Early evaluation of a DBT-informed online intervention for people with eating disorders.

OBJECTIVES: Eating disorders (EDs) have a worldwide prevalence of 7.8%, with towering mortality rates and high healthcare costs. The current recommended treatment for EDs principally works by directly targeting ED thoughts and behaviours, but recovery rates are low. A multifaceted link between difficulties with emotions and EDs is now widely established, and newer third-wave therapies that aim to address these underlying emotion difficulties are promising. The current study piloted an online emotion self-help intervention which was co-developed with clinicians and people with lived experienced of EDs. The intervention aimed to specifically address difficulties with emotion identification and regulation, as well as unhelpful beliefs about emotions, which are believed to give rise to and maintain ED thoughts and behaviours. METHOD: We recruited 39 people with self-reported EDs to test this intervention over a one-week period. Our participants were asked to complete a series of questionnaires measuring emotion processes and psychopathology on Day 1 (T1) before being given access to the intervention. Participants were then asked to practice the newly acquired skills for seven days, before taking the same questionnaires on Day 9 (T2). We also asked participants to qualitatively report on their experience of the intervention. RESULTS: We found significant improvements in ED psychopathology (ED-15), depression (PHQ-9), and anxiety (GAD-7) pre- to post-intervention, with medium to large effect sizes. All our emotion variables namely alexithymia (TAS-20), difficulties regulating emotions (DERS-SF), and unhelpful beliefs about emotions (EBQ) also showed significant changes post-intervention with medium to large effect sizes. Most importantly, changes in emotion regulation processes were linked to improved eating psychopathology. The qualitative analysis corroborated this finding, highlighting how the intervention helped them form new beliefs about emotions, which helped them reduce ED behaviours. DISCUSSION: Significant improvements in emotion processing and regulations, as well as psychopathology, along with positive qualitative feedback, suggest that the intervention effectively met its aims of increasing awareness of the link between emotions and eating psychopathology, providing help to identify and regulate emotions, and normalising emotional experiences. While our results are promising, further research is required to assess its effectiveness longer term and in clinical settings.

About one person dies every hour as a direct result of an eating disorder (ED), in part because of poor treatment outcomes. Current recommended treatments have a limited focus around emotion difficulties, such as the ability to identify emotions and regulate them, which are linked to ED thoughts and behaviours. With the help of clinicians and people with lived experience of EDs, we developed an online intervention that works on these emotion difficulties. We recruited 39 people with EDs to test this intervention over a one-week period and evaluated our results using quantitative and qualitative analyses. Comparing scores before and after the intervention, we found that ED psychopathology, depression and anxiety were significantly lower post-intervention. Beliefs about emotions as well as the ability to identify, describe and regulate emotions were also significantly improved post-intervention. Qualitative analysis showed that our intervention helped people feel better equipped to deal with their feelings in a healthier way, which helped reduce ED behaviours. One person even described the intervention as "life-changing". While our results are promising, further research is required to assess our intervention in a clinical setting.

Sex-specific mechanisms for eating disorder risk in men and women with autistic traits: the role of alexithymia.

BACKGROUND: A poorly understood relationship exists between eating disorders (ED) and autism spectrum conditions (ASC: henceforth 'autism'). ED are more prevalent in autistic people and people with high autistic traits, and autistic features are prognostic of longer illness. Aiming to understand what increases the risk of ED in relation to autism and autistic traits, previous research has implicated alexithymia as a causal mechanism in this relationship. These studies could not, however, disentangle whether alexithymia explains the relationship between ED pathology and autistic traits directly or through its impact on anxious/depressive symptoms, which in turn result in higher ED symptomatology. Moreover, despite evidence for sex differences in the aetiology of ED, little research has examined the impact of sex on these relationships. METHODS: Focusing on the association between autistic traits and ED psychopathology, we examined independent mediating effects of alexithymia and anxious/depressive symptoms, as well as sequential mediation effects where alexithymia affects ED psychopathology via its impact on anxious/depressive symptoms. Participants were 198 men and 265 women with formally diagnosed and suspected ED, who completed an online survey of standardised scales. RESULTS: In men, higher autistic traits were associated with ED psychopathology sequentially via greater alexithymia and through that, greater depressive/anxious symptoms. In women, alexithymia mediated the relationship between autistic traits and ED psychopathology both directly and sequentially through its impact on anxious/depressive symptoms. Interestingly, depressive/anxious symptoms also mediated that relationship independently from alexithymia. CONCLUSIONS: While cross-sectional, these findings suggest that the relationship between autistic traits and ED symptomatology is mediated by other variables. In support of its proposed role in the aetiology of ED, alexithymia was directly associated with ED symptoms in women. It also affected ED symptoms indirectly, in all participants, via its effect on depressive/anxious symptoms. Interventions focusing on alexithymia may facilitate recovery not only via their effect on ED, but via their effect on other forms of state psychopathology which contribute to the maintenance and development of ED. Sex differences, however, reflect that alternative therapeutic targets for men and women may be beneficial.

