The Mental Wellbeing of Child and Adolescent Mental Health Service (CAMHS) Workers in England: A Cross-Sectional Descriptive Study Reporting Levels of Burnout, Wellbeing and Job Satisfaction.

In the UK, there has been a notable increase in referrals to specialist children's mental health services. This, coupled with shortages of qualified staff, has raised concerns about the escalating occupational stress experienced by staff in this sector. In this brief report, we present cross-sectional quantitative data from 97 staff members working in one Child and Adolescent Mental Health Service (CAMHS) in the UK during spring 2023, reporting on their wellbeing, job satisfaction, and burnout. Our findings reveal that over a third of CAMHS staff experienced moderate or high levels of work-related burnout; 39% reported moderate or high levels of personal burnout, but levels of client-related burnout were much lower (13%). Both work- and client-related burnout showed a robust negative relationship with job satisfaction, with higher burnout predicting lower levels of job satisfaction. Only a small proportion of respondents reported high levels of wellbeing, with about a quarter experiencing levels of wellbeing that can be considered indicative of mild or clinical depressive symptoms. Whilst these results are from a small sample in one area of the UK, they present an important snapshot of CAMHS staff wellbeing and are discussed in the context of similar trends reported in the wider NHS sector.

Educational experiences of young people with ADHD in the UK: Secondary analysis of qualitative data from the CATCh-uS mixed-methods study.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity and/or impulsivity. Young people with ADHD have poorer educational and social outcomes than their peers. We aimed to better understand educational experiences of young people with ADHD in the UK, and make actionable recommendations for schools. METHODS: In this secondary analysis of qualitative data, we used Thematic Analysis to analyse information relating to experiences of education from 64 young people with ADHD and 28 parents who participated in the Children and adolescents with ADHD in Transition between Children's services and adult Services (CATCh-uS) study. Emerging patterns within and across codes led to organization of the data into themes and subthemes through an iterative process. RESULTS: Two main themes were generated. The first described young people's early experiences of education, often within a mainstream setting; we labelled this the problematic provision loop, as this was a negative cycle that was repeated several times for some participants. The second theme described young people's more positive progression through education once they progressed out of the problematic loop. CONCLUSIONS: Educational experiences for young people with ADHD are often negative and fraught with complication. Young people with ADHD often found themselves on a more positive trajectory after they were placed in an alternative form of education provision (mainstream or otherwise), or where they were able to study topics that interest them and play to their strengths. We make recommendations that commissioners, local authorities and schools could consider in order to better support those with ADHD.

Barriers and facilitators in the delivery of a proportionate universal parenting program model (E-SEE Steps) in community family services.

BACKGROUND: A proportionate universal (PU) approach to early years' service provision has been advocated to improve children's health and development and to reduce health inequality, by ensuring that services provide timely and high-quality parenting support commensurate with need. Process-oriented research is critical to examine the factors that contribute to, or hinder, the effective delivery/implementation of such a model in community-based family services. This study aimed to assess the delivery, acceptability and feasibility of a new PU parenting intervention model (called E-SEE Steps), using the Incredible Years® (IY) parent program, when delivered by trained health/family service staff in three "steps"-one universal step (the IY Babies Book), and two targeted steps (group-based IY Infant and Toddler programs). METHODS: An embedded mixed-methods process evaluation within a pragmatic parallel two-arm, assessor blinded, randomized controlled trial was conducted in community services in four local authorities in England. The process evaluation used qualitative data gathered via interviews and focus groups with intervention arm parents who were offered the targeted steps (n = 29), practitioners (n = 50), service managers (n = 7) and IY program mentors (n = 3). This was supplemented by quantitative data collected using group leader pre-training (n = 50) and post-delivery (n = 39) questionnaires, and research notes of service design decisions. RESULTS: The E-SEE Steps model was acceptable to most parents, particularly when it was accompanied by engagement strategies that supported attendance, such as providing childcare. Practitioners also highlighted the positive development opportunities provided by the IY training and supervision. However, participant views did not support the provision of the IY Babies book as a standalone universal component, and there were barriers to eligible parents-particularly those with low mood-taking up the targeted programs. Service providers struggled to align the PU model with their commissioned service contracts and with their staff capacity to engage appropriate parents, including tackling common barriers to attendance. CONCLUSIONS: Despite general enthusiasm and support for delivering high-quality parenting programs in community services in the England, several barriers exist to successfully delivering IY in a proportionate universal model within current services/systems.

