Search

OBJECTIVES: To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). METHODS: A systematic literature review was conducted to retrieve data on treatment targets and outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting. The final level of agreement was provided anonymously. RESULTS: Five overarching principles and six-specific recommendations were formulated. Management of GCA and PMR should be based on shared decisions between patient and physician recognising the need for urgent treatment of GCA to avoid ischaemic complications, and it should aim at maximising health-related quality of life in both diseases. The treatment targets are achievement and maintenance of remission, as well as prevention of tissue ischaemia and vascular damage. Comorbidities need to be considered when assessing disease activity and selecting treatment. CONCLUSION: These are the first T2T recommendations for GCA and PMR. Treatment targets, as well as strategies to assess, achieve and maintain these targets have been defined. The research agenda highlights the gaps in evidence and the need for future research.

Abstract 12-oxophytodienoate reductase 3 (OPR3) is a key enzyme in the biosynthesis of jasmonoyl-L-isoleucine, the receptor-active form of jasmonic acid and crucial signaling molecule in plant defense. OPR3 was initially crystallized as a self-inhibitory dimer, implying that homodimerization regulates enzymatic activity in response to biotic and abiotic stresses. Since a sulfate ion is bound to Y364, mimicking a phosphorylated tyrosine, it was suggested that dimer formation might be controlled by reversible phosphorylation of Y364 in vivo. To investigate OPR3 homodimerization and its potential physiological role in more detail, we performed analytical gel filtration and dynamic light scattering on wild-type OPR3 and three variants (R283D, R283E, and Y364P). The experiments revealed a rapid and highly sensitive monomer–dimer equilibrium for all OPR3 constructs. We crystallized all constructs with and without sulfate to examine its effect on the dimerization process and whether reversible phosphorylation of Y364 triggers homodimerization in vivo. All OPR3 constructs crystallized in their monomeric and dimeric forms independent of the presence of sulfate. Even variant Y364P, lacking the putative phosphorylation site, was crystallized as a self-inhibitory homodimer, indicating that Y364 is not required for dimerization. Generally, the homodimer is relatively weak, and our results raise doubts about its physiological role in regulating jasmonate biosynthesis.

Abstract Heat engines are key devices that convert thermal energy into usable energy. Strong thermoelectricity, at the basis of electrical heat engines, is present in superconducting spin tunnel barriers at cryogenic temperatures where conventional semiconducting or metallic technologies cease to work. Here we realize a superconducting spintronic heat engine consisting of a ferromagnetic insulator/superconductor/insulator/ferromagnet tunnel junction (EuS/Al/AlO x /Co). The efficiency of the engine is quantified for bath temperatures ranging from 25 mK up to 800 mK, and at different load resistances. Moreover, we show that the sign of the generated thermoelectric voltage can be inverted according to the parallel or anti-parallel orientation of the two ferromagnetic layers, EuS and Co. This realizes a thermoelectric spin valve controlling the sign and strength of the Seebeck coefficient, thereby implementing a thermoelectric memory cell. We propose a theoretical model that allows describing the experimental data and predicts the engine efficiency for different device parameters.

Abstract Claws, as nature's multifaceted instruments, play fundamental roles across the animal kingdom, aiding in prey capture and enabling movement across diverse terrains. Claw features often reflect the ecologies of the respective taxa and thus can provide important insights into the different lifestyles. This study explores the claw morphology of monodactylous oribatid mites through geometric morphometrics, analyzing 559 specimens from 49 species across various ecosystems. The research identifies distinct claw characteristics associated with specific habitats, revealing a significant correlation between claw morphology and the mites' environmental adaptations. Littoral mites exhibit notably larger claws compared to terrestrial counterparts, with aquatic and semiaquatic species presenting intermediate traits. The analysis shows an inverse relationship between claw curvature and sharpness, differing from patterns observed in larger animals. A trend of increasing claw bluntness with body size in terrestrial mites echoes biomechanical constraints seen in larger species. The study also observes consistent claw shapes within oribatid superfamilies, suggesting a potential, albeit muted, phylogenetic influence alongside environmental factors. These findings reveal how ecological, evolutionary, and functional aspects influence claw morphology in oribatid mites, enhancing our knowledge of arthropod biology and potentially inspiring biomimetic advances in material science and engineering.

