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Summary: Background: Real-world data on gene addition therapy (GAT) with onasemnogene abeparvovec (OA), including all age groups and with or without symptoms of the disease before treatment are needed to provide families with evidence-based advice and realistic therapeutic goals. Aim of this study is therefore a population-based analysis of all patients with SMA treated with OA across Germany, Austria and Switzerland (D-A-CH). Methods: This observational study included individuals with Spinal Muscular Atrophy (SMA) treated with OA in 29 specialized neuromuscular centers in the D-A-CH-region. A standardized data set including WHO gross motor milestones, SMA validated motor assessments, need for nutritional and respiratory support, and adverse events was collected using the SMArtCARE registry and the Swiss-Reg-NMD. Outcome data were analyzed using a prespecified statistical analysis plan including potential predictors such as age at GAT, SMN2 copy number, past treatment, and symptom status. Findings: 343 individuals with SMA (46% male, 54% female) with a mean age at OA of 14.0 months (range 0–90, IQR 20.0 months) were included in the analysis. 79 (23%) patients were clinically presymptomatic at the time of treatment. 172 (50%) patients received SMN2 splice-modifying drugs prior to GAT (risdiplam: n = 16, nusinersen: n = 154, both: n = 2). Functional motor improvement correlated with lower age at GAT, with the best motor outcome in those younger than 6 weeks, carrying 3 SMN2 copies, and being clinically presymptomatic at time of treatment. The likelihood of requiring ventilation or nutritional support showed a significantly increase with older age at the time of GAT and remained stable thereafter. Pre-treatment had no effect on disease trajectories. Liver-related adverse events occurred significantly less frequently up to 8 months of age. All other adverse events showed an even distribution across all age and weight groups. Interpretation: Overall, motor, respiratory, and nutritional outcome were dependent on timing of GAT and initial symptom status. It was best in presymptomatic children treated within the first six weeks of life, but functional motor scores also increased significantly after treatment in all age groups up to 24 months. Additionally, OA was best tolerated when administered at a young age. Our study therefore highlights the need for SMA newborn screening and immediate treatment to achieve the best possible benefit-risk ratio. Funding: The SMArtCARE and Swiss-Reg-NMD registries are funded by different sources (see acknowledgements).

This review examines the latest advancements in compositional and quantitative cartilage MRI techniques, addressing both their potential and challenges. The integration of these advancements promises to improve disease detection, treatment monitoring, and overall patient care. We want to highlight the pivotal task of translating these techniques into widespread clinical use, the transition of cartilage MRI from technical validation to clinical application, emphasizing its critical role in identifying early signs of degenerative and inflammatory joint diseases. Recognizing these changes early may enable informed treatment decisions, thereby facilitating personalized medicine approaches. The evolving landscape of cartilage MRI underscores its increasing importance in clinical practice, offering valuable insights for patient management and therapeutic interventions. This review aims to discuss the old evidence and new insights about the evaluation of articular cartilage through MRI, with an update on the most recent literature published on novel quantitative sequences.

Background: The nationwide study German Health Update (GEDA) 2021/2022-Diabetes was conducted to assess the current healthcare and health situation of adults with diabetes in Germany. Methods: GEDA 2021/2022-Diabetes comprises a sample of adults with diagnosed diabetes from the general population. The analysis focuses on adults aged 45 years and over with type 2 diabetes (N = 1,448) and provides selected indicators on diabetes care as well as mental, social and general health. Results: 87.5 % of participants aged 45 years and over with type 2 diabetes are treated with blood glucose-lowering medication. 36.5 % receive insulin alone or in combination with other antidiabetics; 0.7 % use an insulin pump. Almost 96 % had an HbA1c measurement in the last year and about two thirds each report annual foot and eye examinations, participation in a diabetes self-management education programme and self-monitoring of their feet and of blood glucose (12.0 % with continuous glucose monitoring). On average, the quality of diabetes care is perceived as moderate. 23.8 % rate their mental health as excellent/very good. More than a tenth each have anxiety or depressive symptoms and feelings of loneliness. Half rate their general health as very good/good. Conclusions: There is a potential for improvement in the quality of diabetes care and the mental and physical health of adults with type 2 diabetes.

ABSTRACT: Avian cellulitis in broilers, caused by avian pathogenic Escherichia coli, is a major cause for carcass rejections during meat inspection, resulting in significant economic losses. In this study, we analysed E. coli isolates obtained from broiler chickens affected by cellulitis for their genetic relatedness and antimicrobial resistance phenotype and genotype. The objective was to determine whether there is a clonal spread or whether these clinical isolates differ. For this purpose, E. coli was isolated from swab samples collected from diseased broilers across 77 poultry farms in Germany, resulting in 107 isolates. These isolates were subjected to serotyping, PCR-based phylotyping and macrorestriction analysis with subsequent pulsed-field gel-electrophoresis for typing purposes. In addition, the presence of virulence genes associated with avian pathogenic E. coli (APEC) was investigated by PCR. Antimicrobial susceptibility of the isolates was examined by the disk diffusion method according to CLSI guidelines and subsequently, the presence of corresponding resistance genes was investigated by PCR. Typing results revealed that a significant proportion of the isolates belonged to serotype O78:K80, which is one of the major APEC serotypes. Phylogenetic grouping showed that phylogenetic group D was most commonly represented (n = 49). Macrorestriction analysis showed overall heterogenous results, however, some clustering of closely related isolates was observed. The level of antimicrobial resistance was high, with 83.8% of isolates non-susceptible to at least one class of antimicrobial agents and 40% of isolates showing resistance to at least three classes. The most frequently observed resistance was to ampicillin, mediated by blaTEM (n = 56). However, few isolates were non-susceptible to ciprofloxacin (n = 8) and none of the isolates was resistant to 3rd generation cephalosporins or carbapenems. Overall, the results show that genetically diverse APEC associated with avian cellulitis can be found among and within German poultry farms. While most isolates were antimicrobial resistant, resistance levels to high(est) priority critically important antimicrobials were low.

