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Space radiation exposure from omnipresent Galactic Cosmic Rays (GCRs) in interplanetary space poses a serious carcinogenic risk to astronauts due to the—limited or absent—protective effect of the Earth’s magnetosphere and, in particular, the terrestrial atmosphere. The radiation risk is directly influenced by the quality of the radiation, i.e., its pattern of energy deposition at the micron/DNA scale. For stochastic biological effects, radiation quality is described by the quality factor, $$Q$$ Q , which can be defined as a function of Linear Energy Transfer (LET) or the microdosimetric lineal energy ($$y$$ y ). In the present work, the average $$Q$$ Q of GCR for different mission scenarios was calculated using a modified version of the microdosimetric Theory of Dual Radiation Action (TDRA). NASA’s OLTARIS platform was utilized to generate the radiation environment behind different aluminum shielding (0–30 g/cm2) for a typical mission scenario in low-earth orbit (LEO) and in deep space. The microdosimetric lineal energy spectra of ions ($$Z\ge 1$$ Z ≥ 1 ) in 1 μm liquid water spheres were calculated by a generalized analytical model which considers energy-loss fluctuations and δ-ray transport inside the irradiated medium. The present TDRA-based $$Q$$ Q -values for the LEO and deep space missions were found to differ by up to 10% and 14% from the corresponding ICRP-based $$Q$$ Q -values and up to 3% and 6% from NASA’s $$Q$$ Q -model. In addition, they were found to be in good agreement with the $$Q$$ Q -values measured in the International Space Station (ISS) and by the Mars Science Laboratory (MSL) Radiation Assessment Detector (RAD) which represent, respectively, a LEO and deep space orbit.

Emerging evidence suggests that fatty acids (FAs) and their lipid mediator derivatives can induce both beneficial and detrimental effects on inflammatory processes and joint degradation in osteoarthritis (OA) and autoimmune-driven rheumatoid arthritis (RA). The present study characterized the detailed FA signatures of synovial membranes collected during knee replacement surgery of age- and gender-matched OA and RA patients (n = 8/diagnosis). The FA composition of total lipids was determined by gas chromatography and analyzed with univariate and multivariate methods supplemented with hierarchical clustering (HC), random forest (RF)-based classification of FA signatures, and FA metabolism pathway analysis. RA synovium lipids were characterized by reduced proportions of shorter-chain saturated FAs (SFAs) and elevated percentages of longer-chain SFAs and monounsaturated FAs, alkenyl chains, and C20 n-6 polyunsaturated FAs compared to OA synovium lipids. In HC, FAs and FA-derived variables clustered into distinct groups, which preserved the discriminatory power of the individual variables in predicting the RA and OA inflammatory states. In RF classification, SFAs and 20:3n-6 were among the most important FAs distinguishing RA and OA. Pathway analysis suggested that elongation reactions of particular long-chain FAs would have increased relevance in RA. The present study was able to determine the individual FAs, FA groups, and pathways that distinguished the more inflammatory RA from OA. The findings suggest modifications of FA elongation and metabolism of 20:4n-6, glycerophospholipids, sphingolipids, and plasmalogens in the chronically inflamed RA synovium. These FA alterations could have implications in lipid mediator synthesis and potential as novel diagnostic and therapeutic tools.

