Bacterial Dispersers along Preferential Flow Paths of a Clay Till Depth Profile.

This study assessed the dispersal of five bacterial communities from contrasting compartments along a fractured clay till depth profile comprising plow layer soil, preferential flow paths (biopores and the tectonic fractures below), and matrix sediments, down to 350 cm below the surface. A recently developed expansion of the porous surface model (PSM) was used to capture bacterial communities dispersing under controlled hydration conditions on a soil-like surface. All five communities contained bacteria capable of active dispersal under relatively low hydration conditions (-3.1 kPa). Further testing of the plow layer community revealed active dispersal even at matric potentials of -6.3 to -8.4 kPa, previously thought to be too dry for dispersal on the PSM. Using 16S rRNA gene amplicon sequencing, the dispersing communities were found to be less diverse than their corresponding total communities. The dominant dispersers in most compartments belonged to the genus Pseudomonas and, in the plow layer soil, to Rahnella as well. An exception to this was the dispersing community in the matrix at 350 cm below the surface, which was dominated by Pantoea Hydrologically connected compartments shared proportionally more dispersing than nondispersing amplicon sequence variants (ASVs), suggesting that active dispersal is important for colonizing these compartments. These results highlight the importance of including soil profile heterogeneity when assessing the role of active dispersal and contribute to discerning the importance of active dispersal in the soil environment.IMPORTANCE The ability to disperse is considered essential for soil bacteria colonization and survival, yet very little is known about the dispersal ability of communities from different heterogeneous soil compartments. Important factors for dispersal are the thickness and connectivity of the liquid film between soil particles. The present results from a fractured clay till depth profile suggest that dispersal ability is common in various soil compartments and that most are dominated by a few dispersing taxa. Importantly, an increase in shared dispersers among the preferential flow paths of the clay till suggests that active dispersal plays a role in the successful colonization of these habitats.

Novel Method Reveals a Narrow Phylogenetic Distribution of Bacterial Dispersers in Environmental Communities Exposed to Low-Hydration Conditions.

In this study, we developed a method that provides profiles of community-level surface dispersal from environmental samples under controlled hydration conditions and enables us to isolate and uncover the diversity of the fastest bacterial dispersers. The method expands on the porous surface model (PSM), previously used to monitor the dispersal of individual bacterial strains in liquid films at the surface of a porous ceramic disc. The novel procedure targets complex communities and captures the dispersed bacteria on a solid medium for growth and detection. The method was first validated by distinguishing motile Pseudomonas putida and Flavobacterium johnsoniae strains from their nonmotile mutants. Applying the method to soil and lake water bacterial communities showed that community-scale dispersal declined as conditions became drier. However, for both communities, dispersal was detected even under low-hydration conditions (matric potential, -3.1 kPa) previously proven too dry for P. putida strain KT2440 motility. We were then able to specifically recover and characterize the fastest dispersers from the inoculated communities. For both soil and lake samples, 16S rRNA gene amplicon sequencing revealed that the fastest dispersers were substantially less diverse than the total communities. The dispersing fraction of the soil microbial community was dominated by Pseudomonas species cells, which increased in abundance under low-hydration conditions, while the dispersing fraction of the lake community was dominated by Aeromonas species cells and, under wet conditions (-0.5 kPa), also by Exiguobacterium species cells. The results gained in this study bring us a step closer to assessing the dispersal ability within complex communities under environmentally relevant conditions.IMPORTANCE Dispersal is a key process of bacterial community assembly, and yet, very few attempts have been made to assess bacterial dispersal at the community level, as the focus has previously been on pure-culture studies. A crucial factor for dispersal in habitats where hydration conditions vary, such as soils, is the thickness of the liquid films surrounding solid surfaces, but little is known about how the ability to disperse in such films varies within bacterial communities. Therefore, we developed a method to profile community dispersal and identify fast dispersers on a rough surface resembling soil surfaces. Our results suggest that within the motile fraction of a bacterial community, only a minority of the bacterial types are able to disperse in the thinnest liquid films. During dry periods, these efficient dispersers can gain a significant fitness advantage through their ability to colonize new habitats ahead of the rest of the community.

[General and supportive therapy of pulmonary arterial hypertension]. / Allgemeine und supportive Therapie der pulmonal arteriellen Hypertonie: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted and supportive treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to general and supportive therapy of PAH. This article summarizes the results and recommendations of this working group.

