjugacy was induced using an electronic feedback system in which the calibrated eye movement position signal could be scaled by a factor (the feedback gain) to move the target visible to one eye during binocular viewing. In all BSV participants and 3 of 6 participants with constant strabismus, saccadic adaptation occurred rapidly such that under conditions of visual feedback saccades became increasingly disconjugate. These disconjugacies persisted when normal viewing conditions were restored. The presence of an adaptive mechanism to adjust the binocular co-ordination of saccades in the presence of constant strabismus with suppression and no clinically demonstrable BSV has been demonstrated. Mechanisms that might explain such results are discussed. [Copyright &y& Elsevier]

Abstract: Successful word learning depends on the integration of phonological and semantic information with social cues provided by interlocutors. How then, do children with autism spectrum disorders (ASDs) learn new words when social impairments pervade? We recorded the eye-movements of verbally-able children with ASD and their typical peers while completing a word learning task in a social context. We assessed learning of semantic and phonological features immediately after learning and again four weeks later. Eye-movement data revealed that both groups could follow social cues, but that typically developing children were more sensitive to the social informativeness of gaze cues. In contrast, children with ASD were more successful than peers at mapping phonological forms to novel referents; however, this advantage was not maintained over time. Typical children showed clear consolidation of learning both semantic and phonological information, children with ASD did not. These results provide unique evidence of qualitative differences in word learning and consolidation and elucidate the different mechanisms underlying the unusual nature of autistic language. [ABSTRACT FROM AUTHOR]

A dominant allele at the D locus (also known as I in diploid potato) is required for the synthesis of red and purple anthocyanin pigments in tuber skin. It has previously been reported that D maps to a region of chromosome 10 that harbors one or more homologs of Petunia an2, an R2R3 MYB transcription factor that coordinately regulates the expression of multiple anthocyanin biosynthetic genes in the floral limb. To test whether D acts similarly in tuber skin, RT-PCR was used to evaluate the expression of flavanone 3-hydroxylase ( f3h), dihydroflavonol 4-reductase ( dfr) and flavonoid 3′,5′-hydroxylase ( f3′ 5′ h). All three genes were expressed in the periderm of red- and purple-skinned clones, while dfr and f3′ 5′ h were not expressed, and f3h was only weakly expressed, in white-skinned clones. A potato cDNA clone with similarity to an2 was isolated from an expression library prepared from red tuber skin, and an assay developed to distinguish the two alleles of this gene in a diploid potato clone known to be heterozygous Dd. One allele was observed to cosegregate with pigmented skin in an F1 population of 136 individuals. This allele was expressed in tuber skin of red- and purple-colored progeny, but not in white tubers, while other parental alleles were not expressed in white or colored tubers. The allele was placed under the control of a doubled 35S promoter and transformed into the light red-colored cultivar Désirée, the white-skinned cultivar Bintje, and two white diploid clones known to lack the functional allele of D. Transformants accumulated pigment in tuber skin, as well as in other tissues, including young foliage, flower petals, and tuber flesh. [ABSTRACT FROM AUTHOR]

Evidence of atypical perception in individuals with ASD is mainly based on self report, parental questionnaires or psychophysical/cognitive paradigms. There have been relatively few attempts to establish whether binocular vision is enhanced, intact or abnormal in those with ASD. To address this, we screened visual function in 51 individuals with autistic spectrum disorder and 44 typically developing individuals by measuring visual acuity, stereoacuity, convergence, divergence, ocular motility, incidence of strabismus and integrity of the optokinetic response. The data suggest that many aspects of vision, including visual acuity, are unaffected in ASD, but that convergence is an aspect of visual function that merits further research in those with ASD. [ABSTRACT FROM AUTHOR]