This study aims to evaluate the clinical outcome of stereotactic radiosurgery as the sole treatment for brain metastases and to assess prognostic factors influencing survival. A total of 108 consecutive patients with 213 metastases were retrospectively analyzed. Treatment was determined with close-meshed MRI follow-up. Various prognostic factors were assessed, and several prognostic indices were compared regarding their reliability to estimate overall survival. Median overall survival was 15 months; one-year overall survival was 50.5%. Both one- and two-year local controls were 90.9%. The rate of new metastases after SRS was 49.1%. Multivariate analysis of prognostic factors revealed that the presence of extracranial metastases, male sex, lower KPI, and progressive extracranial disease were significant risk factors for decreased survival. Of all evaluated prognostic indices, the Basic Score for Brain Metastases (BSBMs) showed the best correlation with overall survival. A substantial survival advantage was found for female patients after SRS when compared to male patients (18 versus 9 months, p = 0.003). SRS of brain metastasis is a safe and effective treatment option when frequent monitoring for new metastases with MRI is performed. Common prognostic scores lack reliable estimation of survival times. Female sex should be considered as an additional independent positive prognostic factor influencing survival.

BackgroundThe acquisition of handwriting skills is essential for a child’s academic success, self-confidence, and general school performance. Nevertheless, an estimated 5% to 27% of children face handwriting challenges, where the ability to modulate pressure on the pencil and lead on the paper is a key motor component. ObjectiveWe aimed to investigate the experience with and usability of the SensoGrip system, a pressure-measuring pen system with personalized real-time feedback about pressure modulation, in a clinical setting with children and occupational therapists (OTs). MethodsA multimethods study was conducted, incorporating qualitative interviews and questionnaires with children, user diaries, focus group discussions, and a usability questionnaire with OTs, along with a questionnaire for parents. ResultsThe study involved OTs (n=8), children with handwriting difficulties (n=16), and their parents (n=16), each of whom used the SensoGrip system in up to 5 therapy sessions. OTs reported that the SensoGrip system helped to focus the child’s awareness on handwriting pressure and to measure it objectively. The system received high acceptance and usability ratings from the OTs—usefulness: median score of 4 out of 7; ease of use and ease of learning: median score of 6 out of 7; and satisfaction: median score of 6 out of 7. Participants appreciated that it fosters pressure awareness and motivation to draw and write. ConclusionsThe SensoGrip pressure-sensing system with real-time feedback is a promising tool for pediatric occupational therapy. It supports children with handwriting difficulties to adjust their pressure application during the task. In the future, controlled quantitative trials are warranted to further examine the system’s impact.

Selecting the optimal settings for the production of rubber goods can be a very time-consuming and resource-intensive process. A promising method for optimizing rubber processing in a short period of time is the use of simulation routines. However, process simulations have only recently enabled meaningful predictions of not only the part’s state of cure but also its mechanical characteristics. As a first approach, second-order polynomials were considered suitable for describing the properties of compression-molded parts. However, more precision is required for injection molding due to the narrower distribution of mechanical characteristics of parts produced at different vulcanization temperatures. This became evident when the approximation of mechanical data with second order models partly revealed significant failures of part behavior prediction. To tackle this issue, a combined approach for approximation is proposed in this contribution by means of logistic growth function in addition to second order polynomials. To feed the model, an experimental plan was designed for producing injection-molded parts from an SBR compound at various temperatures and to different degrees of cure. The parts obtained were then characterized mechanically, and the results were opposed to varying degrees of cure and extents of reaction to calculate the model coefficients. Once available, a simulation-based calculation of the mechanical part quality is possible. The comparison of test results from the simulation and the real process has shown a reliable prediction, as simulation results were found within the natural deviation of the real measurements.

