Defective RNA sensing by RIG-I in severe influenza virus infection.

Influenza virus infection causes worldwide seasonal epidemics. Although influenza is usually a mild disease, a minority of patients experience very severe fulminating disease courses. Previous studies have demonstrated a role for type I interferon (IFN) in anti-viral responses during influenza. So far, however, IFN regulatory factor (IRF)7 deficiency is the only genetic cause of severe influenza described in humans. In this study we present a patient with severe influenza A virus (IAV) H1N1 infection during the 2009 swine flu pandemic. By whole exome sequencing we identified two variants, p.R71H and p.P885S, located in the caspase activation and recruitment domain (CARD) and RNA binding domains, respectively, of DExD/H-box helicase 58 (DDX58) encoding the RNA sensor retinoic acid inducible gene 1 (RIG-I). These variants significantly impair the signalling activity of RIG-I. Similarly, patient cells demonstrate decreased antiviral responses to RIG-I ligands as well as increased proinflammatory responses to IAV, suggesting dysregulation of the innate immune response with increased immunopathology. We suggest that these RIG-I variants may have contributed to severe influenza in this patient and advocate that RIG-I variants should be sought in future studies of genetic factors influencing single-stranded RNA virus infections.

STELLA software as a tool for modelling phosphorus removal in a constructed wetland employing dewatered alum sludge as main substrate.

A dynamic simulation model was developed for the removal of soluble reactive phosphorus (SRP) from the vertical flow constructed wetlands (VFCW) using a dynamic software program called STELLA (structural thinking, experiential learning laboratory with animation) 9.1.3 to aid in simulating the environmental nature and succession of relationship between interdependent components and processes in the VFCW system. In particular, the VFCW employed dewatered alum sludge as its main substrate to enhance phosphorus (P) immobilization. Although computer modelling of P in treatment wetland has been well studied especially in recent years, there is still a need to develop simple and realistic models that can be used for investigating the dynamics of SRP in VFCWs. The state variables included in the model are dissolved phosphorus (DISP), plant phosphorus (PLAP), detritus phosphorus (DETP), plant biomass (PLBI) and adsorbed phosphorus (ADSP). The major P transformation processes considered in this study were adsorption, plant and microbial uptake and decomposition. The forcing functions which were considered in the model are temperature, radiation, volume of wastewater, P concentration, contact time, flow rate and the adsorbent (i.e., alum sludge). The model results revealed that up to 72% of the SRP can be removed through adsorption process whereas the uptake by plants is about 20% and the remaining processes such as microbial P utilization and decomposition, accounted for 7% SRP removal based on the mass balance calculations. The results obtained indicate that the model can be used to simulate outflow SRP concentration, and it can also be used to estimate the amount of P removed by individual processes in the VFCW using alum-sludge as a substrate.

Recent developments in lake modelling.

The radical variability of ecosystems such as lakes when reacting to prevailing conditions has in many situations found traditional modelling too inflexible. The introduction of eco-exergy, a measure of a system's distance from thermodynamic equilibrium, has enabled models to deal with ecosystems that can show major structural changes resulting from adaptation and shifts in species composition.

Effects of substrate concentrations on the growth of heterotrophic bacteria and algae in secondary facultative ponds.

This paper presents the effect of substrate concentration on the growth of a mixed culture of algae and heterotrophic bacteria in secondary facultative ponds (SFPs) utilizing settled domestic sewage as a sole source of organic carbon. The growth of the mixed culture was studied at the concentrations ranging between 200 and 800 mg COD/l in a series of batch chemostat reactors. From the laboratory data, the specific growth rate (micro) was determined using the modified Gompertz model. The maximum specific growth rate ( micro(max)) and half saturation coefficients (K(s)) were calculated using the Monod kinetic equation. The maximum observed growth rate ( micro(max)) for heterotrophic bacteria was 3.8 day(-1) with K(s) of 200 mg COD/l. The micro(max) for algal biomass based on suspended volatile solids was 2.7 day(-1) with K(s) of 110 mg COD/l. The micro(max) of algae based on the chlorophyll-a was 3.5 day(-1) at K(s) of 50mg COD/l. The observed specific substrate removal by heterotrophic bacteria varied between the concentrations of substrate used and the average value was 0.82 (mg COD/mg biomass). The specific substrate utilization rate in the bioreactors was direct proportional to the specific growth rate. Hence, the determined Monod kinetic parameters are useful for the definition of the operation of SFPs.

