Child sexual exploitation. An analysis of serious case reviews in England: poor communication, incorrect assumptions and adolescent neglect.

BACKGROUND: Child sexual exploitation (CSE) has evolved from being a largely concealed and unrecognised form of child abuse to being the subject of substantial political and public attention. The purpose of this research was to explore health professionals' role in detection and prevention. METHODS: A systematic thematic analysis and synthesis of serious case review (SCR) reports of CSE in England using a socioecological theoretical framework was undertaken. RESULTS: Themes identified included health professionals' lack of understanding of CSE, limited knowledge of the UK law, reluctance to apply relevant policies, and lack of appropriate action. Suboptimal communication with the child, between agencies and with families, lack of understanding of the young person's context, their vulnerabilities and their continued needs for care and protection were also important. CONCLUSIONS: This is the first time, to our knowledge, that an analysis and synthesis of all SCRs related to CSE in England has been conducted. The potential to recognise young people vulnerable to CSE is essential for public health prevention and intervention. Acknowledging that the SCRs represent the worst case scenario; nevertheless, this research highlighted the multi-factorial and complex nature of CSE and identified factors that require system-level awareness, training and intervention.

Acculturation, resilience, and the mental health of migrant youth: a cross-country comparative study.

OBJECTIVES: Using data from an international collaborative research project on youth resilience in the context of migration, this study aims to investigate how different acculturation patterns (i.e. integration, assimilation, separation and marginalization) influence the mental health of migrant youth, and whether resilience might function as a mediator in the association between acculturation and mental health. STUDY DESIGN: A cross-sectional pilot study conducted in six countries employing a common survey questionnaire. METHODS: The study sample was 194 youths aged 10-17 years (median = 13.6) from six countries (Australia, Canada, China, New Zealand, South Africa, and United Kingdom) and included cross-border and internal migrants. Mental health and well-being was measured by the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS). Resilience was measured by the Child and Youth Resilience Measure-28 (CYRM-28). Acculturation was assessed using the Acculturation, Habits, and Interests Multicultural Scale for Adolescents (AHIMSA). Multivariate regression and path analysis were performed to examine the hypothesized mediation model. RESULTS: Resilience scores correlated strongly with mental health and well-being. Acculturation exerted no significant direct effects on the mental health of migrant youths. Nevertheless, compared to youths who were integration-oriented, assimilation-oriented youths tended to exhibit lower levels of resilience, resulting in poorer mental health. Compared to youths from other countries, migrant youths from China also reported lower levels of resilience, which led to poorer mental health outcome. CONCLUSION: Acculturation plays a significant role in the mental health of migrant youth, with different acculturative orientations exhibiting different influences through the mediation effect of resilience. Fostering resilience and facilitating integration-oriented acculturation are recommended public health strategies for migrant youth.

Systematic review of the evidence for sustained efficacy of dietary interventions for reducing appetite or energy intake.

We assessed evidence for changes in efficacy of food-based interventions aimed at reducing appetite or energy intake (EI), and whether this could be used to provide guidance on trial design. A systematic search identified randomized controlled trials testing sustained efficacy of diets, foods, supplements or food ingredients on appetite and/or EI. Trials had to include sufficient exposure duration (≥3 days) with appetite and/or EI measured after both acute and repeated exposures. Twenty-six trials met the inclusion criteria and reported data allowing for assessment of the acute and chronic effects of interventions. Most (21/26) measured appetite outcomes and over half (14/26) had objective measures of EI. A significant acute effect of the intervention was retained in 10 of 12 trials for appetite outcomes, and six of nine studies for EI. Initial effects were most likely retained where these were more robust and studies adequately powered. Where the initial, acute effect was not statistically significant, a significant effect was later observed in only two of nine studies for appetite and none of five studies for EI. Maintenance of intervention effects on appetite or EI needs to be confirmed but seems likely where acute effects are robust and replicable in adequately powered studies.

Structural violence and marginalisation. The sexual and reproductive health experiences of separated young people on the move. A rapid review with relevance to the European humanitarian crisis.

OBJECTIVE: To explore the main sexual and reproductive health (SRH) issues for separated young migrants. STUDY DESIGN: We conducted a rapid review. METHODS: The search for articles published between 2000 and June 2017 including peer-reviewed and 'grey' published literature from a range of databases including MEDLINE, AMED, Embase, ASSIA, Scopus, Web of Science and websites of international organisations (Missing Children Alliance, United Nations Population Fund (UNFPA), World Health Organization (WHO), United Nations Human Rights Council (UNHRC), Human Rights Watch, United Nations Children's Fund (UNICEF) and FBX Centre for Health and Human Rights) took place over 4 months. Themes emerging from the included studies and articles were synthesised. RESULTS: We found 44 articles from a range of countries of which 64% were peer-reviewed and 36% were from 'grey' literature. Structural violence and marginalisation were the key analytical themes that emerged and included young people's vulnerability to violence, unmet knowledge and service needs, barriers and stigma and poor SRH outcomes. CONCLUSIONS: This is the first known review to summarise the key SRH issues for separated young migrants. As Europe hosts the greatest number of separated young people in recent history, their unique SRH concerns risk being overlooked. Public health practitioners and policy makers are encouraged to challenge the gaps that exist in their services.

