A Multiple Component Intervention to Assist Young Pregnant Smokers to Cease Smoking: A Randomised Controlled Pilot Study

Objective: Australian rates of cigarette smoking are the lowest in the world. Young pregnant smokers are a sub population where smoking remains high. This pilot study assessed the feasibility of a multi-component intervention (Carbon Monoxide testing, motivational interviewing and a non-smoking buddy) to assist young pregnant women to cease smoking. Methods: Between October 2013 and June 2015, this multi-centred West Australian study recruited pregnant smokers aged 16 to 24, attending their first antenatal visit. Women (n=80) were randomised to the intervention and standard smoking cessation advice (n=43) or standard smoking cessation advice alone (n=37). At 36 weeks gestation and six weeks post birth, cessation rates were compared between groups using repeated measures survival analysis and reduction in smoking was examined using repeated measures linear regression on the number of cigarettes smoked. Results: The majority (89%) of women were unemployed or not in education, used illicit drugs (43%) and had experienced sexual abuse (23%). Involvement with child protection services was common (38%). Cigarette initiation occurred at a mean age of 13 years, median number of cigarettes smoked at baseline was 10 in both groups. Smoking cessation in intervention and controls were 17% vs. 14% at 36 weeks and 23% vs. 7% 6 weeks post birth. No significant differences in cessation or smoking reduction between groups were found individually or in the repeated events analysis. Conclusion: Given the low number of participants our findings cannot conclusively rule out this multi-component intervention. We believe it remains possible this intervention may prove effective in a larger group of participants and in another setting. Monitoring trends in this vulnerable, difficult to engage group of pregnant young women is important if we are to continue to devise effective interventions

An Exploration of Young Australian Women's Smoking Cessation Goals across the Trajectory of Pregnancy and Post Birth

Objective: Young pregnant women are more likely than other pregnant women to smoke tobacco during pregnancy and post birth. This study explored young women’s perceptions of the factors which impact their smoking cessation goals throughout pregnancy and post birth. Methods: This qualitative descriptive study was performed at two metropolitan obstetric hospitals in Western Australia. Forty three women aged 16 to 24 years old who reported smoking tobacco at their first antenatal visit were interviewed at each scheduled antenatal visit and every two weeks up to six weeks post birth. Interviews were subjected to thematic analysis. Results: A total of 244 interviews were performed; a mean of six interviews per woman (four in pregnancy and two post birth). Four overarching themes across three time periods were identified: the baby; the social bond of smoking; the chaotic nature of life; and access to social support. Pregnant women had a foetus-centric approach to cessation. Post birth those who sustained cessation held this belief for their newborn, whilst those who relapsed did not. The social bond of smoking highlighted smoking as the norm. Initially, women sought out non-smokers to support them. A partner’s smoking status post birth appeared pivotal to remaining tobacco free. The chaotic nature of life, reflected through multiple stressful, negative events, challenged women in achieving their smoking cessation goals. Women who sought social support appeared to stay smoke free post birth. Conclusion: The longitudinal nature of this study provides new insight into complex issues faced by this marginalised group of young, pregnant, tobacco smokers throughout the journey of pregnancy and post birth. Findings enhance our understanding of the complex real life issues some young pregnant Australian smokers face and may be considered when women focused smoking cessation interventions are developed

Women's reasons and perceptions around planning a homebirth with a registered midwife in Western Australia

Background: Qualitative evidence has provided rich descriptions around reasons for planning a homebirth with a midwife. Reasons and the importance, confidence and support around this option have not been examined by parity with a larger cohort. Aim: Examine women's characteristics, reasons and perceptions of the importance, confidence and support around choosing homebirth based upon parity. Methods: A mixed method approach was undertaken within a prospective cohort study in Western Australia where women planning a homebirth have the option of a publicly funded model or care from privately practising midwives. At recruitment a questionnaire collected demographic data, perceived importance, confidence and support plus reasons for choosing homebirth. A qualitative component included an open ended question that encouraged sharing of opinions providing textual data explored by content analysis. Findings: Reasons noted by 211 pregnant women for choosing homebirth were: avoidance of unnecessary intervention (58.8%), comfort and familiarity of home (34.1%), freedom of making own choices (25.6%), and having more continuity of care (24.2%). Reasons for planning homebirth were similar by parity, except for comfort of home being more important (44.0% vs 28.7%, p = 0.025) and continuity of care (13.3% vs 30.1%, p = 0.006) being less important to primigravid women. Themes revealed common beliefs around childbirth, appreciation for access to homebirth and a desire for greater awareness and less negativity around homebirth. Conclusion: Regardless of parity, homebirth was believed to be safe and supported by partners. Reasons identified from qualitative research to avoid intervention, the comfort of home, choice and continuity of care were supported

