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Ovarian cancer is an aggressive gynaecological cancer with extremely poor prognosis, due to late diagnosis as well as the development of chemoresistance after first-line therapy. Research advances have found stem-like cells present in ovarian tumours, which exist in a dynamic niche and persist through therapy. The stem cell niche interacts extensively with the immune and non-immune components of the tumour microenvironment. Significant pathways associated with the cancer stem cell niche have been identified which interfere with the immune component of the tumour microenvironment, leading to immune surveillance evasion, dysfunction and suppression. This review aims to summarise current evidence-based knowledge on the cancer stem cell niche within the ovarian cancer tumour microenvironment and its effect on immune surveillance. Furthermore, the review seeks to understand the clinical consequences of this dynamic interaction by highlighting current therapies which target these processes.

Microcalcifications are vital mammographic indicators contributing to the early detection of up to 50% of non-palpable tumours and may also be valuable as prognostic markers. However, the precise mechanism by which they form remains incompletely understood. Following development of an in vitro model using human breast cancer cells lines cultured with a combination of mineralisation-promoting reagents, analysis of calcium deposition, alkaline phosphatase (ALP) activity and changes in expression of key genes was used to monitor the calcification process. Two cell lines were identified as successfully mineralising in vitro , MDA-MB-231 and SKBR3. Mineralising cell lines displayed higher levels of ALP activity that was further increased by addition of mineralisation promoting media. qPCR analysis revealed changes in expression of both pro- (RUNX2) and anti- (MGP, ENPP1) mineralisation genes. Mineralisation was suppressed by chelation of intracellular Ca 2+ and inhibition of TRPM7, demonstrating a functional role for the channel in formation of microcalcifications. Increased Mg 2+ was also found to effectively reduce calcium deposition. These results expand the number of human breast cancer cell lines with a demonstrated in vitro mineralisation capability, provide further evidence for the role of an active, cellular process of microcalcification formation and demonstrate for the first time a role for TRPM7 mediated Ca 2+ transport.

Bone is the most common site of metastasis for breast cancer, however the reasons for this remain unclear. We hypothesise that under certain conditions mammary cells possess osteomimetic capabilities that may allow them to adapt to, and flourish within, the bone microenvironment. Mammary cells are known to calcify within breast tissue and we have recently reported a novel in vitro model of mammary mineralization using murine mammary adenocarcinoma 4T1 cells. In this study, the osteomimetic properties of the mammary adenocarcinoma cell line and the conditions required to induce mineralization were characterized extensively. It was found that exogenous organic phosphate and inorganic phosphate induce mineralization in a dose dependent manner in 4T1 cells. Ascorbic acid and dexamethasone alone have no effect. 4T1 cells also show enhanced mineralization in response to bone morphogenetic protein 2 in the presence of phosphate supplemented media. The expression of several bone matrix proteins were monitored throughout the process of mineralization and increased expression of collagen type 1 and bone sialoprotein were detected, as determined by real-time RT-PCR. In addition, we have shown for the first time that 3D collagen glycosaminoglycan scaffolds, bioengineered to represent the bone microenvironment, are capable of supporting the growth and mineralization of 4T1 adenocarcinoma cells. These 3D scaffolds represent a novel model system for the study of mammary mineralization and bone metastasis. This work demonstrates that mammary cells are capable of osteomimicry, which may ultimately contribute to their ability to preferentially metastasize to, survive within and colonize the bone microenvironment.

Microcalcifications are early markers of breast cancer and can provide valuable prognostic information to support clinical decision-making. Current detection of calcifications in breast tissue is based on X-ray mammography, which involves the use of ionizing radiation with potentially detrimental effects, or MRI scans, which have limited spatial resolution. Additionally, these techniques are not capable of discriminating between microcalcifications from benign and malignant lesions. Several studies show that vibrational spectroscopic techniques are capable of discriminating and classifying breast lesions, with a pathology grade based on the chemical composition of the microcalcifications. However, the occurrence of microcalcifications in the breast and the underlying mineralization process are still not fully understood. Using a previously established model of in vitro mineralization, the MDA-MB-231 human breast cancer cell line was induced using two osteogenic agents, inorganic phosphate (Pi) and β-glycerophosphate (βG), and direct monitoring of the mineralization process was conducted using Raman micro-spectroscopy. MDA-MB-231 cells cultured in a medium supplemented with Pi presented more rapid mineralization (by day 3) than cells exposed to βG (by day 11). A redshift of the phosphate stretching peak for cells supplemented with βG revealed the presence of different precursor phases (octacalcium phosphate) during apatite crystal formation. These results demonstrate that Raman micro-spectroscopy is a powerful tool for nondestructive analysis of mineral species and can provide valuable information for evaluating mineralization dynamics and any associated breast cancer progression, if utilized in pathological samples. The mineralization of MDA-MB-231 breast cells was investigated using Raman micro-spectroscopy. Mineralization was induced by two osteogenic agents: inorganic phosphate (Pi) and β-Glycerophosphate (βG). The results show that the uptake of Pi allows a faster mineralization and the uptake of βG indicated the presence of a precursor phase during the hydroxyapatite crystal formation.

