Ischemic Tissue Injury in the Dorsal Skinfold Chamber of the Mouse: A Skin Flap Model to Investigate Acute Persistent Ischemia

Despite profound expertise and advanced surgical techniques, ischemia-induced complications ranging from wound breakdown to extensive tissue necrosis are still occurring, particularly in reconstructive flap surgery. Multiple experimental flap models have been developed to analyze underlying causes and mechanisms and to investigate treatment strategies to prevent ischemic complications. The limiting factor of most models is the lacking possibility to directly and repetitively visualize microvascular architecture and hemodynamics. The goal of the protocol was to present a well-established mouse model affiliating these before mentioned lacking elements. Harder et al. have developed a model of a musculocutaneous flap with a random perfusion pattern that undergoes acute persistent ischemia and results in ~50% necrosis after 10 days if kept untreated. With the aid of intravital epi-fluorescence microscopy, this chamber model allows repetitive visualization of morphology and hemodynamics in different regions of interest over time. Associated processes such as apoptosis, inflammation, microvascular leakage and angiogenesis can be investigated and correlated to immunohistochemical and molecular protein assays. To date, the model has proven feasibility and reproducibility in several published experimental studies investigating the effect of pre-, peri- and postconditioning of ischemically challenged tissue.     

Different Views about Work-Hour Limitations in Medicine: A Qualitative Content Analysis of Surgeons', Lawyers', and Pilots' Positive and Negative Arguments

Background

Whereas work-hour regulations have been taken for granted since 1940 in other occupational settings, such as commercial aviation, they have been implemented only recently in medical professions, where they lead to a lively debate. The aim of the present study was to evaluate arguments in favour of and against work-hour limitations in medicine given by Swiss surgeons, lawyers, and pilots.

Methods

An electronic questionnaire survey with four free-response items addressing the question of what arguments speak in favour of or against work-hour limitations in general and in medicine was sent to a random sample of board-certified surgeons, lawyers in labour law, and pilots from SWISS International Airlines Ltd.

Results

In all, 279/497 (56%) of the respondents answered the survey: 67/117 surgeons, 92/226 lawyers, and 120/154 pilots. Support for work-hour limitations in general and in medicine was present and higher among lawyers and pilots than it was in surgeons (p<0.001). The latter agreed more with work-hour limitations in general than in medicine (p<0.001). The most often cited arguments in favour of work-hour limitations were “quality and patient safety,” “health and fitness,” and “leisure and work-family balance,” whereas the lack of “flexibility” was the most important argument against. Surgeons expected more often that their “education” and the “quality of their work” would be threatened (p<0.001).

Conclusions

Work-hour limitations should be supported in medicine also, but a way must be found to reduce problems resulting from discontinuity in patient care and to minimise the work in medicine, which has no education value.     

A Pilot Study to Assess the Feasibility of Transcutaneous Glomerular Filtration Rate Measurement Using Fluorescence-Labelled Sinistrin in Dogs and Cats

In dogs and cats an assessment of renal function is often needed, however, existing methods including urine and plasma clearances are invasive, cumbersome and time consuming. This pilot study evaluated the feasibility of a transcutaneous glomerular filtration rate (GFR) measurement in dogs and cats. Additionally the optimal dose and location for the transcutaneous measurement device were investigated. Renal elimination of fluorescein-isothiocyanate-labelled sinistrin (FITC-S) was measured transcutaneously for 4 hours. The procedures were performed in awake, freely moving animals using escalating doses of FITC-S (10 mg/kg, 30 mg/kg, 50 mg/kg) with a wash-out period of at least 24 h in between. Multiple devices were placed on each animal. The resulting FITC-S disappearance curves were visually assessed to determine the most suitable location and the appropriate dose to reach an adequate transcutaneous peak signal for kinetic analysis. In both species 30 mg/kg were adequate for kinetic calculation. The most suitable place for the device was the lateral thoracic wall in dogs and the ventral abdominal wall in cats, respectively. Transcutaneous FITC-S clearance was then repeated using the optimal dose and location and in parallel with an additional plasma sinistrin clearance. Plasma elimination half-lives [min] were 26, 31 and 35, and corresponding transcutaneous elimination half-lives [min] were 26, 34 and 55, respectively in the dogs. Plasma elimination half-lives [min] were 51, 60 and 61, and corresponding transcutaneous elimination half-lives [min] were 75, 96 and 83, respectively in the cats. In conclusion, transcutaneous FITC-S clearance is a feasible method for the assessment of GFR in awake dogs and cats. It is noninvasive, well tolerated and easy to perform even in a clinical setting with results being readily available. A dose of 30 mg/kg of FITC-S seems adequate for kinetic assessment. Further studies are now needed to establish reference values and evaluate transcutaneous renal clearance in various conditions.     