Abstract: Biomolecules are susceptible to many different post-translational modifications that have important effects on their function and stability, including glycosylation, glycation, phosphorylation and oxidation chemistries. Specific conversion of aspartic acid to its isoaspartyl derivative or arginine to citrulline leads to autoantibody production in models of rheumatoid disease, and ensuing autoantibodies cross-react with native antigens. Autoimmune conditions associate with increased activation of immune effector cells and production of free radical species via NADPH oxidases and nitric oxide synthases. Generation of neo-antigenic determinants by reactive oxygen and nitrogen species ROS and RNS) may contribute to epitope spreading in autoimmunity. The oxidation of amino acids by peroxynitrite, hypochlorous acid and other reactive oxygen species (ROS) increases the antigenicity of DNA, LDL and IgG, generating ligands for which autoantibodies show higher avidity. This review focuses on the evidence for ROS and RNS in promoting the autoimmune responses observed in diseases rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It considers the evidence for ROS/RNS-induced antigenicity arising as a consequence of failure to remove or repair ROS/RNS damaged biomolecules and suggests that an associated defect, probably in T cell signal processing or/or antigen presentation, is required for the development of disease. [Copyright &y& Elsevier]

The article reports on the 3rd Summer School of the Society for Free Radical Research Europe (SFRR-E) held at Hotel Spetses in Greece between August 30 and September 5, 2008. The event was opened by the principal organiser, Professor Nesrin Kartal-Ozer, who highlighted the quality of the applicants who had expressed an interest in attending the school. The programme for each day of the event focused on one specific theme within the broader scope of the theme, "Lipid Peroxidation and Free Radical-Signalling: Role in Pathophysiology."

Routine cell line maintenance involves removal of waste products and replenishment of nutrients via replacement of cell culture media. Here, we report that routine maintenance of three discrete cell lines (HSB-CCRF-2 and Jurkat T cells, and phaeo-chromocytoma PC12 cells) decreases the principal cellular antioxidant, glutathione, by up to 42% in HSB-CCRF-2 cells between 60 and 120min after media replenishment. However, cellular glutathione levels returned to baseline within 5h after passage. The decrease in glutathione was associated with modulation of the response of Jurkat T cells to apoptotic and mitogenic signals. Methotrexate-induced apoptosis over 16h, measured as accumulation of apoptotic nucleoids, was decreased from 22 to 17% if cells were exposed to cytotoxic agent 30min after passage compared with cells exposed to MTX in the absence of passage. In contrast, interleukin-2 (IL-2) production over 24h in response to the toxin phytohaemagglutinin (PHA), was increased by 34% if cells were challenged 2h after passage compared with PHA treatment in the absence of passage. This research highlights the presence of a window of time after cell passage of non-adherent cells that may lead to over-or under-estimation of subsequent cell responses to toxins, which is dependent on cellular antioxidant capacity or redox state. [Copyright &y& Elsevier]

Abstract: The potential cytotoxicity of two hexanedione food additives (2,3 and 3,4 isomers) was evaluated in comparison with the neurotoxic hexane metabolite 2,5-hexanedione in the human SK-N-SH neuroblastoma line using the MTT assay to indicate mitochondrial dehydrogenase activity and flow cytometry to monitor the cell cycle over 48h. The IC50s of the 2,3-hexanedione (3.3±0.1mM) and 3,4-hexanedione (3.5±0.1mM), indicated that the sensitivity of the cells was approximately seven-fold greater to these toxins compared with the 2,5 derivative (IC50 of 22.4±0.2mM). Comparison between the respective IC50s of the 2,3-hexanedione and 3,4-hexanedione revealed no difference between the two isomers in terms of their effects on MTT turnover. With flow cytometry analysis, all three hexanediones showed increases in apoptosis within their respective concentration ranges of toxicity shown previously by MTT. In the presence of 2,5-hexanedione, between 8.5 and 17mM concentrations, there was a significant increase in apoptotic nucleoids which was accompanied by a significant fall in the percentage of nucleoids in the G0/G1 phase (72.4±0.3–45.3±0.6%,), and a rise in the numbers of cells in the G2/M phase. This is likely to indicate growth arrest at cell cycle G2/M checkpoint in response to toxin damage. G2/M accumulation was also shown with 3,4 and 2,3 HD, which was maximal at much lower concentrations (approximately 4 and 3mM, respectively). Arrest at G1 and G2/M phase is indicative of inhibition of the cell cycle at the stages of DNA replication and chromosome segregation, respectively. It was also apparent that flow cytometry, rather than the MTT assay, did distinguish between the effects of the α-diketones 2,3-hexanedione and 3,4-hexanedione on the cell cycle. At a concentration of 5.8mM 3,4-hexanedione, the percentage of apoptotic nucleoids was 10.9±0.8% whilst apoptosis induced by 3,4-hexanedione had already reached a maximal level of 60.4±0.5%. In summary, flow cytometry indicated that the 3,4-hexanedione derivative was more toxic than its 2,3 isomer and that both food additives caused interruption in the neuroblastoma cell cycle and further investigation may be required to assess if these α-diketones present in diets pose any possible risks to human health. [Copyright &y& Elsevier]

