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- IZKF Nachwuchsgruppe Geweberegeneration für muskuloskelettale Erkrankungen (5)
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Risk prediction in patients with heart failure (HF) is essential to improve the tailoring of preventive, diagnostic, and therapeutic strategies for the individual patient, and effectively use health care resources. Risk scores derived from controlled clinical studies can be used to calculate the risk of mortality and HF hospitalizations. However, these scores are poorly implemented into routine care, predominantly because their calculation requires considerable efforts in practice and necessary data often are not available in an interoperable format. In this work, we demonstrate the feasibility of a multi-site solution to derive and calculate two exemplary HF scores from clinical routine data (MAGGIC score with six continuous and eight categorical variables; Barcelona Bio-HF score with five continuous and six categorical variables). Within HiGHmed, a German Medical Informatics Initiative consortium, we implemented an interoperable solution, collecting a harmonized HF-phenotypic core data set (CDS) within the openEHR framework. Our approach minimizes the need for manual data entry by automatically retrieving data from primary systems. We show, across five participating medical centers, that the implemented structures to execute dedicated data queries, followed by harmonized data processing and score calculation, work well in practice. In summary, we demonstrated the feasibility of clinical routine data usage across multiple partner sites to compute HF risk scores. This solution can be extended to a large spectrum of applications in clinical care.
Chemical warfare or terrorism attacks with organophosphates may place intoxicated subjects under immediate life-threatening and psychologically demanding conditions. Antidotes, such as the oxime HI-6, which must be formulated as a powder for reconstitution reflecting the molecule’s light sensitivity and instability in aqueous solutions, dramatically improve recovery—but only if used soon after exposure. Muscle tremors, anxiety, and loss of consciousness after exposure jeopardize proper administration, translating into demanding specifications for the dissolution of HI-6. Reflecting the patients’ catastrophic situation and anticipated desire to react immediately to chemical weapon exposure, the dissolution should be completed within ten seconds. We are developing multi-dose and single-dose autoinjectors to reliably meet these dissolution requirements. The temporal and spatial course of dissolution within the various autoinjector designs was profiled colorimetrically. Based on these colorimetric insights with model dyes, we developed experimental setups integrating online conductometry to push experiments toward the relevant molecule, HI-6. The resulting blueprints for autoinjector designs integrated small-scale rotor systems, boosting dissolution across a wide range of viscosities, and meeting the required dissolution specifications driven by the use of these drug products in extreme situations.
Husserl’s taxonomy of action
(2022)
In the present article I discuss, in confrontation with the most recent studies on Husserl’s phenomenology of acting and willing, the taxonomy of action that is collected in the volume ‘Wille und Handlung’ of the Husserliana edition Studien zur Struktur des Bewussteins. In so doing, I first present Husserl’s universal characterization of action (Handlung) as a volitional process (willentlicher Vorgang). Then, after clarifying what it means for a process to have a character of volitionality (Willentlichkeit), I illustrate the various types of actions, which Husserl distinguishes as ‘straightforward’ (schlicht) or ‘deciding’ (entscheidend), ‘primary’ (primär) or ‘secondary’ (sekundär), ‘inner’ (innere) or ‘outer’ (äußere), ‘immediate’ (unmittelbar) or mediate (mittelbar), ‘simple’ (einfach) or ‘compound’ (zusammengesetzt). Finally, I consider Husserl’s discussion of the direction and foundation of action.
Charge transfer in ternary solar cells employing two fullerene derivatives: where do electrons go?
