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Objectives The objective of this study was to assess the quality of ECG recordings and the concordance between the automatic detection of cardiac arrhythmia episodes by a patch ECG and an insertable cardiac monitor.Design Prospective cohort study.Setting and participants Endurance athletes diagnosed with paroxysmal atrial fibrillation (AF) and no other relevant comorbidities participating in a randomised controlled trial on the effects of training adaption.Methods A patch ECG (ECG247 Smart Heart Sensor) was sent to 29 non-elite endurance athletes with clinical paroxysmal AF. ECG247 continuously monitors, detects and categorises cardiac arrhythmias. The participants were simultaneously monitored with an insertable cardiac monitor (Confirm Rx, Abbott). ECG recording quality was assessed by an experienced physician. Training sessions were monitored using sports watches.Results Out of 29 invited athletes, 14 athletes (mean age 60.4 years, 2 women) made use of the patch ECG and were monitored for a total of 2987 hours and a median of 14 (range 1–17) days. During this period, the athletes performed a total of 112 training sessions. ECG quality varied between athletes and by type of exercise, with poor quality in 16% and 40% of recordings during cross-country skiing and running, respectively. In two athletes, the patch ECG detected AF episodes that were confirmed with insertable cardiac monitor recordings. One technical artefact was falsely classified as ventricular tachycardia by the ECG247 Smart Heart Sensor system.Conclusion Monitoring with patch ECG was feasible in endurance athletes, but ECG recording quality varied between athletes and by type of exercise.Trial registration NCT04991337 (for the related randomised controlled trial).

The choice of materials challenges the development of Magnetic Resonance Imaging (MRI) phantoms and, to date, is mainly limited to water-filled compartments or gel-based components. Recently, solid materials have been introduced through additive manufacturing (AM) to mimic complex geometrical structures. Nonetheless, no such manufactured solid materials are available with controllable MRI contrast to mimic organ substructures or lesion heterogeneities. Here, we present a novel AM design that allows MRI contrast manipulation by varying the partial volume contribution to a ROI/voxel of MRI-visible material within an imaging object. Two sets of 11 cubes and three replicates of a spherical tumour model were designed and printed using AM. Most samples presented varying MRI-contrast in standard MRI sequences, based mainly on spin density and partial volume signal variation. A smooth and continuous MRI-contrast gradient could be generated in a single-compartment tumour model. This concept supports the development of more complex MRI phantoms that mimic the appearance of heterogeneous tumour tissues.

Trial registration number NCT04991337.Study protocol version 4.7 (Date 9 March 2023).

Aims Endurance sport practice is associated with a high prevalence of atrial fibrillation (AF), which increases the risk of stroke in the general population. However, stroke risk in endurance athletes with AF is sparsely investigated. Most studies have been limited by design and are largely restricted to younger and middle-aged populations. Thus, we aimed to investigate AF and stroke risk in older athletes exposed to prolonged endurance training.Method During a 10-year period, 505 male athletes aged ≥65 years frequently participating in a long-distance ski race were compared with 1867 men of the same age from the general population. The main exposure was endurance sport practice with self-reported AF and stroke as outcomes. Stroke risk was further examined by joint modelling of AF and endurance practice. Statistical analysis was conducted with a modified Poisson model.Results Athletes (median age: 68, range: 65–90) participated in a long-distance ski race over a median of 14 years (range: 1–53). Prevalence (28.5% vs 17.8%) and adjusted risk of AF (risk ratio (RR): 1.88, 95% CI: 1.49 to 2.37) were higher in athletes compared with non-athletes, whereas the prevalence (5.4% vs 9.7%) and risk of stroke were lower (RR: 0.60, 95% CI: 0.37 to 0.95). Compared with athletes without AF, risk of stroke was twofold in athletes (RR: 2.38, 95% CI: 1.08 to 5.24) and nearly fourfold in non-athletes (RR: 3.87, 95% CI: 1.98 to 7.57) with AF.Conclusion Although older male endurance athletes experienced an increased risk of AF, the long-term risk of stroke was substantially reduced compared with non-athletes.

