Student perceptions of a healthy university

As complex environments within which individuals and populations operate, universities present important contexts for understanding and addressing health issues. The healthy university is an example of the settings approach, which adopts a whole system perspective, aiming to make places within which people, learn, live, work and play supportive to health and wellbeing. The UK Healthy Universities Network has formulated an online toolkit, which includes a self-review tool, intended to enable universities to assess what actions they need to take to develop as a healthy university. This paper presents findings from consultative research undertaken with students from universities in England, Scotland and Wales, which explored what they believe represents a healthy university. Methods Student surveys and focus groups were used to collect data across eleven universities in England, Scotland and Wales. A priori themes were used to develop our own model for a healthy university, and for the thematic coding phase of analysis. Findings A healthy university would promote student health and wellbeing in every aspect of its business from its facilities and environment through to its curriculum. Access to reasonably priced healthy food and exercise facilities were key features of a healthy university for students in this study. The Self Review Tool has provided a crucial start for universities undertaking the journey towards becoming a healthy university. In looking to the future both universities and the UK Healthy Universities Network will now need to look at what students want from their whole university experience, and consider how the Self Review Tool can help universities embrace a more explicit conceptual framework. Conclusion The concept of a healthy university that can tailor its facilities and supportive environments to the needs of its students will go some way to developing students who are active global citizens and who are more likely to value and prioritise health and wellbeing, in the short and long term through to their adult lives

Assessment of PULP score in predicting 30-day perforated duodenal ulcer morbidity, and comparison of its performance with Boey and ASA, a retrospective study

Background: /aim: Scores commonly employed to risk stratify perforated peptic ulcer patients include ASA (American Society of Anesthesiologists), Boey and peptic ulcer perforation score (PULP). However, few studies assessed and compared the accuracy indices of these three scores in predicting post PPU repair 30-day morbidity. We assessed accuracy indices of PULP, and compared them to Boey and ASA in predicting post perforated duodenal (PDU) ulcer repair 30-day morbidity. Methods: Retrospective chart review of all PDU patients (perforated duodenal ulcers only) at the largest two hospitals in Qatar (N = 152). Data included demographic, clinical, laboratory, operative, and post repair 30-day morbidity. Area under the Curve (AUC), sensitivity and specificity were computed for each of the 3 scores. Multivariate logistic regression assessed the accuracy indices of each score. Results: All patients were males (M age 37.41 years). Post PDU repair 30-day morbidity was 10.5% (16 morbidities). Older age, higher ASA (?3), Boey (?1) or PULP (?8) scores, shock on admission and preoperative comorbidities; and conversely, lower hemoglobin and albumin were all positively significantly associated with higher post PDU 30-day morbidity. PULP displayed the largest AUC (72%), and was the only score to significantly predict 30-day morbidity. The current study is the first to report the sensitivity and specificity of these three scores for post PDU repair 30-day morbidity; and first to assess accuracy indices for PULP in predicting post PDU repair 30-day morbidity. Conclusion: PULP score had the largest AUC and was the only score to significantly predict post PDU repair 30-day morbidity.Scopu

The combined expression of solute carriers is associated with a poor prognosis in highly proliferative ER+ breast cancer

Purpose: Breast cancer (BC) is a heterogeneous disease characterised by variant biology, metabolic activity, and patient outcome. Glutamine availability for growth and progression of BC is important in several BC subtypes. This study aimed to evaluate the biological and prognostic role of the combined expression of key glutamine transporters, SLC1A5, SLC7A5 and SLC3A2 in BC with emphasis on the intrinsic molecular subtypes. Methods: SLC1A5, SLC7A5 and SLC3A2 were assessed at the protein level, using immunohistochemistry on tissue microarrays constructed from a large well characterised BC cohort (n=2,248). Patients were stratified into accredited clusters based on protein expression and correlated with clinicopathological parameters, molecular subtypes, and patient outcome. Results: Clustering analysis of SLC1A5, SLC7A5 and SLC3A2 identified three clusters Low SLCs (SLC1A5-/SLC7A5-/SLC3A2-), High SLC1A5 (SLC1A5+/SLC7A5-/SLC3A2-) and High SLCs (SLC1A5+/SLC7A5+/SLC3A2+) which had distinct correlations to known prognostic factors and patient outcome (p<0.001). The key regulator of tumour cell metabolism, c-MYC, was significantly expressed in tumours in the High SLCs cluster (p<0.001). When different BC subtypes were considered, the association with the poor outcome was observed in the ER+ high proliferation/luminal B class only (p= 0.003). In multivariate analysis, SLC clusters were independent risk factor for shorter breast cancer specific survival (p= 0.001). Conclusion: The co-operative expression of SLC1A5, SLC7A5 and SLC3A2 appears to play a role in the aggressive subclass of ER+ high proliferation/ luminal BC, driven by c-MYC, and therefore have the potential to act as therapeutic targets, particularly in synergism

The prognostic significance of ALDH1A1 expression in early invasive breast cancer