Autistic individuals seem to be at higher risk of developing eating disorders (ED)­even just having autistic traits seems to elevate risk of ED, although we do not understand why. One possibility is that autism and autistic traits are closely related to alexithymia, a difficulty identifying and describing your emotions, and it may be this that increases risk of ED. To test this, we explored relationships between autistic traits and ED symptoms in men and women with ED, who completed an online survey. In men, we found that autistic traits were associated with ED symptoms because they were associated with alexithymia, and alexithymia was associated with ED symptoms because it was associated with anxious/depressive symptoms. The same was true in women, but anxious/depressive symptoms were also associated with ED symptoms in their own right. While these findings need to be investigated in more thorough longitudinal approaches, they suggest that pathways to ED differ slightly between men and women, autistic and non-autistic, and that therapeutic interventions should also differ. In both sexes, the fact that alexithymia was associated with ED symptoms and those of other mental illnesses that seemed to contribute to ED, suggests that it should be targeted in interventions.

What about males? Exploring sex differences in the relationship between emotion difficulties and eating disorders.

OBJECTIVE: While eating disorders (EDs) are more commonly diagnosed in females, there is growing awareness that men also experience EDs and may do so in a different way. Difficulties with emotion processing and emotion regulation are believed to be important in EDs, but as studies have involved predominantly female samples, it is unclear whether this is also true for males. METHODS: In a sample of 1604 participants (n = 631 males), we assessed emotion processing and emotion regulation in males with EDs (n = 109) and compared results to both females with EDs (n = 220) and males from the general population (n = 522). We also looked at whether emotion processing and emotion regulation difficulties predicted various aspects of eating psychopathology and whether this was moderated by sex. We assessed emotion processing with the Toronto Alexithymia Scale, emotion regulation with the Difficulties in Emotion Regulation Scale and the Emotion Regulation Questionnaire, and eating psychopathology with the Eating Disorder Examination Questionnaire. RESULTS: We found that males with ED, like their female counterparts, suffered from emotion processing and emotion regulation deficits. We did find some sex differences, in that males with EDs tended to report more difficulties with their emotions as well as a more externally oriented thinking style compared to females with EDs. Difficulties with emotion processing and emotion regulation were strongly predictive of various aspects of eating psychopathology in both sexes. Importantly, we found that sex moderated the relationship between cognitive reappraisal and eating restraint. As such, low use of reappraisal was found to be associated with higher levels of restraint in females but not in males. DISCUSSION: Difficulties with emotion processing and emotion regulation are associated with eating psychopathology in both males and females. Reappraisal was not found to be associated with reduced eating psychopathology in males, suggesting a cautious approach to interventions targeting this strategy. Research around explanatory mechanisms and interventions must adopt a broader viewpoint including those that are traditionally overlooked in EDs.