Quality assurance (QA) in magnetic resonance imaging (MRI) requires test objects. ‘Phantoms’ provided by MR manufacturers are homogeneously filled spheres or cylinders, and commercially available products are often too small for abdominal imaging, particularly for enlarged polycystic kidneys. Here we present the design, manufacturing and testing of a dedicated, yet versatile, abdominal MRI phantom, that can be reproduced with relatively low costs. The phantom mimics a human abdomen in size and shape and comprises seven test fluids, representing various tissue types at 3 T. The conductivity and permittivity of the test fluids match the average abdomen and kidney with a relative permittivity (ε) 65 and 72 as well as conductivity 0.6 and 0.7 S/m, respectively. The T1 and T2 relaxation times cover healthy average abdomen and kidney tissue values (T1(abd): 856 ms and T1(kid): 1,106 ms; T2(abd): 52 ms and T2(kid): 67 ms), intermediate (T1: 1,183 ms and 1,271 ms; T2: 128 and 189 ms), and disease values for (polycystic) kidney (T1: 1,428 ms, 1,561 ms and 1763 ms; T2: 319 ms, 424 and 647 ms). T1 and T2 relaxation times were stable over 73 weeks. Our reasonably priced, durable and reproducible abdominal phantom enables single and multi-center QA for future collaborative studies aiming for various challenges around abdominal and, particularly, kidney imaging.

Background and Aim: Numerous studies have found benefits of omega-3 polyunsaturated fatty acids (PUFAs), namely, for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in dogs. The objective of the present study was to assess the efficacy of dietary inclusion of equal amounts of omega-3 FAs in phospholipid (PL) from krill meal to triglyceride structure from fish oil to increase the omega-3 FA profile in red blood cells (RBCs) in dogs. Materials and Methods: Ten adult Alaskan Huskies of both genders were supplemented with daily 1.7 g EPA and DHA from krill meal for 6 weeks, while another ten dogs received 1.7 g EPA and DHA from fish oil. FA and omega-3 index measurements of the two groups were taken after 0, 3, and 6 weeks for comparison. Results: It was mainly the EPA levels that increased in the krill meal group (from 1.84% to 4.42%) compared to the fish oil group (from 1.90% to 2.46%) (p

Acetogens play a very important role in anaerobic digestion and are essential in ensuring process stability. Despite this, targeted studies of the acetogenic community in biogas processes remain limited. Some efforts have been made to identify and understand this community, but the lack of a reliable molecular analysis strategy makes the detection of acetogenic bacteria tedious. Recent studies suggest that screening of bacterial genetic material for formyltetrahydrofolate synthetase (FTHFS), a key marker enzyme in the Wood-Ljungdahl pathway, can give a strong indication of the presence of putative acetogens in biogas environments. In this study, we applied an acetogen-targeted analyses strategy developed previously by our research group for microbiological surveillance of commercial biogas plants. The surveillance comprised high-throughput sequencing of FTHFS gene amplicons and unsupervised data analysis with the AcetoScan pipeline. The results showed differences in the acetogenic community structure related to feed substrate and operating parameters. They also indicated that our surveillance method can be helpful in the detection of community changes before observed changes in physico-chemical profiles, and that frequent high-throughput surveillance can assist in management towards stable process operation, thus improving the economic viability of biogas plants. To our knowledge, this is the first study to apply a high-throughput microbiological surveillance approach to visualise the potential acetogenic population in commercial biogas digesters.

Background and Aim: Choline and its metabolites have multiple physiological roles in the body, which are important for muscle function, memory, methylation reactions, and hepatic lipid transport. This study aimed to investigate, if inclusion of phosphatidylcholine (PC) from Antarctic krill (Euphausia superba) can increase the concentration of choline and its metabolites in plasma of sled dogs in comparison to a control group. Materials and Methods: Ten adult Alaskan Huskies of both genders were supplemented with PC from 8% dietary krill meal inclusion for 6 weeks, while another ten dogs received no krill meal supplementation. Blood measurements of the two groups were taken at baseline and end of the study and compared for choline and its metabolite concentrations. Results: The choline concentration of the krill meal-supplemented dogs was significantly higher after 6 weeks of krill meal feeding compared to the control group (mean increase = 4.53 μmol/L in the supplemented versus 1.21 μmol/L in the control group, p=0.014). Furthermore, krill meal-supplemented dogs showed significantly more pronounced increases in betaine (p