Abstract Process Analytical Technologies (PATs) are taking a key role in the run for automatization in the biopharmaceutical industry. Spectroscopic methods such as Raman spectroscopy or mid‐infrared (MIR) spectroscopy are getting more recognition in the recent years for inline monitoring of bioprocesses due to their ability to measure various molecules simultaneously. However, their dependency on laborious model calibration making them a challenge to implement. In this study, a novel one‐point calibration that requires a single reference point prior to the inline monitoring of glucose and lactate in bioprocesses with MIR spectroscopy is assessed with 22 mammalian cell perfusion (PER) processes in two different scales and four different products. Concentrations are predicted over all PERs runs with a root mean square error (RMSE) of 0.29 g/L for glucose and 0.24 g/L for lactate, respectively. For comparison conventional partial least square regression (PLSR) models were used and trained with spectroscopic data from six bioreactor runs in two different scales and three products. The general accuracy of those models (RMSE of 0.41 g/L for glucose and 0.16 g/L for lactate) are in the range of the accuracy of the one‐point calibration. This shows the potential of the one‐point calibration as an approach making spectroscopy more accessible for bioprocess development.

Der Beitrag berichtet Ergebnisse einer Evaluationsstudie aus dem Projekt SprachReflex, das sprachdidaktisch fundierte, multimediale Medienpakete für die Professionalisierung von angehenden Lehrkräften im berufsbildenden Bereich entwickelt. Die Bearbeitung der Medienpakete soll den Auf- und Ausbau sprachreflexiver Kompetenzen unterstützen, die für die Planung und Durchführung eines sprachbewussten Unterrichts in sprachlich heterogenen Klassen grundlegend sind. Die Medienpakete sind durch einen hohen Anwendungsbezug und durch eine multimediale Gestaltung geprägt. Insgesamt werden drei Medienpakete entwickelt: 1) Mehrsprachigkeit und Schule, 2) Erfassung sprachlicher Fähigkeiten, 3) sprachbewusster Unterricht. Medienpaket 1 wurde bereits in die Hochschullehre implementiert und erprobt. Das Medienpaket zielt auf die Aneignung von Grundlagenwissen über Sprache, Spracherwerb, sprachliche Heterogenität und Mehrsprachigkeit ab, das als Ausgangspunkt für sprachreflexive Handlungskompetenzen gesehen wird. An der Untersuchung nahmen 126 Lehramtsstudierende teil. Mittels eines Interventions-Kontrollgruppen-Designs mit Prä- und Posttestung wurde die Wirksamkeit des Medienpakets überprüft. Die Ergebnisse belegen einen signifikanten Wissenszuwachs der Interventionsgruppe, während sich das Leistungsniveau der Kontrollgruppe nicht verbesserte. Insgesamt deuten die Ergebnisse darauf hin, dass im Rahmen eines selbstregulierten Lernprozesses die Bearbeitung des Medienpakets zu einem Zuwachs an Fachwissen führen kann. Damit eröffnen sich Möglichkeiten, das Medienpaket in der Lehrkräftebildung phasen- und fachübergreifend zu nutzen.

Abstract Invasive nontyphoidal Salmonella (iNTS) causes extraintestinal infections with ~15% case fatality in many countries. However, the mechanism by which iNTS emerged in China remains unaddressed. We conducted clinical investigations of iNTS infection with recurrent treatment failure, caused by underreported Salmonella enterica serovar Livingstone (SL). Genomic epidemiology demonstrated five clades in the SL population and suggested that the international animal feed trade was a likely vehicle for their introduction into China, as evidenced by multiple independent transmission incidents. Importantly, isolates from Clade‐5‐I‐a/b, predominant in China, showed an invasive nature in mice, chicken and zebrafish infection models. The antimicrobial susceptibility testing revealed most isolates (> 96%) in China are multidrug‐resistant (MDR). Overall, we offer exploiting genomics in uncovering international transmission led by the animal feed trade and highlight an emerging hypervirulent clade with increased resistance to frontline antibiotics.

ABSTRACT Bordetella avium causes a highly infectious upper respiratory tract disease in turkeys and other poultry with high economic losses. Considering the antimicrobial resistance crisis, bacteriophages (phages) may be an alternative approach for treating bacterial infections such as bordetellosis. Here, we describe seven B. avium phages, isolated from drinking water and feces from chicken and turkey farms. They showed strong bacteriolytic activity with a broad host range and used lipopolysaccharides (LPS) as a host receptor for their adsorption. All phages are myoviruses based on their structure observed by transmission electron microscopy. Genome sequence analyses revealed genome assembly sizes ranging from 39,087 to 43,144 bp. Their permutated genomes were organized colinearly, with a conserved module order, and were packed according to a predicted headful packing strategy. Notably, they contained genes encoding putative markers of lysogeny, indicative of temperate phages, despite their lytic phenotype. Further investigation revealed that the phages could indeed undergo a lysogenic life cycle with varying frequency. However, the lysogenic bacteria were still susceptible to superinfection with the same phages. This lack of stable superinfection immunity after lysogenization appears to be a characteristic feature of B. avium phages, which is favorable in terms of a potential therapeutic use of phages for the treatment of avian bordetellosis. IMPORTANCE To maintain the effectiveness of antibiotics over the long term, alternatives to treat infectious diseases are urgently needed. Therefore, phages have recently come back into focus as they can specifically infect and lyse bacteria and are naturally occurring. However, there is little information on phages that can infect pathogenic bacteria from animals, such as the causative agent of bordetellosis of poultry, B. avium. Therefore, in this study, B. avium phages were isolated and comprehensively characterized, including whole-genome analysis. Although phenotypically the phages were thought to undergo a lytic cycle, we demonstrated that they undergo a lysogenic phase, but that infection does not confer stable host superinfection immunity. These findings provide important information that could be relevant for potential biocontrol of avian bordetellosis by using phage therapy.

