Adverse alcohol consumption is a major public health concern, which might have been further increased by the COVID-19 pandemic. In this study we investigated the impact of a lockdown stage on the association between alcohol consumption, loneliness, and COVID-19-related worries. We used smartphone-based Ecological Momentary Assessment (EMA) conducted during the COVID-19 pandemic in Germany. We recruited 280 participants from the general population, who experienced at least mild loneliness and distress due to the COVID-19 pandemic. We assessed daily alcohol intake, loneliness, and COVID-19-related worries every evening for 7 consecutive days across a no-lockdown [8th August 2020–1st November 2020] and lockdown stage [2nd November 2020–11th March 2021]. We did not find that a lockdown stage, compared to a no-lockdown stage, is associated with increased alcohol consumption. We found that loneliness, previous day drinking, and COVID-19-related worries were not associated with increased, but with decreased alcohol consumption. Moreover, COVID-19-related worries were more negatively associated with alcohol consumption during a no-lockdown stage compared to a lockdown stage. We found that the effect of COVID-19 related worries on alcohol consumption is mediated by loneliness. Our study suggests that heightened levels of worry can decrease alcohol intake. This association can be explained by loneliness: individuals who worry more are lonelier and thus less likely to engage in social drinking. However, during a lockdown stage, the negative association between worrying and drinking diminishes.

The KCNQ1 + KCNE1 potassium channel complex produces the slow delayed rectifier current (IKs) critical for cardiac repolarization. Loss-of-function mutations in KCNQ1 and KCNE1 cause long QT syndrome (LQTS) types 1 and 5 (LQT1/LQT5), accounting for over one-third of clinical LQTS cases. Despite prior structural work on KCNQ1 and KCNQ1 + KCNE3, the structural basis of KCNQ1 + KCNE1 remains unresolved. Using cryo-electron microscopy and electrophysiology, we determined high-resolution (2.5–3.4 Å) structures of human KCNQ1APO, and KCNQ1 + KCNE1 in both closed and open states. KCNE1 occupies a pivotal position at the interface of three KCNQ1 subunits, inducing six helix-to-loop transitions in KCNQ1 transmembrane segments. Three of them occur at both ends of the S4–S5 linker, maintaining a loop conformation during IKs gating, while the other three, in S6 and helix A, undergo dynamic helix-loop transitions during IKs gating. These structural rearrangements: (1) stabilize the closed pore and the conformation of the intermediate state voltage-sensing domain, thereby determining channel gating, ion permeation, and single-channel conductance; (2) enable a dual-PIP2 modulation mechanism, where one PIP2 occupies the canonical site, while the second PIP2 bridges the S4–S5 linker, KCNE1, and the adjacent S6’, stabilizing channel opening; (3) create a fenestration capable of binding compounds specific for KCNQ1 + KCNE1 (e.g., AC-1). Together, these findings reveal a previously unrecognized large-scale secondary structural transition during ion channel gating that fine-tunes IKs function and provides a foundation for developing targeted LQTS therapy.

Mothers with borderline personality disorder (BPD) are assumed to perceive difficulties in the relationship towards their children. However, a detailed and comprehensive investigation on how mothers with BPD reflect and speak about their children as an indicator for mental representations of the mother-child relationship is yet missing. In two articles drawing from a cross-sectional data set of a multi-center study, we examined these aspects in mothers with BPD compared with a healthy and a clinical control group comprising mothers with anxiety disorders, depression, or both. Using the Five Minute Speech Sample, we focused on Expressed Emotion (EE), Narrative Coherence (NC) – both in the primary data analysis – and an extended assessment of Mind-Mindedness (extended MM) in the secondary data analysis. This article mainly addresses the similarities and differences between the three constructs on a conceptual level and regarding the respective study results, and additionally discusses the overall results from both studies. When comparing the three constructs, we identified differences regarding the level of analyzed content (i.e., characteristics of speech vs. characteristics of representation) and the level of orientation (i.e., reference to the mother herself vs. reference to the child). Three aspects are assessed via all operationalizations: (1) reporting negatively about characteristics or behaviors of the child, (2) reporting weaknesses of the child, and (3) descriptions of relationship quality. Mothers with BPD were more likely to express overt criticism (EE) and express more mental attributes with negative valence (extended MM) than both the clinical and healthy control groups. Given that we found particularities in the parent-child relationship in mothers with BPD across all three coding systems, we assume the overlap to be grounded in a tendency towards greater disapproval of child characteristics and reports of challenges in relationship quality. Considering the results of both studies, this article provides the most a comprehensive examination of these relational aspects in mothers with BPD, including comparisons with both healthy and clinical control groups. These insights contribute to a deeper understanding of the complexities underlying mental representations of the mother-child relationship in the context of BPD.

