National Institute for Health and Care Excellence (NICE) guidance on monitoring and management of Barrett's oesophagus and stage I oesophageal adenocarcinoma.

Barrett's oesophagus is the only known precursor to oesophageal adenocarcinoma, a cancer with very poor prognosis. The main risk factors for Barrett's oesophagus are a history of gastro-oesophageal acid reflux symptoms and obesity. Men, smokers and those with a family history are also at increased risk. Progression from Barrett's oesophagus to cancer occurs via an intermediate stage, known as dysplasia. However, dysplasia and early cancer usually develop without any clinical signs, often in individuals whose symptoms are well controlled by acid suppressant medications; therefore, endoscopic surveillance is recommended to allow for early diagnosis and timely clinical intervention. Individuals with Barrett's oesophagus need to be fully informed about the implications of this diagnosis and the benefits and risks of monitoring strategies. Pharmacological treatments are recommended for control of symptoms, but not for chemoprevention. Dysplasia and stage 1 oesophageal adenocarcinoma have excellent prognoses, since they can be cured with endoscopic or surgical therapies. Endoscopic resection is the most accurate staging technique for early Barrett's-related oesophageal adenocarcinoma. Endoscopic ablation is effective and indicated to eradicate Barrett's oesophagus in patients with dysplasia. Future research should focus on improved accuracy for dysplasia detection via new technologies and providing more robust evidence to support pathways for follow-up and treatment.

Effects of carotenoids on mitochondrial dysfunction.

Oxidative stress, an imbalance between pro-oxidant and antioxidant status, favouring the pro-oxidant state is a result of increased production of reactive oxygen species (ROS) or inadequate antioxidant protection. ROS are produced through several mechanisms in cells including during mitochondrial oxidative phosphorylation. Increased mitochondrial-derived ROS are associated with mitochondrial dysfunction, an early event in age-related diseases such as Alzheimer's diseases (ADs) and in metabolic disorders including diabetes. AD post-mortem investigations of affected brain regions have shown the accumulation of oxidative damage to macromolecules, and oxidative stress has been considered an important contributor to disease pathology. An increase in oxidative stress, which leads to increased levels of superoxide, hydrogen peroxide and other ROS in a potentially vicious cycle is both causative and a consequence of mitochondrial dysfunction. Mitochondrial dysfunction may be ameliorated by molecules with antioxidant capacities that accumulate in mitochondria such as carotenoids. However, the role of carotenoids in mitigating mitochondrial dysfunction is not fully understood. A better understanding of the role of antioxidants in mitochondrial function is a promising lead towards the development of novel and effective treatment strategies for age-related diseases. This review evaluates and summarises some of the latest developments and insights into the effects of carotenoids on mitochondrial dysfunction with a focus on the antioxidant properties of carotenoids. The mitochondria-protective role of carotenoids may be key in therapeutic strategies and targeting the mitochondria ROS is emerging in drug development for age-related diseases.

CHOROIDAL VASCULARITY IN CHRONIC CENTRAL SEROUS CHORIORETINOPATHY AND ITS ASSOCIATION WITH RISK SINGLE-NUCLEOTIDE POLYMORPHISMS.

PURPOSE: To analyze the choroidal parameters of patients with chronic central serous chorioretinopathy (cCSC) and the association with central serous chorioretinopathy susceptibility genes. METHODS: The choroidal vascular index (CVI) was obtained by binarizing spectral domain optical coherence tomography enhanced depth images of patients with cCSC and healthy age-matched controls. Patients with cCSC were genotyped for three central serous chorioretinopathy susceptibility single-nucleotide polymorphisms: rs4844392 ( mir-29b-2/CD46 ), rs1329428 ( CFH ), and rs2379120 (upstream GATA5 ). RESULTS: One hundred three eyes with cCSC and 53 control eyes were included. There was a significant increase in the subfoveal choroidal area in both the affected (2.4 ± 0.6 mm 2 ) and fellow (2.2 ± 0.6 mm 2 ) eyes of patients with cCSC compared with controls (1.8 ± 0.5 mm 2 , P < 0.0001 and P < 0.0001). The CVI was reduced in patients with cCSC 63.5% ± 3.1% compared with controls 65.4% ± 2.3% ( P < 0.001) and also in the affected compared with the fellow eyes 64.6% ± 2.9% ( P < 0.01). There was a significant association between CVI in the cCSC group and presence of the risk single-nucleotide polymorphisms rs2379120 at GATA5 ( P < 0.01). CONCLUSION: The relative reduction of CVI in patients with cCSC may suggest a persistence of vessel hyperpermeability over dilation in chronic disease. GATA5 is associated with CVI in patients with cCSC and therefore may have a role in choroidal vascularity.