Osteoarthritis (OA) is a common musculoskeletal disease that leads to deterioration of articular cartilage, joint pain, and decreased quality of life. When OA develops after a joint injury, it is designated as post-traumatic OA (PTOA). The etiology of PTOA remains poorly understood, but it is known that proteoglycan (PG) loss, cell dysfunction, and cell death in cartilage are among the first signs of the disease. These processes, influenced by biomechanical and inflammatory stimuli, disturb the normal cell-regulated balance between tissue synthesis and degeneration. Previous computational mechanobiological models have not explicitly incorporated the cell-mediated degradation mechanisms triggered by an injury that eventually can lead to tissue-level compositional changes. Here, we developed a 2-D mechanobiological finite element model to predict necrosis, apoptosis following excessive production of reactive oxygen species (ROS), and inflammatory cytokine (interleukin-1)-driven apoptosis in cartilage explant. The resulting PG loss over 30 days was simulated. Biomechanically triggered PG degeneration, associated with cell necrosis, excessive ROS production, and cell apoptosis, was predicted to be localized near a lesion, while interleukin-1 diffusion-driven PG degeneration was manifested more globally. The numerical predictions were supported by several previous experimental findings. Furthermore, the ROS and inflammation mechanisms had longer-lasting effects (over 3 days) on the PG content than localized necrosis. Interestingly, the model also showed proteolytic activity and PG biosynthesis closer to the levels of healthy tissue when pro-inflammatory cytokines were rapidly inhibited or cleared from the culture medium, leading to partial recovery of PG content. The mechanobiological model presented here may serve as a numerical tool for assessing early cartilage degeneration mechanisms and the efficacy of interventions to mitigate PTOA progression.Author summaryOsteoarthritis is one of the most common musculoskeletal diseases. When osteoarthritis develops after a joint injury, it is designated as post-traumatic osteoarthritis. A defining feature of osteoarthritis is degeneration of articular cartilage, which is partly driven by cartilage cells after joint injury, and further accelerated by inflammation. The degeneration triggered by these biomechanical and biochemical mechanisms is currently irreversible. Thus, early prevention/mitigation of disease progression is a key to avoiding PTOA. Prior computational models have been developed to provide insights into the complex mechanisms of cartilage degradation, but they rarely include cell-level cartilage degeneration mechanisms. Here, we present a novel approach to simulate how the early post-traumatic biomechanical and inflammatory effects on cartilage cells eventually influence tissue composition. Our model includes the key regulators of early post-traumatic osteoarthritis: chondral lesions, cell death, reactive oxygen species, and inflammatory cytokines. The model is supported by several experimental explant culture findings. Interestingly, we found that when post-injury inflammation is mitigated, cartilage composition can partially recover. We suggest that mechanobiological models including cell–tissue-level mechanisms can serve as future tools for evaluating high-risk lesions and developing new intervention strategies.

Funding Information: Open access funding provided by University of Eastern Finland (UEF) including Kuopio University Hospital. Financial support for the study was provided by the Academy of Finland (grant #322429 to PN). The funding source had no involvement in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Publisher Copyright: © 2022, The Author(s). Osteoarthritis (OA) and autoimmune-driven rheumatoid arthritis (RA) are inflammatory joint diseases with complex and insufficiently understood pathogeneses. Our objective was to characterize the metabolic fingerprints of synovial fluid (SF) and its adjacent infrapatellar fat pad (IFP) obtained during the same surgical operation from OA and RA knees. Non-targeted metabolite profiling was performed for 5 non-inflammatory trauma controls, 10 primary OA (pOA) patients, and 10 seropositive RA patients with high-resolution mass spectrometry-based techniques, and metabolites were matched with known metabolite identities. Groupwise differences in metabolic features were analyzed with the univariate Welch’s t-test and the multivariate linear discriminant analysis (LDA) and principal component analysis (PCA). Significant discrimination of metabolite profiles was discovered by LDA for both SF and IFP and by PCA for SF based on diagnosis. In addition to a few drug-derived substances, there were 16 and 13 identified metabolites with significant differences between the diagnoses in SF and IFP, respectively. The pathways downregulated in RA included androgen, bile acid, amino acid, and histamine metabolism, and those upregulated included biotin metabolism in pOA and purine metabolism in RA and pOA. The RA-induced downregulation of androgen and bile acid metabolism was observed for both SF and IFP. The levels of 11 lipid metabolites, mostly glycerophospholipids and fatty acid amides, were also altered by these inflammatory conditions. The identified metabolic pathways could be utilized in the future to deepen our understanding of the pathogeneses of OA and RA and to develop not only biomarkers for their early diagnosis but also therapeutic targets.

