Search

BackgroundIn Switzerland, details of current anaesthesia practice are unknown. However, they are urgently needed to manage anaesthesia drug supply in times of drug shortages due to the pandemic.MethodsWe surveyed all Swiss anaesthesia institutions in April 2020 to determine their annual anaesthesia activity. Together with a detailed analysis on anaesthetic drug use of a large, representative Swiss anaesthesia index institution, calculations and projections for the annual need of anaesthetics in Switzerland were made. Only those drugs have been analysed that are either being used very frequently or that have been classified critical with regard to their supply by the pharmacy of the index institution or the Swiss Federal Office of Public Health.ResultsThe response rate to our questionnaire was 98%. Out of the present 188 Swiss anaesthesia institutions, 185 responded. In Switzerland, the annual number of anaesthesias was 1'071'054 (12'445 per 100'000 inhabitants) with a mean anaesthesia time of 2.03 hours. Teaching hospitals (n = 54) performed more than half (n = 572'231) and non-teaching hospitals (n = 103) provided almost half of all anaesthesias (n = 412'531). Thereby, private hospitals conducted a total of 290'690 anaesthesias. Finally, office-based anaesthesia institutions with mainly outpatients (n = 31) administered 86'292 anaesthesias. Regarding type of anaesthesia provided, two thirds were general anaesthesias (42% total intravenous, 17% inhalation, 8% combined), 20% regional and 12% monitored anaesthesia care. Projecting for example the annual need for propofol in anaesthesia, Switzerland requires 48'573 L of propofol 1% which corresponds to 5'644 L propofol 1% per 100'000 inhabitants every year.ConclusionsTo actively manage anaesthesia drug supply in the context of the current pandemic, it is mandatory to have a detailed understanding of the number and types of anaesthesias provided. On this basis, the Swiss annual consumption of anaesthetics could be projected and the replenishment organized.

A trailing joint control pattern, during which a single joint is rotated actively and the mechanical effect of this motion is used to move the other joints, was previously observed during simplified, laboratory-based tasks. We examined whether this simple pattern also underlies control of complex, unconstrained arm movements of daily activities. Six tasks were analyzed. Using kinematic data, we estimated motion of 7 degrees of freedom (DOF) of the shoulder, elbow, and wrist, and the contribution of muscle and passive interaction and gravitational torques to net torque at each joint. Despite task variety, the hand was transported predominantly by shoulder and elbow flexion/extension, although shoulder external/internal rotation also contributed in some tasks. The other DOF were used to orient the hand in space. The trailing pattern represented by production of net torque by passive torques at the shoulder or elbow or both was observed during the biggest portion of each movement. Net torque generation by muscle torque at both joints simultaneously was mainly limited to movement initiation toward the targets and movement termination when returning to the initial position, and associated with needing to overcome gravity. The results support the interpretation of previous studies that prevalence of the trailing pattern is a feature of skillful, coordinated movements. The simplicity of the trailing pattern is promising for quantification of dyscoordination caused by motor disorders and formulation of straightforward instructions to facilitate rehabilitation and motor learning.

Release of extracellular vesicles (EV) by Gram-negative and positive bacteria is being frequently reported. EV are nano-sized, membrane-derived, non-self-replicating, spherical structures shed into the extracellular environment that could play a role in bacteria-host interactions. Evidence of EV production in bacteria belonging to the class Mollicutes, which are wall-less, is mainly restricted to the genus Acholeplasma and is scanty for the Mycoplasma genus that comprises major human and animal pathogens. Here EV release by six Mycoplasma (sub)species of clinical importance was investigated. EV were obtained under nutritional stress conditions, purified by ultracentrifugation and observed by electron microscopy. The membrane proteins of EV from three different species were further identified by mass spectrometry as a preliminary approach to determining their potential role in host-pathogen interactions. EV were shown to be released by all six (sub)species although their quantities and sizes (30-220 nm) were very variable. EV purification was complicated by the minute size of viable mycoplasmal cells. The proteins of EV-membranes from three (sub)species included major components of host-pathogen interactions, suggesting that EV could contribute to make the host-pathogen interplay more complex. The process behind EV release has yet to be deciphered, although several observations demonstrated their active release from the plasma membrane of living cells. This work shed new light on old concepts of "elementary bodies" and "not-cell bound antigens".

