Quality of life in Type 1 (insulin-dependent) diabetic patients prior to and after pancreas and kidney transplantation in relation to organ function

Improvement of the quality of life in Type 1 (insulin-dependent) diabetic patients with severe late complications is one of the main goals of pancreas and/or kidney grafting. To assess the influences of these treatment modalities on the different aspects of the quality of life a cross-sectional study in 157 patients was conducted. They were categorized into patients pre-transplant without dialysis (n=29; Group A), pre-transplant under dialysis (n=44; Group B), post-transplant with pancreas and kidney functioning (n=31; Group C), post-transplant with functioning kidney, but insulin therapy (n=29; Group D), post-transplant under dialysis and insulin therapy again (n=15; Group E) and patients after single pancreas transplantation and rejection, with good renal function, but insulin therapy (n=9; Group F). All patients answered a mailed, self-administered questionnaire (217 questions) consisting of a broad spectrum of rehabilitation criteria. The results indicate a better quality of life in Groups C and D as compared to the other groups. In general the scores are highest in C, but without any significant difference to D. Impressive significant differences between C or D and the other groups were found especially in their satisfaction with physical capacity, leisure-time activities or the overall quality of life. The satisfaction with the latter is highest in C (mean±SEM: 4.0±0.2 on a 1 to 5-rating scale; significantly different from A: 3.1±0.1, B: 2.7±0.2 and E: 2.6±0.3; p<0.01), followed by D (3.8±0.2; significantly different from B and E; p<0.01). Group F shows a mean of 3.1±0.4, which is not significantly different from C. The percentages of patients in each group, who are not working: A: 38 %, B: 64 %, C: 74 %, D: 66 %, E: 87 % and F: 78 % indicate that there is no marked improvement in the vocational situation after successful grafting

Selective Estrogen Receptor Down-Regulator and Selective Estrogen Receptor Modulators Differentially Regulate Lactotroph Proliferation

occupation, differentially modulates the biological outcome of anti-estrogens. expression and release, as well as ERE-mediated transcriptional activity. expression

Chair based exercise in community settings: a cluster randomised feasibility study

Background: Some older people who find standard exercise programmes too strenuous may be encouraged to exercise while remaining seated - chair based exercises (CBE). We previously developed a consensus CBE programme (CCBE) following a modified Delphi process. We firstly needed to test the feasibility and acceptability of this treatment approach and explore how best to evaluate it before undertaking a definitive trial. Methods: A feasibility study with a cluster randomised controlled trial component was undertaken to 1. Examine the acceptability, feasibility and tolerability of the intervention and 2. Assess the feasibility of running a trial across 12 community settings (4 day centres, 4 care homes, 4 community groups). Centres were randomised to either CCBE, group reminiscence or usual care. Outcomes were collected to assess the feasibility of the trial parameters: level of recruitment interest and eligibility, randomisation, adverse events, retention, completion of health outcomes, missing data and delivery of the CCBE. Semi- structured interviews were conducted with participants and care staff following the intervention to explore acceptability. Results: 48% (89 out of 184 contacted) of eligible centres were interested in participating with 12 recruited purposively. 73% (94) of the 128 older people screened consented to take part with 83 older people then randomised following mobility testing. Recruitment required greater staffing levels and resources due to 49% of participants requiring a consultee declaration. There was a high dropout rate (40%) primarily due to participants no longer attending the centres. The CCBE intervention was delivered once a week in day centres and community groups and twice a week in care homes. Older people and care staff found the CCBE intervention largely acceptable. Conclusion: There was a good level of interest from centres and older people and the CCBE intervention was largely welcomed. The trial design and governance procedures would need to be revised to maximise recruitment and retention. If the motivation for a future trial is physical health then this study has identified that further work to develop the CCBE delivery model is warranted to ensure it can be delivered at a frequency to elicit physiological change. If the motivation for a future trial is psychological outcomes then this study has identified that the current delivery model is feasible

