Pancreatogastrostomy versus pancreatojejunostomy for RECOnstruction after partial PANCreatoduodenectomy (RECOPANC): study protocol of a randomized controlled trial UTN U1111-1117-9588

ABSTRACT: BACKGROUND: Pancreatoduodenectomy is one of the most complex abdominal operations, usually performed for tumors of the periampullary region and chronic pancreatitis. Leakage of pancreatic juice from the pancreatoenteric anastomosis, called postoperative pancreatic fistula, is the most prominent postoperative complication. Retrospective studies show a significant reduction of fistula rates with pancreatogastrostomy as compared to pancreatojejunostomy, the most frequently employed method of pancreatoenterostomy. Most single-center prospective trials, however, have not validated this finding. A large multicenter trial is needed for clarification. Methods/design RECOPANC is a prospective, randomized, controlled multicenter trial with two treatment arms, pancreatogastrostomy versus pancreatojejunostomy. The trial hypothesis is that postoperative pancreatic fistula rate is lower after pancreatogastrostomy when compared to pancreatojejunostomy. Fourteen academic centers for pancreatic surgery will participate to allocate 360 patients to the trial. The duration of the entire trial is four years including prearrangement and analyses. DISCUSSION: Postoperative pancreatic fistula is the main reason for clinically important postoperative morbidity after pancreatoduodenectomy. The primary goal of the chosen reconstruction technique for pancreatoenteric anastomosis is to minimize postoperative fistula rate. A randomized trial performed at multiple high-volume centers for pancreatic surgery is the best opportunity to investigate one of the most crucial issues in pancreatic surgery. Trial registration German Clinical Trials Register DRKS00000767 (2011/03/23), FSI 2011/05/31. Universal Trial Number U1111-1117-9588.     

Prostaglandin E2 at new glance: Novel insights in functional diversity offer therapeutic chances

Prostaglandin E₂ (PGE₂) is the most abundant eicosanoid and a very potent lipid mediator. PGE₂ is produced predominantly from arachidonic acid by its tightly regulated cyclooxygenases (COX) and prostaglandin E synthases (PGES). Secreted PGE₂ acts in an autocrine or paracrine manner through its four cognate G protein coupled receptors EP1 to EP4. Under physiological conditions, PGE₂ is key in many biological functions, such as regulation of immune responses, blood pressure, gastrointestinal integrity, and fertility. Deregulated PGE₂ synthesis or degradation is associated with severe pathological conditions like chronic inflammation, Alzheimer's disease, or tumorigenesis. Therefore, pharmacological inhibition of COX enzymes and PGE₂ receptor antagonism is of great therapeutic interest.     

Forest Soil Chemistry and Mesofauna 20 Years After an Amelioration Fertilization

Abstract Soil chemical properties and soil mesofauna composition were assessed at a forest site in northern Austria, where 20 years earlier an amelioration treatment had been performed. The site had been treated with limestone, a high P slag, and ammonium nitrate to replace the poorly growing pine (Pinus sylvestris) forest with a Norway spruce (Picea abies) stand. This treatment was at that time a common means for the amelioration of nutrient‐poor forest soils with recalcitrant forest floor layers. After treatment, a dense cover of a nitrophilic stinging nettle (Urtica dioica) developed. Most likely, the site had been over‐fertilized, and inadvertently, an experiment with extreme N enrichment had been conducted. The abundance of collembolans increased, and dominance structure shifted from Isotomiella minor, Lipothrix lubbocki, and Isotoma notabilis at fertilizer treatment to Friesea mirabilis, Isotomiella minor, and Sphaeridia pumilis in the control, but the abundance of soil mesofauna generally decreased in the fertilizer treatment. Fertilization reduced the mass of the litter layer from 7.6 to 2.4 kg/m². The total carbon pool in the soil was reduced due to reduction of the litter layer. However, the content of soil organic matter in the upper mineral soil was significantly increased. A part of the applied and mineralized nitrogen had been lost from the soil, but N retention in the upper mineral soil was still considerable. Soil pH and the base saturation were sustainably increased. Carbon losses upon mineralization of the litter layer were not offset by the increase in C content of the mineral soil. Presently, the C pool in the soil of the fertilized treatment is lower than in the control. However, the overall nutrient enrichment of the soil may facilitate C sequestration in the fertilized site in the future.     

Crawling to Collapse: Ecologically Unsound Ornamental Invertebrate Fisheries

Background

Fishery management has historically been an inexact and reactionary discipline, often taking action only after a critical stock suffers overfishing or collapse. The invertebrate ornamental fishery in the State of Florida, with increasing catches over a more diverse array of species, is poised for collapse. Current management is static and the lack of an adaptive strategy will not allow for adequate responses associated with managing this multi-species fishery. The last decade has seen aquarium hobbyists shift their display preference from fish-only tanks to miniature reef ecosystems that include many invertebrate species, creating increased demand without proper oversight. The once small ornamental fishery has become an invertebrate-dominated major industry supplying five continents.

Methodology/Principal Findings

Here, we analyzed the Florida Marine Life Fishery (FLML) landing data from 1994 to 2007 for all invertebrate species. The data were organized to reflect both ecosystem purpose (in the wild) and ecosystem services (commodities) for each reported species to address the following question: Are ornamental invertebrates being exploited for their fundamental ecosystem services and economic value at the expense of reef resilience? We found that 9 million individuals were collected in 2007, 6 million of which were grazers.

