Evidence of viral adaptation to HLA class I-restricted immune pressure in chronic hepatitis C virus infection

Cellular immune responses are an important correlate of hepatitis C virus (HCV) infection outcome. These responses are governed by the host's human leukocyte antigen (HLA) type, and HLA-restricted viral escape mutants are a critical aspect of this host-virus interaction. We examined the driving forces of HCV evolution by characterizing the in vivo selective pressure(s) exerted on single amino acid residues within nonstructural protein 3 (NS3) by the HLA types present in two host populations. Associations between polymorphisms within NS3 and HLA class I alleles were assessed in 118 individuals from Western Australia and Switzerland with chronic hepatitis C infection, of whom 82 (69%) were coinfected with human immunodeficiency virus. The levels and locations of amino acid polymorphisms exhibited within NS3 were remarkably similar between the two cohorts and revealed regions under functional constraint and selective pressures. We identified specific HCV mutations within and flanking published epitopes with the correct HLA restriction and predicted escaped amino acid. Additional HLA-restricted mutations were identified that mark putative epitopes targeted by cell-mediated immune responses. This analysis of host-virus interaction reveals evidence of HCV adaptation to HLA class I-restricted immune pressure and identifies in vivo targets of cellular immune responses at the population level.

Preischemic iloprost application for improvement of graft preservation: which route is superior in experimental pig lung transplantation: inhaled or intravenous?

BACKGROUND: Optimal allograft protection is essential in lung transplantation to reduce postoperative organ dysfunction. Although intravenous prostanoids are routinely used to ameliorate reperfusion injury, the latest evidence suggests a similar efficacy of inhaled prostacyclin. Therefore, we compared donor lung-pretreatment using inhaled lioprost (Ventavis) with the commonly used intravenous technique. METHODS: Five pig lungs were each preserved with Perfadex and stored for 27 hours without (group 1) or with (group-2, 100 prior aerosolized of iloprost were (group 3) or iloprost (IV). Following left lung transplantation, hemodynamics, Po(2)/F(i)o(2), compliance, and wet-to-dry ratio were monitored for 6 hours and compared to sham controls using ANOVA analysis with repeated measures. RESULTS: The mortality was 100% in group 3. All other animals survived (P < .001). Dynamic compliance and PVR were superior in the endobronchially pretreated iloprost group as compared with untreated organs (P < .05), whereas oxygenation was comparable overall W/D-ratio revealed significantly lower lung water in group 2 (P = .027) compared with group 3. CONCLUSION: Preischemic alveolar deposition of iloprost is superior to IV pretreatment as reflected by significantly improved allograft function. This strategy offers technique to optimize pulmonary preservation.

Myocardial preservation with the UW solution. First European results in clinical heart transplantation

In recent years, there is a growing body of evidence that the University of Wisconsin (UW) solution offers many advantages in organ preservation with regard to preservation quality and time. We, therefore, conducted the first European prospective, randomized, clinical trial comparing myocardial performance after preservation with UW and St. Thomas Hospital (ST) solution. Preliminary results indicated superior heart function after preservation with UW solution.

Local resection of metanephric adenoma with kidney preservation

Metanephric adenoma (MA) is a rare renal neoplasm present at any age. Usually, a total nephrectomy is performed. Some successful partial nephrectomies or selective tumor resections are described in adults but not in children. We present here the case of a 15-month-old boy, the youngest patient yet to be reported with an MA. We performed a local resection of the tumor. Today, 2 1/2 years after surgery, we can document a favorable clinical course and normal ultrasound findings in the follow-up of the operated kidney. This case gives further evidence that organ-sparing resection of MA is feasible in selected cases. A close clinical and ultrasound follow-up is mandatory for this approach.