[Chronic thromboembolic pulmonary hypertension: Recommendations of the Cologne Consensus Conference 2016]. / Chronisch thromboembolische pulmonale Hypertonie: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH), but also other significant subgroups of pulmonary hypertension (PH). In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. Several working groups were initiated, one of which was dedicated to the diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH). In every patient with PH of unknown cause CTEPH should be excluded. The primary treatment option is surgical pulmonary endarterectomy (PEA) in a specialized multidisciplinary CTEPH center. Inoperable patients or patients with persistent or recurrent CTEPH after PEA are candidates for targeted drug therapy. For balloon pulmonary angioplasty (BPA), there is currently only limited experience. This option - as PEA - is reserved to specialized centers with expertise for this treatment method. In addition, a brief overview is given on pulmonary artery sarcoma, since its surgical treatment is often analogous to PEA. The recommendations of this working group are summarized in the present paper.

The platypnea-orthodeoxia syndrome.

The platypnea orthodeoxia syndrome (POS) is a rare condition characterized by dyspnea and hypoxia in upright position. Pathopysiologic underlying mechanisms are determined by an atrial right-to-left shunt. Coexisting conditions that evolve POS can be of anatomical nature causing interatrial communication or of functional nature producing a deformity of the atrial septum in upright position. Diagnosis is difficult, as it needs to mention about POS. Classically, transthoracic and transesophageal echocardiography in supine and upright position with use of contrast medium and/or Doppler will point the diagnosis. Treatment is predominantly carried out by interventional closure of atrial septal defect that promptly resolves clinical symptoms.

[Chronic thromboembolic pulmonary hypertension--a position paper]. / Chronisch thromboembolische pulmonale Hypertonie (CTEPH) 2014. Ein Positionspapier.

This position paper summarises current developments in chronic thromboembolic pulmonary hypertension (CTEPH) including diagnostic approaches and treatment options. Based on the guidelines of the task force of CTEPH experts at the 5th World Symposium on Pulmonary Hypertension in Nice 2013. Open questions arising during the treatment of patients with CTEPH are addressed. Patients with suspected CTEPH should undergo echocardiography and cardiopulmonary exercise testing. A ventilation/perfusion scan is the recommended imaging test for screening in the diagnostic algorithm for the evaluation of CTEPH. CTEPH-patients should be discussed in an expert center with an interdisciplinary team and an experienced PEA surgeon to decide the further treatment. Pulmonary endarterectomy (PEA) is the treatment of choice for patients with CTEPH. Medical therapy with PH-targeted medications for inoperable CTEPH and residual disease after PEA should only be initiated if evaluation reveals that the patient is no candidate for a PEA. Current data suggest that CTEPH patients treated with PEA have a better long-term survival rate and quality of life than patients treated with medical therapy.

Thrombophilia in patients with chronic venous leg ulcers-a study on patients with or without post-thrombotic syndrome.

BACKGROUND: Chronic venous leg ulcers (CVU) cause considerable burden of disease for the patients as well as enormous costs for health care systems. The pathophysiology of CVU is complex and not entirely understood. So far reliable pathogenic and/or prognostic parameters have not been identified. OBJECTIVES: We studied the role of thrombophilia in patients referred to a University dermatology department for treatment of CVU. PATIENTS AND METHODS: A cohort of 310 patients with active chronic venous leg ulcers (CEAP 6) was stratified into two comparably large groups according to the presence or absence of post-thrombotic syndrome (PTS+; PTS-) as determined using duplex scan and/or phlebography. In addition, several thrombophilia parameters were assessed. RESULTS: The prevalence of protein S deficiency and factor V Leiden mutation was significantly higher in PTS+ patients compared with the PTS- group. However, patients in both subgroups revealed high prevalences of thrombophilia (antithrombin deficiency, protein C deficiency, protein S deficiency, activated protein C resistance, factor V mutation or elevated homocysteine). CONCLUSION: Based on these data, it is conceivable that thrombophilia contributes to the pathogenesis of CVU, possibly through induction of microcirculatory dysregulations.

[Chronic thromboembolic pulmonary hypertension: recommendations of the Cologne Consensus Conference 2010]. / Chronisch thromboembolische pulmonale Hypertonie: Empfehlungen der Kölner Konsensus-Konferenz 2010.

