The FGFRL1 receptor is shed from cell membranes, binds fibroblast growth factors (FGFs), and antagonizes FGF signaling in Xenopus embryos

FGFRL1 (fibroblast growth factor receptor like 1) is the fifth and most recently discovered member of the fibroblast growth factor receptor (FGFR) family. With up to 50% amino acid similarity, its extracellular domain closely resembles that of the four conventional FGFRs. Its intracellular domain, however, lacks the split tyrosine kinase domain needed for FGF-mediated signal transduction. During embryogenesis of the mouse, FGFRL1 is essential for the development of parts of the skeleton, the diaphragm muscle, the heart, and the metanephric kidney. Since its discovery, it has been hypothesized that FGFRL1 might act as a decoy receptor for FGF ligands. Here we present several lines of evidence that support this notion. We demonstrate that the FGFRL1 ectodomain is shed from the cell membrane of differentiating C2C12 myoblasts and from HEK293 cells by an as yet unidentified protease, which cuts the receptor in the membrane-proximal region. As determined by ligand dot blot analysis, cell-based binding assays, and surface plasmon resonance analysis, the soluble FGFRL1 ectodomain as well as the membrane-bound receptor are capable of binding to some FGF ligands with high affinity, including FGF2, FGF3, FGF4, FGF8, FGF10, and FGF22. We furthermore show that ectopic expression of FGFRL1 in Xenopus embryos antagonizes FGFR signaling during early development. Taken together, our data provide strong evidence that FGFRL1 is indeed a decoy receptor for FGFs.

Parenteral nutrition does not improve postoperative recovery from radical cystectomy: results of a prospective randomised trial

After radical cystectomy, patients are in a catabolic state because of postoperative stress response, extensive wound healing, and ileus.

Follicle flushing in monofollicular in vitro fertilization almost doubles the number of transferable embryos

Follicle flushing has been proved to be ineffective in polyfollicular in vitro fertilization. To analyze the effect of flushing in monofollicular in vitro fertilization we aspirated and then flushed the follicles in 164 cycles. Total oocyte yield/aspiration was 44.5% in the aspirate, 20.7% in the 1(st) flush, 10.4% in the 2(nd) flush and 4.3% in the 3(rd) flush. By flushing, the total oocyte yield increased (p < 0.01) by 80.9%, from 44.5 to 80.5%. The total transfer rate increased (p < 0.01) by 91.0%, from 20.1 to 38.4%. The results indicate that the oocyte yield and the number of transferable embryos can be increased significantly by flushing.

ESPEN Guidelines on Enteral Nutrition: Geriatrics

Nutritional intake is often compromised in elderly, multimorbid patients. Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility to increase or to insure nutrient intake in case of insufficient oral food intake. The present guideline is intended to give evidence-based recommendations for the use of ONS and TF in geriatric patients. It was developed by an interdisciplinary expert group in accordance with officially accepted standards and is based on all relevant publications since 1985. The guideline was discussed and accepted in a consensus conference. EN by means of ONS is recommended for geriatric patients at nutritional risk, in case of multimorbidity and frailty, and following orthopaedic-surgical procedures. In elderly people at risk of undernutrition ONS improve nutritional status and reduce mortality. After orthopaedic-surgery ONS reduce unfavourable outcome. TF is clearly indicated in patients with neurologic dysphagia. In contrast, TF is not indicated in final disease states, including final dementia, and in order to facilitate patient care. Altogether, it is strongly recommended not to wait until severe undernutrition has developed, but to start EN therapy early, as soon as a nutritional risk becomes apparent.

Tissue-transplant fusion and vascularization of myocardial microtissues and macrotissues implanted into chicken embryos and rats

Cell-based therapies and tissue engineering initiatives are gathering clinical momentum for next-generation treatment of tissue deficiencies. By using gravity-enforced self-assembly of monodispersed primary cells, we have produced adult and neonatal rat cardiomyocyte-based myocardial microtissues that could optionally be vascularized following coating with human umbilical vein endothelial cells (HUVECs). Within myocardial microtissues, individual cardiomyocytes showed native-like cell shape and structure, and established electrochemical coupling via intercalated disks. This resulted in the coordinated beating of microtissues, which was recorded by means of a multi-electrode complementary metal-oxide-semiconductor microchip. Myocardial microtissues (microm3 scale), coated with HUVECs and cast in a custom-shaped agarose mold, assembled to coherent macrotissues (mm3 scale), characterized by an extensive capillary network with typical vessel ultrastructures. Following implantation into chicken embryos, myocardial microtissues recruited the embryo's capillaries to functionally vascularize the rat-derived tissue implant. Similarly, transplantation of rat myocardial microtissues into the pericardium of adult rats resulted in time-dependent integration of myocardial microtissues and co-alignment of implanted and host cardiomyocytes within 7 days. Myocardial microtissues and custom-shaped macrotissues produced by cellular self-assembly exemplify the potential of artificial tissue implants for regenerative medicine.

[Seasonal fluctuations and influence of nutrition on macular pigment density]

PURPOSE: We have previously reported on measuring macular pigment density (MPD) with a scanning laser ophthalmoscope (HRA, Heidelberg Engineering, Heidelberg, Germany). This study war undertaken to evaluate the variation of MPD over a period of 1 year in healthy subjects. METHOD: We used autofluorescence images recorded with a HRA to evaluate MPD with a 2 degrees circle centered on the fovea. Healthy subjects were included in the study and MPD measurements were repeated every 2 months over a period of 1 year. RESULTS: We included a total of 30 healthy subjects aged 19-34 years (mean: 23+/-2 years). Mean MPD at time point 1 was 0.215+/-0.056 density units (DU), at time point 2 0.235+/-0.051 DU, at time point 3 0.218+/-0.055 DU, at time point 4 0.228+/-0.057 DU, at time point 5 0.225+/-0.053 DU, and at time point 6 0.203+/-0.050 DU. The statistical analysis revealed no significant variation of MPD over the follow-up period of 1 year. CONCLUSION: This study demonstrates that MPD shows no variation over a period of 1 year in healthy subjects.

