Oral tolerance to cancer can be abrogated by T regulatory cell inhibition

Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue – JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups - this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut

Work-related psychological health among clergywomen in Australia

Drawing on the classic model of balanced affect, the Francis Burnout Inventory conceptualises good work-related psychological health among clergy in terms of negative affect being balanced by positive affect. This paper sets out to explore the relationship between work-related psychological health and psychological type (as assessed by the Francis Psychological-Type Scales) among a sample of 212 Australian clergywomen who completed the National Church Life Survey Form L in 2006. The data supported the internal consistency reliability of the Francis Burnout Inventory and Francis Psychological-Type Scales and found that work-related psychological health was positively related to extraversion and sensing

Improving the psychological evaluation of exercise referral: psychometric properties of the Exercise Referral Quality of Life Scale

There is a growing need to assess the psychological outcomes of exercise referral and the National Institute of Health and Care Excellence has called for the routine assessment of life-quality. However, a quality of life scale specific to the requirements of exercise referral is currently unavailable. Therefore, the aim of this study was to produce a quality of life measure for this purpose. The Exercise Referral Quality of Life Scale is a 22-item measure comprising three domains: mental and physical health, injury pain and illness and physical activity facilitators. Exploratory factor analysis determined the initial factor structure and was subsequently confirmed by confirmatory factor analysis. Additional scale properties were also assessed. The scale contributes to the global need for improved consistent psychological outcome assessment of exercise referral

Nutrition Strategies for Triathlon

Contemporary sports nutrition guidelines recommend that each athlete develop a personalised, periodised and practical approach to eating that allows him or her to train hard, recover and adapt optimally, stay free of illness and injury and compete at their best at peak races. Competitive triathletes undertake a heavy training programme to prepare for three different sports while undertaking races varying in duration from 20 min to 10 h. The everyday diet should be adequate in energy availability, provide CHO in varying amounts and timing around workouts according to the benefits of training with low or high CHO availability and spread high-quality protein over the day to maximise the adaptive response to each session. Race nutrition requires a targeted and well-practised plan that maintains fuel and hydration goals over the duration of the specific event, according to the opportunities provided by the race and other challenges, such as a hot environment. Supplements and sports foods can make a small contribution to a sports nutrition plan, when medical supplements are used under supervision to prevent/treat nutrient deficiencies (e.g. iron or vitamin D) or when sports foods provide a convenient source of nutrients when it is impractical to eat whole foods. Finally, a few evidence-based performance supplements may contribute to optimal race performance when used according to best practice protocols to suit the triathlete’s goals and individual responsiveness

The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase

Tumour metastasis is a complex process involving reciprocal interplay between cancer cells and host stroma at both primary and secondary sites, and is strongly influenced by microenvironmental factors such as hypoxia. Tumour-secreted proteins play a crucial role in these interactions and present strategic therapeutic potential. Metastasis of breast cancer to the bone affects approximately 85% of patients with advanced disease and renders them largely untreatable. Specifically, osteolytic bone lesions, where bone is destroyed, lead to debilitating skeletal complications and increased patient morbidity and mortality. The molecular interactions governing the early events of osteolytic lesion formation are currently unclear. Here we show hypoxia to be specifically associated with bone relapse in patients with oestrogen-receptor negative breast cancer. Global quantitative analysis of the hypoxic secretome identified lysyl oxidase (LOX) as significantly associated with bone-tropism and relapse. High expression of LOX in primary breast tumours or systemic delivery of LOX leads to osteolytic lesion formation whereas silencing or inhibition of LOX activity abrogates tumour-driven osteolytic lesion formation. We identify LOX as a novel regulator of NFATc1-driven osteoclastogenesis,independent of RANK ligand, which disrupts normal bone homeostasisleading to the formation of focal pre-metastatic lesions. We show that these lesions subsequently provide a platform for circulating tumour cells to colonize and form bone metastases. Our study identifies a novel mechanism of regulation of bone homeostasis and metastasis, opening up opportunities for novel therapeutic intervention with important clinical implications

How non-native English-speaking staff are evaluated in linguistically diverse organizations: A sociolinguistic perspective

The aim of this paper is to examine the effects of evaluations of non-native speaking staff?s spoken English in international business settings. We adopt a sociolinguistic perspective on power and inequalities in linguistically diverse organizations in an Anglophone environment. The interpretive qualitative study draws on 54 interviews with non-native English-speaking staff in 19 UK business schools. We analyze, along the dimensions of status, solidarity and dynamism, the ways in which non-native speakers, on the basis of their spoken English, are evaluated by themselves and by listeners. We show how such evaluations refer to issues beyond the speaker?s linguistic fluency, and have consequences for her or his actions. The study contributes to the literature on language and power in international business through offering fine-grained insights into and elucidating how the interconnected evaluative processes impact the formation and perpetuation of organizational power relations and inequalities. It also puts forward implications for managing the officially monolingual, yet linguistically diverse organizations

Sexual dimorphism in cancer.

The incidence of many types of cancer arising in organs with non-reproductive functions is significantly higher in male populations than in female populations, with associated differences in survival. Occupational and/or behavioural factors are well-known underlying determinants. However, cellular and molecular differences between the two sexes are also likely to be important. In this Opinion article, we focus on the complex interplay that sex hormones and sex chromosomes can have in intrinsic control of cancer-initiating cell populations, the tumour microenvironment and systemic determinants of cancer development, such as the immune system and metabolism. A better appreciation of these differences between the two sexes could be of substantial value for cancer prevention as well as treatment

Early warnings of the potential for malaria transmission in rural Africa using the hydrology, entomology and malaria transmission simulator (HYDREMATS)

<p>Abstract</p> <p>Background</p> <p>Early warnings of malaria transmission allow health officials to better prepare for future epidemics. Monitoring rainfall is recognized as an important part of malaria early warning systems. The Hydrology, Entomology and Malaria Simulator (HYDREMATS) is a mechanistic model that relates rainfall to malaria transmission, and could be used to provide early warnings of malaria epidemics.</p> <p>Methods</p> <p>HYDREMATS is used to make predictions of mosquito populations and vectorial capacity for 2005, 2006, and 2007 in Banizoumbou village in western Niger. HYDREMATS is forced by observed rainfall, followed by a rainfall prediction based on the seasonal mean rainfall for a period two or four weeks into the future.</p> <p>Results</p> <p>Predictions made using this method provided reasonable estimates of mosquito populations and vectorial capacity, two to four weeks in advance. The predictions were significantly improved compared to those made when HYDREMATS was forced with seasonal mean rainfall alone.</p> <p>Conclusions</p> <p>HYDREMATS can be used to make reasonable predictions of mosquito populations and vectorial capacity, and provide early warnings of the potential for malaria epidemics in Africa.</p

Lasing microbottles

Lasing of an optical microbottle resonator at predetermined resonant wavelengths is feasible via spatial engineering of the pump laser beam