Abstract: Oxidised LDL accumulates in macrophages following scavenger receptor (SR) uptake. The expression of the SR, CD36, is increased by oxidised LDL. The signalling molecule, ceramide, can modulate intracellular peroxides and increase lipid peroxidation. Ceramide also accumulates in atherosclerotic plaques. Thus, we have examined whether ceramide can modulate CD36 expression and function in human monocyte/macrophages. Addition of synthetic short chain ceramides or the action of sphingomyelinase to generate physiological long chain ceramides in situ caused significant reductions in CD36 expression by monocytes/macrophages which was not due to inhibition of mRNA expression. Inhibition of proteasomal degradation using lactacystin had no effect on CD36 expression, however, flow cytometric analysis of permeabilised cells suggested an intracellular trafficking blockade. Ceramide treated monocytes/macrophages showed dose dependent reduction in oxidised LDL uptake. Taken together, it is suggested that ceramide blocks the transport of CD36 to the membrane of monocytes/macrophages, thereby preventing uptake of oxidised LDL. [Copyright &y& Elsevier]

Abstract: We recently reported that methionine-loaded human umbilical vein endothelial cells (HUVECs) exported homocysteine (Hcy) and were associated with hydroxyl radical generation and oxidation of lipids in LDL. Herein we have analysed the Hcy-induced posttranslational modifications (PTMs) of LDL protein. PTMs have been characterised using electrophoretic mobility shift, protein carbonyl ELISA, HPLC with electrochemical detection and Western blotting of 3-nitrotyrosine, and LDL uptake by scavenger receptors on monocyte/macrophages. We have also analysed PTMs in LDL isolated from rheumatoid (RA) and osteo-(OA) arthritis patients with cardiovascular disease (CVD). While reagent Hcy (<50 μM) promoted copper-catalysed LDL protein oxidation, Hcy released from methionine-loaded HUVECs promoted LDL protein nitration. In addition, LDL nitration was associated with enhanced monocyte/macrophage uptake when compared with LDL oxidation. LDL protein nitration and uptake by monocytes, but not carbonyl formation, was elevated in both RA and OA patients with CVD compared with disease-matched patients that had no evidence of CVD. Moreover, a direct correlation between plasma total Hcy (tHcy) and LDL uptake was observed. The present studies suggest that elevated plasma tHcy may promote LDL nitration and increased scavenger receptor uptake, providing a molecular mechanism that may contribute to the clinical link between CVD and elevated plasma tHcy. [Copyright &y& Elsevier]

Abstract: We tested the effect of visual distractors presented monocularly and binocularly on saccade latency and accuracy to determine whether differences occur in saccadic planning with binocular or monocular visual input. For five participants with normal binocular single vision (BSV), saccade latency and accuracy were compared with distractors presented to the dominant eye, non-dominant eye or to both eyes. Eye movements of the dominant eye were recorded using a Skalar infra-red recorder. In the presence of normal BSV, the effect of distractors is significantly larger for saccade latency and accuracy with binocular distractor presentation than for monocular presentations, with no difference between distrators presented to the dominant or non-dominant eye. The implications of these results are discussed with regard to saccade programming. [Copyright &y& Elsevier]

Reactive oxygen species are recognised as important signalling molecules within cells of the immune system. This is, at least in part, due to the reversible activation of kinases, phosphatases and transcription factors by modification of critical thiol residues. However, in the chronic inflammatory disease rheumatoid arthritis, cells of the immune system are exposed to increased levels of oxidative stress and the T cell becomes refractory to growth and death stimuli. This contributes to the perpetuation of the immune response. As many of the effective therapies used in the treatment of rheumatoid arthritis modulate intracellular redox state, this raises the question of whether increased oxidative stress is causative of T-cell hyporesponsiveness. To address this hypothesis, this review considers the putative sources of ROS involved in normal intracellular signalling in T cells and the evidence in support of abnormal ROS fluxes contributing to T-cell hyporesponsiveness. [ABSTRACT FROM AUTHOR]