Recent trends in the development of ecological models applied on aquatic ecosystems.

This paper presents an overview of the application of models on aquatic ecosystems. More than 17% of the models published in the focal journal in the field, Ecological Modelling, are aquatic ecosystem models. An increasing number of papers are dealing with the theoretical aspects of modeling--new modeling approaches and techniques, how models can be used to reveal ecosystem properties, and how models can better reflect the properties of ecosystems. This development implies that today we have more types of models. The characteristics, the advantages, and the disadvantages of these model types are presented briefly. The selection criteria for the presented model types are discussed, and the application of these types to models for aquatic ecosystems is reviewed. A recent improvement in model calibration of particular interest for aquatic ecosystems is presented, and the perspectives resulting from this new calibration procedure and from possible hybrids of the presented model types are discussed.

Ecosystem management and ecological modeling.

It is the intention of this paper to demonstrate that environmental technology must be supplemented by other tools to be able to solve environmental problems properly. Five cases are used to illustrate the possibilities of ecological engineering, a new engineering field based on ecology, as chemical engineering is based on chemistry. It encompasses restoration of ecosystems, utilization of ecosystems to the benefit of both mankind and nature, construction of ecosystems, and ecologically sound planning of ecosystems from a holistic point of view. Ecological engineering requires a good knowledge of the system properties of ecosystems to be able to fully utilize the possibilities that ecosystem management offers. Models reflecting the ecosystem properties are furthermore needed to be able to quantify the effects of the ecological engineering solutions to the environmental problems. This is clearly demonstrated in two of the five case studies presented in the paper.

Toward a consistent pattern of ecosystem theories.

Several ecosystem theories have been presented during the last 2-3 decades. Lately it has been possible to unite these theories into a consistent pattern. Intensive discussions at meetings have been the key to the formation of this pattern of ecosystem theories. Another driving factor has been the reformulation of E.P. Odum's attributes into three growth forms: growth of the physical structure (the biomass), growth of the network (more cycling, more linkages), and growth of information. An analysis of the growth forms shows that through-flow (power), ascendancy, and exergy storage are all increasing as a consequence of all three types of growth. However, exergy dissipation, entropy production, specific exergy (exergy/biomass), retention time, and the ratio indirect/direct effect only increases or decreases with one or two of the growth forms.

Algal toxicity of antibacterial agents applied in Danish fish farming.

Algal toxicity of antibacterial agents applied in fish farming was investigated. The growth-inhibiting effects of amoxicillin (A), flumequine (F), oxolinic acid (OA), oxytetracycline hydrochloride (OT), sarafloxacin hydrochloride (SF), sulfadiazine (SD), and trimethoprim (T) were investigated by a modified test procedure based on the procedure described in the ISO 8692 (1989) protocol on three algal species: the freshwater cyanobacteria Microcystis aeruginosa, the freshwater green alga Selenastrum capricornutum, and the marine cryptophycean Rhodomonas salina. Algal growth was measured as increased chlorophyll concentration by extraction with ethanol followed by measurement of fluorescence. Results were quantified in terms of growth rates using the Weibull equation to describe the concentration response relationship. M. aeruginosa showed higher sensitivity compared to both R. salina and S. capricornutum, whereas the results for the latter two were more or less identical. The toxicity (EC50 value, mg/L) in decreasing order were A (0.0037), SF (0.015), SD (0.135), F (0.159), OA (0.180), OT (0.207), and T (112) for M. aeruginosa; OT (1.6), OA (10), T (16), F (18), SF (24), SD (403), and A (3108) for R. salina; and OT (4.5), F (5.0), SD (7.8), OA (16), SF (16), T (130), and A (NOEC > 250) for S. capricornutum. Applying this test procedure the toxicity of antibacterial agents, being mono- or polyprotic compounds, may be underestimated because of partitioning between ionized and unionized forms.

Recent trends in environmental and ecological modelling.

The paper outlines the history of modelling and presents a status of ecological modelling: what is the modelling effort of various ecosystem and various environmental problems. Typical validation results and prognosis validation results of a eutrophication model are applied as an illustration of what models can do in environmental management. Structural dynamic modelling which considers parameters that are changed currently by optimisation of a so-called goal function is presented as one of the recent development to overcome one of the most crucial problems in modelling, namely to consider adaptation. Two case studies are presented to illustrate this approach, namely application of biomanipulation and eutrophication of a shallow lake. Forecast on the directions of development is finally presented.