Extracellular vesicles (EVs) function as conveyors of fatty acids (FAs) and other bioactive lipids and can modulate the gene expression and behavior of target cells. EV lipid composition influences the fluidity and stability of EV membranes and reflects the availability of lipid mediator precursors. Fibroblast-like synoviocytes (FLSs) secrete EVs that transport hyaluronic acid (HA). FLSs play a central role in inflammation, pannus formation, and cartilage degradation in joint diseases, and EVs have recently emerged as potential mediators of these effects. The aim of the present study was to follow temporal changes in HA and EV secretion by normal FLSs, and to characterize the FA profiles of FLSs and EVs during proliferation. The methods used included nanoparticle tracking analysis, confocal laser scanning microscopy, sandwich-type enzyme-linked sorbent assay, quantitative PCR, and gas chromatography. The expression of hyaluronan synthases 1–3 in FLSs and HA concentrations in conditioned media decreased during cell proliferation. This was associated with elevated proportions of 20:4n-6 and total n-6 polyunsaturated FAs (PUFAs) in high-density cells, reductions in n-3/n-6 PUFA ratios, and up-regulation of cluster of differentiation 44, tumor necrosis factor α, peroxisome proliferator-activated receptor (PPAR)-α, and PPAR-γ. Compared to the parent FLSs, 16:0, 18:0, and 18:1n-9 were enriched in the EV fraction. EV counts decreased during cell growth, and 18:2n-6 in EVs correlated with the cell count. To conclude, FLS proliferation was featured by increased 20:4n-6 proportions and reduced n-3/n-6 PUFA ratios, and FAs with a low degree of unsaturation were selectively transferred from FLSs into EVs. These FA modifications have the potential to affect membrane fluidity, biosynthesis of lipid mediators, and inflammatory processes in joints, and could eventually provide tools for translational studies to counteract cartilage degradation in inflammatory joint diseases.

Regardless of the model for identifying the relationship between science and religion–conflict, independence, dialogue, integration–insufficient attention has been given to the way evidence is proc...

Injurious overloading and inflammation perturbate homeostasis of articular cartilage, leading to abnormal tissue-level loading during post-traumatic osteoarthritis. Our objective was to gain time- and cartilage depth-dependent insights into the early-stage disease progression with an in vitro model incorporating for the first time the coaction of (1) mechanical injury, (2) pro-inflammatory interleukin-1 challenge, and (3) cyclic loading mimicking walking and considered beneficial for cartilage health. Cartilage plugs (n = 406) were harvested from the patellofemoral grooves of young calves (N = 6) and subjected to injurious compression (50% strain, rate 100%/s; INJ), interleukin-1α-challenge (1 ng/ml; IL), and cyclic loading (intermittent 1 h loading periods, 15% strain, 1 Hz; CL). Plugs were assigned to six groups (control, INJ, IL, INJ-IL, IL-CL, INJ-IL-CL). Bulk and localized glycosaminoglycan (GAG) content (DMMB assay, digital densitometry), aggrecan biosynthesis (

Dihomo-γ-linolenic acid (DGLA) has emerged as a significant molecule differentiating healthy and inflamed tissues. Its position at a pivotal point of metabolic pathways leading to anti-inflammatory derivatives or via arachidonic acid (ARA) to pro-inflammatory lipid mediators makes this n-6 polyunsaturated fatty acid (PUFA) an intriguing research subject. The balance of ARA to DGLA is probably a critical factor affecting inflammatory processes in the body. The aim of this narrative review was to examine the potential roles of DGLA and related n-6 PUFAs in inflammatory conditions, such as obesity-associated disorders, rheumatoid arthritis, atopic dermatitis, asthma, cancers, and diseases of the gastrointestinal tract. DGLA can be produced by cultured fungi or be obtained via endogenous conversion from γ-linolenic acid (GLA)-rich vegetable oils. Several disease states are characterized by abnormally low DGLA levels in the body, while others can feature elevated levels. A defect in the activity of ∆6-desaturase and/or ∆5-desaturase may be one factor in the initiation and progression of these conditions. The potential of GLA and DGLA administrations as curative or ameliorating therapies in inflammatory conditions and malignancies appears modest at best. Manipulations with ∆6- and ∆5-desaturase inhibitors or combinations of long-chain PUFA supplements with n-3 PUFAs could provide a way to modify the body’s DGLA and ARA production and the concentrations of their pro- and anti-inflammatory mediators. However, clinical data remain scarce and further well-designed studies should be actively promoted.

