Oral human papillomavirus (HPV) infection in men who have sex with men: prevalence and lack of anogenital concordance.

To estimate the prevalence of oral detectable human papillomavirus (HPV) DNA in HIV-negative men who have sex with men (MSM) attending a sexual health clinic in London and concordance with anogenital HPV infection. Such data are important to improve our understanding of the epidemiology of oral HPV and the potential use of vaccines to prevent oropharyngeal cancers

The rod domain is not essential for the function of plectin in maintaining tissue integrity

This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.-- et al.Epidermolysis bullosa simplex associated with late-onset muscular dystrophy (EBS-MD) is an autosomal recessive disorder resulting from mutations in the plectin gene. The majority of these mutations occur within the large exon 31 encoding the central rod domain and leave the production of a low-level rodless plectin splice variant unaffected. To investigate the function of the rod domain, we generated rodless plectin mice through conditional deletion of exon 31. Rodless plectin mice develop normally without signs of skin blistering or muscular dystrophy. Plectin localization and hemidesmosome organization are unaffected in rodless plectin mice. However, superresolution microscopy revealed a closer juxtaposition of the C-terminus of plectin to the integrin β4 subunit in rodless plectin keratinocytes. Wound healing occurred slightly faster in rodless plectin mice than in wild-type mice, and keratinocytes migration was increased in the absence of the rod domain. The faster migration of rodless plectin keratinocytes is not due to altered biochemical properties because, like full-length plectin, rodless plectin is a dimeric protein. Our data demonstrate that rodless plectin can functionally compensate for the loss of full-length plectin in mice. Thus the low expression level of plectin rather than the absence of the rod domain dictates the development of EBS-MD.This work was supported financially by grants from DEBRA UK and the Netherlands Organization for Scientific Research (NWO/ALW). J.M.d.P. was supported by the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (Grant BFU2012-32847).Peer Reviewe

T helper cell subsets specific for pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis

Background: We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis. Methods: Peripheral blood human memory CD4+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines. Results: Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood. Conclusions: Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions

Forming new sex partnerships while overseas: findings from the third British national survey of sexual attitudes & lifestyles (Natsal-3)

Objectives: Travelling away from home presents opportunities for new sexual partnerships, which may be associated with sexually transmitted infection (STI) risk. We examined the prevalence of, and factors associated with, reporting new sexual partner(s) while overseas, and whether this differed by partners’ region of residence. Methods: We analysed data from 12 530 men and women aged 16–74 years reporting ≥1 sexual partner(s) in the past 5 years in Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a probability survey undertaken 2010–2012. Results: 9.2% (95% CI 8.3% to 10.1%) of men and 5.3% (4.8% to 5.8%) of women reported new sexual partner(s) while overseas in the past 5 years. This was strongly associated with higher partner numbers and other sexual and health risk behaviours. Among those with new partners while overseas, 72% of men and 58% of women reported partner(s) who were not UK residents. Compared with those having only UK partners while abroad, these people were more likely to identify as ‘White Other’ or ‘Non-White’ (vs White British ethnicity), report higher partner numbers, new partners from outside the UK while in the UK and paying for sex (men only) all in the past 5 years. There was no difference in reporting STI diagnosis/es during this time period. Conclusions: Reporting new partners while overseas was associated with a range of sexual risk behaviours. Advice on sexual health should be included as part of holistic health advice for all travellers, regardless of age, destination or reason for travel

Pharmacological inhibition of c-Abl compromises genetic stability and DNA repair in Bcr-Abl-negative cells

Imatinib inhibits the kinase activity of Bcr-Abl and is currently the most effective drug for treatment of chronic myeloid leukemia (CML). Imatinib also blocks c-Abl, a physiological tyrosine kinase activated by a variety of stress signals including damaged DNA. We investigated the effect of pharmacological inhibition of c-Abl on the processing of irradiation-induced DNA damage in Bcr-Abl-negative cells. Cell lines and peripheral blood mononuclear cells (PBMCs) from healthy volunteers were treated with imatinib or dasatinib before gamma-irradiation. Inhibition of c-Abl caused an enhanced irradiation-induced mutation frequency and slowdown of DNA repair, whereas imatinib was ineffective in cells expressing a T315I variant of c-Abl. Mutation frequency and repair kinetics were also studied in c-Abl-/- murine embryonic fibroblasts (MEFs) retransfected with wild-type c-Abl (wt-Abl) or a kinase-defect variant of Abl (KD-Abl). Enhanced mutation frequency as well as delayed DNA repair was observed in cells expressing KD-Abl. These data indicate that pharmacological inhibition of c-Abl compromises DNA-damage response

HIV testing, risk perception, and behaviour in the British population.

