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"Schmidt, M"
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African hosts & their guests : cultural dynamics of tourism
Tourism is important for Africa: international tourist arrivals to Africa continue to grow, income from tourism is crucial to national economies, and tourism investments are considered among the most profitable. This edited volume deals with the interaction of local communities with tourists coming into their areas and villages. Based upon a common theoretical approach, fourteen cases of African tourism are discussed which involve direct contact between 'hosts' and 'guests'. The viewpoint throughout is from the side of the locals, establishing how the processes of interaction shape each small scale destination. Crucial in Africa is the fact that the large majority of tourism is game oriented and the interaction between locals and visitors is very much 'tainted' by this fact. Central is the notion of the tourist bubble - the infrastructure that is generated locally (and internationally) for hosting tourists, as it is this institutional interface that tends to impact on the local society and culture, not the tourists themselves directly. The examples come from all over Africa, from the Sahara to the Eastern Cape, and from Kenya to Ghana. All contributions are based upon original fieldwork. -- Publisher description.
Book
Methodological guidance for the evaluation and updating of clinical prediction models: a systematic review
Background
Clinical prediction models are often not evaluated properly in specific settings or updated, for instance, with information from new markers. These key steps are needed such that models are fit for purpose and remain relevant in the long-term. We aimed to present an overview of methodological guidance for the evaluation (i.e., validation and impact assessment) and updating of clinical prediction models.
Methods
We systematically searched nine databases from January 2000 to January 2022 for articles in English with methodological recommendations for the post-derivation stages of interest. Qualitative analysis was used to summarize the 70 selected guidance papers.
Results
Key aspects for validation are the assessment of statistical performance using measures for discrimination (e.g., C-statistic) and calibration (e.g., calibration-in-the-large and calibration slope). For assessing impact or usefulness in clinical decision-making, recent papers advise using decision-analytic measures (e.g., the Net Benefit) over simplistic classification measures that ignore clinical consequences (e.g., accuracy, overall Net Reclassification Index). Commonly recommended methods for model updating are recalibration (i.e., adjustment of intercept or baseline hazard and/or slope), revision (i.e., re-estimation of individual predictor effects), and extension (i.e., addition of new markers). Additional methodological guidance is needed for newer types of updating (e.g., meta-model and dynamic updating) and machine learning-based models.
Conclusion
Substantial guidance was found for model evaluation and more conventional updating of regression-based models. An important development in model evaluation is the introduction of a decision-analytic framework for assessing clinical usefulness. Consensus is emerging on methods for model updating.
Journal Article
Diversity of intrinsically photosensitive retinal ganglion cells: circuits and functions
The melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) are a relatively recently discovered class of atypical ganglion cell photoreceptor. These ipRGCs are a morphologically and physiologically heterogeneous population that project widely throughout the brain and mediate a wide array of visual functions ranging from photoentrainment of our circadian rhythms, to driving the pupillary light reflex to improve visual function, to modulating our mood, alertness, learning, sleep/wakefulness, regulation of body temperature, and even our visual perception. The presence of melanopsin as a unique molecular signature of ipRGCs has allowed for the development of a vast array of molecular and genetic tools to study ipRGC circuits. Given the emerging complexity of this system, this review will provide an overview of the genetic tools and methods used to study ipRGCs, how these tools have been used to dissect their role in a variety of visual circuits and behaviors in mice, and identify important directions for future study.
