In the mature nervous system, changes in synaptic strength correlate with changes in neuronal structure. Members of the Nogo-66 receptor family have been implicated in regulating neuronal morphology. Nogo-66 receptor 1 (NgR1) supports binding of the myelin inhibitors Nogo-A, MAG (myelin-associated glycoprotein), and OMgp (oligodendrocyte myelin glycoprotein), and is important for growth cone collapse in response to acutely presented inhibitors in vitro. After injury to the corticospinal tract, NgR1 limits axon collateral sprouting but is not important for blocking long-distance regenerative growth in vivo. Here, we report on a novel interaction between NgR1 and select members of the fibroblast growth factor (FGF) family. FGF1 and FGF2 bind directly and with high affinity to NgR1 but not to NgR2 or NgR3. In primary cortical neurons, ectopic NgR1 inhibits FGF2-elicited axonal branching. Loss of NgR1 results in altered spine morphologies along apical dendrites of hippocampal CA1 neurons in vivo. Analysis of synaptosomal fractions revealed that NgR1 is enriched synaptically in the hippocampus. Physiological studies at Schaffer collateral-CA1 synapses uncovered a synaptic function for NgR1. Loss of NgR1 leads to FGF2-dependent enhancement of long-term potentiation (LTP) without altering basal synaptic transmission or short-term plasticity. NgR1 and FGF receptor 1 (FGFR1) are colocalized to synapses, and mechanistic studies revealed that FGFR kinase activity is necessary for FGF2-elicited enhancement of hippocampal LTP in NgR1 mutants. In addition, loss of NgR1 attenuates long-term depression of synaptic transmission at Schaffer collateral-CA1 synapses. Together, our findings establish that physiological NgR1 signaling regulates activity-dependent synaptic strength and uncover neuronal NgR1 as a regulator of synaptic plasticity.

BackgroundYouth-friendly health services are a key strategy for improving young people’s health. This is the first study investigating provision of the Youth Friendly Services programme in South Africa since the national Department of Health took over its management in 2006. In a rural area of South Africa, we aimed to describe the characteristics of the publicly-funded primary healthcare facilities, investigate the proportion of facilities that provided the Youth Friendly Services programme and examine healthcare workers’ perceived barriers to and facilitators of the provision of youth-friendly health services.MethodsSemi-structured interviews were conducted with nurses of all eight publicly-funded primary healthcare facilities in Agincourt sub-district, Mpumalanga Province, South Africa. Thematic analysis of interview transcripts was conducted and data saturation was reached.ResultsParticipants largely felt that the Youth Friendly Services programme was not implemented in their primary healthcare facilities, with the exception of one clinic. Barriers to provision reported by nurses were: lack of youth-friendly training among staff and lack of a dedicated space for young people. Four of the eight facilities did not appear to uphold the right of young people aged 12 years and older to access healthcare independently. Breaches in young people’s confidentiality to parents were reported.ConclusionsParticipants reported that provision of the Youth Friendly Services programme is limited in this sub-district, and below the Department of Health’s target that 70% of primary healthcare facilities should provide these services. Whilst a dedicated space for young people is unlikely to be feasible or necessary, all facilities have the potential to be youth-friendly in terms of staff attitudes and actions. Training and on-going support should be provided to facilitate this; the importance of such training is emphasised by staff. More than one member of staff per facility should be trained to allow for staff turnover. As one of a few countrywide, government-run youth-friendly clinic programmes in a low or middle-income country, these results may be of interest to programme managers and policy makers in such settings.

BackgroundSexual orientation encompasses three dimensions: sexual identity, attraction and behaviour. There is increasing demand for data on sexual orientation to meet equality legislation, monitor potential inequalities and address public health needs. We present estimates of all three dimensions and their overlap in British men and women, and consider the implications for health services, research and the development and evaluation of public health interventions.MethodsAnalyses of data from Britain’s third National Survey of Sexual Attitudes and Lifestyles, a probability sample survey (15,162 people aged 16–74 years) undertaken in 2010–2012.FindingsA lesbian, gay or bisexual (LGB) identity was reported by 2·5% of men and 2·4% of women, whilst 6·5% of men and 11·5% of women reported any same-sex attraction and 5·5% of men and 6·1% of women reported ever experience of same-sex sex. This equates to approximately 547,000 men and 546,000 women aged 16–74 in Britain self-identifying as LGB and 1,204,000 men and 1,389,000 women ever having experience of same-sex sex. Of those reporting same-sex sex in the past 5 years, 28% of men and 45% of women identified as heterosexual.InterpretationThere is large variation in the size of sexual minority populations depending on the dimension applied, with implications for the design of epidemiological studies, targeting and monitoring of public health interventions and estimating population-based denominators. There is also substantial diversity on an individual level between identity, behaviour and attraction, adding to the complexity of delivering appropriate services and interventions.