Parent/caregiver attitudes, motivations and behaviours in relation to alcohol use among offspring aged 13-18 years: a qualitative study.

BACKGROUND: Parental alcohol consumption and alcohol-related behaviour play a critical role in shaping adolescent alcohol use, but comparatively little is known about the perspectives of parents regarding adolescent alcohol use from qualitative studies in England. This study aimed to explore parental views and attitudes towards alcohol use during adolescence, among their offspring and among young people in general. METHODS: Twenty-three parents (21 mothers, 2 fathers) of children aged 13-18 years were recruited via schools, workplaces and community settings, predominantly in the West of England (n = 19) between 2017 and 2018. Data were collected via in-depth one-to-one interviews and analysed thematically, using an inductive, constructionist approach. RESULTS: Five major themes were identified in the data: (1) the parental alcohol environment, (2) balance and acceptance, (3) influences of the parental approach, (4) boundaries and parental monitoring, and (5) wider influences shaping young people's behaviour. Overall, parents were aware of the risks and consequences of alcohol use and the wide range of influences shaping drinking behaviour, and expressed broad disapproval of alcohol use among young people. However, adolescent alcohol use was viewed as inevitable, and set within a context of a tolerant drinking culture. Many parents therefore chose a balanced and reluctantly accepting approach. This approach was determined by weighing disapproval of drinking against consistency with wider culture and parental behaviour, support for autonomy of the child, and avoidance of social sanctions. Parents' responses were also determined by a desire to protect the parent-child relationship, maintain an open, communicative and trusting relationship, and ultimately limit risk and minimise harm. Various boundaries and strategies were employed to this end, including care around role modelling, gradual introductions to alcohol, boundaried provision, clear risk reduction messaging and parental monitoring. CONCLUSIONS: Parents employ a range of mechanisms to reduce alcohol-related risk and to balance harms of alcohol use among their offspring against adolescent behavioural norms. A downward shift in community consumption and changing socio-cultural norms could alter the accepting context in which parents are required to navigate adolescent alcohol use.

In transition with attention deficit hyperactivity disorder (ADHD): children's services clinicians' perspectives on the role of information in healthcare transitions for young people with ADHD.

BACKGROUND: National clinical guidelines emphasise the need for good communication of information by clinicians to young people and their parent/carers about what to expect during transition into adult services. Recent research indicates that of young people in need of transition for attention deficit hyperactivity disorder (ADHD), only a minority experience continuity of care into adulthood, with additional concerns about quality of transition. This qualitative analysis explored the role that information plays in the transition from child to adult mental health services for young people with ADHD, from the perspectives of clinicians working in children's services. METHODS: Participants were recruited from National Health Service (NHS) Trusts located across the United Kingdom (UK), with varying service configurations. Twenty-two qualitative interviews were conducted with 15 paediatricians and seven psychiatrists working in child services and supporting young people with ADHD. The Framework Method was used to complete a thematic analysis of data related to the role of information in transitional care. RESULTS: Two themes were identified in relation to the role of information in supporting transition and promoting continuity of care. Information for clinicians; about adult mental health services, the young person and their ADHD, and exchanged between services. Sharing information with young people; about transition processes, self-management, to support service engagement, and tailored to be accessible to young people with ADHD. Clinicians in children's services reported variable access to information. Clear protocols and being able to communicate about ADHD as a long-term condition, were described as having a positive impact on the transition process. CONCLUSIONS: These findings illustrate that clear information on the transition process, and communication of evidence based and up-to-date information on ADHD as a long-term condition are essential components for clinicians supporting transition into adult services. Information exchange can be supported through transition discussions with young people, and joint meetings between services Discussions should be accompanied by accessible resources for young people and parents/carers such as leaflets and websites. Further efforts should be focussed on enabling clinicians to provide timely and appropriate information to young people with ADHD to support transition.

A randomized controlled trial of a proportionate universal parenting program delivery model (E-SEE Steps) to enhance child social-emotional wellbeing.