Green endoscopy: British Society of Gastroenterology (BSG), Joint Accreditation Group (JAG) and Centre for Sustainable Health (CSH) joint consensus on practical measures for environmental sustainability in endoscopy.

GI endoscopy is highly resource-intensive with a significant contribution to greenhouse gas (GHG) emissions and waste generation. Sustainable endoscopy in the context of climate change is now the focus of mainstream discussions between endoscopy providers, units and professional societies. In addition to broader global challenges, there are some specific measures relevant to endoscopy units and their practices, which could significantly reduce environmental impact. Awareness of these issues and guidance on practical interventions to mitigate the carbon footprint of GI endoscopy are lacking. In this consensus, we discuss practical measures to reduce the impact of endoscopy on the environment applicable to endoscopy units and practitioners. Adoption of these measures will facilitate and promote new practices and the evolution of a more sustainable specialty.

Pre-conditioning of gingival epithelial cells with sub-apoptotic concentrations of curcumin prevents pro-inflammatory cytokine release.

BACKGROUND AND OBJECTIVE: Plaque-induced gingival inflammation (gingivitis) is ubiquitous in humans. The epithelial barrier reacts to the presence of oral bacteria and induces inflammatory cascades. The objective of this study was to investigate the mechanism by which the small molecule micronutrient curcumin could decrease inflammatory response in vitro to oral bacterium heat-killed Fusobacterium nucleatum as curcumin could be a useful compound for combatting gingivitis already consumed by humans. METHODS: H400 oral epithelial cell line was pre-conditioned with curcumin and the production of cytokines was measured by enzyme-linked immunosorbent assay (ELISA) and translocation of transcription factors was used to monitor inflammatory responses. Haem oxygenase (HO-1) expression and molecules that HO-1 releases were evaluated for their potential to reduce the quantity of cytokine production. Immunofluorescence microscopy and Western blotting were used to evaluate changes in transcription factor and enzyme location. RESULTS: Pre-conditioning of H400 cells with a sub-apoptotic concentration of curcumin (20 µM) attenuated secretion of Granulocyte-Macrophage - Colony-Stimulating Factor (GM-CSF) and reduced NFkB nuclear translocation. This pre-conditioning caused an increase in nuclear Nrf2; an initial drop (at 8 h) followed by an adaptive increase (at 24 h) in glutathione; and an increase in haem oxygenase (HO-1) expression. Inhibition of HO-1 by SnPPIX prevented the curcumin-induced attenuation of GM-CSF production. HO-1 catalyses the breakdown of haem to carbon monoxide, free iron and biliverdin: the HO-1/CO anti-inflammatory pathway. Elevations in carbon monoxide, achieved using carbon monoxide releasing molecule-2 (CORM2) treatment alone abrogated F. nucleatum-induced cytokine production. Biliverdin is converted to bilirubin by biliverdin reductase (BVR). This pleiotropic protein was found to increase in cell membrane expression upon curcumin treatment. CONCLUSION: Curcumin decreased inflammatory cytokine production induced by Fusobacterium nucleatum in H400 oral epithelial cells. The mechanism of action appears to be driven by the increase of haem oxygenase and the production of carbon monoxide.

Trajectories of Screen Time across Adolescence and Their Associations with Adulthood Mental Health and Behavioral Outcomes.