Effects of mowing on vegetation parameters have been well studied. However, less is known about mowing effects on soil fauna and if soil properties alter this. We investigated earthworm communities in a long-term experiment 14 years after its establishment in 5 dry, fresh and moist grassland plots located in the Natura 2000 site Lainzer Tiergarten near Vienna, Austria (238–402 m a.s.l., 48°10′ N, 16°12′ E). The grasslands were either mowed once a year or every second year, or not mowed since being established. Earthworms were assessed using the non-destructive octet electro-shocking method. Additionally, vegetation composition, soil conductivity, temperature and moisture were assessed. We found 13 earthworm species across all treatments, although their abundance was generally low with 6.1 ± 4.7 worms m−2. The total earthworm abundance and species diversity was higher in dry compared to fresh and moist grasslands but was not affected by mowing frequency. Endogeic earthworms (Aporrectodea caliginosa, Aporrectodea rosea) and epigeics (Lumbricus rubellus) were more tolerant to mowing than anecics (Lumbricus terrestris, Allolobophora longa). Since plant species richness was highest in annually mown grasslands and earthworm species richness was positively related to plant species numbers, we recommend regular, low-input management to promote above- and belowground biodiversity in these grasslands.

Local policies are part of the toolbox available to decision makers to improve air quality but their effectiveness is underevaluated and underreported. We evaluate the impact of the pedestrianization of a street in the city centre of Berlin on the local air pollution. Nitrogen dioxide (NO _2 ) was measured on the street where the policy was implemented and on two parallel streets using low-cost sensor systems supported by periodic calibrations against reference-grade instruments and constrained by passive samplers. Further measurements of NO _2 were conducted with a reference-grade instrument mounted on a mobile platform. The concentrations were evaluated against the urban background (UB) to isolate the policy-related signal from natural fluctuations, long-term trends and the COVID-19 lockdown. Our analysis shows that the most likely result of the intervention is a reduced NO _2 concentrations to the level of the UB on weekdays for the pedestrian zone. Kerbside NO _2 concentrations exhibited substantial differences to the concentrations measured at lampposts highlighting the difficulty for such measurements to capture personal exposure. The results have implications for policy, showing that an intervention on the local traffic patterns can possibly be effective in improving local air quality.

Background: Breast-implant-based reconstruction is one of the most performed procedures in plastic surgery. Despite the high durability of breast implants, various complications are accompanied with prolonged inlay duration, particularly implant rupture. Many aftereffects can be associated with implant rupture, especially siliconoma and BIA-ALCL. Without regular implant check-ups, implant-related issues may remain underrecognized. Here, we analyzed the number of breast implant carriers needing revisions and if patients adhered to annual implant follow-up recommendations. Methods: We reviewed 1128 breast procedures at the department of plastic surgery at the University Clinic of St. Poelten between August 1st 2018 and December 31st 2023. Patients were analyzed to see whether regular check-ups of their breast implants were performed. Additionally, implant-related complications were investigated, as well as if they were noticed by implant carriers. Results: Only 15.46% of breasts implants were regularly checked at least once a year in our cohort. The remaining 84.54% of patients consulted our department due to pain or aesthetic discomfort without periodical follow-ups. Most implant ruptures (73.8%) were diagnosed in patients consulting acutely due to pain or capsular contraction after an average of 17.36 ± 10.57 years. Routine examination uncovered 26.2% of silent implant ruptures without patients yet complaining of clinical symptoms as early as 15.44 ± 11.17 years. Conclusions: Most implant ruptures develop clinical symptoms as an indicator that removal is warranted. However, only regular follow-ups can identify implant complications several years earlier and possibly reduce severe sequalae such as BIA-ALCL. This highlights the significance and necessity of annual breast implant controls by surgeons and radiologic imaging to prevent devastating implant-associated aftereffects. [ABSTRACT FROM AUTHOR]

The oxidized form of Macrophage Migration Inhibitory Factor (oxMIF) has been identified as the disease-related isoform of MIF, exerting pathological functions in inflamed tissue. In this study, we aimed to explore the in vivo effects of the neutralizing anti-oxMIF antibody ON104 in a rat model of crescentic glomerulonephritis (CGN), to better understand its disease modifying activities. WKY rats received a single intravenous injection of a rabbit nephrotoxic serum (NTS), targeting rat glomerular basement membrane to induce CGN. On day 4 and day 6, ON104 was given intraperitoneally (i.p.) and on day 8 urine, blood and kidney tissue were collected. ON104 substantially attenuated the severity of CGN demonstrated by reduced proteinuria, hematuria, as well as lower levels of kidney injury molecule (KIM)-1. ON104 treatment preserved the glomerular morphology and suppressed crescent formation, a hallmark of the disease. On the cellular level, oxMIF neutralization by ON104 strongly reduced the number of macrophages and neutrophils within the inflamed kidneys. In vitro, we identified human neutrophils, but not monocytes, as main producers of oxMIF among total peripheral cells. The present study demonstrates that oxMIF is a pertinent therapeutic target in a model of CGN which mechanistically resembles human immune mediated CGN. In this model, neutralization of oxMIF by ON104 leads to an improvement in both urinary abnormalities and histological pathological characteristics of the disease. ON104, thus has the potential to become a novel disease-modifying drug for the treatment of glomerulonephritis and other inflammatory kidney diseases. [ABSTRACT FROM AUTHOR]

