Search

Introduction: The prevalence of self-harm is high; UK guidelines recommend harm-minimisation (HM), where people who frequently self-harm are supported to do so more safely using strategies such as using rubber bands or sterile blades, despite a lack of evidence. Objectives: To determine the prevalence and characteristics of those who self-harm and practice HM within a London mentalhealth trust. Methods: Electronic health records from 2006-2016 for patients within Camden & Islington NHS trust were included. Keywords such as 'self-harm', 'reduce harm' and 'harm minimisation' were used to search records. Once identified, these were manually screened to identify patients who used HM for self-harm. Patients were matched with a control group that self-harm, but don't use HM techniques, to compare demographics using logistic regression. Results: 1133 documents were identified and manually coded; 210 of these 146 patients using HM. HM was categorised into four techniques: 'sensation' such as rubber bands (57%), 'process'-using red pens (2%), 'damage reduction' such as the self-injury location (6%), 'damage limitation'-antiseptic techniques (5%) or no details (30%). On comparison to 7242 control patients self-harming, those that practice HM were more likely to be younger (mean age=29.3, p<0.001), female (75% p<0.001), (white ethnicity 73%), employed (25% p<0.001) and have more previous admissions p<0.001. Conclusions:HMis being used in clinical practice despite the lack of guidelines. Although half of HM described sensation techniques, a third had no details described, demonstrating the lack of clarification without clear guidelines. More research is required to determine the most effective techniques to inform policies and guidelines. [ABSTRACT FROM AUTHOR]

Purpose: Genome sequencing (GS)-specific diagnostic rates in prospective tightly ascertained exome sequencing (ES)-negative intellectual disability (ID) cohorts have not been reported extensively., Methods: ES, GS, epigenetic signatures, and long-read sequencing diagnoses were assessed in 74 trios with at least moderate ID., Results: The ES diagnostic yield was 42 of 74 (57%). GS diagnoses were made in 9 of 32 (28%) ES-unresolved families. Repeated ES with a contemporary pipeline on the GS-diagnosed families identified 8 of 9 single-nucleotide variations/copy-number variations undetected in older ES, confirming a GS-unique diagnostic rate of 1 in 32 (3%). Episignatures contributed diagnostic information in 9% with GS corroboration in 1 of 32 (3%) and diagnostic clues in 2 of 32 (6%). A genetic etiology for ID was detected in 51 of 74 (69%) families. Twelve candidate disease genes were identified. Contemporary ES followed by GS cost US$4976 (95% CI: $3704; $6969) per diagnosis and first-line GS at a cost of $7062 (95% CI: $6210; $8475) per diagnosis., Conclusion: Performing GS only in ID trios would be cost equivalent to ES if GS were available at $2435, about a 60% reduction from current prices. This study demonstrates that first-line GS achieves higher diagnostic rate than contemporary ES but at a higher cost., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Background: 'Early Intervention in Psychosis' (EIP) services have been associated with improved outcomes for early psychosis. However, these services are heterogeneous and many provide different components of treatment. The impact of this variation on the sustained treatment effects is unknown., Methods: We performed a systematic review and component network meta-analysis (cNMA) of randomised controlled trials (RCTs) that compared specialised intervention services for early psychosis. We searched CENTRAL (published and unpublished), EMBASE, MEDLINE, CINAHL, PsycINFO and Web of Science from inception to February 2023. Primary outcomes were negative and positive psychotic symptoms at 3-month and 1-year follow-up and treatment dropouts. Secondary outcomes were depressive symptoms and social functioning at 1-year follow-up. We registered a protocol for our study in PROSPERO (CRD42017057420)., Findings: We identified 37 RCTs including 4599 participants. Participants' mean age was 25.8 years (SD 6.0) and 64.0% were men. We found evidence that psychological interventions (this component grouped all psychological treatment intended to treat, or ameliorate the consequences of, psychotic symptoms) are beneficial for reducing negative symptoms (iSMD -0.24, 95% CI -0.44 to -0.05, p = 0.014) at 3-month follow-up and may be associated with clinically relevant benefits in improving social functioning scores at 1-year follow-up (iSMD -0.52, 95% CI -1.05 to 0.01, p = 0.052). The addition of case management has a beneficial effect on reducing negative symptoms (iSMD -1.17, 95% CI -2.24 to -0.11, p = 0.030) and positive symptoms (iSMD -1.05, 95% CI -2.02 to -0.08, p = 0.033) at 1-year follow-up. Pharmacotherapy was present in all trial arms, meaning it was not possible to examine the specific effects of this component., Interpretation: Our findings suggest psychological interventions and case management in addition to pharmacotherapy as the core components of services for early psychosis to achieve sustained clinical benefits. Our conclusions are limited by the small number of studies and sparsely connected networks., Funding: National Institute for Health and Care Research., Competing Interests: EGO has received research and consultancy fees from Angelini Pharma, for work not related to this project. FDC is an employee of Boehringer Ingelheim International. AC has received research, educational and consultancy fees from INCiPiT (Italian Network for Paediatric Trials), CARIPLO Foundation, Lundbeck and Angelini Pharma, for work not related to this project. RW is supported by an NIHR Doctoral Fellowship (grant NIHR302320)., (© 2024 The Authors.)