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.

Metacognitive training for negative symptoms: Support for the cognitive model.

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.

Developmental associations between bullying victimization and suicidal ideation and direct self-injurious behavior in adolescence and emerging adulthood.

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 (ß = .10) and age 17 suicidal ideation on age 20 general bullying victimization (ß = .14). CONCLUSIONS: General bullying victimization and suicidal ideation may have detrimental effects on each other over development but at different stages.

Impact of the COVID-19 pandemic on individuals with nystagmus and an exploration of public assumptions about the condition: an electronic questionnaire study.

PURPOSE: Nystagmus is a disorder characterized by uncontrolled, rhythmic oscillations of the eyes. It often causes reduced visual function beyond reduced visual acuity alone. There is a paucity of literature regarding the public understanding of nystagmus, and there are no published data on the impact of the COVID-19 pandemic on people living with the condition. This study explores the self-reported impact of the COVID-19 pandemic on those with nystagmus, and examines both public understanding of how nystagmus affects people who have it and the perceptions of public understanding by those with the condition and their carers. METHODS: A qualitative questionnaire was designed following a stakeholder engagement process. This questionnaire was advertised via social media platforms and charity websites to achieve widespread recruitment. Data were collected between November and December 2020. Participants were divided into two groups based on their response to the question: "Do you, or anyone you know well, have nystagmus?". Questions were posed to participants in a purpose-built, branching survey. The resulting data were analyzed using descriptive and inferential statistical methods. RESULTS: One thousand six hundred forty-five respondents were recruited, of which 849 (51.6%) answered "Yes" to the initial filtering question. Analysis showed that, broadly, public understanding of nystagmus differs from the perception of it by those with nystagmus and their carers, that the COVID-19 pandemic has had a significant impact on those with nystagmus, and that respondents who have met someone with nystagmus, even briefly, tend to have a greater understanding of the impact of the condition. CONCLUSION: This study highlights the lack of public awareness regarding nystagmus and suggests opportunities to increase the awareness of nystagmus without the need for extensive knowledge of the condition. The COVID-19 pandemic has posed additional difficulties for those living with nystagmus, which is likely to be comparable among those with similar ocular disorders.

Developmental Relations Between Bullying Victimization and Suicidal Ideation in Middle Adolescence and Emerging Adulthood: Do Internalizing Problems and Substance Use Mediate Their Links?

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.

Metacognitive training modified for negative symptoms: A feasibility study.

OBJECTIVE: Although patients often prioritize the treatment of negative symptoms, few psychological interventions targeting negative symptoms exist. This study attempts to fill this gap by piloting a modified metacognitive training programme, specifically targeted at negative symptoms (MCT-N), with a group of patients with prominent negative symptoms. METHOD: We adopted a mixed methods case series design, providing detailed quantitative data on changes over time, to focus on potential mechanisms underlying the intervention, in combination with qualitative interviews. RESULTS: The intervention showed good feasibility as demonstrated by the attendance rate, the positive feedback from participants and the multidisciplinary team, and the improvements on negative symptoms observed following the intervention. Multilevel modelling showed that depression, internalized stigma and reflective functioning explained the variance in negative symptoms. DISCUSSION: The pilot study indicated that the intervention has high feasibility and that improvements in negative symptoms can be partially explained by improvements on depression, stigma and reflective functioning.

Patient reported experiences and treatment outcomes of orthodontic patients treated within secondary care settings in the South West of England during the COVID-19 pandemic.