Can decision making in general surgery be based on evidence? An empirical study of Cochrane Reviews

BACKGROUND: This empirical study analyzes the current status of Cochrane Reviews (CRs) and their strength of recommendation for evidence-based decision making in the field of general surgery. METHODS: Systematic literature search of the Cochrane Database of Systematic Reviews and the Cochrane Collaboration's homepage to identify available CRs on surgical topics. Quantitative and qualitative characteristics, utilization, and formulated treatment recommendations were evaluated by 2 independent reviewers. Association of review characteristics with treatment recommendation was analyzed using univariate and multivariate logistic regression models. RESULTS: Ninety-three CRs, including 1,403 primary studies and 246,473 patients, were identified. Mean number of included primary studies per CR was 15.1 (standard deviation [SD] 14.5) including 2,650 (SD 3,340) study patients. Two and a half (SD 8.3) nonrandomized trials were included per analyzed CR. Seventy-two (77%) CRs were published or updated in 2005 or later. Explicit treatment recommendations were given in 45 (48%). Presence of a treatment recommendation was associated with the number of included primary studies and the proportion of randomized studies. Utilization of surgical CRs remained low and showed large inter-country differences. The most surgical CRs were accessed in UK, USA, and Australia, followed by several Western and Eastern European countries. CONCLUSION: Only a minority of available CRs address surgical questions and their current usage is low. Instead of unsystematically increasing the number of surgical CRs it would be far more efficient to focus the review process on relevant surgical questions. Prioritization of CRs needs valid methods which should be developed by the scientific surgical community.

Ridge preservation techniques for implant therapy

PURPOSE: The aim of this review was to evaluate the techniques and outcomes of postextraction ridge preservation and the efficacy of these procedures in relation to subsequent implant placement. MATERIALS AND METHODS: A MEDLINE/PubMed search was conducted and the bibliographies of reviews from 1999 to March 2008 were assessed for appropriate studies. Randomized clinical trials, controlled clinical trials, and prospective/retrospective studies with a minimum of five patients were included. RESULTS: A total of 135 abstracts were identified, from which 53 full-text articles were further examined, leading to 37 human studies that fulfilled the search criteria. Many different techniques, methodologies, durations, and materials were presented in the publications reviewed, making direct comparison difficult. CONCLUSIONS: Despite the heterogeneity of the studies, it was concluded that ridge preservation procedures are effective in limiting horizontal and vertical ridge alterations in postextraction sites. There is no evidence to support the superiority of one technique over another. There is also no conclusive evidence that ridge preservation procedures improve the ability to place implants.

Recent environmental change and trace metal pollution in World Heritage Bathurst Harbour, southwest Tasmania, Australia

Bathurst Harbour in World Heritage southwest Tasmania, Australia, is one of the world’s most pristine estuarine systems. At present there is a lack of data on pollution impacts or long-term natural variability in the harbor. A ca. 350-year-old 210Pb-dated sediment core was analysed for trace metals to track pollution impacts from local and long-range sources. Lead and antimony increased from AD 1870 onwards, which likely reflects remote (i.e. mainland Australian and global) atmospheric pollution sources. Variability in the concentrations of copper and zinc closely followed the history of mining activities in western Tasmania, which began in the AD 1880s. Tin was generally low throughout the core, except for a large peak in AD 1989 ± 0.5 years, which may be a consequence of input from a local small-scale alluvial tin mine. Changes in diatom assemblages were also investigated. The diatom flora was composed mostly of planktonic freshwater and benthic brackish-marine species, consistent with stratified estuarine conditions. Since mining began, however, an overall decrease in the proportion of planktonic to benthic taxa occurred, with the exception of two distinct peaks in the twentieth century that coincided with periods of high rainfall. Despite the region’s remoteness, trace metal analyses revealed evidence of atmospheric pollution from Tasmanian and possibly longer-range mining activities. This, together with recent low rainfall, appears to have contributed to altering the diatom assemblages in one of the most pristine temperate estuaries in the world.