While eating disorders (EDs) are more common in females, males also suffer from these conditions and are generally neglected in research around EDs. Difficulty identifying and managing emotions is believed to be important in the development and maintenance of EDs, but as studies have been conducted mostly in females, it is unclear whether this is also true for males. We recruited 1604 participants (631 were males, and 329 were diagnosed with EDs comprising 109 males and 220 females) and compared how males and females processed and regulated their emotions. We found that males with EDs, like their female counterparts, suffered from difficulties identifying and regulating their emotions, though they showed a slightly different profile of difficulties. While difficulties with emotions were associated with ED behaviours in both sexes, difficulties using reappraisal, an emotion regulation strategy where one reinterprets an event from a different perspective, were associated with restraint in females but not in males. This suggests that while interventions to help with emotional functioning could be beneficial for both women and men with EDs, the different emotional profiles of men with EDs must be considered, as interventions targeting particular emotional processes (e.g. reappraisal) may be relevant for women but not men.

The relevance of the interpersonal theory of suicide for predicting past-year and lifetime suicidality in autistic adults.

BACKGROUND: While there are known risk factors for suicidality in autistic adults, these are often unconnected from theoretical frameworks that might explain why risk is elevated and guide clinical interventions. The present study investigated the relevance of constructs from the Interpersonal Theory of Suicide (ITS), including perceived burdensomeness, thwarted belongingness and acquired capability for suicide, and explored mechanisms through which certain risk factors (relationship status, age at diagnosis) might elevate suicide risk. METHODS: Autistic adults (n = 314) completed an online study including measures of depression, anxiety and constructs from the ITS. Linear and multinomial regression analysis disentangled contributions of ITS variables from effects of depression and anxiety for past-year suicide ideation, past-year and lifetime suicide attempts. Mediation analyses examined associations between risk factors and these suicide outcomes via mechanisms proposed by the ITS. RESULTS: Past-year suicide ideation was associated with burdensomeness, mental rehearsal of suicide plans (a facet of acquired capability), and depression. Greater feelings of burdensomeness, and reduced fear of death, marked out participants who had attempted suicide in comparison to those who had experienced suicide ideation in the past year. Relationship status was indirectly associated with past-year suicide ideation via the mediators of depression and burdensomeness, and was associated with past-year attempts via its effect on ideation. Age at diagnosis was unrelated to any variables. LIMITATIONS: Cross-sectional research is insensitive to causality and temporal dynamics, which is likely why interaction hypotheses from the ITS were unsupported. Normative measures may be invalid in autistic samples. There was no control group. The autistic sample was unrepresentative of the whole population, particularly autistic people with intellectual disabilities, ethnic/racial minorities, and gender minorities. CONCLUSIONS: Perceived burdensomeness and acquired capability appear potentially important to suicide in autistic people, and may mediate the effects of some risk factors. Future research should explore the temporal dynamics of suicide trajectories in longitudinal, prospective designs.

Levels of Self-representation and Their Sociocognitive Correlates in Late-Diagnosed Autistic Adults.

The cognitive representation of oneself is central to other sociocognitive processes, including relations with others. It is reflected in faster, more accurate processing of self-relevant information, a "self-prioritisation effect" (SPE) which is inconsistent across studies in autism. Across two tasks with autistic and non-autistic participants, we explored the SPE and its relationship to autistic traits, mentalizing ability and loneliness. A SPE was intact in both groups, but together the two tasks suggested a reduced tendency of late-diagnosed autistic participants to differentiate between familiar and unfamiliar others and greater ease disengaging from the self-concept. Correlations too revealed a complex picture, which we attempt to explore and disentangle with reference to the inconsistency across self-processing studies in autism, highlighting implications for future research.

Low-frequency rTMS to the parietal lobe increases eye-movement carryover and decreases hazard rating.

The persistence of attentional set from one task to a secondary unrelated task, revealed through carryover of eye movements, has been attributed to increased activation in the parietal lobe and decreased activation to the frontal lobe. To directly test this, we adopted a modified version of the Thompson and Crundall (2011) paradigm using low-frequency repetitive TMS to P3 and F3. In each trial, participants viewed letter-strings that were arranged horizontally, vertically, or randomly across the screen before viewing a road image and providing a hazardousness rating for it. The orientation of the letter search influenced eye movements to the road images and this carryover was greater following stimulation to F3 than to P3 (or sham). Furthermore, hazardous ratings were lower following P3 stimulation. These results confirm the involvement of attentional orienting and switching mechanisms in the carryover of eye movements. It is suggested that this "attentional inertia" effect will increase with greater orienting of attentional resources in an initial task and poor inhibition of previously-relevant settings between tasks.