IMPORTANCE There is concern about outcomes of midurethral mesh sling insertion for women with stress urinary incontinence. However, there is little evidence on long-term outcomes. OBJECTIVE To examine long-term mesh removal and reoperation rates in women who had a midurethral mesh sling insertion for stress urinary incontinence. DESIGN, SETTING, AND PARTICIPANTS This population-based retrospective cohort study included 95 057 women aged 18 years or older who had a first-ever midurethral mesh sling insertion for stress urinary incontinence in the

BackgroundFew youth-friendly health services worldwide have been scaled up or evaluated from young people’s perspectives. South Africa’s Youth Friendly Services (YFS) programme is one of the few to have been scaled up. This study investigated young people’s experiences of using sexual and reproductive health services at clinics providing the YFS programme, compared to those that did not, using the simulated client method.DesignFifteen primary healthcare clinics in Soweto were randomly sampled: seven provided the YFS programme. Simulated clients conducted 58 visits; young men requested information on condom reliability and young women on contraceptive methods. There were two outcome measures: a single measure of the overall clinic experience (clinic visit score) and whether or not simulated clients would recommend a clinic to their peers. The clinic visit score was based on variables relating to the simulated clients’ interactions with staff, details of their consultation, privacy, confidentiality, the healthcare workers’ characteristics, and the clinic environment. A larger score corresponds to a worse experience than a smaller one. Multilevel regression models and framework analysis were used to investigate young people’s experiences.ResultsHealth facilities providing the YFS programme did not deliver a more positive experience to young people than those not providing the programme (mean difference in clinic visit score: −0.18, 95% CI: −0.95, 0.60, p=0.656). They were also no more likely to be recommended by simulated clients to their peers (odds ratio: 0.48, 95% CI: 0.11, 2.10, p=0.331). More positive experiences were characterised by young people as those where healthcare workers were friendly, respectful, knew how to talk to young people, and appeared to value them seeking health information. Less positive experiences were characterised by having to show soiled sanitary products to obtain contraceptives, healthcare workers expressing negative opinions about young people seeking information, lack of privacy, and inadequate information.ConclusionsThe provision and impact of the YFS programme are limited. Future research should explore implementation. Regular training and monitoring could enable healthcare workers to address young people’s needs.

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ObjectiveTo estimate the prevalence of painful sex among women in Britain, and to explore associated sexual, relationship and health factors that should be considered in assessment.DesignMulti‐stage, clustered and stratified population probability sample survey, using computer‐assisted self‐interview. Sample frame was the British Postcode Address File.SettingParticipants interviewed at home between 2010 and 2012.SampleA total of 15 162 adults aged 16–74 years (8869 women). Data reported from 6669 sexually active women.MethodsAge‐adjusted logistic regressions to examine associations between painful sex and indicators of sexual, relational, mental and physical health.Main outcome measurePhysical pain as a result of sex for ≥3 months in the past year, plus measures of symptom severity.ResultsPainful sex was reported by 7.5% (95% CI 6.7–8.3) of sexually active women, of whom one‐quarter experienced symptoms very often or always, for ≥6 months, and causing distress. Reporting painful sex was strongly associated with other sexual function problems, notably vaginal dryness (age adjusted odds ratio 7.9; 6.17–10.12), anxiety about sex (6.34; 4.76–8.46) and lacking enjoyment in sex (6.12; 4.81–7.79). It was associated with sexual relationship factors [such as not sharing same level of interest in sex (2.56; 1.97–3.33)], as well as with adverse experiences such as non‐volitional sex (2.17; 1.68–2.80). Associations were also found with measures of psychological and physical health, including depressive symptoms (1.68; 1.28–2.21).ConclusionPainful sex is reported by a sizeable minority of women in Britain. Health professionals should be supported to undertake holistic assessment and treatment which takes account of the sexual, relationship and health context of symptoms.Tweetable abstractPainful sex—reported by 7.5% of women in Britain—is linked to poorer sexual, physical, relational and mental health.

SummaryBackgroundIn 2000, a 10-year Teenage Pregnancy Strategy was launched in England to reduce conceptions in women younger than 18 years and social exclusion in young parents. We used routinely collected data and data from Britain's National Surveys of Sexual Attitudes and Lifestyles (Natsal) to examine progress towards these goals.MethodsIn this observational study, we used random-effects meta-regression to analyse the change in conception rates from 1994–98 to 2009–13 by top-tier local authorities in England, in relation to Teenage Pregnancy Strategy-related expenditure per head, socioeconomic deprivation, and region. Data from similar probability sample surveys: Natsal-1 (1990–91), Natsal-2 (1999–2001), and Natsal-3 (2010–12) were used to assess the prevalence of risk factors and their association with conception in women younger than 18 years in women aged 18–24 years; and the prevalence of participation in education, work, and training in young mothers.FindingsConception rates in women younger than 18 years declined steadily from their peak in 1996–98 and more rapidly from 2007 onwards. More deprived areas and those receiving greater Teenage Pregnancy Strategy-related investment had higher rates of conception in 1994–98 and had greater declines to 2009–13. Regression analyses assessing the association between Teenage Pregnancy Strategy funding and decline in conception rates in women younger than 18 years showed an estimated reduction in the conception rate of 11·4 conceptions (95% CI 9·6–13·2; p<0·0001) per 1000 women aged 15–17 years for every £100 Teenage Pregnancy Strategy spend per head and a reduction of 8·2 conceptions (5·8–10·5; p<0·0001) after adjustment for socioeconomic deprivation and region. The association between conception in women younger than 18 years and lower socioeconomic status weakened slightly between Natsal-2 and Natsal-3. The prevalence of participation in education, work, or training among young women with a child conceived before age 18 years was low, but the odds of them doing so doubled between Natsal-2 and Natsal-3 (odds ratio 1·99, 95% CI 0·99–4·00).InterpretationA sustained, multifaceted policy intervention involving health and education agencies, alongside other social and educational changes, has probably contributed to a substantial and accelerating decline in conceptions in women younger than 18 years in England since the late 1990s.FundingMedical Research Council, Wellcome Trust, Economic and Social Research Council, and Department of Health.