Objectives: To describe and compare the association between suicidality and subsequent readmission for patients hospitalized for eating disorder treatment, within 2 years of discharge, at two large academic medical centers in two different countries., Methods: Over an 8-year study window from January 2009 to March 2017, we identified all inpatient eating disorder admissions at Weill Cornell Medicine, New York, USA (WCM) and South London and Maudsley Foundation NHS Trust, London, UK (SLaM). To establish each patient's-suicidality profile, we applied two natural language processing (NLP) algorithms, independently developed at the two institutions, and detected suicidality in clinical notes documented in the first week of admission. We calculated the odds ratios (OR) for any subsequent readmission within 2 years postdischarge and determined whether this was to another eating disorder unit, other psychiatric unit, a general medical hospital admission or emergency room attendance., Results: We identified 1126 and 420 eating disorder inpatient admissions at WCM and SLaM, respectively. In the WCM cohort, evidence of above average suicidality during the first week of admission was significantly associated with an increased risk of noneating disorder-related psychiatric readmission (OR 3.48 95% CI = 2.03-5.99, p-value < .001), but a similar pattern was not observed in the SLaM cohort (OR 1.34, 95% CI = 0.75-2.37, p = .32), there was no significant increase in risk of admission. In both cohorts, personality disorder increased the risk of any psychiatric readmission within 2 years., Discussion: Patterns of increased risk of psychiatric readmission from above average suicidality detected via NLP during inpatient eating disorder admissions differed in our two patient cohorts. However, comorbid diagnoses such as personality disorder increased the risk of any psychiatric readmission across both cohorts., Public Significance: Suicidality amongst is eating disorders is an extremely common presentation and it is important we further our understanding of identifying those most at risk. This research also provides a novel study design, comparing two NLP algorithms on electronic health record data based in the United States and United Kingdom on eating disorder inpatients. Studies researching both UK and US mental health patients are sparse therefore this study provides novel data., (© 2023 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Introduction: Self-harm and suicide are major public health concerns among children and adolescents. Many risk and protective factors for suicide and self-harm have been identified and reported in the literature. However, the capacity of these identified risk and protective factors to guide assessment and management is limited due to their great number. This protocol describes an ongoing systematic review and meta-analysis which aims to examine longitudinal studies of risk factors for self-harm and suicide in children and adolescents, to provide a comparison of the strengths of association of the various risk factors for self-harm and suicide and to shed light on those that require further investigation., Methods and Analysis: We perform a systematic search of the literature using the databases EMBASE, PsycINFO, Medline, CINAHL and HMIC from inception up to 28 October 2020, and the search will be updated before the systematic review publication. Additionally, we will contact experts in the field, including principal investigators whose peer-reviewed publications are included in our systematic review as well as investigators from our extensive research network, and we will search the reference lists of relevant reviews to retrieve any articles that were not identified in our search. We will extract relevant data and present a narrative synthesis and combine the results in meta-analyses where there are sufficient data. We will assess the risk of bias for each study using the Newcastle-Ottawa Scale and present a summary of the quantity and the quality of the evidence for each risk or protective factor., Ethics and Dissemination: Ethical approval will not be sought as this is a systematic review of the literature. Results will be published in mental health journals and presented at conferences focused on suicide prevention., Prospero Registration Number: CRD42021228212., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objectives: The objective of this study was to determine risk factors for those diagnosed with eating disorders who report self-harm and suicidality., Design and Setting: This study was a retrospective cohort study within a secondary mental health service, South London and Maudsley National Health Service Trust., Participants: All diagnosed with an F50 diagnosis of eating disorder from January 2009 to September 2019 were included., Intervention and Measures: Electronic health records (EHRs) for these patients were extracted and two natural language processing tools were used to determine documentation of self-harm and suicidality in their clinical notes. These tools were validated manually for attribute agreement scores within this study., Results: The attribute agreements for precision of positive mentions of self-harm were 0.96 and for suicidality were 0.80; this demonstrates a 'near perfect' and 'strong' agreement and highlights the reliability of the tools in identifying the EHRs reporting self-harm or suicidality. There were 7434 patients with EHRs available and diagnosed with eating disorders included in the study from the dates January 2007 to September 2019. Of these, 4591 (61.8%) had a mention of self-harm within their records and 4764 (64.0%) had a mention of suicidality; 3899 (52.4%) had mentions of both. Patients reporting either self-harm or suicidality were more likely to have a diagnosis of anorexia nervosa (AN) (self-harm, AN OR=3.44, 95% CI 1.05 to 11.3, p=0.04; suicidality, AN OR=8.20, 95% CI 2.17 to 30.1; p=0.002). They were also more likely to have a diagnosis of borderline personality disorder (p≤0.001), bipolar disorder (p<0.001) or substance misuse disorder (p<0.001)., Conclusion: A high percentage of patients (>60%) diagnosed with eating disorders report either self-harm or suicidal thoughts. Relative to other eating disorders, those diagnosed with AN were more likely to report either self-harm or suicidal thoughts. Psychiatric comorbidity, in particular borderline personality disorder and substance misuse, was also associated with an increase risk in self-harm and suicidality. Therefore, risk assessment among patients diagnosed with eating disorders is crucial., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Massively parallel sequencing has markedly improved mendelian diagnostic rates. This study assessed the effects of custom alterations to a diagnostic genomic bioinformatic pipeline in response to clinical need and derived practice recommendations relative to diagnostic rates and efficiency. The Genomic Annotation and Interpretation Application (GAIA) bioinformatics pipeline was designed to detect panel, exome, and genome sample integrity and prioritize gene variants in mendelian disorders. Reanalysis of selected negative cases was performed after improvements to the pipeline. GAIA improvements and their effect on sensitivity are described, including addition of a PubMed search for gene-disease associations not in the Online Mendelian Inheritance of Man database, inclusion of a process for calling low-quality variants (known as QPatch), and gene symbol nomenclature consistency checking. The new pipeline increased the diagnostic rate and reduced staff costs, resulting in a saving of US$844.34 per additional diagnosis. Recommendations for genomic analysis pipeline requirements are summarized. Clinically responsive bioinformatics pipeline improvements increase diagnostic sensitivity and increase cost-effectiveness., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Background: Prevalence of self-harm in the UK was reported as 6.4% in 2014. Despite sparse evidence for effectiveness, guidelines recommend harm minimisation; a strategy in which people who self-harm are supported to do so safely., Aims: To determine the prevalence, sociodemographic and clinical characteristics of those who self-harm and practise harm minimisation within a London mental health trust., Method: We included electronic health records for patients treated by South London and Maudsley NHS Trust. Using an iterative search strategy, we identified patients who practise harm minimisation, then classified the approaches using a content analysis. We compared the sociodemographic characteristics with that of a control group of patients who self-harm and do not use harm minimisation., Results: In total 22 736 patients reported self-harm, of these 693 (3%) had records reporting the use of harm-minimisation techniques. We coded the approaches into categories: (a) 'substitution' (>50% of those using harm minimisation), such as using rubber bands or using ice; (b) 'simulation' (9%) such as using red pens; (c) 'defer or avoid' (7%) such as an alternative self-injury location; (d) 'damage limitation' (9%) such as using antiseptic techniques; the remainder were unclassifiable (24%). The majority of people using harm minimisation described it as helpful (>90%). Those practising harm minimisation were younger, female, of White ethnicity, had previous admissions and were less likely to have self-harmed with suicidal intent., Conclusions: A small minority of patients who self-harm report using harm minimisation, primarily substitution techniques, and the large majority find harm minimisation helpful. More research is required to determine the acceptability and effectiveness of harm-minimisation techniques and update national clinical guidelines.