Psychotria acutiflora was described in 1830 by de Candolle in his Prodromus, and was based on a single collection by Thaddäus Haenke from near Guayaquil, Ecuador. Although the identity of the name has never been studied since its original publication, it is currently treated as a species endemic to Ecuador. It is shown here that the type of the name belongs to Bertiera procumbens, which was described much later. Therefore, the new combination Bertiera acutiflora is provided here for the Columbian and Ecuadorian endemic and a lectotype is designated for the name.

Abstract Adrenomedullin (ADM) is a multifaceted peptide hormone involved in numerous physiological processes, including vascular stability, vasodilation, angiogenesis, and anti-inflammatory responses. The processing of ADM results in several fragments, including midregional proadrenomedullin (MR-proADM), and glycine-extended ADM (ADM-Gly) and bioactive ADM (bio-ADM). MR-proADM, the stable ADM fragment, and bio-ADM, the active form of ADM with a short half-life, have been shown to be potent biomarkers in a variety of pathologies. ADM-Gly, the direct precursor of bio-ADM, is a predominant form in human plasma, but remains less understood and least investigated. This study presents the development of a specific immunoluminometric assay for the quantification of ADM-Gly and offers a robust one-step approach for large-scale sample screening. Applied to human and rodent plasma, it elucidates the release kinetics and plasma half-life of ADM-Gly. Our findings confirm the predominance of ADM-Gly in healthy individuals and its significant release under pathological conditions. Our immunoluminometric assay enables precise measurement of ADM-Gly, advancing research into ADM-related pathophysiology and supporting its use as a biomarker and therapeutic target in various diseases.

Background: Physical activity (PA) is associated with reduced mortality. However, whether there is an added benefit of long‐term endurance training is unclear. Thus, we aimed to examine 10‐year mortality in older male endurance athletes compared with an older male general population. Method: Male athletes (n = 503) participating in an annual long‐distance ski race (median years of participation: 14, range: 1–53) from the Norwegian Birkebeiner Aging study (BiAS), and non‐athletic men (n = 1867) attending the sixth Tromsø Study (Tromsø6) aged ≥65 years were included. Associations with endurance sport practice and joint exposures of endurance sport practice and self‐reported leisure‐time PA with all‐cause mortality were examined. We analyzed the data with Cox proportional hazard models and regression standardization. Results: After 10 years (median: 10.4, range: 0.5–11.1) the mortality rate was lower in athletes (hazard ratio (HR) 0.34, 95% confidence interval (CI): 0.24–0.49) compared with non‐athletes, corresponding to a 15% (95% CI: 12–19%) absolute risk reduction associated with endurance sport practice. In joint analyses categorized according to PA and endurance sport practice, we observed an inverse dose–response relationship with mortality (p < 0.001). Compared to inactive non‐athletes, PA was associated with lower mortality in both active non‐athletes and athletes. However, the observed benefit among participants reporting moderate‐to‐vigorous PA was larger in athletes (HR: 0.21, 95% CI: 0.14–0.32) than non‐athletes (HR: 0.43, 95% CI: 0.31–0.59) (p < 0.01). Conclusion: Endurance sport practice was associated with reduced 10‐year mortality, beyond the effect of PA in older men. This study suggests that long‐term endurance sport practice maintained into older adulthood promotes longevity. [ABSTRACT FROM AUTHOR]

