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Introduction:The role of vitamin in COVID-19 remains controversial. We investigated the association between endogenous vitamin D and the severity of COVID-19 as well as the mechanisms of action of vitamin D supplementation. Methods:25(OH)D3 in serum was associated with disease severity and outcome in 190 COVID-19 patients. In a COVID-19 animal model using intravenous injection of plasma from patients with COVID-19 acute respiratory distress syndrome into C57/BL6 mice, mice were treated with 0.25 μg human 1,25(OH)D3 or vehicle. Mice were sacrificed on day 4. Cytokines and myeloperoxidase (MPO) in tissues were measured. Changes in gene expression after vitamin D supplementation were measured. Results:Vitamin D deficiency and insufficiency were associated with increased severity and unfavorable outcome after 28 days. Vitamin D levels were negatively associated with biomarkers of COVID-19 severity. Vitamin D supplementation after challenge of mice with COVID-19 plasma led to reduced levels of TNFα, IL-6, IFNγ, and MPO in the lung, as well as down-regulation of pro-inflammatory pathways. Conclusion:Normal levels of endogenous vitamin D are associated with reduced severity and risk of unfavorable outcome in COVID-19, possibly through attenuation of tissue-specific hyperinflammation.

Acute respiratory distress syndrome (ARDS) in COVID-19 has been associated with catastrophic inflammation. We present measurements in humans and a new animal model implicating a role in danger-associated molecular patterns. Calprotectin (S100A8/A9) and high-mobility group box 1 (HMGB1) were measured in patients without/with ARDS, and admission calprotectin was associated with soluble urokinase plasminogen activator receptor (suPAR). An animal model was developed by intravenous injection of plasma from healthy or patients with COVID-19 ARDS into C57/BL6 mice once daily for 3 consecutive days. Mice were treated with one anti-S100A8/A9 antibody, the IL-1 receptor antagonist anakinra or vehicle, and Flo1-2a anti-murine anti-IL-1α monoclonal antibody or the specific antihuman IL-1α antibody XB2001 or isotype controls. Cytokines and myeloperoxidase (MPO) were measured in tissues. Calprotectin, but not HMGB1, was elevated in ARDS. Higher suPAR indicated higher calprotectin. Animal challenge with COVID-19 plasma led to inflammatory reactions in murine lung and intestines as evidenced by increased levels of TNFα, IL-6, IFNγ, and MPO. Lung inflammation was attenuated with anti-S100A8/A9 pre-treatment. Anakinra treatment restored these levels. Similar decrease was found in mice treated with Flo1-2a but not with XB2001. Circulating alarmins, specifically calprotectin, of critically ill COVID-19 patients induces tissue-specific inflammatory responses through an IL-1-mediated mechanism. This could be attenuated through inhibition of IL-1 receptor or of IL-1α.

Oleuropein (OLE), the main constituent of Olea europaea, displays pleiotropic beneficial effects in health and disease, which are mainly attributed to its anti-inflammatory and cardioprotective properties. Several food supplements and herbal medicines contain OLE and are available without a prescription. This study investigated the effects of OLE on the main cytochrome P450s (P450s) catalyzing the metabolism of many prescribed drugs. Emphasis was given to the role of peroxisome proliferator-activated receptor α (PPARα), a nuclear transcription factor regulating numerous genes including P450s. 129/Sv wild-type and Ppara-null mice were treated with OLE for 6 weeks. OLE induced Cyp1a1, Cyp1a2, Cyp1b1, Cyp3a14, Cyp3a25, Cyp2c29, Cyp2c44, Cyp2d22, and Cyp2e1mRNAs in liver of wild-type mice, whereas no similar effects were observed in Ppara-null mice, indicating that the OLE-induced effect on these P450s is mediated by PPARα. Activation of the pathways related to phosphoinositide 3-kinase/protein kinase B (AKT)/forkhead box protein O1, c-Jun N-terminal kinase, AKT/p70, and extracellular signal-regulated kinase participates in P450 induction by OLE. These data indicate that consumption of herbal medicines and food supplements containing OLE could accelerate the metabolism of drug substrates of the above-mentioned P450s, thus reducing their efficacy and the outcome of pharmacotherapy. Therefore, OLE-induced activation of PPARα could modify the effects of drugs due to their increased metabolism and clearance, which should be taken into account when consuming OLE-containing products with certain drugs, in particular those of narrow therapeutic window.