Intimate partner violence in early adolescence:the role of gender; socioeconomic factors and the school

BACKGROUND:Intimate partner violence (IPV) among adolescents is common worldwide; but our understanding of perpetration; gender differences and the role of social-ecological factors remains limited.OBJECTIVES:To explore the prevalence of physical and sexual IPV perpetration and victimisation by gender; and associated risk and protective factors.METHODS:Young adolescents (N=2 839) from 41 randomly selected public high schools in the Western Cape region of South Africa (SA); participating in the PREPARE study; completed a self-administered questionnaire. RESULTS:The participants' mean age was 13.65 years (standard deviation 1.01); with 19.1% (541/2 839) reporting being victims/survivors of IPV and 13.0% (370/2 839) reporting perpetrating IPV. Girls were less likely to report being a victim/survivor of physical IPV (odds ratio (OR) 0.72; 95% confidence interval (CI) 0.57 - 0.92) and less likely to be a perpetrator of sexual IPV than boys (OR 0.33; 95% CI 0.21 - 0.52). Factors associated with perpetration of physical and sexual IPV were similar and included being a victim/survivor (physical IPV: OR 12.42; 95% CI 8.89 - 17.36; sexual IPV: OR 20.76; 95% CI 11.67 - 36.93); being older (physical IPV: OR 1.26; 95% CI 1.08 - 1.47; sexual IPV: OR 1.36; 95% CI 1.14 - 1.62 ); having lower scores on school connectedness (physical IPV: OR 0.59; 95% CI 0.46 - 0.75; sexual IPV: OR 0.56; 95% CI 0.42 - 0.76) and scoring lower on feelings of school safety (physical IPV: OR 0.66; 95% CI 0.57 - 0.77; sexual IPV: OR 0.50; 95% CI 0.40 - 0.62).CONCLUSIONS:Physical and sexual IPV was commonly reported among young adolescents in SA. Further qualitative exploration of the role of reciprocal violence by gender is needed; and the role of 'school climate'-related factors should be taken into account when developing preventive interventions

Herpes simplex virus type 2 infection as a biomarker for sexual debut among young people in sub-Saharan Africa: a literature review.

Biological markers are needed in order to provide objective measures to validate self-reported sexual behaviour and interpret prevention trial data. In this review, we evaluated herpes simplex type 2 virus (HSV-2), one of the most prevalent sexually transmitted infections in sub-Saharan Africa as a biological marker of sexual debut. Based on our findings, we do not recommend using HSV-2 as a biomarker for sexual debut due to its low transmission probabilities and the fact that HSV-2 prevalence is not 100% among potential sexual partners. We recommend that the validation of alternative biological measures should be prioritized, and included in future studies and trials of interventions to reduce sexual health risk.

Traumatic haemorrhage into an occult phaeochromocytoma: presentation and management in a patient with septic shock.

Phaeochromocytomas can have a variety of presentations; however, traumatic haemorrhage into a phaeochromocytoma is a rare presentation. Diagnosing and managing a critically ill, septic patient with a phaeochromocytoma can be very challenging. We report a case of a 57-year-old man, with a previously undiagnosed phaeochromocytoma, who presented initially with bowel perforation following an assault. Following a laparotomy for bowel resection and anastomosis, whilst on the intensive care unit, he developed paroxysmal severe hypertension overlying septic shock. Phaeochromocytoma was confirmed using a computed tomography scan and urinary assay of metanephrines and catecholamines. We managed the haemodynamic instability using labetalol and noradrenaline infusions. As his septic state improved he was started on conventional therapy and following control of his symptoms over the next few weeks, he underwent an uncomplicated right sided adrenalectomy. He made a full recovery.

The use of an animal immunogenicity model in the development of Protropin somatrem (methionyl human growth hormone).

The clinical development of methionyl human growth hormone, with particular emphasis on immunogenicity and the effects of antibody development, are summarized. In an animal model in rhesus monkeys, the immunogenicity of dinical preparations was reduced by the inclusion of additional purification steps in the manufacturing process. The immunogenic response in patients was also decreased by these improvements. No safety consequences related to antibody formation were observed and the occurrence of growth attenuation due to antibodies was found to be extremely low (<0.1%). The data suggest that the immunogenicity was not due to the N-terminal methionine or E. coli protein impurities: rather it was probably caused by small amounts of growth hormone with subtle structural alterations whose nature remains unknown.

