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BackgroundCurrent practice methods are unclear as to the most safe and effective prophylactic pharmacotherapy and method of delivery to reduce postoperative endophthalmitis occurrence.MethodsA systematic review and meta-analysis using Meta-analysis of Observational Studies in Epidemiology guidelines was performed to compare the efficacy of intracameral cefuroxime, moxifloxacin and vancomycin in preventing postphacoemulsification cataract surgery endophthalmitis. A safety analysis of intracameral antibiotics was concurrently performed.Data sourcesBIOSIS Previews, CINAHL, ClinicalTrials.gov, Cochrane Library, Dissertations & Theses, EMBASE, PubMed, ScienceDirect and Scopus were searched from inception to January 2017. Data were pooled using a random effects model. All articles were individually reviewed and data were extracted by two independent reviewers. Funnel plot, risk of bias and quality of evidence analyses were performed.ResultsSeventeen studies with over 900 000 eyes were included, which favoured the use of intracameral antibiotics at the end of cataract surgery (OR 0.20; 95% CI 0.13 to 0.32; P<0.00001). The average weighted postoperative endophthalmitis incidence rates with intracameral cefuroxime, moxifloxacin and vancomycin were 0.0332%, 0.0153% and 0.0106%, respectively. Secondary analyses showed no difference in efficacy between intracameral plus topical antibiotics versus intracameral alone (P>0.3). Most studies had low to moderate risk of bias. The safety analysis showed minimal toxicity for moxifloxacin. Dosing errors led to the majority of toxicities with cefuroxime. Although rare, vancomycin was associated with toxic retinal events.ConclusionIntracameral cefuroxime and moxifloxacin reduced endophthalmitis rates compared with controls with minimal or no toxicity events at standard doses. Additionally, intracameral antibiotics alone may be as effective as intracameral plus topical antibiotics.

Isocitrate dehydrogenase-1 (Idh1) is an important metabolic enzyme that produces NADPH by converting isocitrate to α -ketoglutarate. Idh1 is known to reduce reactive oxygen species (ROS) induced in cells by treatment with lipopolysaccharide (LPS) in vitro . Here, we used Idh1-deficient knockout (Idh1 KO) mice to investigate the role of Idh1 in antioxidant defense in vivo . Idh1 KO mice showed heightened susceptibility to death induced by LPS and exhibited increased serum levels of inflammatory cytokines such as tumor necrosis factor- α and interleukin-6. The serum of LPS-injected Idh1 KO mice also contained elevated levels of AST, a marker of inflammatory liver damage. Furthermore, after LPS injection, livers of Idh1 KO mice showed histological evidence of elevated oxidative DNA damage compared with livers of wild-type (WT) mice. Idh1 KO livers showed a faster and more pronounced oxidative stress than WT livers. In line with that, Idh1 KO hepatocytes showed higher ROS levels and an increase in the NADP + /NADPH ratio when compared with hepatocytes isolated from WT mice. These results suggest that Idh1 has a physiological function in protecting cells from oxidative stress by regulating the intracellular NADP + /NADPH ratio. Our findings suggest that stimulation of Idh1 activity may be an effective therapeutic strategy for reducing oxidative stress during inflammatory responses, including the early stages of septic shock.

The likelihood of success of a marine protected area (MPA) is strongly dependent on stakeholders’ support. A concern often raised by local fishers is their lack of involvement in the design or management of a MPA and their loss of income owing to lost fishing grounds. We used Algoa Bay, South Africa, as a case study to analyse fisher’s and fish-processing factory managers’ concerns and perceived economic losses from fishing closures using structured interviews. Since 2009, a 20 km-radius purse-seine fishing-exclusion zone has been tested in Algoa Bay to assess the benefit to population recovery of the endangered African penguin Spheniscus demersus . Costs to the industry were estimated in terms of loss of catches and additional travel time to fishing grounds with and without closures. Fisher responses to interviews revealed general support for conservation and MPAs, but individuals interviewed did not feel that the 20 km fishing exclusion zones in Algoa Bay would aid African penguin conservation. While they systematically raised concerns about potential economic costs to their industry from closures, neither their catch sizes nor travel times varied significantly with fishing exclusion measures. Acknowledgement and assessment of the economic concerns may aid in initiating an informed dialogue amongst the various stakeholders in Algoa Bay, which may increase compliance and success of the newly proclaimed Addo elephant National Park MPA. Continued dialogue may also act as a catalyst for more integrated ocean management of biodiversity and human uses in the bay.

