Implementation of routine outcome measurement in child and adolescent mental health services in the United Kingdom: a critical perspective

The aim of this commentary is to provide an overview of clinical outcome measures that are currently recommended for use in UK Child and Adolescent Mental Health Services (CAMHS), focusing on measures that are applicable across a wide range of conditions with established validity and reliability, or innovative in their design. We also provide an overview of the barriers and drivers to the use of Routine Outcome Measurement (ROM) in clinical practice

Deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes

<p>Background: Filarial nematodes are tissue-dwelling parasites that can be killed by Th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. As a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.</p> <p>Methodology and Principal Findings: We immunised mice with DNA plasmids expressing functionally-inactivated forms of two immunomodulatory molecules expressed by the filarial parasite Litomosoides sigmodontis: the abundant larval transcript-1 (LsALT) and cysteine protease inhibitor-2 (LsCPI). The mutant proteins enhanced antibody and cytokine responses to live parasite challenge, and led to more leukocyte recruitment to the site of infection than their native forms. The immune response was further enhanced when the antigens were targeted to dendritic cells using a single chain Fv-αDEC205 antibody and co-administered with plasmids that enhance T helper 2 immunity (IL-4) and antigen-presenting cell recruitment (Flt3L, MIP-1α). Mice immunised simultaneously against the mutated forms of LsALT and LsCPI eliminated adult parasites faster and consistently reduced peripheral microfilaraemia. A multifactorial analysis of the immune response revealed that protection was strongly correlated with the production of parasite-specific IgG1 and with the numbers of leukocytes present at the site of infection.</p> <p>Conclusions: We have developed a successful strategy for DNA vaccination against a nematode infection that specifically targets parasite-driven immunosuppression while simultaneously enhancing Th2 immune responses and parasite antigen presentation by dendritic cells.</p&gt

Helminth Genomics: The Implications for Human Health

More than two billion people (one-third of humanity) are infected with parasitic roundworms or flatworms, collectively known as helminth parasites. These infections cause diseases that are responsible for enormous levels of morbidity and mortality, delays in the physical development of children, loss of productivity among the workforce, and maintenance of poverty. Genomes of the major helminth species that affect humans, and many others of agricultural and veterinary significance, are now the subject of intensive genome sequencing and annotation. Draft genome sequences of the filarial worm Brugia malayi and two of the human schistosomes, Schistosoma japonicum and S. mansoni, are now available, among others. These genome data will provide the basis for a comprehensive understanding of the molecular mechanisms involved in helminth nutrition and metabolism, host-dependent development and maturation, immune evasion, and evolution. They are likely also to predict new potential vaccine candidates and drug targets. In this review, we present an overview of these efforts and emphasize the potential impact and importance of these new findings

Effect of treating Schistosoma haematobium infection on Plasmodium falciparum-specific antibody responses

<p>Abstract</p> <p>Background</p> <p>The overlapping geographical and socio-economic distribution of malaria and helminth infection has led to several studies investigating the immunological and pathological interactions of these parasites. This study focuses on the effect of treating schistosome infections on natural human immune responses directed against plasmodia merozoite surface proteins MSP-1 (DPKMWR, MSP1₁₉), and MSP-2 (CH150 and Dd2) which are potential vaccine candidates as well as crude malaria (schizont) and schistosome (whole worm homogenate) proteins.</p> <p>Methods</p> <p>IgG1 and IgG3 antibody responses directed against <it>Schistosoma haematobium </it>crude adult worm antigen (WWH) and <it>Plasmodium falciparum </it>antigens (merozoite surface proteins 1/2 and schizont extract), were measured by enzyme linked immunosorbent assay (ELISA) in 117 Zimbabweans (6–18 years old) exposed to <it>S. haematobium </it>and <it>P. falciparum </it>infection. These responses were measured before and after anti-helminth treatment with praziquantel to determine the effects of treatment on anti-plasmodial/schistosome responses.</p> <p>Results</p> <p>There were no significant associations between antibody responses (IgG1/IgG3) directed against <it>P. falciparum </it>and schistosomes before treatment. Six weeks after schistosome treatment there were significant changes in levels of IgG1 directed against schistosome crude antigens, plasmodia crude antigens, MSP-1₁₉, MSP-2 (Dd2), and in IgG3 directed against MSP-1₁₉. However, only changes in anti-schistosome IgG1 were attributable to the anti-helminth treatment.</p> <p>Conclusion</p> <p>There was no association between anti-<it>P. falciparum </it>and <it>S. haematobium antibody </it>responses in this population and <it>a</it>nti-helminth treatment affected only anti-schistosome responses and not responses against plasmodia crude antigens or MSP-1 and -2 vaccine candidates.</p