In the 2009 European Guidelines on pulmonary hypertension one section covers aspects of pathophysiology, diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH). The practical implementation of the guidelines for this disease is of crucial importance, because CTEPH is a form of pulmonary hypertension which can be surgically cured. It is, however, frequently diagnosed late in the course of disease and often treated not correctly. In the European Guidelines CTEPH is addressed relatively briefly, although it is a common form of PH which is often overlooked. Any patient with unexplained PH should be evaluated for the presence of CTEPH. A ventilation/perfusion lung scan is recommended as the first step to exclude CTEPH. If the ventilation/perfusion lung scan or multislice CT angiography reveals perfusions defects suggesting the diagnosis of CTEPH, the patient should be referred to a centre with expertise in the medical and surgical management of these patients. After diagnosis of CTEPH the case has to be reviewed by an experienced surgeon in a PEA centre for assessment of operability. The recommendations of the European guidelines are summarized in the current manuscript with additional comments regarding diagnosis and treatment according to most recent evidence.

Generation of tau aggregates and clearance by autophagy in an inducible cell model of tauopathy.

We have studied the mechanism of aggregation in an inducible cell model of Tau pathology. When the repeat domain of human Tau (Tau(RD)) carrying the FTDP-17 mutation DeltaK280 is expressed, the cells develop aggregates, as seen by thioflavin S fluorescence, electron microscopy, and sarkosyl extraction methods. By contrast, mutants of Tau(RD) that are unable to generate beta-structure do not aggregate. Enhanced aggregation leads to enhanced toxicity, visible by live cell microscopy and LDH release assay. The aggregation process is initiated by the sequential cleavage of Tau(RD) which yields highly amyloidogenic fragments. This cleavage occurs only with proaggregant Tau(RD), and not with the nonaggregating mutants, indicating that beta-structure makes Tau(RD) vulnerable to both proteolytic degradation and aggregation. Aggregation is reversed by switching off the expression of Tau(RD), by inhibitor compounds, and by certain protease inhibitors. In all cases, the enhanced toxicity is rescued. The clearance of the aggregates involves autophagy, whereas proteasomal degradation plays only a minor role.

Distal and proximal interleukin (IL)-10 promoter polymorphisms associated with risk of cutaneous melanoma development: a case--control study.

Inherited promoter polymorphisms of the interleukin (IL)-10 gene resulting in altered IL-10 production may contribute to a genetic susceptibility for melanoma. We investigated the role of a haplotype from distal as well as proximal polymorphic sites [-7400InDel, -6752AT (rs6676671), -3538AT (rs1800890), -1087AG (rs1800896), -597AC (rs1800872)] of the IL-10 5'-flanking region in a hospital-based case-control study of 165 Caucasian patients with cutaneous melanoma from Germany in comparison with 162 healthy cancer-free Caucasian control participants from the same area matched by age. Using multivariate analysis for the number of nevi and skin type, the IL-10 'higher producing' haplotype ITAGC was found to be significantly associated with a reduced risk of developing melanoma (adjusted P=0.02). Although our findings need to be confirmed by independent and larger multicenter studies, we have described for the first time the association of distal gene variants of the IL-10 gene as an independent risk factor for melanoma.

Association analysis of IL20RA and IL20RB genes in psoriasis.

The interleukin-20-receptor I complex (IL-20-RI) is composed of two chains, IL20RA and IL20RB. Its ligands are the three members of the IL19 subfamily of cytokines, IL-19, IL-20 and IL-24. These cytokines are important in the manifestation of psoriatic lesions and, recently, an association of polymorphisms of IL20 with psoriasis has been described. In the present study we tested the hypotheses that genetic variations of the IL-20-RI influence susceptibility to psoriasis and investigated single nucleotide polymorphisms (SNPs) in the IL20RA and IL20RB genes in psoriasis patients (n=254) and healthy controls (n=224). We found no association of any of the investigated SNPs with the disease. Analysis of pairwise linkage disequilibrium (LD) across studied markers revealed a strong level of LD between SNPs within the IL20RA gene and SNPs within the IL20RB gene, and, for both genes six common haplotypes were identified with an estimated frequency >or=1%. Haplotype analyses suggested that the IL20RA haplotype CCG (rs1184860, rs1167846, rs1167849) is significantly associated with psoriasis (OR 3.14, 95% CI 1.61-6.14), whereas the TTG haplotype had a protective effect (OR 0.20, 95% CI 0.07-0.55). The risk haplotype defining SNPs 1167846 and 1184860 were found to modify paired box 5 and homeobox A9 sites, respectively, two transcription factors related to the differentiation of immune cells. Further studies are needed to confirm the genetic association and to investigate the functional relevance of IL20RA haplotypes in psoriasis.