OBJECTIVE: To assess the impact of the temporary cessation of orthodontic services on patients undergoing treatment during the COVID-19 pandemic. DESIGN: Two-phase multicentre service evaluation. SETTING: Secondary care orthodontic departments in the South West of England. MATERIALS AND METHODS: Phase 1 - Patient-Reported Experience Measure questionnaire (PREM). The questionnaire was distributed to patients who had undergone orthodontic treatment during the COVID-19 pandemic once services had resumed. Phase 2 - assessment of treatment outcomes, specifically with the Peer Assessment Rating (PAR) Index. A total of 280 PAR scores were obtained from a cohort of patients treated before and during the pandemic. RESULTS: A total of 711 PREM questionnaires were completed. Participants generally felt relaxed when visiting secondary care settings, orthodontic departments and whilst wearing orthodontic appliances during the pandemic. Nearly 40% of participants were concerned that the pandemic would impact on their treatment, particularly treatment length. Treatment outcomes revealed that patients treated before and during the pandemic experienced percentage PAR score reductions of 83.9% and 80.6%, respectively. Patients receiving treatment during the pandemic experienced longer treatment durations of 126 days. CONCLUSION: During the pandemic, low levels of anxiety were reported with respect to receiving orthodontic treatment in secondary care settings. Irrespective of the pandemic, a high standard of orthodontic treatment was provided. However, patient concerns regarding treatment length were justified.

Do attachment-related differences in reflective functioning explain associations between expressed emotion and youth self-harm?

Youth self-harm is associated with poor health outcomes and attempted and completed suicide. Associations exist between self-harm and expressed emotion (EE), attachment insecurity, and reflective functioning (RF), but these associations are poorly understood. This study evaluates a mediation model in which perceived caregiver EE (pEE) exerts an indirect effect on youth self-harm through attachment insecurity and RF uncertainty. 461 participants aged 16-24 years completed an online survey. Statistical analyses revealed significant direct effects of pEE on attachment insecurity, and of RF uncertainty on self-harm; however, some direct effects were specific to pEE from female caregivers, and attachment insecurity in youth relationships with female caregivers. A significant direct effect of pEE on self-harm was found for pEE from male caregivers only. Significant indirect effects of pEE on self-harm through attachment anxiety and RF uncertainty were found only in relation to female caregivers. The findings encourage family-, attachment-, and mentalization-based approaches to preventing and treating youth self-harm, with a recommendation that caregivers are given adequate support, education, and skills-based training following youth disclosures of self-harm. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03614-w.

Oxidative stress links periodontal inflammation and renal function.

AIMS: Patients with chronic kidney disease (CKD) are also susceptible to periodontitis. The causal link between periodontitis and CKD may be mediated via systemic inflammation/oxidative stress. Using structural equation modelling (SEM), this cross-sectional study aimed to explore the causal relationship between periodontal inflammation (PI) and renal function. MATERIALS AND METHODS: Baseline data on 770 patients with stage 3-5 (pre-dialysis) CKD from an ongoing cohort study were used. Detailed, bioclinical data on PI and renal function, as well as potential confounders and mediators of the relationship between the two, were collected. SEMs of increasing complexity were created to test the causal assumption that PI affects renal function and vice versa. RESULTS: Structural equation modelling confirmed the assumption that PI and renal function are causally linked, mediated by systemic oxidative stress. The magnitude of this effect was such that a 10% increase in PI resulted in a 3.0% decrease in renal function and a 10% decrease in renal function resulted in a 25% increase in PI. CONCLUSIONS: Periodontal inflammation represents an occult source of oxidative stress in patients with CKD. Further clinical studies are needed to confirm whether periodontal therapy, as a non-pharmacological approach to reducing systemic inflammatory/oxidative stress burden, can improve outcomes in CKD.

An Intraocular Pressure Polygenic Risk Score Stratifies Multiple Primary Open-Angle Glaucoma Parameters Including Treatment Intensity.