Surplus embryos in Switzerland in 2003: legislation and availability of human embryos for research

Legislation influences the availability of embryos for research. The law in Switzerland, and in some other European countries, is restrictive concerning medically assisted reproduction and stem cell research. Swiss law prohibits the creation of embryos for research purposes. It permits the derivation of human embryonic stem cells for research from surplus embryos but prohibits research with intact surplus embryos and embryo donation to other couples. Swiss law defines all embryos generated during a reproductive cycle and not used for reproduction as surplus embryos. The aim of this study was to evaluate the surplus embryos generated in Switzerland in 2003. A detailed questionnaire was sent to all registered IVF units in Switzerland (n = 22). 11727 embryos were generated during 2003. Of these, 93.5% were transferred into the uterus and 0.4% were cryopreserved. The remaining 6.1% (n = 711) became surplus. Of these, 2.7% were transferred intravaginally and the rest discarded due to poor quality (1.6%), development arrest (1.5%), renunciation by the couple (0.2%) or for other reasons (0.1%). The number of surplus embryos in Switzerland in 2003 was evaluated. Most surplus embryos became so during a therapeutic cycle. The restrictive legal regulation decreases the availability of human embryos for research.

Inducible endothelial cell-specific gene expression in transgenic mouse embryos and adult mice

Utilizing both the TET-OFF and TET-ON systems in combination with transcriptional control elements of the Tie-2 gene, we have established a series of transgenic activator and responder mice for TET-regulated endothelial cell-specific transgene expression in double transgenic mouse embryos and in adult mice. TET-regulated expression of LacZ reporter genes could be achieved in virtually all endothelia in mid gestation stage mouse embryos. In contrast in adult mice, using the very same Tie-2 tTA activator mouse strain, we observed striking differences of TET-induced gene expression from various inducible expression constructs in different vascular beds. Non-endothelial expression was never detected. The prominent differences in completeness of TET-induced endothelial expression highlight the still underestimated critical role of the responder mouse lines for uniform TET-induced gene expression in heterogeneous cell populations such as endothelial cells. Interestingly, in double transgenic mice inducibly expressing several different adhesion molecules, no adverse effects were observed even though these proteins were robustly expressed on endothelial cells in adult tissues. These transgenic model systems provide versatile tools for the TET-regulated manipulation of endothelial cell-specific gene expression in the entire embryonic vasculature and distinct vascular beds in adult mice.

Nutrition in clinical practice-the refeeding syndrome: illustrative cases and guidelines for prevention and treatment

The refeeding syndrome is a potentially lethal complication of refeeding in patients who are severely malnourished from whatever cause. Too rapid refeeding, particularly with carbohydrate may precipitate a number of metabolic and pathophysiological complications, which may adversely affect the cardiac, respiratory, haematological, hepatic and neuromuscular systems leading to clinical complications and even death. We aimed to review the development of the refeeding syndrome in a variety of situations and, from this and the literature, devise guidelines to prevent and treat the condition. We report seven cases illustrating different aspects of the refeeding syndrome and the measures used to treat it. The specific complications encountered, their physiological mechanisms, identification of patients at risk, and prevention and treatment are discussed. Each case developed one or more of the features of the refeeding syndrome including deficiencies and low plasma levels of potassium, phosphate, magnesium and thiamine combined with salt and water retention. These responded to specific interventions. In most cases, these abnormalities could have been anticipated and prevented. The main features of the refeeding syndrome are described with a protocol to anticipate, prevent and treat the condition in adults.

Nutrition with 'light and water'? In strict isolation for 10 days without food - a critical case study

In her book 'Living on Light', Jasmuheen tries to animate people worldwide to follow her drastic nutrition rules in order to boost their quality of life. Several deaths have been reported as a fatal consequence. A doctor of chemistry who believably claimed to have been 'living on light' for 2 years, except for the daily intake of up to 1.5 l of fluid containing no or almost no calories was interested in a scientific study on this phenomenon. PARTICIPANT AND METHODS: The 54-year-old man was subjected to a rigorous 10-day isolation study with complete absence of nutrition. During the study he obtained an unlimited amount of tea and mineral water but had no caloric intake. Parameters to monitor his metabolic and psychological state and vital parameters were measured regularly and the safety of the individual was ensured throughout the study. The subject agreed on these terms and the study was approved by the local ethics committee.

Role of nutrition in liver transplantation for end-stage chronic liver disease

Patients with end-stage liver disease often reveal significant protein-energy malnutrition, which may deteriorate after listing for transplantation. Since malnutrition affects post-transplant survival, precise assessment must be an integral part of pre- and post-surgical management. While there is wide agreement that aggressive treatment of nutritional deficiencies is required, strong scientific evidence supporting nutritional therapy is sparse. In practice, oral nutritional supplements are preferred over parenteral nutrition, but enteral tube feeding may be necessary to maintain adequate calorie intake. Protein restriction should be avoided and administration of branched-chain amino acids may help yield a sufficient protein supply. Specific problems such as micronutrient deficiency, fluid balance, cholestasis, encephalopathy, and comorbid conditions need attention in order to optimize patient outcome.