Combining sedimentological, trace metal (Mn, Mo) and molecular evidence for reconstructing past water-column redox conditions: The example of meromictic Lake Cadagno (Swiss Alps)

Here, we present sedimentological, trace metal, and molecular evidence for tracking bottom water redox-state conditions during the past 12,500 years in nowadays sulfidic and meromictic Lake Cadagno (Switzerland). A 10.5 m long sediment core from the lake covering the Holocene period was investigated for concentration variations of the trace metals Mn and Mo (XRF core scanning and ICP-MS measurements), and for the presence of anoxygenic phototrophic sulfur bacteria (carotenoid pigment analysis and 16S rDNA real time PCR). Our trace metal analysis documents an oxic-intermediate-sulfidic redox-transition period beginning shortly after the lake formation similar to 12.5 kyr ago. The oxic period is characterized by low sedimentary Mn and Mo concentrations, as well as by the absence of any remnants of anoxygenic phototrophic sulfur bacteria. Enhanced accumulation/preservation of Mn (up to 5.6 wt%) in the sediments indicates an intermediate, Mn-enriched oxygenation state with fluctuating redox conditions during a similar to 2300-year long transition interval between similar to 12.1 and 9.8 kyr BP. We propose that the high Mn concentrations are the result of enhanced Mn2+ leaching from the sediments during reducing conditions and subsequent rapid precipitation of Mn-(oxyhydr) oxide minerals during episodic and short-term water-column mixing events mainly due to flood-induced underflows. At 9800 +/- 130 cal yr BP, a rapid transition to fully sulfidic conditions is indicated by the marked enrichment of Mo in the sediments (up to 490 ppm), accompanied by an abrupt drop in Mn concentrations and the increase of molecular biomarkers that indicate the presence of anoxygenic photosynthetic bacteria in the water column. Persistently high Mo concentrations >80 ppm provide evidence that sulfidic conditions prevailed thereafter until modern times, without any lasting hypolimnetic ventilation and reoxygenation. Hence, Lake Cadagno with its persistently stable chemocline offers a framework to study in great temporal detail over similar to 12 kyr the development of phototrophic sulfur bacteria communities and redox processes in a sulfidic environment, possibly depicting analogous conditions in an ancient ocean. Our study underscores the value of combining sedimentological, geochemical, and microbiological approaches to characterize paleo-environmental and -redox conditions in lacustrine and marine settings.

Light noble gases in 12 meteorites from the Omani desert, Australia, Mauritania, Canada, and Sweden

We measured the concentrations and isotopic compositions of He, Ne, and Ar in 14 fragments from 12 different meteorites: three carbonaceous chondrites, six L chondrites (three most likely paired), one H chondrite, one R chondrite, and one ungrouped chondrite. The data obtained for the CV3 chondrites Ramlat as Sahmah (RaS) 221 and RaS 251 support the hypothesis of exposure age peaks for CV chondrites at approximately 9 Ma and 27 Ma. The exposure age for Shişr 033 (CR chondrite) of 7.3 Ma is also indicative of a possible CR chondrite exposure age peak. The three L chondrites Jiddat al Harasis (JaH) 091, JaH 230, and JaH 296, which are most likely paired, fall together with Hallingeberg into the L chondrite exposure age peak of approximately 15 Ma. The two L chondrites Shelburne and Lake Torrens fall into the peaks at approximately 40 Ma and 5 Ma, respectively. The ages for Bassikounou (H chondrite) and RaS 201 (R chondrite) are approximately 3.5 Ma and 5.8 Ma, respectively. Six of the studied meteorites show clear evidence for 3He diffusive losses, the deficits range from approximately 17% for one Lake Torrens aliquot to approximately 45% for RaS 211. The three carbonaceous chondrites RaS 221, RaS 251, and Shişr 033 all have excess 4He, either of planetary or solar origin. However, very high 4He/20Ne ratios occur at relatively low 20Ne/22Ne ratios, which is unexpected and needs further study. The measured 40Ar ages fit well into established systematics. They are between 2.5 and 4.5 Ga for the carbonaceous chondrites, older than 3.6 Ga for the L and H chondrites, and about 2.4 Ga for the R chondrite as well as for the ungrouped chondrite. Interestingly, none of our studied L chondrites has been degassed in the 470 Ma break-up event. Using the amount of trapped 36Ar as a proxy for noble gas contamination due to terrestrial weathering we are able to demonstrate that the samples studied here are not or only very slightly affected by terrestrial weathering (at least in terms of their noble gas budget).