Purpose: Track structure Monte Carlo (MC) codes have achieved successful outcomes in the quantitative investigation of radiation-induced initial DNA damage. The aim of the present study is to extend a Geant4-DNA radiobiological application by incorporating a feature allowing for the prediction of DNA rejoining kinetics and corresponding cell surviving fraction along time after irradiation, for a Chinese hamster V79 cell line, which is one of the most popular and widely investigated cell lines in radiobiology. Methods: We implemented the Two-Lesion Kinetics (TLK) model, originally proposed by Stewart, which allows for simulations to calculate residual DNA damage and surviving fraction along time via the number of initial DNA damage and its complexity as inputs. Results: By optimizing the model parameters of the TLK model in accordance to the experimental data on V79, we were able to predict both DNA rejoining kinetics at low linear energy transfers (LET) and cell surviving fraction. Conclusion: This is the first study to demonstrate the implementation of both the cell surviving fraction and the DNA rejoining kinetics with the estimated initial DNA damage, in a realistic cell geometrical model simulated by full track structure MC simulations at DNA level and for various LET. These simulation and model make the link between mechanistic physical/chemical damage processes and these two specific biological endpoints.

Post-traumatic osteoarthritis is a degenerative musculoskeletal condition where homeostasis of articular cartilage is perturbated by lesions and inflammation, leading to abnormal tissue-level loading. These mechanisms have rarely been included simultaneously inin vitroosteoarthritis models. We modeled the early disease progression in bovine cartilage regulated by the coaction of(1)mechanical injury,(2)pro-inflammatory interleukin-1α challenge, and(3)cyclic loading mimicking walking and considered beneficial (15% strain, 1 Hz). Surprisingly, cyclic loading did not protect cartilage from accelerated glycosaminoglycan loss over 12 days of interleukin-1-culture despite promoting aggrecan biosynthesis. Our time-dependent data suggest that this loading regime could be beneficial in the first days following injury but later turn detrimental in interleukin-1-inflamed cartilage. Consequently, early anti-catabolic drug intervention may inhibit, whereas cyclic loading during chronic inflammation may promote osteoarthritis progression. Our data on the early stages of post-traumatic osteoarthritis could be utilized in the development of countermeasures for disease progression.

We present the analysis of data taken by the Space Application of Timepix Radiation Monitor (SATRAM). It is centred on a Timepix detector (300 μ m thick silicon sensor, pixel pitch 55 μ m, 256 × 256 pixels). It was flown on Proba-V, an Earth observing satellite of the European Space Agency (ESA) from an altitude of 820 km on a sun-synchronous orbit, launched on May 7, 2013. A Monte Carlo simulation was conducted to determine the detector response to electrons (0.5–7 MeV) and protons (10–400 MeV) in an omnidirectional field taking into account the shielding of the detector housing and the satellite. With the help of the simulation, a strategy was developed to separate electrons, protons and ions in the data. The measured dose rate and stopping power distribution are presented as well as SATRAM’s capability to measure some of the stronger events in Earth’s magnetosphere. The stopping power, the cluster height and the shape of the particle tracks in the sensor were used to separate electrons, protons and ions. The results are presented as well. Finally, the pitch angles for a short period of time were extracted from the data and corrected with the angular response determined by the simulation.

Purpose of Review Osteoarthritis (OA) and rheumatoid arthritis (RA) are characterized by abnormal lipid metabolism manifested as altered fatty acid (FA) profiles of synovial fluid and tissues and in the way dietary FA supplements can influence the symptoms of especially RA. In addition to classic eicosanoids, the potential roles of polyunsaturated FA (PUFA)-derived specialized pro-resolving lipid mediators (SPM) have become the focus of intensive research. Here, we summarize the current state of knowledge of the roles of FA and oxylipins in the degradation or protection of synovial joints. Recent Findings There exists discordance between the large body of literature from cell culture and animal experiments on the adverse and beneficial effects of individual FA and the lack of effective treatments for joint destruction in OA and RA patients. Saturated 16:0 and 18:0 induce mostly deleterious effects, while long-chain n-3 PUFA, especially 20:5n-3, have positive influence on joint health. The situation can be more complex for n-6 PUFA, such as 18:2n-6, 20:4n-6, and its derivative prostaglandin E2, with a combination of potentially adverse and beneficial effects. SPM analogs have future potential as analgesics for arthritic pain. Summary Alterations in FA profiles and their potential implications in SPM production may affect joint lubrication, synovial inflammation, pannus formation, as well as cartilage and bone degradation and contribute to the pathogeneses of inflammatory joint diseases. Further research directions include high-quality randomized controlled trials on dietary FA supplements and investigations on the significance of lipid composition of microvesicle membrane and cargo in joint diseases.