Peer reviewed: environmental management in the 21st century.

The solution of complex environmental problems will require comprehensive system considerations, as well as multidisciplinary and holistic approaches.

Occurrence, fate and effects of pharmaceutical substances in the environment--a review.

Medical substances (pharmaceuticals) are a group of substances that until recently have been exposed to the environment with very little attention. The reason why they may be interesting as environmental micropollutants, is that medical substances are developed with the intention of performing a biological effect. Especially antibiotics used as growth promoters, as feed additives in fish farms are anticipated to end up in the environment. Very little is known about the exposure routes of the medical substances to the environment. Only few investigations have reported findings of medical substances in other field samples than sediment or treated waste water samples. Several substances seem to be persistent in the environment. This paper outlines the different anticipated exposure routes to the environment, summarises the legislation on the subject and gives an outline of present knowledge of occurrence, fate and effect on both the aquatic and terrestrial environments of medical substances. Present knowledge does not reveal if regular therapeutic use may be the source of a substance carried by sewage effluent into the aquatic system, even though clofibrate, a lipid lowering agent, has been identified in ground and tap water samples from Berlin. Further research would be necessary to assess the environmental risk involved in exposing medical substances and metabolites to the environment.

Effect of Escherichia coli hemolysin on permeability of erythrocyte membranes to calcium.

The extracellular hemolysin produced by porcine strains of E. coli effects a marked increase in the calcium permeability of erythrocyte membranes. This hemolysin promotes both calcium efflux from either calcium-loaded erythrocytes or erythrocyte ghosts and calcium accumulation during the pre-lytic period. Erythrocyte membrane calcium permeability was determined using either the radioisotope 45Ca or a calcium electrode. When similar concentrations of erythrocytes (35% packed cell volume) were treated with increasing amounts of hemolysin there was an increase in both the rate and the extent of calcium accumulation by the erythrocytes. These increases were due to increased numbers of erythrocytes becoming permeable to calcium as hemolysin concentrations increased, rather than increasing amounts of calcium being accumulated by individual erythrocytes. Hemolysins produced by porcine strains of E. coli from five geographical areas all increased calcium permeability of erythrocyte membranes.

Production of a bacteriolysin by a hemolytic Escherichia coli strain.

Nonhemolytic Escherichia coli were outnumbered by hemolytic E. coli within 24 h after being inoculated in a mixed culture at an initial ratio of 200 nonhemolytic to 1 hemolytic organism. The hemolytic strain was found to produce a cell-free, filterable substance which causes lysis of nonhemolytic E. coli B when grown in liquid cultures but not when grown on agar plates. The bacteriolysin is inactivated by boiling, by freezing and thawing, and by incubation with trypsin. The inability to inhibit growth on an agar plate, dependence on cell concentration for its effect, lysis of the sensitive cells, and appearance of phage particles in the cell lysates suggest that this substance is not like colicins or microcins previously described. After lysis of E. coli B, bacteriophage particles were visible in transmission electron micrographs of material pelleted by ultracentrifugation. However, no bacteriophage were observed in pellets from the bacteriolysin-containing supernatants before lysis of E. coli B. Failure to find bacteriophage in these preparations, and the fact that some bacteriolysin activity remains in the supernatant solution after centrifugation at 150,000 X g for 6.5 h, indicate that the bacteriolysin is not itself a bacteriophage. Exposure of E. coli B to UV light and mitomycin C did not induce production of a temperate phage. The properties of this system, in which a cell-free substance produced by one strain of bacteria causes lysis of another strain, appear to differ from those of the various types of bacteriocins and bacteriophages described to date.

Calcium accumulation in human and sheep erythrocytes that is induced by Escherichia coli hemolysin.

The membrane permeability of both human and sheep erythrocytes is modified by an Escherichia coli-produced extracellular hemolysin. Alterations in membrane permeability were determined by measuring changes in the extracellular concentration of radiolabeled compounds that had been added to a 30-35% erythrocyte suspension. During the pre-lytic period, the E. coli hemolysin promotes calcium accumulation by both human and sheep erythrocytes. The concentration of calcium associated with the cells rises to a level that is approximately 1.5 (sheep) to 3 (human) times higher than that in a comparable volume of extracellular solution. Hemolysin also causes a rapid depletion of the high intracellular potassium levels normally present in human erythrocytes. That neither inulin, sucrose nor phosphate is accumulated by hemolysin-treated erythrocytes indicates that hemolysin makes the membrane selectively permeable to cations.