(2022)
Earlier reports demonstrated that ternary organic solar cells (OSC) made of donor polymers (D) blended with different mixtures of fullerene acceptors (A : A) performed very similarly. This finding is surprising, as the corresponding fullerene LUMO levels are slightly different, which might result in decisive differences in the charge transfer step. We investigate ternary OSC (D : A : A) made of the donor polymer P3HT with stoichiometric mixtures of different fullerene derivatives, PC\(_{60}\)BM : PC\(_{70}\)BM and PC\(_{70}\)BM : IC\(_{60}\)BA, respectively. Using quantitative electron paramagnetic resonance (EPR) we can distinguish between positive and negative polarons, localized on the specific molecules. We found that after the initial charge transfer step, the electrons are re-distributed over two nearby acceptors in agreement with their stoichiometry and their relative LUMO energy difference. Remarkably, the measured ΔLUMO differences in fullerene mixtures are reduced by an order of magnitude compared to that of the pristine materials, i. e., below 1 meV for PC\(_{60}\)BM : PC\(_{70}\)BM and (20±5) meV for PC\(_{70}\)BM : IC\(_{60}\)BA. Furthermore, we found that this reduced ΔLUMO explains the shift in open circuit voltage for D : A : A organic solar cells. We attribute these findings to hybridization, leading to an effective fullerene LUMO. Consequently, multi-acceptor blends are indeed a viable option for photodetectors and solar cells, as they combine the best electron acceptor and light absorbing properties.
The A\(_{2A}\) adenosine receptor (A\(_{2A}\)AR) is one of the four subtypes activated by nucleoside adenosine, and the molecules able to selectively counteract its action are attractive tools for neurodegenerative disorders. In order to find novel A\(_{2A}\)AR ligands, two series of compounds based on purine and triazolotriazine scaffolds were synthesized and tested at ARs. Compound 13 was also tested in an in vitro model of neuroinflammation. Some compounds were found to possess high affinity for A\(_{2A}\)AR, and it was observed that compound 13 exerted anti-inflammatory properties in microglial cells. Molecular modeling studies results were in good agreement with the binding affinity data and underlined that triazolotriazine and purine scaffolds are interchangeable only when 5- and 2-positions of the triazolotriazine moiety (corresponding to the purine 2- and 8-positions) are substituted.
Fabry disease (FD) is a rare life-threatening disorder caused by deficiency of the alpha-galactosidase A (GLA) enzyme with a characteristic pain phenotype. Impaired GLA production or function leads to the accumulation of the cell membrane compound globotriaosylceramide (Gb3) in the neurons of the dorsal root ganglia (DRG) of FD patients. Applying immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT PCR) analysis on DRG tissue of the GLA knockout (KO) mouse model of FD, we address the question of how Gb3 accumulation may contribute to FD pain and focus on the immune system and pain-associated ion channel gene expression. We show a higher Gb3 load in the DRG of young (<6 months) (p < 0.01) and old (≥12 months) (p < 0.001) GLA KO mice compared to old wildtype (WT) littermates, and an overall suppressed immune response in the DRG of old GLA KO mice, represented by a reduced number of CD206\(^+\) macrophages (p < 0.01) and lower gene expression levels of the inflammation-associated targets interleukin(IL)1b (p < 0.05), IL10 (p < 0.001), glial fibrillary acidic protein (GFAP) (p < 0.05), and leucine rich alpha-2-glycoprotein 1 (LRG1) (p < 0.01) in the DRG of old GLA KO mice compared to old WT. Dysregulation of immune-related genes may be linked to lower gene expression levels of the pain-associated ion channels calcium-activated potassium channel 3.1 (KCa3.1) and transient receptor potential ankyrin 1 channel (TRPA1). Ion channel expression might further be disturbed by impaired sphingolipid recruitment mediated via the lipid raft marker flotillin-1 (FLOT1). This impairment is represented by an increased number of FLOT1\(^+\) DRG neurons with a membranous expression pattern in old GLA KO mice compared to young GLA KO, young WT, and old WT mice (p < 0.001 each). Further, we provide evidence for aberrant behavior of GLA KO mice, which might be linked to dysregulated ion channel gene expression levels and disturbed FLOT1 distribution patterns. Behavioral testing revealed mechanical hypersensitivity in young (p < 0.01) and old (p < 0.001) GLA KO mice compared to WT, heat hypersensitivity in young GLA KO mice (p < 0.001) compared to WT, age-dependent heat hyposensitivity in old GLA KO mice (p < 0.001) compared to young GLA KO mice, and cold hyposensitivity in young (p < 0.001) and old (p < 0.001) GLA KO mice compared to WT, which well reflects the clinical phenotype observed in FD patients.
