The Antarctic green alga Chlamydomonas sp. UWO241 is an obligate psychrophile that thrives in the cold (4-6°C) but is unable to survive at temperatures ≥18°C. Little is known how exposure to heat affects its physiology or whether it mounts a heat stress response in a manner comparable to mesophiles. Here, we dissect the responses of UWO241 to temperature stress by examining its growth, primary metabolome and transcriptome under steady-state low temperature and heat stress conditions. In comparison with Chlamydomonas reinhardtii, UWO241 constitutively accumulates metabolites and proteins commonly considered as stress markers, including soluble sugars, antioxidants, polyamines, and heat shock proteins to ensure efficient protein folding at low temperatures. We propose that this permanent stress metabolism is an adaptive advantage to life at extreme conditions. A shift from 4°C to a non-permissive temperature of 24°C alters the UWO241 primary metabolome and transcriptome, but growth of UWO241 at higher permissive temperatures (10°C and 15°C) does not provide enhanced heat protection. UWO241 also fails to induce the accumulation of HSPs when exposed to heat, suggesting that it has lost the ability to fine-tune its heat stress response. Our work adds to the growing body of research on temperature stress in psychrophiles, many of which are threatened by climate change.

Objective: To review a case of acute urticaria, and to explore the links this presentation shares with hyperthyroidism and anti-thyroid medications, along with management strategies for patients presenting with new-onset urticaria and pre-existing thyroid disease. Design: A retrospective case report on a 23-year-old female with hyperthyroidism, on carbimazole therapy.

Seagrasses play a vital role in structuring coastal marine ecosystems, but their distributional range and genetic diversity have declined rapidly over the past decades. In order to improve conservation of seagrass species, it is important to predict how climate change may impact their ranges. Such predictions are typically made with correlative species distribution models (SDMs), which can estimate a species’ potential distribution under present and future climatic scenarios given species’ presence data and climatic predictor variables. However, these models are typically constructed with species-level data, and thus ignore intraspecific genetic variability of populations that potentially have adaptations to heterogeneous climatic conditions. Here, we explore the link between intraspecific adaptation and niche differentiation in Thalassia hemprichii, a seagrass broadly distributed in the tropical Indo-Pacific Ocean and a crucial provider of habitat for numerous marine species. Using microsatellite-based genotyping, we identified two distinct phylogeographical lineages within the nominal species and found an intermediate level of differentiation in their multidimensional environmental niches, suggesting the possibility for local adaptation. We then compared projections of the species’ habitat suitability under climate change scenarios using species-level and lineage-level SDMs. In the Central Tropical Indo-Pacific region, both models predicted considerable range contraction in the future, but the lineage-level model predicted more severe habitat loss. The two modelling approaches predicted opposite pattern in habitat change in the Western Tropical Indo-Pacific region. Our results highlight the necessity of conserving distinct populations and genetic pools under climate change and have important implications for guiding future management of seagrasses.

The International Classification of Diseases (ICD) provides a common language for use worldwide as a diagnostic and classification tool for epidemiology, clinical purposes and health management. Since its first edition, the ICD has maintained a framework distributing conditions according to topography, with the result that some complex conditions, such as allergies and hypersensitivity disorders (A/H) including anaphylaxis, have been poorly represented. The change in hierarchy in ICD-11 permitted the construction of the pioneer section addressed to A/H, which may result in more accurate mortality and morbidity statistics, including more accurate accounting for mortality due to anaphylaxis, strengthen classification, terminology and definitions. The ICD-11 was presented and adopted by the 72nd World Health Assembly in May 2019 and the implementation is ongoing worldwide. We here present the outcomes from an online survey undertaken to reach out the allergy community worldwide in order to peer review the terminology, classification and definitions of A/H introduced into ICD-11 and to support their global implementation. Data are presented here for 406 respondents from 74 countries. All of the sub-sections of the new A/H section of the ICD-11 had been considered with good accuracy by the majority of respondents. We believe that, in addition to help during the implementation phase, all the comments provided will help to improve the A/H classification and to increase awareness by different disciplines of what actions are needed to ensure more accurate epidemiological data and better clinical management of A/H patients.