The impact of the COVID-19 pandemic on individuals with eating disorders: the role of emotion regulation and exploration of online treatment experiences.

OBJECTIVE: The Covid-19 pandemic has wrought disruption to everyday life and services, and emerging evidence suggests that those with eating disorders (EDs) are likely to experience marked distress and exacerbation of their symptoms. However, little is known around the most relevant factors to symptom change; whether certain emotion regulation and coping strategies are linked to better outcomes; and how people with EDs are adjusting to psychological interventions moving online. METHOD: In a mixed-method design, we collected qualitative and quantitative data from 207 (76 males) self-selected UK residents with self-reported ED, who described and ranked impacts of the pandemic on their symptoms. Regression analysis examined whether emotion regulation strategies were associated with self-reported symptom change, ED symptomatology, and negative emotional states. Thematic analysis explored participants' experiences of the pandemic, particularly factors affecting their ED, coping strategies used, and experiences of psychological intervention. RESULTS: Most participants (83.1%) reported worsening of ED symptomatology, though factors affecting symptom change differed between specific EDs. Emotion regulation, such as having fewer strategies, poorer emotional clarity, and non-acceptance of emotions, explained nearly half of the variance in emotional distress during the pandemic. Qualitative findings indicated that difficult emotions (such as fear and uncertainty), changes to routine, and unhelpful social messages were triggering for participants during the pandemic. While some participants described employing positive coping strategies (such as limiting social media exposure), many reported using ED behaviours (among other maladaptive strategies, like alcohol use) to cope with the pandemic. Finally, loss of treatment support, feeling underserving of support and experiencing a 'detached connection' online were further exacerbating factors for these participants. DISCUSSION: While our sample was self-selected and may not represent all people with EDs, our results suggest that people with EDs have been strongly affected by the pandemic. Some aspects of online treatment were found to be beneficial but our findings suggest it also needs some improvement. Our paper discusses implications for online treatment such as taking into account personal circumstances and, in a time where people have limited control over the antecedents of negative emotion, the need to develop skills to manage emotions when they arise.

Alexithymia may explain the relationship between autistic traits and eating disorder psychopathology.

BACKGROUND: Autistic people are disproportionately vulnerable to anorexia nervosa and other eating disorders (ED), and within the general population, autistic traits correlate with ED psychopathology. A putative mechanism which may underpin this heightened risk is alexithymia, a difficulty identifying and describing emotional states which is observed in both autism and ED. In two experiments with independent non-clinical samples, we explored whether alexithymia might mediate the heightened risk of eating psychopathology in individuals high in autistic traits. METHODS: Our first experiment used the PROCESS macro for SPSS to examine relationships between alexithymia (measured by the Toronto Alexithymia Scale (TAS-20)), autistic traits (autism quotient (AQ)), and eating psychopathology (Eating Attitudes Test (EAT-26)) in 121 participants. Our second experiment (n = 300) replicated and furthered this analysis by examining moderating effects of sex and controlling for anxiety and depression as covariates. We also included an additional performance-based measure of alexithymia, the Levels of Emotional Awareness Scale (LEAS). RESULTS: Study 1 suggested that TAS-20 scores mediated the relationship between heightened autistic traits and eating psychopathology. Replication and further scrutiny of this finding, in study 2, revealed that this mediation effect was partial and specific to the female participants in this sample. The mediation effect appeared to be carried by the difficulty identifying feelings subscale of the TAS-20, even when depression and anxiety were controlled for. LEAS scores, however, were not significantly related to autistic traits or eating psychopathology. LIMITATIONS: Cross-sectional data prevents any conclusions around the direction and causality of relationships between alexithymia, autistic traits, and eating psychopathology (alongside depression and anxiety), necessitating longitudinal research. Our non-clinical sample was predominantly Caucasian undergraduate students, so it remains to be seen if these results would extrapolate to clinical and/or autistic samples. Divergence between the TAS-20 and LEAS raises crucial questions regarding the construct validity of these measures. CONCLUSIONS: Our findings with respect to autistic traits suggest that alexithymia could partially explain the prevalence of ED in autistic people and may as such be an important consideration in the pathogenesis and treatment of ED in autistic and non-autistic people alike. Further research with clinical samples is critical to explore these ideas. Differences between men and women, furthermore, emphasize the importance of looking for sex-specific as well as generic risk factors in autistic and non-autistic men and women.

