A System Out of Breath: How Hypoxia Possibly Contributes to the Pathogenesis of Systemic Sclerosis

Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular alterations and immunological disturbances and fibrosis, the order of which remains to be fully determined. Clinically, patients show clear signs of hypoxia in skin and internal organs. The low oxygen tension is potentially caused by a yet to be indentified circuitry involving the three features that typify SSc. In addition, once present, the hypoxia creates a vicious circle of ongoing pathology. In this paper, we provide an overview of the evidence that points towards the mechanisms causing hypoxia in SSc. In addition, data that suggest how hypoxia itself may orchestrate worsening of symptoms is presented. Altogether, it is clear that hypoxia is an important hallmark in SSc patients. By providing an overview of the mechanisms at play and the possible therapeutic avenues that have emerged, we hope to stimulate researchers to provide novel clues into the conundrum in SSc patients

Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter

In an effort to maximize outcomes, recent expert guidelines recommend more-intensive vancomycin dosing schedules to maintain vancomycin troughs between 15 and 20 mg/liter.The widespread use of these more-intensive regimens has been associated with an increase in vancomycin-induced nephrotoxicity reports.The purpose of this systematic literature review is to determine the nephrotoxicity potential of maintaining higher troughs in clinical practice.All studies pertaining to vancomycin-induced nephrotoxicity between 1996 and April 2012 were identified from PubMed, Embase, Cochrane Controlled Trial Registry, and Medline databases and analyzed according to Cochrane guidelines.Of the initial 240 studies identified, 38 were reviewed, and 15 studies met the inclusion criteria.Overall, higher troughs ( >15 mg/liter) were associated with increased odds of nephrotoxicity (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.95 to 3.65) relative to lower troughs of >15 mg/liter.The relationship between a trough of >15 mg/liter and nephrotoxicity persisted when the analysis was restricted to studies that examined only initial trough concentrations (OR, 3.12; 95% CI, 1.81 to 5.37).The relationship between troughs of >15 mg/liter and nephrotoxicity persisted after adjustment for covariates known to independently increase the risk of a nephrotoxicity event.An incremental increase in nephrotoxicity was also observed with longer durations of vancomycin administration.Vancomycin-induced nephrotoxicity was reversible in the majority of cases, with short-term dialysis required only in 3% of nephrotoxic episodes.The collective literature indicates that an exposure-nephrotoxicity relationship for vancomycin exists.The probability of a nephrotoxic event increased as a function of the trough concentration and duration of therapy

Data availibility for the fisheries impact assessment of the FIMPAS project

The project Fisheries Measures in Protected Areas (FIMPAS) aims to introduce fisheries measures in the marine Natura 2000 sites within the Exclusive Economic Zone of the Dutch part of the North Sea by the end of 2011. The FIMPAS project covers three such areas, the Dogger Bank and the Cleaver Bank (both to be designated for protection under the Habitats Directive) and the Frisian Front (to be designated for protection under the Birds Directive). These sites are beyond the Dutch 12 nm zone and several EU Member States fish within these areas. Therefore fisheries measures must be implemented through the Common Fisheries Policy. These marine protected areas, as well as the potential fisheries measures, are a consequence of the implementation of the European Birds and Habitats Directives and will be proposed to the European Commission by the Dutch government. The Dutch Ministry for Agriculture, Nature and Food Quality (LNV), together with Dutch environmental NGOs and the Dutch fishing industry, are cooperating within the FIMPAS project to develop the necessary fisheries measures to achieve the conservation objectives for the Dutch Natura 2000 sites of the North Sea. LNV has asked the International Council for the Exploration of the Sea (ICES) to organize the necessary scientific processes and give advice on the desired fisheries measures involving the relevant stakeholders in this process

Biodiversity hotspots on the Dutch Continental Shelf: a marine strategy framework directive perspective

