JACK trial protocol: a phase III multicentre cluster randomised controlled trial of a school-based relationship and sexuality education intervention focusing on young male perspectives.

Introduction: Teenage pregnancy remains a worldwide health concern which is an outcome of, and contributor to, health inequalities. The need for gender-aware interventions with a focus on males in addressing teenage pregnancy has been highlighted as a global health need by WHO and identified in systematic reviews of (relationship and sexuality education (RSE)). This study aims to test the effectiveness of an interactive film-based RSE intervention, which draws explicit attention to the role of males in preventing an unintended pregnancy by reducing unprotected heterosexual teenage sex among males and females under age 16 years.

Can Teenage Men Be Targeted to Prevent Teenage Pregnancy? A Feasibility Cluster Randomised Controlled Intervention Trial in Schools.

The World Health Organisation advocates a direct focus on adolescent men in reducing adolescent pregnancy; however, no trials have been conducted. This trial (ISRCTN11632300; NCT02092480) determines whether a novel Relationship and Sexuality Educational intervention, If I Were Jack, is acceptable and feasible to implement in mixed sex UK classrooms. The intervention is a teacher-delivered intervention that emphasises male alongside female  responsibility in preventing unintended pregnancies and is designed to prevent unprotected sex.

Hirschsprung's disease prevalence in Europe: a register based study.

Background: Hirschsprung's disease is a congenital gut motility disorder, characterised by the absence of the enteric ganglion cells along the distal gut. The aim of this study was to describe the epidemiology of Hirschsprung's disease, including additional congenital anomalies, total prevalence, trends, and association with maternal age.

Methods: Cases of Hirschsprung's disease delivered during 1980 to 2009 notified to 31 European Surveillance of Congenital Anomaly registers formed the population-based case-series.

European recommendations for primary prevention of congenital anomalies: a joined effort of EUROCAT and EUROPLAN projects to facilitate inclusion of this topic in the National Rare Disease Plans.

Congenital anomalies (CA) are the paradigm example of rare diseases liable to primary prevention actions due to the multifactorial etiology of many of them, involving a number of environmental factors together with genetic predispositions. Yet despite the preventive potential, lack of attention to an integrated preventive strategy has led to the prevalence of CA remaining relatively stable in recent decades. The 2 European projects, EUROCAT and EUROPLAN, have joined efforts to provide the first science-based and comprehensive set of recommendations for the primary prevention of CA in the European Union.

Microneedle mediated intradermal delivery of adjuvanted recombinant HIV-1 CN54gp140 effectively primes mucosal boost inoculations.

Dissolving polymeric microneedle arrays formulated to contain recombinant CN54 HIVgp140 and the TLR4 agonist adjuvant MPLA were assessed for their ability to elicit antigen-specific immunity. Using this novel microneedle system we successfully primed antigen-specific responses that were further boosted by an intranasal mucosal inoculation to elicit significant antigen-specific immunity. This prime-boost modality generated similar serum and mucosal gp140-specific IgG levels to the adjuvanted and systemic subcutaneous inoculations.

Characterisation of protein stability in rod-insert vaginal rings.

A major goal in vaccine development is elimination of the 'cold chain', the transport and storage system for maintenance and distribution of the vaccine product. This is particularly pertinent to liquid formulation of vaccines. We have previously described the rod-insert vaginal ring (RiR) device, comprising an elastomeric body into which are inserted lyophilised, rod-shaped, solid drug dosage forms, and having potential for sustained mucosal delivery of biomacromolecules, such as HIV envelope protein-based vaccine candidates.

Molecular investigations into vaginal immunization with HIV gp41 antigenic construct H4A in a quick release solid dosage form.

A robust vaginal immune response is considered essential for an effective prophylactic vaccine that prevents transmission of HIV and other sexually acquired diseases. Considerable attention has recently focused on the potential of vaginally administered vaccines as a means to induce such local immunity. However, the potential for vaccination at this site remains in doubt as the vaginal mucosa is generally considered to have low immune inductive potential.

Development of liposome gel based formulations for intravaginal delivery of the recombinant HIV-1 envelope protein CN54gp140.