Links between self-injury and suicidality in autism.

BACKGROUND: Autistic individuals without intellectual disability are at heightened risk of self-injury, and appear to engage in it for similar reasons as non-autistic people. A wide divergence of autistic perspectives on self-injury, including those who frame it as a helpful coping mechanism, motivate investigating the link between self-injury, suicide ideation, and attempts which has been reported in typically developing individuals. METHOD: One hundred three autistic participants completed the Non-Suicidal Self-Injury Assessment Tool (NSSI-AT), the Suicide Behaviors Questionnaire (SBQ-R), and the Interpersonal Social Evaluation List (ISEL-12) across two online studies. Logistic regression was conducted to predict self-harming status via responses to questions on suicidality, and to predict whether certain self-injurious behaviors, including cutting, were especially associated with suicide ideation and attempts. Non-parametric correlation analysis examined relationships between suicide ideation/attempts and other variables that might characterize self-harmers especially at risk of suicidality. These included perceived access to social support, purposes or reasons for self-injury, the number of different self-injurious behaviors engaged in, the duration and lifetime incidence of self-injury, and the individual's feelings about their self-injury. RESULTS: While self-injuring status was significantly predicted by responses to a question on suicide ideation and attempts, there was no relationship between suicide ideation/attempts and a participant's personal feelings about their self-injury. The method of cutting was also predicted by suicide ideation and attempts, though other methods common in autistic people were at borderline significance. Use of self-injury for the regulation of low-energy emotional states like depression, for self-punishment or deterrence from suicide, and for sensory stimulation, was associated with suicide ideation and attempts, as was the number of self-injurious behaviors engaged in. There was no significant relationship between suicide ideation/attempts and the duration and lifetime incidence of self-injury or social support. CONCLUSIONS: These preliminary data suggest that while individuals might frame their self-injury as a positive or neutral thing, there remains a concerning relationship between self-injury and suicidality which exists regardless of individual feelings on self-injury. This is consistent with the theoretical perspective that self-injury can be a "gateway" through which individuals acquire capability for lethal suicidal behaviors. The data highlight that particular methods (cutting) and reasons for self-injury may be of significant concern, but this information, which might be of extreme value for clinicians, requires further investigation and validation.

A 'choice', an 'addiction', a way 'out of the lost': exploring self-injury in autistic people without intellectual disability.

Background: Non-suicidal self-injury (NSSI) describes a phenomenon where individuals inflict deliberate pain and tissue damage to their bodies. Self-injurious behaviour is especially prevalent across the autism spectrum, but little is understood about the features and functions of self-injury for autistic individuals without intellectual disability, or about the risk factors that might be valuable for clinical usage in this group. Methods: One hundred and three autistic adults who responded to an online advertisement were classified as current, historic or non-self-harmers in accordance with responses to the Non-Suicidal Self-Injury Assessment Tool (NSSI-AT). Multinomial regression aimed to predict categorisation of participants in accordance with scores on tests of autistic traits, alexithymia, depression, anxiety, mentalising and sensory sensitivity. Linear regression examined relationships between these predictors and the range, frequency, lifetime occurrence and functional purposes of NSSI. Qualitative analysis explored the therapeutic interventions that participants had found helpful, and what they wished people understood about self-injury. Results: Current, historic and non-self-harming participants did not differ in age, age at diagnosis, male-to-female ratio, level of employment or education (the majority qualified to at least degree level). The most common function of NSSI was the regulation of low-energy affective states (depression, dissociation), followed by the regulation of high-energy states such as anger and anxiety. Alexithymia significantly predicted the categorisation of participants as current, historic or non-self-harmers, and predicted use of NSSI for regulating high-energy states and communicating distress to others. Depression, anxiety and sensory-sensitivity also differentiated participant groups, and sensory differences also predicted the range of bodily areas targeted, lifetime incidence and frequency of NSSI. Sensory differences, difficulty expressing and identifying emotions also emerged as problematic in the qualitative analysis, where participants expressed the need for compassion, patience, non-judgement and the need to recognise diversity between self-harmers, with some participants perceiving NSSI as a practical, non-problematic coping strategy. Conclusions: Alexithymia, depression, anxiety and sensory differences may place some autistic individuals at especial risk of self-injury. Investigating the involvement of these variables and their utility for identification and treatment is of high importance, and the voices of participants offer guidance to practitioners confronted with NSSI in their autistic clients.

