Oral treatment of chickens with Lactobacillus reuteri LM1 reduces Brachyspira pilosicoli-induced pathology

Avian intestinal spirochaetosis (AIS) results from the colonization of the caeca and colon of poultry by pathogenic Brachyspira, notably Brachyspira pilosicoli. Following the ban on the use of antibiotic growth promoters in the European Union in 2006, the number of cases of AIS has increased, which, alongside emerging antimicrobial resistance in Brachyspira, has driven renewed interest in alternative intervention strategies. Lactobacillus-based probiotics have been shown to protect against infection with common enteric pathogens in livestock. Our previous studies have shown that Lactobacillus reuteri LM1 antagonizes aspects of the pathobiology of Brachyspira in vitro. Here, we showed that L. reuteri LM1 mitigates the clinical symptoms of AIS in chickens experimentally challenged with B. pilosicoli. Two groups of 15 commercial laying hens were challenged experimentally by oral gavage with B. pilosicoli B2904 at 18 weeks of age; one group received unsupplemented drinking water and the other received L. reuteri LM1 in drinking water from 1 week prior to challenge with Brachyspira and thereafter for the duration of the study. This treatment regime was protective. Specifically, B. pilosicoli was detected by culture in fewer birds, bird weights were higher, faecal moisture contents were significantly lower (P<0.05) and egg production as assessed by egg weight and faecal staining score was improved (P<0.05). Also, at post-mortem examination, significantly fewer B. pilosicoli were recovered from treated birds (P<0.05), with only mild–moderate histopathological changes observed. These data suggest that L. reuteri LM1 may be a useful tool in the control of AIS.

Opposing neural effects of naltrexone on food reward and aversion: implications for the treatment of obesity

Rationale: Opioid antagonism reduces the consumption of palatable foods in humans but the neural substrates implicated in these effects are less well understood. Objectives: The aim of the present study was to examine the effects of the opioid antagonist, naltrexone, on neural response to rewarding and aversive sight and taste stimuli. Methods: We used functional magnetic resonance imaging (fMRI) to examine the neural responses to the sight and taste of pleasant (chocolate) and aversive (mouldy strawberry) stimuli in 20 healthy volunteers who received a single oral dose of naltrexone (50 mg) and placebo in a double-blind, repeated-measures cross-over, design. Results: Relative to placebo, naltrexone decreased reward activation to chocolate in the dorsal anterior cingulate cortex and caudate, and increased aversive-related activation to unpleasant strawberry in the amygdala and anterior insula. Conclusions: These findings suggest that modulation of key brain areas involved in reward processing, cognitive control and habit formation such as the dorsal anterior cingulate cortex (dACC) and caudate might underlie reduction in food intake with opioid antagonism. Furthermore we show for the first time that naltrexone can increase activations related to aversive food stimuli. These results support further investigation of opioid treatments in obesity.

Children and adolescents referred for treatment of anxiety disorders: differences in clinical characteristics

Background: Reports of the clinical characteristics of children and adolescents with anxiety disorders are typically based on community populations or from clinical samples with exclusion criterion applied. Little is known about the clinical characteristics of children and adolescents routinely referred for treatment for anxiety disorders. Furthermore, children and adolescents are typically treated as one homogeneous group although they may differ in ways that are clinically meaningful. Methods: A consecutive series of children (n = 100, aged 6-12 years) and adolescents (n = 100, aged 13-18 years), referred to a routine clinical service, were assessed for anxiety and comorbid disorders, school refusal and parental symptoms of psychopathology. Results: Children were significantly more likely to be diagnosed with separation anxiety disorder than adolescents. Adolescents with a primary anxiety disorder had significantly higher self and clinician rated anxiety symptoms and had more frequent primary diagnoses of social anxiety disorder, diagnoses and symptoms of mood disorders, and irregular school attendance. Limitations: Childhood and adolescence were considered categorically as distinct, developmental periods; in reality changes would be unlikely to occur in such a discrete manner. Conclusions: The finding that children and adolescents with anxiety disorders have distinct clinical characteristics has clear implications for treatment. Simply adapting treatments designed for children to make the materials more ‘adolescent-friendly’ is unlikely to sufficiently meet the needs of adolescents.

Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability

Epilepsy is the most common neurological disorder, with over 50 million people worldwide affected. Recent evidence suggests that the transient receptor potential cation channel subfamily V member 1 (TRPV1) may contribute to the onset and progression of some forms of epilepsy. Since the two nonpsychotropic cannabinoids cannabidivarin (CBDV) and cannabidiol (CBD) exert anticonvulsant activity in vivo and produce TRPV1-mediated intracellular calcium elevation in vitro, we evaluated the effects of these two compounds on TRPV1 channel activation and desensitization and in an in vitro model of epileptiform activity. Patch clamp analysis in transfected HEK293 cells demonstrated that CBD and CBDV dose-dependently activate and rapidly desensitize TRPV1, as well as TRP channels of subfamily V type 2 (TRPV2) and subfamily A type 1 (TRPA1). TRPV1 and TRPV2 transcripts were shown to be expressed in rat hippocampal tissue. When tested on epileptiform neuronal spike activity in hippocampal brain slices exposed to a Mg2+-free solution using multielectrode arrays (MEAs), CBDV reduced both epileptiform burst amplitude and duration. The prototypical TRPV1 agonist, capsaicin, produced similar, although not identical effects. Capsaicin, but not CBDV, effects on burst amplitude were reversed by IRTX, a selective TRPV1 antagonist. These data suggest that CBDV antiepileptiform effects in the Mg2+-free model are not uniquely mediated via activation of TRPV1. However, TRPV1 was strongly phosphorylated (and hence likely sensitized) in Mg2+-free solution-treated hippocampal tissue, and both capsaicin and CBDV caused TRPV1 dephosphorylation, consistent with TRPV1 desensitization. We propose that CBDV effects on TRP channels should be studied further in different in vitro and in vivo models of epilepsy.

Curl free pressure gradients over orography in a solution of the fully compressible Euler equations with implicit treatment of acoustic and gravity waves

Steep orography can cause noisy solutions and instability in models of the atmosphere. A new technique for modelling flow over orography is introduced which guarantees curl free gradients on arbitrary grids, implying that the pressure gradient term is not a spurious source of vorticity. This mimetic property leads to better hydrostatic balance and better energy conservation on test cases using terrain following grids. Curl-free gradients are achieved by using the co-variant components of velocity over orography rather than the usual horizontal and vertical components. In addition, gravity and acoustic waves are treated implicitly without the need for mean and perturbation variables or a hydrostatic reference profile. This enables a straightforward description of the implicit treatment of gravity waves. Results are presented of a resting atmosphere over orography and the curl-free pressure gradient formulation is advantageous. Results of gravity waves over orography are insensitive to the placement of terrain-following layers. The model with implicit gravity waves is stable in strongly stratified conditions, with N∆t up to at least 10 (where N is the Brunt-V ̈ais ̈al ̈a frequency). A warm bubble rising over orography is simulated and the curl free pressure gradient formulation gives much more accurate results for this test case than a model without this mimetic property.

A randomised controlled trial of positive memory training for the treatment of depression within schizophrenia