MRI plays a major role in follow-up of patients with malignant bone tumors. However, after limb salvage surgery, orthopaedic tumor endoprostheses might cause significant metal-induced susceptibility artifacts.To evaluate the benefit of view-angle tilting (VAT) and slice-encoding metal artifact correction (SEMAC) for MRI of large-sized orthopaedic tumor endoprostheses in an experimental model and to demonstrate clinical benefits for assessment of periprosthetic soft tissue abnormalities.In an experimental setting, tumor endoprostheses (n=4) were scanned at 1.5T with three versions of optimized high-bandwidth turbo-spin-echo pulse sequences: (i) standard, (ii) VAT and (iii) combined VAT and SEMAC (VAT&SEMAC). Pulse sequences included coronal short-tau-inversion-recovery (STIR), coronal T1-weighted (w), transverse T1-w and T2-w TSE sequences. For clinical evaluation, VAT&SEMAC was compared to conventional metal artifact-reducing MR sequences (conventional MR) in n=25 patients with metal implants and clinical suspicion of tumor recurrence or infection. Diameters of artifacts were measured quantitatively. Qualitative parameters were assessed on a five-point scale (1=best, 5=worst): "image distortion", "artificial signal changes at the edges" and "diagnostic confidence". Imaging findings were correlated with pathology. T-tests and Wilcoxon-signed rank tests were used for statistical analyses.The true size of the prostheses was overestimated on MRI (P

Diffusion-weighted magnetic resonance imaging (DW-MRI) and imaging of glucose metabolism by positron emission tomography (FDG-PET) provide quantitative information on tissue characteristics. Combining the two methods might provide novel insights into tumor heterogeneity and biology. Here, we present a solution to analyze and visualize the relationship between the apparent diffusion coefficient (ADC) and glucose metabolism on a spatially resolved voxel-by-voxel basis using dedicated quantitative software.In 12 patients with non small cell lung cancer (NSCLC), the primary tumor or metastases were examined with DW-MRI and PET using 18F-fluorodeoxyglucose (FDG). The ADC's from DW-MRI were correlated with standardized-uptake-values on a voxel-by-voxel basis using custom made software (Anima M3P). For cluster analysis, we used prospectively defined thresholds for 18F-FDG and ADC to define tumor areas of different biological activity.Combined analysis and visualization of ADC maps and PET data was feasible in all patients. Spatial analysis showed relatively homogeneous ADC values over the entire tumor area, whereas FDG showed a decreasing uptake towards the tumor center. As expected, restricted water diffusivity was notable in areas with high glucose metabolism but was also found in areas with lower glucose metabolism. In detail, 72% of all voxels showed low ADC values (3.6). However, 83% of the voxels with low FDG uptake also showed low ADC values, increasingly towards the tumor center.Multiparametric analysis and visualization of DW-MRI and FDG-PET is feasible on a spatially resolved voxel-by-voxel respectively cluster basis using dedicated imaging software. Our preliminary data suggest that water diffusivity and glucose metabolism in metastatic NSCLC are not necessarily correlated in all tumor areas.

Steroid hormones organize many aspects of development, including that of the nervous system. Steroids also play neuromodulatory and other activational roles, including regulation of sensitivity to painful stimuli in mammals. In Drosophila, ecdysteroids are the only steroid hormones, and therefore the fly represents a simplified model system in which to explore mechanisms of steroid neuromodulation of nociception. In this report, we present evidence that ecdysteroids, acting through two isoforms of their nuclear ecdysone receptor (EcR), modulate sensitivity to noxious thermal and mechanical stimuli in the fly larva. We show that EcRA and EcRB1 are expressed by third instar larvae in the primary nociceptor neurons, known as the class IV multidendritic neurons. Suppression of EcRA by RNA interference in these cells leads to hyposensitivity to noxious stimulation. Suppression of EcRB1 leads to reduction of dendritic branching and length of nociceptor neurons. We show that specific isoforms of the ecdysone receptor play critical cell autonomous roles in modulating the sensitivity of nociceptor neurons and may indicate human orthologs that represent targets for novel analgesic drugs.

Anaplasma phagocytophilum is a Gram-negative obligate intracellular bacterium that replicates in neutrophils. It is transmitted via tick-bite and causes febrile disease in humans and animals. Human granulocytic anaplasmosis is regarded as an emerging infectious disease in North America, Europe and Asia. However, although increasingly detected, it is still rare in Europe. Clinically apparent A. phagocytophilum infections in animals are mainly found in horses, dogs, cats, sheep and cattle. Evidence from cross-infection experiments that A. phagocytophilum isolates of distinct host origin are not uniformly infectious for heterologous hosts has led to several approaches of molecular strain characterization. Unfortunately, the results of these studies are not always easily comparable, because different gene regions and fragment lengths were investigated. Multilocus sequence typing is a widely accepted method for molecular characterization of bacteria. We here provide for the first time a universal typing method that is easily transferable between different laboratories. We validated our approach on an unprecedented large data set of almost 400 A. phagocytophilum strains from humans and animals mostly from Europe. The typability was 74% (284/383). One major clonal complex containing 177 strains was detected. However, 54% (49/90) of the sequence types were not part of a clonal complex indicating that the population structure of A. phagocytophilum is probably semiclonal. All strains from humans, dogs and horses from Europe belonged to the same clonal complex. As canine and equine granulocytic anaplasmosis occurs frequently in Europe, human granulocytic anaplasmosis is likely to be underdiagnosed in Europe. Further, wild boars and hedgehogs may serve as reservoir hosts of the disease in humans and domestic animals in Europe, because their strains belonged to the same clonal complex. In contrast, as they were only distantly related, roe deer, voles and shrews are unlikely to harbor A. phagocytophilum strains infectious for humans, domestic or farm animals.