Light pollution modelling and monitoring has traditionally used zenith sky brightness as its main indicator. Several other indicators (e.g. average sky radiance, horizontal irradiance, average sky radiance at given interval of zenith distances) may be more useful, both for general and for specific purposes of ecology studies, night sky and environmental monitoring. These indicators can be calculated after the whole sky radiance is known with sufficient angular detail. This means, for each site, to integrate the contribution in each direction of the sky of each light source in the radius of hundreds of km. This approach is extremely high time consuming if the mapping is desired for a large territory. Here we present a way to obtain maps of large territories for a large subset of useful indicators, bypassing the need to calculate first the radiance map of the whole sky in each site to obtain from it the desired indicator in that site. For each indicator, a point spread function (PSF) is calculated from the whole sky radiance maps generated by a single source at sufficiently dense number of distances from the observing site. If the PSF is transversally shift-invariant, i.e. if it depends only on the relative position of source and observer, then we can further speed up the map calculation via the use of fast Fourier-transform (FFT). We present here examples of maps for different indicators. Precise results can be calculated for any single site, taking into account the site and light sources altitudes, by means of specific inhomogeneous (spatially-variant) and anisotropic (non rotationally symmetric) PSFs.

Molecular mechanisms and process kinetics of crystallizing concomitant polymorphs remain poorly understood. Solvent-mediated phase transformation is often mistaken as concomitant crystallization, mainly due to the two processes sharing similar kinetic profiles. Herein, we developed a population balance model to simulate a concomitant crystallization process of two polymorphs of tolfenamic acid (TFA). The kinetic modeling aims to better understand concomitant crystallization and help guide form selection of such a molecular system. Crystallization kinetics of ethanolic TFA solutions were uncovered from induction time measurements, as well as seeded and unseeded crystallization experiments. Both experimental and simulation results demonstrate that the stable form I crystallizes concomitantly with the metastable form II. The faster growing form II results in an intermediate decline in the kinetic profile of form I composition in crystallized samples, a characteristic feature of the concomitantly crystallized system. A four-quadrant scheme of attainable polymorph outcome was simulated under various crystallization conditions.

Background It has been hypothesized that epigenomic modifications such as genomic methylation changes are an intermediate step linking environmental exposures with allergic disease development. Associations between individual DNA methylation CpG sites and allergic diseases have been reported, but they have not been assessed regarding their joint predictive capability. Methods Data were obtained from 240 children of the German LISA cohort. Blood-based DNA methylation was measured at six and ten years. Aeroallergen sensitization, at least RAST class 1, was measured in blood at six, ten and 15 years. We calculated six methylation risk scores (MRS) for allergy-related phenotypes based on available publications and assessed their performance both cross-sectionally and prospectively. Dose-response associations between aeroallergen sensitization and MRS, their correlation and mapping of common hits were evaluated. Results All six atopy-related MRS were highly correlated (r>0.86) and seven CpGs were included in more than one MRS. Cross-sectionally, we observed an 80% increased risk for aeroallergen sensitization at six years with an increased risk score by one standard deviation (best MRS: relative risk = 1.81, 95% confidence interval = [1.43; 2.27]). Significant associations were also seen at ten years and in prospective models, though the effect of the latter was attenuated when only including participants not sensitized at baseline. A clear dose-response relationship with RAST classes of aeroallergen sensitization could be established cross-sectionally, but not prospectively. Conclusion We found good classification and prediction capabilities of calculated allergy-related MRS, particularly cross-sectionally for the allergy prevalence, underlining the relevance of altered gene-regulation in allergic diseases.

Proton pump inhibitors (PPIs) are invaluable therapeutic options in a variety of dyspeptic diseases. In addition to their well-known risk profile, PPI consumption is related to food and environmental allergies, dysbiosis, osteoporosis, as well as immediate and delayed hypersensitivity reactions (HSRs). The latter, although a rare event, around 1-3%, due to the extraordinarily high rate of prescription and consumption of PPIs are related to a substantial risk. In this Position Paper, we provide clinicians with practical evidence-based recommendations for the diagnosis and management of HSRs to PPIs. Furthermore, the unmet needs proposed in the document aim to stimulate more in-depth investigations in the topic.

