University of Erlangen-Nuremberg

For psychoneuroendocrinology, accurate measurement of progesterone (P4) and estradiol (E2) in saliva is crucial for understanding the menstrual cycle phase and its impact on physiology and behavior. Although enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) are the preferred methods and are more often found in research labs, liquid chromatography-mass spectrometry (LC-MS/MS) may provide a more valid salivary steroids assessment. In this study, we aimed to compare the performance of LC-MS/MS, ELISA, and RIA to measure salivary P4 and E2. Samples were collected from 120 participants, 81 men and 39 women, in the morning and evening. Additionally, women provided samples during the early follicular (cycle days 3-5) and luteal cycle phases (cycle days 21-23) using the forward-count method. The study considered natural hormone fluctuations (e.g., the diurnal and menstrual cycles) and quality control samples as validity criteria for method evaluation. A total of 336 samples and quality control samples were analyzed using one RIA, two ELISA, and two LC-MS/MS methods across four labs. Correlational analyses were performed to assess inter-lab x inter-method reliability, intra-lab x inter-method reliability, and inter-lab x intra-method reliability. For P4, natural hormone fluctuations in menstrual cycles were detected by all methods. However, in contrast to both LC-MS/MS methods, all immunoassays (IAs) detected an unexpected diurnal decline of P4. For E2, they were found only by LC-MS/MS and RIA. In terms of means, for P4 and E2, ELISA and RIA produced higher values compared to LC-MS/MS. For P4, the inter- and intra-method convergence was r ≥ .92. As for E2, inter-method correlations were between r = -.12 and r = .23, while the ELISA intra-method comparison showed a correlation coefficient of r = .85. Our findings suggest that while LC-MS/MS, RIA, and ELISA were capable of meeting most of the specified criteria for P4, only LC-MS/MS and RIA were able to perform similarly sufficiently at low E2 levels. LC-MS/MS provided more accurate and reliable measurements for P4 and E2, especially at low concentrations, but encountered challenges, too. Although RIA showed comparable performance to LC-MS/MS, it still suffered partly from cross-reactivity. ELISA often overestimated hormone levels and exhibited greater divergence. These differences highlight the importance of carefully selecting methods and considering their limitations in research applications.

The univentricular Fontan circulation is associated with long-term multiorgan complications, including protein-losing enteropathy (PLE). While hemodynamic and lymphatic contributors to PLE have been described, its systemic metabolic signature remains incompletely characterized. We aimed to identify PLE-associated alterations in circulating metabolites using targeted serum metabolomics. Targeted serum metabolomic profiling was performed by liquid chromatography–tandem mass spectrometry (LC–MS/MS) using the AbsoluteIDQ p180 kit. Forty-nine individuals were included: Fontan patients with PLE (FPLE, n = 10), Fontan patients without PLE (F, n = 30), and clinically stable biventricular controls (C, n = 9). Data were analyzed using MetaboAnalyst v6.0, including multivariate modeling (PLS-DA), univariate statistics with false discovery rate correction, correlation analyses, and receiver operating characteristic (ROC) analyses. Compared with controls, Fontan patients without PLE showed reduced concentrations of cholesterol, triacylglycerols, and several phosphatidylcholine (PC) species, whereas Fontan patients with PLE demonstrated relative increases in these lipid classes. Among 90 quantified PCs, 11 showed a consistent gradient with the lowest concentrations in F and the highest in FPLE. FPLE was further characterized by marked hypoalbuminemia and hypogammaglobulinemia, accompanied by elevated renin, aldosterone, and copeptin levels, indicating pronounced renal–neurohormonal activation of the renin-angiotensin-aldosterone system (RAAS) and vasopressin. Bile acid derivatives, including taurodeoxycholic acid and glycodeoxycholic acid, tended to be lower in FPLE and showed group-specific associations with both renin and selected PC species. Exploratory ROC-based screening identified the immunoglobulin G (IgG)-to-aldosterone and the albumin-to-PC ae C40:3 ratios as the most informative biomarker combinations distinguishing FPLE from non-PLE Fontan patients. These findings are exploratory and hypothesis-generating and require validation in independent cohorts. Fontan patients with PLE show a distinct metabolic phenotype integrating protein loss, lipid alterations, bile acid perturbations, and activation of the renin–angiotensin–aldosterone system. These findings suggest that metabolic and renal–neurohormonal pathways extend beyond lymphatic dysfunction in PLE and identify candidate biomarker patterns for further investigation rather than established diagnostic tools. Further studies are required to clarify causality, mechanistic links, and clinical generalizability.