This report presenst hotspots of biodiversity for benthos, fish, birds, marine mammals and habitats on the Dutch Continental Shelf. These hotspots are based on a spatial application of biodiversity metrics developed in this study for the GES(Good Environmental Status)-descriptor 1 ‘Biological diversity is maintained’ of the Marine Strategy Framework Directive (MSFD) (EU 2008). The choice of the biodiversity metrics is based on the proposed indicators of biodiversity in the Commission Decision (EU 2010). The purpose of this study is to provide insight in possibilities for spatial protection measures in the framework of the MSFD. This report feeds information and ideas into further work for the MSFD in the Netherlands. IMARES has compiled this report for the Dutch Ministry of Economic Affairs, Agriculture and Innovation (Ministry of EL&I) and the Ministry of Infrastructure and the Environment (I&M)

Unravelling the complex interplay between antibiotic consumption and adaptive changes in methicillin-resistant Staphylococcus aureus

Funding: This study was supported by internal funding.Objectives This study aims to elucidate the genomic dynamics driving the emergence of antimicrobial resistance (AMR), with a specific focus on the interplay between AMR and antimicrobial usage. Methods We conducted a comprehensive analysis using a ST239 methicillin-resistant Staphylococcus aureus (MRSA) dataset over a continuous 12-year period from a single hospital. Genomic analyses were performed tracking the changes in MRSA populations, particularly the emergence of reduced vancomycin susceptibility, and assessing the impact of glycopeptide use on these emergence events. Results Our findings reveal a significant correlation between hospital glycopeptide usage and the selection of MRSA strains with reduced vancomycin susceptibility. Genomic analyses provided insights into the molecular mechanisms driving resistance emergence, including the slowing of the molecular clock rate in response to heightened antimicrobial consumption. Conclusions In conclusion, this study the highlights the complex dynamics between AMR and antimicrobial use at the hospital level. The observed correlation between antimicrobial consumption and the development of less susceptible MRSA strains underscores the importance of antimicrobial stewardship programmes and the establishment of optimal consumption thresholds for mitigating AMR effectively.Peer reviewe

Vangstadviezen voor snoekbaars, baars, blankvoorn en brasem in het IJsselmeer en Markermeer

Het ministerie wil in het kader van de visserijwet en de Kaderrichtlijn Water komen tot wetenschappelijk onderbouwd beheer van de belangrijkste commerciële schubvisbestanden. In 2013 zijn vangstadviezen gegeven voor vier schubvissoorten in het IJsselmeer en Markermeer; snoekbaars, baars, brasem en blankvoorn. In het huidige rapport worden voor het visseizoen 2015/2016 opnieuw vangstadviezen gegeven. De doelstelling is aangescherpt van ‘voorkomen van achteruitgang’ naar ‘herstel’ van de bestanden. Bovendien zijn vanaf juli 2014 sterke vangstbeperkingen voor deze soorten.

Reply to "vancomycin-induced nephrotoxicity"

[No abstract available

Glucocorticoid receptor expression in human bronchial epithelial cells: effects of smoking and COPD.

Previously, we found that inflammatory mediators modulated the number and binding affinity of glucocorticoid receptors (GR) in human bronchial epithelial cell lines. In this study we investigated whether smoking and chronic obstructive pulmonary disease (COPD), both characterized by airway inflammation with increased levels of inflammatory mediators, affect GR characteristics in cultured human bronchial epithelial cells (HBEC). A statistically significant difference was found between the dissociation constant (Kd) values in HBEC from smoking (Kd = 0.98+/-0.08 nM; n = 6) and nonsmoking controls (Kd = 0.76+/-0.10 nM, P = 0.03; n = 5), but no significant difference was found between the mean number of binding sites. Our results are the first indication that cultured HBEC from smokers possess GR with a lower binding affinity. This may result from the inflammation found in the airways from smokers. Furthermore, these results provide further evidence that the bronchial epithelium may be an actual target for inhaled glucocorticoid therapy

Extending the voltage window in the characterization of electrical transport of large-area molecular junctions

A large bias window is required to discriminate between different transport models in large-area molecular junctions. Under continuous DC bias, the junctions irreversibly break down at fields over 9 MV/cm. We show that, by using pulse measurements, we can reach electrical fields of 35 MV/cm before degradation. The breakdown voltage is shown to depend logarithmically on both duty cycle and pulse width. A tentative interpretation is presented based on electrolysis in the polymeric top electrode. Expanding the bias window using pulse measurements unambiguously shows that the electrical transport exhibits not an exponential but a power-law dependence on bias. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3608154