Natural Killer Cell Mediated Cytotoxic Responses in the Tasmanian Devil

The Tasmanian devil (Sarcophilus harrisii), the world's largest marsupial carnivore, is under threat of extinction following the emergence of an infectious cancer. Devil facial tumour disease (DFTD) is spread between Tasmanian devils during biting. The disease is consistently fatal and devils succumb without developing a protective immune response. The aim of this study was to determine if Tasmanian devils were capable of forming cytotoxic antitumour responses and develop antibodies against DFTD cells and foreign tumour cells. The two Tasmanian devils immunised with irradiated DFTD cells did not form cytotoxic or humoral responses against DFTD cells, even after multiple immunisations. However, following immunisation with xenogenic K562 cells, devils did produce cytotoxic responses and antibodies against this foreign tumour cell line. The cytotoxicity appeared to occur through the activity of natural killer (NK) cells in an antibody dependent manner. Classical NK cell responses, such as innate killing of DFTD and foreign cancer cells, were not observed. Cells with an NK-like phenotype comprised approximately 4 percent of peripheral blood mononuclear cells. The results of this study suggest that Tasmanian devils have NK cells with functional cytotoxic pathways. Although devil NK cells do not directly recognise DFTD cancer cells, the development of antibody dependent cell-mediated cytotoxicity presents a potential pathway to induce cytotoxic responses against the disease. These findings have positive implications for future DFTD vaccine research

Asteroseismology and Interferometry

Asteroseismology provides us with a unique opportunity to improve our understanding of stellar structure and evolution. Recent developments, including the first systematic studies of solar-like pulsators, have boosted the impact of this field of research within Astrophysics and have led to a significant increase in the size of the research community. In the present paper we start by reviewing the basic observational and theoretical properties of classical and solar-like pulsators and present results from some of the most recent and outstanding studies of these stars. We centre our review on those classes of pulsators for which interferometric studies are expected to provide a significant input. We discuss current limitations to asteroseismic studies, including difficulties in mode identification and in the accurate determination of global parameters of pulsating stars, and, after a brief review of those aspects of interferometry that are most relevant in this context, anticipate how interferometric observations may contribute to overcome these limitations. Moreover, we present results of recent pilot studies of pulsating stars involving both asteroseismic and interferometric constraints and look into the future, summarizing ongoing efforts concerning the development of future instruments and satellite missions which are expected to have an impact in this field of research.Comment: Version as published in The Astronomy and Astrophysics Review, Volume 14, Issue 3-4, pp. 217-36

Climate Change and Trophic Response of the Antarctic Bottom Fauna

BACKGROUND: As Earth warms, temperate and subpolar marine species will increasingly shift their geographic ranges poleward. The endemic shelf fauna of Antarctica is especially vulnerable to climate-mediated biological invasions because cold temperatures currently exclude the durophagous (shell-breaking) predators that structure shallow-benthic communities elsewhere. METHODOLOGY/PRINCIPAL FINDINGS: We used the Eocene fossil record from Seymour Island, Antarctic Peninsula, to project specifically how global warming will reorganize the nearshore benthos of Antarctica. A long-term cooling trend, which began with a sharp temperature drop approximately 41 Ma (million years ago), eliminated durophagous predators-teleosts (modern bony fish), decapod crustaceans (crabs and lobsters) and almost all neoselachian elasmobranchs (modern sharks and rays)-from Antarctic nearshore waters after the Eocene. Even prior to those extinctions, durophagous predators became less active as coastal sea temperatures declined from 41 Ma to the end of the Eocene, approximately 33.5 Ma. In response, dense populations of suspension-feeding ophiuroids and crinoids abruptly appeared. Dense aggregations of brachiopods transcended the cooling event with no apparent change in predation pressure, nor were there changes in the frequency of shell-drilling predation on venerid bivalves. CONCLUSIONS/SIGNIFICANCE: Rapid warming in the Southern Ocean is now removing the physiological barriers to shell-breaking predators, and crabs are returning to the Antarctic Peninsula. Over the coming decades to centuries, we predict a rapid reversal of the Eocene trends. Increasing predation will reduce or eliminate extant dense populations of suspension-feeding echinoderms from nearshore habitats along the Peninsula while brachiopods will continue to form large populations, and the intensity of shell-drilling predation on infaunal bivalves will not change appreciably. In time the ecological effects of global warming could spread to other portions of the Antarctic coast. The differential responses of faunal components will reduce the endemic character of Antarctic subtidal communities, homogenizing them with nearshore communities at lower latitudes