Background: Antenatal screening is vital to identifying couples at risk of having children with a clinically significant haemoglobinopathy. In Australia, immigration is increasing carrier incidence., Methods: A retrospective analysis was performed of full blood count, high-performance liquid chromatography and haemoglobin electrophoresis of women and their partners who underwent antenatal haemoglobinopathy screening over three years at a major NSW laboratory. Genetic testing results were included where available., Results: One thousand six hundred and twenty-eight women and 729 male partners were screened at a median gestation of 14 weeks. 8.2% of women had a clinically significant result, with a median 16-day interval to partner testing. In 35% of couples screened simultaneously, the partner did not require testing. Genetic confirmatory testing was performed in 65% of high risk couples., Conclusion: There was a significant delay to antenatal haemoglobinopathy screening for mothers, limiting time for genetic diagnosis, prenatal diagnosis and management of affected pregnancies. Screening should be performed earlier. Simultaneous couple testing is not cost-effective., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Importance: Widespread adoption of rapid genomic testing in pediatric critical care requires robust clinical and laboratory pathways that provide equitable and consistent service across health care systems., Objective: To prospectively evaluate the performance of a multicenter network for ultra-rapid genomic diagnosis in a public health care system., Design, Setting, and Participants: Descriptive feasibility study of critically ill pediatric patients with suspected monogenic conditions treated at 12 Australian hospitals between March 2018 and February 2019, with data collected to May 2019. A formal implementation strategy emphasizing communication and feedback, standardized processes, coordination, distributed leadership, and collective learning was used to facilitate adoption., Exposures: Ultra-rapid exome sequencing., Main Outcomes and Measures: The primary outcome was time from sample receipt to ultra-rapid exome sequencing report. The secondary outcomes were the molecular diagnostic yield, the change in clinical management after the ultra-rapid exome sequencing report, the time from hospital admission to the laboratory report, and the proportion of laboratory reports returned prior to death or hospital discharge., Results: The study population included 108 patients with a median age of 28 days (range, 0 days to 17 years); 34% were female; and 57% were from neonatal intensive care units, 33% were from pediatric intensive care units, and 9% were from other hospital wards. The mean time from sample receipt to ultra-rapid exome sequencing report was 3.3 days (95% CI, 3.2-3.5 days) and the median time was 3 days (range, 2-7 days). The mean time from hospital admission to ultra-rapid exome sequencing report was 17.5 days (95% CI, 14.6-21.1 days) and 93 reports (86%) were issued prior to death or hospital discharge. A molecular diagnosis was established in 55 patients (51%). Eleven diagnoses (20%) resulted from using the following approaches to augment standard exome sequencing analysis: mitochondrial genome sequencing analysis, exome sequencing-based copy number analysis, use of international databases to identify novel gene-disease associations, and additional phenotyping and RNA analysis. In 42 of 55 patients (76%) with a molecular diagnosis and 6 of 53 patients (11%) without a molecular diagnosis, the ultra-rapid exome sequencing result was considered as having influenced clinical management. Targeted treatments were initiated in 12 patients (11%), treatment was redirected toward palliative care in 14 patients (13%), and surveillance for specific complications was initiated in 19 patients (18%)., Conclusions and Relevance: This study suggests feasibility of ultra-rapid genomic testing in critically ill pediatric patients with suspected monogenic conditions in the Australian public health care system. However, further research is needed to understand the clinical value of such testing, and the generalizability of the findings to other health care settings.