Increasing population-level physical activity (PA) requires system-level policy action. However, public policies targeting the general population, without addressing socially disadvantaged populations, might unintentionally increase socioeconomic inequities in PA. This is particularly concerning since disadvantaged groups are less likely to meet PA recommendations to begin with. This systematic review assesses evidence on the effects of public policies on equity in PA. A literature search was performed in seven bibliographic databases on May 7, 2024, in collaboration with a librarian. Studies were included if they a) focused on changes in PA behaviour, PA proxies, or the PA environment as outcomes, b) examined public policy as the independent variable, and c) included a low socioeconomic status (SES) (sub)population. Screening was done in duplicate. Key data extracted included: public policy information, target population and/or SES subgroup measures, PA outcomes, and equity-related findings. Policies were grouped into domains aligned with the eight investments of the International Society for Physical Activity and Health and categorized based on their impact on inequities: reduction, increase, no effect, or mixed effects. Out of 10,350 records screened, 81 studies were included. Results showed that 27% of the public policies reduced inequities, 38% had no effect, 10% increased them, and 25% had mixed effects. The fewest PA policies were identified in the healthcare (n = 2) and workplace (n = 0) domains, the most in the community-wide domain (n = 22). Based on the available evidence, the school, transport, community-wide, and mass media policy domains most frequently demonstrated potential to reduce inequities in PA and/or to benefit high and low SES populations equally. Policies that most consistently reduced inequities or had a neutral equity effect included a) infrastructure policies, b) financial incentives supporting active transport, c) multi-component school-based PA and health policy programmes, d) school physical education policies, and e) policies supporting mass media campaigns. Conversely, urban design and sport for all policies varied in their effects on inequities. Most policies do not appear to exacerbate inequities. Policies in the school, transport, community-wide, and mass media domains show particular promise for promoting PA in an equitable way. These findings offer valuable insights for future policymaking.

Abstract In both (some varieties of) Modern South Arabian (MSA) and Ṭuroyo the apparent co-occurrence of the definite article and the possessive pronominal suffix constitutes a synchronically puzzling phenomenon, at least from a Semiticist perspective. This paper explores both morpho-phonological and morpho-syntactic aspects of this feature and also offers a diachronic Semitic as well as a synchronic typological perspective (therefore the tentative use of the adjective ‘apparent’ in the title of this article).

Rheumatoid arthritis (RA) pathogenesis involves early gut immune alterations that precede clinical onset and systemic bone involvement. Using mouse and human imaging mass cytometry (IMC) and tissue sequencing, this study shows that intestinal endothelial and immune changes emerge before or coincide with arthritis symptom development. In the collagen-induced arthritis (CIA) model, intestinal vascular permeability and endothelial gene activation promoting leukocyte trafficking appeared prior to synovial inflammation. Spatial mapping of murine and human ileal tissues predicted enhanced epithelial–immune interactions and lymphoid activation, suggesting mucosal immune priming before joint pathology. Both gut–selective α4β7 integrin blockade with vedolizumab and endothelial barrier enhancement by imatinib significantly reduced arthritis severity in CIA mice. After clinical onset, microbiota–specific IgG responses expanded to recognize rare gut bacteria, reflecting increased microbial exposure. Bone marrow endothelium exhibited interferon I–driven inflammation and vascular activation, indicating tissue–specific endothelial dysfunction. Microbiota–reactive IgG increased during CIA – likely a response to translocating gut bacteria and immune cell activation. Integrating mouse and human data, these findings define a mechanistic framework where endothelial barrier impairment, microbial translocation, and systemic endothelial activation initiate RA autoimmunity, revealing endothelial and mucosal pathways as targets for early intervention.

