Effects of streptozotocin-induced diabetes on the pharmacology of rat conduit and resistance intrapulmonary arteries

Abstract Background Poor control of blood glucose in diabetes is known to promote vascular dysfunction and hypertension. Diabetes was recently shown to be linked to an increased prevalence of pulmonary hypertension. The aim of this study was to determine how the pharmacological reactivity of intrapulmonary arteries is altered in a rat model of diabetes. Methods Diabetes was induced in rats by the β-cell toxin, streptozotocin (STZ, 60 mg/kg), and isolated conduit and resistance intrapulmonary arteries studied 3–4 months later. Isometric tension responses to the vasoconstrictors phenylephrine, serotonin and PGF2α, and the vasodilators carbachol and glyceryl trinitrate, were compared in STZ-treated rats and age-matched controls. Results STZ-induced diabetes significantly blunted the maximum response of conduit, but not resistance pulmonary arteries to phenylephrine and serotonin, without a change in pEC50. Agonist responses were differentially reduced, with serotonin (46% smaller) affected more than phenylephrine (32% smaller) and responses to PGF2α unaltered. Vasoconstriction caused by K+-induced depolarisation remained normal in diabetic rats. Endothelium-dependent dilation to carbachol and endothelium-independent dilation to glyceryl trinitrate were also unaffected. Conclusion The small resistance pulmonary arteries are relatively resistant to STZ-induced diabetes. The impaired constrictor responsiveness of conduit vessels was agonist dependent, suggesting possible loss of receptor expression or function. The observed effects cannot account for pulmonary hypertension in diabetes, rather the impaired reactivity to vasoconstrictors would counteract the development of pulmonary hypertensive disease.</p

Effectiveness of interventions aimed at reducing HIV acquisition and transmission among gay and bisexual men who have sex with men (GBMSM) in high income settings: A systematic review.

INTRODUCTION: HIV transmission continues among gay and bisexual men who have sex with men (GBMSM), with those who are younger, or recent migrants, or of minority ethnicity or who are gender diverse remaining at increased risk. We aimed to identify and describe recent studies evaluating the effectiveness of HIV prevention interventions for GBMSM in high income countries. METHODS: We searched ten electronic databases for randomized controlled trials (RCTs), conducted in high income settings, and published since 2013 to update a previous systematic review (Stromdahl et al, 2015). We predefined four outcome measures of interest: 1) HIV incidence 2) STI incidence 3) condomless anal intercourse (CLAI) (or measure of CLAI) and 4) number of sexual partners. We used the National Institute for Health and Care Excellence (UK) Quality Appraisal of Intervention Studies tool to assess the quality of papers included in the review. As the trials contained a range of effect measures (e.g. odds ratio, risk difference) comparing the arms in the RCTs, we converted them into standardized effect sizes (SES) with 95% confidence intervals (CI). RESULTS: We identified 39 original papers reporting 37 studies. Five intervention types were identified: one-to-one counselling (15 papers), group interventions (7 papers), online interventions (9 papers), Contingency Management for substance use (2 papers) and Pre-exposure Prophylaxis (PrEP) (6 papers). The quality of the studies was mixed with over a third of studies rated as high quality and 11% rated as poor quality. There was some evidence that one-to-one counselling, group interventions (4-10 participants per group) and online (individual) interventions could be effective for reducing HIV transmission risk behaviours such as condomless anal intercourse. PrEP was the only intervention that was consistently effective at reducing HIV incidence. CONCLUSIONS: Our systematic review of the recent evidence that we were able to analyse indicates that PrEP is the most effective intervention for reducing HIV acquisition among GBMSM. Targeted and culturally tailored behavioural interventions for sub-populations of GBMSM vulnerable to HIV infection and other STIs should also be considered, particularly for GBMSM who cannot access or decline to use PrEP