Aim Energy drinks are widely consumed worldwide and are recognised for their adverse health effects, usually due to their high caffeine content. However, little is known about their impact on oral and general health. The aim of this investigation was to review the most popular energy drinks sold in the UK, for their possible effect on oral health and contribution to obesity. Materials and methods Five drinks representing 75% of the UK energy drinks market were purposively selected (Lucozade, Red Bull, Monster, Rockstar and Relentless). pH and sugar content were measured and their ingredients reviewed in the context of oral and general health, focusing on dental caries and erosion and obesity. Results All five energy drinks investigated had pH values below the critical value (5.5) associated with dental erosion; the lowest pH was 2.72 (Lucozade) and the highest was 3.37 (Monster). The drinks also contained excessive amounts of free sugars, ranging from 25.5 g (Red Bull) to 69.2 g (Rockstar). Differences in sugar content were mainly explained by portion size. Other ingredients contained within the energy drinks, caffeine and various acids, are also linked to oral and general health. Conclusion Regular consumption of energy drinks could contribute to dental erosion and the development of obesity. Lucozade and Rockstar were found to potentially have the greatest impact on oral health and obesity. Achieving a healthy product by reformulation is highly unlikely due to the very high initial free sugar content. Thus, health professionals need to acknowledge the popularity of these products and help their clients to reduce their use. This is the first study which compares in detail the potential oral and general health consequences of overuse of a selection of energy drinks popular in the UK.

Background Over the past decade, the rise of consumers following a gluten-free diet has increased greatly. The majority of people following a gluten-free diet have not been diagnosed with coeliac disease or gluten or wheat intolerance but believe it to be a health benefit.Aim To assess the differences between gluten-free and gluten-containing products with regards to the implications this might have on oral (and wider) health.Method In total, 50 purposively selected products (25 gluten-free and gluten-containing pairs) available to UK consumers, classified using the UK National Diet and Nutrition Survey food categories, were analysed using content analysis of food packaging. The European Union front-of-pack labelling system revealed the nutritional composition of each product, focusing on carbohydrates, sugars and energy. Cost and use of emotive language to market products was also assessed.Results A nutritional comparison of the 25 product pairings found that, on average, all gluten-free products contained more calories, total carbohydrates and total sugar. The majority of the gluten-free products were classified as 'confectionary' or 'baked goods,' emphasising that products primarily consisted of foods high in sugar. The average sugar per 100 g for each category of food ranged from 2.5-37.0 g/100 g (gluten-free) compared to 2.1-30 g/100 g (gluten-containing). All gluten-free products were considerably more expensive when compared with the conventional version; the average price difference ranged from £0.08 to £4.40.Conclusion This study emphasises the 'health halo' phenomena, where foods for special diets are regarded by consumers as healthy when in fact they are not. This results partly from the products being mainly high-sugar 'treats', which are not a core of the UK Eatwell Guide food-based dietary guidelines. As many people consuming gluten-free products in the UK do not need them from a medical perspective, this could have implications for oral and wider health. It is important that members of the dental team are aware of the possible implications of a gluten-free diet where it is not medically indicated, coupled with reliance on convenience foods.

Background Early prediction of Gestational Diabetes Mellitus (GDM) risk is of particular importance as it may enable more efficacious interventions and reduce cumulative injury to mother and fetus. The aim of this study is to develop machine learning (ML) models, for the early prediction of GDM using widely available variables, facilitating early intervention, and making possible to apply the prediction models in places where there is no access to more complex examinations. Methods The dataset used in this study includes registries from 1,611 pregnancies. Twelve different ML models and their hyperparameters were optimized to achieve early and high prediction performance of GDM. A data augmentation method was used in training to improve prediction results. Three methods were used to select the most relevant variables for GDM prediction. After training, the models ranked with the highest Area under the Receiver Operating Characteristic Curve (AUCROC), were assessed on the validation set. Models with the best results were assessed in the test set as a measure of generalization performance. Results Our method allows identifying many possible models for various levels of sensitivity and specificity. Four models achieved a high sensitivity of 0.82, a specificity in the range 0.72–0.74, accuracy between 0.73–0.75, and AUCROC of 0.81. These models required between 7 and 12 input variables. Another possible choice could be a model with sensitivity of 0.89 that requires just 5 variables reaching an accuracy of 0.65, a specificity of 0.62, and AUCROC of 0.82. Conclusions The principal findings of our study are: Early prediction of GDM within early stages of pregnancy using regular examinations/exams; the development and optimization of twelve different ML models and their hyperparameters to achieve the highest prediction performance; a novel data augmentation method is proposed to allow reaching excellent GDM prediction results with various models.