Conclusions/Significance

The number of grazers now exceeds, by two-fold, the number of specimens collected for curio and ornamental purposes altogether, representing a major categorical shift. In general, landings have increased 10-fold since 1994, though the number of licenses has been dramatically reduced. Thus, despite current management strategies, the FLML Fishery appears to be crawling to collapse.     

IVC CLAMP: infrahepatic inferior vena cava clamping during hepatectomy - a randomised controlled trial in an interdisciplinary setting

Background

To compare two approaches to the statistical analysis of the relationship between the baseline incidence of adverse events and the effect of medical emergency teams (METs).

Methods

Using data from a cluster randomized controlled trial (the MERIT study), we analysed the relationship between the baseline incidence of adverse events and its change from baseline to the MET activation phase using quadratic modelling techniques. We compared the findings with those obtained with conventional subgroup analysis.

Results

Using linear and quadratic modelling techniques, we found that each unit increase in the baseline incidence of adverse events in MET hospitals was associated with a 0.59 unit subsequent reduction in adverse events (95%CI: 0.33 to 0.86) after MET implementation and activation. This applied to cardiac arrests (0.74; 95%CI: 0.52 to 0.95), unplanned ICU admissions (0.56; 95%CI: 0.26 to 0.85) and unexpected deaths (0.68; 95%CI: 0.45 to 0.90). Control hospitals showed a similar reduction only for cardiac arrests (0.95; 95%CI: 0.56 to 1.32). Comparison using conventional subgroup analysis, on the other hand, detected no significant difference between MET and control hospitals.

Conclusions

Our study showed that, in the MERIT study, when there was dependence of treatment effect on baseline performance, an approach based on regression modelling helped illustrate the nature and magnitude of such dependence while sub-group analysis did not. The ability to assess the nature and magnitude of such dependence may have policy implications. Regression technique may thus prove useful in analysing data when there is a conditional treatment effect.     

The amphioxus (Branchiostoma floridae) genome contains a highly diversified set of G protein-coupled receptors

Background

When natural hybridization occurs at sites where the hybridizing species differ in abundance, the pollen load delivered to the rare species should be predominantly from the common species. Previous authors have therefore proposed a hypothesis on the direction of hybridization: interspecific hybrids are more likely to have the female parent from the rare species and the male parent from the common species. We wish to test this hypothesis using data of plant hybridizations both from our own experimentation and from the literature.

Results

By examining the maternally inherited chloroplast DNA of 6 cases of F1 hybridization from four genera of plants, we infer unidirectional hybridization in most cases. In all 5 cases where the relative abundance of the parental species deviates from parity, however, the direction is predominantly in the direction opposite of the prediction based strictly on numerical abundance.

Conclusion

Our results show that the observed direction of hybridization is almost always opposite of the predicted direction based on the relative abundance of the hybridizing species. Several alternative hypotheses, including unidirectional postmating isolation and reinforcement of premating isolation, were discussed.     

The integrin beta1 subunit cytoplasmic tail forms oligomers: a potential role in beta1 integrin clustering

Integrins are alpha/beta heterodimeric cell surface receptors devoid of enzymatic activity. Signal transduction therefore requires the association of cytosolic and cytoskeletal proteins with the integrin subunit intracellular regions. This association is initiated upon ligand binding to the integrin receptor and includes clustering of the integrins and recruitment of focal adhesion-associated proteins. Whether integrin clustering is solely dependent on ligand binding to the integrin extracellular parts or involves also interactions between the intracellular tails of integrins is so far unknown. To investigate intracellular events in integrin clustering, we have used peptides corresponding to the integrin beta1 cytoplasmic region. Loading of cells with the peptides results in a decreased cell adhesion and in an inhibition of cell spreading in agreement with the previously reported dominant negative effect of the beta1 integrin cytoplasmic tail on integrin clustering. Direct protein-protein interaction studies by surface plasmon resonance demonstrate that integrin beta1 cytoplasmic peptides self-associate in contrast to integrin beta3 cytoplasmic tails. Size exclusion chromatography and SDS-PAGE analysis of the peptides further show that the integrin beta1 cytoplasmic parts form oligomers and that they assume alpha helical conformation to the extent of about 13% and that this fraction is increased upon aggregation. Thus self-association of the integrin beta1 subunit cytoplasmic regions may be central to beta1 integrin clustering.     

Collagen XVII is destabilized by a glycine substitution mutation in the cell adhesion domain Col15

Collagen XVII is a hemidesmosomal transmembrane molecule important for epithelial adhesion in the skin. It exists in two forms, as a full-length protein and as a soluble ectodomain that is shed from the keratinocyte surface by furin-mediated proteolysis. To obtain information on the conformation and the functions of this unusual collagen, its largest collagenous domain, Col15, was expressed in a eukaryotic episomal expression system and purified by DEAE and fast protein liquid- Mono S chromatography. The protein was triple-helical (T(m) of 26.5 degrees C) when produced in cultures containing ascorbic acid. When the vitamin supply was limited, the 4-hydroxyproline content was reduced from 74 to 9%, which, in turn, resulted in a drastic reduction of the stability of the triple helix. The glycine substitution mutation G627V associated with junctional epidermolysis bullosa, a human blistering skin disease, also had a striking effect on thermal stability of rCol15 causing partial unfolding already at 4 degrees C. Col15 promoted cell adhesion of epithelial and fibroblastic cell lines with a beta1 integrin-mediated mechanism. In concert with this, in acquired autoimmune blistering skin diseases, circulating IgG and IgA autoantibodies were found to target rCol15r.