Contemporary Approaches to the Discovery and Development of Broad-Spectrum Natural Product Prototypes for the Control of Coronaviruses.

The pressing need for SARS-CoV-2 controls has led to a reassessment of strategies to identify and develop natural product inhibitors of zoonotic, highly virulent, and rapidly emerging viruses. This review article addresses how contemporary approaches involving computational chemistry, natural product (NP) and protein databases, and mass spectrometry (MS) derived target-ligand interaction analysis can be utilized to expedite the interrogation of NP structures while minimizing the time and expense of extraction, purification, and screening in BioSafety Laboratories (BSL)3 laboratories. The unparalleled structural diversity and complexity of NPs is an extraordinary resource for the discovery and development of broad-spectrum inhibitors of viral genera, including Betacoronavirus, which contains MERS, SARS, SARS-CoV-2, and the common cold. There are two key technological advances that have created unique opportunities for the identification of NP prototypes with greater efficiency: (1) the application of structural databases for NPs and target proteins and (2) the application of modern MS techniques to assess protein-ligand interactions directly from NP extracts. These approaches, developed over years, now allow for the identification and isolation of unique antiviral ligands without the immediate need for BSL3 facilities. Overall, the goal is to improve the success rate of NP-based screening by focusing resources on source materials with a higher likelihood of success, while simultaneously providing opportunities for the discovery of novel ligands to selectively target proteins involved in viral infection.

Review: The effectiveness of Theraplay for children under 12 - a systematic literature review.

BACKGROUND: Theraplay is a relationship-focused model of treatment based on attachment theory involving both adult and child. The study aims to review the quality of Theraplay research and Theraplay's effectiveness for children aged 12 years and under with a range of presenting difficulties, to inform future practice and identify areas for further research. METHODS: A systematic literature search was conducted using PsycINFO, CINAHL, MEDLINE and Web of Science. Quantitative studies using Theraplay only as a treatment for children aged 12 years and under with any presenting difficulty were identified. Additional manual searching was conducted, including eligible studies' reference lists. Critical appraisal tools were used to provide a narrative synthesis of Theraplay's effectiveness and research quality. RESULTS: Only six eligible articles were identified, meaning there was a lack of rigorous evidence eligible to offer conclusions into Theraplay's effectiveness. The review highlighted the small evidence base, mixed quality research methodology and high levels of heterogeneity in how Theraplay is practiced and evaluated. Of the eligible studies, Theraplay was found promising in its effectiveness when used with internalising and externalising difficulties, dual diagnoses and developmental disabilities. CONCLUSIONS: Theraplay is regularly practiced across the world; however, the evidence base of rigorous research to inform Theraplay's effectiveness and mechanisms of change is lacking. Firm conclusions could not be offered, although Theraplay was shown to be promising intervention for some presentations. Further research into Theraplay's effectiveness and key mechanisms of change are recommended to enhance the quality and depth of Theraplay literature.

Review: Transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS): a meta-synthesis of parental and professional perspectives.

BACKGROUND: Transition between Child and Adolescent Mental Health Services (CAMHS) and Adult Mental Health Services (AMHS) can be stressful for the young person and family alike. Previous reviews have focused on specific aspects of transition or perspectives of young people, or have not used systematic approaches to data identification and analysis. The objective of this review was to develop the understanding of the transition between CAMHS and AMHS by systematically identifying and synthesising evidence regarding professionals' and parents/carers' perspectives. METHOD: A systematic search in July 2018 was conducted on Medline, PsycINFO and CINAHL. Google Scholar and references of selected articles were also searched. Papers were included if they presented empirical qualitative research in peer-reviewed journals with a primary focus on experiences of parents/carers and/or mental health professionals in relation to adolescents making the CAMHS-AMHS transition. Data were extracted from each full-text paper. The quality of included studies was appraised using an expanded Critical Appraisal Skills Programme (2018) tool, and studies' results were synthesised using meta-ethnography. RESULTS: Fourteen studies of variable quality were identified. Four main third-order constructs were developed through synthesis: (a) Service cultures; (b) Service resources and gaps; (c) Working relationships between the services; and (d) Leaving secure relationships for new ones. CONCLUSIONS: Professionals and parents experience adolescents' transition from nurturing and comprehensive CAMHS to more individualistic AMHS as having many barriers. There is desire for better preparation for transition between services and relationships, more joint working and better CAMHS-AMHS communication. AMHS service gaps exist, for example for those with neurodevelopmental conditions.