Objective: Suicide attempts requiring hospitalization are known to be common in patients who are diagnosed with eating disorders. Attempting suicide is a major indicator for those at risk of completed suicide. Both the specific eating disorder diagnosis and the influence of psychiatric comorbidities on suicide attempts requiring hospitalization were investigated, with demographic and socioeconomic variables as confounders, over a 10-year observation period from January 2007 to March 2017., Methods: Anonymized health-record data from the South London and Maudsley NHS Foundation Trust (SLaM) were retrieved through the Clinical Record Interactive Search (CRIS) data resource; this is linked to national Hospital Episode Statistics (HES) data. These data include all diagnoses for inpatient admissions. Hazard ratios, with 95% confidence intervals (CIs), were calculated from cox regression analyses and the effects of a number of confounders were estimated by performing multivariable analyses., Results: In total, 4,895 patients were diagnosed with anorexia nervosa (AN), bulimia nervosa (BN), or eating disorder otherwise not specified (EDNOS). Of these, 331 (6.7%) had attempted suicide requiring hospitalization and 21 (0.04%) completed suicide. The eating disorder category associated with the highest risk of a suicide attempt was AN (HR: 1.43, 95%CI: 1.08-1.89, p = .01). The risk was significantly increased further if the patient had a comorbid diagnosis of personality disorder, depression, bipolar affective disorder, and substance misuse., Discussion: Suicide attempts requiring hospitalization have a high incidence rate among patients with eating disorders, and the risk is significantly increased in AN. Comorbid psychiatric illness and suicidal ideation should be carefully assessed in all eating disorder patients., (© 2020 Wiley Periodicals, Inc.)