Self-reported sex differences in high-functioning adults with autism: a meta-analysis.

Background: Sex differences in autistic symptomatology are believed to contribute to the mis- and missed diagnosis of many girls and women with an autism spectrum condition (ASC). Whilst recent years have seen the emergence of clinical and empirical reports delineating the profile of young autistic girls, recognition of sex differences in symptomatology in adulthood is far more limited. Methods: We chose here to focus on symptomatology as reported using a screening instrument, the Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R). In a meta-analysis, we pooled and analysed RAADS-R data from a number of experimental groups. Analysis of variance (ANOVA) searched for the presence of main effects of Sex and Diagnosis and for interactions between these factors in our sample of autistic and non-autistic adults. Results: In social relatedness and circumscribed interests, main effects of Diagnosis revealed that as expected, autistic adults reported significantly greater lifetime prevalence of symptoms in these domains; an effect of Sex, in circumscribed interests, also suggested that males generally reported more prevalent symptoms than females. An interaction of Sex and Diagnosis in language symptomatology revealed that a normative sex difference in language difficulties was attenuated in autism. An interaction of Sex and Diagnosis in the sensorimotor domain revealed the opposite picture: a lack of sex differences between typically developing men and women and a greater prevalence of sensorimotor symptoms in autistic women than autistic men. Conclusions: We discuss the literature on childhood sex differences in relation to those which emerged in our adult sample. Where childhood sex differences fail to persist in adulthood, several interpretations exist, and we discuss, for example, an inherent sampling bias that may mean that only autistic women most similar to the male presentation are diagnosed. The finding that sensorimotor symptomatology is more highly reported by autistic women is a finding requiring objective confirmation, given its potential importance in diagnosis.

Whole-brain functional hypoconnectivity as an endophenotype of autism in adolescents.

Endophenotypes are heritable and quantifiable markers that may assist in the identification of the complex genetic underpinnings of psychiatric conditions. Here we examined global hypoconnectivity as an endophenotype of autism spectrum conditions (ASCs). We studied well-matched groups of adolescent males with autism, genetically-related siblings of individuals with autism, and typically-developing control participants. We parcellated the brain into 258 regions and used complex-network analysis to detect a robust hypoconnectivity endophenotype in our participant group. We observed that whole-brain functional connectivity was highest in controls, intermediate in siblings, and lowest in ASC, in task and rest conditions. We identified additional, local endophenotype effects in specific networks including the visual processing and default mode networks. Our analyses are the first to show that whole-brain functional hypoconnectivity is an endophenotype of autism in adolescence, and may thus underlie the heritable similarities seen in adolescents with ASC and their relatives.

'Young' oral fibroblasts are geno/phenotypically distinct.

Wound healing within the oral mucosa results in minimal scar formation compared with wounds within the skin. We have recently demonstrated distinct differences in the aging profiles of cells (oral mucosal and patient-matched skin fibroblasts) isolated from these tissues. We hypothesized that the increased replicative potential of oral mucosal fibroblasts may confer upon them preferential wound-healing capacities. Passage-matched early cultures of oral mucosal fibroblasts and skin fibroblasts demonstrated distinct gene expression profiles, with several genes linked to wound healing/tissue repair. This was related to an increased ability of the 'replicatively younger' oral mucosal fibroblasts to repopulate a wound space and reorganize their surrounding extracellular matrix environment, key activities during the wound-healing process. We conclude that oral mucosal fibroblasts exhibit a preferential healing response in vivo, due to their 'replicatively younger' phenotype when compared with that of patient-matched skin fibroblasts.