Exploring the Experiences of Parents Whose Child has Received a Diagnosis of Autistic Spectrum Disorder in Adulthood.

There is a growing trend of adult diagnosis of Autism Spectrum Disorder (ASD). Research has found that diagnosis can prompt a process of sense-making which may be disrupted by lack of post-diagnostic support. Given the continued involvement of many parents in supporting their adult son or daughter with ASD, it is vital to understand their experiences to meet their needs in adapting to the diagnosis. Eleven parents of recently diagnosed adults participated in semi-structured interviews which were analysed thematically. Findings demonstrate that the new knowledge of diagnosis facilitates changes in attributions, interactions and relationships, but can result in unmet emotional and relational support needs. Findings are relevant to those involved in adult diagnosis, and the provision of post-diagnostic support.

Mental health mobile application self-help for adolescents exhibiting psychological distress: A single case experimental design.

OBJECTIVES: The present demand for child and adolescent mental health services exceeds the capacity for service provision. Greater research is required to understand the utility of accessible self-help interventions, such as mobile apps. This study sought to investigate whether use of a mental health app, underpinned by CBT, led to changes in psychological distress amongst adolescents. Mechanisms of change were examined, specifically whether changes are attributable to cognitive strategies. DESIGN: This study utilised a multiple-baseline single-case experimental design, tracking variables across baseline and intervention phases. Surveys assessing participant experience were also administered. METHODS: Five participants with moderate-to-severe levels of psychological distress engaged with a CBT-based app over five weeks. Participants were recruited from both a well-being service and the general population. Supplementary weekly calls to participants offered clarification of app content. RESULTS: A small overall effect of the intervention of psychological distress was evident; however, outcomes were dependent on the analysis conducted. The intervention appeared to promote an increase in use of adaptive cognitive strategies but not negative thinking styles. The CBT app did not promote changes in participant well-being. Participant feedback highlighted practical challenges of utilising the app. CONCLUSIONS: The clinical benefits of app-based CBT were small, and a range of barriers to engagement were recognised. While further research is required, caution should be exercised in the interpretation of studies reporting on app effectiveness.

De Novo Self-Assembling Peptides Mediate the Conversion of Temozolomide and Delivery of a Model Drug into Glioblastoma Multiforme Cells.

Glioblastoma multiforme (GBM) is the most aggressive central nervous system tumor, and standard treatment, including surgical resection, radiation, and chemotherapy, has not significantly improved patient outcomes over the last 20 years. Temozolomide (TMZ), the prodrug most commonly used to treat GBM, must pass the blood-brain barrier and requires a basic pH to convert to its active form. Due to these barriers, less than 30% of orally delivered TMZ reaches the central nervous system and becomes bioactive. In this work, we have developed a novel biomaterial delivery system to convert TMZ to its active form and that shows promise for intracellular TMZ delivery. Self-assembling peptides were characterized under several different assembly conditions and evaluated for TMZ loading and conversion. Both solvent and method of assembly were found to affect the supramolecular and secondary structure of peptide assemblies. Additionally, as peptides degraded in phosphate-buffered saline, TMZ was rapidly converted to its active form. This work demonstrates that peptide-based drug delivery systems can effectively create a local stimulus during drug delivery while remaining biocompatible. This principle could be used in many future biomedical applications in addition to cancer treatment, such as wound healing and regenerative medicine.

Obstetric haemorrhage in the perioperative environment.

Massive haemorrhage remains a serious complication of childbirth despite advances in knowledge and surgical technique, with the number of mothers dying in the UK from haemorrhage appearing to be on the increase.

Compartment syndrome. The silent danger related to patient positioning and surgery.

Compartment syndrome affecting the limbs is a well-documented condition and there are cases where it has become evident following surgery undertaken with the patient in the Lloyd Davies position. This article explores the contributory factors and the devastating effect it can have on the patient, and questions whether we practise evidence-based care when patients are undergoing certain types of surgery. It also discusses factors related to abdominal compartment syndrome, a condition usually affecting the critically ill patient.