Abstract Background: Depression is highly prevalent within individuals diagnosed with schizophrenia, and is associated with an increased risk of suicide. There are no current evidence based treatments for low mood within this group. The specific targeting of co-morbid conditions within complex mental health problems lends itself to the development of short-term structured interventions which are relatively easy to disseminate within health services. A brief cognitive intervention based on a competitive memory theory of depression, is being evaluated in terms of its effectiveness in reducing depression within this group. Methods/Design: This is a single blind, intention-to-treat, multi-site, randomized controlled trial comparing Positive Memory Training plus Treatment as Usual with Treatment as Usual alone. Participants will be recruited from two NHS Trusts in Southern England. In order to be eligible, participants must have a DSM-V diagnosis of schizophrenia or schizo-affective disorder and exhibit at least a mild level of depression. Following baseline assessment eligible participants will be randomly allocated to either the Positive Memory Training plus Treatment as Usual group or the Treatment as Usual group. Outcome will be assessed at the end of treatment (3-months) and at 6-month and 9-month post randomization by assessors blind to group allocation. The primary outcome will be levels of depression and secondary outcomes will be severity of psychotic symptoms and cost-effectiveness. Semi-structured interviews will be conducted with all participants who are allocated to the treatment group so as to explore the acceptability of the intervention. Discussion: Cognitive behaviour therapy is recommended for individuals diagnosed with schizophrenia. However, the number of sessions and length of training required to deliver this intervention has caused a limit in availability. The current trial will evaluate a short-term structured protocol which targets a co-morbid condition often considered of primary importance by service users. If successful the intervention will be an important addition to current initiatives aimed at increasing access to psychological therapies for people diagnosed with severe mental health problems. Trial registration: Current Controlled Trials. ISRCTN99485756. Registered 13 March 2014.

Treatment of child anxiety in the context of maternal anxiety disorder: a randomised controlled trial and economic analysis

Background Cognitive–behavioural therapy (CBT) for childhood anxiety disorders is associated with modest outcomes in the context of parental anxiety disorder. Objectives This study evaluated whether or not the outcome of CBT for children with anxiety disorders in the context of maternal anxiety disorders is improved by the addition of (i) treatment of maternal anxiety disorders, or (ii) treatment focused on maternal responses. The incremental cost-effectiveness of the additional treatments was also evaluated. Design Participants were randomised to receive (i) child cognitive–behavioural therapy (CCBT); (ii) CCBT with CBT to target maternal anxiety disorders [CCBT + maternal cognitive–behavioural therapy (MCBT)]; or (iii) CCBT with an intervention to target mother–child interactions (MCIs) (CCBT + MCI). Setting A NHS university clinic in Berkshire, UK. Participants Two hundred and eleven children with a primary anxiety disorder, whose mothers also had an anxiety disorder. Interventions All families received eight sessions of individual CCBT. Mothers in the CCBT + MCBT arm also received eight sessions of CBT targeting their own anxiety disorders. Mothers in the MCI arm received 10 sessions targeting maternal parenting cognitions and behaviours. Non-specific interventions were delivered to balance groups for therapist contact. Main outcome measures Primary clinical outcomes were the child’s primary anxiety disorder status and degree of improvement at the end of treatment. Follow-up assessments were conducted at 6 and 12 months. Outcomes in the economic analyses were identified and measured using estimated quality-adjusted life-years (QALYs). QALYS were combined with treatment, health and social care costs and presented within an incremental cost–utility analysis framework with associated uncertainty. Results MCBT was associated with significant short-term improvement in maternal anxiety; however, after children had received CCBT, group differences were no longer apparent. CCBT + MCI was associated with a reduction in maternal overinvolvement and more confident expectations of the child. However, neither CCBT + MCBT nor CCBT + MCI conferred a significant post-treatment benefit over CCBT in terms of child anxiety disorder diagnoses [adjusted risk ratio (RR) 1.18, 95% confidence interval (CI) 0.87 to 1.62, p = 0.29; adjusted RR CCBT + MCI vs. control: adjusted RR 1.22, 95% CI 0.90 to 1.67, p = 0.20, respectively] or global improvement ratings (adjusted RR 1.25, 95% CI 1.00 to 1.59, p = 0.05; adjusted RR 1.20, 95% CI 0.95 to 1.53, p = 0.13). CCBT + MCI outperformed CCBT on some secondary outcome measures. Furthermore, primary economic analyses suggested that, at commonly accepted thresholds of cost-effectiveness, the probability that CCBT + MCI will be cost-effective in comparison with CCBT (plus non-specific interventions) is about 75%. Conclusions Good outcomes were achieved for children and their mothers across treatment conditions. There was no evidence of a benefit to child outcome of supplementing CCBT with either intervention focusing on maternal anxiety disorder or maternal cognitions and behaviours. However, supplementing CCBT with treatment that targeted maternal cognitions and behaviours represented a cost-effective use of resources, although the high percentage of missing data on some economic variables is a shortcoming. Future work should consider whether or not effects of the adjunct interventions are enhanced in particular contexts. The economic findings highlight the utility of considering the use of a broad range of services when evaluating interventions with this client group. Trial registration Current Controlled Trials ISRCTN19762288. Funding This trial was funded by the Medical Research Council (MRC) and Berkshire Healthcare Foundation Trust and managed by the National Institute for Health Research (NIHR) on behalf of the MRC–NIHR partnership (09/800/17) and will be published in full in Health Technology Assessment; Vol. 19, No. 38.