Environmental gradients generate and maintain biodiversity on Earth. Mountain slopes are among the most pronounced terrestrial environmental gradients, and the elevational structure of species and their interactions can provide unique insight into the processes that govern community assembly and function in mountain ecosystems. We recorded bumble bee–flower interactions over 3 years along a 1400‐m elevational gradient in the German Alps. Using nonlinear modeling techniques, we analyzed elevational patterns at the levels of abundance, species richness, species β‐diversity, and interaction β‐diversity. Though floral richness exhibited a midelevation peak, bumble bee richness increased with elevation before leveling off at the highest sites, demonstrating the exceptional adaptation of these bees to cold temperatures and short growing seasons. In terms of abundance, though, bumble bees exhibited divergent species‐level responses to elevation, with a clear separation between species preferring low versus high elevations. Overall interaction β‐diversity was mainly caused by strong turnover in the floral community, which exhibited a well‐defined threshold of β‐diversity rate at the tree line ecotone. Interaction β‐diversity increased sharply at the upper extreme of the elevation gradient (1800–2000 m), an interval over which we also saw steep decline in floral richness and abundance. Turnover of bumble bees along the elevation gradient was modest, with the highest rate of β‐diversity occurring over the interval from low‐ to mid‐elevation sites. The contrast between the relative robustness bumble bee communities and sensitivity of plant communities to the elevational gradient in our study suggests that the strongest effects of climate change on mountain bumble bees may be indirect effects mediated by the responses of their floral hosts, though bumble bee species that specialize in high‐elevation habitats may also experience significant direct effects of warming.
Patterns of resource use by animals can clarify how ecological communities have assembled in the past, how they currently function and how they are likely to respond to future perturbations. Bumble bees (Hymentoptera: Bombus spp.) and their floral hosts provide a diverse yet tractable system in which to explore resource selection in the context of plant–pollinator networks. Under conditions of resource limitation, the ability of bumble bees species to coexist should depend on dietary niche overlap. In this study, we report patterns and dynamics of floral morphotype preferences in a mountain bumble bee community based on ~13 000 observations of bumble bee floral visits recorded along a 1400 m elevation gradient. We found that bumble bees are highly selective generalists, rarely visiting floral morphotypes at the rates predicted by their relative abundances. Preferences also differed markedly across bumble bee species, and these differences were well-explained by variation in bumble bee tongue length, generating patterns of preference similarity that should be expected to predict competition under conditions of resource limitation. Within species, though, morphotype preferences varied by elevation and season, possibly representing adaptive flexibility in response to the high elevational and seasonal turnover of mountain floral communities. Patterns of resource partitioning among bumble bee communities may determine which species can coexist under the altered distributions of bumble bees and their floral hosts caused by climate and land use change.
Agrochemicals like systemic active ingredients (AI) need to penetrate the outermost barrier of the plant, known as the plant cuticle, to reach its right target site. Therefore, adjuvants are added to provide precise and efficient biodelivery by i.a. modifying the cuticular barrier and increasing the AI diffusion. This modification process is depicted as plasticization of the cuticular wax which mainly consists of very long-chain aliphatic (VLCA) and cyclic compounds. Plasticization of cuticular waxes is pictured as an increase of amorphous domains and/or a decrease of crystalline fractions, but comprehensive, experimental proof is lacking to date. Hence, the objective of this thesis was to i) elucidate the permeation barrier of the plant cuticle to AIs in terms of the different wax fractions and ii) holistically investigate the modification of this barrier using selected oil and surface active adjuvants, an aliphatic leaf wax and an artificial model wax. Therefore, the oil adjuvant methyl oleate (MeO) and other oil derivatives like methyl linolenate (MeLin), methyl stearate (MeSt) and oleic acid (OA) were selected. Three monodisperse, non-ionic alcohol ethoxylates with increasing ethylene oxide monomer (EO) number (C10E2, C10E5, C10E8) were chosen as representatives of the group of surface active agents (surfactants). Both adjuvant classes are commonly used as formulation aids for agrochemicals which are known for its penetration enhancing effect. The aliphatic leaf wax of Schefflera elegantissima was selected, as well as a model wax comprising the four most abundant cuticular wax compounds of this species. Permeation, transpiration and penetration studies were conducted using enzymatically isolated cuticles of Prunus laurocerasus and Garcinia xanthochymus.