Purpose Hematotoxicity is a common side-effect of cytotoxic gastrointestinal (GI) cancer therapies. An unsolved problem is to predict the individual risk therefore to decide on treatment adaptions. We applied an established biomathematical prediction model and primarily evaluated its predictive value in patients undergoing chemotherapy for GI cancers in curative intent.

Methods In a prospective, observational multicenter study on patients with gastro-esophageal or pancreatic cancer (n = 28) receiving myelosuppressive adjuvant or neoadjuvant chemotherapy (FLO(T) or FOLFIRINOX), individual model parameters were learned based on patients’ observed laboratory values during the first chemotherapy cycle and further external data resources. Grades of hematotoxicity of subsequent cycles were predicted by model simulation and compared with observed data.

Results The most common high-grade hematological toxicity was neutropenia [19/28 patients (68%)]. For the FLO(T) regimen, individual grades of thrombocytopenia and leukopenia could be well predicted for cycles 2–4, as well as grades of neutropenia for cycle 2. Prediction accuracy for neutropenia in the third and fourth cycle differed by one toxicity grade on average. For the FOLFIRINOX-regimen, thrombocytopenia predictions showed a maximum deviation of one toxicity grade up to the end of therapy (8 cycles). Deviations of predictions were less than one degree on average up to cycle 4 for neutropenia, and up to cycle 6 for leukopenia.

Conclusion The biomathematical model showed excellent short-term and decent long-term prediction performance for all relevant hematological side effects associated with FLO(T)/FOLFIRINOX. Clinical utility of this precision-medicine approach needs to be further investigated in a larger cohort.

Background Upper respiratory tract infections usually peak during winter months.

Objective The purpose of this study was to evaluate whether imaging of complicated upper airway infection in children increased during the winter season of 2022/2023.

Materials and methods In a retrospective study setting, pediatric magnetic resonance imaging (MRI) and computed tomography (CT) scans for evaluation of upper respiratory tract infection performed between October 2022 and April 2023 were analyzed regarding presence of the following complications: mastoiditis, abscess, phlegmon, meningitis, reactive vasculitis, and sinus vein thrombosis. Pathogen detection, surgery, and infection parameters were obtained. Data were compared with MRI and CT scans performed in the same months of the preceding five years, distinguishing between pandemic and pre-pandemic years.

Results During the 2022/2023 winter season, the number of MRI and CT scans in children with upper airway infections, the complication rate, the rate of detected streptococcal infections, and the rate of surgery increased significantly compared to expectations based on the five prior winter seasons (all P<0.05). During the first complete pandemic winter season in Europe (2020/2021), the number of MRI and CT scans in children with upper airway infection, the complication rate, and the rates of streptococcal detection and surgery decreased significantly compared to expectations based on the pre-pandemic, the second pandemic, and the post-pandemic winter seasons (all P<0.05).

Conclusion After a decline during the first pandemic winter season, there was a marked rebound in complicated upper airway infection in children, with a significant increase in cases during the 2022/2023 winter season compared to the pre-pandemic and pandemic years.

Aims We investigated the implementation of new guidelines in ST-segment elevation myocardial infarction (STEMI) patients in a large real-world patient population in the metropolitan area of Berlin (Germany) over a 20-year period.

Methods From January 2000 to December 2019, a total of 25 792 patients were admitted with STEMI to one of the 34 member hospitals of the Berlin-Brandenburg Myocardial Infarction Registry (B2HIR) and were stratified for sex and age < 75 and ≥ 75 years.