Rhabdomyolysis (destruction of striated muscle) is a novel form of mushroom poisoning in Europe and Asia indicated by increased circulating creatine kinase levels. Particular wild fungi have also been reported to induce elevated creatine kinase activities in mice. Flammulina velutipes (enokitake or winter mushroom) is one of the most actively cultivated mushroom species globally. As it is marketed as a medicinal mushroom and functional food, it is important to examine whether it could induce potentially harmful health effects similar to some previously studied edible fungi. The present study examined the effects of F. velutipes consumption on the plasma clinical chemistry, hematology, and organ histology of laboratory mice. Wild F. velutipes were dried, pulverized, mixed with a regular laboratory rodent diet, and fed to the animals at 0, 3, 6, or 9 g/kg body mass/day for five days ( n = 6/group). F. velutipes consumption caused increased activities of plasma creatine kinase and the MB-fraction of creatine kinase at 6–9 g/kg/d, indicating potentially deleterious effects on both skeletal and cardiac muscle. The plasma total and high-density lipoprotein cholesterol concentrations (at 9 g/kg/d) and white blood cell and lymphocyte counts (at 6–9 g/kg/d) decreased. Although the cholesterol-lowering properties of F. velutipes can be beneficial, the previously unexamined, potentially hazardous side effects of mushroom consumption (myo- and cardiotoxicity) should be thoroughly investigated before recommending this mushroom species as a health-promoting food item. Impact statement This work is important to the field of functional foods, as it provides novel information about the potential myo- and cardiotoxic properties of an edible mushroom, Flammulina velutipes. The results are useful and of importance because F. velutipes is an actively cultivated mushroom and marketed as a health-promoting food item. The findings contribute to the understanding of the complexity of the balance between the beneficial and potentially harmful effects of mushroom consumption.

Orthopedic abnormalities of farm-reared blue foxes (Vulpes lagopus) have increased recently, creating new concerns about their welfare. Therefore, skeletal condition of obese juvenile blue foxes was evaluated for relationships to degree of obesity. Two pilot study groups included less obese foxes (N = 5) and more obese foxes (N = 5); the latter group had visible carpal joint laxity and locomotor deficits. The principal aims were to examine forelimb deformities snd abnormal locomotion in light of degree of obesity. Overt and incipient (mild or developing) vvpathology were prevalent and reflected degree of obesity. It is likely that genetic selection and feeding practices were primary underlying problems, but disrupted mineral nutrition and housing practices may have been involved as well. These observations underscore the importance of new actions and additional studies of breeding, nutrition, and housing practices, with the ultimate goal of enhancing the welf are of farmed foxes.

The second L-class (large) mission in European Space Agency’s Cosmic Vision program will be an X-ray telescope named Athena, planned to operate at the L2 Lagrange point of the Sun–Earth system. Current large X-ray space telescopes like XMM-Newton and Chandra have encountered periods of unexpectedly high background due to protons in the energy range from 10 keV to 1 MeV (called “soft protons” hereafter). This is an important issue for Athena, as no X-ray telescope has been deployed at L2 so far and the soft proton environment there is poorly known. We analyze data from the Artemis and Advanced Composition Explorer spacecraft and find that fluxes of both solar and geomagnetospheric origin significantly contribute to the soft proton populations in earth’s magnetotail. We then estimate the background from the measured fluxes in Athena’s X-ray instruments and compare it with the science requirement. Our findings reinforce the argument for developing a means to suppress the soft proton flux before it reaches the detectors such as with a magnetic diverter.

The raccoon dog (Nyctereutes procyonoides) is an invasive canid originating from eastern Asia. Here, we review its physiological adaptations to wintering, with an emphasis on northern Europe, where the raccoon dog spends the coldest part of the year in winter sleep. The timing of physiological changes related to wintering is connected to photoperiod by melatonin. In preparation to winter, raccoon dogs display autumnal hyperphagia and fattening probably regulated by the interaction of several peptide hormones. Sufficient fat deposition is essential for survival through the cold season and for reproduction in spring. The wintering strategy includes alternating periods of physical activity and passivity. Effective arousal and foraging during warmer bouts are enabled by normoglycaemia. During active periods, raccoon dogs are opportunistic participants in the food web, and they mainly utilize ungulate carcasses, plant material, and small mammals. Preferred wintertime habitats include watersides, forests, wetlands, and gardens. However, many food items become limited in mid-winter and snow restricts foraging leading to a negative energy balance. During passivity, energy is preserved by denning and by modest metabolic suppression, probably enabled by decreased thyroid hormone levels. Sleepiness and satiety could be maintained by high growth hormone and leptin concentrations. Several hormones participate in the extension of phase II of fasting with selective fatty acid mobilization and efficient protein conservation. The blood count, organ function tests, bone mass, and bone biomechanical properties exhibit high resistance against catabolism, and breeding can be successful after significant weight loss. The flexible physiological response to wintering is probably one reason enabling the successful colonization of this species into new areas.