Left panel: Scheme of the XPAG-immune thrombocytopenia trial. The dexamethasone (DEX) arm consisted of DEX 40 mg/day for days 1-4 for one to three cycles every 28 days to a maximum of 12 weeks, cycles 2 + 3 were optional. Patients randomised to eltrombopag (ETB) + DEX received eltrombopag in combination with a short course of high-dose DEX beginning on day 1 (40 mg/day during days 1-4). The starting dose of ETB was 50 mg/day for 2 weeks; thereafter, the ETB dose was increased by 25 mg for all patients who did not achieve the target platelet count of ≥50 × 109/L. The ETB tapering was performed by decreasing the dose by 25 mg every 2 weeks to a minimum dose of 25 mg every other day for all patients. Right upper panel: Clinical outcomes in patients treated with first-line ETB + DEX. Patients displayed a qualitatively longer response duration and qualitatively reduced usage of rescue medication. Right lower panel: The immunological T-cell response was different in treatment responders and non-responders. Patients with sustained response (responders) displayed a high T-cell clonality at baseline. Clones are depicted as bubbles (right side).

Exercise intensity is often prescribed as a percentage of a "maximum" reference point. Both the choice of reference and the protocol to obtain it may bias apparent female-male differences in relative intensity. The objective of this study is to examine whether female-male differences in relative intensity expressed relative to a maximum reference [V̇o2max or peak power output (PPO)] differ depending on the protocol used to determine it (ramp vs. step). Fifty trained cyclists (30 males, 20 females, 31 ± 8 yr old, V̇o2max 3,866 ± 840 mL/min) completed a ramp-incremental and a 3-min step test on a cycle ergometer. Thresholds were determined in the step test from fixed and individualized blood lactate concentrations and from ventilation. Relative intensity was expressed in relation to PPO and V̇o2max derived from each protocol. Linear mixed-effects models with participant as random intercept tested the fixed effects of Sex, Protocol, and their interaction. Agreement between ramp- and step-derived V̇o2max values was evaluated using Bland-Altman analysis. For V̇o2-based relative intensity, only protocol effects were small but significant (all P < 0.01). For Power, Sex had a significant influence in the models with males displaying higher relative intensities in all lactate-based thresholds (all P ≤ 0.02). Sex × Protocol interactions emerged for the onset of 2 mmol/L blood lactate (BLa2) and Onset of minimum+ 0.5 mmol/l blood lactate (BLamin+0.5) (both P < 0.05), indicating that using step or ramp protocols as reference can alter the magnitude or direction of female-male differences. Apparent sex differences in relative intensity depend on how "maximum" is defined and obtained. The same relative intensity does not ensure equivalent physiological strain across sexes.NEW & NOTEWORTHY Method matters when comparing men and women in exercise physiology. In trained cyclists, we show that apparent female-male differences in exercise intensity at lactate and ventilatory thresholds depend on how "maximum" is defined (V̇o2max vs. peak power output) and the protocol used (ramp vs. step). Some sex effects appeared only under specific methodological choices, highlighting that differences often attributed to biology may, in fact, be artifacts of test design.