Results The median age of women was 72 years (IQR 61–81) compared to 61 years in men (IQR 51–71). PCI treatment as a standard of care was implemented in men earlier than in women across all age groups. It took two years from the 2017 class IA ESC STEMI guideline recommendation to prefer the radial access route rather than femoral until > 60% of patients were treated accordingly. In 2019, less than 60% of elderly women were treated via a radial access. While the majority of patients < 75 years already received ticagrelor or prasugrel as antiplatelet agent in the year of the class IA ESC STEMI guideline recommendation in 2012, men ≥ 75 years lagged two years and women ≥ 75 three years behind. Amongst the elderly, in-hospital mortality was 22.6% (737) for women and 17.3% (523) for men (p < 0.001). In patients < 75 years fatal outcome was less likely with 7.2% (305) in women and 5.8% (833) in men (p < 0.001). After adjustment for confounding variables, female sex was an independent predictor of in-hospital mortality in patients ≥ 75 years (OR 1.37, 95% CI 1.12–1.68, p = 0.002), but not in patients < 75 years (p = 0.076).

Conclusion In-hospital mortality differs considerably by age and sex and remains highest in elderly patients and in particular in elderly females. In these patient groups, guideline recommended therapies were implemented with a significant delay.

Decreased hippocampal connectivity and disruption of functional networks are established resting-state functional MRI (rs-fMRI) features that are associated with neuropsychiatric symptom severity in human anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, the underlying pathophysiology of NMDAR encephalitis remains poorly understood. Application of patient-derived monoclonal antibodies against the NR1 (GluN1) subunit of the NMDAR now allows for the translational investigation of functional connectivity in experimental murine NMDAR antibody disease models with neurodevelopmental disorders. Using rs-fMRI, we studied functional connectivity alterations in (1) adult C57BL/6 J mice that were intrathecally injected with a recombinant human NR1 antibody over 14 days (n = 10) and in (2) a newly established mouse model with in utero exposure to a human recombinant NR1 antibody (NR1-offspring) at the age of (2a) 8 weeks (n = 15) and (2b) 10 months (n = 14). Adult NR1-antibody injected mice showed impaired functional connectivity within the left hippocampus compared to controls, resembling impaired connectivity patterns observed in human NMDAR encephalitis patients. Similarly, NR1-offspring showed significantly reduced functional connectivity in the hippocampus after 8 weeks, and impaired connectivity in the hippocampus was likewise observed in NR1-offspring at the age of 10 months. We successfully reproduced functional connectivity changes within the hippocampus in different experimental murine systems that were previously observed in human NMDAR encephalitis patients. Translational application of this method within a combined imaging and histopathological framework will allow future experimental studies to identify the underlying biological mechanisms and may eventually facilitate non-invasive monitoring of disease activity and treatment responses in autoimmune encephalitis.

Purpose Humoral and cellular immune responses were described after COVID-19 vaccination in patients with common variable immunodeficiency disorder (CVID). This study aimed to investigate SARS-CoV-2-specific antibody quality and memory function of B cell immunity as well as T cell responses after COVID-19 vaccination in seroresponding and non-responding CVID patients.

Methods We evaluated antibody avidity and applied a memory B cell ELSPOT assay for functional B cell recall memory response to SARS-CoV-2 after COVID-19 vaccination in CVID seroresponders. We comparatively analyzed SARS-CoV-2 spike reactive polyfunctional T cell response and reactive peripheral follicular T helper cells (pTFH) by flow cytometry in seroresponding and non-seroresponding CVID patients. All CVID patients had previously failed to mount a humoral response to pneumococcal conjugate vaccine.

Results SARS-CoV-2 spike antibody avidity of seroresponding CVID patients was significantly lower than in healthy controls. Only 30% of seroresponding CVID patients showed a minimal memory B cell recall response in ELISPOT assay. One hundred percent of CVID seroresponders and 83% of non-seroresponders had a detectable polyfunctional T cell response. Induction of antigen-specific CD4+CD154+CD137+CXCR5+ pTFH cells by the COVID-19 vaccine was higher in CVID seroresponder than in non-seroresponder. Levels of pTFH did not correlate with antibody response or avidity.

Conclusion Reduced avidity and significantly impaired recall memory formation after COVID-19 vaccination in seroresponding CVID patients stress the importance of a more differentiated analysis of humoral immune response in CVID patients. Our observations challenge the clinical implications that follow the binary categorization into seroresponder and non-seroresponder.