Investigation of the potential of polymer therapeutics in corneal re-epithelialisation.

In this study, the first use of a bioresponsive polymer therapeutic agent in the promotion of corneal re-epithelialisation after injury in an ex vivo whole-eye organ culture model was described. A polymer-protein conjugate consisting of dextrin and recombinant human epidermal growth factor was synthesised and applied as a single dose to a 2 mm ex vivo corneal ulcer, in culture. Enhanced wound healing was observed in response to dextrin-recombinant human epidermal growth factor, when exposed to α-amylase, compared with controls. This highlights the potential for polymer therapeutics to provide a platform for bioresponsive drug/protein delivery in the field of ophthalmology.

Increased oral fibroblast lifespan is telomerase-independent.

Oral mucosal wound-healing is characterized by rapid re-epithelialization and remodeling, with minimal scar formation. This may be attributed to the distinct phenotypic characteristics of the resident fibroblasts. To test this hypothesis, we investigated patient-matched oral mucosal and skin fibroblasts. Compared with skin fibroblasts, oral mucosal fibroblasts had longer proliferative lifespans, underwent more population doublings, and experienced senescence later, which was directly related to longer telomere lengths within oral mucosal fibroblasts. The presence of these longer telomeres was independent of telomerase expression, since both oral oral mucosal fibroblasts and skin fibroblasts were negative for active telomerase, as assessed according to the Telomeric Repeat Amplification Protocol. This study has demonstrated that, compared with skin fibroblasts, oral mucosal fibroblasts are 'younger', with a more embryonic/fetal-like phenotype that may provide a notable advantage for their ability to repair wounds in a scarless fashion.

Optimisation of the hydrogen peroxide pre-treatment of titanium: surface characterisation and protein adsorption.

BACKGROUND: Researchers have attempted to enhance titanium osseointegration by modifying its surface properties, including via H(2)O(2) pre-treatment, with reported treatment regimes varying from minutes/hours, to weeks. OBJECTIVE: This study examined the effects of various H(2)O(2) treatments on titanium surface topography/roughness, chemical composition/oxide thickness, hydrophilicity and plasma protein adsorption. MATERIALS AND METHODS: Titanium discs were treated with 30% H(2)O(2) for 0-24 h or 1-4 weeks and subjected to atomic force microscopy (AFM), scanning electron microscopy (SEM), profilometry, X-ray photon spectroscopy and contact angle analysis. For protein adsorption, whole plasma and FITC-conjugated serum albumin were added to 0-24 h and 1-4 week H(2)O(2)-treated discs and examined by SEM and fluorescence microscopy, respectively. RESULTS: AFM, SEM and profilometry demonstrated that 1-6 h H(2)O(2)-treated discs exhibited subtle alterations in surface topography/roughness at the nanometre scale, although 24 h and 1-4 week H(2)O(2)-treated discs exhibited much greater increases in surface roughness, in the micrometre range. Maximal increases in surface oxide thickness and chemical modification were identified between 1 h-4 weeks and 3 h-4 weeks, respectively, although no increases in oxygen/titanium (O1s : Ti2p) molar ratio or in hydrophilicity were evident. Plasma and serum albumin adsorption increased on 1-24 h H(2)O(2)-treated discs, with further increases on 1-4 week H(2)O(2)-treated discs. CONCLUSIONS: Based upon the present data and previous findings, this study supports the concept that surface topography/roughness and oxide composition/thickness, are more significantly modified by H(2)O(2) treatment and more influential to protein adsorption than hydrophilicity. Additionally, it can be hypothesized that the 24 h H(2)O(2) treatment of titanium surfaces, which induced micrometre scale changes in roughness and protein adsorption, to those associated with enhanced osteoblast attachment/behaviour, mineralisation and subsequent implant osseointegration, would be most beneficial.

Effect of margin status on cervical intraepithelial neoplasia recurrence following LLETZ in women over 50 years.