Background/AimsMen with depression often experience stigmatising attitudes from the general public, which can cause distress and affect their help-seeking behaviours. This study aims to expand the research on public stigma by exploring public attitudes towards men with depression.MethodsFive women and two men who had not experienced depression personally were recruited to this study and took part in semi-structured interviews. Thematic analysis was employed to analyse their data.ResultsThe main themes that emerged concerned awareness, depression as a gendered phenomenon and the generational divide. The participants conveyed that older generations exhibit greater stigmatising attitudes, that awareness in men's experience of depression is lacking and that public stigma is intrinsically linked to societal expectations of how a man should behave.ConclusionsThese themes highlight areas for further research, and the themes that have been identified should be taken into consideration when creating destigmatisation materials aimed at the general public.

abstract:Although the professional sector of heritage in Greece has experienced profound transformations, in recent years, due to the ongoing financial crisis, another key shift that calls for serious consideration is the (implicit and/or explicit) requirement for heritage professionals to manage a variety of tasks associated with different scientific fields. In the wake of these developments, Greek universities have begun to reconfigure their role in knowledge production. The article presents an in-depth examination of postgraduate programs in cultural heritage offered by Greek universities and how they relate to emerging agendas in the professional sector of heritage in Greece. This twofold investigation (a) demonstrates that most postgraduate programs currently put a surplus of emphasis on instrumentalism, professional experience, and the coverage of a wide range of module topics and (b) explains the reasons why this triad in academic education also forms the dominant vision for the heritage workforce of the twenty-first century.

This paper introduces a holistic approach to the study of Greco-Roman (G-R) lithotherapeutics. These are the minerals or mineral combinations that appear in the medical and scientific literature of the G-R world. It argues that they can best be described not simply in terms of their bulk chemistry/mineralogy but also their ecological microbiology and nanofraction component. It suggests that each individual attribute may have underpinned the bioactivity of the lithotherapeutic as an antibacterial, antifungal or other. We focus on miltos, the highly prized, naturally fine, red iron oxide-based mineral used as a pigment, in boat maintenance, agriculture and medicine. Five samples (four geological (from Kea, N. Cyclades) and one archaeological (from Lemnos, NE Aegean)) of miltoswere analyzed with physical and biological science techniques. We show that: a. Kean miltosand Lemnian earth/miltosmust have been chemically and mineralogically different; b. Lemnian miltosmust have been more effective as an antibacterial against specific pathogens (Gram + and Gram − bacteria) than its Kean counterpart; c. two samples of Kean miltos, although similar, chemically, mineralogically and eco-microbiologically (phylum/class level), nevertheless, displayed different antibacterial action. We suggest that this may constitute proof of microbial ecology playing an important role in effecting bioactivity and, interestingly, at the more specific genus/species level. From the perspective of the historian of G-R science, we suggest that it may have been on account of its bioactivity, rather than simply its 'red-staining' effect, that miltosgained prominent entry into the scientific and medical literature of the G-R world.

Using spacecraft potential observations with and without active spacecraft potential control (on/off) from the Magnetospheric Multiscale (MMS) mission, we estimate the average photoelectron emission as well as derive the plasma density information from spacecraft potential variations and active spacecraft potential control ion current. Such estimates are of particular importance especially during periods when the plasma instruments are not in operation and also when electron density observations with higher time resolution than the ones available from particle detectors are necessary. We compare the average photoelectron emission of different spacecraft and discuss their differences. We examine several time intervals when we performed our density estimations in order to understand the strengths and weaknesses of our data set. We finally compare our derived density estimates with the plasma density observations provided by plasma detectors onboard MMS, whenever available, and discuss the overall results. The estimated electron densities should only be used as a proxy of the electron density, complimentary to the plasma moments derived by plasma detectors, especially when the latter are turned off or when higher time resolution observations are required. While the derived data set can often provide valuable information about the plasma environment, the actual values may often be very far from the actual plasma density values and should therefore be used with caution. The average photoelectron emission was derived for each MMS spacecraft, and density estimates for the same period are available upon requestLarge differences are observed between the average photoelectron emission of MMS4 and those of the other spacecraftOur density estimates are typically more accurate on the density range above 2 cm−3; below that our data sets are overestimating the density

In the healthcare domain, there is a challenge on how to design a scalable, dynamic, robust and secure network for provisioning personalized healthcare services remotely with an efficient and accurate manner. In the present work, motivated by innovations in the networking domain and the benefits of clustering in the peer-to-peer networks as well as the group-based approach of the social networks, we propose a novel hierarchical peer-to-peer overlay healthcare network for communication and collaboration among healthcare professionals, paramedical staff and patients. The proposed network includes two types of hierarchy: the first type is used for regular requests and communication while the second type handles emergency requests. The network architecture is based on multiple and enhanced structured overlays that provide scalability, dynamic features, load-balancing and low response times with guaranteed information retrieval. Moreover, a novel and effective lookup mechanism supports complex queries with significantly lower response time and messaging overhead.