Understanding the complex ways that biodiversity change influences Nature’s Contributions to People (NCPs) is at the heart of current debates on coastal conservation, as researchers and practitioners seek to translate ecological shifts into meaningful impacts for society and policy. Specifically, we often lack quantitative evaluations of this relationship. We address this gap through a survey of biodiversity experts, focusing on the Wadden Sea located along the coasts of Germany, Denmark, and the Netherlands, as well as Algoa Bay in South Africa. We asked the experts to assess which changes in Essential Biodiversity Variables (EBVs) of selected marine organism groups (phytoplankton, macrozoobenthos, birds, and fish) link to which NCP category. Expert opinions indicated a significant influence of biodiversity changes on non-material NCPs compared to material and regulating NCPs. Specifically, experts perceive significant impacts on experiences, learning, inspiration, and cultural identities derived from the marine environment. However, there is a lack of conservation focus on non-material NCPs with regards to marine biodiversity change, indicating a gap between stakeholder perceptions policy priorities. Our study emphasises the importance of integrating relational values into conservation strategies and calls for knowledge co-production involving diverse stakeholders to address power imbalances and develop more inclusive and effective management approaches for marine biodiversity.

Mitochondria play a key part in the regulation of apoptosis (cell death) 1 , 2 . Their intermembrane space contains several proteins that are liberated through the outer membrane in order to participate in the degradation phase of apoptosis 3 , 4 , 5 , 6 , 7 , 8 , 9 . Here we report the identification and cloning of an apoptosis-inducing factor, AIF 5 , which is sufficient to induce apoptosis of isolated nuclei. AIF is a flavoprotein of relative molecular mass 57,000 which shares homology with the bacterial oxidoreductases; it is normally confined to mitochondria but translocates to the nucleus when apoptosis is induced. Recombinant AIF causes chromatin condensation in isolated nuclei and large-scale fragmentation of DNA. It induces purified mitochondria to release the apoptogenic proteins cytochrome c and caspase-9. Microinjection of AIF into the cytoplasm of intact cells induces condensation of chromatin, dissipation of the mitochondrial transmembrane potential, and exposure of phosphatidylserine in the plasma membrane. None of these effects is prevented by the wide-ranging caspase inhibitor known as Z-VAD.fmk. Overexpression of Bcl-2, which controls the opening of mitochondrial permeability transition pores, prevents the release of AIF from the mitochondrion but does not affect its apoptogenic activity. These results indicate that AIF is a mitochondrial effector of apoptotic cell death.

The development of second primary tumors has a negative impact on the prognosis of head and neck squamous cell carcinoma. Previously, we detected genetically altered and tumor-related mucosal lesions in the resection margins in 25% of unselected head and neck squamous cell carcinoma patients (Tabor MP, Brakenhoff RH, van Houten VMM, Kummer JA, Snel MHJ, Snijders PJF, Snow GB, Leemans CR, Braakhuis BJM: Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications. Clin Cancer Res 2001, 7: 1523–1532). The aim of this study was to determine whether first and second primary tumors are clonally related and originate from a single genetically altered field. From 10 patients we analyzed the first tumor of the oral cavity or oropharynx, the >3-cm remote second primary tumor, and the mucosa from the tumor-free margins from both resection specimens. We compared TP53 mutations and loss of heterozygosity profiles using 19 microsatellite markers at chromosomes 3p, 9p, 13q, and 17p. In all patients, genetically altered mucosal lesions were detected in at least one resection margin from both first and second primary tumor. Evidence for a common clonal origin of the first tumor, second primary tumor, and the intervening mucosa was found for at least 6 of 10 patients. Our results indicate that a proportion of multiple primary tumors have developed within a single preneoplastic field. Based on different etiology and clinical consequences, we propose that independent second primary tumors should be distinguished from second field tumors, that arise from the same genetically altered field the first tumor has developed from.