OBJECTIVE: To establish the effect of margin status on recurrence following large loop excision of the transformation zone (LLETZ) in women over 50 years. STUDY DESIGN: Prospectively collected data of women over 50 years, who underwent LLETZ for suspected cervical intraepithelial neoplasia between 1998 and 2003, were analysed. Women were followed up for up to over 6 years. SETTING: District colposcopy service based at a gynae-oncology cancer centre. MAIN OUTCOME MEASURES: The main outcome measure included histologically detected recurrence. Any abnormal cytology on follow up was also documented. METHODS: Prospectively collected data were analysed from the colposcopy database. Recurrence was analysed using Kaplan-Meir plots and Cox regression. Fisher's exact test was used to determine the association between margins and grade. The Kruskal-Wallis and Mann-Whitney U tests were used to compare age and duration of follow up between groups. RESULTS: A total of 118 women underwent LLETZ and 92 were included in the final analysis. Margins were designated as clear (n = 62), involved (n = 22) or uncertain (n = 8). Histological recurrence occurred in 12 while abnormal cytology was demonstrated in 17 women. One woman with involved margins developed cervical cancer. Individuals with clear margins were less likely to have recurrence than those with involved margins (Hazard Ratio (HR) 0.18, 95% CI: 0.06-0.59). Involved margins were more common with high-grade than low-grade lesions (P = 0.002). CONCLUSION: The data show an association between disease recurrence and the finding of involved margins in this cohort.

A UK-based investigation of inter- and intra-observer reproducibility of Gleason grading of prostatic biopsies.

AIMS: The frequency of prostatic core biopsies to detect cancer has been increasing with more widespread prostate specific antigen (PSA) testing. Gleason score has important implications for patient management but morphological reproducibility data for British practice are limited. Using literature-based criteria nine uropathologists took part in a reproducibility study. METHODS: Each of the nine participants submitted slides from consecutive cases of biopsy-diagnosed cancer assigned to the Gleason score groups 2-4, 5-6, 7 and 8-10 in the original report. A random selection of slides was taken within each group and examined by all pathologists, who were blind to the original score. Over six circulations, new slides were mixed with previously read slides, resulting in a total of 47 of 81 slides being read more than once. RESULTS: For the first readings of the 81 slides, the agreement with the consensus score was 78% and overall interobserver agreement was kappa 0.54 for Gleason score groups 2-4, 5-6, 7, 8-10. Kappa values for each category were 0.33, 0.56, 0.44 and 0.68, respectively. For the 47 slides read more than once, intra-observer agreement was 77%, kappa 0.66. The study identified problems in core biopsy interpretation of Gleason score at levels 2-4 and 7. Patterns illustrated by Gleason as 2 tended to be categorized as 3 because of the variable acinar size and unassessable lesional margin. In slides with consensus Gleason score 7, 13% of readings were scored 6 and in slides with consensus 6, 18% of readings were scored 7. CONCLUSIONS: Recommendations include the need to increase objectivity of the Gleason criteria but limits of descriptive morphology may have to be accepted.

A study of Gleason score interpretation in different groups of UK pathologists; techniques for improving reproducibility.

AIMS: To test the effectiveness of a teaching resource (a decision tree with diagnostic criteria based on published literature) in improving the proficiency of Gleason grading of prostatic cancer by general pathologists. METHODS: A decision tree with diagnostic criteria was developed by a panel of urological pathologists during a reproducibility study. Twenty-four general histopathologists tested this teaching resource. Twenty slides were selected to include a range of Gleason score groups 2-4, 5-6, 7 and 8-10. Interobserver agreement was studied before and after a presentation of the decision tree and criteria. The results were compared with those of the panel of urological pathologists. RESULTS: Before the teaching session, 83% of readings agreed within +/- 1 of the panel's consensus scores. Interobserver agreement was low (kappa = 0.33) compared with that for the panel (kappa = 0.62). After the presentation, 90% of readings agreed within +/- 1 of the panel's consensus scores and interobserver agreement amongst the pathologists increased to kappa = 0.41. Most improvement in agreement was seen for the Gleason score group 5-6. CONCLUSIONS: The lower level of agreement among general pathologists highlights the need to improve observer reproducibility. Improvement associated with a single training session is likely to be limited. Additional strategies include external quality assurance and second opinion within cancer networks.