Cuticular permeability to the three organic solutes theobromine, caffeine and azoxystrobin differing in lipophilicity was measured using a steady-state two-chamber system separated by the isolated leaf cuticles of the evergreen species P. laurocerasus and G. xanthochymus. Treating the isolated cuticles with methanol selectively removed the cyclic fraction, and membrane permeability to the organic compounds was not altered. In contrast, fully dewaxing the membranes using chloroform resulted in a statistically significant increase in permeance for all compounds and species, except caffeine with cuticles of G. xanthochymus due to a matrix-specific influence on the semi-hydrophilic compound. Crystalline regions may reduce the accessibility to the lipophilic pathway across the waxes and also block hydrophilic domains in the cuticle.
Knowing that the aliphatic wax fraction builds the cuticular diffusion barrier, the influence of the adjuvants on the phase behaviour of an aliphatic cuticular wax as well as the influence on the cuticular penetration of AIs were investigated. Differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) were selected to investigate the phase behaviour and thus possible plasticization of pure Schefflera elegantissima leaf wax, its artificial model wax comprising the four most abundant compounds (n-nonacosane, n-hentriacontane, 1-triacontanol and 1-dotriacontanol) and wax adjuvant mixtures. DSC thermograms showed a shift of the melting ranges to lower temperatures and decreased absolute values of the total enthalpy of transition (EOT) for all adjuvant leaf wax blends at 50 % (w/w) adjuvant proportion. The highest decrease was found for C10E2 followed by MeO > OA and C10E8 > MeLin > MeSt. The aliphatic crystallinity determined by FTIR yielded declined values for the leaf and the artificial wax with 50 % MeO. All other adjuvant leaf wax blends did not show a significant decrease of crystallinity. As it is assumed that the cuticular wax is formed by crystalline domains which consist of aliphatic hydrocarbon chains and an amorphous fraction comprising aliphatic chain ends and functional groups, the plasticizers are depicted as wax disruptors influencing amorphization and/or crystallization. The adjuvants can increase crystalline domains using the aliphatic tail whereas their more hydrophilic head is embedded in the amorphous wax fraction. DSC and FTIR showed similar trends using the leaf wax and the model wax in combination with the adjuvants.
In general, cuticular transpiration increased after adding the pure adjuvants to the surface of isolated cuticles or leaf envelopes. As waxes build the cuticular permeation barrier not only to AIs but also to water, the adjuvant wax interaction might affect the cuticular barrier properties leading to increased transpiration. Direct evidence for increased AI penetration with the adjuvants was given using isolated cuticles of P. laurocerasus in combination with the non-steady-state setup simulation of foliar penetration (SOFP) and caffeine at relative humidity levels (RH) of 30, 50 and 80 %. The increase in caffeine penetration was much more pronounced using C10E5 and C10E8 than MeO but always independent of RH. Only C10E2 exhibited an increased penetration enhancing effect positively related to RH. The role of the molecular structure of adjuvants in terms of humectant and plasticizer properties are discussed.
Hence, the current work shows for the first time that the cuticular permeation barrier is associated with the VLCAs rather than the cyclic fraction and that adjuvants structurally influence this barrier resulting in penetration enhancing effects. Additionally, this work demonstrates that an artificial model wax is feasible to mimic the wax adjuvant interaction in conformity with a leaf wax, making it feasible for in-vitro experiments on a larger scale (e.g. screenings). This provides valuable knowledge about the cuticular barrier modification to enhance AI penetration which is a crucial factor concerning the optimization of AI formulations in agrochemistry.
Latency is an inherent problem of computing systems. Each computation takes time until the result is available. Virtual reality systems use elaborated computer resources to create virtual experiences. The latency of those systems is often ignored or assumed as small enough to provide a good experience.