Alvin Plantinga's evolutionary argument against naturalism states that evolution cannot produce warranted beliefs. In contrast, according to Plantinga, Christian theism provides (I) properly functioning cognitive faculties in (II) an appropriate cognitive environment, in accordance with (III) a design plan aimed at producing true beliefs. But does theism fulfill criteria I–III? Judging from the Bible, God employs deceit in his relations with humanity, rendering our cognitive functions unreliable (I). Moreover, there is no reason to suppose that God's purpose would be to produce true beliefs in humans (III). Finally, from the theistic/religious perspective, it is impossible to tell whether observations have natural or supernatural causes, which undermines an appropriate cognitive environment (II). Reliable identification of deceit or miracles could alleviate these problems, but the theistic community has failed to resolve this issue. Dismissal of parts of the Bible, or attempts to find alternative interpretations, would collapse into skepticism or deism. Thus, Plantinga's problem of epistemic warrant backfires on theism.

On January 6, 2014 a Solar Energetic Particle (SEP) event started that led to a 1030 cm $^{-2}$ $\text{s}^{-1}$ sr $^{-1}$ peak flux of E > 10 MeV protons on January 9, 2014 at geosynchronous orbit, an event exceeded only by about 15% of all SEP events. Such high flux events contribute the most to solar event-induced radiation effects in space equipment, while being easy to characterize based on data acquired by spectrometers, such as the EPT. The EPT instrument provides fluxes of electrons (0.5–20 MeV), H (9.5–300 MeV) and He (38–1200 MeV) ions. It presently flies on the PROBA-V satellite, launched into a Low Earth Orbit on May 7, 2013. As it has been reported that the He contribution to Total Non-Ionizing Dose (TNID) may be comparable to that of H in representative space environments, a data analysis to identify periods of high He flux as compared to H, and conditions under which both ions must be accounted for during radiation effect analyses, was performed. From the study of the positional variation of solar H and He fluxes, a formulation of the minimum L-value reached by these particles for a given rigidity is provided. The shape of solar H and He energy spectra as well as the H/He fluence ratio and pitch angle distributions are characterized. The contribution of He compared to H for Total Ionizing Dose (TID) and TNID effects is below 5% for devices shielded by >2mm Al.

Background: Infrapatellar fat pad (IFP) has recently emerged as a potential source of inflammation in knee arthropathies. It has been proposed to be one source of adipocytokines, fatty acids (FA), and FA-derived lipid mediators that could contribute to the pathophysiological processes in the knee joint. Alterations in synovial fluid (SF) lipid composition have been linked to both osteoarthritis (OA) and rheumatoid arthritis (RA). The aim of the present study was to compare the FA signatures in the IFP and SF of RA and OA patients. Methods: Pairs of IFP and SF samples were collected from the same knees of RA (n = 10) and OA patients (n = 10) undergoing total joint replacement surgery. Control SF samples (n = 6) were harvested during diagnostic or therapeutic arthroscopic knee surgery unrelated to RA or OA. The FA composition in the total lipids of IFP and SF was determined by gas chromatography with flame ionization and mass spectrometric detection. Results: Arthropathies resulted in a significant reduction in the SF proportions of n-6 polyunsaturated FA (PUFA), more pronouncedly in OA than in RA. OA was also characterized with reduced percentages of 22:6n-3 and lower product/precursor ratios of n-3 PUFA. The proportions of total monounsaturated FA increased in both RA and OA SF. Regarding IFP, RA patients had lower proportions of 20:4n-6, total n-6 PUFA, and 22:6n-3, as well as lower product/precursor ratios of n-3 PUFA compared to OA patients. The average chain length of SF FA decreased in both diagnoses and the double bond index in OA. Conclusions: The observed complex alterations in the FA signatures could have both contributed to but also limited the inflammatory processes and cartilage destruction in the RA and OA knees.