12-oxophytodienoate reductase 3 (OPR3) is a key enzyme in the biosynthesis of jasmonoyl-L-isoleucine, the receptor-active form of jasmonic acid and crucial signaling molecule in plant defense. OPR3 was initially crystallized as a self-inhibitory dimer, implying that homodimerization regulates enzymatic activity in response to biotic and abiotic stresses. Since a sulfate ion is bound to Y364, mimicking a phosphorylated tyrosine, it was suggested that dimer formation might be controlled by reversible phosphorylation of Y364 in vivo. To investigate OPR3 homodimerization and its potential physiological role in more detail, we performed analytical gel filtration and dynamic light scattering on wild-type OPR3 and three variants (R283D, R283E, and Y364P). The experiments revealed a rapid and highly sensitive monomer–dimer equilibrium for all OPR3 constructs. We crystallized all constructs with and without sulfate to examine its effect on the dimerization process and whether reversible phosphorylation of Y364 triggers homodimerization in vivo. All OPR3 constructs crystallized in their monomeric and dimeric forms independent of the presence of sulfate. Even variant Y364P, lacking the putative phosphorylation site, was crystallized as a self-inhibitory homodimer, indicating that Y364 is not required for dimerization. Generally, the homodimer is relatively weak, and our results raise doubts about its physiological role in regulating jasmonate biosynthesis. [ABSTRACT FROM AUTHOR]

Selecting the optimal settings for the production of rubber goods can be a very time-consuming and resource-intensive process. A promising method for optimizing rubber processing in a short period of time is the use of simulation routines. However, process simulations have only recently enabled meaningful predictions of not only the part's state of cure but also its mechanical characteristics. As a first approach, second-order polynomials were considered suitable for describing the properties of compression-molded parts. However, more precision is required for injection molding due to the narrower distribution of mechanical characteristics of parts produced at different vulcanization temperatures. This became evident when the approximation of mechanical data with second order models partly revealed significant failures of part behavior prediction. To tackle this issue, a combined approach for approximation is proposed in this contribution by means of logistic growth function in addition to second order polynomials. To feed the model, an experimental plan was designed for producing injection-molded parts from an SBR compound at various temperatures and to different degrees of cure. The parts obtained were then characterized mechanically, and the results were opposed to varying degrees of cure and extents of reaction to calculate the model coefficients. Once available, a simulation-based calculation of the mechanical part quality is possible. The comparison of test results from the simulation and the real process has shown a reliable prediction, as simulation results were found within the natural deviation of the real measurements. [ABSTRACT FROM AUTHOR]

Objectives: The capacity to assess male physical strength from facial cues may be adaptive given health and fitness‐related associations with muscular strength. Our study complements recent research on strength‐related face perceptions of male Maasai by applying the protocol to male European faces and assessors. Methods: Five distinct facial morphs calibrated for handgrip strength (HGS) were manufactured with geometric morphometrics performing regressions of the Procrustes shape coordinates on HGS in a sample of 26 European men (18–32 years). Young adult men and women (n = 445) rated these morphs on physical strength, attractiveness, and aggressiveness. Results: Facial morphs calibrated to lower HGS were rated as less strong, less attractive, and more aggressive than those calibrated to higher HGS. Medium levels of HGS were associated with the highest attractiveness ratings. Conclusions: The rating patterns of physical strength, attractiveness, and aggressiveness for European male facial morphs exhibit similarity to previous ratings of Maasai male faces. Therefore, the current findings corroborate the suggestion of a common mechanism for social attributions based on facial cues to physical strength, modulated by local ecology and societal context. [ABSTRACT FROM AUTHOR]