Based on in silico, in vitro, in situ, and in vivo evaluations, this study aims to establish and optimize the chemical exchange saturation transfer (CEST) imaging of lactate (Lactate-CEST—LATEST). To this end, we optimized LATEST sequences using Bloch–McConnell simulations for optimal detection of lactate with a clinical 3 T MRI scanner. The optimized sequences were used to image variable lactate concentrations in vitro (using phantom measurements), in situ (using nine human cadaveric lower leg specimens), and in vivo (using four healthy volunteers after exertional exercise) that were then statistically analyzed using the non-parametric Friedman test and Kendall Tau-b rank correlation. Within the simulated Bloch–McConnell equations framework, the magnetization transfer ratio asymmetry (MTRasym) value was quantified as 0.4% in the lactate-specific range of 0.5–1 ppm, both in vitro and in situ, and served as the imaging surrogate of the lactate level. In situ, significant differences (p < 0.001) and strong correlations (τ = 0.67) were observed between the MTRasym values and standardized intra-muscular lactate concentrations. In vivo, a temporary increase in the MTRasym values was detected after exertional exercise. In this bench-to-bedside comprehensive feasibility study, different lactate concentrations were detected using an optimized LATEST imaging protocol in vitro, in situ, and in vivo at 3 T, which prospectively paves the way towards non-invasive quantification and monitoring of lactate levels across a broad spectrum of diseases.

Chemical Exchange Saturation Transfer (CEST) magnetic resonance imaging (MRI) provides a novel method for analyzing biomolecule concentrations in tissues without exogenous contrast agents. Despite its potential, achieving a high signal-to-noise ratio (SNR) is imperative for detecting small CEST effects. Traditional metrics such as Magnetization Transfer Ratio Asymmetry (MTRasym) and Lorentzian analyses are vulnerable to image noise, hampering their precision in quantitative concentration estimations. Recent noise-reduction algorithms like principal component analysis (PCA), nonlocal mean filtering (NLM), and block matching combined with 3D filtering (BM3D) have shown promise, as there is a burgeoning interest in the utilization of neural networks (NNs), particularly autoencoders, for imaging denoising. This study uses the Bloch–McConnell equations, which allow for the synthetic generation of CEST images and explores NNs efficacy in denoising these images. Using synthetically generated phantoms, autoencoders were created, and their performance was compared with traditional denoising methods using various datasets. The results underscored the superior performance of NNs, notably the ResUNet architectures, in noise identification and abatement compared to analytical approaches across a wide noise gamut. This superiority was particularly pronounced at elevated noise intensities in the in vitro data. Notably, the neural architectures significantly improved the PSNR values, achieving up to 35.0, while some traditional methods struggled, especially in low-noise reduction scenarios. However, the application to the in vivo data presented challenges due to varying noise profiles. This study accentuates the potential of NNs as robust denoising tools, but their translation to clinical settings warrants further investigation.

(1) Background: In children, SARS-CoV-2 infection is mostly accompanied by mild COVID-19 symptoms. However, multisystem inflammatory syndrome (MIS-C) and long-term sequelae are often severe complications. Therefore, the protection of the pediatric population against SARS-CoV-2 with effective vaccines is particularly important. Here, we compare the humoral and cellular immune responses elicited in children (n = 15, aged 5–11 years) vaccinated with the RBD-based vaccines SOBERANA® 02 and SOBERANA® Plus combined in a heterologous scheme with those from children (n = 10, aged 4–11 years) who recovered from mild symptomatic COVID-19. (2) Methods: Blood samples were taken 14 days after the last dose for vaccinated children and 45–60 days after the infection diagnosis for COVID-19 recovered children. Anti-RBD IgG and ACE2-RBD inhibition were assessed by ELISA; IgA, cytokines, and cytotoxic-related proteins were determined by multiplex assays. Total B and T cell subpopulations and IFN-γ release were measured by multiparametric flow cytometry using a large panel of antibodies after in vitro stimulation with S1 peptides. (3) Results: Significant higher levels of specific anti-RBD IgG and IgA and ACE2-RBD inhibition capacity were found in vaccinated children in comparison to COVID-19 recovered children. Th1-like and Th2-like CD4+ T cells were also significantly higher in vaccinated subjects. IFN-γ secretion was higher in central memory CD4+ T cells of COVID-19 recovered children, but no differences between both groups were found in the CD4+ and CD8+ T cell effector, terminal effector, and naïve T cell subpopulations. In contrast to low levels of IL-4, high levels of IL-2, IL-6, IFN-γ, and IL-10 suggest a predominant Th1 cell polarization. Cytotoxic-related proteins granzyme A and B, perforin, and granulin were also found in the supernatant after S1 stimulation in both vaccinated and recovered children. (4) Conclusions: Vaccination with the heterologous scheme of SOBERANA® 02/SOBERANA® Plus induces a stronger antibody and cellular immune response compared to natural infections in young children.