Introduction The mechanisms that drives SLE remission.The aim of the present study was to measure CD4+ and CD8+ T cell exhaustion in SLE patients in prolonged remission (PR-SLE) and compared them with patients with active SLE (Act-SLE) and healthy subjects Methods We included 15 PR-SLE patients, 15 Act-SLE and 29 healthy subjects. T-cell exhaustion was determined by flow cytometry according to the expression of PD-1, Tim-3, 2B4, EOMES and T-bet in CD4+ and CD8+ T cells. Dimensionality reduction using the t-Distributed Stochastic Neighbor Embedding algorithm and Clustering Analysis was used for the identification of relevant populations. Results Percentages of CD3+, CD4+ and CD8+ T cells were similar among groups. We identified five subpopulations of CD8+ and seven of CD4+ cells. The CD4+Tbet+CD45RO+ cells identified in the unsupervised analysis were significantly increased in PR-SLE vs Act-SLE (median: 10.20, IQR: 1.74-30.50 vs. 1.68, IQR: 0.4-2.83; p<0.01). CD4+EOMES+ cells were also increased in PR-SLE vs Act-SLE (5.24, IQR: 3.38-14.70 vs. 1.39, IQR: 0.48-2.87; p<0.001). CD8+ EOMES+ cells were increased in PR-SLE vs Act-SLE (37.6, IQR: 24.9-53.2 vs 8.13, IQR: 2.33-20.5; p<0.001). Exhausted and activated T cells presented an increased frequency of PD-1, CD57 and EOMES in SLE patients vs healthy subjects. Conclusions Some subpopulations of T cells expressing markers associated with exhaustion are increased in patients in remission, supporting T-cell exhaustion as a tolerance mechanism in SLE. Exhaustion of specific populations of T cells might represent a potential therapeutic tool that will contribute to the goal of achieving sustained remission in these patients.

The advanced use of a pH-responsive biomaterial-based injectable liquid implant for effective chemotherapeutic delivery in glioblastoma multiforme brain (GBM) tumour treatment is presented. As an implant, we proposed a water-in-oil-in-water multiple emulsion with encapsulated doxorubicin. The effectiveness of the proposed therapy was evaluated by comparing the cancer cell viability achieved in classical therapy (chemotherapeutic solution). The experimental study included doxorubicin release rates and consumption for two emulsions differing in drop sizes and structures in the presence of GBM-cells (LN229, U87 MG), and a cell viability. The results showed that the multiple emulsion implant was significantly more effective than classical therapy when considering the reduction in cancer cell viability: 85% for the emulsion-implant, and only 43% for the classical therapy. A diffusion-reaction model was adapted to predict doxorubicin release kinetics and elimination by glioblastoma cells. CFD simulations confirmed that the drug release kinetics depends on multiple emulsion structures and drop sizes.

Magnesium-based hydrogen storage material (MgH2) has attracted much attention due to its high hydrogen storage density (7.6 wt%). However, the high hydrogen dissociation enthalpy and slow hydrogen dissociation rate in bulk Mg hinder its wide application in the efficient hydrogen storage. In the present work, we study the hydrogen adsorption and desorption reactions of MgmHn (m = 1-6) nanoclusters using density functional theory (DFT). From the global search for the configurations of MgmHn nanoclusters, we found not only stable saturated MgmHn (n = 2m) nanoclusters, but four hydrogen-enriched MgmHn (n:m>2:1) nanoclusters, Mg3H7, Mg4H9, Mg5H11, Mg6H13, with the hydrogen storage density higher than 8.3 wt%. The electronic-structure calculations indicate that the stability of the hydrogen-enriched cluster gets relatively higher for larger nanocluster. The ab initio dynamics simulations shows that all hydrogen-enriched clusters have very fast hydrogen dissociation rates, which is promising for the hydrogen dissociation at ambient temperature and pressure. This work provides insights into the hydrogen storage mechanism of nano-magnesium materials.

