In vitro impact of platinum nanoparticles on inner ear related cell culture models.

So far, it was supposed that the increase of electrical impedance following cochlear implant (CI) insertion was due to technical defects of the electrode, inflammatory and/or formation of scar tissue along the electrode. However, it was recently reported that corrosion of the platinum electrode contacts may be the reason for high impedances. It could be shown that platinum particles were stripped from the electrode surfaces. Its potential cytotoxic effects within the inner ear remains to be examined. In this study in vitro cell culture models of the mouse organ of Corti cell line (HEI-OC1) and the spiral ganglion (SG) cells derived from the cochleae neonatal rats were used to investigate the effects of the polyvinylpyrrolidone coated platinum nanoparticles (Pt-NPPVP, 3 nm) on cell metabolism, neuronal survival and neurite outgrowth. Our data revealed no decrease of the metabolic activity of the HEI-OC1 cells at Pt-NPPVP concentrations between 50-150 µg/ml. Also, staining with Calcein AM/EthD demonstrated prevalent presence of vital cells. As shown by transmission electron microscopy no Pt-NPPVP could be found at the cell surface or in the cytosol of the HEI-OC1 cells. Similarly, the SG cells exposed to 20-100 µg/ml Pt-NPPVP did not show any reduced survival rate and neurite outgrowth following staining of the neurofilament antigen even at the highest Pt-NPPVP concentration. Although the SG cells were exposed to Pt-NPPVP for further 72 h and 96 h immunocytochemical staining of the glial cells and fibroblasts presented normal cell morphology and growth independently of the cultivation period. Our data indicates that the used Pt-NPPVP do not trigger the cellular uptake and, thus, presumable do not initiate apoptotic pathways in cells of the organ of Corti cell line or the auditory nerve. The protection mechanisms to the Pt-NPPVP interactions remain to be clarified.

Linking environmental with biological data: Low sampling frequencies of chemical pollutants and nutrients in rivers reduce the reliability of model results.

Linking environmental and biological data using ecological models can provide crucial knowledge about the effects of water quality parameters on freshwater ecosystems. However, a model can only be as reliable as its input data. Here, the influence of sampling frequency of temporal variable environmental input data on the reliability of model results when linked to biological data was investigated using Threshold Indicator Taxa Analysis (TITAN) and species sensitivity distributions (SSDs). Large-scale biological data from benthic macroinvertebrates and matching water quality data including four metals and four nutrients of up to 559 site-year combinations formed the initial data sets. To compare different sampling frequencies, the initial water quality data sets (n = 12 samples per year, set as reference) were subsampled (n = 10, 8, 6, 4, 2 and 1), annual mean values calculated and used as input data in the models. As expected, subsampling significantly reduced the reliability of the environmental input data across all eight substances. For TITAN, the use of environmental input data with a reduced reliability led to a considerable (1) loss of information because valid taxa were no longer identified, (2) gain of unreliable taxon-specific change points due to false positive taxa, and (3) bias in the change point estimation. In contrast, the reliability of the SSD results appeared to be much less reduced. However, closer examination of the SSD input data indicated that existing effects were masked by poor model performance. The results confirm that the sampling frequency of water quality data significantly influences the reliability of model results when linked with biological data. For studies limited to low sampling frequencies, the discussion provides recommendations on how to deal with low sampling frequencies of temporally variable water quality data when using them in TITAN, in SSDs, and in other ecological models.

Social-ecological interactions in the Draa River Basin, southern Morocco: Towards nature conservation and human well-being using the IPBES framework.

Water is essential to human societies and a prerequisite for flourishing nature, especially in arid regions. Yet, climate change and socio-economic developments are expected to exacerbate current and future stresses on water resources, demanding innovative approaches to balance water needs for society and nature conservation. In this study, we use the IPBES conceptual framework to combine ecological and socio-economic insights and analyse the connections between people and nature in the water scarce Draa River Basin, southern Morocco. We study the diversity of desert benthic macroinvertebrates as one component of nature using DNA barcoding and their potential to serve as bioindicators of human impact by relating species occurrences to environmental parameters. Furthermore, based on 87 interviews with farmers and key institutional stakeholders, we investigate how farmers perceive water related changes and how water is managed in the basin. Regarding benthic macroinvertebrates, 41 families were identified, 475 DNA barcodes generated and assigned to 118 putative species (Barcode Index Numbers) of which 60 were first records. This indicates a lack of reference sequences for known, but also a potentially high number of undescribed species. Environmental parameters, which are partly influenced by human activities, such as aquatic stages, salinity and intermittency, were the most important variables explaining invertebrate richness and community composition in generalized linear models. We further describe farmers' perceptions of decreasing water quality and quantity. Farmers generally believe that they are able to cope with water related changes, although perceptions are regionally differentiated with farmers downstream being less optimistic. With growing concerns, water policies currently focus on increasing water supply and less on reducing water demands. Based on these findings, the usefulness of the IPBES framework for understanding social-ecological system dynamics is reflected, and recommendations for future freshwater management and research are derived.

