Development of an efficient reproducible cell-cell transmission assay for rapid quantification of SARS-CoV-2 spike interaction with hACE2.

Efficient quantitative assays for measurement of viral replication and infectivity are indispensable for future endeavors to develop prophylactic or therapeutic antiviral drugs or vaccines against SARS-CoV-2. We developed a SARS-CoV-2 cell-cell transmission assay that provides a rapid and quantitative readout to assess SARS-CoV-2 spike hACE2 interaction in the absence of pseudotyped particles or live virus. We established two well-behaved stable cell lines, which demonstrated a remarkable correlation with standard cell-free viral pseudotyping for inhibition by convalescent sera, small-molecule drugs, and murine anti-spike monoclonal antibodies.

A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery.

Cell penetrating peptides (CPPs) offer great potential to deliver therapeutic molecules to previously inaccessible intracellular targets. However, many CPPs are inefficient and often leave their attached cargo stranded in the cell's endosome. We report a versatile platform for the isolation of peptides delivering a wide range of cargos into the cytoplasm of cells.

A pragmatic randomised controlled trial and economic evaluation of family therapy versus treatment as usual for young people seen after second or subsequent episodes of self-harm: the Self-Harm Intervention - Family Therapy (SHIFT) trial.

Background: Self-harm in adolescents is common and repetition rates high. There is limited evidence of the effectiveness of interventions to reduce self-harm.

Objectives: To assess the clinical effectiveness and cost-effectiveness of family therapy (FT) compared with treatment as usual (TAU).

Effectiveness of systemic family therapy versus treatment as usual for young people after self-harm: a pragmatic, phase 3, multicentre, randomised controlled trial.

Background: Self-harm in adolescents is common and repetition occurs in a high proportion of these cases. Scarce evidence exists for effectiveness of interventions to reduce self-harm.

Methods: This pragmatic, multicentre, randomised, controlled trial of family therapy versus treatment as usual was done at 40 UK Child and Adolescent Mental Health Services (CAMHS) centres.

High Resolution Phonon-assisted Quasi-resonance Fluorescence Spectroscopy.

High resolution optical spectroscopy methods are demanding in terms of either technology, equipment, complexity, time or a combination of these. Here we demonstrate an optical spectroscopy method that is capable of resolving spectral features beyond that of the spin fine structure and homogeneous linewidth of single quantum dots (QDs) using a standard, easy-to-use spectrometer setup. This method incorporates both laser and photoluminescence spectroscopy, combining the advantage of laser line-width limited resolution with multi-channel photoluminescence detection.

GFP-complementation assay to detect functional CPP and protein delivery into living cells.

Efficient cargo uptake is essential for cell-penetrating peptide (CPP) therapeutics, which deliver widely diverse cargoes by exploiting natural cell processes to penetrate the cell's membranes. Yet most current CPP activity assays are hampered by limitations in assessing uptake, including confounding effects of conjugated fluorophores or ligands, indirect read-outs requiring secondary processing, and difficulty in discriminating internalization from endosomally trapped cargo. Split-complementation Endosomal Escape (SEE) provides the first direct assay visualizing true cytoplasmic-delivery of proteins at biologically relevant concentrations.

Optophononics with coupled quantum dots.

Modern technology is founded on the intimate understanding of how to utilize and control electrons. Next to electrons, nature uses phonons, quantized vibrations of an elastic structure, to carry energy, momentum and even information through solids. Phonons permeate the crystalline components of modern technology, yet in terms of technological utilization phonons are far from being on par with electrons.

Design, structure-activity relationship and in vivo efficacy of piperazine analogues of fenarimol as inhibitors of Trypanosoma cruzi.

A scaffold hopping exercise undertaken to expand the structural diversity of the fenarimol series of anti-Trypanosoma cruzi (T. cruzi) compounds led to preparation of simple 1-[phenyl(pyridin-3-yl)methyl]piperazinyl analogues of fenarimol which were investigated for their ability to inhibit T. cruzi in vitro in a whole organism assay.

Analogues of fenarimol are potent inhibitors of Trypanosoma cruzi and are efficacious in a murine model of Chagas disease.