Identification of recruitment and retention strategies for rehabilitation professionals in Ontario, Canada: results from expert panels

<p>Abstract</p> <p>Background</p> <p>Demand for rehabilitation services is expected to increase due to factors such as an aging population, workforce pressures, rise in chronic and complex multi-system disorders, advances in technology, and changes in interprofessional health service delivery models. However, health human resource (HHR) strategies for Canadian rehabilitation professionals are lagging behind other professional groups such as physicians and nurses. The objectives of this study were: 1) to identify recruitment and retention strategies of rehabilitation professionals including occupational therapists, physical therapists and speech language pathologists from the literature; and 2) to investigate both the importance and feasibility of the identified strategies using expert panels amongst HHR and education experts.</p> <p>Methods</p> <p>A review of the literature was conducted to identify recruitment and retention strategies for rehabilitation professionals. Two expert panels, one on <it>Recruitment and Retention </it>and the other on <it>Education </it>were convened to determine the importance and feasibility of the identified strategies. A modified-delphi process was used to gain consensus and to rate the identified strategies along these two dimensions.</p> <p>Results</p> <p>A total of 34 strategies were identified by the <it>Recruitment and Retention </it>and <it>Education </it>expert panels as being important and feasible for the development of a HHR plan for recruitment and retention of rehabilitation professionals. Seven were categorized under the <it>Quality of Worklife and Work Environment </it>theme, another seven in <it>Financial Incentives and Marketing</it>, two in <it>Workload and Skill Mix</it>, thirteen in <it>Professional Development </it>and five in <it>Education and Training</it>.</p> <p>Conclusion</p> <p>Based on the results from the expert panels, the three major areas of focus for HHR planning in the rehabilitation sector should include strategies addressing <it>Quality of Worklife and Work Environment</it>, <it>Financial Incentives and Marketing </it>and <it>Professional Development</it>.</p

A randomised controlled feasibility trial for an educational school-based mental health intervention: study protocol

Background: With the burden of mental illness estimated to be costing the English economy alone around £22.5 billion a year [1], coupled with growing evidence that many mental disorders have their origins in adolescence, there is increasing pressure for schools to address the emotional well-being of their students, alongside the stigma and discrimination of mental illness. A number of prior educational interventions have been developed and evaluated for this purpose, but inconsistency of findings, reporting standards, and methodologies have led the majority of reviewers to conclude that the evidence for the efficacy of these programmes remains inconclusive. Methods/Design: A cluster randomised controlled trial design has been employed to enable a feasibility study of 'SchoolSpace', an intervention in 7 UK secondary schools addressing stigma of mental illness, mental health literacy, and promotion of mental health. A central aspect of the intervention involves students in the experimental condition interacting with a young person with lived experience of mental illness, a stigma reducing technique designed to facilitate students' engagement in the project. The primary outcome is the level of stigma related to mental illness. Secondary outcomes include mental health literacy, resilience to mental illness, and emotional well-being. Outcomes will be measured pre and post intervention, as well as at 6 month follow-up. Discussion: The proposed intervention presents the potential for increased engagement due to its combination of education and contact with a young person with lived experience of mental illness. Contact as a technique to reduce discrimination has been evaluated previously in research with adults, but has been employed in only a minority of research trials investigating the impact on youth. Prior to this study, the effect of contact on mental health literacy, resilience, and emotional well-being has not been evaluated to the authors' knowledge. If efficacious the intervention could provide a reliable and cost-effective method to reduce stigma in young people, whilst increasing mental health literacy, and emotional well-being. Trial registration: ISRCTN: ISRCTN0740602

