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