BACKGROUND: Evidence for parenting programs to improve wellbeing in children under three is inconclusive. We investigated the fidelity, impact, and cost-effectiveness of two parenting programs delivered within a longitudinal proportionate delivery model ('E-SEE Steps'). METHODS: Eligible parents with a child ≤ 8 weeks were recruited into a parallel two-arm, assessor blinded, randomized controlled, community-based, trial with embedded economic and process evaluations. Post-baseline randomization applied a 5:1 (intervention-to-control) ratio, stratified by primary (child social-emotional wellbeing (ASQ:SE-2)) and key secondary (maternal depression (PHQ-9)) outcome scores, sex, and site. All intervention parents received the Incredible Years® Baby Book (IY-B), and were offered the targeted Infant (IY-I)/Toddler (IY-T) program if eligible, based on ASQ:SE-2/PHQ-9 scores. Control families received usual services. Fidelity data were analysed descriptively. Primary analysis applied intention to treat. Effectiveness analysis fitted a marginal model to outcome scores. Cost-effectiveness analysis involved Incremental Cost-Effectiveness Ratios (ICERs). RESULTS: The target sample (N = 606) was not achieved; 341 mothers were randomized (285:56), 322 (94%) were retained to study end. Of those eligible for the IY-I (n = 101), and IY-T (n = 101) programs, 51 and 21 respectively, attended. Eight (of 14) groups met the 80% self-reported fidelity criteria. No significant differences between arms were found for adjusted mean difference scores; ASQ:SE-2 (3.02, 95% CI: -0.03, 6.08, p = 0.052), PHQ-9 (-0.61; 95% CI: -1.34, 0.12, p = 0.1). E-SEE Steps had higher costs, but improved mothers' Health-related Quality of Life (0.031 Quality Adjusted Life Year (QALY) gain), ICER of £20,062 per QALY compared to control. Serious adverse events (n = 86) were unrelated to the intervention. CONCLUSIONS: E-SEE Steps was not effective, but was borderline cost-effective. The model was delivered with varying fidelity, with lower-than-expected IY-T uptake. Changes to delivery systems and the individual programs may be needed prior to future evaluation. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number: ISRCTN11079129.

Spanish language resources for patients with adolescent idiopathic scoliosis.

BACKGROUND: Despite an increasing Spanish-speaking population, United States health care remains English dominant. The purpose of this study was to analyze the availability and readability of written patient education materials on adolescent idiopathic scoliosis (AIS) provided by the top pediatric orthopedic hospitals and the major professional societies. METHODS: We performed a cross sectional analysis by determining the proportion of top pediatric orthopedic hospitals and major orthopedic professional societies providing English and Spanish resources. We also assessed the readability of information provided via three measures of readability. Descriptive, univariate, and multivariate analyses were performed. RESULTS: Approximately 90% of hospitals provided English-language education, but only 37% of hospitals provided Spanish-language education. English and Spanish hospital resources were equivalent in readability across Reading Ease scores (p > 0.05), but Spanish-language resources ranked lower in grade level (8th grade vs. 10th grade, p = 0.01) and readability measures (9.6 vs. 11.6, p < 0.01). Two of the three major orthopedic professional organizations provided Spanish-language resources. The availability and readability of resources in states where more than 20% of the population spoke Spanish did not differ compared to institutions in states with fewer Spanish-speaking patients (p > 0.05). CONCLUSIONS: The availability of Spanish-language resources for patients with AIS is limited, and the reading level for all educational resources is above the suggested level for patient education. Additional effort and resources should be allocated to the improvement of patient education as well as the development of Spanish-language resources for patients with AIS.

Healthy Parent Carers programme: mixed methods process evaluation and refinement of a health promotion intervention.