Based on the isometric hypothesis, belowground plant biomass (MB) should scale isometrically with aboveground biomass (MA) and the scaling exponent should not vary with environmental factors. We tested this hypothesis using a large forest biomass database collected in China. Allometric scaling functions relating MB and MA were developed for the entire database and for different groups based on tree age, diameter at breast height, height, latitude, longitude or elevation. To investigate whether the scaling exponent is independent of these biotic and abiotic factors, we analyzed the relationship between the scaling exponent and these factors. Overall MB was significantly related to MA with a scaling exponent of 0.964. The scaling exponent of the allometric function did not vary with tree age, density, latitude, or longitude, but varied with diameter at breast height, height, and elevation. The mean of the scaling exponent over all groups was 0.986. Among 57 scaling relationships developed, 26 of the scaling exponents were not significantly different from 1. Our results generally support the isometric hypothesis. MB scaled near isometrically with MA and the scaling exponent did not vary with tree age, density, latitude, or longitude, but increased with tree size and elevation. While fitting a single allometric scaling relationship may be adequate, the estimation of MB from MA could be improved with size-specific scaling relationships.

Enzootic abortion of ewes (EAE) due to infection with the obligate intracellular pathogen Chlamydia (C.) abortus is an important zoonosis leading to considerable economic loss to agriculture worldwide. The pathogen can be transmitted to humans and may lead to serious infection in pregnant women. Knowledge about epidemiology, clinical course and transmission to humans is hampered by the lack of reliable diagnostic tools. Immunoreactive proteins, which are expressed in infected animals and humans, may serve as novel candidates for diagnostic marker proteins and represent putative virulence factors. In order to broaden the spectrum of immunogenic C. abortus proteins we applied 2D immunoblot analysis and screening of an expression library using human and animal sera. We have identified 48 immunoreactive proteins representing potential diagnostic markers and also putative virulence factors, such as CAB080 (homologue of the "macrophage infectivity potentiator", MIP), CAB167 (homologue of the "translocated actin recruitment protein", TARP), CAB712 (homologue of the "chlamydial protease-like activity factor", CPAF), CAB776 (homologue of the "Polymorphic membrane protein D", PmpD), and the "hypothetical proteins" CAB063, CAB408 and CAB821, which are predicted to be type III secreted. We selected two putative virulence factors for further characterization, i.e. CAB080 (cMIP) and CAB063, and studied their expression profiles at transcript and protein levels. Analysis of the subcellular localization of both proteins throughout the developmental cycle revealed CAB063 being the first C. abortus protein shown to be translocated to the host cell nucleus.

Junctional epidermolysis bullosa (JEB) is a hereditary mechanobullous skin disease in humans and animals. A Herlitz type JEB was identified in German Black Headed Mutton (BHM) sheep and affected lambs were reproduced in a breeding trial. Affected lambs showed skin and mucous membranes blistering and all affected lambs died within the first weeks of life. The pedigree data were consistent with a monogenic autosomal recessive inheritance. Immunofluorescence showed a reduced expression of laminin 5 protein which consists of 3 subunits encoded by the genes LAMA3, LAMB3 and LAMC2. We screened these genes for polymorphisms. Linkage and genome-wide association analyses identified LAMC2 as the most likely candidate for HJEB. A two base pair deletion within exon 18 of the LAMC2 gene (FM872310:c.2746delCA) causes a frameshift mutation resulting in a premature stop codon (p.A928*) 13 triplets downstream of this mutation and in addition, introduces an alternative splicing of exon 18 LAMC2. This deletion showed a perfect co-segregation with HJEB in all 740 analysed BHM sheep. Identification of the LAMC2 deletion means an animal model for HJEB is now available to develop therapeutic approaches of relevance to the human form of this disease.

Microphthalmia in sheep is an autosomal recessive inherited congenital anomaly found within the Texel breed. It is characterized by extremely small or absent eyes and affected lambs are absolutely blind. For the first time, we use a genome-wide ovine SNP array for positional cloning of a Mendelian trait in sheep. Genotyping 23 cases and 23 controls using Illumina's OvineSNP50 BeadChip allowed us to localize the causative mutation for microphthalmia to a 2.4 Mb interval on sheep chromosome 22 by association and homozygosity mapping. The PITX3 gene is located within this interval and encodes a homeodomain-containing transcription factor involved in vertebrate lens formation. An abnormal development of the lens vesicle was shown to be the primary event in ovine microphthalmia. Therefore, we considered PITX3 a positional and functional candidate gene. An ovine BAC clone was sequenced, and after full-length cDNA cloning the PITX3 gene was annotated. Here we show that the ovine microphthalmia phenotype is perfectly associated with a missense mutation (c.338G>C, p.R113P) in the evolutionary conserved homeodomain of PITX3. Selection against this candidate causative mutation can now be used to eliminate microphthalmia from Texel sheep in production systems. Furthermore, the identification of a naturally occurring PITX3 mutation offers the opportunity to use the Texel as a genetically characterized large animal model for human microphthalmia.