Interleukin-17 regulation: an attractive therapeutic approach for asthma

Interleukin (IL)-17 is recognized to play a critical role in numerous immune and inflammatory responses by regulating the expression of various inflammatory mediators, which include cytokines, chemokines, and adhesion molecules. There is growing evidence that IL-17 is involved in the pathogenesis of asthma. IL-17 orchestrates the neutrophilic influx into the airways and also enhances T-helper 2 (Th2) cell-mediated eosinophilic airway inflammation in asthma. Recent studies have demonstrated that not only inhibitor of IL-17 per se but also diverse regulators of IL-17 expression reduce antigen-induced airway inflammation, bronchial hyperresponsiveness, and Th2 cytokine levels in animal models of asthma. This review will summarize the role of IL-17 in the context of allergic airway inflammation and discuss the therapeutic potential of various strategies targeting IL-17 for asthma

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Annual cycles are the most common reproductive strategy in African tropical tree communities

We present the first cross continental comparison of the flowering and fruiting phenology of tropical forests across Africa. Flowering events of 5,446 trees from 196 species across 12 sites, and fruiting events of 4,595 trees from 191 species, across 11 sites were monitored over periods of 6 to 29 years, and analysed to describe phenology at the continental level. To study phenology we used Fourier analysis to identify the dominant cycles of flowering and fruiting for each individual tree and we identified the time of year African trees bloom and bear fruit and their relationship to local seasonality. Reproductive strategies were diverse and no single regular cycle was found in >50% of individuals across all 12 sites. Additionally, we found annual flowering and fruiting cycles to be the most common. Sub-annual cycles were the next most common for flowering whereas supra-annual patterns were the next most common for fruiting. We also identify variation in different subsets of species, with species exhibiting mainly annual cycles most common in West and West-Central African tropical forests, while more species at sites in East-Central and Eastern African forests showed cycles ranging from sub-annual to supra-annual. Despite many trees showing strong seasonality, at most sites some flowering and fruiting occurred all year round. Environmental factors with annual cycles are likely to be important drivers of seasonal periodicity in trees across Africa, but proximate triggers are unlikely to be constant across the continen

Pyrrolizidine alkaloids in honey: comparison of analytical methods

Pyrrolizidine alkaloids (PAs) are a structurally diverse group of toxicologically relevant secondary plant metabolites. Currently, two analytical methods are used to determine PA content in honey. To achieve reasonably high sensitivity and selectivity, mass spectrometry detection is demanded. One method is an HPLC-ESI-MS-MS approach, the other a sum parameter method utilising HRGC-EI-MS operated in the selected ion monitoring mode (SIM). To date, no fully validated or standardised method exists to measure the PA content in honey. To establish an LC-MS method, several hundred standard pollen analysis results of raw honey were analysed. Possible PA plants were identified and typical commercially available marker PA-N-oxides (PANOs). Three distinct honey sets were analysed with both methods. Set A consisted of pure Echium honey (61–80% Echium pollen). Echium is an attractive bee plant. It is quite common in all temperate zones worldwide and is one of the major reasons for PA contamination in honey. Although only echimidine/echimidine-N-oxide were available as reference for the LC-MS target approach, the results for both analytical techniques matched very well (n¿=¿8; PA content ranging from 311 to 520¿µg¿kg-1). The second batch (B) consisted of a set of randomly picked raw honeys, mostly originating from Eupatorium spp. (0–15%), another common PA plant, usually characterised by the occurrence of lycopsamine-type PA. Again, the results showed good consistency in terms of PA-positive samples and quantification results (n¿=¿8; ranging from 0 to 625¿µg¿kg-1 retronecine equivalents). The last set (C) was obtained by consciously placing beehives in areas with a high abundance of Jacobaea vulgaris (ragwort) from the Veluwe region (the Netherlands). J. vulgaris increasingly invades countrysides in Central Europe, especially areas with reduced farming or sites with natural restorations. Honey from two seasons (2007 and 2008) was sampled. While only trace amounts of ragwort pollen were detected (0–6.3%), in some cases extremely high PA values were detected (n¿=¿31; ranging from 0 to 13019¿µg¿kg-1, average¿=¿1261 or 76¿µg¿kg-1 for GC-MS and LC-MS, respectively). Here the results showed significantly different quantification results. The GC-MS sum parameter showed in average higher values (on average differing by a factor 17). The main reason for the discrepancy is most likely the incomplete coverage of the J. vulgaris PA pattern. Major J. vulgaris PAs like jacobine-type PAs or erucifoline/acetylerucifoline were not available as reference compounds for the LC-MS target approach. Based on the direct comparison, both methods are considered from various perspectives and the respective individual strengths and weaknesses for each method are presented in detai

X-ray Linear Dichroism in Apatite.

The recent observation in parrotfish teeth of X-ray linear dichroism motivated an in-depth investigation into this spectroscopic effect in various apatite crystals, including geologic hydroxyapatite (Ca5(PO4)3OH), fluorapatite (Ca5(PO4)3F), and their biogenic counterparts in human bone, mouse enamel, and in parrotfish bone, dentin, and enameloid, the equivalent of dental enamel in certain fish. These data are important because they now enable visualization of the nano- to microscale structure of apatite crystals in teeth and bone. Polarization-dependent imaging contrast (PIC) maps of lamellar bone, obtained with a new method that minimizes space-charge and charging effects, show the expected rotating apatite crystal orientations. PIC maps of mouse enamel reveal a complex arrangement of hydroxyapatite crystals perpendicular to the dentin-enamel junction, with rods arranged in a decussation pattern in inner enamel and nearly parallel to one another in outer enamel. In both inner and outer enamel crystal c-axes are not always aligned with the rod elongation direction