In situRaman spectroscopy at temperatures up to 450 °C is used to probe the structural and redox properties of Ce1–xZrxO2−δsolids (x= 0–0.8) prepared by the citrate sol–gel and coprecipitation with urea methods. The anionic sublattice structure of the solids is dependent on the preparation route. The composition effects exhibited by the Raman spectra are adequate for characterizing the phases present and/or eventual phase segregations. For x= 0.5 the pseudocubic t″ phase occurs for the solid prepared by the citrate sol–gel method, while phase segregation (cubic, tetragonal) is evidenced for the corresponding material prepared by the coprecipitation with urea method. A larger extent of defects and interstitial O atoms is evidenced for the materials prepared by the citrate sol–gel method. The well-known “defect” (“D”) band around 600 cm–1for CeO2as well as for Ce1–xZrxO2−δconsists of at least two components: “D1” above 600 cm–1and “D2” below 600 cm–1. Doping of Ce0.8Zr0.2O2−δwith rare earth cations (La3+, Nd3+, Y3+, Pr3+) results in strengthening of the “D2” band that, however, is found to be insensitive under reducing conditions of flowing 5% H2/He at 450 °C. A novel approach based on sequential in situRaman spectra under alternating oxidizing (20% O2/He) and reducing (5% H2/He) gas atmospheres showed that the “D1” band is selectively attenuated under reducing conditions at 450 °C and is therefore assigned to a metal–oxygen vibrational mode involving interstitial oxygen atoms that can be delivered under suitable conditions. A reversible temperature-dependent evolution of the anionic sublattice structures of Ce1–xZrxO2−δsolids is evidenced by in situRaman spectroscopy. The results are corroborated by powder XRD and oxygen storage capacity measurements, and observed structure/function relationships are discussed. It is shown that at low temperatures (e.g., 450 °C) the function of oxygen release and refill is based on a mechanism involving oxygen atoms in interstitial sites rather than on defects induced by hetrovalent M4+→ RE3+doping, the latter improving the pertinent function at high (e.g., >600 °C) temperatures.

An interesting form of “zipper‐like” magnetosonic waves consisting of two bands of interleaved periodic rising‐tone spectra was newly observed by the Van Allen Probes, the Time History of Events and Macroscale Interactions during Substorms (THEMIS), and the Magnetospheric Multiscale (MMS) missions. The two discrete bands are distinct in frequency and intensity; however, they maintain the same periodicity which varies in space and time, suggesting that they possibly originate from one single source intrinsically. In one event, the zipper‐like magnetosonic waves exhibit the same periodicity as a constant‐frequency magnetosonic wave and an electrostatic emission, but the modulation comes from neither density fluctuations nor ULF waves. A statistical survey based on 3.5 years of multisatellite observations shows that zipper‐like magnetosonic waves mainly occur on the dawnside to noonside, in a frequency range between 10 fcpand fLHR. The zipper‐like magnetosonic waves may provide a new clue to nonlinear excitation or modulation process, while its cause still remains to be fully understood. “Zipper‐like” magnetosonic waves consist of two‐frequency bands with interleaved periodic emissionsThe two bands differ in frequency and intensity but probably originate from one single sourceZipper‐like magnetosonic waves were mainly observed on dawnside to noonside in frequencies between 10 fcpand fLHR.

Itaconate is an immunomodulatory metabolite produced by immune cells under microbial stimulation and certain pro-inflammatory conditions and triggers antioxidant and anti-inflammatory responses. We show that dimethyl itaconate, a derivative of itaconate previously linked to suppression of inflammation and widely employed as an alternative to the endogenous metabolite, can induce long-term transcriptional, epigenomic, and metabolic changes, characteristic of trained immunity. Dimethyl itaconate alters glycolytic and mitochondrial energetic metabolism, ultimately leading to increased responsiveness to microbial ligand stimulation. Subsequently, mice treated with dimethyl itaconate present increased survival to infection with Staphylococcus aureus. Additionally, itaconate levels in human plasma correlate with enhanced ex vivopro-inflammatory cytokine production. Collectively, these findings demonstrate that dimethyl itaconate displays short-term anti-inflammatory characteristics and the capacity to induce long-term trained immunity. This pro-and anti-inflammatory dichotomy of dimethyl itaconate is likely to induce complex immune responses and should be contemplated when considering itaconate derivatives in a therapeutic context.

