Spatial distribution of metabolites in the retina and its relevance to studies of metabolic retinal disorders

Introduction: The primate retina has evolved regional specialisations for specific visual functions. The macula is specialised towards high acuity vision and is an area that contains an increased density of cone photoreceptors and signal processing neurons. Different regions in the retina display unique susceptibility to pathology, with many retinal diseases primarily affecting the macula. Objectives: To better understand the properties of different retinal areas we studied the differential distribution of metabolites across the retina. Methods: We conducted an untargeted metabolomics analysis on full-thickness punches from three different regions (macula, temporal peri-macula and periphery) of healthy primate retina. Results: Nearly half of all metabolites identified showed differential abundance in at least one comparison between the three regions. Furthermore, mapping metabolomics results from macula-specific eye diseases onto our region-specific metabolite distributions revealed differential abundance defining systemic metabolic dysregulations that were region specific. Conclusions: The unique metabolic phenotype of different retinal regions is likely due to the differential distribution of different cell types in these regions reflecting the specific metabolic requirements of each cell type. Our results may help to better understand the pathobiology of retinal diseases with region specificity

‘Because it’s our culture!’ (Re)negotiating the meaning of lobola in Southern African secondary schools

Payment of bridewealth or lobola is a significant element of marriage among the Basotho of Lesotho and the Shona of Zimbabwe. However, the functions and meanings attached to the practice are constantly changing. In order to gauge the interpretations attached to lobola by young people today, this paper analyses a series of focus group discussions conducted among senior students at two rural secondary schools. It compares the interpretations attached by the students to the practice of lobola with academic interpretations (both historical and contemporary). Among young people the meanings and functions of lobola are hotly contested, but differ markedly from those set out in the academic literature. While many students see lobola as a valued part of ‘African culture’, most also view it as a financial transaction which necessarily disadvantages women. The paper then seeks to explain the young people’s interpretations by reference to discourses of ‘equal rights’ and ‘culture’ prevalent in secondary schools. Young people make use of these discourses in (re)negotiating the meaning of lobola, but the limitations of the discourses restrict the interpretations of lobola available to them

The effect of gender, age, and geographical location on the incidence and prevalence of renal replacement therapy in Wales

BACKGROUND: This study used a cross sectional survey to examine the effect of gender, age, and geographical location on the population prevalence of renal replacement therapy (RRT) provision in Wales. METHODS: Physicians in renal centres in Wales and in adjacent areas of England were asked to undertake a census of patients on renal replacement therapy on 30 June 2004 using an agreed protocol. Data were collated and analysed in anonymous form. RESULTS: 2434 patients were on RRT in Wales at the census date. Median age of patients on RRT was 56 years, peritoneal dialysis 58 years, haemodialysis 66 years and transplantation 50 years. The three treatment modalities had significantly different age-specific peak prevalence rates and distributions. RRT age-specific prevalence rates peaked at around 70 years (1790 pmp), transplantation at around 60 years (924 pmp), haemodialysis at around 80 years (1080 pmp) and peritoneal dialysis did not have a clear peak prevalence rate. Age-specific incidence of RRT peaked at a rate of 488 pmp at 79 years, as did incidence rates for haemodialysis, which peaked at the same age. Age had less effect on the initiation of peritoneal dialysis, which had a broad plateau between the early fifties and late seventies. Kidney transplantation rates were highest in the early fifties but were markedly absent in old age. CONCLUSION: Differences in the provision of RRT are evident, particularly in the very elderly, where the gender difference for haemodialysis is particularly marked. The study illustrates that grouping patients over 75 years into a single age-band may mask significant diversity within this age group. Significant numbers of very elderly patients who are currently not receiving RRT may wish to receive RRT as the elderly population increases, and as technology improves survival and quality of life on RRT. The study suggests that if technologies that are more effective were developed, and which had a lower impact on quality of life, there might be up to a 17% increase in demand for RRT in those aged over 75 years; around 90% of this increased demand would be for haemodialysis

How did the latest increase in fees in England affect student enrolment and inequality?