Background: This paper explores ethical concerns arising in healthcare integration. We argue that integration is necessary imperative for meeting contemporary and future healthcare challenges, a far stronger evidence base for the conditions of its effectiveness is required. In particular, given the increasing emphasis at the policy level for the entire healthcare infrastructure to become better integrated, our analysis of the ethical challenges that follow from the logic of integration itself is timely and important and has hitherto received insufficient attention., Methods: We evaluated an educational intervention which aims to improve child health outcomes by making transitions between primary to secondary care more efficient, ensuring children and parents are better supported throughout. The programme provided skills for trainee paediatricians and general practitioners (GPs) in co-designing integrated clinical services., Results: The key ethical challenges of integrated care that arose from a clinical perspective are: professional identity and autonomy in an integrated working environment; the concomitant extent of professional responsibility in such an environment; and the urgent need for more evidence to be produced on which strategies for integrating at scale can be based., Conclusions: From our analysis we suggest a tentative way forward, viewed from a normative position broadly situated at the intersection of deontology and care ethics. We adopt this position because the primary clinical ethical issues in the context of integrated care concern: how to ensure that all duties of care to individual patients are met in a newly orientated working environment where clinical responsibility may be ambiguous; and the need to orientate care around the patient by foregrounding their autonomous preferences and ensuring good patient clinician relationships in clinical decision-making.

We review the international literature on a neglected aspect of maternal mortality: maternal homicide. Reported rates range from 0.97 to 10.6 per 100,000 live births. Women murdered in the perinatal period constituted a highly vulnerable group: they were younger, more likely to be from minority ethnic groups, and unmarried. Domestic violence was a significant risk factor for attempted and completed homicide. Compared to other countries, pregnancy-associated homicide rates were highest in the US. It is unclear how much of the difference to attribute to better case identification or to actual risk. Our review demonstrates pregnancy-associated homicide is an important contributor to maternal mortality, with rates comparable to suicide. Central to any prevention strategy will be identification of those at risk. The predictions are very weak because definitions, data collection, and analysis are so variable from study to study. Our findings reinforce the importance of screening for current and previous domestic violence.

Background: Integrated care unites funding, administrative, organisational, service delivery and clinical levels to create connectivity, alignment and collaboration within and between care delivery and prevention sectors. It aims to improve efficiency by avoiding unnecessary duplication of resources. Consequently, implementing integrated care is increasingly important; however, there are many barriers and how we teach healthcare practitioners to work across systems is under-researched. This paper explores an innovative educational curriculum, the Programme for Integrated Child Health (PICH)., Methods: The PICH involved an experiential learning approach supported by taught sessions on specific issues relevant to integrated care. A qualitative study was conducted by interviewing 23 participants using semi-structured one-to-one interviews. Participants included trainees (general practice, paediatrics) and programme mentors. Data was thematically analysed., Results: Results are coded under three main themes: integrated care curriculum components, perceptions of a curriculum addressing integrated care and organisational change, and personal and professional learning. The data highlights the importance of real-world projects, utilising healthcare data, and considering patient perspectives to understand and develop integrated practices. Trainees received guidance from mentors but, more crucially learnt from, with, and about one another. They learnt about the context in which GPs and paediatricians work and developed a deeper understanding through which integrated services could be meaningfully developed., Conclusions: This study explored participants' experiences and can be taken forward by educationalists to design curricula to better prepare healthcare practitioners to work collaboratively. The emergence of integrated care brings about challenges for traditional pedagogical approaches as learners have to re-align their discipline-specific approaches with evolving healthcare structures. PICH demonstrated that trainees acquired knowledge through real-word projects and experiential learning; and that this facilitated integration, empowering doctors to become leaders of organisational change. However, there are also many challenges of implementing integrated curricula which need to be addressed, including breaking down professional silos and integrating resourceful healthcare. This study begins to demonstrate the ability of an integrated curriculum to support trainees to work collaboratively, but further work is needed to develop the wider efficacy of the programme incorporating other professional groups, and to assess its longer term impact.