Among the Brassica oleracea L. crops, kale has gained increased global recognition in recent years as a healthy food item due to its high nutritional value and versatility. Additionally, the diversity of different kale varieties has started to be explored across large latitudes from the Mediterranean to north temperate climates. Specifically, glucosinolates are the predominant phytochemicals found in kale leaves, contributing to the specific taste of this vegetable, and they are affected by environmental factors such as temperature. To date, no study has investigated the effect of chilling on glucosinolate diversity and, thus, the taste in genetically different kale cultivars at the same time. Given the variability of glucosinolates observed among cultivars, we evaluated the impact of acclimation to cold temperatures on glucosinolate levels in curly kale, Lacinato kale, and a feral type using high-performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-ESI-qTOF-MS). We targeted the short-term impact (after 12 h) on glucosinolates as well as the longer-term effect (after seven days) of cold acclimation. Our results revealed different molecular patterns regarding the change in glucosinolates in the feral type compared to curly kale and Lacinato-type kale. In the latter ones, primary aliphatic glucosinolates were induced (the glucoraphanin in Lacinato kale increased by more than 200%). The indole glucobrassicin was not significantly affected. Conversely, in the feral type the indole glucobrassicin was reduced by 35% after cold acclimation, whereas aliphatic glucosinolates were hardly affected. The results indicate that both genetic and environmental factors are important for the composition of glucosinolate patterns in kale. In conclusion, to obtain plants with an improved nutritional value, considering both temperature and the choice of cultivar is crucial during kale cultivation. Future breeding attempts of kale should also emphasize the cultivar-dependent cold acclimation patterns reported here.

Between April 2019 and September 2020, 23,001 people aged 15 or over responded to questions about their health and living conditions for the German Health Update (GEDA 2019/2020-EHIS). The results are representative of the German resident population aged 15 or above. The response rate was 21.6%. The study used a questionnaire based on the third wave of the European Health Interview Survey (EHIS), which was carried out in all EU member states. EHIS consists of four modules on health status, health care provision, health determinants, and socioeconomic variables. The data are collected in a harmonised manner and therefore have a high degree of international comparability. They constitute an important source of information for European health policy and health reporting and are made available by the Statistical Office of the European Union (Eurostat). They also form the basis of the Federal Health Reporting undertaken in Germany. Data collection began in April 2019, just under a year before the beginning of the SARS-CoV-2 pandemic, and continued into its initial phase, as of March 2020. As such, data from the current GEDA wave can also be used to conduct research into the health impact of the SARS-CoV-2 pandemic.

Digital teaching interventions allow for tailor-made university teaching. This is especially relevant for teacher education, where applicable professional teaching knowledge needs to be promoted for later professional success. Digital teaching tools have been shown to be a promising supplement for this purpose. Even though the corresponding demands in teacher education have been increasing in recent years, the need to develop digital learning tools usable in instruction is still urgent. The TWIND project develops digital learning tools for teacher education and evaluates them in a quasi-experimental design. The present work investigates the usability and application of these newly developed tools. Sixty-three trainee teachers worked independently over four weeks with one of two digital learning tools, focusing on either ‘Multilingualism in Classrooms’ or ‘Professional Communication in Classrooms.’ This study includes a pre-post-test of pedagogical knowledge facets as well as student and instructor ratings on the digital tools. The digital learning tools led to a positive change in the respective target facets of pedagogical knowledge. The student and instructor feedback reflected positively on the usability and usefulness of the new digital tools. Based on these findings, the limitations of the study as well as implications for further research and teacher education practice have been outlined.

(1) Background: We aim to investigate age-related changes in cartilage structure and composition in the metacarpophalangeal (MCP) joints using magnetic resonance (MR) biomarkers. (2) Methods: The cartilage tissue of 90 MCP joints from 30 volunteers without any signs of destruction or inflammation was examined using T1, T2, and T1ρ compositional MR imaging techniques on a 3 Tesla clinical scanner and correlated with age. (3) Results: The T1ρ and T2 relaxation times showed a significant correlation with age (T1ρ: Kendall-τ-b = 0.3, p < 0.001; T2: Kendall-τ-b = 0.2, p = 0.01). No significant correlation was observed for T1 as a function of age (T1: Kendall-τ-b = 0.12, p = 0.13). (4) Conclusions: Our data show an increase in T1ρ and T2 relaxation times with age. We hypothesize that this increase is due to age-related changes in cartilage structure and composition. In future examinations of cartilage using compositional MRI, especially T1ρ and T2 techniques, e.g., in patients with osteoarthritis or rheumatoid arthritis, the age of the patients should be taken into account.

Back and neck pain are widespread and can significantly reduce quality of life. A cross-sectional telephone survey (N=5,009) was carried out between October 2019 and March 2020 to gain a valid estimate of the prevalence of back and neck pain among adults in Germany. In addition to the frequency and intensity of back and neck pain, the study collected information about quality of life and comorbidity. The findings showed that 61.3% of respondents reported back pain in the last twelve months. Lower back pain was reported about twice as often as upper back pain, with 15.5% of respondents stating that they experienced chronic back pain. 45.7% reported neck pain, and 15.6% of respondents have experienced lower and upper back pain in addition to neck pain in the past year. Women are affected by all types of pain more often than men. About half of the respondents categorise their back or neck pain as moderate; older respondents report significantly more pain episodes per month than younger respondents. The results described here provide a comprehensive picture of the population-related limitations associated with back and neck pain and are used within the framework of the BURDEN 2020 study to quantify key indicators of burden of disease calculation.