State of the art of integrated therapy approaches in the treatment of schizophrenia: empirical evidence and clinical relevance

Objective: Integrated behavior therapy approaches are defined by the combination of behavioral and or cognitive interventions targeting neurocognition combined with other goal-oriented treatment targets such as social cognition, social skills, or educational issues. The Integrated Psychological Therapy Program (IPT) represents one of the very first behavior therapy approaches combining interventions of neurocognition, social cognition, and social competence. This comprehensive group-based bottom-up and top-down approach consists of five subprograms, each with incremental steps. IPT has been successfully implemented in several countries in Europe, America, Australia and in Asia. IPT worked as a model for some other approaches designed in the USA. IPT was undergone two further developments: based on the social competence part of IPT, the three specific therapy programs focusing residential, occupational or recreational topics were developed. Recently, the cognitive part of INT was rigorously expanded into the Integrated Neurocognitive Therapy (INT) designed exclusively for outpatient treatment: INT includes interventions targeting all neurocognitive and social cognitive domains defined by the NIMH-MATRICS initiative. These group and partially PC-based exercises are structured into four therapy modules, each starting with exercises on neurocognitive domains followed by social cognitive targets. Efficacy: The evidence of integrated therapy approaches and its advantage compared to of one-track interventions was becoming a discussion tool in therapy research as well as in mental health systems. Results of meta-analyses support superiority of integrated approaches compared to one-track interventions in more distal outcome areas such as social functioning. These results are in line with the large body of 37 independent IPT studies in 12 countries. Moreover, IPT research indicates the maintenance of therapy effects after the end of therapy and some evidence generalization effects. Additionally, the international randomized multi-center study on INT with 169 outpatients strongly supports the successful therapy of integrated therapy in proximal and distal outcome such as significant effects in cognition, functioning and negative symptoms. Clinical implication: therapy research as well as expert’s clinical experience recommends integrated therapy approaches such as IPT to be successful agents within multimodal psychiatric treatment concepts. Finally, integrated group therapy based on cognitive remediation seems to motivate and stimulate schizophrenia inpatients and outpatients to more successful and independent life also demanded by the recovery movement.

Experimental evidence for the immediate impact of fertilization and irrigation upon the plant and invertebrate communities of mountain grasslands

The response of montane and subalpine hay meadow plant and arthropod communities to the application of liquid manure and aerial irrigation – two novel, rapidly spreading management practices – remains poorly understood, which hampers the formulation of best practice management recommendations for both hay production and biodiversity preservation. In these nutrient-poor mountain grasslands, a moderate management regime could enhance overall conditions for biodiversity. This study experimentally assessed, at the site scale, among low-input montane and subalpine meadows, the short-term effects (1 year) of a moderate intensification (slurry fertilization: 26.7–53.3 kg N·ha−1·year−1; irrigation with sprinklers: 20 mm·week−1; singly or combined together) on plant species richness, vegetation structure, hay production, and arthropod abundance and biomass in the inner European Alps (Valais, SW Switzerland). Results show that (1) montane and subalpine hay meadow ecological communities respond very rapidly to an intensification of management practices; (2) on a short-term basis, a moderate intensification of very low-input hay meadows has positive effects on plant species richness, vegetation structure, hay production, and arthropod abundance and biomass; (3) vegetation structure is likely to be the key factor limiting arthropod abundance and biomass. Our ongoing experiments will in the longer term identify which level of management intensity achieves an optimal balance between biodiversity and hay production.