Context and Objective:Adipose tissue insulin resistance may cause hepatic and skeletal muscle insulin resistance by releasing excess free fatty acids (FFAs). Because no consensus exists on how to quantify adipose tissue insulin sensitivity we compared three methods for measuring adipose tissue insulin sensitivity: the single step insulin clamp, the multistep pancreatic clamp, and the adipose tissue insulin resistance index (Adipo-IR).Design and Participants:We studied insulin sensitivity in 25 adults by measuring the insulin concentration resulting in 50% suppression of palmitate flux (IC50) using both a multistep pancreatic clamp and a one-step hyperinsulinemic-euglycemic clamp. Palmitate kinetics were measured using a continuous infusion of [U-13C]palmitate. Adipo-IR was calculated from fasting insulin and fasting FFA concentrations.Results:Adipo-IR was reproducible (sample coefficient of variability, 10.0%) and correlated with the IC50 measured by the multistep pancreatic clamp technique (r, 0.86; P < 0.001). Age and physical fitness were significant predictors of the residual variation between Adipo-IR and IC50, with a positive relationship with age (r, 0.47; P = 0.02) and a negative association with VO2 peak (r, −0.46; P = 0.02). Likewise, IC50 measured by the multistep pancreatic clamp technique correlated with IC50 measured using the one-step hyperinsulinemic-euglycemic clamp technique (r, 0.73; P < 0.001).Conclusion:Adipo-IR and the one-step hyperinsulinemic-euglycemic clamp technique using a palmitate tracer are good predictors of a gold standard measure of adipose tissue insulin sensitivity. However, age and physical fitness systematically affect the predictive values. Although Adipo-IR is suitable for larger population studies, the multistep pancreatic clamp technique is probably needed for mechanistic studies of adipose tissue insulin action.A one-step hyperinsulinemic-euglycemic clamp with FFA tracers and Adipo-IR correlate with a gold standard measure of adipose insulin sensitivity, but age and physical fitness affect the relationships.

Introduction and context This paper describes how research and evidence influenced Welsh Government policy to fund a programme (Gwên am Byth - A Lasting Smile) with the aim of improving the oral health of older people living in care homes. It describes how collaborative multi-agency working supported development and delivery of the programme. The context was policy in Wales. This included the Welsh Government response to the public inquiry into Mid Staffordshire NHS Foundation Trust, the report into care homes by the Older People's Commissioner for Wales, and the Welsh Government Health and Care Standards for Wales which include a standard relating to oral health. The aim was to introduce a programme, Gwên am Byth, to support 'oral hygiene and mouth care for older people living in care homes through the development of a consistent all-Wales approach'; this aligns with contemporaneous NICE guidelines.Materials and methods Recurrent Welsh Government funding was identified to support a community dental service (CDS) led programme (Gwên am Byth). A multi-professional team led the development and testing of materials and resources to support the programme, underpin training for care home staff, and allow them to assess and provide safe mouth care for residents. A Welsh Health Circular was published to ensure a consistent all-Wales approachResults New staff have been employed in all health boards, and an assessment tool has been developed and is in the final stages of validation. All Wales resources have been published for induction, training and education, and to support care home staff. Evidence-based care plans have been produced which link to individual residents' risks and needs. There is close working with other health and social care professionals. By March 2019, half of all care homes were participating in the programme to a greater or lesser extent. Over 5,000 health and care staff had been trained, and over 5,600 residents had been assessed and supported with delivery of an individual mouth care plan. There has been positive feedback from care home staff, residents, carers and CDS staff, although barriers to delivery remain.Discussion This paper describes programme delivery in the four years since Gwên am Byth began. The drivers for change are described and the need to influence Welsh Government policy decisions when funding was available. The authors discuss issues which can impact on the pace of change, and ways in which health and care staff can effectively work together to implement improvements.Conclusions Starting with a blank page, a national programme has been established with the aim of improving the oral health of older people living in care homes in Wales. The paper describes the lessons learnt in implementing the programme and notes that Welsh Government has recognised the value of Gwên am Byth by committing to double the recurrent programme funding.Key pointsOlder people living in care homes may require day-to-day support with tasks such as oral hygiene; therefore, care home staff require training to safely support residents with effective and appropriate mouth care.A Welsh Government-funded programme (Gwên am Byth) is described which ensures a consistent approach across Wales with the aim to improve the oral health of older people living in care homes.Includes practical pointers for those who want to secure resources for vulnerable older people living in care homes and turn policy into action.

Background Case-based learning (CBL) is a useful pedagogical approach, for which learner experience has been well researched. The experience of faculty is less known. CBL was integrated into the first year of a new pre-licensure medical curriculum, so the faculty experience of transition from large group teaching to structured CBL was investigated. Methodology Interpretative phenomenological analysis (IPA) was undertaken to explore the facilitator lived experience through reflective inquiry. Ten CBL facilitators were purposively selected from a diverse pool of faculty using maximum variation; faculty were involved in patient care, research, and education, and were a mix of ages, ethnicities and genders. Semi-structured interviews were conducted and analysed according to the IPA structure. Results Overall experiences were positive. Facilitators repeatedly expressed the enjoyment felt from closer student interaction. They reported that CBL afforded an authentic and active teaching approach. Other themes included: initial uncertainty regarding their role, anxiety around standardisation of the student experience and concerns regarding the level of content expertise required. However, confidence generally improved with experience facilitating. Conclusion These insights provide a deeper understanding of faculty perceptions of the CBL facilitator’s role and will better inform future faculty development initiatives, as well as the iterative design of the CBL teaching resources.