The potatoPlocus is required for the production of blue/purple anthocyanin pigments in any tissue of the potato plant such as tubers, flowers, or stems. We have previously reported, based on RFLP mapping in tomato, that the gene coding for the anthocyanin biosynthetic enzyme flavonoid 3',5'-hydroxylase (f3'5'h) maps to the same region of the tomato genome asPmaps in potato. To further evaluate this association aPetunia f3'5'hgene was used to screen a potato cDNA library prepared from purple-colored flowers and stems. Six positively hybridizing cDNA clones were sequenced and all appeared to be derived from a single gene that shares 85% sequence identity at the amino acid level withPetunia f3'5'h. The potato gene cosegregated with purple tuber color in a diploid F1 sub-population of 37 purple and 25 red individuals and was found to be expressed in tuber skin only in the presence of the anthocyanin regulatory locusI. A potatof3'5'hcDNA clone was placed under the control of a doubled CaMV 35S promoter and introduced into the red-skinned cultivar ‘Désirée’. Tuber and stem tissues that are colored red in Désirée were purple in nine of 17 independently transformed lines. [ABSTRACT FROM AUTHOR]

Generation of neoepitopes on apolipoprotein B within oxidised low-density lipoprotein (LDL) is important in the unregulated uptake of LDL by monocytic scavenger receptors (CD36, SR-AI, LOX-1). Freshly isolated LDL was oxidised by peroxyl radicals generated from the thermal decomposition of an aqueous azo-compound. We describe that formation of carbonyl groups on the protein component is early as protein oxidation was seen after 90 min. This is associated with an increased propensity for LDL uptake by U937 monocytes. Three classes of antioxidants (quercetin, dehydroepiandrosterone (DHEA) and ascorbic acid) have been examined for their capacity to inhibit AAPH-induced protein oxidation, (protein carbonyls, Δ electrophoretic mobility and LDL uptake by U937 monocytes). CD36 expression was assessed by flow cytometry and was seen to be unaltered by oxidised LDL uptake. All three classes were effective antioxidants, quercetin (P<0.01), ascorbic acid (P<0.01), DHEA (P<0.05). As LDL protein is the control point for LDL metabolism, the degree of oxidation and protection by antioxidants is likely to be of great importance for (patho)-physiological uptake of LDL by monocytes. [Copyright &y& Elsevier]

Presents a study which investigated the hypothesis that A Β neurotoxicity is mediated by reactive oxygen species, where trophic factor cytoprotection against oxidative stress is achieved through regulation of glutathione levels at the gene level. Methods; Results and discussion.

Protein oxidation can be perceived as essential for the control of intracellular signalling and gene expression on the one hand, but in contrast, a potentially cytotoxic hazard of aerobic life. Reduction and oxidation of thiol groups on specific cysteine residues can act as critical molecular switches, in modulating response to growth factors, apoptotic and inflammatory stimuli to name a few. Such oxidative reactions are likely to be transient and represent low levels of oxidative modification to a protein. Sustained oxidative stress conditions through absence of essential dietary antioxidant or low activity of endogenous enzyme scavengers can cause irreversible damage and loss of function. Such modifications are believed to be important in many diseases associated with ageing. Therefore, it has been postulated that diet may exert an influence on the steady state of protein oxidation and thus offer potential health benefits through preservation of normal protein function. In the present paper, the current evidence from in vivo studies on the effects of dietary antioxidants and oxidants on protein oxidation will be evaluated, and needs for future research will be highlighted. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including the role DNA technology for protein-based vaccines development, challenges linked with vaccine development, and the use of yeast for vaccine production.

The article discusses research done on GDF-15 in atrial fibrillation (AF). It references the study "Growth Differentiation Factor 15, a Marker of Oxidative Stress and Inflammation, for Risk Assessment in Patients With Atrial Fibrillation: Insights From the Apaxaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial" by L. Wallentin and colleagues, published in the 2014 issue. The authors discuss the relevance and limitations of the study.