Unstable interpersonal relationships and fear of abandonment are core symptoms of borderline personality disorder (BPD) that often intensify during stress. Psychosocial stress, which includes components of social exclusion and increases cortisol secretion, enhances emotional empathy in healthy individuals. Women with BPD, on the contrary, react with reduced emotional empathy. The aim of the present study was to investigate the effects of perceived social exclusion without accompanying cortisol increase on empathy in women with BPD and healthy women. To induce social exclusion, we randomized 98 women with BPD and 98 healthy women to either an exclusion or an overinclusion (control) condition of Cyberball, a virtual ball game. Subsequently, participants underwent the Multifaceted Empathy Test (MET), which assesses cognitive and emotional empathy. There was no increase in cortisol release after Cyberball. Cognitive empathy did not differ between groups or conditions. Women with BPD reported lower emotional empathy for positive emotions (group by valence interaction), but not for negative emotions. Exploratory analyses suggested that this effect might be more pronounced after social exclusion. Our results confirm previous findings that cognitive empathy does not differ between women with BPD and healthy women and extend this evidence to social exclusion. Emotional empathy in women with BPD seems to be more sensitive to the effects of stress or ambiguous social situations. Specifically, emotional empathy seems to be reduced for positive emotions, and might further decline after social exclusion. Empathic reactions to emotional stimuli of different valences and to specific emotions should be further investigated.

Purpose The study aims to evaluate changes in contrast sensitivity (CS) during therapy with intravitreal vascular endothelial growth factor (VEGF) inhibitors in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).

Methods Prospective, uncontrolled, multicenter study on patients with neovascular AMD or DME who underwent intravitreal injection therapy with Ranibizumab, Aflibercept, or Bevacizumab was conducted. Best corrected visual acuity (BCVA) and CS measured by Mars Letter Contrast Sensitivity Test (MLCS) and Freiburg Visual Acuity and Contrast Test (FrACT) in logCS were evaluated before 3 consecutive VEGF inhibitor injections, which followed the pro renata regimen in treatment-naïve and pretreated eyes with a maximum of 9 injections. Correlation of MLCS and FrACT was calculated by the Spearman’s rank correlation coefficient.

Results Eighty eyes of 74 patients (mean age 72.7; SD ± 9.96) were included. BCVA improved significantly from 0.44 (SD ± 0.21) logMAR to 0.38 (SD ± 0.23) logMAR by 0.06 (SD ± 0.14) logMAR values (p < 0.001). CS measured by MLCS increased significantly from 1.27 (SD ± 0.25) logCS to 1.39 (SD ± 0.22) logCS (p < 0.001). CS measured by FrACT also improved significantly from 1.22 (SD ± 0.32) logCS to 1.30 (SD ± 0.29) logCS (p = 0.035). A positive correlation between MLCS and FrACT was found (r = 0.389; p < 0.001). Despite statistical significance, results for BCVA, MLCS, and FrACT failed clinical significance. Overall best test results were achieved with MLCS.

Conclusions Intravitreal injection therapy with VEGF inhibitors led to an improvement of BCVA and CS measured by MLCS and FrACT. MLCS was superior and more sensitive compared to FrACT and even BCVA to evaluate CS in elderly patients with macular pathology.

Objectives To identify biomarkers at the gene expression level to predict response to methotrexate (MTX) in patients with rheumatoid arthritis (RA).

Methods MTX-naïve patients with RA were started on MTX and followed up over three months. The disease activity score 28 (DAS28) was used to classify patients into responders and non-responders. Genome-wide gene expression analysis was performed in CD4 + and CD14 + mononuclear cells sampled from whole blood at baseline to identify differentially expressed genes in responders versus non-responders. Gene selection methods and prediction modelling obtained the most relevant differentially expressed genes. A logistic regression prediction model was subsequently constructed and validated via bootstrapping. The area under the receiver operating characteristic (AUC) curve was calculated to judge model quality.

Results Seventy-nine patients with RA (53.4 ± 13.9 years, 74.7% females) were enrolled, and 70 finished the study with a documented treatment EULAR response (77.1% responders). Forty-six differentially expressed genes were found. The most promising genes were KRTAP4-11, LOC101927584, and PECAM1 in CD4 + cells and PSMD5 and ID1 in CD14 + cells. The final prediction model using these genes reached an AUC of 90%; the validation set’s AUC was 82%.