Abstract Background To compare the glycosaminoglycan (GAG) content of lumbar intervertebral disks (IVDs) of patients with ankylosing spondylitis (AS) and healthy volunteers and to investigate the association of GAG depletion and disease-related clinical and imaging features. Methods Lumbar spines of 50 AS patients (mean age 50 ± 10.5 years) and 30 age-matched volunteers were studied with 3-T magnetic resonance imaging (MRI) and conventional radiographs (CR). The MRI protocol included high-resolution morphological sequences and the compositional GAG chemical exchange saturation transfer imaging technique (gagCEST). Morphological images were analyzed by three raters for inflammatory activity, fat deposition, disk degeneration, and structural changes on CR. Clinical and serological measures included the Bath AS Disease Activity (BASDAI) and Bath AS Function (BASFI) Indices and C-reactive protein (CRP) levels. GagCEST values of both groups were compared using a linear mixed model. Kendall-Tau correlation analyses were performed. Results GagCEST values were significantly lower in AS patients (2.0 ± 1.7%) vs. healthy volunteers (2.4 ± 1.8%), p = 0.001. Small, yet significant correlations were found between gagCEST values and CRP levels (τ = − 0.14, p = 0.007), BASFI (τ = − 0.18, p

The prototype fexA gene confers combined resistance to chloramphenicol and florfenicol. However, fexA variants mediating resistance only to chloramphenicol have been identified, such as in the case of a Staphylococcus aureus isolate recovered from poultry meat illegally imported to Germany. The effects of the individual mutations detected in the fexA sequence of this isolate were investigated in this study. A total of 11 fexA variants, including prototype fexA and variants containing the different previously described mutations either alone or in different combinations, were generated by on-chip gene synthesis and site-directed mutagenesis. The constructs were inserted into a shuttle vector and transformed into three recipient strains (Escherichia coli, Staphylococcus aureus, and Salmonella Typhimurium). Subsequently, minimal inhibitory concentrations (MIC) of florfenicol and chloramphenicol were determined. In addition, protein modeling was used to predict the structural effects of the mutations. The lack of florfenicol-resistance mediating properties of the fexA variants could be attributed to the presence of a C110T and/or G98C mutation. Transformants carrying fexA variants containing either of these mutations, or both, showed a reduction of florfenicol MICs compared to those transformants carrying prototype fexA or any of the other variants. The significance of these mutations was supported by the generated protein models, indicating a substitution toward more voluminous amino-acids in the substrate-binding site of FexA. The remaining mutations, A391G and C961A, did not result in lower florfenicol-resistance compared to prototype fexA.

In recent years, much research evaluating the radiographic destruction of finger joints in patients with rheumatoid arthritis (RA) using deep learning models was conducted. Unfortunately, most previous models were not clinically applicable due to the small object regions as well as the close spatial relationship. In recent years, a new network structure called RetinaNets, in combination with the focal loss function, proved reliable for detecting even small objects. Therefore, the study aimed to increase the recognition performance to a clinically valuable level by proposing an innovative approach with adaptive changes in intersection over union (IoU) values during training of Retina Networks using the focal loss error function. To this end, the erosion score was determined using the Sharp van der Heijde (SvH) metric on 300 conventional radiographs from 119 patients with RA. Subsequently, a standard RetinaNet with different IoU values as well as adaptively modified IoU values were trained and compared in terms of accuracy, mean average accuracy (mAP), and IoU. With the proposed approach of adaptive IoU values during training, erosion detection accuracy could be improved to 94% and an mAP of 0.81 ± 0.18. In contrast Retina networks with static IoU values achieved only an accuracy of 80% and an mAP of 0.43 ± 0.24. Thus, adaptive adjustment of IoU values during training is a simple and effective method to increase the recognition accuracy of small objects such as finger and wrist joints.

Antimicrobial resistance is a global health threat that involves complex, opaque transmission processes in the environment. In particular, wildlife appears to function as a reservoir and vector for antimicrobial-resistant bacteria as well as resistance genes. In the present study, the occurrence of antimicrobial-resistant Escherichia coli was determined in marine mammals and various fish species of the North and Baltic Seas. Rectal or faecal swabs were collected from 66 live-caught or stranded marine mammals and 40 fish specimens. The antimicrobial resistance phenotypes and genotypes of isolated E. coli were determined using disk diffusion tests and PCR assays. Furthermore, isolates were assigned to the four major phylogenetic groups of E. coli. Additionally, post mortem examinations were performed on 41 of the sampled marine mammals. The investigations revealed resistant E. coli in 39.4% of the marine mammal samples, while no resistant isolates were obtained from any of the fish samples. The obtained isolates most frequently exhibited resistance against aminoglycosides, followed by β-lactams. Of the isolates, 37.2% showed multidrug resistance. Harbour porpoises (Phocoena phocoena) mainly carried E. coli isolates belonging to the phylogenetic group B1, while seal isolates were most frequently assigned to group B2. Regarding antimicrobial resistance, no significant differences were seen between the two sampling areas or different health parameters, but multidrug-resistant isolates were more frequent in harbour porpoises than in the sampled seals. The presented results provide information on the distribution of antimicrobial-resistant bacteria in the North and Baltic Seas, and highlight the role of these resident marine mammal species as sentinels from a One Health perspective.

Antimicrobial-resistant bacteria pose a serious global health risk for humans and animals, while the role of wildlife in the dynamic transmission processes of antimicrobial resistance in environmental settings is still unclear. This study determines the occurrence of antimicrobial-resistant Escherichia coli in the free-living great cormorants (Phalacrocorax carbo) of the North and Baltic Sea coasts of Schleswig-Holstein, Germany. For this, resistant E.coli were isolated from cloacal or faecal swabs and their antimicrobial resistance pheno- and genotypes were investigated using disk diffusion tests and PCR assays. The isolates were further assigned to the four major phylogenetic groups, and their affiliation to avian pathogenic E. coli (APEC) was tested. Resistant E. coli were isolated from 66.7% of the 33 samples, and 48.9% of all the resistant isolates showed a multidrug resistance profile. No spatial differences were seen between the different sampling locations with regard to the occurrence of antimicrobial resistance or multidrug resistance. Most commonly, resistance percentages occurred against streptomycin, followed by tetracycline and sulfonamides. More than half of the isolates belonged to the phylogenetic group B1. Of all the isolates, 24.4% were classified as APEC isolates, of which almost 82% were identified as multidrug-resistant. These results add information on the dispersal of antimicrobial-resistant bacteria in wild birds in Germany, thereby allowing conclusions on the degree of environmental contamination and potential public health concerns.