Examination of paraben release from baby teethers through migration tests and GC-MS analysis using a stable isotope dilution assay.

Parabens and sorbic acid are commonly used as food preservatives due to their antimicrobial effect. However, their use in foods for infants and young children is not permitted in the European Union. Previous studies found these compounds in some gel-filled baby teethers, whereby parabens, which are well-known as endocrine disruptors, were identified in the polymer-based chewing surface consisting of ethylene-vinyl acetate (EVA). To assess the exposure of infants and young children to these products, the application of parabens in teethers should be thoroughly investigated. Therefore, the present study aimed to apply a representative migration test procedure combined with an accurate analytical method to examine gel-filled baby teethers without elaborate sample preparation, high costs, and long processing times. Accordingly, solid-phase extraction (SPE), in combination with a stable isotope dilution assay (SIDA) and subsequent gas chromatography-mass spectrometry (GC-MS) for analysis of methyl-, ethyl-, and n-propylparaben (MeP, EtP, and n-PrP), was found to be well-suited, with recoveries ranging from 93 to 99%. The study compared the release of these parabens from intact teether surfaces into water and saliva simulant under real-life conditions, with total amounts of detected parabens found to be in the range of 101-162 µg 100 mL-1 and 57-148 µg 100 mL-1, respectively. Furthermore, as a worst-case scenario, the release into water was examined using a long-term migration study.

Salinity impacts on river ecosystem processes: a critical mini-review.

In many dry parts of the world, salinization of water resources threatens freshwater biodiversity and the livelihood of people. However, ecological impact studies remain scarce. Here, we review field-observations of salinity impacts on ecosystem processes such as leaf decomposition, metabolism, biomass production and nutrient cycling, with a special emphasis on dryland ecosystems. In addition, we discuss the potential linkages of these processes to ecosystem service delivery-the benefits that humans derive from ecosystems-as additional nature conservation arguments and the challenges associated with this endeavour.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.

Towards stressor-specific macroinvertebrate indices: Which traits and taxonomic groups are associated with vulnerable and tolerant taxa?

Monitoring of macroinvertebrate communities is frequently used to define the ecological health status of rivers. Ideally, biomonitoring should also give an indication on the major stressors acting on the macroinvertebrate communities supporting the selection of appropriate management measures. However, most indices are affected by more than one stressor. Biological traits (e.g. size, generation time, reproduction) could potentially lead to more stressor-specific indices. However, such an approach has rarely been tested. In this study we classify 324 macroinvertebrate taxa as vulnerable (decreasing abundances) or tolerant (increasing abundances) along 21 environmental gradients (i.e. nutrients, major ions, oxygen and micropollutants) from 422 monitoring sites in Germany using Threshold Indicator Taxa Analysis (TITAN). Subsequently, we investigate which biological traits and taxonomic groups are associated with taxa classified as vulnerable or tolerant with regard to specific gradients. The response of most taxa towards different gradients was similar and especially high for correlated gradients. Traits associated with vulnerable taxa across most gradients included: larval aquatic life stages, isolated cemented eggs, reproductive cycle per year <1, scrapers, aerial and aquatic active dispersal and plastron respiration. Traits associated with tolerant taxa included: adult aquatic life stages, polyvoltinism, ovoviviparity or egg clutches in vegetation, food preference for dead animals or living microinvertebrates, substrate preference for macrophytes, microphytes, silt or mud and a body size >2-4cm. Our results question whether stressor-specific indices based on macroinvertebrate assemblages can be achieved using single traits, because we observed that similar taxa responded to different gradients and also similar traits were associated with vulnerable and tolerant taxa across a variety of water quality gradients. Future studies should examine whether combinations of traits focusing on specific taxonomic groups achieve higher stressor specificity.

Water quality variables and pollution sources shaping stream macroinvertebrate communities.