PURPOSE: To examine the combined effects of common genetic variants associated with intraocular pressure (IOP) on primary open-angle glaucoma (POAG) phenotype using a polygenic risk score (PRS) stratification. DESIGN: Cross-sectional study. PARTICIPANTS: For the primary analysis, we examined the glaucoma phenotype of 2154 POAG patients enrolled in the Australian and New Zealand Registry of Advanced Glaucoma, including patients recruited from the United Kingdom. For replication, we examined an independent cohort of 624 early POAG patients. METHODS: Using IOP genome-wide association study summary statistics, we developed a PRS derived solely from IOP-associated variants and stratified POAG patients into 3 risk tiers. The lowest and highest quintiles of the score were set as the low- and high-risk groups, respectively, and the other quintiles were set as the intermediate risk group. MAIN OUTCOME MEASURES: Clinical glaucoma phenotype including maximum recorded IOP, age at diagnosis, number of family members affected by glaucoma, cup-to-disc ratio, visual field mean deviation, and treatment intensity. RESULTS: A dose-response relationship was found between the IOP PRS and the maximum recorded IOP, with the high genetic risk group having a higher maximum IOP by 1.7 mmHg (standard deviation [SD], 0.62 mmHg) than the low genetic risk group (P = 0.006). Compared with the low genetic risk group, the high genetic risk group had a younger age of diagnosis by 3.7 years (SD, 1.0 years; P < 0.001), more family members affected by 0.46 members (SD, 0.11 members; P < 0.001), and higher rates of incisional surgery (odds ratio, 1.5; 95% confidence interval, 1.1-2.0; P = 0.007). No statistically significant difference was found in mean deviation. We further replicated the maximum IOP, number of family members affected by glaucoma, and treatment intensity (number of medications) results in the early POAG cohort (P ≤ 0.01). CONCLUSIONS: The IOP PRS was correlated positively with maximum IOP, disease severity, need for surgery, and number of affected family members. Genes acting via IOP-mediated pathways, when considered in aggregate, have clinically important and reproducible implications for glaucoma patients and their close family members.

Low protein diet and methyl-donor supplements modify testicular physiology in mice.

The link between male diet and sperm quality has received significant investigation. However, the impact diet and dietary supplements have on the testicular environment has been examined to a lesser extent. Here, we establish the impact of a sub-optimal low protein diet (LPD) on testicular morphology, apoptosis and serum fatty acid profiles. Furthermore, we define whether supplementing a LPD with specific methyl donors abrogates any detrimental effects of the LPD. Male C57BL6 mice were fed either a control normal protein diet (NPD; 18% protein; n = 8), an isocaloric LPD (LPD; 9% protein; n = 8) or an LPD supplemented with methyl donors (MD-LPD; choline chloride, betaine, methionine, folic acid, vitamin B12; n = 8) for a minimum of 7 weeks. Analysis of male serum fatty acid profiles by gas chromatography revealed elevated levels of saturated fatty acids and lower levels of mono- and polyunsaturated fatty acids in MD-LPD males when compared to NPD and/or LPD males. Testes of LPD males displayed larger seminiferous tubule cross section area when compared to NPD and MD-LPD males, while MD-LPD tubules displayed a larger luminal area. Furthermore, TUNNEL staining revealed LPD males possessed a reduced number of tubules positive for apoptosis, while gene expression analysis showed MD-LPD testes displayed decreased expression of the pro-apoptotic genes Bax, Csap1 and Fas when compared to NPD males. Finally, testes from MD-LPD males displayed a reduced telomere length but increased telomerase activity. These data reveal the significance of sub-optimal nutrition for paternal metabolic and reproductive physiology.

Dietary protein insufficiency: an important consideration in fatty liver disease?

Dietary protein insufficiency has been linked to excessive TAG storage and non-alcoholic fatty liver disease (NAFLD) in developing countries. Hepatic TAG accumulation following a low-protein diet may be due to altered peroxisomal, mitochondrial and gut microbiota function. Hepatic peroxisomes and mitochondria normally mediate metabolism of nutrients to provide energy and substrates for lipogenesis. Peroxisome biogenesis and activities can be modulated by odd-chain fatty acids (OCFA) and SCFA that are derived from gut bacteria, for example, propionate and butyrate. Also produced during amino acid metabolism by peroxisomes and mitochondria, propionate and butyrate concentrations correlate inversely with risk of obesity, insulin resistance and NAFLD. In this horizon-scanning review, we have compiled available evidence on the effects of protein malnutrition on OCFA production, arising from loss in mitochondrial, peroxisomal and gut microbiota function, and its association with lipid accumulation in the liver. The methyl donor amino acid composition of dietary protein is an important contributor to liver function and lipid storage; the presence and abundance of dietary branched-chain amino acids can modulate the composition and metabolic activity of the gut microbiome and, on the other hand, can affect protective OCFA and SCFA production in the liver. In preclinical animal models fed with low-protein diets, specific amino acid supplementation can ameliorate fatty liver disease. The association between low dietary protein intake and fatty liver disease is underexplored and merits further investigation, particularly in vulnerable groups with dietary protein restriction in developing countries.