Objective: Even though cartilage loss is a known feature of psoriatic arthritis (PsA), research is sparse on its role in the pathogenesis of PsA and its potential use for disease detection and monitoring. Using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and dynamic contrast-enhanced MRI (DCE MRI), research has shown that early cartilage loss is strongly associated with synovial inflammation in rheumatoid arthritis (RA). The aim of this study was to determine if acute inflammation is associated with early cartilage loss in small finger joints of patients with PsA.Methods: Metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints of 17 patients with active PsA were evaluated by high-resolution 3 Tesla dGEMRIC and DCE MRI using a dedicated 16-channel hand coil. Semi-quantitative and quantitative perfusion parameters were calculated. Images were analyzed by two independent raters for dGEMRIC indices, PsA MRI scores (PsAMRIS), total cartilage thickness (TCT), and joint space width (JSW).Results: We found significant negative correlations between perfusion parameters (except Kep) and dGEMRIC indices, with the highest value at the MCP joints (KTrans: τ = −0.54, p = 0.01; Kep: τ = −0.02, p = 0.90; IAUC: τ = −0.51, p = 0.015; Initial Slope: τ = −0.54, p = 0.01; Peak: τ = −0.67, p = 0.002). Heterogeneous correlations were detected between perfusion parameters and both, total PsAMRIS and PsAMRIS synovitis sub-scores. No significant correlation was seen between any perfusion parameter and JSW and/or TCT.Conclusion: As examined by DCE MRI and dGEMRIC, there is a potential association between early cartilage loss and acute synovial inflammation in small finger joints of PsA patients.

BACKGROUND:Bacteria that have acquired antimicrobial resistance, in particular ESBL-producing Enterobacteriaceae, are an important healthcare concern. Therefore, transmission routes and risk factors are of interest, especially for the carriage of ESBL-producing E. coli. Since there is an enhanced risk for pig slaughterhouse employees to carry ESBL-producing Enterobacteriaceae, associated with animal contact as potential risk factor, the present study investigated the occurrence of ESBL-producing Enterobacteriaceae in poultry slaughterhouse employees. Due to the higher level of resistant Enterobacteriaceae in primary poultry production than in pig production, a higher risk of intestinal colonization of poultry slaughterhouse employees was expected. RESULTS:ESBL-producing Enterobacteriaceae were detected in 5.1% (5 of 99) of the fecal samples of slaughterhouse workers. The species of these isolates was confirmed as E. coli. PCR assays revealed the presence of the genes blaCTX-M-15 (n = 2) and blaSHV-12 (n = 3) in these isolates, partly in combination with the β-lactamase gene blaTEM-135. Participants were divided into two groups according to their occupational exposure and results indicated an increased probability of colonization with ESBL-producing Enterobacteriaceae for the group of 'higher exposure' (OR 3.7, exact 95% CI 0.6-23.5; p = 0.4). For intestinal colonization with ESBL-producing Enterobacteriaceae, a prevalence of 10% (3/30) was observed in the group of 'higher exposure' versus 2.9% (2/69) in the group of 'lower exposure'. Employees in working steps such as 'hanging' poultry in the process of slaughter and 'evisceration' seemed to have a higher risk for intestinal colonization with ESBL-producing Enterobacteriaceae compared to the group of 'lower exposure'. CONCLUSION:This study is the first of its kind to collect data on the occupational exposure of slaughterhouse workers to ESBL-producing Enterobacteriaceae in Europe. The results suggested that colonization with ESBL-producing Enterobacteriaceae is associated with occupational exposure in poultry slaughterhouses. However, the presence of ESBL-producing E. coli isolates in only 5.1% (5/99) of the tested employees in poultry slaughterhouses suggests a lower transmission risk than in pig slaughterhouses.

The Robert Koch Institute (RKI) regularly conducts nationally representative cross-sectional studies (KiGGS, DEGS and GEDA) as part of the nationwide health monitoring system. In addition to these health surveys, data is collected in telephone interviews either on specific thematic fields (such as diabetes) or specific groups (such as medical staff) that were not or only insufficiently covered by the larger health surveys. As they are flexible and fast, ad hoc surveys conducted via telephone interviews can respond to specific epidemiological and health political questions. This article describes the procedures applied in ad hoc telephone interview surveys, which were newly introduced as a standardised method in 2017 and are applied by the Laboratory for Health Surveys at the RKI. The article presents the stages of project management such as concept development, establishment of a concept for data protection, questionnaire development, pre-test and field phase, calculation of weighting factors and provision of the final data set. The aim is to describe the process and shed light on the standardised procedures, the reported quality indicators and the breadth of possible scenarios of application.

