Low expression of aldehyde deyhdrogenase 1A1 (ALDH1A1) is a prognostic marker for poor survival in pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Aldehyde deyhdrogenase 1 (ALDH1) has been characterised as a cancer stem cell marker in different types of tumours. Additionally, it plays a pivotal role in gene regulation and endows tumour cells with augmented chemoresistance. Recently, ALDH1A1 has been described as a prognostic marker in a pancreatic cancer tissue microarray. The aim of this study was to reevaluate the expression of ALDH1A1 as a prognostic marker on whole-mount tissue sections.</p> <p>Methods</p> <p>Real-time-quantitative-PCR (qRT-PCR) and Western blotting were used to evaluate the expression profile of ALDH1A1 in seven pancreatic cancer cell lines and one non-malignant pancreatic cell line. Immunostaining against ALDH1A1 and Ki-67 was performed on paraffin-embedded samples from 97 patients with pancreatic cancer. The immunohistochemical results were correlated to histopathological and clinical data.</p> <p>Results</p> <p>qRT-PCR and Western blotting revealed a different expression pattern of ALDH1A1 in different malignant and non-malignant pancreatic cell lines. Immunohistochemical analysis demonstrated that ALDH1A1 was confined to the cellular cytoplasm and occurred in 72 cases (74%), whereas it was negative in 25 cases (26%). High expression of ALDH1A1 was significantly correlated to an increased proliferation rate (Spearman correlation, p = 0.01). Univariate and multivariate analyses showed that decreased expression of ALDH1A1 is an independent adverse prognostic factor for overall survival.</p> <p>Conclusions</p> <p>Immunonhistochemical analysis on whole-mount tissue slides revealed that ALDH1A1 is more abundantly expressed in pancreatic cancer than initially reported by a tissue microarray analysis. Moreover, high expression of ALDH1A1 correlated significantly with the proliferation of tumour cells. Intriguingly, this study is the first which identifies low expression of ALDH1A1 as an independent adverse prognostic marker for overall survival in pancreatic cancer.</p

Inhibition of Hypoxia-Inducible Factor-1α (HIF-1α) Protein Synthesis by DNA damage inducing agents

10.1371/journal.pone.0010522PLoS ONE55

Priorities and strategies for improving disabled women's access to maternity services when they are affected by domestic abuse:a multi-method study using concept maps

BACKGROUND: Domestic abuse is a significant public health issue. It occurs more frequently among disabled women than those without a disability and evidence suggests that a great deal of domestic abuse begins or worsens during pregnancy. All women and their infants are entitled to equal access to high quality maternity care. However, research has shown that disabled women who experience domestic abuse face numerous barriers to accessing care. The aim of the study was to identify the priority areas for improving access to maternity services for this group of women; develop strategies for improved access and utilisation; and explore the feasibility of implementing the identified strategies. METHODS: This multi-method study was the third and final part of a larger study conducted in the UK between 2012 and 2014. The study used a modified concept mapping approach and was theoretically underpinned by Andersen’s model of healthcare use. Seven focus group interviews were conducted with a range of maternity care professionals (n = 45), incorporating quantitative and qualitative components. Participants ranked perceived barriers to women’s access and utilisation of maternity services in order of priority using a 5-point Likert scale. Quantitative data exploration used descriptive and non-parametric analyses. In the qualitative component of each focus group, participants discussed the barriers and identified potential improvement strategies (and feasibility of implementing these). Qualitative data were analysed inductively using a framework analysis approach. RESULTS: The three most highly ranked barriers to women’s access and utilisation of maternity services identified in the quantitative component were: 1) staff being unaware and not asking about domestic abuse and disability; 2) the impact of domestic abuse on women; 3) women’s fear of disclosure. The top two priority strategies were: providing information about domestic abuse to all women and promoting non-judgemental staff attitude. These were also considered very feasible. The qualitative analysis identified a range of psychosocial and environmental barriers experienced by this group of women in accessing maternity care. Congruent with the quantitative results, the main themes were lack of awareness and fear of disclosure. Key strategies were identified as demystifying disclosure and creating physical spaces to facilitate disclosure. CONCLUSIONS: The study supports findings of previous research regarding the barriers that women face in accessing and utilising maternity services, particularly regarding the issue of disclosure. But the study provides new evidence on the perceived importance and feasibility of strategies to address such barriers. This is an important step in ensuring practice-based acceptability and ease with which improvement strategies might be implemented in maternity care settings

NeOProM: Neonatal Oxygenation Prospective Meta-analysis Collaboration study protocol

Background: The appropriate level of oxygenation for extremely preterm neonates ( 90%) have been reported to have greater rates of morbidity including retinopathy of prematurity and chronic lung disease. In order to answer this clinical dilemma reliably, large scale trial evidence is needed.Methods/Design: To detect a small but important 4% increase in death or severe disability in survivors, over 5000 neonates would need to be recruited. As extreme prematurity affects 1% of births, such a project undertaken by one trial group would be prohibitively lengthy and expensive. Hence, the Neonatal Oxygenation Prospective Meta-analysis (NeOProM) Collaboration has been formed. A prospective meta-analysis (PMA) is one where studies are identified, evaluated, and determined to be eligible before the results of any included studies are known or published, thereby avoiding some of the potential biases inherent in standard, retrospective meta-analyses. This methodology provides the same strengths as a single large-scale multicentre randomised study whilst allowing greater pragmatic flexibility. The NeOProM Collaboration protocol (NCT01124331) has been agreed prior to the results of individual trials being available. This includes pre-specifying the hypotheses, inclusion criteria and outcome measures to be used. Each trial will first publish their respective results as they become available and the combined meta-analytic results, using individual patient data, will be published when all trials are complete. The primary outcome to be assessed is a composite outcome of death or major disability at 18 months - 2 years corrected age. Secondary outcomes include several measures of neonatal morbidity. The size of the combined dataset will allow the effect of the interventions to be explored more reliably with respect to pre-specified patient- and intervention-level characteristics.Discussion: Results should be available by 2014

The effects of swaddling on oxygen saturation and respiratory rate of healthy infants in Mongolia.

BACKGROUND: Infant swaddling is common practice in some developing countries where infant respiratory morbidity is also prevalent. Little is known about the effect of swaddling on respiratory variables in healthy infants. Such information could have important implications for respiratory diseases. AIMS: To compare respiratory rates (RR) and arterial oxygen saturations (SaO2) of healthy swaddled infants and non-swaddled infants during different conditions of sleep and arousal. SETTING: Community based, nested case control study in Ulaanbaatar, Mongolia. SUBJECTS AND METHODS: Habitually swaddled and non-swaddled infants aged 9-10 weeks taking part in a randomised controlled trial of swaddling. Respiratory rate and SaO2 were measured during quiet wakefulness, feeding, quiet and active sleep. Habitually swaddled infants were studied in swaddled and non-swaddled conditions. Habitually non-swaddled infants were studied only in the non-swaddled state. RESULTS: SaO2 was higher during awake states compared with sleep states in all groups of infants. Habitually swaddled infants had lower mean SaO2 in the swaddled compared with non-swaddled condition (96.5% vs. 96.9%, p < 0.01) but these were not significantly different from the mean SaO2 of non-swaddled infants (96.9%, minimum p = 0.22). Habitually swaddled infants in the swaddled and non-swaddled states had similar respiratory rates, but these were, in both cases, significantly lower than in habitually non-swaddled infants. CONCLUSION: Swaddling has little or no clinical effect on SaO2 or respiratory rates in healthy 9-10-week-old infants in Mongolia