Primary consumers in aquatic ecosystems are frequently limited by the quality of their food, often expressed as phytoplankton elemental and biochemical composition. Effects of these food quality indicators vary across studies, and the relative importance of elemental (nitrogen and phosphorus) versus biochemical (fatty acid and sterol) limitation in aquatic food webs has been debated. Here we present results of a meta-analysis using >100 experimental studies, which confirms that limitation by N, P, essential fatty acids, and sterols all have significant negative effects on zooplankton performance. However, effects varied by grazer response (growth versus reproduction), specific manipulation, and across taxa. P limitation had greater effects on zooplankton growth than fatty acids, but P and fatty acid limitation had equal effects on reproduction. Furthermore, we show that nutrient co-limitation in zooplankton occurs, that indirect effects induced by P limitation exceed direct effects of mineral P limitation, that effects of nutrient amendments using laboratory phytoplankton isolates exceed those using natural field communities, and that algal physiology mediates zooplankton responses to nutrient limitation. Our meta-analysis reconciles contrasting views about the role of various food quality indicators, and their interactions, for zooplankton performance, and provides a mechanistic understanding of how environmental change affects trophic transfer.

Patterns of δ18O and δ2H in Earth’s precipitation provide essential scientific data for use in hydrological, climatological, ecological and forensic research. Insufficient global spatial data coverage promulgated the use of gridded datasets employing geostatistical techniques (isoscapes) for spatiotemporally coherent isotope predictions. Cluster-based isoscape regionalization combines the advantages of local or regional prediction calibrations into a global framework. Here we present a revision of a Regionalized Cluster-Based Water Isotope Prediction model (RCWIP2) incorporating new isotope data having extensive spatial coverage and a wider array of predictor variables combined with high-resolution gridded climatic data. We introduced coupling of δ18O and δ2H (e.g. d-excess constrained) in the model predictions to prevent runaway isoscapes when each isotope is modelled separately. We validated RCWIP2 isoscape performance by cross-checking observed versus modelled d-excess values. We improved model error quantification by adopting full uncertainty propagation in all calculations. RCWIP2 improved the RMSE over previous isoscape models by ca. 0.6 ‰ for δ18O and 5 ‰ for δ2H with an uncertainty <1.0 ‰ for δ18O and <8 ‰ for δ2H for most regions of the world. The improved RCWIP2 isoscape grids and maps (season, monthly, annual, regional) are available for download at https://isotopehydrologynetwork.iaea.org.

The Impella 5.5 with SmartAssist (Abiomed; Danvers, MA) is a life-saving treatment option in acute heart failure which utilizes a continuous heparin purge solution to prevent thrombosis. In patients with contraindications to heparin, alternative anticoagulation strategies are required. We describe the stepwise management of anticoagulation in a coagulopathic patient with persistent cardiogenic shock following a coronary artery bypass procedure who underwent Impella 5.5 placement. A direct thrombin inhibitor-based purge solution was utilized while evaluating for heparin-induced thrombocytopenia. Use of a novel bicarbonate-based purge solution (BBPS) was successfully used due to severe coagulopathy. There were no episodes of pump thrombosis or episodes of severe bleeding on the BBPS and systemic effects of alkalosis and hypernatremia were minimal.

In the biopharmaceutical industry, Raman spectroscopy is now a proven PAT tool that enables in-line simultaneous monitoring of several CPPs and CQAs in real-time. However, as Raman monitoring requires multivariate modeling, variabilities unknown by models can impact the monitoring prediction accuracy. With the widespread use of Raman PAT tools, it is necessary to fix instrumental variability impacts, encountered for instance during a device replacement. In this work, we investigated the impact of instrumental variability between probes inside a multi-channel analyzer and between two analyzers, and explored solutions to correct them on model prediction errors in cell cultures. We found that the Kennard Stone Piecewise Direct Standardization (KS PDS) method enables to lower model prediction errors and that only one batch with the unknown device in the calibration dataset was sufficient to correct the prediction gap induced by instrumental variability. As a matter of fact, during device replacement a first cell culture monitoring can be performed with the KS PDS method. Then, the new data obtained can be inserted in the calibration dataset to integrate instrumental variability in the chemometric model. This methodology provides good multivariate calibration model prediction errors throughout the instrumental changes.