BackgroundIntraoperative cone‐beam computed tomography (CBCT) provides a valuable option for accurate three‐dimensional applicator positioning in gynecologic brachytherapy, but is associated with radiation exposure and increased intervention time especially in case of repeated CBCT imaging being required for creating a sufficient implant arrangement.PurposeTo reduce the need for multiple CBCT scans for corresponding applicator verification, this work proposes two methods for needle path navigation, including corrections of potential bending in situ, by combining infrared tracking with planar x‐ray imaging for enabling accurate intraoperative needle guidance.MethodsAn examined 200 mm brachytherapy needle was rigidly mounted on an infrared‐reflective tracking tool to enable real time tracking. Two planar x‐ray images, acquired from varying distinct angles, were used to determine the exact 3D position of the needle tip region via backprojection. A spline was fitted through the obtained coordinates to reconstruct the full needle path. Based on this, only a single initial CBCT scan was required to visualize the predicted needle path within this scan. Additionally, a second approach for needle prediction was presented focusing on only one planar x‐ray image by incorporating prior needle bending information from the initial CBCT scan. Both methods were evaluated in preclinical studies and validated against a corresponding ground‐truth obtained from CBCT.ResultsThe proposed method considering two planar x‐ray images successfully reconstructed the needle path with deviations of less than 1 mm from the CBCT reference scan, when using at least 20° offset between the x‐ray image acquisitions. The single‐scan approach, using prior bending information, yielded promising results with deviations at the tip of below 1.3 mm.ConclusionsBoth described methods demonstrated their feasibility in preclinical studies, showing potential to improve and accelerate clinical implantation workflows by means of needle navigation in the future.

ABSTRACT Laser ablation is a widely used technique for the fabrication of periodic structures on solids to manipulate their surface properties. A fundamental challenge in the formation of laser‐induced periodic surface structures (LIPSS) is ascertaining the correlation between laser parameters and LIPSS characteristics. This study focuses on the characterization of LIPSS in terms of the period of low spatial frequency LIPSS (LSFL) and their homogeneity as a function of single pulse fluence and effective fluence dose in the range from 0.067 to 1.070 J cm −2 and from 50 to 1280 J cm −2 , respectively. Here, a 1064 nm laser with a pulse duration of 13 ps was utilized to create LIPSS on Ti6Al4V alloy. The morphology of the formed structures was analyzed using the two‐dimensional fast Fourier transform method applied to scanning electron microscopy images. Homogeneous LSFL with spatial periods are obtained for effective fluence doses of 50 and 160 J cm −2 . However, an increase in the effective fluence dose up to 640 J cm −2 led to the formation of so‐called large LIPSS and the disappearance of homogeneous LSFL. The evolution of LIPSS that has been observed is attributed to changes in the ratio and absolute values of the ablative and heating components of the laser pulse energy at different single and effective fluence doses. Our study contributes to the development of tailored surfaces with periodic structures on Ti alloys.

Superparamagnetic iron oxide nanoparticles (SPIONs) represent an emerging class of nanoparticles that face increasing applications in medicine, in particular in nanoparticle-based oncology. Their superparamagnetic properties allow for the magnetic steering and the interlinked targeted and localized delivery of pharmaceuticals. The development of nanoparticle-based therapies requires a deep understanding of geometry-hydrodynamics-adhesion interactions, motivating the generation of blood vessel models. The present work addresses the geometry-dependent propagation of SPIONs under magnetic steering through generalized, transferable geometries. Such geometries were derived based on generalized, statistical considerations of branch-dependent vessel diameters, yielding a reproducible and transferable testing environment independent of individual angiographic data. Based on stereolithographic additive manufacturing, fluidic models with varied blood vessel diameters and branching orders were manufactured and tested under varying magnetic steering conditions, injected SPION concentration, and flow rate. Through optical in situ measurements and complementary ex situ scanning electron microscopy, a significant influence of flow-regime-dependent hydrodynamic effects on magnetic steerability could be identified. Experimental findings suggest that while reduced flow rates were associated with locally laminar flows that promoted sedimentation and enabled limited magnetic redistribution of SPION-containing colloidal solutions at a magnetic flux density of B = 0.35 T, increased flow rates and interlinked unsteady flows were shown to impair the magnetically controlled, local SPION deposition. Hence, flow conditions present in larger arteries and bifurcations during SPION injection can be shown to significantly influence the quantitative magnetic steering of SPIONs in vascular-inspired fluidic channel structures, displaying enhanced local particle residence times and redistribution of SPIONs under low-flow conditions.