Conclusions Our prediction model constructed via genome-wide gene expression analysis in CD4 + and CD14 + mononuclear cells yielded excellent predictions. Our findings necessitate confirmation in other cohorts of MTX-naïve RA patients. Especially if used in conjunction with previously identified clinical and laboratory (bio)markers, our results could help predict response to MTX in RA to guide treatment decisions.

Background Increasing evidence suggests that secondary sclerosing cholangitis (SSC), which can lead to cirrhosis or liver failure, may be a hepatobiliary long-term complication of COVID-19. The aim of this study was to estimate the frequency and outcome of this COVID-19 sequela and to identify possible risk factors.

Methods This observational study, conducted at University Hospital Charité Berlin and Unfallkrankenhaus Berlin, Germany, involved hospitalized patients with COVID-19 pneumonia, including 1082 ventilated COVID-19 patients. We compared COVID-19 patients who developed SSC with a COVID-19 control group by univariate and multivariate analyses.

Results SSC occurrence after COVID-19 was observed exclusively in critically ill patients with invasive ventilation, albeit with extreme clustering among them. One in every 43 invasively ventilated COVID-19 patients developed this complication. Risk factors preceding the development of secondary sclerosing cholangitis in critically ill COVID-19 patients (SSC-CIP) were signs of systemic reduced blood oxygen supply (e.g., low PaO2/FiO2, ischemic organ infarctions), multi-organ failure (high SOFA score) at admission, high fibrinogen levels and intravenous ketamine use. Multivariate analysis confirmed fibrinogen and increased plasma lactate dehydrogenase as independent risk factors associated with cholangiopathy onset. The 1-year transplant-free survival rate of COVID-19-associated SSC-CIP was 40%.

Conclusions COVID-19 causes SSC-CIP in a substantial proportion of critically ill patients. SSC-CIP most likely develops due to severe tissue hypoxia and fibrinogen-associated circulatory disturbances. A significant increase of patients with SSC-CIP is to be expected in the post-COVID era.

Objectives Clinical data on retaining extensively damaged teeth using forced orthodontic extrusion followed by restorative rehabilitation are scarce, and economic evaluations are basically absent. A health economic evaluation of this method was performed based on a clinical study.

Materials and methods In a convenience sample of individuals recruited from routine care, extensively damaged teeth were orthodontically extruded prior to restoration. Patients were followed up for up to 6 years. The health outcome was tooth retention time. Direct medical, non-medical, and indirect initial and follow-up costs were estimated using the private payer’s perspective in German healthcare. Association of initial direct medical treatment costs and cofounding variables was analyzed using generalized linear models. Success and survival were secondary outcomes.

Results A total of 35 teeth in 30 patients were followed over a mean ± SD of 49 ± 19 months. Five patients (14%) dropped out during that period. Median initial costs were 1941€ (range: 1284–4392€), median costs for follow-up appointments were 215€ (range: 0–5812€), and median total costs were 2284€ (range: 1453 to 7109€). Endodontic re-treatment and placement of a post had a significant impact on total costs. Three teeth had to be extracted and in three patients orthodontic relapse was observed. The survival and success rates were 91% and 83%, respectively.

Conclusions Within the limitations of this clinical study, total treatment costs for orthodontic extrusion and subsequent restoration of extensively damaged teeth were considerable. Costs were by large generated initially; endodontic and post-endodontic therapies were main drivers. Costs for retreatments due to complications were limited, as only few complications arose.

Clinical relevance The restoration of extensively damaged teeth after forced orthodontic extrusion comes with considerable initial treatment costs, but low follow-up costs. Overall and over the observational period and within German healthcare, costs are below those for tooth replacement using implant-supported crowns.

Trial registration ClinicalTrials.gov Identifier: DRK S00026697).