Abstract Background Food products of animal origin brought into the EU from third countries, both legally and illegally, can harbor foodborne pathogens such as Salmonella enterica. In this study, we examined five S. enterica isolates recovered either from legally imported chicken meat (n = 3) or from meat products confiscated from air travel passengers arriving in Germany (n = 2). The isolates were serotyped and further characterized by antimicrobial susceptibility testing, PCR-detection and sequencing of genes associated with antimicrobial resistances, and macrorestriction analysis. Transferability of resistance to third-generation cephalosporins was assessed by conjugation experiments and the plasmids tested for their incompatibility groups. Results The three isolates from legal imports were identified as S. Heidelberg or as non-flagellated. All three isolates were identified as AmpC producers carrying bla CMY-2 and as non-susceptible to ciprofloxacin. They were additionally resistant to tetracycline and sulfamethoxazole. The bla CMY-2-carrying plasmids were transferable by conjugation and belonged to incompatibility groups IncI1 or IncA/C. The two isolates from illegally imported meat belonged to the serovars Infantis or Weltevreden. The former was phenotypically resistant to five classes of antimicrobial agents while the S. Weltevreden isolate was fully susceptible to all agents tested. Conclusion The results of this study demonstrate that meat products imported from third countries, both legally and illegally, can harbor multiresistant Salmonella enterica. Consequently, these imports could constitute a source for the dissemination of antimicrobial resistant isolates, including those resistant to third-generation cephalosporins and fluoroquinolones.

Abstract Background Wound healing represents a dynamic process involving directional migration of different cell types. Chemokines, a family of chemoattractive proteins, have been suggested to be key players in cell-to-cell communication and essential for directed migration of structural cells. Today, the role of the chemokine network in cutaneous wound healing is not fully understood. Unraveling the chemokine-driven communication pathways in this complex process could possibly lead to new therapeutic strategies in wound healing disorders. Methods We performed a systematic, comprehensive time-course analysis of the expression and function of a broad variety of cytokines, growth factors, adhesion molecules, matrixmetalloproteinases and chemokines in a murine cutaneous wound healing model. Results Strikingly, chemokines were found to be among the most highly regulated genes and their expression was found to coincide with the expression of their matching receptors. Accordingly, we could show that resting and activated human primary keratinocytes (CCR3, CCR4, CCR6, CXCR1, CXCR3), dermal fibroblasts (CCR3, CCR4, CCR10) and dermal microvascular endothelial cells (CCR3, CCR4, CCR6, CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3) express a distinct and functionally active repertoire of chemokine receptors. Furthermore, chemokine ligand–receptor interactions markedly improved the wound repair of structural skin cells in vitro. Conclusion Taken together, we here present the most comprehensive analysis of mediators critically involved in acute cutaneous wound healing. Our findings suggest therapeutic approaches for the management of wound closure by targeting the chemokine network.

Okra is an important crop species for smallholder farmers in many tropical and subtropical regions of the world. Its interaction with mycorrhiza has been rarely studied, and little is known about its mycorrhizal dependency, especially under drought stress. In a glasshouse experiment, we investigated the effect of Arbuscular Mycorrhiza Fungi (AMF) inoculation on growth, evapotranspiration, mineral nutrition and root morphology of five okra cultivars under ample water and drought stress conditions. ‘Khartoumia’, ‘HSD6719’, ‘HSD7058’, ‘Sarah’ and ‘Clemson Spineless’-cultivars commonly used by farmers in Sudan were chosen for their geographical, morphological and breeding background variations. The plants were either inoculated with R. irregulare or mock-inoculated. Seven weeks after seeding, the soil–water content was either maintained at 20% w/w or reduced to 10% w/w to impose drought stress. Drought stress resulted in plant P deficiency and decreased shoot dry biomass (DB), especially in HSD7058 and Clemson Spineless (69% and 56% decrease in shoot DB, in the respective cultivars). Plant inoculation with AMF greatly enhanced the shoot total content of P and the total DB in all treatments. The mycorrhizal dependency (MD)—the degree of total plant DB change associated with AM colonization—differed among the cultivars, irrespective of the irrigation treatment. Key determinants of MD were the root phenotype traits. Khartoumia (with the highest MD) had the lowest root DB, root-to-shoot ratio, and specific root length (SRL). Meanwhile, HSD6719 (with the lowest MD) had the highest respective root traits. Moreover, our data suggest a relationship between breeding background and MD. The improved cultivar Khartoumia showed the highest MD compared with the wild-type Sarah and the HSD7058 and HSD6719 landraces (higher MD by 46%, 17% and 32%, respectively). Interestingly, the drought-affected HSD7058 and Clemson Spineless exhibited higher MD (by 27% and 15%, respectively) under water-deficiency compared to ample water conditions. In conclusion, the mediation of drought stress in the okra plant species by AMF inoculation is cultivar dependent. The presence of AMF propagules in the field soil might be important for increasing yield production of high MD and drought susceptible cultivars, especially under drought/low P environments.

Sodium MRI has the potential to depict cartilage health accurately, but synovial fluid can influence the estimation of sodium parameters of cartilage. Therefore, this study aimed to reduce the impact of synovial fluid to render the quantitative compositional analyses of cartilage tissue technically more robust. Two dedicated protocols were applied for determining sodium T1 and T2* relaxation times. For each protocol, data were acquired from 10 healthy volunteers and one patient with patellar cartilage damage. Data recorded with multiple repetition times for T1 measurement and multi-echo data acquired with an additional inversion recovery pulse for T2* measurement were analysed using biexponential models to differentiate longitudinal relaxation components of cartilage (T1,car) and synovial fluid (T1,syn), and short (T2s*) from long (T2l*) transversal relaxation components. Sodium relaxation times and concentration estimates in patellar cartilage were successfully determined: T1,car = 14.5 ± 0.7 ms; T1,syn = 37.9 ± 2.9 ms; c(T1-protocol) = 200 ± 48 mmol/L; T2s* = 0.4 ± 0.1 ms; T2l* = 12.6 ± 0.7 ms; c(T2*-protocol) = 215 ± 44 mmol/L for healthy volunteers. In conclusion, a robust determination of sodium relaxation times is possible at a clinical field strength of 3T to quantify sodium concentrations, which might be a valuable tool to determine cartilage health.