Association analysis of IL19, IL20 and IL24 genes in palmoplantar pustulosis.

BACKGROUND: Interleukin (IL) 19, IL-20 and IL-24 belong to the IL-10 cytokine family and have been identified to play a role in the regulation of epidermal functions and in inflammation. The genes encoding IL-19, IL-20 and IL-24 are located within a gene cluster on chromosome 1q31-32 and carry frequent genetic variations. OBJECTIVES: This study investigated whether variations in the IL19, IL20 and IL24 genes that have previously been associated with plaque-type psoriasis may also play a role in palmoplantar pustulosis (PPP). PATIENTS: Fifteen polymorphisms were analysed in 43 patients with PPP and in 149 healthy control subjects. RESULTS: The rare allele of IL20 1380 A-->G (rs2981573) was less frequent in patients with PPP compared with healthy controls (OR 1 x 95, 95% CI 1 x 00-3 x 79). Haplotype analyses of IL19 and IL20 suggested an increased risk for PPP associated with IL20 haplotype GAA (OR 2 x 39, 95% CI 1 x 17-4 x 86) and a reduced risk for PPP associated both with IL19 haplotype GATGATA (OR 0 x 41, 95% CI 0 x 16-1 x 05) and IL20 haplotype GGG (OR 0 x 48, 95% CI 0 x 23-0 x 98). Extended haplotype analysis revealed an association of IL19/IL20 haplotype GACACCGGAA with a higher risk for PPP (OR 2 x 31, 95% CI 1 x 05-5 x 10) and of IL20/IL24 haplotype CAAAC with a reduced risk for PPP (OR 0 x 12, 95% CI 0 x 02-0 x 82). CONCLUSIONS: This exploratory study supports the hypothesis that variations of genes of the IL-19 subfamily of cytokines influence susceptibility to PPP. However, due to the limited size of the study samples, this current concept should be considered as preliminary and the results need to be confirmed in future independent studies.

Correlation of intimal hyperplasia development and shear stress distribution at the distal end-side-anastomosis, in vitro study using particle image velocimetry.

Low shear areas at the distal anastomosis of peripheral bypasses are thought to promote neointimal hyperplasia. In this study we evaluated the fluid dynamic environment at the distal anastomosis of peripheral bypasses by means of a new method for in vitro flow visualization and quantitative velocity field measurement. A silastic model of a distal end-side anastomosis was attached to a mock circulation loop driven by an artificial heart. High resolution velocity fields were measured by means of particle image velocimetry (PIV). The velocity vector data were used to calculate vorticity omega, strain rates ex, shear rates h and shear stresses tau. Two separations and a stagnation zone were identified by means of flow visualization. Measured velocities inside the three zones were significantly lower than in the high velocity mainstream. Calculated shear rates and shear stresses inside the zones were significantly lower than human wall shear rates. At the transition between the effective mainstream and the boundary layers high vorticity and compressive strain fields existed, indicating the presence of high shear forces. The locations of these areas corresponded to the well known zones of intimal hyperplasia. The high resolution shear stress analysis supports the low shear theory of intimal hyperplasia development. A wall diversion angle greater than 6 degrees leads to flow separation and presumed IH promotion until high shear transition areas are reached.

Local haemodynamics and shear stress in cuffed and straight PTFE-venous anastomoses: an in-vitro comparison using particle image velocimetry.

