711 research outputs found
Extended schools survey of schools, pupils and parents : a quantitative study of perceptions and usage of extended services in schools
Pushing the Boundaries: Understanding Women's Participation and Empowerment
TrĂłcaire undertook three year multi-country research on women's participation within decision making spaces at the grassroots level. 'Empowerment' was defined in the research as the process of pushing against the boundaries to shape new fields of possible action, by increasing the capacity of those with less power to engage with those with more power. The research was undertaken in three countries, Democratic Republic of Congo, India and Nicaragua, implementing governance and gender equality programmes through local partner organisations. It set out to better understand how participation contributes to processes of empowerment and the reduction of oppressive power relations between men and women, as well as citizens and the state. A bibliography is included. More information is available on: http://www.trocaire.org/resources/policyandadvocacy/pushing-boundaries-understanding-womens-participation-and-empowermen
Young childrenâs and familiesâ experiences of services aimed at reducing the impact of low-income: participation work with children and families
Reconceputualising security strategies for courts: developing a typology for safer court environments
There have been heightened concerns about security in courts in recent years, prompting a strong response that has largely been focused on perimeter security. This paper draws on recent research conducted in Australian on court userâs safety needs, to propose a typology for designing safer courtroom environments that moves beyond the entry point to the court, and incorporates consideration of process and design elements
Recommended from our members
Re-assemblage of plant communities: a survey of floodplain meadow restoration projects in the UK
Re-assemblage of plant communities on the restoration sites is a slow process, largely dependent on historic use of the sites prior to restoration, the amount of applied propagules, site management during early restoration stages, and speed of ontogenesis of the target species. Use of the MAVIS calculator of similarity scores between existing vegetation and standard plant communities as described in British NVC, showed the potential of measuring restoration progress. Most of the restoration sites and most of forming plant communities scored 50-60%, which is slightly indicative towards a good progress in community re-assemblag
Risk and protective factors for suicidality among lesbian, gay, bisexual, transgender and queer (LGBTQ+) young people, from countries with a high global acceptance index (GAI), within the context of the socio-ecological model: A scoping review
Introduction: Lesbian, gay, bisexual, transgender, and queer (LGBTQ+) young people experience higher prevalence rates of suicidality than their heterosexual and/or cisgender peers. However, there is limited research that can inform suicide prevention efforts. Our aim was to synthesize quantitative, qualitative, and mixed methods research on risk and protective factors among LGBTQ+ young people, from countries with a high Global Acceptance Index.Methods: A scoping review guided by Arksey and O'Malley's fiveâstage framework, using the Preferred Reporting Items for Systematic Reviews and Metaâanalysis Extension for Scoping Reviews protocol. Five databases and grey literature were searched for relevant studies. Identified factors were clustered by thematic type, according to the socioâecological model to identify empirical trends and knowledge gaps. The mixed methods appraisal tool was used for quality assessment of studies. Results: Sixtyâsix studies met our inclusion criteria. Overall, 59 unique risk factors and 37 unique protective factors were identified. Key risk factors include past suicidality, adverse childhood experiences, internalized queerphobia, minority stress, interpersonal violence, bullying, familial conflict, and antiâLGBTQ+ policies/ legislation. Key protective factors include selfâaffirming strategies, adult/peer support, atâschool safety, access to inclusive healthcare, family connectedness, positive coming out experiences, genderâaffirming services and LGBTQ+ inclusive policies and legislation.Conclusions: Overall, our findings affirm that multiple risk and protective factors, at all levels of the socioâecological model, interact in complex, unique and diverse ways upon suicidality among LGBTQ+ young people. Implications for suicide prevention are discussed. Further empirical studies are required, particularly at the communities, policies, and societal levels of the socioâecological model, and these studies should include a focus on protective factors and significant withinâgroup differences
A sex-specific microRNA-96/5HT1B axis influences development of pulmonary hypertension
Women develop pulmonary arterial hypertension (PAH) more frequently than men suggesting that female sex and/or female sex hormones i.e. estrogens play a role in disease pathogenesis. Building evidence also implicates a role for microRNAs (miRNAs) in PAH. Little is known surrounding the interplay between sex/estrogens and miRNAs in PAH. Examining the sexual dymorphism in miRNAs with regards to PAH disease may provide insight into the sex bias observed in PAH.