Competing Interests: Competing interests: None declared.

Competing Interests: The authors declare that no competing interests exist.

Competing Interests: The authors declare that no competing interests exist.

Competing Interests: Competing interests: None declared.

In this review, we introduce the topic of transgender medicine, aimed at the non-specialist clinician working in the UK. Appropriate terminology is provided alongside practical advice on how to appropriately care for transgender people. We offer a brief theoretical discussion on transgenderism and consider how it relates to broader understandings of both gender and disease. In respect to epidemiology, while it is difficult to assess the exact size of the transgender population in the UK, population surveys suggest a prevalence of between 0.2 and 0.6% in adults, with rates of referrals to gender identity clinics in the UK increasing yearly. We outline the legal framework that protects the rights of transgender people, showing that is not legal for physicians to deny transgender people access to services based on their personal beliefs. Being transgender is often, although not always, associated with gender dysphoria, a potentially disabling condition in which the discordance between a person's natal sex (that assigned to them at birth) and gender identity results in distress, with high associated rates of self-harm, suicidality and functional impairment. We show that gender reassignment can be a safe and effective treatment for gender dysphoria with counselling, exogenous hormones and surgery being the mainstay of treatment. The role of the general practitioner in the management of transgender patients is discussed and we consider whether hormone therapy should be initiated in primary care in the absence of specialist advice, as is suggested by recent General Medical Council guidance.

Background: Anti-N-methyl-D-aspartate receptor encephalitis is a recently discovered disease entity of paraneoplastic limbic encephalitis. It largely affects young women and is often associated with an ovarian teratoma. It is a serious yet treatable condition if diagnosed early. Its remedy involves immunotherapy and surgical removal of the teratoma of the ovaries. This case of anti-N-methyl-D-aspartate receptor encephalitis involves an early surgical intervention with bilateral oophorectomy, despite negative imaging evidence of a teratoma., Case Presentation: A 25-year-old white woman with anti-N-methyl-D-aspartate receptor encephalitis presented with behavioral changes and seizures that were confirmed to be secondary to anti-N-methyl-D-aspartate receptor encephalitis. She required an admission to our intensive care unit for ventilator support and received a number of immunological therapies. Multiple imaging investigations showed no evidence of an ovarian teratoma; she had a bilateral oophorectomy 29 days after admission. Ovarian histology confirmed the presence of a teratoma with neuronal cells. A few days after the operation she began to show signs of improvement and, apart from mild short-term memory loss, she returned to normal function., Conclusions: Our patient is an example of teratoma-associated anti-N-methyl-D-aspartate receptor encephalitis, in which the teratoma was identified only microscopically. Her case highlights that even with negative imaging evidence of a teratoma, ovarian pathology should still be considered and explored.

Disruption of the reconsolidation of conditioned fear memories has been suggested as a non-pharmacological means of preventing the return of learned fear in human populations. A reconsolidation update paradigm was developed in which a reconsolidation window is opened by a single isolated retrieval trial of a previously reinforced CS+ which is then followed by Extinction Training within that window. However, follow-up studies in humans using multi-methods fear conditioning indices (e.g., fear-potentiated startle, skin conductance, US-expectancy) have failed to replicate the retrieval+extinction effects. In the present study, we further investigated the retrieval+extinction reconsolidation update paradigm by directly comparing the acquisition, extinction, and return of fear-potentiated startle in the absence or presence of US-expectancy measures (using a trial-by-trial response keypad) with and without retrieval of a previously acquired CS-US association. Participants were fear conditioned to two visual cue CS+'s, one of which was presented as a single, isolated retrieval trial before Extinction Training and one that was extinguished as usual. The results show that the inclusion of US-expectancy measures strengthens the CS-US association to provide enhanced fear conditioning and maintenance of fear memories over the experimental sessions. In addition, in the groups that used on-line US-expectancy measures, the retrieval+extinction procedure reduced reinstatement of fear-potentiated startle to both previously reinforced CS+'s, as compared to the extinction as usual group., (Published by Elsevier Inc.)