Exposure to chromium from hospital cleaning.

The relevance of a positive chromium patch test in females with hand eczema is very often obscure. In order to investigate the exposure to chromium in an everyday event as cleaning, the chromium content of water samples from various steps of the cleaning process in a Danish hospital was analyzed. During cleaning the chromium contamination increased above the theoretical limit necessary for sensitization. House dust contains considerable amounts of chromium, and will readily liberate it into suspension. All the chromium was found in the trivalent form.

The role of pressure damage in pathogenesis of the downer cow syndrome.

Experimental downer cows were produced by maintaining healthy cows in sternal recumbency for 6, 9, or 12 hours with the right pelvic limb positioned under the body. Halothane anesthesia was used to create this artificial parturient paresis-like position. In 8 of 16 experiments, cows were able to stand within 3 hours after anesthesia, but the others remained recumbent until death or euthanasia. There was no correlation between duration of the treatment and ability to stand after enforced recumbency. The appearance of the right pelvic limb of downer cows resembled the injured limbs of human patients with compartmental/crush syndrome, as well as the limbs of clinical downer cows. The affected limbs were swollen and held in rigid extension. Some animals which were able to stand also had swollen right pelvic limbs. Systemic signs of crush syndrome included dark yellow or brown urine suggestive of myoglobinuria, and marked elevation of serum creatine kinase enzyme levels. Highest creatine kinase levels were observed at 24 hours in the ambulatory group and at 48 hours in the downer group. Necropsy of downer animals revealed ischemic necrosis of the caudal thigh muscles and inflammation of the sciatic nerve caudal to the proximal end of the femur. Evidence of peroneal nerve damage was observed in at least 9 animals.

Effects of a single hit from the alpha hemolysin produced by Escherichia coli on the morphology of sheep erythrocytes.

Scanning electron micrographs of sheep erythrocytes showed that attachment of the alpha hemolysin produced by Escherichia coli resulted in the formation of spherocytes, with 10 to 20 small projections spaced relatively evenly over the surface of the erythrocyte membrane. This shape change was induced within 5 min after treatment. If the hemolysin concentration was reduced to a level which would lyse only a fraction of the total erythrocytes, the affected cells were easily identified against a background of normal, unaffected cells. Unlike sodium lauryl sulfate and other amphipathic agents which enter cell membranes and increase their flexibility, low concentrations of hemolysin did not provide protection against hypotonic hemolysis. These findings indicate that the surface projections were not the result of membrane expansion caused by incorporation of hemolysin into the outer portion of the lipid bilayer. The ability of a given amount of hemolysin to release a constant amount of hemoglobin in the presence of increasing concentrations of red cells confirmed that a single hit is sufficient for lysis. These results suggest that a single hemolysin molecule can bind to a sheep erythrocyte and trigger internal reactions which result in the derangement of membrane integrity at multiple sites on the surface. Confirmation of one-hit kinetics indicates that measurement of E. coli hemolysin activity should be carried out at low ratios of hemolysin to erythrocyte to decrease the possibility of multiple hits on a single cell.

[Laparoscopic sterilization with the Falope ring]. / Laparoskopisk sterilisation med Falope-ring.

PIP: 53 women, 27-45 years of age, underwent laparoscopic sterilization by the Falope ring. 2 pregnancies were reported, and an HSG (hysterosalpingography) examination revealed an open Fallopian tube in 1 patient. One pregnancy was caused by an incorrectly placed ring, while an ectopic pregnancy occurred in spite of a correctly placed one. The average length of the oepration was 8.3 minutes, with a maximum length of 35 minutes. 12 patients had minor immediate peroperative complications, e.g. bleeding, laceration of the Fallopian tube. 9% complained of bleeding irregularities and 6% of pelvic pain.^ieng

Torsion of the internal female genital apparatus.

A case of a huge right-sided ovarian cyst associated with torsion of the whole internal female genital apparatus around the uterine collum, herniation of the transverse colon into the thoracic cavity and mechanical obstruction of the ileum is described. The symptomatology, pathogenesis and treatment of the condition is discussed.