Background and aims: The rate of cardiac implantable electronic device (CIED) implantations and the need for transvenous lead extraction (TLE) are growing worldwide. This study examined a large Swedish cohort with the aim of identifying possible predictors of post-TLE mortality with special focus on systemic infection patients and frailty. Methods: This was a single centre study. Records of patients undergoing TLE between 2010 and 2018 were analysed. Statistical analyses were conducted to compare baseline characteristics of patients with different indications and identify risk factors of 30-day and 1-year mortality. Results: A total of 893 patients were identified. Local infection was the dominant indication and pacemaker was the most common CIED. The mean age was 65 ± 16 years, 73 % were male and median follow-up was 3.9 years. Heart failure was the most common comorbidity. Patients with systemic infection were significantly older, frailer and had significantly higher levels of comorbidities. 30-day mortality and 1-year mortality rates were 2.5 % and 9.9 %, respectively. Systemic infection and chronic kidney disease (CKD) were independently associated with 30-day and 1-year mortality. Clinical frailty scale (CFS) 5–7 correlated independently with 1-year mortality in the entire cohort and specifically in systemic infection patients. CKD, cardiac resynchronization therapy and CFS 5–7 were significant risk factors for long-term mortality (death >1 year after TLE) in multivariable analysis. Conclusions: Systemic infection, kidney failure in addition to the novel parameter of frailty were associated with post-TLE all-cause mortality. These risk factors should be considered during pre-procedure risk stratification to improve post-TLE outcomes.

Summary: Background & Aims: Polyphenols are plant secondary compounds that possess antioxidant properties associated with preventing inflammation-mediated ailments such as cardiovascular disease and cancer. Recent studies hint at their capacity to enhance exercise performance. Berries, in addition to containing high amounts of essential vitamins and minerals, are extremely rich in polyphenols. Therefore, the aim of this systematic review and meta-analysis was to compile relevant human randomized controlled trials exploring the potential of polyphenol-rich berries to enhance exercise performance and associated biomarkers. Methods: The PubMed, Web of Science, and SPORTDiscus databases were searched using keywords related to berry supplementation, exercise performance, and biomarkers of performance. In total, 2374 articles were screened and 14 were included in the analysis. Results: The results indicate no statistically significant effect of berry supplementation on exercise performance and its associated biomarkers. However, there is a trend towards a positive pooled effect size of berry supplementation on time to exhaustion (SMD: 0.57, Z: 1.51, P-value: 0.13). Furthermore, all pooled effect sizes favor berry supplementation. Conclusions: Due to variations in testing protocols and biomarkers of interest among the studies included, no more than 7 articles were included for any given outcome measure. This underscores the necessity for additional high-quality randomized controlled trials (RCTs) to strengthen the evidence and allow for recommendations to be made regarding the performance enhancing effects of berry consumption. This systematic review and meta-analysis was registered on Open Science Framework (DOI 10.17605/OSF.IO/NCAVJ).

Infectious Pancreatic Necrosis virus (IPNV) is one of the major threats to the animal welfare and economy of the rainbow trout farming industry. Previous research has demonstrated significant genetic variation for resistance against IPNV. The main objective of the study was to investigate the genetic architecture of resistance against IPNV in rainbow trout fry. To achieve this, 610 rainbow trout fry, from a full factorial mating between 5 sires and 5 dams, were bath challenged with the IPNV isolate (IPNV-AS) from Atlantic salmon reared at a commercial farm. The resistance against IPNV was accessed using three different phenotypes; binary survival (BS), total days survived (TDS) and virus load (VL) recorded on the fish throughout the 40-day challenge test. All fish were genotyped using a 57K Affymetrix SNP array. The IPNV-AS isolate resulted in an overall mortality of 62.1%. The heritability estimates for survival (BS h2 = 0.21 ± 0.06, TDS h2 = 0.25 ± 0.07) and VL traits (h2 = 0.23 ± 0.08) were moderate and indicative of potential use of selection for increased resistance to IPNV in rainbow trout selective breeding programs. The unity estimated genetic correlation between the two survival traits (BS and TDS) indicates that the traits can be considered the same trait. In contrast, a moderate favourable negative genetic correlation was found between VL and the two survival traits (−0.61 ± 0.22 to −0.70 ± 0.19). The GWAS of the traits with many QTLs crossing the chromosome-wide Bonferroni corrected threshold indicates the polygenic nature of the studied traits. Most of the 10 possible identified genes were found to be linked with immunity or viral pathogenesis, which could be potentially responsible for the significant genetic variation in survival against the IPNV-AS. The QTL validation analysis revealed no significant difference in the mortalities and VL among the three genotypes of the detected QTL. The VL trait showed larger variation among the dead fry and with a concordant pattern with the two survival phenotypes, but with no significant difference in the proportion of IPNV VL positive samples in the dead and the survived fry. Overall, the results indicate the polygenic nature of the studied traits and support the use of genomic selection to improve resistance against IPNV in rainbow trout breeding companies.