Fear conditioning methodologies have often been employed as testable models for assessing learned fear responses in individuals with anxiety disorders such as post-traumatic stress disorder (PTSD) and specific phobia. One frequently used paradigm is measurement of the acoustic startle reflex under conditions that mimic anxiogenic and fear-related conditions. For example, fear-potentiated startle is the relative increase in the frequency or magnitude of the acoustic startle reflex in the presence of a previously neutral cue (e.g., colored shape; termed the conditioned stimulus or CS+) that has been repeatedly paired with an aversive unconditioned stimulus (e.g., airblast to the larynx). Our group has recently used fear-potentiated startle paradigms to demonstrate impaired fear extinction in civilian and combat populations with PTSD. In the current study, we examined the use of either auditory or visual CSs in a fear extinction protocol that we have validated and applied to human clinical conditions. This represents an important translational bridge in that numerous animal studies of fear extinction, upon which much of the human work is based, have employed the use of auditory CSs as opposed to visual CSs. Participants in both the auditory and visual groups displayed robust fear-potentiated startle to the CS+, clear discrimination between the reinforced CS+ and non-reinforced CS-, significant extinction to the previously reinforced CS+, and marked spontaneous recovery. We discuss the current results as they relate to future investigations of PTSD-related impairments in fear processing in populations with diverse medical and psychiatric histories.

New statistical techniques and software have improved our ability to quantify fine-scale population structure. We isolated 11 microsatellite markers for eastern foxsnakes (Elaphe gloydi) and surveyed the variability of each using 115-136 individuals from one population in southwestern Ontario. We determined that all loci were variable and conformed to Hardy-Weinberg expectations and that no locus demonstrated linkage disequilibrium. We are using these markers to quantify the scale of gene flow, and to assess the effect of variable landscapes on connectivity and genetic diversity of three disjunct regional populations in the northern portion of the species' range., (© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.)

Background: A 35-year-old postpartum woman presented with myocardial infarction (MI) due to spontaneous coronary artery dissection (SCAD). In addition to conventional medical therapy, she was treated with immunosuppressive agents (prednisone and cytoxan) because of five noncontiguous coronary dissections, surgical inoperability, and postinfarction angina. Repeat angiography 94 days later demonstrated angiographically normal vessels., Methods: A literature review of 42 additional cases of peripartum SCAD was performed, and the results were compared with this patient., Results: Mortality was 48.8% (21/43). Sudden cardiac death was the initial presentation in 27.9% (12/43) of cases. The left coronary artery was involved in 78.6% (44/56) of dissections with left main segment dissection in 10 cases. In women who survived > 24 h post infarction, recurrent MI, usually due to a second coronary dissection, occurred in 20.8% (5/24). Histopathologic studies have often shown periadventitial inflammation (80%, 16/20), in which eosinophils predominate (68.8%, 11/16), and may be linked to the medial degeneration often found in these cases., Conclusions: The common observation of eosinophilic periadventitial inflammation suggests a role in the pathophysiology of this rare, yet serious condition. Aggressive immunosuppressive therapy in this case of multivessel dissection resulted in spontaneous angiographic healing of all lesions.

Lipid hapten-containing monolayer membranes with bound, anti-hapten antibody molecules serve as model immunological target membranes. Targets with bound-IgG trigger guinea pig macrophages to (a) adhere, (b) spread, (c) release lysosomal enzymes, and (d) increase cyanide-insensitive oxygen consumption. When the target membranes are derivatized with fluorescein, there is a 2-3-fold enhancement in the rate of fluorescein photobleaching in regions of cell-monolayer contact. This effect is due to release of O2- from macrophages, as shown by inhibition with superoxide dismutase and by the fact that enhanced photobleaching is not observed with cells of the RAW264 macrophage line, which undergo responses (a)-(d), but do not release O2- extracellularly. The O2- dependent photobleaching reaction appears to be relatively specific for fluorescein, as it did not occur with two other fluorophores, 4-nitrobenz-2-oxa-1,3-diazole and tetramethyl-rhodamine. Because stimulated neutrophils release large quantities of O2-, the photobleaching of fluorescein-labeled target membranes in response to neutrophils was examined. Monolayer membranes with specifically bound IgG caused neutrophils to adhere and become markedly motile during incubation at 37 degrees C. Like macrophages, neutrophils induced O2- -dependent photobleaching of fluorescein-labeled IgG in regions of cell-monolayer contact. In addition, neutrophils gave rise to a slower, nonphotochemical loss of fluorescence in the same contact regions. The latter effect is apparently due to cleavage of target-bound fluorescent IgG by proteolytic enzymes secreted by the neutrophils in response to the target surface.