This cumulative thesis is comprised of published peer reviewed research papers exploring the behaviour and effects of latency. Contrary to the common description of time invariant latency, latency is shown to fluctuate. Few other researchers have looked into this time variant behaviour. This thesis explores time variant latency with a focus on randomly occurring latency spikes. Latency spikes are observed both for small algorithms and as end to end latency in complete virtual reality systems. Most latency measurements gather close to the mean latency with potentially multiple smaller clusters of larger latency values and rare extreme outliers. The latency behaviour differs for different implementations of an algorithm. Operating system schedulers and programming language environments such as garbage collectors contribute to the overall latency behaviour. The thesis demonstrates these influences on the example of different implementations of message passing.
The plethora of latency sources result in an unpredictable latency behaviour. Measuring and reporting it in scientific experiments is important. This thesis describes established approaches to measuring latency and proposes an enhanced setup to gather detailed information. The thesis proposes to dissect the measured data with a stacked z-outlier-test to separate the clusters of latency measurements for better reporting.
Latency in virtual reality applications can degrade the experience in multiple ways. The thesis focuses on cybersickness as a major detrimental effect. An approach to simulate time variant latency is proposed to make latency available as an independent variable in experiments to understand latency's effects. An experiment with modified latency shows that latency spikes can contribute to cybersickness. A review of related research shows that different time invariant latency behaviour also contributes to cybersickness.
When interacting with sophisticated digital technologies, people often fall back on the same interaction scripts they apply to the communication with other humans—especially if the technology in question provides strong anthropomorphic cues (e.g., a human-like embodiment). Accordingly, research indicates that observers tend to interpret the body language of social robots in the same way as they would with another human being. Backed by initial evidence, we assumed that a humanoid robot will be considered as more dominant and competent, but also as more eerie and threatening once it strikes a so-called power pose. Moreover, we pursued the research question whether these effects might be accentuated by the robot’s body size. To this end, the current study presented 204 participants with pictures of the robot NAO in different poses (expansive vs. constrictive), while also manipulating its height (child-sized vs. adult-sized). Our results show that NAO’s posture indeed exerted strong effects on perceptions of dominance and competence. Conversely, participants’ threat and eeriness ratings remained statistically independent of the robot’s depicted body language. Further, we found that the machine’s size did not affect any of the measured interpersonal perceptions in a notable way. The study findings are discussed considering limitations and future research directions.
Purpose: To treat patients with tricompartimental knee osteoarthritis (OA), a customized cruciate-retaining total knee arthroplasty (CCR-TKA) system can be used, including both individualized instrumentation and implants. The objective of this monocentric cohort study was to analyze patient-reported and functional outcomes in a series of patients implanted with the second generation of this customized implant. Methods: At our arthroplasty center, we prospectively recruited a cohort of patients with tricompartmental gonarthrosis to be treated with total knee replacement (TKA) using a customized cruciate-retaining (CCR) implant design. Inclusion criteria for patients comprised the presence of intact posterior cruciate and collateral ligaments and a knee deformity that was restricted to <15° varus, valgus, or flexion contracture. Patients were assessed for their range of motion (ROM), Knee Society Score (KSS), Western Ontario and McMaster University osteoarthritis index (WOMAC), and short form (SF)-12 physical and mental scores, preoperatively, at 3 and 6 months, as well as at 1, 2, 3, and 5 years of follow-up (FU) postoperatively. Results: The average age of the patient population was 64 years (range: 40–81), the average BMI was 31 (range: 23–42), and in total, 28 female and 45 male patients were included. Implant survivorship was 97.5% (one septic loosening) at an average follow-up of 2.5 years. The KSS knee and function scores improved significantly (p < 0.001) from, respectively, 41 and 53 at the pre-operative visit, to 92 and 86, respectively, at the 5-year post-operative time point. The SF-12 Physical and Mental scores significantly (p < 0.001) improved from the pre-operative values of 28 and 50, to 50 and 53 at the 5-year FU, respectively. Patients experienced significant improvements in their overall knee range of motion, from 106° at the preoperative visit to 122°, on average, 5 years postoperatively. The total WOMAC score significantly (p < 0.001) improved from 49.1 preoperatively to 11.4 postoperatively at 5-year FU. Conclusions: Although there was no comparison to other implants within this study, patients reported high overall satisfaction and improvement in functional outcomes within the first year from surgery, which continued over the following years. These mid-term results are excellent compared with those reported in the current literature. Comparative long-term studies with this device are needed. Level of evidence 3b (individual case–control study).