Oil spill models are used to forecast the transport and fate of oil after it has been released. CranSLIK is a model that predicts the movement and spread of a surface oil spill at sea via a stochastic approach. The aim of this work is to identify parameters that can further improve the forecasting algorithms and expand the functionality of CranSLIK, while maintaining the run-time efficiency of the method. The results from multiple simulations performed using the operational, validated oil spill model, MEDSLIK-II, were analysed using multiple regression in order to identify improvements which could be incorporated into CranSLIK. This has led to a revised model, namely CranSLIK v2.0, which was validated against MEDSLIK-II forecasts for real oil spill cases. The new version of CranSLIK demonstrated significant forecasting improvements by capturing the oil spill accurately in real validation cases and also proved capable of simulating a broader range of oil spill scenarios.

In this newly updated third edition, learn step-by-step how to effectively teach English abroad. Gain valuable tips and resources for teaching in an unfamiliar educational system, working with students of varying ages and skill levels, and adapting to life in a different culture.

Clinical trials are testing the hypothesis that fetal nigral grafts are effective in the treatment of Parkinson's disease. In rodents and nonhuman primates, grafts of fetal nigral neurons consistently survive, produce dopamine, form synaptic connections, and ameliorate many behavioral deficits due to lesions of the nigrostriatal pathway. 1 However, the results of fetal-tissue transplantation in patients with Parkinson's disease have been variable. Some studies report a benefit after nigral grafting, 2 – 5 whereas others report little if any improvement. 6 , 7 This variation in the clinical response may be related to differences in the survival of implanted dopamine neurons, which has been shown . . .

Can local observations and indigenous knowledge be used to provide information that complements research on climate change? Using participatory research methodology and semi-directed interviews, we explored local and traditional knowledge about changes in sea ice in the area of Sachs Harbour, Northwest Territories. In this small Inuvialuit community, we interviewed all of the 16 community members and elders considered to be local experts on sea ice to ask about their observations. We organized their comments under the headings multiyear ice, first-year ice, fractures and pressure ridges, breakup and freezeup seasons, and other climate-related variables that influence sea ice (such as changes in winter, spring and summer temperatures, wind, rain, and thunderstorms). Observations were remarkably consistent in providing evidence of local change in such variables as multiyear ice distribution, first-year ice thickness, and ice breakup dates. The changes observed in the 1990s were said to be without precedent and outside the normal range of variation. In assessing the relevance of Inuvialuit knowledge to scientific research on climate change, we note some of the areas in which sharing of information between the two systems of knowledge may be mutually beneficial. These include the analysis of options for adapting to climate change and the generation of research questions and hypotheses for future studies. /// Est-ce que les observations locales et le savoir des Autochtones peuvent aider à fournir de l'information complétant la recherche sur le changement climatique? En faisant appel à une méthodologie de recherche participative et des entrevues semidirigées, on a examiné le savoir local et traditionnel concernant les changements de la banquise dans la région de Sachs Harbour (Territoires du Nord-Ouest). Dans cette petite communauté inuvialuite, on a interviewé les 16 membres et aînés de la communauté considérés comme des experts locaux de la banquise pour les interroger sur leurs observations. On a organisé leurs commentaires sous les rubriques suivantes: glace pluriannuelle, glace de l'année, crêtes de fractures et de pression, saisons de débâcle et d'engel, ainsi que d'autres variables reliées au climat qui influencent la banquise (comme les changements dans les températures hivernale, printanière et estivale, le vent, la pluie et les orages). Il y avait une concordance frappante dans les observations quant aux preuves de changements à l'échelle locale dans des variables comme la distribution de la glace pluriannuelle, l'épaisseur de la glace de l'année et les dates de la débâcle. Les changements observés au cours des années 1990 étaient, selon les Autochtones, sans précédent et ils dépassaient la gamme normale des variations. En évaluant la pertinence du savoir des Inuvialuits pour la recherche scientifique sur le changement climatique, on souligne certains des domaines dans lesquels le partage de l'information entre les deux systèmes de savoir pourrait être mutuellement profitable. Ces domaines comprennent l'analyse des options visant l'adaptation au changement climatique et la formulation de questions et hypothèses de recherche pour des études ultérieures.