OBJECTIVES: Parent carers of children with special educational needs or disability are at risk of poorer mental and physical health. In response to these needs, we codeveloped the 'Healthy Parent Carers' (HPC) programme. This study examined the views and experiences of participants in the HPC feasibility trial to inform programme refinement. INTERVENTION, SETTING AND PARTICIPANTS: HPC is a peer-led group-based intervention (supported by online materials) for primary carers of disabled children, encouraging behaviours linked with health and well-being. It was delivered by two lead and six assistant peer facilitators in six community sites (one lead and one assistant per group) in South West England over six or 12 sessions. Control participants had online materials only. The trial involved 47 intervention and 45 control parent carers (97% female and 97% white) and eight facilitators (one male). DESIGN: A preplanned mixed methods process evaluation using questionnaires and checklists (during and after the intervention), qualitative interviews with participants after intervention (n=18) and a focus group with facilitators after trial. RESULTS: HPC was highly acceptable to participants and facilitators and experiences were very positive. Participants reported that the programme increased awareness of what parent carers could and could not change and their self-efficacy to engage in health-promoting behaviours. The intended mechanisms of action (social identification and peer support) matched participants' expectations and experiences. Control participants found the online-only programme flexible but isolating, as there were no opportunities to share ideas and problem solve with peers, the key function of the programme. Areas for improvement were identified for programme content, facilitator training and delivery. CONCLUSION: HPC was acceptable, well received and offers considerable potential to improve the health of parent carers. Under the pandemic, the challenge going forward is how best to maintain reach and fidelity to function while delivering a more virtual programme. TRIAL REGISTRATION NUMBER: ISRCTN151144652.

Qualitative Evaluation of Web-Based Digital Intervention to Prevent and Reduce Excessive Alcohol Use and Harm Among Young People Aged 14-15 Years: A "Think-Aloud" Study.

BACKGROUND: In the United Kingdom, despite some downward trends in alcohol use among young people, over one-fifth of young people reported excessive alcohol use in the past month, which is associated with short- and long-term harm to health. Digital interventions to reduce alcohol use, such as websites, among young people present an appealing and cost-effective mode of intervention that can be integrated into the education system. However, relatively few school-based digital alcohol-focused interventions have been developed and evaluated for young people in the United Kingdom. OBJECTIVE: This study aims to develop a novel web-based intervention, Rethink Alcohol, to prevent and reduce excessive alcohol use and related harm among young people aged between 14 and 15 years, and explore the views of young people, teachers, and youth workers in relation to the content, design, and usability of the intervention. METHODS: Intervention development followed the person-based approach, using theories of social norms and social influence. Qualitative "Think-Aloud" interviews, either one-to-one or paired, were conducted while participants perused and worked through the web-based intervention, talking aloud. Participants included 20 young people (12 female, 8 male), 5 youth workers (4 female, 1 male), 3 teachers (2 male, 1 female), and 1 (male) clinical professional, recruited via youth groups and professional networks. Interviews were audio recorded, transcribed verbatim, and analyzed thematically. RESULTS: The prototype web-based intervention included normative feedback, information, a quiz, interactive activities, and scenarios. On a rating scale of impressions from poor (1) to excellent (5), participants gave an average score of 3.6/5. A total of 5 themes were identified: content, credibility of the website, making the website easy to understand, design and navigation, and suitability for the audience. These themes reflected views that the content was interesting, credible, informative, and embodied a neutral and nonjudgmental tone, but stronger messaging was needed regarding social pressures and short-term risks regarding safety and risk behavior alongside clarity around pathways of risk; credibility and trustworthiness of information were critical features, determined in part, by the professionalism of design and referencing of sources of information provided; and messages should be succinct and come to life through design and interactive features. CONCLUSIONS: Together, the data illustrated the importance and challenge of communicating nuanced alcohol-focused public health messages to young people in concise, clear, nonjudgmental, and appealing ways. Young people report interest in clear, credible, neutral, and interactive messages regarding social pressures and short-term risks of alcohol use via a web-based intervention. There is scope for optimization and feasibility testing of the Rethink Alcohol intervention.

A Randomized, Crossover Study of the Acute Cognitive and Cerebral Blood Flow Effects of Phenolic, Nitrate and Botanical Beverages in Young, Healthy Humans.

BACKGROUND: In whole foods, polyphenols exist alongside a wide array of other potentially bioactive phytochemicals. Yet, investigations of the effects of combinations of polyphenols with other phytochemicals are limited. OBJECTIVE: The current study investigated the effects of combining extracts of beetroot, ginseng and sage with phenolic-rich apple, blueberry and coffee berry extracts. DESIGN: This randomized, double-blind, placebo-controlled crossover design investigated three active beverages in 32 healthy adults aged 18-49 years. Each investigational beverage comprised extracts of beetroot, ginseng and sage. Each also contained a phenolic-rich extract derived from apple (containing 234 mg flavanols), blueberry (300 mg anthocyanins) or coffee berry (440 mg chlorogenic acid). Cognition, mood and CBF parameters were assessed at baseline and then again at 60, 180 and 360 min post-drink. RESULTS: Robust effects on mood and CBF were seen for the apple and coffee berry beverages, with increased subjective energetic arousal and hemodynamic responses being observed. Fewer effects were seen with the blueberry extract beverage. CONCLUSIONS: Either the combination of beetroot, ginseng and sage was enhanced by the synergistic addition of the apple and coffee berry extract (and to a lesser extent the blueberry extract) or the former two phenolic-rich extracts were capable of evincing the robust mood and CBF effects alone.

