Total intermittent Pringle maneuver during liver resection can induce intestinal epithelial cell damage and endotoxemia

Objectives

The intermittent Pringle maneuver (IPM) is frequently applied to minimize blood loss during liver transection. Clamping the hepatoduodenal ligament blocks the hepatic inflow, which leads to a non circulating (hepato)splanchnic outflow. Also, IPM blocks the mesenteric venous drainage (as well as the splenic drainage) with raising pressure in the microvascular network of the intestinal structures. It is unknown whether the IPM is harmful to the gut. The aim was to investigate intestinal epithelial cell damage reflected by circulating intestinal fatty acid binding protein levels (I-FABP) in patients undergoing liver resection with IPM.

Methods

Patients who underwent liver surgery received total IPM (total-IPM) or selective IPM (sel-IPM). A selective IPM was performed by selectively clamping the right portal pedicle. Patients without IPM served as controls (no-IPM). Arterial blood samples were taken immediately after incision, ischemia and reperfusion of the liver, transection, 8 hours after start of surgery and on the first post-operative day.

Results

24 patients (13 males) were included. 7 patients received cycles of 15 minutes and 5 patients received cycles of 30 minutes of hepatic inflow occlusion. 6 patients received cycles of 15 minutes selective hepatic occlusion and 6 patients underwent surgery without inflow occlusion. Application of total-IPM resulted in a significant increase in I-FABP 8 hours after start of surgery compared to baseline (p<0.005). In the no-IPM group and sel-IPM group no significant increase in I-FABP at any time point compared to baseline was observed.

Conclusion

Total-IPM in patients undergoing liver resection is associated with a substantial increase in arterial I-FABP, pointing to intestinal epithelial injury during liver surgery.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01099475","term_id":"NCT01099475"}}NCT01099475     

Variation in the plant-mediated methane transport and its importance for methane emission from intact wetland peat mesocosms

Aims and Methods Vascular plants are known to influence the production, transport and oxidation of methane in wetland soils, but these processes are not well understood. Using plants grown in intact peat cores, we compared the influence upon methane emissions of 20 forb and graminoid species from European wetlands. We measured plant-mediated transport of methane (conduit or chimney effect) using a novel agar-sealing technique that prevented methane exchange from the bare soil to the atmosphere.Important Findings The plant-mediated transport (chimney effect) represented between 30% and almost 100% of the total methane flux, with graminoids exhibiting greater internal transport than forbs. In general, plants with less dense root tissues and a relatively larger root volume exhibited a larger chimney effect. Most species (12 out of 20) significantly reduced methane emissions compared to bare soil and only one species, Succisa pratensis, increased them. We suggest that characterising vegetation in terms of plant functional traits and plant processes offers an effective method for estimating methane emissions from wetlands. However, we found no correlation between the magnitude of the chimney effect and the overall influence of different plant species on methane emissions. Besides introducing a useful tool to study plant-mediated transport, this work suggests that characterising vegetation in terms of functional traits could improve estimates of methane emissions from wetlands, which in turn could help in designing mitigation strategies.     

'Well doctor, it is all about how life is lived': cues as a tool in the medical consultation

Introduction During consultations, the perspective of the patient and the family physician come together. In order to reach a shared view about the symptoms it is important to know the agenda of the patient. Cues (i.e. non-explicit remarks that can enclose a special meaning) can serve as a tool to clarify the agenda.Case report In this article, we describe a patient with unexplained palpitations during vacuuming. During one of the following consultations she provided an important psychosocial cue which changed my perspective on her palpitations, resulting in a deeper understanding of her symptoms.Discussion Recognition and exploration of cues is important for reaching mutual understanding of doctors and patients about the symptoms. Moreover, it enhances the therapeutic relationship and improves illness outcomes and patient satisfaction.Conclusion Noticing cues in the medical consultation helps the doctor to understand the patient's real worries. It gives us, as doctors, a better understanding of the patient's perspective.     

Enhanced bone marrow stromal cell adhesion and growth on segmented poly(ether ester)s based on poly(ethylene oxide) and poly(butylene terephthalate)

In previous studies in rats and goats, hydrophilic compositions of the PEOT/PBT block copolymer family have shown in vivo calcification and bone bonding. These copolymers are therefore interesting candidates as scaffolding materials in bone tissue engineering applications. Model studies using goat bone marrow stromal cells, however, showed that it was not possible to culture bone marrow stromal cells in vitro on these hydrophilic copolymers. In this paper two ways of surface modifying these materials to improve in vitro bone marrow stromal cell attachment and growth are discussed. Two different approaches are described: (1) blending of hydroxyapatite (HA) followed by CO(2) gas plasma etching; (2) surface modification using CO(2) gas plasma treatments. It was observed that not only HA but also the CO(2) plasma treatment by itself has a positive effect on bone marrow stromal cell attachment and growth. Gas plasma treatment appeared to be the most successful approach, resulting in a large increase in the amount of bone marrow stromal cells present on the surface (determined by a DNA assay). The amount of DNA present on the plasma-treated copolymer 1000/70/30 PEOT/PBT, based on poly(ethylene oxide, M(w) = 1000, 70 m% soft segment), was comparable to the amount present on PDLLA and significantly higher than the amount present on PCL after 7 days of cell culturing. The fact that after gas plasma treatment bone marrow stromal cells do attach to PEOT/PBT copolymers, enables in vitro bone marrow stromal cell culturing, making bone tissue engineering applications of these materials possible.     