Are shrubs really a sign of declining ecosystem function? Disentangling the myths and truths of woody encroachment in Australia

Since European settlement, there has been a dramatic increase in the density, cover and distribution of woody plants in former grassland and open woodland. There is a widespread belief that shrub encroachment is synonymous with declines in ecosystem functions, and often it is associated with landscape degradation or desertification. Indeed, this decline in ecosystem functioning is considered to be driven largely by the presence of the shrubs themselves. This prevailing paradigm has been the basis for an extensive program of shrub removal, based on the view that it is necessary to reinstate the original open woodland or grassland structure from which shrublands are thought to have been derived. We review existing scientific evidence, particularly focussed on eastern Australia, to question the notion that shrub encroachment leads to declines in ecosystem functions. We then summarise this scientific evidence into two conceptual models aimed at optimising landscape management to maximise the services provided by shrub-encroached areas. The first model seeks to reconcile the apparent conflicts between the patch- and landscape-level effects of shrubs. The second model identifies the ecosystem services derived from different stages of shrub encroachment. We also examined six ecosystem services provided by shrublands (biodiversity, soil C, hydrology, nutrient provision, grass growth and soil fertility) by using published and unpublished data. We demonstrated the following: (1) shrub effects on ecosystems are strongly scale-, species- and environment-dependent and, therefore, no standardised management should be applied to every case; (2) overgrazing dampens the generally positive effect of shrubs, leading to the misleading relationship between encroachment and degradation; (3) woody encroachment per se does not hinder any of the functions or services described above, rather it enhances many of them; (4) no single shrub-encroachment state (including grasslands without shrubs) will maximise all services; rather, the provision of ecosystem goods and services by shrublands requires a mixture of different states; and (5) there has been little rigorous assessment of the long-term effectiveness of removal and no evidence that this improves land condition in most cases. Our review provides the basis for an improved, scientifically based understanding and management of shrublands, so as to balance the competing goals of providing functional habitats, maintaining soil processes and sustaining pastoral livelihoods.

First Molecular Evidence for Puumala Hantavirus in Poland

Puumala virus (PUUV) causes mild to moderate cases of haemorrhagic fever with renal syndrome (HFRS), and is responsible for the majority of hantavirus infections of humans in Fennoscandia, Central and Western Europe. Although there are relatively many PUUV sequences available from different European countries, little is known about the presence of this virus in Poland. During population studies in 2009 a total of 45 bank voles were trapped at three sites in north-eastern Poland, namely islands on Dejguny and Dobskie Lakes and in a forest near Mikołajki. S and M segment-specific RT-PCR assays detected PUUV RNA in three animals from the Mikołajki site. The obtained partial S and M segment sequences demonstrated the highest similarity to the corresponding segments of a PUUV strain from Latvia. Analysis of chest cavity fluid samples by IgG ELISA using a yeast-expressed PUUV nucleocapsid protein resulted in the detection of two seropositive samples, both being also RT-PCR positive. Interestingly, at the trapping site in Mikołajki PUUV-positive bank voles belong to the Carpathian and Eastern genetic lineages within this species. In conclusion, we herein present the first molecular evidence for PUUV in the rodent reservoir from Poland.

Graft preservation solutions in cardiovascular surgery.

Vein grafts are still the most commonly used graft material in cardiovascular surgery and much effort has been spent in recent years on investigating the optimal harvesting technique. One other related topic of similar importance remained more or less an incidental one. The storage solutions of vein grafts following procurement and prior to implantation are, despite their assumed impact, a relatively neglected theme. There is no doubt that the endothelium plays a key role in long-term patency of vein grafts, but the effects of the different storage solutions on the endothelium remain unclear : In a review of the literature, we could find 20 specific papers that addressed the question, of which the currently available preservation solutions are superior, harmless, damaging or ineffective. The focus lies on saline and autologous whole blood. Besides these two storage media, novel or alternative solutions have been investigated with surprising findings. In addition, a few words will be spent on potential alternatives and novel solutions on the market. As there is currently no randomized clinical trial regarding saline versus autologous whole blood available, this review compares all previous studies and methods of analysis to provide a certain level of evidence on this topic. In summary, saline has negative effects on the endothelial layers and therefore may compromise graft patency. Related factors, such as distension pressure, may outbalance the initial benefit of autologous whole blood or storage solutions and intensify the harmful effects of warm saline. In addition, there is no uniform consent on the superiority of autologous whole blood for vein graft storage. This may open the door to alternatives such as the University of Wisconsin solution or one of the specific designed storage solutions like TiProtec™ or Somaluthion™. Whether these preservation solutions are superior or advantageous remains the subject of further studies.