Urban green spaces are important components of city spaces that are vulnerable to degradation in soil–water–climate processes. This vulnerability is exacerbated by current climate change and park usage density. This study examines the dynamics of soil water repellency in the topsoils of selected urban parks in Berlin, aiming to assess the relationships between weather conditions, soil water content, and soil water repellency. This study is based on monthly sampled soils from spots originating from three selected parks—Fischtal Park, Stadtpark Steglitz, and Rudolph-Wilde Park—between September 2022 and October 2023; two of the parks are exclusively rainwater fed, and one is irrigated during summer months. For each sample soil, water repellency persistence and severity were analyzed. Time series analysis was conducted including soil water content. In addition, the total organic carbon content (TOC) and sample texture were analyzed. The results show that the rainfall amount, number of dry days, and maximum temperature during different time intervals prior to the sampling date predominantly control the variation in the soil water repellency via the soil water content. Soil water repellency variations observed appear more event-related than monthly or seasonal, as rainfall is evenly distributed through the years without a distinct dry or wet season in Berlin. The non-repellency of the soil samples was usually observed when the associated water content was increased, which is linked to high cumulative rainfall and short dry periods. Low rainfall amounts and long dry periods in summer result in the re-establishment of the soil water repellency, possibly affecting increased runoff generation and soil erosion risk. Spatially, the repellency properties were observed at locations under healthy vegetation cover, while soils located on the upper slope locations and on the pathways lacked repellency characteristics.

Purpose While gram negative (GN) periprosthetic joint infections (PJI) have previously been described as difficult to treat pathogens with high rates of reinfection, limited investigations have addressed midterm outcomes and risk of infection persistence by the same pathogen. This study analyzed (1) baseline demographics, treatment strategy, and midterm outcomes of GN PJIs, as well as (2) differences in reinfection and relapse rates compared to gram positive (GP) PJIs.

Methods We identified 29 patients that were revised for 30 GN PJIs of total hip arthroplasties (THAs) between 2010 and 2020 using a university-based hip registry. Mean age was 77 years, 63% were females (19), and mean BMI was 27 kg/m2. Major causative pathogens included Escherichia coli (12), Klebsiella pneumoniae (5), Pseudomonas aeruginosa (5), and Enterobacter cloacae complex (5). Mean follow-up was 3.5 years. Study outcomes included (1) Kaplan–Meier survivorship analyses of all 30 GN PJIs, and (2) comparison of 18 two-stage exchanges for GN PJIs and 104 two-stage exchanges for GP PJIs, performed during the time from 2013 to 2017.

Results (1) The 5-year survivorship free of recurrent PJI was 69%, and there were 7 recurrent PJIs at a mean of 2 years. There were 2 further suprafascial wound infections, resulting in a 61% survivorship free of any infection at 5-years. At a mean of 2 years, there were 7 patients with reinfection by the same GN pathogen (6 PJIs, one wound infection) as at index revision (23%). (2) Following two-stage exchange, the 5-year survivorship free of recurrent PJI (GN: 74%; GP: 91%; p = 0.072), any infection (GN: 61%; GP: 91%; p = 0.001), and reinfection by the same pathogen was significantly lower among GN PJIs (GN: 73%; GP: 98%; p < 0.001).

Conclusions Patients revised for GN PJIs are at increased risk of reinfection as opposed to GP infections. Affected patients must be counseled on the exceptionally high risk of infection persistence with one in four developing relapses.

Level of evidence Therapeutic Level III.

Every year, millions of people worldwide suffer from bone tissue damage caused by bone trauma and surgical operations, as well as diseases such as osteoporosis, osteoarthritis, osteomyelitis, and periodontitis. Bone defect repair is one of the major challenges in the field of regenerative medicine. Although bone grafts are the gold standard for treating bone defects, factors such as donor sources and immune responses limit their application. Functionalized nanomaterials have become an effective means of treating bone diseases due to their good biocompatibility and osteoinductivity, anti-inflammatory, and antibacterial properties. Metal–organic frameworks (MOFs) are porous coordination polymers composed of metal ions and organic ligands, featuring unique physical properties, including a high surface area–volume ratio and porosity. In regenerative medicine, MOFs function as the functions of drug carriers, metal ion donors, nanozymes, and photosensitizers. When combined with other functional materials, they regulate cellular reactive oxygen species, macrophage phenotypic transformation, bone resorption, osteogenesis, and mineralization, providing a new paradigm for bone tissue engineering. This study reviews the classification of functionalized MOF composites in biomedicine and the application of their synthesis techniques in bone diseases. The unique in vivo and in vitro applications of MOFs in bone diseases, including osteoarthritis, osteoporosis, bone tumors, osteomyelitis, and periodontitis, are explored. Their properties include excellent drug loading and sustained release abilities, high antibacterial activity, and bone induction abilities. This review enables readers to better understand the cutting-edge progress of MOFs in bone regeneration applications, which is crucial for the design of and functional research on MOF-related nanomaterials.