Loss-of-function BMPR-II mutations underlie heritable PAH. Here, we showed that in pulmonary artery smooth muscle cells (PASMCs) explanted from a pulmonary hypertensive mouse model with a knock-in BMPR-II mutation (BMPR-IIR899X+/-) there were differences in miRNA expression between sexes. Among the 20 miRNAs examined, 9 miRNAs exhibited significant change in expression within female BMPR-IIR899X+/- compared to female wild-type (WT) PASMCs but remained unchanged in male PASMCs. Of interest miRNA-96 demonstrated significant down-regulation in female BMPR-IIR899X+/- but remained unchanged in male BMPR-IIR899X+/-. In silico prediction software demonstrates the 5-HT1B receptor as a putative target of miRNA-96. The 5-HT1B receptor has previously been implicated in PAH development as it is thought to play a role in pulmonary artery vasoconstriction and pulmonary artery remodelling, two major hallmarks of PAH. To verify if 5-HT1B was a true target of miRNA-96 we carried out a 3âUTR luciferase reporter assay. Indeed we found over-expression of miRNA-96 could down-regulate the luciferase output of the luciferase reporter construct containing the 3âUTR of the 5-HT1B receptor. The down-regulation of miRNA-96 within the female BMPR-IIR899X+/- mouse PASMCs was associated with a concomitant increase in 5-HT1B mRNA and protein. This expression pattern was re-iterated in PASMCs explanted from female PAH patients. Here, we found female PAH patients had a decrease in miRNA-96 expression and an increase in 5-HT1B mRNA and protein but again expression remained unchanged in male patients compared to non-PAH controls. Interestingly we also found only female PAH patient PASMCs were proliferative to the mitogen serotonin (5-HT). This could be explained by the expression pattern of 5-HT1B observed. Next we examined the effect of miRNA-96 over-expression in human PASMCs. Here, we demonstrated that over-expressing miRNA-96 had the ability to reduce 5-HT1B protein expression; however, mRNA expression remained unchanged. In addition, we found that over-expressing miRNA-96 prevented serotonin-induced proliferation in PASMCs from female PAH patients.
We have previously shown a relationship between estrogen and 5-HT1B as 17β-estradiol, the main pre-menopausal circulating estrogen, increases the protein expression of 5-HT1B in human PASMCs. Here, we examined the effect of 17β-estradiol on miRNA-96 expression. We found that 17β-estradiol decreased miRNA-96 expression suggesting 17β-estradiolâs effect on 5-HT1B expression could be mediated through a decrease in miRNA-96. To determine if endogenous 17β-estradiol also influences miRNA-96 expression we assessed the expression of miRNA-96 and 5-HT1B expression within whole lung homogenates from female and male mice that had been dosed with an aromatase (estrogen synthesising enzyme) inhibitor anastrozole. These mice have depleted circulating and local lung synthesis of estrogen, and elevated BMPR-II signalling. MiRNA-96 was elevated in the lungs from the estrogen-depleted female mice and this was accompanied by a decrease in 5-HT1B mRNA expression. No changes in miRNA-96 and 5-HT1B mRNA expression were observed within male lung tissue. These results further implicated a role for estrogen in regulating miRNA-96 and subsequently 5-HT1B.
As over-expression of miRNA-96 in cell culture prevented a proliferative phenotype in human PASMCs we sought to assess the effect of over-expressing miRNA-96 in vivo. We utilised both the BMPR-IIR899X+/- and hypoxic mouse model of pulmonary hypertension (PH) to examine whether a miRNA-96 mimic could both reverse and prevent a PH phenotype. The miRNA-96 mimic was administered intravenously via the tail vein once a week for 2 weeks using the MaxSuppressor⢠In Vivo RNA-LANCEr II delivery method. We first confirmed that in both of these models miRNA-96 was significantly depleted in the lungs of diseased mice. Secondly we showed that intravenous injection delivered miRNA-96 mimic to the pulmonary arteries. Our in vivo results demonstrated that dosing with miRNA-96 mimic reduced the right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH) and % of remodelled vessels in hypoxic and BMPR-IIR899X+/- female mice. Mice dosed with a negative control mimic showed no effect on PAH indices. Interestingly we also showed that hypoxic and BMPR-IIR899X+/- mice dosed with miRNA-96 mimic had a reduction in 5-HT1B protein expression compared to those dosed with negative control mimic.
This is the first study to observe sexual dimorphism in miRNA expression with regards to PAH. We have provided novel data demonstrating how miRNA-96, under the potential influence of estrogen, plays a role in the development of PH in a sex-dependent manner, by regulating 5-HT1B expression and serotonin-induced proliferation. Restoring depleted miRNA-96 levels may present a novel therapeutic approach in PAH
- âŚ