We conducted an EMS mutagenesis screen on chromosome arm 2L to identify recessive suppressors of GMR-hid-induced apoptosis in the Drosophila eye. Through this screen, we recovered three alleles of the lysine demethylase gene Kdm5. Kdm5, a member of the JmjC-domain-containing protein family, possesses histone demethylase activity towards H3K4me3. Our data suggest that Kdm5 specifically regulates Hid-induced cell death during development, as we did not observe control of Reaper- or Grim-induced cell death by Kdm5. Interestingly, GMR-hid-induced apoptosis is suppressed independently of Kdm5’s demethylase activity. Our findings indicate that Rbf and dMyc are necessary for Kdm5 mosaics to suppress GMR-hid-induced cell death. Moreover, Kdm5 mosaics failed to suppress apoptosis induced by a mutant form of Hid that is resistant to inhibition by Erk-type MAPK activity. Additionally, Kdm5 dominantly enhances the wing phenotype of an activated MAPK mutant. These results collectively suggest that Kdm5 controls Hid-induced apoptosis by regulating the Rbf, dMyc, and MAPK pathways.

An enzyme known as caspase, which initiates apoptosis, has a central role in the regeneration of cells and repair of tissue that can occur after necrosis.

Abstract Introduction Papillary renal cell carcinoma (pRCC) is the second most common histology of renal cell carcinoma (RCC), accounting for 10–15% of cases. Traditionally, pRCC is divided into type 1 and type 2, although this division is currently debated as a prognostic factor of survival. Our aim was to investigate the epidemiology and survival of the pRCC subtypes in a whole nation cohort of patients during a 50-year period. Materials and methods A Population based retrospective study including consecutive cases of RCC in Iceland from 1971–2020. Comparisons were made between histological classifications of RCC, with emphasis on pRCC subtypes (type 1 vs. 2) for outcome estimation. Changes in RCC incidence were analyzed in 5-year intervals after age standardization. The Kaplan–Meier method and Cox regression were used for outcome analysis. Results A total of 1.725 cases were identified, with 74.4%, 2.1% and 9.2% having clear cell (ccRCC), chromophobe (chRCC), and pRCC, respectively. The age standardized incidence (ASI) of pRCC was 1.97/100.000 for males and 0.5/100.000 for females, and the proportion of pRCC increased from 3.7% to 11.5% between the first and last intervals of the study (p

Protein aggregation is a common pathological occurrence in neurodegenerative diseases. This often leads to neuroinflammation, which exacerbates the aggregation and progression of diseases like Parkinson’s and Alzheimer’s. Here, we focus on immune responses and neurotoxicity in a Parkinson’s disease model in Drosophila. Mutations in the SNCA gene that encodes the alpha (α)-Synuclein protein have been linked to familial Parkinson’s disease, disrupting autophagy regulation in neuronal cells and promoting the formation of Lewy bodies, a hallmark of Parkinson’s pathology. This results in the loss of dopaminergic neurons, manifesting as movement disorders. α-Synuclein aggregation triggers innate immune responses by activating microglial cells, leading to phagocytic activity and the expression of neuroprotective antimicrobial peptides (AMPs). However, sustained AMP expression or chronic inflammation resulting from inadequate microglial phagocytosis can induce neuronal toxicity and apoptosis, leading to severe dopaminergic neuron loss. This review underscores the mechanistic connection between immune response pathways and α-Synuclein-mediated neurodegeneration using Drosophila models. Furthermore, we extensively explore factors influencing neuroinflammation and key immune signaling pathways implicated in neurodegenerative diseases, particularly Parkinson’s disease. Given the limited success of traditional treatments, recent research has focused on therapies targeting inflammatory signaling pathways. Some of these approaches have shown promising results in animal models and clinical trials. We provide an overview of current therapeutic strategies showing potential in treating neurodegenerative diseases, offering new avenues for future research and treatment development.