Aims: Aldehyde dehydrogenase family 1 member A1 (ALDH1A1)is reportedly a key ALDH isozyme linked to the cancer stem cells (CSC) of many solid tumours, where it is involved in self-renewal, differentiation and self-protection. In this study, the prognostic significance of ALDH1A1 expression in early invasive breast cancer (BC) and its role as a BC stem cell (BCSC) were evaluated.Methods: ALDH1A1 expression was assessed, using immunohistochemistry and tissue microarrays, in a large well- characterised BC cohort. ALDH1A1 mRNA expression was also assessed at the transcriptomic levels, utilising data from the Molecular Taxonomy of Breast Cancer International Consortium. The associations of ALDH1A1 with clinicopathological parameters, other stem cell markers and patient outcomes were determined.Results: ALDH1A1 was expressed in 71% of BC cases, at both the protein and mRNA levels. High ALDH1A1 expression was associated with poor prognostic features, including high grade, poor Nottingham Prognostic Index (NPI), lymph node metastasis and highly proliferative ER+ (luminal B) and triple negative (TNBC) subtypes. ALDH1A1 expression was positively correlated with the expression of CD44, CD24, TWIST, SOX9, EPCAM and CD133. The high immunoexpression of ALDH1A1 was significantly associated with poor BC-specific survival [less than] 0.001), and specifically in the luminal B and TNBC subtypes (P=0.042 and P=0.003, respectively). The immunoexpression of ALDH1A1 was an independent predictor of poor prognosis (P=0.015).Conclusions: ALDH1A1, as assessed using IHC, seems to act as a BCSC marker associated not only with other BCSC markers but also with poor prognostic characteristics and poor outcomes, particularly in the luminal B and TNBC subtypes

PPFIA1 expression associates with poor response to endocrine treatment in luminal breast cancer

BackgroundPPFIA1 is an important regulator of cell migration and invasion, regulating focal adhesion signalling and disassembly. PPFIA1 is frequently amplified in breast cancer, and recent functional studies indicate that PPFIA1 is an important promoter of migration and invasion in breast cancer. This study aims to evaluate the utility of PPFIA1 expression in the luminal breast cancer as a prognostic marker to predict the response to endocrine therapy.MethodsLarge, well-characterised cohorts of primary luminal breast cancer patients with long-term follow-up was assessed for the clinical impact of PPFIA1 expression at the transcriptomic and proteomic levels. Prognostic significance of PPFIA1 and its relationship with clinical outcome and benefit of endocrine therapy were analysed. In addition, its association with other related-genes was analysed.ResultsThere was significant association between PPFIA1 expression and a member of the liprin family that involves in cell invasion (PPFIBPI), and the cell cycle regulator (CCND1), whereas a negative association was observed with the tumour suppressor gene (CD82). Patients with high PPFIA1 expression were associated with high risk of recurrence, distant metastasis and death from breast cancer (P< 0.05). Importantly, high PPFIA1 expression predicted relapse in a subset of patients who were subject to endocrine treatment alone, and was an independent prognostic marker of unfavourable outcome in these patients (P< 0.05).ConclusionsThese findings support the proposed role for PPFIA1 as a regulator of cell migration in breast cancer and provides definitive evidence for the clinical utility of PPFIA1 expression in patients with luminal breast cancer. Most importantly, our data suggests that PPFIA1 might be a potential predictive marker for poor benefit from endocrine therapy

CDC20 expression in oestrogen receptor positive breast cancer predicts poor prognosis and lack of response to endocrine therapy

PurposeEndocrine therapy is the standard treatment for oestrogen receptor positive (ER+) breast cancer. Despite its efficacy, around half of patients will develop resistance to this treatment and eventually relapse. Identification of effective and reliable biomarkers to predict the efficacy of endocrine therapy is of crucial importance in the management of ER+ breast cancer. Emerging evidence has revealed that the cell division regulator CDC20 exhibits an oncogenic function and plays important roles in tumourigenesis and progression of solid tumours. In this study, we investigated the prognostic and predictive role of CDC20 in early ER+ breast cancer patients.MethodsThe biological and clinical impact of CDC20 expression was assessed in large clinical annotated cohort of ER+ breast cancer with long-term follow-up at the mRNA level, using METABRIC and KM-Plotter datasets, and the protein level using immunohistochemistry on patients presenting at Nottingham. CDC20 expression was correlated with clinico-pathological parameters, molecular subtypes, clinical outcome and efficacy of endocrine therapy.ResultsHigh CDC20 mRNA expression was associated with poor clinico-pathological parameters including large tumour size and high tumour grade (P

Educating the public health workforce: Issues and challenges

Background: In public health, as well as other health education contexts, there is increasing recognition of the transformation in public health practice and the necessity for educational providers to keep pace. Traditionally, public health education has been at the postgraduate level; however, over the past decade an upsurge in the growth of undergraduate public health degrees has taken place. Discussion: This article explores the impact of these changes on the traditional sphere of Master of Public Health programs, the range of competencies required at undergraduate and postgraduate levels, and the relevance of these changes to the public health workforce. It raises questions about the complexity of educational issues facing tertiary institutions and discusses the implications of these issues on undergraduate and postgraduate programs in public health. Conclusion: The planning and provisioning of education in public health must differentiate between the requirements of undergraduate and postgraduate students – while also addressing the changing needs of the health workforce. Within Australia, although significant research has been undertaken regarding the competencies required by postgraduate public health students, the approach is still somewhat piecemeal, and does not address undergraduate public health. This paper argues for a consistent approach to competencies that describe and differentiate entry-level and advanced practice