Imaging aspects of cardiovascular disease at the cell and molecular level

Cell and molecular imaging has a long and distinguished history. Erythrocytes were visualized microscopically by van Leeuwenhoek in 1674, and microscope technology has evolved mightily since the first single-lens instruments, and now incorporates many types that do not use photons of light for image formation. The combination of these instruments with preparations stained with histochemical and immunohistochemical markers has revolutionized imaging by allowing the biochemical identification of components at subcellular resolution. The field of cardiovascular disease has benefited greatly from these advances for the characterization of disease etiologies. In this review, we will highlight and summarize the use of microscopy imaging systems, including light microscopy, electron microscopy, confocal scanning laser microscopy, laser scanning cytometry, laser microdissection, and atomic force microscopy in conjunction with a variety of histochemical techniques in studies aimed at understanding mechanisms underlying cardiovascular diseases at the cell and molecular level

Presynaptic External Calcium Signaling Involves the Calcium-Sensing Receptor in Neocortical Nerve Terminals

Nerve terminal invasion by an axonal spike activates voltage-gated channels, triggering calcium entry, vesicle fusion, and release of neurotransmitter. Ion channels activated at the terminal shape the presynaptic spike and so regulate the magnitude and duration of calcium entry. Consequently characterization of the functional properties of ion channels at nerve terminals is crucial to understand the regulation of transmitter release. Direct recordings from small neocortical nerve terminals have revealed that external [Ca(2+)] ([Ca(2+)](o)) indirectly regulates a non-selective cation channel (NSCC) in neocortical nerve terminals via an unknown [Ca(2+)](o) sensor. Here, we identify the first component in a presynaptic calcium signaling pathway.By combining genetic and pharmacological approaches with direct patch-clamp recordings from small acutely isolated neocortical nerve terminals we identify the extracellular calcium sensor. Our results show that the calcium-sensing receptor (CaSR), a previously identified G-protein coupled receptor that is the mainstay in serum calcium homeostasis, is the extracellular calcium sensor in these acutely dissociated nerve terminals. The NSCC currents from reduced function mutant CaSR mice were less sensitive to changes in [Ca(2+)](o) than wild-type. Calindol, an allosteric CaSR agonist, reduced NSCC currents in direct terminal recordings in a dose-dependent and reversible manner. In contrast, glutamate and GABA did not affect the NSCC currents.Our experiments identify CaSR as the first component in the [Ca(2+)](o) sensor-NSCC signaling pathway in neocortical terminals. Decreases in [Ca(2+)](o) will depress synaptic transmission because of the exquisite sensitivity of transmitter release to [Ca(2+)](o) following its entry via voltage-activated Ca(2+) channels. CaSR may detects such falls in [Ca(2+)](o) and increase action potential duration by increasing NSCC activity, thereby attenuating the impact of decreases in [Ca(2+)](o) on release probability. CaSR is positioned to detect the dynamic changes of [Ca(2+)](o) and provide presynaptic feedback that will alter brain excitability

Cathelicidin-like Helminth Defence Molecules (HDMs) Absence of Cytotoxic, Anti-microbial and Anti-protozoan Activities Imply a Specific Adaptation to Immune Modulation

Host defence peptides (HDPs) are expressed throughout the animal and plant kingdoms. They have multifunctional roles in the defence against infectious agents of mammals, possessing both bactericidal and immune-modulatory activities. We have identified a novel family of molecules secreted by helminth parasites (helminth defence molecules; HDMs) that exhibit similar structural and biochemical characteristics to the HDPs. Here, we have analyzed the functional activities of four HDMs derived from Schistosoma mansoni and Fasciola hepatica and compared them to human, mouse, bovine and sheep HDPs. Unlike the mammalian HDPs the helminth-derived HDMs show no antimicrobial activity and are non-cytotoxic to mammalian cells (macrophages and red blood cells). However, both the mammalian- and helminth-derived peptides suppress the activation of macrophages by microbial stimuli and alter the response of B cells to cytokine stimulation. Therefore, we hypothesise that HDMs represent a novel family of HDPs that evolved to regulate the immune responses of their mammalian hosts by retaining potent immune modulatory properties without causing deleterious cytotoxic effects. © 2013 Thivierge et al