Virtual multidisciplinary teams for cancer care.

A recent report on cancer services in Wales recommended an integrated cancer service. The proposed model was difficult to introduce in rural areas, where health-care sites and staff are far apart. Videoconferencing equipment was installed in the Singleton Hospital, Swansea, and the Bronglais General Hospital, Aberystwyth, 120 km away. During the first year, 42 videoconferencing multidisciplinary team meetings were held using ISDN at 384 kbit/s. A total of 202 cases were reviewed. The cancers were colorectal, breast and lung. There was only one aborted session, which was due to an ISDN line fault. The average attendance at the meetings was 15 staff, of whom eight were essential team members. Regular multidisciplinary team meetings reduced the need for patients to travel. They also increased access to expert opinion and reduced the delay in implementing treatment.

Comparison between light induced and chemically induced oxidation of rhVEGF.

PURPOSE: The primary objective of this study was to compare the effects of light-and chemical-induced oxidation of recombinant human vascular endothelial growth factor (rhVEGF) and the impact of these reactions on protein formulation. METHODS: A liquid formulation of rhVEGF was exposed to fluorescent light (2 x 10(4) lux for up to 4 weeks), hydrogen peroxide (H2O2), or t-butythydroperoxide (t-BHP) to induce oxidation of rhVEGF. All samples were then treated by tryptic digest and analyzed by reversed phase HPLC to determine the extent of oxidation. Chemically treated samples were also examined by near-UV and far-UV circular dichroism spectroscopy to determine the effect of oxidation on the structure of the protein. RESULTS: Exposure to light for 2 weeks resulted in 8 to 40% oxidation of all 6 methionine residues of rhVEGF (Met3 > Met18 > Met55 > Met78.81 > Met94). This amount of oxidation did not affect the binding activity of rhVEGF to its kinase domain receptor (KDR). Light exposure for 4 weeks increased metsulfoxide formation at Met3 and Met18 by an additional 16%, but did not affect the other residues. This oxidation decreased the receptor binding capacity to 73%. possibly due to the role of Met 18in receptor binding. Chemical oxidation of rhVEGF resulted in a greater extent of oxidation at all 6 methionines. Complete oxidation of Met3, Met18 and Met55 was observed after treatment with H2O2, while these residues underwent 40 to 60% oxidation after treatment with t-BHP. The receptor binding capacity was significantly reduced to 25% and 55% after treatment with H2O2 and t-BHP, respectively. After chemical oxidation, no changes in the secondary or tertiary structure were observed by far-UV and near-UV CD spectroscopy, respectively. CONCLUSIONS: Methionine residues with exposed surface areas greater than 65 A2 and sulfur surface areas greater than 16 A2 were most susceptible to oxidation. Chemical oxidation resulted in higher metsulfoxide formation and decreased binding activity of the protein to KDR than light-induced oxidation. The reduction in KDR binding was not caused by measurable conformational changes in the protein. Photooxidation was dependent on the amount of energy imparted to the protein, while the ability of t-BHP or H2O2 to react with methionine was governed by solvent accessibility of the methionine residues and steric limitations of the oxidizing agent. Significant chemical oxidation occurred on sulfurs with minimum surface areas of 16 A2, while increased photooxidation occurred as a function of increasing surface areas of solvent exposed sulfur atoms. Such differences in the extent of oxidation should be considered during protein formulation since it may help predict potential oxidation problems.

Glycoengineering of therapeutic glycoproteins: in vitro galactosylation and sialylation of glycoproteins with terminal N-acetylglucosamine and galactose residues.

Therapeutic glycoproteins produced in different host cells by recombinant DNA technology often contain terminal GlcNAc and Gal residues. Such glycoproteins clear rapidly from the serum as a consequence of binding to the mannose receptor and/or the asialoglycoprotein receptor in the liver. To increase the serum half-life of these glycoproteins, we carried out in vitro glycosylation experiments using TNFR-IgG, an immunoadhesin molecule, as a model therapeutic glycoprotein. TNFR-IgG is a disulfide-linked dimer of a polypeptide composed of the extracellular portion of the human type 1 (p55) tumor necrosis factor receptor (TNFR) fused to the hinge and Fc regions of the human IgG(1) heavy chain. This bivalent antibody-like molecule contains four N-glycosylation sites per polypeptide, three in the receptor portion and one in the Fc. The heterogeneous N-linked oligosaccharides of TNFR-IgG contain sialic acid (Sia), Gal, and GlcNAc as terminal sugar residues. To increase the level of terminal sialylation, we regalactosylated and/or resialylated TNFR-IgG using beta-1,4-galactosyltransferase (beta1,4GT) and/or alpha-2,3-sialyltransferase (alpha2,3ST). Treatment of TNFR-IgG with beta1,4GT and UDP-Gal, in the presence of MnCl(2), followed by MALDI-TOF-MS analysis of PNGase F-released N-glycans showed that the number of oligosaccharides with terminal GlcNAc residues was significantly decreased with a concomitant increase in the number of terminal Gal residues. Similar treatment of TNFR-IgG with alpha2,3ST and CMP-sialic acid (CMP-Sia), in the presence of MnCl(2), produced a molecule with an approximately 11% increase in the level of terminal sialylation but still contained oligosaccharides with terminal GlcNAc residues. When TNFR-IgG was treated with a combination of beta1,4GT and alpha2,3ST (either in a single step or in a stepwise fashion), the level of terminal sialylation was increased by approximately 20-23%. These results suggest that in vitro galactosylation and sialylation of therapeutic glycoproteins with terminal GlcNAc and Gal residues can be achieved in a single step, and the results are similar to those for the stepwise reaction. This type of in vitro glycosylation is applicable to other glycoproteins containing terminal GlcNAc and Gal residues and could prove to be useful in increasing the serum half-life of therapeutic glycoproteins.