In 2015, over 90 percent of German rivers failed to reach a good ecological status as demanded by the EU Water Framework Directive (WFD). Deficits in water quality, mainly from diffuse pollution such as agricultural run-off, but also from wastewater treatment plants (WWTPs), have been suggested as important drivers of this decline in ecological quality. We modelled six macroinvertebrate based metrics indicating ecological quality for 184 streams in response to a) PCA-derived water quality gradients, b) individual water quality variables and c) catchment land use and wastewater exposure indices as pollution drivers. The aim was to evaluate the relative importance of key water quality variables and their sources. Indicator substances (i.e. carbamazepine and caffeine indicating wastewater exposure; herbicides indicating agricultural run-off) represented micropollutants in the analyses and successfully related water quality variables to pollution sources. Arable and urban catchment land covers were strongly associated with reduced ecological quality. Electric conductivity, oxygen concentration, caffeine, silicate and toxic units with respect to pesticides were identified as the most significant in-stream predictors in this order. Our results underline the importance to manage diffuse pollution, if ecological quality is to be improved. However, we also found a clear impact of wastewater on ecological quality through caffeine. Thus, improvement of WWTPs, especially preventing the release of poorly treated wastewater, will benefit freshwater communities.

The Glycoproteins of All Filovirus Species Use the Same Host Factors for Entry into Bat and Human Cells but Entry Efficiency Is Species Dependent.

Ebola and marburgviruses, members of the family Filoviridae, can cause severe hemorrhagic fever in humans. The ongoing Ebola virus (EBOV) disease epidemic in Western Africa claimed more than 11,300 lives and was associated with secondary cases outside Africa, demonstrating that filoviruses pose a global health threat. Bats constitute an important natural reservoir of filoviruses, including viruses of the recently identified Cuevavirus genus within the Filoviridae family. However, the interactions of filoviruses with bat cells are incompletely understood. Here, we investigated whether filoviruses employ different strategies to enter human and bat cells. For this, we examined host cell entry driven by glycoproteins (GP) from all filovirus species into cell lines of human and fruit bat origin. We show that all GPs were able to mediate entry into human and most fruit bat cell lines with roughly comparable efficiency. In contrast, the efficiency of entry into the cell line EidNi/41 derived from a straw-colored fruit bat varied markedly between the GPs of different filovirus species. Furthermore, inhibition studies demonstrated that filoviruses employ the same host cell factors for entry into human, non-human primate and fruit bat cell lines, including cysteine proteases, two pore channels and NPC1 (Niemann-Pick C1 molecule). Finally, processing of GP by furin and the presence of the mucin-like domain in GP were dispensable for entry into both human and bat cell lines. Collectively, these results show that filoviruses rely on the same host cell factors for entry into human and fruit bat cells, although the efficiency of the usage of these factors might differ between filovirus species.

Field data reveal low critical chemical concentrations for river benthic invertebrates.

River ecosystems are of immense ecological and social importance. Despite the introduction of wastewater treatment plants and advanced chemical authorization procedures in Europe, chemical pollution is still a major threat to freshwater ecosystems. Here, large-scale monitoring data was exploited to identify taxon-specific chemical concentrations beyond which benthic invertebrate taxa are unlikely to occur using Threshold Indicator Taxa Analysis (TITAN). 365 invertebrate taxa and 25 organic chemicals including pesticides, pharmaceuticals, plasticisers, flame retardants, complexing agents, a surfactant and poly- and monocyclic aromatic hydrocarbons from a total of 399 sites were analysed. The number of taxa that responded to each of these chemicals varied between 0% and 21%. These sensitive taxa belonged predominantly to the groups Plecoptera, Coleoptera, Trichoptera, Ephemeroptera, Turbellaria, Megaloptera, Crustacea, and Diptera. Strong effects were observed in response to wastewater-associated compounds, confirming that wastewater is an important cause of biological degradation. The majority of change points identified for each compound were well below predicted no-effect concentrations derived from laboratory toxicity studies. Thus, the results show that chemicals are likely to induce effects in the environment at concentrations much lower than expected based on laboratory experiments. Overall, it is confirmed that chemical pollution is still an important factor shaping the distribution of invertebrate taxa, suggesting the need for continued efforts to reduce chemical loads in rivers.

Training of verbal creativity modulates brain activity in regions associated with language- and memory-related demands.