Participatory politics, environmental journalism and newspaper campaigns

This is an Author's Accepted Manuscript of an article published in Journalism Studies, 13(2), 210 - 225, 2012, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/1461670X.2011.646398.This article explores the extent to which approaches to participatory politics might offer a more useful alternative to understanding the role of environmental journalism in a society where the old certainties have collapsed, only to be replaced by acute uncertainty. This uncertainty not only generates acute public anxiety about risks, it has also undermined confidence in the validity of long-standing premises about the ideal role of the media in society and journalistic professionalism. The consequence, this article argues, is that aspirations of objective reportage are outdated and ill-equipped to deal with many of the new risk stories environmental journalism covers. It is not a redrawing of boundaries that is needed but a wholesale relocation of our frameworks into approaches better suited to the socio-political conditions and uncertainties of late modernity. The exploration of participatory approaches is an attempt to suggest one way this might be done

Towards an ecological understanding of readiness to engage with interventions for children exposed to domestic violence and abuse: Systematic review and qualitative synthesis of perspectives of children, parents and practitioners.

Children who grow up in homes affected by domestic violence and abuse (DVA) are at risk of poor outcomes across the lifespan, yet there is limited evidence on the acceptability and effectiveness of interventions for them. A recent review of child-focused interventions highlighted a gap in understanding the factors influencing the willingness of parents and children to engage with these programmes. We conducted a systematic review of qualitative evidence on the experiences of receiving and delivering interventions with the aim of identifying factors at different levels of the social-ecological context that may influence parent and child readiness to take up interventions. We searched literature till April 2016 and found 12 reports of eight programmes. Two authors independently screened papers for inclusion, extracted data and identified the first- and second-order constructs. The third-order constructs were derived and fitted to the ecological framework to inform a picture of readiness to engage with interventions. Three key findings emerged from this review: (a) parent and child readiness is influenced by a complex interplay of individual, relationship and organisational factors, highlighting that individual readiness to take up child-focussed interventions must be viewed in an ecological context; (b) the specific process through which women become ready to engage in or facilitate child-focussed interventions may differ from that related to uptake of safety-promoting behaviours and requires parents to be aware of the impact of DVA on children and to focus on children's needs; (c) there are distinct but interlinked processes through which parents and children reach a point of readiness to engage in an interventions aimed at improving child outcomes. We discuss the implications of these findings for both practice and research

Modulating autophagy as a therapeutic strategy for the treatment of paediatric high‐grade glioma

Paediatric high grade glioma (pHGG) represent a therapeutically challenging group of tumours. Despite decades of research there has been a minimal improvement in treatment and the clinical prognosis remains poor. Autophagy, a highly conserved process for recycling metabolic substrates is upregulated in pHGG, promoting tumour progression and evading cell death. There is significant cross talk between autophagy and a plethora of critical cellular pathways, many of which Accepted Article This article is protected by copyright. All rights reserved. are dysregulated in pHGG. The following article will discuss our current understanding of autophagy signalling in pHGG and the potential modulation of this network as a therapeutic target

Difficulty accessing condoms because of the COVID-19 pandemic reported by gay, bisexual and other men who have sex with men in the UK: findings from a large, cross-sectional, online survey

BACKGROUND: COVID-19 restrictions severely reduced face-to-face sexual health services, an important access point for condoms. We examine whether gay, bisexual and other men who have sex with men (GBMSM) in the UK had difficulty accessing condoms during the first year of the pandemic, and if so, which groups were most affected. METHODS: Questions about difficulty accessing condoms were asked as part of a short, online cross-sectional survey of GBMSM undertaken November/December 2021, recruited via social media and Grindr. Eligible participants were UK-resident GBMSM (cis/trans/gender-diverse person assigned male at birth [AMAB]), aged ≥16 years who were sexually active (reported sex with men in the last year). Multivariable logistic regression was used to examine if and how reporting this outcome varied by key sociodemographic, health and behavioural factors independent of the potential confounding effect of numbers of new male sex partners. RESULTS: Of all participants (N = 1039), 7.4% (n = 77) reported difficulty accessing condoms due to the pandemic. This was higher among younger GBMSM (aged 16-29 years vs. ≥45; 12.8% vs. 4.9%; aOR: 2.78); trans/gender-diverse AMAB participants (vs. cis gender males; 24.4% vs. 6.6%; aOR = 4.86); bisexually-identifying participants (vs. gay-identifying; 11.1% vs. 6.5%; aOR = 1.78); and those without degree level education (vs. having a degree; 9.8% vs. 5.6%; aOR = 2.01). CONCLUSIONS: A minority of sexually active GBMSM reported difficulty accessing condoms because of the pandemic, however, this was more common amongst those who already experience a disproportionate burden of poor sexual health. Interventions are needed to address these inequalities in accessing this important primary STI/HIV prevention measure