The radiation data collected by the Standard Radiation Environment Monitor (SREM) aboard ESA missions INTEGRAl, ROSETTA, HERSCHEL, PLANCK and PROBA-1, and by the High Energy Neutron Detector (HEND) instrument aboard Mars Odyssey are analysed with an emphasis on characterising Galactic Cosmic Rays (GCRs) in the inner heliosphere. A cross-calibration between all sensors was performed for this study, which can also be used in subsequent works. We investigate the stability of the SREM detectors over long-term periods. The radiation data is compared qualitatively and quantitatively with the corresponding solar activity. Based on INTEGRAL and Rosetta SREM data, a GCR helioradial gradient of 2.96 %/AU is found between 1 and 4.5 AU. In addition, the data during the last phase of the Rosetta mission around comet 67P/Churyumov-Gerasimenko were studied in more detail. An unexpected and yet unexplained 8 % reduction of the Galactic Comic Ray flux measured by Rosetta SREM in the vicinity of the comet is noted.

Background The infrapatellar fat pad (IFP) of the knee joint has received lots of attention recently due to its emerging role in the pathogenesis of osteoarthritis (OA), where it displays an inflammatory phenotype. The aim of the present study was to examine the infrapatellar fatty acid (FA) composition in a rabbit (Oryctolagus cuniculus) model of early OA created by anterior cruciate ligament transection (ACLT). Methods OA was induced randomly in the left or right knee joint of skeletally mature New Zealand White rabbits by ACLT, while the contralateral knee was left intact. A separate group of unoperated rabbits served as controls. The IFP of the ACLT, contralateral, and control knees were harvested following euthanasia 2 or 8 weeks post-ACLT and their FA composition was determined with gas chromatography–mass spectrometry. Results The n-3/n-6 polyunsaturated FA (PUFA) ratio shifted in a pro-inflammatory direction after ACLT, already observed 2 weeks after the operation (0.20 ± 0.008 vs. 0.18 ± 0.009). At 8 weeks, the FA profile of the ACLT group was characterized with increased percentages of 20:4n-6 (0.44 ± 0.064 vs. 0.98 ± 0.339 mol-%) and 22:6n-3 (0.03 ± 0.014 vs. 0.07 ± 0.015 mol-%) and with decreased monounsaturated FA (MUFA) sums (37.19 ± 1.586 vs. 33.20 ± 1.068 mol-%) and n-3/n-6 PUFA ratios (0.20 ± 0.008 vs. 0.17 ± 0.008). The FA signature of the contralateral knees resembled that of the unoperated controls in most aspects, but had increased proportions of total n-3 PUFA and reduced MUFA sums. Conclusions These findings provide novel information on the effects of early OA on the infrapatellar FA profile in the rabbit ACLT model. The reduction in the n-3/n-6 PUFA ratio of the IFP is in concordance with the inflammation and cartilage degradation in early OA and could contribute to disease pathogenesis. Electronic supplementary material The online version of this article (10.1186/s12944-019-1008-5) contains supplementary material, which is available to authorized users.

The advancement of multidisciplinary research fields dealing with ionising radiation induced biological damage – radiobiology, radiation physics, radiation protection and, in particular, medical physics – requires a clear mechanistic understanding of how cellular damage is induced by ionising radiation. Monte Carlo (MC)simulations provide a promising approach for the mechanistic simulation of radiation transport and radiation chemistry, towards the in silico simulation of early biological damage. We have recently developed a fully integrated MC simulation that calculates early single strand breaks (SSBs)and double strand breaks (DSBs)in a fractal chromatin based human cell nucleus model. The results of this simulation are almost equivalent to past MC simulations when considering direct/indirect strand break fraction, DSB yields and fragment distribution. The simulation results agree with experimental data on DSB yields within 13.6% on average and fragment distributions agree within an average of 34.8%. © 2019 Associazione Italiana di Fisica Medica