This functional magnetic resonance (fMRI) study was designed to investigate changes in functional patterns of brain activity during creative ideation as a result of a computerized, 3-week verbal creativity training. The training was composed of various verbal divergent thinking exercises requiring participants to train approximately 20 min per day. Fifty-three participants were tested three times (psychometric tests and fMRI assessment) with an intertest-interval of 4 weeks each. Participants were randomly assigned to two different training groups, which received the training time-delayed: The first training group was trained between the first and the second test, while the second group accomplished the training between the second and the third test session. At the behavioral level, only one training group showed improvements in different facets of verbal creativity right after the training. Yet, functional patterns of brain activity during creative ideation were strikingly similar across both training groups. Whole-brain voxel-wise analyses (along with supplementary region of interest analyses) revealed that the training was associated with activity changes in well-known creativity-related brain regions such as the left inferior parietal cortex and the left middle temporal gyrus, which have been shown as being particularly sensitive to the originality facet of creativity in previous research. Taken together, this study demonstrates that continuous engagement in a specific complex cognitive task like divergent thinking is associated with reliable changes of activity patterns in relevant brain areas, suggesting more effective search, retrieval, and integration from internal memory representations as a result of the training.

Effect-directed identification of endocrine disruptors in plastic baby teethers.

Concerns have been raised regarding the human health effects of endocrine disrupting chemicals (EDCs), many of which are associated with and leaching from plastics. As infants are particularly vulnerable to EDCs, we have investigated whether plastic teethers for babies represent a relevant source of exposure. Applying effect-directed analysis, we use bioassays to screen teethers, toys used to soothe a baby's teething ache, for endocrine activity and chemical analysis to identify the causative compounds. We detected significant endocrine activity in two of 10 plastic teethers. Those samples leached estrogenic and/or antiandrogenic activity as detected in the Yeast Estrogen Screen and Yeast Antiandrogen Screen. After sample fractionation, gas chromatography-mass spectrometry non-target screening revealed that methyl-, ethyl- and propylparaben were responsible for the observed estrogenic and antiandrogenic activity in one product. The second product is likely to contain at least six different antiandrogenic compounds that remain so far unidentified. This study demonstrates that plastic teethers can be a source of infant exposure to well-established and unknown EDCs. Because of their limited value to the product, but potential toxicity, manufacturers should critically revisit the use of parabens in plastic teethers and further toys. Moreover, plastic teethers might leach EDCs that escape routine analysis and, thus, toxicological evaluation. The resulting uncertainty in product safety poses a problem to consumers, producers and regulators that remain to be resolved.

Globalization of leptospirosis through travel and migration.

Leptospirosis remains the most widespread zoonotic disease in the world, commonly found in tropical or temperate climates. While previous studies have offered insight into intra-national and intra-regional transmission, few have analyzed transmission across international borders. Our review aimed at examining the impact of human travel and migration on the re-emergence of Leptospirosis. Results suggest that alongside regional environmental and occupational exposure, international travel now constitute a major independent risk factor for disease acquisition. Contribution of travel associated leptospirosis to total caseload is as high as 41.7% in some countries. In countries where longitudinal data is available, a clear increase of proportion of travel-associated leptospirosis over the time is noted. Reporting patterns is clearly showing a gross underestimation of this disease due to lack of diagnostic facilities. The rise in global travel and eco-tourism has led to dramatic changes in the epidemiology of Leptospirosis. We explore the obstacles to prevention, screening and diagnosis of Leptopirosis in health systems of endemic countries and of the returning migrant or traveler. We highlight the need for developing guidelines and preventive strategies of Leptospirosis related to travel and migration, including enhancing awareness of the disease among health professionals in high-income countries.

Gradient evolution of body colouration in surface- and cave-dwelling Poecilia mexicana and the role of phenotype-assortative female mate choice.

Ecological speciation assumes reproductive isolation to be the product of ecologically based divergent selection. Beside natural selection, sexual selection via phenotype-assortative mating is thought to promote reproductive isolation. Using the neotropical fish Poecilia mexicana from a system that has been described to undergo incipient ecological speciation in adjacent, but ecologically divergent habitats characterized by the presence or absence of toxic H2S and darkness in cave habitats, we demonstrate a gradual change in male body colouration along the gradient of light/darkness, including a reduction of ornaments that are under both inter- and intrasexual selection in surface populations. In dichotomous choice tests using video-animated stimuli, we found surface females to prefer males from their own population over the cave phenotype. However, female cave fish, observed on site via infrared techniques, preferred to associate with surface males rather than size-matched cave males, likely reflecting the female preference for better-nourished (in this case: surface) males. Hence, divergent selection on body colouration indeed translates into phenotype-assortative mating in the surface ecotype, by selecting against potential migrant males. Female cave fish, by contrast, do not have a preference for the resident male phenotype, identifying natural selection against migrants imposed by the cave environment as the major driver of the observed reproductive isolation.