Co-Expression Effect of SLC7A5/SLC3A2 to Predict Response to Endocrine Therapy in Oestrogen-Receptor-Positive Breast Cancer

The majority of breast cancers are oestrogen receptor positive (ER+) and are subject to endocrine therapy however, an unpredictable subgroup of patients will develop resistance to endocrine therapy. SLC7A5/SLC3A2 complex is a major route for the transport of large neutral essential amino acids through the plasma membrane. Alterations in the expression and function of those amino acid transporters lead to metabolic reprogramming, which contributing to the tumorigenesis and drug resistance. This study aims to assess the effects and roles of SLC7A5/SLC3A2 co-expression in predicting response to endocrine therapy in patients with ER+ breast cancer. The biological and clinical impact of SLC7A5/SLC3A2 co-expression was assessed in large annotated cohorts of ER+/HER2- breast cancer with long-term follow-up at the mRNA and protein levels. In vitro experiments were conducted to investigate the effect of SLC7A5/SLC3A2 knockdown in the proliferation of cancer cells and to the sensitivity to tamoxifen. We found that proliferation-related genes are highly expressed in subgroup of patients with high SLC7A5/SLC3A2, and knockdown of SLC7A5/SLC3A2 decreased proliferation of ER+ breast cancer cells. In patients treated with endocrine therapy, high SLC7A5/SLC3A2 co-expression was associated with poor patient outcome, and depletion of SLC7A5/SLC3A2 using siRNA increased the sensitivity of breast cancer cells to tamoxifen. On the basis of our findings, SLC7A5/SLC3A2 co-expression has the potential of identifying a subgroup of ER+/HER2- breast cancer patients who fail to benefit from endocrine therapy and could guide the choice of other alternative therapy

NADPH Oxidase Pathway Is Involved in Aortic Contraction Induced by A3 Adenosine Receptor in Mice

The NADPH oxidase (Nox) subunits 1, 2 (gp91 phox), and 4 are the major sources for reactive oxygen species (ROS) in vascular tissues. In conditions such as ischemia-reperfusion and hypoxia, both ROS and adenosine are released, suggesting a possible interaction. Our aim in this study was to examine the A3 adenosine receptor (A3AR)-induced vascular effects and its relation to ROS and Nox1, 2, and 4 using aortic tissues from wild-type (WT) and A3AR knockout (A3KO) mice. The selective A3AR agonist 2-chloro-N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (Cl-IBMECA) (10−10–10−5 M) induced contraction of the aorta from WT but not from A3KO mice, and this contraction was inhibited by the Nox inhibitor apocynin (10−5 M) and the ROS scavengers superoxide dismutase-polyethylene glycol and catalase-polyethylene glycol (100 U/ml each). Cl-IBMECA-induced contraction was not affected by the mast cell degranulator compound 48/80 (100 μg/ml) or the stabilizer cromolyn sodium (10−4 M). In addition, Cl-IBMECA (10−7 M) increased intracellular ROS generation by 35 ± 14% in WT but not in A3KO aorta, and this increase was inhibited by apocynin (10−5 M), diphenyleneiodonium chloride (10−5 M), and the A3AR antagonist 3-propyl-6-ethyl-5-[(ethylthio)carbonyl]-2 phenyl-4-propyl-3-pyridine carboxylate (MRS1523) (10−5 M). Furthermore, Cl-IBMECA selectively increased the protein expression of the Nox2 subunit by 150 ± 15% in WT but not in A3KO mice without affecting either Nox1 or 4, and this increase was inhibited by apocynin. The mRNA of Nox2 was unchanged by Cl-IBMECA in either WT or A3KO aortas. In conclusion, A3AR enhances ROS generation, possibly through activation of Nox2, with subsequent contraction of the mouse aorta

Glutamate dehydrogenase (GLUD1) expression in breast cancer

Dysregulated cellular metabolism is regarded as one of the hallmarks of cancer with some tumours utilising the glutamine metabolism pathway for their sustained proliferation and survival. Glutamate dehydrogenase (GLUD1) is a key enzyme in glutaminolysis converting glutamate to α-Ketoglutarate for entry into the TCA cycle. Breast cancer (BC) comprises a heterogeneous group of tumours in terms of molecular biology and clinical behaviour, and we have previously shown that altered glutamine metabolism varies substantially among the different molecular subtypes. We hypothesise that the prognostic value of GLUD1 expression will differ between the BC molecular subtypes and may act as a potential therapeutic target for BC tumours.Methods: GLUD1 was assessed at the DNA, mRNA (n=1,980) and protein (n=1,300) levels in large and well-characterised cohorts and correlated with clinicopathological parameters, molecular subtypes, patient outcome and treatments. Results: There was a correlation between GLUD1 mRNA and GLUD1 protein expression which were highly expressed in low grade Luminal/ER+ BC (