Experiences of delayed maturation in female vocational ballet students: An interpretative phenomenological analysis.

INTRODUCTION: There is a well-established bias toward late maturing females in the context of ballet, with up to 70% of professionals delayed in maturation. The timing of maturation has implications for physical and psychological outcomes which are likely to be amplified in dance. The aim of this research was to explore the role of maturity timing in adolescent dance students' experiences of vocational ballet training. METHODS: Semi-structured interviews were carried out with 28 adolescent female dancers of differing maturity timing across three vocational ballet schools in the UK. Interpretative phenomenological analysis was employed in the analysis of data. This study comprises findings from the nine late maturing dancers within the sample. RESULTS: Late maturing dancers perceived a number of aesthetic and functional advantages. The aesthetic advantages noted by the dancers are congruent with the well-established bias toward a later maturing physique for ballet; being 'small' and not having 'bits' is advantageous for these dancers in terms of maintaining a more pre-pubescent look and thereby conforming more easily to the expectations of the ballet world. However, dancers in this study perceived some significant drawbacks. Despite aesthetic advantages, later maturing dancers were disadvantaged by the current training system which sees them undertaking the most crucial training period during their most rapid period of growth. CONCLUSIONS: Greater consideration of maturation is needed within training systems and further research is warranted to understand these experiences in more depth and their implications for the physical and psychological wellbeing of young people in dance.

Coordination of GPR40 and Ketogenesis Signaling by Medium Chain Fatty Acids Regulates Beta Cell Function.

Diabetes prevalence increases with age, and ß-cell dysfunction contributes to the incidence of the disease. Dietary lipids have been recognized as contributory factors in the development and progression of the disease. Unlike long chain triglycerides, medium chain triglycerides (MCT) increase fat burning in animal and human subjects as well as serum C-peptide in type 2 diabetes patients. We evaluated the beneficial effects of MCT on ß-cells in vivo and in vitro. MCT improved glycemia in aged rats via ß-cell function assessed by measuring insulin secretion and content. In ß-cells, medium chain fatty acid (MCFA)-C10 activated fatty acid receptor 1 FFAR1/GPR40, while MCFA-C8 induced mitochondrial ketogenesis and the C8:C10 mixture improved ß cell function. We showed that GPR40 signaling positively impacts ketone body production in ß-cells, and chronic treatment with ß-hydroxybutyrate (BHB) improves ß-cell function. We also showed that BHB and MCFA help ß-cells recover from lipotoxic stress by improving mitochondrial function and increasing the expression of genes involved in ß-cell function and insulin biogenesis, such as Glut2, MafA, and NeuroD1 in primary human islets. MCFA offers a therapeutic advantage in the preservation of ß-cell function as part of a preventative strategy against diabetes in at risk populations.

Premier League academy soccer players' experiences of competing in a tournament bio-banded for biological maturation.

Individual differences in the growth and maturation have been shown to impact player performance and development in youth soccer. This study investigated Premier League academy players' experiences of participating in a tournament bio-banded for biological maturation. Players (N = 66) from four professional soccer clubs aged 11 and 14 years and between 85-90% of adult stature participated in a tournament. Players competed in three 11 vs 11 games on a full size pitch with 25-min halves. Sixteen players participated in four 15-min focus groups and were asked to describe their experiences of participating in the bio-banded tournament in comparison to age group competition. All players described their experience as positive and recommended the Premier League integrate bio-banding into the existing games programme. In comparison to age-group competitions, early maturing players described the bio-banded games more physically challenging, and found that they had to adapt their style of play placing a greater emphasis on technique and tactics. Late maturing players considered the games to be less physically challenging, yet appreciated the having more opportunity to use, develop and demonstrate their technical, physical, and psychological competencies. Bio-banding strategies appear to contribute positively towards the holistic development of young soccer players.