FOXP3+ regulatory T cells (Treg cells) are key for immune homeostasis. Here, we reveal that nuclear receptor corepressor 1 (NCOR1) controls naïve and effector Treg cell states. Upon NCOR1 deletion in T cells, effector Treg cell frequencies were elevated in mice and in in vitro-generated human Treg cells. NCOR1-deficient Treg cells failed to protect mice from severe weight loss and intestinal inflammation associated with CD4+ T cell transfer colitis, indicating impaired suppressive function. NCOR1 controls the transcriptional integrity of Treg cells, since effector gene signatures were already upregulated in naïve NCOR1-deficient Treg cells while effector NCOR1-deficient Treg cells failed to repress genes associated with naïve Treg cells. Moreover, genes related to cholesterol homeostasis including targets of liver X receptor (LXR) were dysregulated in NCOR1-deficient Treg cells. However, genetic ablation of LXRβ in T cells did not revert the effects of NCOR1 deficiency, indicating that NCOR1 controls naïve and effector Treg cell subset composition independent from its ability to repress LXRβ-induced gene expression. Thus, our study reveals that NCOR1 maintains naïve and effector Treg cell states via regulating their transcriptional integrity. We also reveal a critical role for this epigenetic regulator in supporting the suppressive functions of Treg cells in vivo.

Abstract Aims Heart failure (HF) patients with anaemia tend to have a worse outcome, with increased hospitalization rates, decreased exercise tolerance, and higher mortality compared to those without anaemia. Limited research exists on the association between selenium deficiency and anaemia specifically in HF patients, despite previous findings of a correlation in different populations. The BIOSTAT‐CHF study demonstrated that higher selenium levels in HF patients were associated to a lower risk of anaemia and iron deficiency. This study investigates the relationship between selenoprotein P (SELENOP) concentrations, a major contributor and functional biomarker of selenium transport, and anaemia, Hb levels, and iron status in hospitalized HF patients. Methods and results SELENOP was analysed in 320 hospitalized HF subjects, with complete data available for 310 subjects. The relationships between continuous SELENOP concentrations and 1) Hb concentrations, 2) anaemia (Hb

The new species, Thliphthisa sapphus sp. nov. (Rubiaceae, Rubieae), a narrow endemic of the white cliffs of Lefkátas on the southwest coast of Lefkada (Greece) is described and illustrated and an IUCN assessment is presented. Vegetation relevés were performed at the single known locality, limestone cliffs facing the sea and revealed a new association, the Thliphthisa sapphus-Lomelosietum dallaportae. The chromosome number of Thliphthisa sapphus was determined as 2n = 4x = 44, being the single tetraploid species in the genus to date. The species also differs markedly morphologically from its morphologically closest relatives, two Greek steno-endemic oreophytes, Th. baenitzii and Th. muscosa by the following characters: densely setose mericarps and corolla, tetraploidy and by its distribution. An identification key for the Greek species of Thliphthisa is provided. Th. sapphus constitutes the westernmost outpost of a group of Greek steno-endemics, highlighting the importance of coastal habitats and their protection as refugia for poorly competitive chamaephytes.

Abstract Background Continuous surveillance for healthcare-associated infections such as central venous catheter-related bloodstream infections (CVC-BSI) is crucial for prevention. However, traditional surveillance methods are resource-intensive and prone to bias. This study aimed to develop and validate fully-automated surveillance algorithms for CVC-BSI. Methods Two algorithms were developed using electronic health record data from 1000 admissions with a positive blood culture (BCx) at Karolinska University Hospital from 2017: (1) Combining microbiological findings in BCx and CVC cultures with BSI symptoms; (2) Only using microbiological findings. These algorithms were validated in 5170 potential CVC-BSI-episodes from all admissions in 2018–2019, and results extrapolated to all potential CVC-BSI-episodes within this period (n = 181,354). The reference standard was manual record review according to ECDC’s definition of microbiologically confirmed CVC-BSI (CRI3-CVC). Results In the potential CVC-BSI-episodes, 51 fulfilled ECDC’s definition and the algorithms identified 47 and 49 episodes as CVC-BSI, respectively. Both algorithms performed well in assessing CVC-BSI. Overall, algorithm 2 performed slightly better with in the total period a sensitivity of 0.880 (95%-CI 0.783–0.959), specificity of 1.000 (95%-CI 0.999–1.000), PPV of 0.918 (95%-CI 0.833–0.981) and NPV of 1.000 (95%-CI 0.999–1.000). Incidence according to the reference and algorithm 2 was 0.33 and 0.31 per 1000 in-patient hospital-days, respectively. Conclusions Both fully-automated surveillance algorithms for CVC-BSI performed well and could effectively replace manual surveillance. The simpler algorithm, using only microbiology data, is suitable when BCx testing adheres to recommendations, otherwise the algorithm using symptom data might be required. Further validation in other settings is necessary to assess the algorithms’ generalisability.