OBJECTIVES: To use particle image velocimetry (PIV) to study the haemodynamics and shear stress associated with cuffed and straight PTFE-venous anastomoses. METHODS: Silastic models of a straight and cuffed (Venaflo) PTFE-venous anastomoses were attached to a pulsatile flow 'Berlin Heart' circuit filled with glycerine/water and hollow glass tracer spheres. Instantaneous velocity fields were obtained PIV and shear rates and patterns calculated from frame-by-frame analysis. RESULTS: A high velocity jet struck the anastomotic 'floor' and was deflected toward the venous outflow. Shear stresses near the floor were significantly higher, in the straight anastomosis. Sites of high shear stress correlated well with the known sites of intimal hyperplasia. CONCLUSIONS: A cuffed anastomosis type may be favourable in terms of local haemodynamics so enhancing the long-term patency of PTFE-venous grafts.

Use of near-infrared reflection spectroscopy to study the effects of X-ray contrast media on renal tolerance in rats: effects of a prostacyclin analogue and of phosphodiesterase inhibitors.

RATIONALE AND OBJECTIVES: Use of near-infrared reflection spectroscopy (NIR-RS) as a new model to assess renal tolerance of contrast agents and determination of the effects of a prostacyclin analogue and of two phosphodiesterase inhibitors on renal tolerance. MATERIALS AND METHODS: NIR-RS was used to measure total hemoglobin, oxygenated hemoglobin and tissue oxygen saturation in the renal cortex of rats and the effect of diatrizoate, iopromide and iotrolan injected at 1 g iodine/kg alone or together with the prostacyclin derivative, iloprost, or the phosphodiesterase inhibitors, rolipram and mesopram, on these parameters. RESULTS: Injection of the contrast media alone resulted in a 10% to 35% depression of total hemoglobin, oxygenated hemoglobin, and tissue oxygen saturation approximately 40 to 100 seconds after administration, whereas saline showed no effect and mannitol solution only a minor effect. Coadministration of iloprost or pretreatment with the phosphodiesterase inhibitors, rolipram or mesopram, significantly attenuated the contrast media-induced effects. CONCLUSION: NIR-RS might be useful for the determination of contrast media-induced side effects. Stable prostacyclin analogues or phosphodiesterase inhibitors have the potential to mitigate these side effects.

Performance of a bioreactor with submerged membranes for aerobic treatment of municipal waste water.

Aerobic treatment of municipal waste water in a membrane bioreactor was studied for 535 d. Apart from sampling, sludge was retained completely by a submerged hollow fibre membrane with a pore-size of 0.2 microm. The pilot plant comprised an anoxic zone to enable denitrification. The maximum liquid hold-up of the plant was 3.9 m3. In this study the reactor performance and the stability of the process and the membrane capacity were investigated. A stable flux of 181 m(-2)h(-1) could be realised with a mean transmembrane pressure difference of 0.3bar with air-bubbling and backflushing the membrane and cleaning it in place every two months for one or two hours. For about 140d, a flux of 271 m(-2)h(-1) was achieved, but cleaning became necessary more often. The hydraulic retention time (HRT) varied between 10.4 and 15.6h. Accordingly the volumetric loading rate was between 1.1 and 1.7kg CODm(-3)d(-1). No inoculum was used. The mixed liquor suspended solids (MLSS) concentration gradually increased to 18-20g MLSSl(-1). The feed to microorganism (F/M) ratio varied according to the operation conditions but decreased against a value of 0.07 kg COD kg(-1) MLSSd(-1). Treatment performance was very stable and on a high level. The COD was reduced by 95%. Nitrification was complete and up to 82% of the total nitrogen could be denitrified.

Filamentous fungi and yeasts on mattresses covered with different encasings.

Besides mites, filamentous fungi and yeasts play an important role as domestic allergens. Among different allergen avoidance strategies the efficacy of synthetic mattress encasings has been demonstrated for the reduction of house dust mites. Whether these synthetic encasings are also able to reduce the growth of fungi on the mattress under domestic conditions has not been assessed so far. To determine if the fungal growth on mattresses can be reduced by the use of synthetic encasings we assessed the fungal colonisation of mattresses covered either by conventional cotton encasings or by polyurethane encasings impermeable to particles > 3 mum. Within a 12-month period dust samples were obtained from the mattresses. Fungal quantities were measured by counting colonies on agar plates incubated at 20 degrees C and 37 degrees C. The counts of fungi were significantly higher on mattresses with cotton encasings. Penicillium spp. and Aspergillus spp. were isolated most frequently. Therefore the application of synthetic encasings with similar properties to the encasings used in this investigation is recommended as part of an allergen avoidance strategy for patients sensitised to fungal allergens.