Bortezomib combined with low-dose cytarabine in Intermediate-2 and high risk myelodysplastic syndromes. A phase I/II Study by the GFM.

Marrow cells from patients with higher-risk myelodysplastic syndrome (MDS) exhibit constitutive nuclear factor (NF)-κB activation. The proteasome inhibitor, bortezomib, has limited efficacy as a single agent in acute myeloid leukaemia. Its activity on leukaemic cell lines is potentiated by chemotherapy. We treated 43 higher-risk MDS patients with bortezomib (1·5 mg/m(2) , days 1, 4, 8 and 11) and low dose cytarabine arabinoside (LDAC; 10 mg/m(2) , then 20 mg/m(2) from days 1-14), every 28 d for four cycles. Median follow-up was 29·7 months. Responses were seen in 12 of the 43 patients (28%), including complete response (CR, n = 1), marrow-CR (n = 3), partial response (PR, n = 5) and haematological improvement (HI, n = 3). Responses were seen in 12 (36%) of the 33 previously untreated patients (11% CR, 13% PR, 2·5% HI), compared to none in the 12 previously treated patients (P < 0·01). Responders had better overall survival (median 18·2 vs. 10 months). One CR and 3 marrow-CRs were seen in patients with complex karyotypes. Main toxicity was haematological, responsible for infection in six patients and bleeding in 3. Three patients with Grade 1-2 pre-treatment haematotoxicity developed Grade 3-4 toxicity. Neuropathy was seen in 12% of patients. The addition of bortezomib to LDAC in higher-risk MDS may improve results obtained with LDAC alone, especially in patients with unfavourable karyotypes.

Implementation and evaluation of a web based system for pharmacy stock management in rural Haiti.

Managing the stock and supply of medication is essential for the provision of health care, especially in resource poor areas of the world. We have developed an innovative, web-based stock management system to support nine clinics in rural Haiti. Building on our experience with a web-based EMR system for our HIV patients, we developed a comprehensive stock tracking system that is modeled on the appearance of standardized WHO stock cards. The system allows pharmacy staff at all clinics to enter stock levels and also to request drugs and track shipments. Use of the system over the last 2 years has increased rapidly and we now track 450 products supporting care for 1.78 million patient visits annually. Over the last year drug stockouts have fallen from 2.6% to 1.1% and 97% of stock requests delivered were shipped within 1 day. We are now setting up this system in our clinics in rural Rwanda.

The Budd-Chiari syndrome: outcome after treatment with the transjugular intrahepatic portosystemic shunt.

BACKGROUND: The role of portosystemic shunting in the treatment of the Budd-Chiari syndrome is still under debate. Medical therapy and liver transplantation are alternative treatments. The aim of this study was to determine the outcome of a transjugular intrahepatic portosystemic shunt implantation. METHODS: Thirty-five patients with severe Budd-Chiari syndrome and a Child-Pugh score of 9.2+/-1.9, who were not responsive to medical therapy, were elected for the transjugular shunt treatment, which was successfully accomplished in 33. Eleven patients had a fulminant/acute (history <2 months); 13, a subacute (<6 months); and 11, a chronic course of the disease. The shunt was established by using conventional self-expandable stents in 25 patients and polytetrafluoroethylene-covered stents in 8 patients. The mean follow-up was 37+/-29 months. RESULTS: The shunt reduced the portosystemic pressure gradient from 29+/-7 to 10+/-4 mm Hg and improved the portal flow velocity from 9.2+/-11 to 51+/-17 cm/s. Clinical symptoms as well as the biochemical test results improved significantly during 4 weeks after shunt treatment. Three patients died and 2 received liver transplants. The cumulative 1- and 5-year survival rate without transplantation in all patients was 93% and 74%, respectively, and in patients with fulminant/acute disease 91% and 91% respectively (no deaths in this time period). On the average, 1.4+/-2.2 revisions per patient were needed during the mean follow-up of 3 years with a 1-year probability of 47%. CONCLUSIONS: The transjugular shunt provides an excellent outcome in patients with severe fulminant/acute, subacute, and chronic Budd-Chiari syndrome. It may be regarded as a treatment for the acute and long-term management of these patients.