Staphylococcal enterotoxins (SEs) are major contributors to foodborne intoxications. Reliable detection methods for SEs are essential to maintain food safety and protect public health. Since the heat-stable toxins also exert their toxic effect in the absence of the bacterium, reliance on DNA detection alone can be misleading: it does not allow for determining which specific toxins encoded by a given strain are produced and epidemiologically linked with a given outbreak. Commercially available diagnostic assays for SE detection are so far limited in sensitivity and specificity as well as in the range of targeted toxins (SEA–SEE), thus non-targeted SEs linked to foodborne illness remain undetected at the protein level. This study aimed to develop a highly sensitive and specific multiplex suspension immunoassay (SIA) for SEA to SEI. To this end, high-affinity monoclonal antibodies (mAbs) for the specific detection of the individual SEs were generated. When implemented in sandwich ELISAs and multiplex SIA, these mAbs demonstrated exceptional sensitivity with detection limits in the low picogram per millilitre range. When applied for the analysis of SE production in liquid cultures of a panel of 145 whole-genome sequenced strains of Staphylococcus spp. and Enterococcus faecalis, the novel multiplex SIA detected and differentiated the eight SEs with assay accuracies of 86.9–100%. Notably, the multiplex SIA covered one to four sequence variants for each of the individual SEs. Validation confirmed high recovery rates and reliable performance in three representative complex food matrices. The implementation of the novel mAbs in a multiplex SIA enabled, for the first time, simultaneous detection, differentiation, and quantification of multiple SEs from minimal sample volumes using Luminex® technology. As a result, the multiplex SIA will help strengthen food safety protocols and public health response capabilities.

Love and economics are usually considered to be opposites: While love is seen as an irrational, unexplainable and ungovernable feeling towards another person, economics is regarded as the art of egoistic, profit-oriented, rational calculations and actions. But are they, really? By examining a wide range of literary and historical sources throughout European modernity, the papers assembled in this volume investigate how the process of finding a partner or spouse interlaces love and economics. In their analysis of Early Modern marriage legislation, drama, Spanish novellas, Jane Austen’s novels, films, dating apps and more, they reveal major cultural-historical changes in the notions of love and economics, and stress the role that concepts of gender, epistemic discourse, and media play in their interrelated history. Yet, despite their differing findings, they all show one thing: that „opposition“ is far too simple a term to grasp the complicated relation of emotion and calculation.

Dietary fibre can modify colostrum and milk composition in sows. Bile acids (BA) aid in fat digestion and lipid absorption and are important signalling molecules for the digestive tract. The aim of this study was to determine BA concentration in colostrum from sows fed two different sources of dietary fibre during gestation and lactation and from the intestinal digesta of their 4-6-days-old suckling offspring. Twenty sows were fed diets enriched with either 15% high-fermentable sugar beet pulp (SBP, n = 10) or 15% low-fermentable lignocellulose (LNC, n = 10). Sow colostrum, piglet gallbladder content, ileum and colon digesta were assessed for BA using high-performance liquid chromatography coupled to triple-quadrupole mass spectrometry. In colostrum, lithocholic acid and oxolithocholic acid were higher in sows fed SBP vs. LNC (p = 0.005 and p = 0.003, respectively), while 3α,7α,12α-trihydroxycholestanoic acid and glycohyodeoxycholic acid were higher in colostrum from sows fed LNC vs. SBP (p = 0.039, p = 0.002, respectively). In the piglet bile, cholic acid and taurodeoxycholic acid were higher in SBP vs. LNC group (p = 0.02, p = 0.001, respectively), while taurochenodeoxycholic acid was higher in LNC vs. SBP group (p = 0.035). In the piglet ileum digesta, lithocholic acid was higher in SBP vs. LNC (p = 0.015). In the piglet colon digesta, lithocholic acid and ursodeoxycholic acid were higher in SBP vs. LNC (p = 0.001 and p = 0.007, respectively). Addition of specific dietary fibres to sow diets differentially influences the BA in colostrum. Dietary fibres in sow diets can impact on the intestinal BA composition in piglets with a possible consequence on the digestive physiology and health in the offspring.