Does phosphorus limitation promote species-rich plant communities?

It is known that the number of limiting nutrients may affect the species richness of plant communities, but it is unclear whether the type of nutrient limitation is also important. I place the results from a study in Patagonia (elsewhere in this issue) in the context of the number and types of nutrients that are limiting. I present four mechanisms through which N or P limitation may potentially influence species richness. These mechanisms are related to: (i) the number of forms in which P or N are present in soil and the plant traits needed to acquire them, (ii) the mechanisms and traits that control species competition and coexistence under N or P limitation, (iii) the regional species pools of plants capable of growing under N- and P-limited conditions, and (iv) the interaction between the type of nutrient limitation and community productivity. It appears likely that P limitation can favour a higher species richness than N limitation, in at least in a variety of low productive plant communities, but evidence to support this conclusion is so far lacking. The four mechanisms proposed here offer a framework for exploring whether the type of nutrient limitation per se, or an interaction with productivity, is a potential driver for variation in species diversity.     

Towards a functional basis for predicting vegetation patterns; incorporating plant traits in habitat distribution models

Reliably predicting vegetation distribution requires habitat distribution models (HDMs) that are ecologically sound. Current correlative HDMs are increasingly criticized because they lack sufficient functional basis. To include functional information into these models, we integrated two concepts from community ecology into a new type of HDM. We incorporated: 1) species selection by their traits in which only those species that pass the environmental filter can be part of the community (assembly theory); 2) that the occurrence probability of a community is determined by the extent to which the community mean traits fit the required traits as set by the environment. In this paper, our trait‐based HDM is presented and its predictive capacity explored. Our approach consists of two steps. In step 1, four plant traits (stem‐specific density and indicator values for nutrients, moisture and acidity) are predicted from four dominant environmental drivers (disturbance, nutrient supply, moisture supply and acidity) using regression. In step 2, these traits are used to predict the occurrence probability of 13 vegetation types, covering the majority of vegetation types across the Netherlands. The model was validated by comparison to the observed vegetation type for 263 plots in the Netherlands. Model performance was within the range of conventional HDMs and decreased with increasing uncertainty in the environment‐trait relationships and with an increasing number of vegetation types. This study shows that including functionality into HDMs is not necessarily at the cost of model performance, while it has several conceptual advantages among including an increased insight in the functional characteristics of the vegetation and sources of unpredictability in community assembly. As such it is a promising first step towards more functional HDMs. Further development of a trait‐based HDM hinges on replacing indicator values by truly functional traits and the translation of these relationships into mechanistic relationships.     

Parallel reverse genetic screening in mutant human cells using transcriptomics

Reverse genetic screens have driven gene annotation and target discovery in model organisms. However, many disease‐relevant genotypes and phenotypes cannot be studied in lower organisms. It is therefore essential to overcome technical hurdles associated with large‐scale reverse genetics in human cells. Here, we establish a reverse genetic approach based on highly robust and sensitive multiplexed RNA sequencing of mutant human cells. We conduct 10 parallel screens using a collection of engineered haploid isogenic cell lines with knockouts covering tyrosine kinases and identify known and unexpected effects on signaling pathways. Our study provides proof of concept for a scalable approach to link genotype to phenotype in human cells, which has broad applications. In particular, it clears the way for systematic phenotyping of still poorly characterized human genes and for systematic study of uncharacterized genomic features associated with human disease.     

Protective effects of agomelatine on testicular damage caused by bortezomib

Bortezomib is a chemotherapeutic agent used to treat several cancers; however, it exhibits severe side effects in testicular tissue. We investigated the use of agomelatine to prevent testicular tissue damage caused by bortezomib. We used 36 male Sprague-Dawley rats divided randomly into six equal groups: group 1, no treatment control; group 2, agomelatine treatment only; group 3, bortezomib treatment only for 48 h; group 4, bortezomib + agomelatine treatment for 48 h; group 5, bortezomib treatment only for 72 h; and group 6, bortezomib + agomelatine treatment for 72 h. After treatments, the rats were sacrificed and testicular tissue was harvested. Lipid oxidation (LPO) and superoxide dismutase (SOD) levels in the tissues were determined using biochemical methods. Tissue samples also were examined using histopathological and immunohistochemical techniques. The LPO level was increased, while the SOD level was decreased in the bortezomib treated groups. We found that agomelatine treatment normalized LPO and SOD activities in the bortezomib treated groups. In the spermatogonia and Sertoli cells, the staining density of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and caspase 3 were decreased in the bortezomib + agomelatine groups at both 48 and 72 h compared to bortezomib only treated groups. We observed maturation arrest, basal membrane thickening, increase in inflammatory cells and connective tissue, and edema between germ cells in the bortezomib only treated groups. By contrast, normal basal membrane, less edema and more normal maturation were observed in the bortezomib + agomelatine groups at 48 and 72 h. We found that agomelatine reduced the damaging effects of bortezomib. The use of agomelatine to prevent bortezomib induced testicular tissue damage in human patients should be investigated further.