A high-confidence human plasma proteome reference set with estimated concentrations in PeptideAtlas

Human blood plasma can be obtained relatively noninvasively and contains proteins from most, if not all, tissues of the body. Therefore, an extensive, quantitative catalog of plasma proteins is an important starting point for the discovery of disease biomarkers. In 2005, we showed that different proteomics measurements using different sample preparation and analysis techniques identify significantly different sets of proteins, and that a comprehensive plasma proteome can be compiled only by combining data from many different experiments. Applying advanced computational methods developed for the analysis and integration of very large and diverse data sets generated by tandem MS measurements of tryptic peptides, we have now compiled a high-confidence human plasma proteome reference set with well over twice the identified proteins of previous high-confidence sets. It includes a hierarchy of protein identifications at different levels of redundancy following a clearly defined scheme, which we propose as a standard that can be applied to any proteomics data set to facilitate cross-proteome analyses. Further, to aid in development of blood-based diagnostics using techniques such as selected reaction monitoring, we provide a rough estimate of protein concentrations using spectral counting. We identified 20,433 distinct peptides, from which we inferred a highly nonredundant set of 1929 protein sequences at a false discovery rate of 1%. We have made this resource available via PeptideAtlas, a large, multiorganism, publicly accessible compendium of peptides identified in tandem MS experiments conducted by laboratories around the world.     

Multiple stressors on biotic interactions: how climate change and alien species interact to affect pollination

Global change may substantially affect biodiversity and ecosystem functioning but little is known about its effects on essential biotic interactions. Since different environmental drivers rarely act in isolation it is important to consider interactive effects. Here, we focus on how two key drivers of anthropogenic environmental change, climate change and the introduction of alien species, affect plant–pollinator interactions. Based on a literature survey we identify climatically sensitive aspects of species interactions, assess potential effects of climate change on these mechanisms, and derive hypotheses that may form the basis of future research. We find that both climate change and alien species will ultimately lead to the creation of novel communities. In these communities certain interactions may no longer occur while there will also be potential for the emergence of new relationships. Alien species can both partly compensate for the often negative effects of climate change but also amplify them in some cases. Since potential positive effects are often restricted to generalist interactions among species, climate change and alien species in combination can result in significant threats to more specialist interactions involving native species.     

Effects of Land-Use Change on Carbon Stocks in Switzerland

We assessed how consequences of future land-use change may affect size and spatial shifts of C stocks under three potential trends in policy—(a) business-as-usual: continuation of land-use trends observed during the past 15 years; (b) extensification: full extensification of open-land; and (c) liberalization: full reforestation potential. The build-up times for the three scenarios are estimated at 30, 80 and 100 years, respectively. Potential C-stock change rates are derived from the literature. Whereas the business-as-usual scenario would cause marginal changes of 0.5%, liberalization would provoke a 13% increase in C stocks (+62 MtC). Gains of 24% would be expected for forests (+95 MtC), whereas open-land C stock would decrease 27% (−33 MtC). Extensification would lead to a C stock decrease of 3% (−12 MtC). Whereas forest C is expected to increase 12% (+36.5 MtC) at high elevations, stocks of open-land C would decline 38.5% (−48.5 MtC). Most affected are unfavorable grasslands, which increase in area (+59%) but contribute only 14.5% to the C stocks. C sinks would amount to 0.6 MtC y⁻¹ assuming a build-up time of 100 years for the liberalization scenario. C stocks on the current forest area are increasing by 1 MtC y⁻¹. The maximal total C sink of 1.6 MtC might thus suffice to compensate for agricultural greenhouse gases (2004: 1.4 Mt CO₂–C equivalents), but corresponds only to 11–13% of the anthropogenic greenhouse gas emission in Switzerland. Thus, even the largest of the expected terrestrial C stocks under liberalization will be small in comparison with current emissions of anthropogenic greenhouse gases.     

A graphical simulation software for instruction in cardiovascular mechanics physiology

Background  

Computer supported, interactive e-learning systems are widely used in the teaching of physiology. However, the currently available complimentary software tools in the field of the physiology of cardiovascular mechanics have not yet been adapted to the latest systems software. Therefore, a simple-to-use replacement for undergraduate and graduate students' education was needed, including an up-to-date graphical software that is validated and field-tested.