Aticaprant: (a κ-opioid receptor antagonist) for major depressive disorder

INTRODUCTION: Major depression is a common, disabling mental health condition associated with the highest disease burden for any neuropsychiatric disorder worldwide, according to the WHO. Due to the imperfect efficacy and tolerability profiles of existing treatments, investigational compounds in novel treatment classes are needed. Opioid-receptor antagonists are a potential new class of treatments currently under investigation.AREAS COVERED: Major depressive disorder is first overviewed. Existing treatments, both their mechanisms of action and their place within the antidepressant space, are discussed herein. Then, the profile of Aticaprant and the wider context of kappa-opioid antagonism for depression are discussed in focus.EXPERT OPINION: Early evidence indicates that Aticaprant may possess desirable pharmacodynamic and pharmacokinetic properties. A lack of convincing efficacy data at the time of writing precludes any definitive statement on its potential as an antidepressant.</p

Relative growth and morphological variation in the skull of Aelurognathus (therapsida: gorgonopsia)

Gorgonopsia represent a group of specialised carnivorous therapsids that filled the role of apex predator during the Late Permian of Gondwana. Skull size in the Gorgonopsia ranges from that of a cat, to larger than any extant, terrestrial predator. Despite this degree of size variation, the observed morphological variation in the skull is relatively conservative. This study set out to better understand the extent of size and morphological variation among species attributed to the South African genus, Aelurognathus, with the aim of possibly refining the taxonomy of the genus. Aelurognathus was chosen, as it contains the largest number of described specimens (16) of any of the Rubidgeinid genera. Previous work has led to numerous revisions to the taxonomic assignment of each specimen, at both the generic and specific levels. All available specimens were studied and morphological differences at both the intraspecific and interspecific levels noted. Morphological variations allowed for the division of the six previously recognised species into three morphotaxa based on the character state of the preparietal and the extent of contact by the frontal on the supraorbital margin. Both characters have been shown to vary among individuals of extant taxa. Taking this into account, a hypothesis that all 16 specimens represent a single taxon, exhibiting a high degree of morphological variation, was tested using allometric techniques. Linear measurements of the skull were selected, such that variation in skull size and shape was accounted for in all dimensions. Results of the bivariate analyses showed a high level of correlation with the bivariate fitted lines plotted, supporting the single taxon hypothesis. While Aelurognathus has previously been divided into six species, using morphological characters, this study has shown that the characters used in the past have been unreliable. As such it is proposed that all species attributed to Aelurognathus be synonymised with the type, Aelurognathus tigriceps

Falling through the gaps: exploring the role of integrated commissioning in improving transition from children’s to adults' services for young people with long-term health conditions in England

Objectives: To explore the role of integrated commissioning in improving the transition of young people with longterm conditions from child to adult services. We aimed to identify organizational and policy gaps around transition services and provide recommendations for integrated commissioning practice. Methods: Semi-structured in-depth interviews were conducted with two groups of participants: (1) twenty-four stakeholders involved in the commissioning and provision of transition services for young people with long-term conditions in two regions in England; (2) five professionals with national roles in relation to planning for transition. Transcripts were interrogated using thematic analysis. Results: There is little evidence of integrated commissioning for transitional care for young people with long-term conditions. Commissioners perceive there to be a lack of national and local policy to guide integrated commissioning for transitional care; and limited resources for transition. Furthermore, commissioning organizations responsible for transition have different cultures, funding arrangements and related practices which make inter- and intra-agency co-ordination and cross-boundary continuity of care difficult to achieve. Conclusions: Integrated commissioning may be an effective way to achieve successful transitional care for young people with long-term health conditions. However, this innovative relational approach to commissioning requires a national steer together with recognition of common values and joint ownership between relevant stakeholders

Outcome after Mild Traumatic Brain Injury: the Interplay of Concussion and Post-traumatic Stress Symptoms

Background and aims The provenance of post-concussion symptoms (PCS) and post-traumatic stress (PTSD) after mild traumatic brain injury (mTBI) is controversial. This thesis investigated factors influencing these two conditions separately, as well as the interplay between PCS and PTSD, in individuals with mTBI and a control sample without mTBI (orthopaedic injuries). Method Consecutive adult attendees of an Emergency Department with mTBI or orthopaedic injury were prospectively recruited and completed the Rivermead Post-concussion Questionnaire (RPQ) and Trauma Screening Questionnaire (TSQ) for PTSD at two weeks (T1) and three months (T2) post-injury. The sample at T1 consisted of 34 with complicated mTBI, 76 with uncomplicated mTBI and 47 with orthopaedic injury, and 18 with complicated mTBI, 43 with uncomplicated mTBI and 33 orthopaedic controls at T2. Results Although there were no differences in overall PCS symptomology between groups, a subset of PCS symptoms (headaches, dizziness and nausea) was found to be specific to mTBI at both time points. These symptoms are proposed to have a neurological basis, as opposed to a psychological basis. PTSD interacted with PCS, particularly in mTBI, such that PTSD was associated with greater “neurogenic” and “psychogenic” symptomology in this group, but only a moderate increase in psychogenic symptoms for controls. A model of the influence of PTSD on PCS is presented. PTSD was influenced by poor memory quality for the traumatic event and attribution of blame to others, but not by mTBI. Discussion and conclusions Though mTBI may set the scene for at least neurogenic symptoms of PCS to occur, psychological mechanisms, particularly PTSD, have a significant role in the persistence of PCS. Our findings suggest the need for a clear story and sense of meaning for a traumatic event for good recovery from PTSD. Taken together, the results suggest that psychological interventions, particularly aimed at PTSD, may be most effective after mTBI