Mucosally-administered vaccine strategies are widely investigated as a promising means of preventing HIV infection. This study describes the development of liposomal gel formulations, and novel lyophilised variants, comprising HIV-1 envelope glycoprotein, CN54gp140, encapsulated within neutral, positively charged or negatively charged liposomes. The CN54gp140 liposomes were evaluated for mean vesicle diameter, polydispersity, morphology, zeta potential and antigen encapsulation efficiency before being incorporated into hydroxyethyl cellulose (HEC) aqueous gel and subsequently lyophilised to produce a rod-shaped solid dosage form for practical vaginal application.

Measurements of immune responses for establishing correlates of vaccine protection against HIV.

Well-defined correlates of protective immunity are an essential component of rational vaccine development. Despite years of basic science and three HIV vaccine efficacy trials, correlates of immunological protection from HIV infection remain undefined. In December 2010, a meeting of scientists engaged in basic and translational work toward developing HIV-1 vaccines was convened.

Intravaginal immunization using the recombinant HIV-1 clade-C trimeric envelope glycoprotein CN54gp140 formulated within lyophilized solid dosage forms.

Vaccine-mediated prevention of primary HIV-1 infection at the heterosexual mucosal portal of entry may be facilitated by highly optimised formulations or drug delivery devices for intravaginal (i.vag) immunization. Previously we described hydroxyethylcellulose (HEC)-based rheologically structured gel vehicles (RSVs) for vaginal immunization of an HIV-1 vaccine candidate, a soluble recombinant trimeric HIV-1 clade-C envelope glycoprotein designated CN54gp140.

Sustained release of proteins from a modified vaginal ring device.

A new vaginal ring technology, the insert vaginal ring (InVR), is presented. The InVR overcomes the current shortfall of conventional vaginal rings (VRs) that are generally ineffectual for the delivery of hydrophilic and/or macromolecular actives, including peptides, proteins and antibodies, due to their poor permeation characteristics in the hydrophobic polymeric elastomers from which VRs are usually fabricated. Release of the model protein BSA from a variety of insert matrices for the InVR is demonstrated, including modified silicone rods, directly compressed tablets and lyophilised gels, which collectively provided controlled release profiles from several hours to beyond 4 weeks.

Vaginal delivery of the recombinant HIV-1 clade-C trimeric gp140 envelope protein CN54gp140 within novel rheologically structured vehicles elicits specific immune responses.

Rheologically structured vehicle (RSV) gels were developed as delivery systems for vaginal mucosal vaccination with an HIV-1 envelope glycoprotein (CN54gp140). RSVs comprised a mucoadhesive matrix-forming and vaginal fluid absorbing polymer. The mucoadhesive and rheological properties of the RSVs were evaluated in vitro, and the distribution, antigenicity and release of CN54gp140 were analysed by ELISA.

Characterization of the rheological, mucoadhesive, and drug release properties of highly structured gel platforms for intravaginal drug delivery.

This investigation describes the formulation and characterization of rheologically structured vehicles (RSVs) designed for improved drug delivery to the vagina. Interactive, multicomponent, polymeric platforms were manufactured containing hydroxyethylcellulose (HEC, 5% w/w) polyvinylpyrrolidone (PVP, 4% w/w), Pluronic (PL, 0 or 10% w/w), and either polycarbophil (PC, 3% w/w) or poly(methylvinylether-co-maleic anhydride) (Gantrez S97, 3% w/w) as a mucoadhesive agent. The rheological (torsional and dynamic), mechanical (compressional), and mucoadhesive properties were characterized and shown to be dependent upon the mucoadhesive agent used and the inclusion/exclusion of PL.

Development of a monoclonal antibody binding okadaic acid and dinophysistoxins-1, -2 in proportion to their toxicity equivalence factors.

Okadaic acid (OA) and structurally related toxins dinophysistoxin-1 (DTX-1), and DTX-2, are lipophilic marine biotoxins. The current reference method for the analysis of these toxins is the mouse bioassay (MBA). This method is under increasing criticism both from an ethical point of view and because of its limited sensitivity and specificity.