The unfolded protein response and its relevance to connective tissue diseases

The unfolded protein response (UPR) has evolved to counter the stresses that occur in the endoplasmic reticulum (ER) as a result of misfolded proteins. This sophisticated quality control system attempts to restore homeostasis through the action of a number of different pathways that are coordinated in the first instance by the ER stress-senor proteins IRE1, ATF6 and PERK. However, prolonged ER-stress-related UPR can have detrimental effects on cell function and, in the longer term, may induce apoptosis. Connective tissue cells such as fibroblasts, osteoblasts and chondrocytes synthesise and secrete large quantities of proteins and mutations in many of these gene products give rise to heritable disorders of connective tissues. Until recently, these mutant gene products were thought to exert their effect through the assembly of a defective extracellular matrix that ultimately disrupted tissue structure and function. However, it is now becoming clear that ER stress and UPR, because of the expression of a mutant gene product, is not only a feature of, but may be a key mediator in the initiation and progression of a whole range of different connective tissue diseases. This review focuses on ER stress and the UPR that characterises an increasing number of connective tissue diseases and highlights novel therapeutic opportunities that may arise

Palatal development of preterm and low birthweight infants compared to term infants – What do we know? Part 1: The palate of the term newborn

BACKGROUND: The evidence on prematurity as 'a priori' a risk for palatal disturbances that increase the need for orthodontic or orthognathic treatment is still weak. Further well-designed clinical studies are needed. The objective of this review is to provide a fundamental analysis of methodologies, confounding factors, and outcomes of studies on palatal development. One focus of this review is the analysis of studies on the palate of the term newborn, since knowing what is 'normal' is a precondition of being able to assess abnormalities. METHODS: A search profile based on Cochrane search strategies applied to 10 medical databases was used to identify existing studies. Articles, mainly those published before 1960, were identified from hand searches in textbooks, encyclopedias, reference lists and bibliographies. Sources in English, German, and French of more than a century were included. Data for term infants were recalculated if particular information about weight, length, or maturity was given. The extracted values, especially those from non-English paper sources, were provided unfiltered for comparison. RESULTS: The search strategy yielded 182 articles, of which 155 articles remained for final analysis. Morphology of the term newborn's palate was of great interest in the first half of the last century. Two general methodologies were used to assess palatal morphology: visual and metrical descriptions. Most of the studies on term infants suffer from lack of reliability tests. The groove system was recognized as the distinctive feature of the infant palate. The shape of the palate of the term infant may vary considerably, both visually and metrically. Gender, race, mode of delivery, and nasal deformities were identified as causes contributing to altered palatal morphology. Until today, anatomical features of the newborn's palate are subject to a non-uniform nomenclature. CONCLUSION: Today's knowledge of a newborn's 'normal' palatal morphology is based on non-standardized and limited methodologies for measuring a three-dimensional shape. This shortcoming increases bias and is the reason for contradictory research results, especially if pathologic conditions like syndromes or prematurity are involved. Adequate measurement techniques are needed and the 'normal palatal morphology' should be defined prior to new clinical studies on palatal development

Coevolution of Interacting Fertilization Proteins

Reproductive proteins are among the fastest evolving in the proteome, often due to the consequences of positive selection, and their rapid evolution is frequently attributed to a coevolutionary process between interacting female and male proteins. Such a process could leave characteristic signatures at coevolving genes. One signature of coevolution, predicted by sexual selection theory, is an association of alleles between the two genes. Another predicted signature is a correlation of evolutionary rates during divergence due to compensatory evolution. We studied female–male coevolution in the abalone by resequencing sperm lysin and its interacting egg coat protein, VERL, in populations of two species. As predicted, we found intergenic linkage disequilibrium between lysin and VERL, despite our demonstration that they are not physically linked. This finding supports a central prediction of sexual selection using actual genotypes, that of an association between a male trait and its female preference locus. We also created a novel likelihood method to show that lysin and VERL have experienced correlated rates of evolution. These two signatures of coevolution can provide statistical rigor to hypotheses of coevolution and could be exploited for identifying coevolving proteins a priori. We also present polymorphism-based evidence for positive selection and implicate recent selective events at the specific structural regions of lysin and VERL responsible for their species-specific interaction. Finally, we observed deep subdivision between VERL alleles in one species, which matches a theoretical prediction of sexual conflict. Thus, abalone fertilization proteins illustrate how coevolution can lead to reproductive barriers and potentially drive speciation