OBJECTIVE: To examine the relationship between HIV risk behaviour, risk perception and testing in Britain. DESIGN: A probability sample survey of the British population. METHODS: We analyzed data on sexual behaviour, self-perceived HIV risk and HIV testing (excluding testing because of blood donation) from 13 751 sexually experienced men and women aged 16-74, interviewed between 2010 and 2012 using computer-assisted face-to-face and self-interviewing. RESULTS: Altogether, 3.5% of men and 5.4% of women reported having an HIV test in the past year. Higher perceived risk of HIV was associated with sexual risk behaviours and with HIV testing. However, the majority of those rating themselves as 'greatly' or 'quite a lot' at risk of HIV (3.4% of men, 2.5% of women) had not tested in the past year. This was also found among the groups most affected by HIV: MSM and black Africans. Within these groups, the majority reporting sexual risk behaviours did not perceive themselves as at risk and had not tested for HIV. Overall, 29.6% of men and 39.9% of women who tested for HIV in the past year could be classified as low risk across a range of measures. CONCLUSION: Most people who perceive themselves as at risk of HIV have not recently tested, including among MSM and black Africans. Many people tested in Britain are at low risk, reflecting current policy that aims to normalize testing. Strategies to further improve uptake of testing are needed, particularly in those at greatest risk, to further reduce undiagnosed HIV infection at late diagnoses

IL-22 mediates goblet cell hyperplasia and worm expulsion in intestinal helminth infection.

Type 2 immune responses are essential in protection against intestinal helminth infections. In this study we show that IL-22, a cytokine important in defence against bacterial infections in the intestinal tract, is also a critical mediator of anti-helminth immunity. After infection with Nippostrongylus brasiliensis, a rodent hookworm, IL-22-deficient mice showed impaired worm expulsion despite normal levels of type 2 cytokine production. The impaired worm expulsion correlated with reduced goblet cell hyperplasia and reduced expression of goblet cell markers. We further confirmed our findings in a second nematode model, the murine whipworm Trichuris muris. T.muris infected IL-22-deficient mice had a similar phenotype to that seen in N.brasiliensis infection, with impaired worm expulsion and reduced goblet cell hyperplasia. Ex vivo and in vitro analysis demonstrated that IL-22 is able to directly induce the expression of several goblet cell markers, including mucins. Taken together, our findings reveal that IL-22 plays an important role in goblet cell activation, and thus, a key role in anti-helminth immunity

Illicit drug use and its association with key sexual risk behaviours and outcomes: Findings from Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)

OBJECTIVES: We explore the hypothesis that using illicit drugs other than, or in addition to, cannabis is associated with sexual risk behaviour and sexual health outcomes in the British population. METHODS: We analysed data, separately by gender, reported by sexually-active participants (those reporting > = 1 partners/past year) aged 16-44 years (3,395 men, 4,980 women) in Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a probability survey undertaken 2010-12 involving computer-assisted personal-interview and computer-assisted self-interview. Analyses accounted for the stratification, clustering and weighting of the data. Multivariable logistic regression was used to calculate adjusted odds ratios. RESULTS: Use of illicit drugs other than, or in addition to, cannabis in the past year was reported by 11.5% (95%CI:10.4%-12.8%) of men and 5.5% (4.8%-6.3%) of women. Use of these types of drugs was more common among those = weekly (age-adjusted ORs, aAORs, 10.91 (6.27-18.97) men; 9.95 (6.11-16.19) women); having > = 2 condomless partners in the past year (aAOR:5.50 (3.61-8.39) men; 5.24 (3.07-8.94) women). Participants reporting illicit drug use were more likely (than those who did not) to report sexual health clinic attendance (ORs after adjusting for age, sexual identity and partner numbers: 1.79 (1.28-2.51) men; 1.99 (1.34-2.95) women), chlamydia testing (1.42 (1.06-1.92) men; 1.94 (1.40-2.70) women), unplanned pregnancy (2.93 (1.39-6.17) women), and among men only, sexually transmitted infection diagnoses (3.10 (1.63-5.89)). CONCLUSIONS: In Britain, those reporting recent illicit drug use were more likely to report other markers of poor general and sexual health. They were also more likely to attend sexual health clinics so these should be considered appropriate settings to implement holistic interventions to maximise health gain