Arf family GTP loading is activated by, and generates, positive membrane curvature

Small G-proteins belonging to the Arf (ADP-ribosylation factor) family serve as regulatory proteins for numerous cellular processes through GTP-dependent recruitment of effector molecules. In the present study we demonstrate that proteins in this family regulate, and are regulated by, membrane curvature. Arf1 and Arf6 were shown to load GTP in a membrane-curvature-dependent manner and stabilize, or further facilitate, changes in membrane curvature through the insertion of an amphipathic helix

Developing pedagogies that work for Pre-Service and Early Career Teachers to reduce the Attainment Gap in Literacy, Numeracy and Health and Wellbeing. Research Question 3: What other practice or research might assist us in our purpose?

This report contributes to the Scottish Council of Deans of Education project related to the Scottish Attainment Challenge. It presents a literature review that responds to the third research question of the SCDE collaborative project: What other practice or research might assist us in our purpose? The purpose of this phase was to resource professional conversations and thinking in the teacher education sector, and to inform the final trial phase of the project. A literature search was undertaken using a range of strategies, to identify published accounts of innovative work from beyond Scotland in the following fields: initial teacher education for high poverty settings; pedagogies in literacy, numeracy and health and wellbeing; mentoring and induction. Each group of studies is summarised under themes with their potential for the SAC, ITE programmes and professional learning noted

Prolyl hydroxylase-1 regulates hepatocyte apoptosis in an NF-kB-dependent manner

Hepatocyte death is an important contributing factor in a number of diseases of the liver. PHD1 confers hypoxic sensitivity upon transcription factors including the hypoxia inducible factor (HIF) and nuclear factor-kappaB (NF-κB). Reduced PHD1 activity is linked to decreased apoptosis. Here, we investigated the underlying mechanism(s) in hepatocytes. Basal NF-κB activity was elevated in PHD1(-/-) hepatocytes compared to wild type controls. ChIP-seq analysis confirmed enhanced binding of NF-κB to chromatin in regions proximal to the promoters of genes involved in the regulation of apoptosis. Inhibition of NF-κB (but not knock-out of HIF-1 or HIF-2) reversed the anti-apoptotic effects of pharmacologic hydroxylase inhibition. We hypothesize that PHD1 inhibition leads to altered expression of NF-κB-dependent genes resulting in reduced apoptosis. This study provides new information relating to the possible mechanism of therapeutic action of hydroxylase inhibitors that has been reported in pre-clinical models of intestinal and hepatic disease.status: publishe

Persistence of SARS-CoV-2 antibodies over 18 months following infection: UK Biobank COVID-19 Serology Study

Background Little is known about the persistence of antibodies after the first year following SARS-CoV-2 infection. We aimed to determine the proportion of individuals that maintain detectable levels of SARS-CoV-2 antibodies over an 18-month period following infection. Methods Population-based prospective study of 20 000 UK Biobank participants and their adult relatives recruited in May 2020. The proportion of SARS-CoV-2 cases testing positive for immunoglobulin G (IgG) antibodies against the spike protein (IgG-S), and the nucleocapsid protein (IgG-N), was calculated at varying intervals following infection. Results Overall, 20 195 participants were recruited. Their median age was 56 years (IQR 39–68), 56% were female and 88% were of white ethnicity. The proportion of SARS-CoV-2 cases with IgG-S antibodies following infection remained high (92%, 95% CI 90%–93%) at 6 months after infection. Levels of IgG-N antibodies following infection gradually decreased from 92% (95% CI 88%–95%) at 3 months to 72% (95% CI 70%–75%) at 18 months. There was no strong evidence of heterogeneity in antibody persistence by age, sex, ethnicity or socioeconomic deprivation. Conclusion This study adds to the limited evidence on the long-term persistence of antibodies following SARS-CoV-2 infection, with likely implications for waning immunity following infection and the use of IgG-N in population surveys