This paper presents a first analysis of the increase of undergraduate tuition fees to £9,000 (€11.000) in English higher education in 2012. I use a semi-experimental research design to estimate the effect of the reforms, based on student enrolment data drawn from the Higher Education Statistics Agency (HESA). Taking into account possible anticipation effects of the fee increase, I find that enrolment declined by 15 % in the treated groups as a result of the tuition fee increase. This number is almost three times higher than what previous studies have found, and may represent a serious long term cost for the English economy. The decline in enrolments is particularly pronounced for students in older age groups and students from the service class and the middle class. No effect is visible for students from the working class, indicating that the reforms did not lead to a much-feared increase in class bias in higher education enrolment. The reforms also seem not to have exacerbated ethnic inequality in higher education, as all ethnic groups were negatively affected by the reforms. These results are consistent with earlier research in the United States and the United Kingdom, although they expand our understanding of student price responsiveness in other important ways. The paper argues that younger and older students face different costs and benefits. Older students may be less certain about their benefits, and therefore be more sensitive towards price increases. The strong decrease in mature learners may require a policy response, taking into account these differing incentives

Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin

There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters

A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma

The phosphatidylinositol 3-kinase signal transduction pathway members are often activated in tumor samples from patients with non-Hodgkin's lymphoma (NHL). Everolimus is an oral agent that targets the raptor mammalian target of rapamycin (mTORC1). The goal of this trial was to learn the antitumor activity and toxicity of single-agent everolimus in patients with relapsed/refractory aggressive NHL. Patients received everolimus 10 mg PO daily. Response was assessed after two and six cycles, and then every three cycles until progression. A total of 77 patients with a median age of 70 years were enrolled. Patients had received a median of three previous therapies and 32% had undergone previous transplant. The overall response rate (ORR) was 30% (95% confidence interval: 20–41%), with 20 patients achieving a partial remission and 3 a complete remission unconfirmed. The ORR in diffuse large B cell was 30% (14/47), 32% (6/19) in mantle cell and 38% (3/8) in follicular grade 3. The median duration of response was 5.7 months. Grade 3 or 4 anemia, neutropenia and thrombocytopenia occurred in 14, 18 and 38% of patients, respectively. Everolimus has single-agent activity in relapsed/refractory aggressive NHL and provides proof-of-concept that targeting the mTOR pathway is clinically relevant

HDL Proteome in Hemodialysis Patients: A Quantitative Nanoflow Liquid Chromatography-Tandem Mass Spectrometry Approach

Aside from a decrease in the high-density lipoprotein (HDL) cholesterol levels, qualitative abnormalities of HDL can contribute to an increase in cardiovascular (CV) risk in end-stage renal disease (ESRD) patients undergoing chronic hemodialysis (HD). Dysfunctional HDL leads to an alteration of reverse cholesterol transport and the antioxidant and anti-inflammatory properties of HDL. In this study, a quantitative proteomics approach, based on iTRAQ labeling and nanoflow liquid chromatography mass spectrometry analysis, was used to generate detailed data on HDL-associated proteins. The HDL composition was compared between seven chronic HD patients and a pool of seven healthy controls. To confirm the proteomics results, specific biochemical assays were then performed in triplicate in the 14 samples as well as 46 sex-matched independent chronic HD patients and healthy volunteers. Of the 122 proteins identified in the HDL fraction, 40 were differentially expressed between the healthy volunteers and the HD patients. These proteins are involved in many HDL functions, including lipid metabolism, the acute inflammatory response, complement activation, the regulation of lipoprotein oxidation, and metal cation homeostasis. Among the identified proteins, apolipoprotein C-II and apolipoprotein C-III were significantly increased in the HDL fraction of HD patients whereas serotransferrin was decreased. In this study, we identified new markers of potential relevance to the pathways linked to HDL dysfunction in HD. Proteomic analysis of the HDL fraction provides an efficient method to identify new and uncharacterized candidate biomarkers of CV risk in HD patients