Telomeres have been advocated to be important markers of biological age in evolutionary and ecological studies. Telomeres usually shorten with age, and shortening is frequently associated with environmental stressors and increased subsequent mortality. Telomere lengthening – an apparent increase in telomere length between repeated samples from the same individual – also occurs. However, the exact circumstances, and consequences, of telomere lengthening are poorly understood. Using longitudinal data from the Seychelles warbler (Acrocephalus sechellensis), we tested whether telomere lengthening – which occurs in adults of this species – is associated with specific stressors (reproductive effort, food availability, malarial infection and cooperative breeding) and predicts subsequent survival. In females, telomere shortening was observed under greater stress (i.e. low food availability, malaria infection), while telomere lengthening was observed in females experiencing lower stress (i.e. high food availability, assisted by helpers, without malaria). The telomere dynamics of males were not associated with the key stressors tested. These results indicate that, at least for females, telomere lengthening occurs in circumstances more conducive to self-maintenance. Importantly, both females and males with lengthened telomeres had improved subsequent survival relative to individuals that displayed unchanged, or shortened, telomeres – indicating that telomere lengthening is associated with individual fitness. These results demonstrate that telomere dynamics are bidirectionally responsive to the level of stress that an individual faces, but may poorly reflect the accumulation of stress over the lifetime. This study challenges how we think of telomeres as a marker of biological age.

Background and aim of the study: Patients with severe coronavirus disease 2019 (COVID-19) develop a profound cytokine-mediated pro-inflammatory response. This study reports outcomes in 10 patients with COVID-19 supported on veno-venous extracorporeal membrane oxygenation (VV-ECMO) who were selected for the emergency use of a hemoadsorption column integrated in the ECMO circuit. Materials and Methods: Pre and post treatment, clinical data and inflammatory markers were assessed to determine the safety and feasibility of using this system, and to evaluate the clinical effect. Results: During hemoadsorption, median levels of interleukin (IL)-2R, IL-6, and IL-10 decreased by 54%, 86%, and 64% respectively. Reductions in other markers were observed for LDH (-49%), ferritin (-46%), D-dimer (-7%), C-reactive protein (-55%), procalcitonin (-76%) and lactate (-44%). Vasoactive-inotrope scores decreased significantly over the treatment interval (-80%). The median hospital length of stay was 53 days (36-85) and at 90-days post cannulation, survival was 90% which was similar to a group of patients without the use of hemoadsorption. Conclusions: Addition of hemoadsorption to VV-ECMO in patients with severe COVID-19 is feasible and reduces measured cytokine levels. However, in this small series, the precise impact on the overall clinical course and survival benefit still remains unknown.

Background: We aimed to determine the relationship between HbA1c levels and the development of postoperative atrial fibrillation (PoAF) . Methods: 288 patients diagnosed with diabet and undergoing on-pump coronary bypass were included in the study. Those with serum HbA1c levels between 5.5-7.0% were defined as Group 1, those with serum HbA1c levels between 7.1-8.9% were defined as group 2, while those with serum HbA1c levels 9.0% and above formed Group 3. Data between groups were compared. The predictive values of the independent variables for the development of PoAF were measured. Results: We did not found difference between groups in terms of development PoAF (p=0.170). Presence of hypertension was determined as an independent predictor for the development of PoAF (p=0.003) but not HbA1c levels (p=0.134). There was 50.5% sensitivity and 61.1% specificity for HbA1c values of 9.06% and above to predict PoAF (AUC: 0.571, p=0.049) Conclusions: HbA1c levels were not an independent predictor of PoAF development. However, we think that high HbA1c levels may be a risk factor for the development of PoAF.