Abstract FLASH-radiotherapy may provide significant sparing of healthy tissue through ultra-high dose rates in protons, electrons, and x-rays while maintaining the tumor control. Key factors for the FLASH effect might be oxygen depletion, the immune system, and the irradiated blood volume, but none could be fully confirmed yet. Therefore, further investigations are necessary. We investigated the protective (tissue sparing) effect of FLASH in proton treatment using an in-vivo mouse ear model. The right ears of Balb/c mice were irradiated with 20 MeV protons at the ion microprobe SNAKE in Garching near Munich by using three dose rates (Conv = 0.06 Gy/s, Flash9 = 9.3 Gy/s and Flash930 = 930 Gy/s) at a total dose of 23 Gy or 33 Gy. The ear thickness, desquamation, and erythema combined in an inflammation score were measured for 180 days. The cytokines TGF-β1, TNF-α, IL1α, and IL1β were analyzed in the blood sampled in the first 4 weeks and at termination day. No differences in inflammation reactions were visible in the 23 Gy group for the different dose rates. In the 33 Gy group, the ear swelling and the inflammation score for Flash9 was reduced by (57 ± 12) % and (67 ± 17) % and for Flash930 by (40 ± 13) % and (50 ± 17) % compared to the Conv dose rate. No changes in the cytokines in the blood could be measured. However, an estimation of the irradiated blood volume demonstrates, that 100-times more blood is irradiated when using Conv compared to using Flash9 or Flash930. This indicates that blood might play a role in the underlying mechanisms in the protective effect of FLASH.

The relationship between the Reformation movement and print media has long fascinated scholars, yet much of the focus has centered on renowned figures, often overlooking local lay protagonists. This article shifts the spotlight onto one such unsung figure: Pamphilus Gengenbach, a Basel writer, printer, and publisher. Gengenbach, a fervent supporter of political and religious reform, emerged as a leading advocate of Protestant thought in Basel. His aggressive promotion of the vernacular and his adept use of intertextual references to contemporary debates and events reveal a sophisticated grasp of print media’s potential beyond mere dissemination. Leveraging his experience as an author, printer, and publisher, Gengenbach engaged his audience effectively, translating and transmitting Protestant teachings with remarkable impact. This article asserts that Gengenbach’s strategic communication and local influence were instrumental in paving the way for the Basel Reformation, underscoring the vital role of grassroots actors in the Reformation’s success.

Abstract Seeking to enhance the strength of the interlayer Dzyaloshinskii-Moriya interaction (IL-DMI) through a combination of atomic and Rashba type spin-orbit coupling (SOC) we studied the strength and the thickness evolution of effective interlayer coupling in Co/Ag/Co trilayers by means of surface sensitive magneto-optical measurements that take advantage of the light penetration depth. Here, we report the observation of oscillatory, thickness-dependent chiral interaction between ferromagnetic layers. Despite the weakness of the Ag atomic SOC, the IL-DMI in our trilayers is orders of magnitude larger than that of known systems using heavy metals as a spacer except of recently reported −0.15 mJ/m2 in Co/Pt/Ru(t)/Pt/Co and varies between ≈ ±0.2 mJ/m2. In contrast to known multilayers Co/Ag/Co promotes in-plane chirality between magnetic layers. The strength of IL-DMI opens up new routes for design of three-dimensional chiral spin structures combining intra- and interlayer DMI and paves the way for enhancements of the DMI strength.