Background: Almost a quarter of children and young people (CYP) in England have a long-term health condition (LTC), which increases the risk of developing mental health difficulties. There is a lack of understanding regarding the routine provision and efficacy of mental health interventions for CYP with LTCs within Children and Young People's Mental Health Services (CYPMHS). Methods: This study analysed national service-reported data in England from two secondary datasets. Data were submitted by services between 2011 and 2019. We evaluated data on the presence or absence of a serious physical health or neurological issue, and which interventions were offered. Results: A total of 789 CYP had serious physical health issues and 635 had neurological issues. The most common interventions delivered to CYP in either group have some evidence in the literature. Most CYP showed improvements across a range of outcomes. Conclusions: This study found that prevalence rates and psychological intervention and outcome data were widely under-reported across both datasets, posing questions about their utility for this population. Such data would benefit from triangulation with data from other sources to understand pathways of care for these young people and the extent to which clinical datasets underreport the number of CYP with LTCs. Plain language summary: Almost a quarter of children and young people (CYP) in England have a long-term health condition (LTC), such as asthma, diabetes, or epilepsy. We know that these young people are at increased risk of developing mental health difficulties. It is important these young people are able to access safe and effective treatments for their mental health. Therefore, they are sometimes referred to Children and Young People's Mental Health Services (CYPMHS) for appropriate treatment. However, at the moment, not much is known about the types of mental health support these services offer to children with co-existing physical health needs, or if this support is effective. The aim of this study was to try and find this out. We used data that had already been collected from mental health services across England. We looked at specific parts of this data that gave us information about the type of mental health treatments delivered to children with a long-term health condition. We separated long-term health conditions into two categories: physical health, such as diabetes or asthma; and neurological, such as epilepsy. In the sample we looked at, a range of mental health treatments were delivered to young people in both groups. Encouragingly, many of the young people's mental health improved. However, a lot of information we would hope to find was not available in the datasets. Also, the number of children with a long-term health condition was much lower than we expected. This might have been for a number of reasons, which we recommend other future research tries to find out. Going forward, it is important to think about how to make sure that accurate information about these children is collected from mental health services. This will help ensure that the right decisions are made for the care of young people with long-term health conditions. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

We have shown that in semantic dementia (Snowden, Griffiths, & Neary, 1994, 1995, 1996) patients' knowledge is significantly influenced by its relevance to their autobiographical experience. Graham, Lambon Ralph, and Hodges (1997), in an investigation of the autobiographical effect, found that general knowledge of sports in which their semantic dementia patients participated was no better than that for other sports and inferred that their data contradict the hypothesis that experience helps to preserve meaning. The purpose of this paper is to address the apparent conflict of views. First, we show that the hypothesis under investigation in the Graham et al. study, that experience maintains all the knowledge about a concept, is not one to which we subscribe and that much of their data is in fact consistent with our own findings. We highlight similarities in our interpretation of the autobiographical effect. We then examine those areas in which our opinions appear to diverge. We argue that autobiographically relevant knowledge can be explicit and is not merely implicit and is semantic and not merely procedural. We argue, moreover, that it is truly semantic and not merely semantic-like. We reconsider the nature of semantic knowledge and the relationship between medial temporal and temporal neocortical memory systems. [ABSTRACT FROM AUTHOR]

Semantic dementia refers to a multi-modal loss of semantic knowledge, resulting from degeneration of the anterior temporal neocortex. Loss of information is not absolute. We have previously demonstrated (Snowden, Griffiths, & Neary, 1994, 1995) that autobiographical experience has an important role in influencing information preservation, and have argued that patients` preserved experiential memory helps to invest words and objects with meaning that would otherwise be lost. Those studies suggested a particularly critical role of current autobiographical experience. The present study aimed to explore the generality of the observed current information superiority in an investigation of patients` knowledge of celebrities, understanding of a contemporary and obsolete monetary system, and autobiographical memory. Performance was superior for contemporary (recent) than for past (remote) information, both factual and autobiographic, suggesting an inverse of the temporally graded pattern of retrograde memory found in classical amnesia. It is argued that the findings are consistent with explanations of the "temporal gradient" effect of retrograde amnesia in terms of qualitative differences in recent and remote memories. The findings indicate a bidirectional interaction between autobiographic and semantic memorising, and emphasise a continuous, dynamic interrelationship rather than a time-limited role. An important distinction is highlighted between autobiographical and impersonal episodic memory. The findings have significant theoretical implications both for the understanding of retrograde memory function and the interrelationship between episodic and semantic memory. [ABSTRACT FROM AUTHOR]