Efficacy of Mentalization-based group therapy for adolescents: the results of a pilot randomised controlled trial.

BACKGROUND: Mentalization Based Therapy (MBT) has yielded promising outcomes for reducing self-harm, although to date only one study has reported MBT's effectiveness for adolescents (Rossouw and Fonagy, J Am Acad Child Adolesc Psychiatry 51:1304-1313, 2012) wherein the treatment protocol consisted of an intensive programme of individual and family therapy. We sought to investigate an adaptation of the adult MBT introductory manual in a group format for adolescents. METHODS: The present study is a randomised controlled single blind feasibility trial that aims to (1) adapt the original explicit MBT introductory group manual for an adolescent population (MBT-Ai) and to (2) assess the feasibility of a trial of MBT-Ai through examination of consent rates, attendance, attrition and self-harm. Repeated measures ANOVAs were conducted to examine change over time in independent and dependent variables between groups, and multi level models (MLM) were conducted to examine key predictors in relation to change over time with self-report self-harm and emergency department presentation for harm as the primary outcome variables. RESULTS: Fifty-three young people consented to participate and were randomised to MBT-Ai + TAU or TAU alone. Five participants withdrew from the trial. Trial procedures seemed appropriate and safe, with acceptable group attendance. Self-reported self-harm and emergency department presentation for self-harm significantly decreased over time in both groups, though there were no between group differences. Social anxiety, emotion regulation, and borderline traits also significantly decreased over time in both groups. Mentalization emerged as a significant predictor of change over time in self reported self harm and hospital presentation for self-harm. CONCLUSIONS: It was feasible to carry out an RCT of MBT-Ai for adolescents already attending NHS CAMHS who have recently self-harmed. Our data gave signals that suggested a relatively brief group-based MBT-Ai intervention may be a promising intervention with potential for service implementation. Future research should consider the appropriate format, dosage and intensity of MBT for the adolescent population. TRIAL REGISTRATION: NCT02771691 ; Trial Registration Date: 25/04/2016.

UK guidelines on oesophageal dilatation in clinical practice.

These are updated guidelines which supersede the original version published in 2004. This work has been endorsed by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG) under the auspices of the oesophageal section of the BSG. The original guidelines have undergone extensive revision by the 16 members of the Guideline Development Group with representation from individuals across all relevant disciplines, including the Heartburn Cancer UK charity, a nursing representative and a patient representative. The methodological rigour and transparency of the guideline development processes were appraised using the revised Appraisal of Guidelines for Research and Evaluation (AGREE II) tool.Dilatation of the oesophagus is a relatively high-risk intervention, and is required by an increasing range of disease states. Moreover, there is scarcity of evidence in the literature to guide clinicians on how to safely perform this procedure. These guidelines deal specifically with the dilatation procedure using balloon or bougie devices as a primary treatment strategy for non-malignant narrowing of the oesophagus. The use of stents is outside the remit of this paper; however, for cases of dilatation failure, alternative techniques-including stents-will be listed. The guideline is divided into the following subheadings: (1) patient preparation; (2) the dilatation procedure; (3) aftercare and (4) disease-specific considerations. A systematic literature search was performed. The Grading of Recommendations Assessment, Develop-ment and Evaluation (GRADE) tool was used to evaluate the quality of evidence and decide on the strength of recommendations made.

Communicating with the dead: lipids, lipid mediators and extracellular vesicles.

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.