Implementing within‐cross genomic prediction to reduce oat breeding costs

A barrier to the adoption of genomic prediction in small breeding programs is the initial cost of genotyping material. Although decreasing, marker costs are usually higher than field trial costs. In this study we demonstrate the utility of stratifying a narrow‐base biparental oat population genotyped with a modest number of markers to employ genomic prediction at early and later generations. We also show that early generation genotyping data can reduce the number of lines for later phenotyping based on selections of siblings to progress. Using sets of small families selected at an early generation could enable the use of genomic prediction for adaptation to multiple target environments at an early stage in the breeding program. In addition, we demonstrate that mixed marker data can be effectively integrated to combine cheap dominant marker data (including legacy data) with more expensive but higher density codominant marker data in order to make within generation and between lineage predictions based on genotypic information. Taken together, our results indicate that small programs can test and initiate genomic predictions using sets of stratified, narrow‐base populations and incorporating low density legacy genotyping data. This can then be scaled to include higher density markers and a broadened population base

COVID-19 infection and vaccination uptake in men and gender-diverse people who have sex with men in the UK: analyses of a large, online community cross-sectional survey (RiiSH-COVID) undertaken November–December 2021

BACKGROUND: Men and gender-diverse people who have sex with men are disproportionately affected by health conditions associated with increased risk of severe illness due to COVID-19 infection. METHODS: An online cross-sectional survey of men and gender-diverse people who have sex with men in the UK recruited via social networking and dating applications from 22 November-12 December 2021. Eligible participants included self-identifying men, transgender women, or gender-diverse individuals assigned male at birth (AMAB), aged ≥ 16, who were UK residents, and self-reported having had sex with an individual AMAB in the last year. We calculated self-reported COVID-19 test-positivity, proportion reporting long COVID, and COVID-19 vaccination uptake anytime from pandemic start to survey completion (November/December 2021). Logistic regression was used to assess sociodemographic, clinical, and behavioural characteristics associated with SARS-CoV-2 (COVID-19) test positivity and complete vaccination (≥ 2 vaccine doses). RESULTS: Among 1,039 participants (88.1% white, median age 41 years [interquartile range: 31-51]), 18.6% (95% CI: 16.3%-21.1%) reported COVID-19 test positivity, 8.3% (95% CI: 6.7%-10.1%) long COVID, and 94.5% (95% CI: 93.3%-96.1%) complete COVID-19 vaccination through late 2021. In multivariable models, COVID-19 test positivity was associated with UK country of residence (aOR: 2.22 [95% CI: 1.26-3.92], England vs outside England) and employment (aOR: 1.55 [95% CI: 1.01-2.38], current employment vs not employed). Complete COVID-19 vaccination was associated with age (aOR: 1.04 [95% CI: 1.01-1.06], per increasing year), gender (aOR: 0.26 [95% CI: 0.09-0.72], gender minority vs cisgender), education (aOR: 2.11 [95% CI: 1.12-3.98], degree-level or higher vs below degree-level), employment (aOR: 2.07 [95% CI: 1.08-3.94], current employment vs not employed), relationship status (aOR: 0.50 [95% CI: 0.25-1.00], single vs in a relationship), COVID-19 infection history (aOR: 0.47 [95% CI: 0.25-0.88], test positivity or self-perceived infection vs no history), known HPV vaccination (aOR: 3.32 [95% CI: 1.43-7.75]), and low self-worth (aOR: 0.29 [95% CI: 0.15-0.54]). CONCLUSIONS: In this community sample, COVID-19 vaccine uptake was high overall, though lower among younger age-groups, gender minorities, and those with poorer well-being. Efforts are needed to limit COVID-19 related exacerbation of health inequalities in groups who already experience a greater burden of poor health relative to other men who have sex with men