Journal Article
Dynamics of Human Gut Microbiota and Short-Chain Fatty Acids in Response to Dietary Interventions with Three Fermentable Fibers
These results reveal that not all fermentable fibers are equally capable of stimulating SCFA production, and they highlight the importance of the composition of an individual’s microbiota in determining whether or not they respond to a specific dietary supplement. In particular, R. bromii or C. chartatabidum may be required for enhanced butyrate production in response to RS. Bifidobacteria, though proficient at degrading RS and inulin, may not contribute to the butyrogenic effect of those fermentable fibers in the short term. Production of short-chain fatty acids (SCFAs), especially butyrate, in the gut microbiome is required for optimal health but is frequently limited by the lack of fermentable fiber in the diet. We attempted to increase butyrate production by supplementing the diets of 174 healthy young adults for 2 weeks with resistant starch from potatoes (RPS), resistant starch from maize (RMS), inulin from chicory root, or an accessible corn starch control. RPS resulted in the greatest increase in total SCFAs, including butyrate. Although the majority of microbiomes responded to RPS with increases in the relative abundance of bifidobacteria, those that responded with an increase in Ruminococcus bromii or Clostridium chartatabidum were more likely to yield higher butyrate concentrations, especially when their microbiota were replete with populations of the butyrate-producing species Eubacterium rectale . RMS and inulin induced different changes in fecal communities, but they did not generate significant increases in fecal butyrate levels. IMPORTANCE These results reveal that not all fermentable fibers are equally capable of stimulating SCFA production, and they highlight the importance of the composition of an individual’s microbiota in determining whether or not they respond to a specific dietary supplement. In particular, R. bromii or C. chartatabidum may be required for enhanced butyrate production in response to RS. Bifidobacteria, though proficient at degrading RS and inulin, may not contribute to the butyrogenic effect of those fermentable fibers in the short term.
Journal Article
The bleeding edge
\"It's a new beginning for Dick Grayson, as novelist Benjamin Percy takes the vigilante on a high-octane, adrenaline-fueled adventure in Nightwing VOL. 1, a great jumping on point for new readers! Change is on the horizon. A new technologist sets his sights on Blèudhaven, creating a holographic, interconnected city where everyone is an individual and part of a larger network. It's the internet made physical. Gentrification on gigabyte-laced steroids. But when this new utopia encroaches on his turf, Nightwing starts to uncover a sinister plot based not on revenge...but on a reckoning.\"-- Provided by publisher.
Book
H2 generated by fermentation in the human gut microbiome influences metabolism and competitive fitness of gut butyrate producers
Background
Hydrogen gas (H
2
) is a common product of carbohydrate fermentation in the human gut microbiome and its accumulation can modulate fermentation. Concentrations of colonic H
2
vary between individuals, raising the possibility that H
2
concentration may be an important factor differentiating individual microbiomes and their metabolites. Butyrate-producing bacteria (butyrogens) in the human gut usually produce some combination of butyrate, lactate, formate, acetate, and H
2
in branched fermentation pathways to manage reducing power generated during the oxidation of glucose to acetate and carbon dioxide. We predicted that a high concentration of intestinal H
2
would favor the production of butyrate, lactate, and formate by the butyrogens at the expense of acetate, H
2
, and CO
2
. Regulation of butyrate production in the human gut is of particular interest due to its role as a mediator of colonic health through anti-inflammatory and anti-carcinogenic properties.
Results
For butyrogens that contained a hydrogenase, growth under a high H
2
atmosphere or in the presence of the hydrogenase inhibitor CO stimulated production of organic fermentation products that accommodate reducing power generated during glycolysis, specifically butyrate, lactate, and formate. Also as expected, production of fermentation products in cultures of
Faecalibacterium prausnitzii
strain A2-165, which does not contain a hydrogenase, was unaffected by H
2
or CO. In a synthetic gut microbial community, addition of the H
2
-consuming human gut methanogen
Methanobrevibacter smithii
decreased butyrate production alongside H
2
concentration. Consistent with this observation,
M. smithii
metabolic activity in a large human cohort was associated with decreased fecal butyrate, but only during consumption of a resistant starch dietary supplement, suggesting the effect may be most prominent when H
2
production in the gut is especially high. Addition of
M. smithii
to the synthetic communities also facilitated the growth of
E. rectale
, resulting in decreased relative competitive fitness of
F. prausnitzii.
Conclusions
H
2
is a regulator of fermentation in the human gut microbiome. In particular, high H
2
concentration stimulates production of the anti-inflammatory metabolite butyrate. By consuming H
2
, gut methanogenesis can decrease butyrate production. These shifts in butyrate production may also impact the competitive fitness of butyrate producers in the gut microbiome.