Beyond Repair Foci: DNA Double-Strand Break Repair in Euchromatic and Heterochromatic Compartments Analyzed by Transmission Electron Microscopy

DNA double-strand breaks (DSBs) generated by ionizing radiation pose a serious threat to the preservation of genetic and epigenetic information. The known importance of local chromatin configuration in DSB repair raises the question of whether breaks in different chromatin environments are recognized and repaired by the same repair machinery and with similar efficiency. An essential step in DSB processing by non-homologous end joining is the high-affinity binding of Ku70-Ku80 and DNA-PKcs to double-stranded DNA ends that holds the ends in physical proximity for subsequent repair.Using transmission electron microscopy to localize gold-labeled pKu70 and pDNA-PKcs within nuclear ultrastructure, we monitored the formation and repair of actual DSBs within euchromatin (electron-lucent) and heterochromatin (electron-dense) in cortical neurons of irradiated mouse brain.While DNA lesions in euchromatin (characterized by two pKu70-gold beads, reflecting the Ku70-Ku80 heterodimer) are promptly sensed and rejoined, DNA packaging in heterochromatin appears to retard DSB processing, due to the time needed to unravel higher-order chromatin structures. Complex pKu70-clusters formed in heterochromatin (consisting of 4 or ≥ 6 gold beads) may represent multiple breaks in close proximity caused by ionizing radiation of highly-compacted DNA. All pKu70-clusters disappeared within 72 hours post-irradiation, indicating efficient DSB rejoining. However, persistent 53BP1 clusters in heterochromatin (comprising ≥ 10 gold beads), occasionally co-localizing with γH2AX, but not pKu70 or pDNA-PKcs, may reflect incomplete or incorrect restoration of chromatin structure rather than persistently unrepaired DNA damage.Higher-order organization of chromatin determines the accessibility of DNA lesions to repair complexes, defining how readily DSBs are detected and processed. DNA lesions in heterochromatin appear to be more complex, with multiple breaks in spatial vicinity inducing severe chromatin disruptions. Imperfect restoration of chromatin configurations may leave DSB-induced epigenetic memory of damage with potentially pathological repercussions

Genome-wide association meta-analyses to identify common genetic variants associated with hallux valgus in Caucasian and African Americans

Objective Hallux valgus (HV) affects ∼36% of Caucasian adults. Although considered highly heritable, the underlying genetic determinants are unclear. We conducted the first genome-wide association study (GWAS) aimed to identify genetic variants associated with HV. Methods HV was assessed in three Caucasian cohorts (n=2263, n=915 and n=1231 participants, respectively). In each cohort, a GWAS was conducted using 2.5 M imputed SNPs. Mixed-effect regression with the additive genetic model adjusted for age, sex, weight and within-family correlations was used for both sex-specific and combined analyses. To combine GWAS results across cohorts, fixed-effect inverse-variance meta-analyses were used. Following meta-analyses, top-associated findings were also examined in an African American cohort (n=327). Results The proportion of HV variance explained by genome-wide genotyped SNPs was 50% in men and 48% in women. A higher proportion of genetic determinants of HV were sex specific. The most significantly associated SNP in men was rs9675316 located on chr17q23-a24 near the AXIN2 gene (p=0.000000546×10−7); the most significantly associated SNP in women was rs7996797 located on chr13q14.1-q14.2 near the ESD gene (p=0.000000721×10−7). Genome-wide significant SNP-by-sex interaction was found for SNP rs1563374 located on chr11p15.1 near the MRGPRX3 gene (interaction p value =0.0000000041×10−9). The association signals diminished when combining men and women. Conclusions The findings suggest that the potential pathophysiological mechanisms of HV are complex and strongly underlined by sex-specific interactions. The identified genetic variants imply contribution of biological pathways observed in osteoarthritis as well as new pathways, influencing skeletal development and inflammation