Virtual environments (VEs) can evoke and support emotions, as experienced when playing emotionally arousing games. We theoretically approach the design of fear and joy evoking VEs based on a literature review of empirical studies on virtual and real environments as well as video games’ reviews and content analyses. We define the design space and identify central design elements that evoke specific positive and negative emotions. Based on that, we derive and present guidelines for emotion-inducing VE design with respect to design themes, colors and textures, and lighting configurations. To validate our guidelines in two user studies, we 1) expose participants to 360° videos of VEs designed following the individual guidelines and 2) immerse them in a neutral, positive and negative emotion-inducing VEs combining all respective guidelines in Virtual Reality. The results support our theoretically derived guidelines by revealing significant differences in terms of fear and joy induction.
Purpose
Patients suffering from aggressive systemic peripheral lymphoma with primary central nervous system involvement (PCL) are a rare and sparsely investigated population. Recommended treatment regimens include a combination of intrathecal and systemic chemotherapy as well as whole brain radiotherapy while offering relatively poor survival.
Methods
We conducted a single-center retrospective study that analyzed safety and outcome of 4 + 4 cycles Rituximab (R)-CHOP and R-high-dose Methotrexate (HD-MTX) for newly diagnosed, transplant-eligible patients ("Ping-Pong"), followed by Cytarabine (AraC)/Thiotepa (TT), BCNU/TT, and autologous hematologic stem cell transplantation (aHSCT). We retrospectively analyzed a set of 16 patients with high-intermediate or high-risk IPI status.
Results
Overall response rate to Ping-Pong was 100% measured by CT/MRI, including 93.75% complete remissions after BCNU/TT followed by PBSCT. One patient failed to qualify for high-dose chemotherapy due to progression when receiving Cytarabine/TT. All patients experienced grade III adverse events, 3 of them a grade IV adverse event. Estimated progression-free survival is 93.75% after a 4.8-year follow-up currently.
Conclusion
Our study suggests high effectivity of R-CHOP with mid-cycle MTX with aHSCT consolidation towards acceptable OS results in this challenging patient population.
There has been a steady increase (annual percentage growth rate of 19.2%, average of 18.3 citations per document) in capsule endoscopy (CE) publications from a global, interdisciplinary research community on a growing range of CE applications over the last 20+ years. We here present the status of CE as a field of research, tracing its evolution over time and providing insight into its potential for diagnostics, prevention and treatment of gastrointestinal (GI) tract diseases. To portray the development of the CE research landscape in the 2000–2021 time span, we analyzed 5764 scientific publications. Analyses were performed using the R language and environment for statistical computing and graphics and VOSviewer, a software developed for scientific literature analysis by scientometricians. The aim of this paper is to provide a wide comprehensive analysis of the trends in CE publications. We thus performed subgroup analysis on the selected papers, including indications, annual percentage growth rate, average citations per document, most publications from research areas/interdisciplinary field of the articles, geography, collaboration networks through institutions, specific clinical keywords and device type. The firm increase in CE publications over the last two decades highlights the overall strength of the technology in GI applications. Furthermore, the introduction to the field of artificial intelligence (AI) tools has been promoting a range of technological advances that keep on affecting the diagnostic potential of CE.
There is a lack of standardized treatment recommendations for orofacial granulomatosis, a chronic inflammatory condition aetiologically related to Crohn disease. To assess clinical baseline parameters and treatment strategies, we retrospectively analysed 61 consecutive cases from our institutional database. Disease-related functional/psychological impairment and long-term outcomes were descriptively evaluated using a standardized self-reporting questionnaire. The median age of patients was 45 (7–77) years. Oral steroids were given in 41.0% of cases, but only produced short-term disease control, while response to steroid-sparing agents was inconsistent. Only a minority of patients reported relevant disease-related functional impairment in eating (21.7%) or speaking (4.3%), but the majority perceived psychological distress due to the cosmetic aspects of the disease (69.6%), comments from others (65.2%) and/or general anxiety/insecurity (73.9%). Regardless of the initial treatment, long-term outcomes after 71 months (range 7–304 months) were beneficial, with most patients being in complete remission (52.2%) or reporting only mild residual swelling (43.5%).