Each spacecraft of the recently launched magnetospheric multiscale MMS mission is equipped with Active Spacecraft Potential Control (ASPOC) instruments, which control the spacecraft potential in order to reduce spacecraft charging effects. ASPOC typically reduces the spacecraft potential to a few volts. On several occasions during the commissioning phase of the mission, the ASPOC instruments were operating only on one spacecraft at a time. Taking advantage of such intervals, we derive photoelectron curves and also perform reconstructions of the uncontrolled spacecraft potential for the spacecraft with active control and estimate the electron plasma density during those periods. We also establish the criteria under which our methods can be applied. For ASPOC currents up to 30 microampere spacecraft potential reconstructions are largely viableComparison of our plasma density estimates with measurements from the FPI detector is in good agreementOur methods allow us to derive relative density variations and recognize boundary crossings in magnetosphere

The unique properties of fibers have received great attention from the scientific community as suitable candidates for biomedical engineering and drug delivery applications. Their properties include, high surface-to-volume ratio, high porosity, adjustable pore size and morphological similarity to the extracellular matrix. Polymeric fibrous structures have been recognized as drug-delivery system candidates and various techniques have been employed to tailor-made their characteristics, such as the electro-hydrodynamic techniques (EHD). The latter methods exploit the electrostatic forces in order to create particles or fibers of tunable microstructure.

Variations of the floating potential on spacecraft are often used to derive plasma densities, complementing the plasma instrument measurements. All spacecraft of the Cluster mission are equipped with Active Spacecraft POtential Control (ASPOC) instruments that control the spacecraft potential. Although the ASPOC operation increases the accuracy of electric field and plasma measurements, it prevents a direct use of the spacecraft potential variations to derive plasma densities. In this work we develop a new reconstruction method of uncontrolled spacecraft potential from controlled spacecraft potential data and a derived photoelectron curve, using multispacecraft observations. We assume that the same curve governs the plasma environment for the spacecraft with ASPOC on and off. The current work focuses on reconstructions in the magnetotail region. The period that was more extensively studied was the one from August to October 2003, when the spacecraft were close to each other, while results from the periods of August–October 2001, 2002, and 2004, when the Cluster spacecraft had their apogee in the magnetotail region, are also presented. In this way, we investigate how the photoelectron curve varies at different time intervals and also how the reconstruction results are modified when the distance between the spacecraft is increasing. Finally, by using the reconstructed results, we proceed by estimating the plasma densities and we discuss the uncertainties of such estimations. While, on average, spacecraft potential measurements are successfully reconstructed, plasma and solar activity variations on short timescales seem to affect the reconstructions, requiring in some cases more detailed analysis in order to achieve results with higher accuracy. Moreover, there are some limitations while deriving results in very tenuous plasma regions due to increased uncertainties in some of the scientific measurements used there. The results and the methods developed for this work can be applied for any other current and future mission with instruments that control the spacecraft potential, such as the recently launched Magnetospheric Multiscale Mission. We derive average photoelectron curves for the 2001–2004 period using multispacecraft observationsWe successfully reconstruct spacecraft potential from data with active spacecraft potential controlPlasma and solar activity variations seem to affect reconstructions in some cases

Interchange injection events are commonly observed by the Cassini spacecraft in the region between about 6 and 12 Rs(1 Rs= 60,268 km) and even frequently beyond. In this study, 13 examples of interchange injection events are identified in Cassini/Cassini Plasma Spectrometer data under special conditions such that time‐of‐flight (TOF) mass spectra could be obtained from entirely within the events. Using the TOF data to separate the main ion species H+, H2+, and W+, approximate densities of each species are calculated under the assumption that all distributions were isotropic. The light‐ion density ratios, H2+/H+, in the injection events are not discernibly different from those ratios in control intervals from the ambient plasma. However, the water‐group ratio, W+/H+, is significantly lower than ambient. The comparison of the measured density ratios with the range of values observed throughout Saturn's magnetosphere indicates that the values of W+/H+that are as low as those observed within the injection events are found primarily beyond L~14 (where Lis the equatorial crossing distance, in Saturn radius, of a dipole field line), indicating that the injection events are delivering plasma from the outer magnetosphere at times traveling at least 6 Rs. Ion composition (H2+/H+and W+/H+) is measured in 13 interchange injectionsW+/H+is significantly reduced compared to nearby inner magnetospheric plasmaThe composition suggests an injection origin beyond L~14

Qualitative and quantitative determinations are reported for constituents of the essential oil of Satureia thymbra L., from different regions of Greece.

We describe the case of a patient presented with isolated right heart failure with atrial fibrillation and severe tricuspid regurgitation due to hyperthyroidism. Treatment of the thyroid disease resulted in the disappearance of signs of right heart failure and resolution of the valve incompetence and normalization of the heart rhythm. Although thyrotoxicosis may be associated with congestive heart failure, isolated right heart failure with marked tricuspid regurgitation is rarely seen.