Species-specific variation in glycosylation of IgG: evidence for the species-specific sialylation and branch-specific galactosylation and importance for engineering recombinant glycoprotein therapeutics.

Immunoglobulins (IgG) are soluble serum glycoproteins in which the oligosaccharides play significant roles in the bioactivity and pharmacokinetics. Recombinant immuno-globulins (rIgG) produced in different host cells by recombinant DNA technology are becoming major therapeutic agents to treat life threatening diseases such as cancer. Since glycosylation is cell type specific, rIgGs produced in different host cells contain different patterns of oligosaccharides which could affect the biological functions. In order to determine the extent of this variation N-linked oligosaccharide structures present in the IgGs of different animal species were characterized. IgGs of human, rhesus, dog, cow, guinea pig, sheep, goat, horse, rat, mouse, rabbit, cat, and chicken were treated with peptide-N-glycosidase-F (PNGase F) and the oligosaccharides analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for neutral and acidic oligosaccharides, in positive and negative ion modes, respectively. The data show that for neutral oligosaccharides, the proportions of terminal Gal, core Fuc and/or bisecting GlcNAc containing oligosaccharides vary from species to species; for sialylated oligosaccharides in the negative mode MALDI-TOF-MS show that human and chicken IgG contain oligosaccharides with N-acetylneuraminic acid (NANA), whereas rhesus, cow, sheep, goat, horse, and mouse IgGs contain oligosaccharides with N-glycolylneuraminic acid (NGNA). In contrast, IgGs from dog, guinea pig, rat, and rabbit contain both NANA and NGNA. Further, the PNGase F released oligosaccharides were derivatized with 9-aminopyrene 1,4,6-trisulfonic acid (APTS) and analyzed by capillary electrophoresis with laser induced fluorescence detection (CE-LIF). The CE-LIF results indicate that the proportion of the two isomers of monogalactosylated, biantennary, complex oligosaccharides vary significantly, suggesting that the branch specificity of beta1, 4-galactosyltransferase might be different in different species. These results show that the glycosylation of IgGs is species-specific, and reveal the necessity for appropriate cell line selection to express rIgGs for human therapy. The results of this study are useful for people working in the transgenic area.

Comparison of the rates of deamidation, diketopiperazine formation and oxidation in recombinant human vascular endothelial growth factor and model peptides.

In this work, we examine the way in which stability information obtained from studies on small model peptides correlates with similar information acquired from a protein. The rates of deamidation, oxidation, and diketopiperazine reactions in model peptide systems were compared to those of recombinant human vascular endothelial growth factor (rhVEGF). The N-terminal residues of rhVEGF, a potent mitogen in angiogenesis, are susceptible to the aforementioned reactions. The degradation of the peptides L-Ala-L-Pro-L-Met (APM) and Gly-L-Gln-L-Asn-L-His-L-His (GQNHH), residues 1-3 and 8-12 of rhVEGF, respectively, and rhVEGF were examined at pH 5 and 8 at 37 degrees C. Capillary electrophoresis and high-performance liquid chromatography (HPLC) stability-indicating assays were developed to monitor the degradation of the penta- and tripeptides, respectively. The degradation of rhVEGF was determined by tryptic mapping and quantified by RP-HPLC. The rates of degradation of both peptides and the protein followed apparent first-order kinetics and increased with increasing pH. The tripeptide APM underwent diketopiperazine formation (Ala-Pro-diketopiperazine) and oxidation of the Met residue, whereas the pentapeptide GQNHH degraded via the deamidation pathway. The results indicate that the rates of deamidation and oxidation of the protein are comparable to those observed in the model peptides at both pH values. However, the rate of the diketo-piperazine reaction was slower in the protein than in the model peptide, which may be the result of differences in the cis-trans equilibrium of the X-Pro peptide bonds in the 2 molecules.