We report the discovery of nontoxic fungicide fenarimol (1) as an inhibitor of Trypanosoma cruzi ( T. cruzi ), the causative agent of Chagas disease, and the results of structure-activity investigations leading to potent analogues with low nM IC(50)s in a T. cruzi whole cell in vitro assay.

Group therapy for adolescents with repeated self harm: randomised controlled trial with economic evaluation.

Objective: To examine the effectiveness and cost-effectiveness of group therapy for self harm in young people.

Design: Two arm, single (assessor) blinded parallel randomised allocation trial of a group therapy intervention in addition to routine care, compared with routine care alone. Randomisation was by minimisation controlling for baseline frequency of self harm, presence of conduct disorder, depressive disorder, and severity of psychosocial stress.

The health and well-being of neglected, abused and exploited children: the Kyiv Street Children Project.

Objective: To report on the backgrounds and physical and emotional well-being of street children using two street shelters in Kyiv, Ukraine. This study is important because personal accounts of street children may highlight individual or family factors that are associated with vulnerability for and risk of poor mental health, and these could have serious repercussions for the future. This study also poses a challenge to research because street children are a highly elusive population that services find hard to reach.

Early adult outcomes of adolescents who deliberately poisoned themselves.

Objective: To describe the early adult psychopathological and social outcomes of adolescents who deliberately poisoned themselves.

Method: Prospective cohort study with a 6-year follow-up of 132 of 158 (84%) adolescents who, between ages 11 and 16 years, had taken part in a randomized trial of a brief family intervention after deliberate self-poisoning. Comparisons were made with a sample of participants matched for age, gender, and childhood social class.

Social Services and CAMHS: A National Survey.

Background:   Links between Social Service Departments (SSDs) and CAMHS are explored and described through a national survey and a number of site visits.

Method:   Data were collected via (1) a national questionnaire survey yielding a response rate of 75%, and (2) pre-selected site visits to seven SSDs.

Results:   Additional to existing CAMHS assessment and treatment provision to SSDs, there is increasing outreach consultation and support, some provided through primary mental health workers and dedicated clinical psychology sessions.

A Home and School Support Project for Children Excluded from Primary and First Year Secondary School.

Background:   In the last 10 years the problem of exclusion has reached a crisis point. Research suggests that exclusion is a complex phenomenon that needs involvement from all the involved services such as Health, Education and Social Services.

Method:   One hundred and twenty-four pupils, aged 4-12 years who, through school and social exclusion, were at risk of developing more serious mental health difficulties, were randomly allocated to standard care (n = 62) or standard care plus the new intervention (n = 62).

A step too far? Randomized trial of cognitive-behaviour therapy delivered by social workers to depressed adolescents.

Objective: To test the hypothesis that depressed adolescents given brief cognitive behaviour therapy by trained social workers will be less depressed after this treatment than depressed adolescents who have routine care from their social workers.

Method: Open study, two randomized parallel groups. 86 social workers were randomized to training in brief CBT or delayed training by remote telephone randomization.

Developing needs led child and adolescent mental health services: issues and prospects.

For many years mental health services for children have been developed incrementally with little attention to the needs of the local population. However, over the past decade there have been attempts to develop more rational ways of planning child mental health services. This paper describes the information required to develop a needs-led child mental health service and, within that context, discusses how priorities should be set.

Cost-effectiveness analysis of a home-based social work intervention for children and adolescents who have deliberately poisoned themselves. Results of a randomised controlled trial.

Background: Little evidence exists regarding the effectiveness or cost-effectiveness of alternative treatment services in the field of child and adolescent psychiatry.

Aims: To assess the cost-effectiveness of a home-based social work intervention for young people who have deliberately poisoned themselves.

Method: Children aged < or = 16 years, referred to child mental health teams with a diagnosis of deliberate self-poisoning were randomly allocated to either routine care (n = 77) or routine care plus the social work intervention (n = 85).

Correlates and short-term course of self-poisoning in adolescents.

Background: The features of adolescents who had taken an overdose were assessed to determine the focus for a treatment trial.

Method: Overdose cases were compared with psychiatric and community controls who had not taken an overdose in respect of mental disorders and family background.

Results: Overdose cases had high rates of major depression, but most of them recovered from depression within six weeks of the overdose.