Recognition, assessment and treatment of social anxiety disorder: summary of NICE guidance

Social anxiety disorder is one of the most persistent and common of the anxiety disorders, with lifetime prevalence rates in Europe of 6.7% (range 3.9-13.7%).1 It often coexists with depression, substance use disorder, generalised anxiety disorder, panic disorder, and post-traumatic stress disorder.2 It can severely impair a person’s daily functioning by impeding the formation of relationships, reducing quality of life, and negatively affecting performance at work or school. Despite this, and the fact that effective treatments exist, only about half of people with this condition seek treatment, many after waiting 10-15 years.3 Although about 40% of those who develop the condition in childhood or adolescence recover before adulthood,4 for many the disorder persists into adulthood, with the chance of spontaneous recovery then limited compared with other mental health problems. This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE) on recognising, assessing, and treating social anxiety disorder in children, young people, and adults.5

Graceful remedies: understanding grace in the Catholic Church's treatment of clerical child sexual abuse

This article examines advocacy of Catholic restorative justice for clerical child sexual abuse from the standpoint of feminist criminological critiques of the use of restorative mediation in sexual offence cases. In particular, it questions the Catholic invocation of grace and forgiveness of survivors of abuse in light of critical feminist concerns about the exploitation of emotions in restorative practices, especially in regard to sexual and other gender-based offences. In the context of sexual abuse, the Catholic appeal to grace has the potential for turning into an extraordinary demand made of victims not only to rehabilitate offenders and the church in the eyes of the community, but also to work towards the spiritual absolution of the abuser. This unique feature of Catholic-oriented restorative justice raises important concerns in terms of feminist critiques of the risk of abuses of power within mediation, and is also incompatible with orthodox restorative justice theory, which, although it advocates a ‘spiritual’ response to crime, is concerned foremost with the rights, needs and experiences of victims.

Children’s physic: medical perceptions and treatment of sick children in early modern England, c. 1580-1720

Historians of medicine, childhood, and paediatrics, have often assumed that early modern doctors neither treated children, nor adapted their medicines to suit the peculiar temperaments of the young. Through an examination of medical textbooks and doctors’ casebooks, this article refutes these assumptions. It argues that medical authors and practising doctors regularly treated children, and were careful to tailor their remedies to complement the distinctive constitutions of children. Thus, this article proposes that a concept of ‘children’s physic’ existed in early modern England: this term refers to the notion that children were physiologically distinct, requiring special medical care. Children’s physic was rooted in the ancient traditions of Hippocratic and Galenic medicine: it was the child’s humoral makeup that underpinned all medical ideas about children’s bodies, minds, diseases, and treatments. Children abounded in the humour blood, which made them humid and weak, and in need of medicines of a particularly gentle nature.

Designing care bundle documentation to support the recognition and treatment of acute kidney injury: a route to quality improvement

The chapter describes development of care bundle documentation, through an iterative, user-centred design process, to support the recognition and treatment of acute kidney injury (AKI). The chapter details stages of user and stakeholder consultation, employed to develop a design response that was sensitive to user experience and need, culminating in simulation testing of a near final prototype. The development of supplementary awareness-raising materials, relating to the main care bundle tool is also discussed. This information design response to a complex clinical decision-making process is contrasted to other approaches to promoting AKI care. The need for different but related approaches to the working tool itself and the tool’s communication are discussed. More general recommendations are made for the development of communication tools to support complex clinical processes.