The role of puberty in the making and breaking of young ballet dancers: Perspectives of dance teachers.

Physical changes associated with puberty may conflict with functional and aesthetic ideals for a career in ballet. The dance teacher is in a position to guide young dancers through the pubertal transition, although dancers rather than teachers are often the focus of research. This study explores the social stimulus value of the female body in ballet as perceived by the dance teacher and how value may change during puberty. Ten UK dance teachers were interviewed; interpretative phenomenological analysis was used. Four main themes perceived by dance teachers emerged as central to the social stimulus value of the body among adolescent dancers: the ideal body; teacher approaches to managing puberty in the dance environment; puberty as a 'make or break' stage in ballet; and teacher awareness of pubertal onset and the implications of timing. Dance teachers can play an important role in moderating external and individual expectations during the pubertal transition.

Making sense of it: a brief programme to improve reading comprehension in adolescents with language impairments in main stream school.

BACKGROUND: Children with language impairment show academic outcomes that are consistently poorer than those of their typically developing peers. A contributor to this is difficulty with reading comprehension. Although these difficulties are reported to continue well into adolescence, this population is generally underserved with regard to therapy. The efficacy of interventions for reading comprehension is well established in the research literature, but whether the same effects are achievable within a reasonable time reflecting available resources in real-life circumstances is less clear. AIMS: Efficacy trials may significantly overestimate how strong an effect will be when the treatment is used under more natural conditions and within local constraints. The aim was to discover whether a short classroom intervention would be effective in improving reading comprehension in adolescents with the heterogeneous profiles of general or specific learning disabilities, additional diagnoses and behavioural and socio-emotional problems found in mainstream schools today. METHOD & PROCEDURES: Twenty-eight adolescents with heterogeneous language and reading profiles were recruited from a mainstream school. The intervention programme comprised eight sessions of instruction in multiple reading comprehension strategies, held over 4 weeks. Experiment 1 had 10 participants. Experiment 2 had 18 participants who underwent the same programme, plus the addition of a session dedicated to decoding skills. Efficacy was evaluated within a pre- and post-study design, with baseline and post-therapy measures taken using the York Assessment of Reading for Comprehension (YARC). OUTCOMES & RESULTS: Both experiments showed a significant group difference pre/post-intervention, with similar large effect sizes. Experiment 2 also showed a significant group difference in decoding ability pre and post the single intervention session. CONCLUSIONS & IMPLICATIONS: This short intervention programme proved effective in a population with heterogeneous profiles, and fitted well with delivery in a mainstream school setting. It showed significant gains can be attained for this client group with relatively few resources.

Could polyunsaturated fatty acids deficiency explain some dysfunctions found in ADHD? Hypotheses from animal research.

OBJECTIVES: The objective is to evaluate possible mechanisms explaining the link between polyunsaturated fatty acid (PUFA) deficiencies and ADHD, based on findings from animal research. METHOD: The authors consulted peer-reviewed publications from the last 10 years (Medline and resulting reference lists). RESULTS: PUFA deficiency in rodents results in behavioral changes (increased motor activity and decreased learning abilities) and dysregulations of monoamine neurotransmission. Behavioral improvement following a PUFA recovery diet is observed, but recovery of brain monoamine dysregulation is not fully demonstrated. Anti-inflammatory processes could damage neural membranes, but the direct link with ADHD model is not documented. Synaptic growth and neurogenesis impairment could account for working memory dysregulations, but research is at its early start. CONCLUSION: Induced PUFA deficiencies in animals show several noteworthy similarities with brain dysregulations seen in ADHD human children. However, the mechanisms of partial recovery after PUFA supplementation are not fully understood, and rigorous clinical trials have yet to show PUFA supplementation is an effective complementary treatment for ADHD.

Hepatitis C virus targets the T cell secretory machinery as a mechanism of immune evasion.