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Video Abstract
Journal Article
Efficacy of CytoSorb®: a systematic review and meta-analysis
Introduction
Cytokine adsorption using the CytoSorb® adsorber has been proposed in various clinical settings including sepsis, ARDS, hyperinflammatory syndromes, cardiac surgery or recovery after cardiac arrest. The aim of this analysis is to provide evidence for the efficacy of the CytoSorb® adsorber with regard to mortality in various settings.
Methods
We searched PubMed, Cochrane Library database and the database provided by Cytosorbents™ (01.1.2010–29.5.2022). We considered randomized controlled trials and observational studies with control groups. The longest reported mortality was defined as the primary endpoint. We computed risk ratios and 95%-confidence intervals and used DerSimonian and Lairds random effects model. We analysed all studies combined and divided them into the subgroups: sepsis, cardiopulmonary bypass surgery (CPB), other severe illness, SARS-CoV-2 infection and recovery from cardiac arrest. The meta-analysis was registered in advance (PROSPERO: CRD42022290334).
Results
Of an initial 1295 publications, 34 studies were found eligible, including 1297 patients treated with CytoSorb® and 1314 controls. Cytosorb® intervention did not lower mortality (RR [95%-CI]: all studies 1.07 [0.88; 1.31], sepsis 0.98 [0.74; 1.31], CPB surgery 0.91 [0.64; 1.29], severe illness 0.95 [0.59; 1.55], SARS-CoV-2 1.58 [0.50; 4.94]). In patients with cardiac arrest, we found a significant survival advantage of the untreated controls (1.22 [1.02; 1.46]). We did not find significant differences in ICU length of stay, lactate levels, or IL-6 levels after treatment. Of the eligible 34 studies only 12 were randomized controlled trials. All observational studies showed moderate to serious risk of bias.
Interpretation
To date, there is no evidence for a positive effect of the CytoSorb® adsorber on mortality across a variety of diagnoses that justifies its widespread use in intensive care medicine.
Journal Article
Host cell interactions of outer membrane vesicle-associated virulence factors of enterohemorrhagic Escherichia coli O157: Intracellular delivery, trafficking and mechanisms of cell injury
Outer membrane vesicles (OMVs) are important tools in bacterial virulence but their role in the pathogenesis of infections caused by enterohemorrhagic Escherichia coli (EHEC) O157, the leading cause of life-threatening hemolytic uremic syndrome, is poorly understood. Using proteomics, electron and confocal laser scanning microscopy, immunoblotting, and bioassays, we investigated OMVs secreted by EHEC O157 clinical isolates for virulence factors cargoes, interactions with pathogenetically relevant human cells, and mechanisms of cell injury. We demonstrate that O157 OMVs carry a cocktail of key virulence factors of EHEC O157 including Shiga toxin 2a (Stx2a), cytolethal distending toxin V (CdtV), EHEC hemolysin, and flagellin. The toxins are internalized by cells via dynamin-dependent endocytosis of OMVs and differentially separate from vesicles during intracellular trafficking. Stx2a and CdtV-B, the DNase-like CdtV subunit, separate from OMVs in early endosomes. Stx2a is trafficked, in association with its receptor globotriaosylceramide within detergent-resistant membranes, to the Golgi complex and the endoplasmic reticulum from where the catalytic Stx2a A1 fragment is translocated to the cytosol. CdtV-B is, after its retrograde transport to the endoplasmic reticulum, translocated to the nucleus to reach DNA. CdtV-A and CdtV-C subunits remain OMV-associated and are sorted with OMVs to lysosomes. EHEC hemolysin separates from OMVs in lysosomes and targets mitochondria. The OMV-delivered CdtV-B causes cellular DNA damage, which activates DNA damage responses leading to G2 cell cycle arrest. The arrested cells ultimately die of apoptosis induced by Stx2a and CdtV via caspase-9 activation. By demonstrating that naturally secreted EHEC O157 OMVs carry and deliver into cells a cocktail of biologically active virulence factors, thereby causing cell death, and by performing first comprehensive analysis of intracellular trafficking of OMVs and OMV-delivered virulence factors, we provide new insights into the pathogenesis of EHEC O157 infections. Our data have implications for considering O157 OMVs as vaccine candidates.
Journal Article