Using the eSexual Health Clinic to access chlamydia treatment and care via the internet: a qualitative interview study.

OBJECTIVE: We developed the eSexual Health Clinic (eSHC), an innovative, complex clinical and public health intervention, embedded within a specialist sexual health service. Patients with genital chlamydia access their results online and are offered medical management via an automated online clinical consultation, leading to antibiotic collection from community pharmacy. A telephone helpline, staffed by Sexual Health Advisers, is available to support patients and direct them to conventional services if appropriate. We sought to understand how patients used this ehealth intervention. METHODS: Within exploratory studies of the eSHC (2014-2015), we conducted in-depth interviews with a purposive sample of 36 patients diagnosed with chlamydia, who had chosen to use the eSHC (age 18-35, 20 female, 16 male). Thematic analysis was conducted. RESULTS: Participants described choosing to use this ehealth intervention to obtain treatment rapidly, conveniently and privately, within busy lifestyles that hindered clinic access. They described completing the online consultation promptly, discreetly and with ease. The information provided online was considered comprehensive, reassuring and helpful, but some overlooked it in their haste to obtain treatment. Participants generally described being able to collect treatment from pharmacies discreetly and promptly, but for some, poor awareness of the eSHC by pharmacy staff undermined their ability to do this. Those unsuitable for remote management, who were directed to clinic, described frustration and concern about health implications and clinic attendance. However, the helpline was a highly valued source of information, assistance and support. CONCLUSION: The eSHC is a promising adjunct to traditional care. Its users have high expectations for convenience, speed and privacy, which may be compromised when transitioning from online to face-to-face elements of the eSHC. Managing expectations and improving implementation of the pharmacy process, could improve their experiences. Positive views on the helpline provide further support for embedding this ehealth intervention within a specialist clinical service

Male Circumcision and STI Acquisition in Britain: Evidence from a National Probability Sample Survey.

BACKGROUND: It is well-established that male circumcision reduces acquisition of HIV, herpes simplex virus 2, chancroid, and syphilis. However, the effect on the acquisition of non-ulcerative sexually transmitted infections (STIs) remains unclear. We examined the relationship between circumcision and biological measures of three STIs: human papillomavirus (HPV), Chlamydia trachomatis and Mycoplasma genitalium. METHODS: A probability sample survey of 15,162 men and women aged 16-74 years (including 4,060 men aged 16-44 years) was carried out in Britain between 2010 and 2012. Participants completed a computer-assisted personal interview, including a computer-assisted self-interview, which asked about experience of STI diagnoses, and circumcision. Additionally, 1,850 urine samples from sexually-experienced men aged 16-44 years were collected and tested for STIs. Multivariable logistic regression was used to calculate adjusted odds ratios (AOR) to quantify associations between circumcision and i) self-reporting any STI diagnosis and ii) presence of STIs in urine, in men aged 16-44 years, adjusting for key socio-demographic and sexual behavioural factors. RESULTS: The prevalence of circumcision in sexually-experienced men aged 16-44 years was 17.4% (95%CI 16.0-19.0). There was no association between circumcision and reporting any previous STI diagnoses, and specifically previous chlamydia or genital warts. However, circumcised men were less likely to have any HPV type (AOR 0.26, 95% confidence interval (CI) 0.13-0.50) including high-risk HPV types (HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and/or 68) (AOR 0.14, 95% CI 0.05-0.40) detected in urine. CONCLUSIONS: Circumcised men had reduced odds of HPV detection in urine. These findings have implications for improving the precision of models of STI transmission in populations with different circumcision prevalence and in designing interventions to reduce STI acquisition