Background
Correct recognition of risk factors enables individualized management and treatment of venom allergic patients.
Methods
Systematic research and review of current literature regarding the risk of (1) severe sting-induced anaphylaxis, (2) anaphylactic adverse event during venom immunotherapy (VIT), and (3) treatment failure.
Results and discussion
(1) Mastocytosis is the most important risk factor for severe sting-induced anaphylaxis. Hereditary α‑tryptasemia was recently identified as a genetic predictor of severe reactions. Older age is clearly associated with an increased risk; the respective impact of defined cardiovascular comorbidities has yet to be determined. Recent data do not support an aggravation of venom-induced anaphylaxis by intake of β‑blockers or angiotensin-converting enzyme (ACE) inhibitors. A higher risk in men can be attributed to more intensive exposure to stinging insects. (2) Anaphylactic side effects of VIT are most common during the buildup phase, particularly in the course of (ultra-)rush protocols involving a high number of injections and high cumulative daily doses. They are significantly more frequent during honeybee compared to Vespula VIT. Data supporting a negative effect of mastocytosis on the tolerability of VIT are scarce. Older age and cardiovascular medication are not associated with a higher incidence of VIT-induced anaphylaxis. (3) Relapsing anaphylactic reactions to both field and challenge stings are significantly more common during and after honeybee compared to Vespula VIT. Reports of severe field-sting reactions in mastocytosis patients suggest an increased risk of treatment failure which may be overcome by higher maintenance doses and longer duration of VIT.
To counteract insect decline, it is essential to understand the underlying causes, especially for key pollinators such as nocturnal moths whose ability to orientate can easily be influenced by ambient light conditions. These comprise natural light sources as well as artificial light, but their specific relevance for moth orientation is still unknown. We investigated the influence of moonlight on the reproductive behavior of privet hawkmoths (Sphinx ligustri) at a relatively dark site where the Milky Way was visible while the horizon was illuminated by distant light sources and skyglow. We show that male moths use the moon for orientation and reach females significantly faster with increasing moon elevation. Furthermore, the choice of flight direction depended on the cardinal position of the moon but not on the illumination of the horizon caused by artificial light, indicating that the moon plays a key role in the orientation of male moths.
Background: Muscle injuries are common in humans and are often associated with irrecoverable damage and disability. Upon muscle injury, TNF-α signaling pathways modulate the healing process and are predominantly associated with tissue degradation. In this study we assumed that TNF-α inhibition could reduce the TNF-α-associated tissue degradation after muscle injury. Materials and methods: Therefore, the left soleus muscle of 42 male Wistar rats was injured using a standardized open muscle injury model. All rats were treated immediately after injury either with infliximab (single i.p. injection; 10 mg/kg b.w.) or saline solution i.p. Final measurements were conducted at day one, four, and 14 post injury. The muscle force, the muscle cell proliferation, the muscle cell coverage as well as the myofiber diameter served as read out parameters of our experiment. Results: Systemic application of infliximab could significantly reduce the TNF-α levels in the injured muscle at day four upon trauma compared to saline treated animals. The ratio of muscle weight to body weight was increased and the twitch muscle force showed a significant rise 14 days after trauma and TNF-α inhibition. Quantification of myofiber diameter in the penumbra zone showed a significant difference between both groups at day one and four after injury, indicated by muscle hypertrophy in the infliximab group. Planimetric analysis of the injured muscle at day 14 revealed increased muscle tissue fraction in the infliximab group compared to the control animals. Muscle cell proliferation did not differ between both groups. Conclusions: These data provide evidence that the TNF-α blockade positively regulates the restauration of skeletal muscles upon injury.