Extracellular vesicles (EVs) function in intercellular signaling by transporting different membrane and cytosolic molecules, including hyaluronan (HA) and its synthesis machinery. As both EVs and HA are abundant in synovial fluid, we hypothesized that HA synthesized in synovial membrane would be carried on the surface of EVs. Synovial fluid (n = 15) and membrane samples (n = 5) were obtained from knee surgery patients. HA concentrations were analyzed in synovial fluid and HA and its synthesis machinery were examined with histochemical stainings in synovial membrane. To assess the size distribution of EVs in synovial fluid and to visualize HA on EVs, nanoparticle tracking analysis (NTA), confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM) were utilized. The average HA concentration in synovial fluid was 2.0 ± 0.21 mg/ml without significant differences between the patients with trauma/diagnostic arthroscopy and primary or post-traumatic osteoarthritis. Positive stainings of HA synthases (HAS1-3), HA and its receptor CD44 in synovial cells indicated active HA secretion in synovial membrane. According to NTA, EVs were abundant in synovial fluid and their main populations were ≤300 nm in diameter after differential centrifugation. There were no significant differences in the EV counts between the patients with primary or post-traumatic osteoarthritis. TEM verified that HA-positive particles detected by CLSM were lipid membrane vesicles surrounded by a HA coat. Our results provide the first in vivo evidence that human synovial fluid contains HA-positive EVs, one source of which presumably is the long HAS-positive protrusions of synovial fibroblasts. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1960-1968, 2016.

Nonalcoholic fatty liver disease is among the most common liver diseases worldwide and one cause of cirrhosis that can result in the development of hepatocellular carcinoma (HCC). Hyaluronan (HA) is a high-molecular-mass glycosaminoglycan with diverse functions in tissue injury and repair, for instance, in inflammation and fibrogenesis. The aim of the present study was to investigate the relationships between the HA synthesizing and degrading enzymes in a spectrum of liver pathologies. This was realized by histological staining of liver sections from controls and patients with simple steatosis, steatohepatitis, cirrhosis and HCC (n = 90). HA-positive staining intensified in connective tissue in all liver pathologies, and staining of CD44, the major HA receptor, similarly increased in steatohepatitis and cirrhosis. HA synthase 1 (HAS1)-positive staining was reduced in steatosis, steatohepatitis and HCC. Staining of HAS3, which produces HA of a lower molecular mass, promotes inflammation and is pathogenic in animal models, increased in all diagnoses. The responses in staining intensity of HAS2 and hyaluronidases 1-2 were specific for different cell types. These findings suggest that HAS1-2 are responsible for HA synthesis in healthy livers, while HAS3 increases in importance in liver diseases. It is noteworthy that the pathological changes in HA metabolism are already visible in simple steatosis and, thus, precede the histological changes of inflammation and fibrosis. It could be possible to intervene in disease progression at an early stage by influencing HA metabolism. The results could have potential clinical applications with HAS3 immunostaining supplementing the existing HCC diagnostics.

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Fatty acid (FA) signatures (FAS) are important tools to assess the foraging ecology of wild animals. The present study was conducted to assess how well the general FAS and the proportions of individual FA are preserved in fat samples stored at different temperatures (196, -80, -20, +4 and +20 degrees C). Using three species (laboratory rat, American mink and rainbow trout), FAS were determined immediately upon sampling. Thereafter, eight subsamples per storage temperature from the inner part of the sample unaffected by oxygen and light were re-analyzed after 1, 2, 3, 7, 28, 84 and 168 days. Each time the remaining sample was sealed in its vial after replacing air with nitrogen gas. The results were tested with the mixed model and discriminant analyses. Generally, the FAS were well preserved regardless of storage temperature, and only a few major FA showed significant changes even after the 6-month period at room temperature. After an initial first-day change in proportions, presumably due to post-mortem enzymatic activities, the remaining minor changes could not be clearly attributed to either further autolysis, decomposition or autoxidation. In the discriminant analysis, the species-specific differences dominated and remained distinct even after 6 months. Furthermore, the analysis mostly classified the samples preserved at sub- and above-freezing temperatures separate from each other, and the general deviation from the initial analysis results was present as early as after 1 day. If FAS are to be analyzed in a very precise manner, the analysis should be performed immediately upon sampling. However, FAS remain adequately reliable for long periods of time even without preservation in deep freeze, widening the availability of potential samples for studies on foraging ecology and related disciplines.