UNLABELLED: T cell activation and the resultant production of interleukin (IL-2) is a central response of the adaptive immune system to pathogens, such as hepatitis C virus (HCV). HCV uses several mechanisms to evade both the innate and adaptive arms of the immune response. Here we demonstrate that liver biopsy specimens from individuals infected with HCV had significantly lower levels of IL-2 compared with those with other inflammatory liver diseases. Cell culture-grown HCV particles inhibited the production of IL-2 by normal peripheral blood mononuclear cells, as did serum from HCV-infected patients. This process was mediated by the interaction of HCV envelope protein E2 with tetraspanin CD81 coreceptor. HCV E2 attenuated IL-2 production at the level of secretion and not transcription by targeting the translocation of protein kinase C beta (PKCß), which is essential for IL-2 secretion, to lipid raft microdomains. The lipid raft disruptor methyl-ß-cyclodextrin reversed HCV E2-mediated inhibition of IL-2 secretion, but not in the presence of a PKCß-selective inhibitor. HCV E2 further inhibited the secretion of other cytokines, including interferon-γ. CONCLUSION: These data suggest that HCV E2-mediated disruption of the association of PKCß with the cellular secretory machinery represents a novel mechanism for HCV to evade the human immune response and to establish persistent infection.

The impact of polyunsaturated fatty acids in reducing child attention deficit and hyperactivity disorders.

OBJECTIVES: To review the impact of polyunsaturated fatty acids (PUFA) in reducing ADHD symptoms in children. METHODS: Peer-reviewed experimental literature published from 1980 to Mai 2009 is consulted (Psychinfo, Medline, and resulting reference lists). RESULTS: Placebo-controlled studies with ADHD or hyperactive children show no effects on behaviors or cognition when only n-6 (omega-6) PUFA, only docosahexaenoic acid (DHA), or n-6 and n-3 (omega-3) short-chain PUFA are supplemented. Yet three out of four studies suggest that a combination of long-chain n-3 and n-6 fatty acids (DHA, eicosapentaenoic acid [EPA], and gamma-linolenic acid [GLA]) supplemented daily for 3 to 4 months could lead to a reduction in ADHD symptomatology. Results on cognitive outcomes are inconsistent. CONCLUSIONS: Evidence is too limited to reach definitive conclusions but suggests that research on the impact of long-chain PUFA (n-3 and n-6) should continue with special focus on individual differences (genetic and fatty acid markers), mechanisms (brain imaging), and new enhanced methods of systematic observations of behaviors.

Probing cell-type-specific intracellular nanoscale barriers using size-tuned quantum dots.

The compartmentalization of size-tuned luminescent semiconductor nanocrystal quantum dots (QDs) in four distinctive cell lines, which would be representative of the most likely environmental exposure routes to nanoparticles in humans, is studied. The cells are fixed and permeabilized prior to the addition of the QDs, thus eliminating any cell-membrane-associated effects due to active QD uptake mechanisms or to specificity of signaling routes in different cell types, but leaving intact the putative physical subcellular barriers. All quantitative assays are performed using a high content analysis (HCA) platform, thereby obtaining robust data on large cell populations. While smaller QDs 2.1 nm in diameter enter the nuclei and localize to the nucleoli in all cell types, the rate and dynamics of their passage vary depending on the cell origin. As the QD size is increased to 4.4 nm, penetration into the cell is reduced but each cell line displays its own cutoff size thresholds reflecting cell-type-determined cytoplasmic and nuclear pore penetration specificity. These results give rise to important considerations regarding the differential compartmentalization and susceptibility of organs, tissues, and cells to nanoparticles, and may be of prime importance for biomedical imaging and drug-delivery research employing nanoparticle-based probes and systems.

Nonfunctionalized nanocrystals can exploit a cell's active transport machinery delivering them to specific nuclear and cytoplasmic compartments.

We use high content cell analysis, live cell fluorescent imaging, and transmission electron microscopy approaches combined with inhibitors of cellular transport and nuclear import to conduct a systematic study of the mechanism of interaction of nonfunctionalized quantum dots (QDs) with live human blood monocyte-derived primary macrophages and cell lines of phagocytic, epithelial, and endothelial nature. Live human macrophages are shown to be able to rapidly uptake and accumulate QDs in distinct cellular compartment specifically to QDs size and charge. We show that the smallest QDs specifically target histones in cell nuclei and nucleoli by a multistep process involving endocytosis, active cytoplasmic transport, and entering the nucleus via nuclear pore complexes. Treatment of the cells with an anti-microtubule agent nocodazole precludes QDs cytoplasmic transport whereas a nuclear import inhibitor thapsigargin blocks QD import into the nucleus. These results demonstrate that the nonfunctionalized QDs exploit the cell's active transport machineries for delivery to specific intranuclear destinations.