Insects as novel foods are gaining popularity in Europe. Regulation (EU) 2015/2283 laid the framework for the application process to market food insects in member states, but potential hazards are still being evaluated. The aim of this study was to investigate samples of edible insect species for the presence of antimicrobial-resistant and Shiga toxin-producing Escherichia coli (STEC). Twenty-one E. coli isolates, recovered from samples of five different edible insect species, were subjected to antimicrobial susceptibility testing, PCR-based phylotyping, and macrorestriction analysis. The presence of genes associated with antimicrobial resistance or virulence, including stx1, stx2, and eae, was investigated by PCR. All isolates were subjected to genome sequencing, multilocus sequence typing, and serotype prediction. The isolates belonged either to phylogenetic group A, comprising mostly commensal E. coli, or group B1. One O178:H7 isolate, recovered from a Zophobas atratus sample, was identified as a STEC. A single isolate was resistant to tetracyclines and carried the tet(B) gene. Overall, this study shows that STEC can be present in edible insects, representing a potential health hazard. In contrast, the low resistance rate among the isolates indicates a low risk for the transmission of antimicrobial-resistant E. coli to consumers.

Although alpacas are not used for milk production a detailed knowledge on the composition of the colostrum and milk is needed for development of colostrum and milk replacers. The aim of the present study was to measure the concentration of fat, protein, lactose, and minerals in alpaca colostrum and milk. Colostrum samples were taken daily over four days after parturition from 20 multiparous alpaca mares. Milk samples were obtained monthly, during the first four months of lactation from 17 alpacas. Composition of colostrum and milk differed in numerous indicators. The concentrations of fat and lactose increased from day 1 (0.5%, 4.0%) to day 4 (5.3%, 5.0%), protein decreased from 20.4% on day 1 to 8.3% on day 4. In milk these three indicators did not change during the lactation. Minerals have been little studied in alpaca colostrum and milk in the past, many of which had the highest concentrations in colostrum immediately after birth. The results of the present study do not support that goat’s milk is the preferred substitute for feeding crias. This study contributes to the knowledge of the composition of alpaca colostrum and milk which can be of particular use in developing replacers.

While morphologic magnetic resonance imaging (MRI) is the imaging modality of choice for the evaluation of ligamentous wrist injuries, it is merely static and incapable of diagnosing dynamic wrist instability. Based on real-time MRI and algorithm-based image post-processing in terms of convolutional neural networks (CNNs), this study aims to develop and validate an automatic technique to quantify wrist movement. A total of 56 bilateral wrists (28 healthy volunteers) were imaged during continuous and alternating maximum ulnar and radial abduction. Following CNN-based automatic segmentations of carpal bone contours, scapholunate and lunotriquetral gap widths were quantified based on dedicated algorithms and as a function of wrist position. Automatic segmentations were in excellent agreement with manual reference segmentations performed by two radiologists as indicated by Dice similarity coefficients of 0.96 ± 0.02 and consistent and unskewed Bland–Altman plots. Clinical applicability of the framework was assessed in a patient with diagnosed scapholunate ligament injury. Considerable increases in scapholunate gap widths across the range-of-motion were found. In conclusion, the combination of real-time wrist MRI and the present framework provides a powerful diagnostic tool for dynamic assessment of wrist function and, if confirmed in clinical trials, dynamic carpal instability that may elude static assessment using clinical-standard imaging modalities.

Lumbar intervertebral disc (IVD) degeneration is characterized by structural and compositional changes. This study aimed to assess the glycosaminoglycan (GAG) content of IVDs of patients with adolescent idiopathic scoliosis (AIS) and healthy controls using GAG chemical exchange saturation transfer (gagCEST) imaging. Ten AIS patients (mean age 18.3 ± 8.2 years) and 16 healthy controls (mean age 25.5 ± 1.7 years) were included. Clinical standard morphologic MR images (T1w-, T2w-, and STIR-sequences), to rule out further spinal disorders and assess IVD degeneration using the Pfirrmann score, and compositional gagCEST sequences were acquired on a 3T MRI. In AIS patients, the most distal scoliotic curve was determined on whole-spine conventional radiographs and morphological MRI and IVDs were divided as to whether they were affected by scoliotic deformity, i.e., proximal (affected, aIVDs) or distal (unaffected, uaIVDs) to the stable vertebra of the most distal scoliotic curve. Linear mixed models were used to compare mean gagCEST-values. Over all segments, AIS-patients’ IVDs exhibited significantly lower gagCEST-values than the controls: 2.76 [2.32, 3.20]% (AIS), 3.51 [3.16, 3.86]% (Control); p = 0.005. Meanwhile, no significant differences were found for gagCEST values comparing aIVDs with uaIVDs. In conclusion, as a powerful diagnostic adjunct, gagCEST imaging may be prospectively applied to detect early compositional degenerative changes in patients suffering from AIS.

Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) represent major healthcare concerns. The role of wildlife in the epidemiology of these bacteria is unclear. The purpose of this study was to determine their prevalence in wild boars in Germany and to characterize individual isolates. A total of 375 fecal samples and 439 nasal swabs were screened for the presence of ESBL-/AmpC-E. coli and MRSA, respectively. The associations of seven demographic and anthropogenic variables with the occurrence of ESBL-/AmpC-E. coli were statistically evaluated. Collected isolates were subjected to antimicrobial susceptibility testing, molecular typing methods, and gene detection by PCR and genome sequencing. ESBL-/AmpC-E. coli were detected in 22 fecal samples (5.9%) whereas no MRSA were detected. The occurrence of ESBL-/AmpC-E. coli in wild boars was significantly and positively associated with human population density. Of the 22 E. coli, 19 were confirmed as ESBL-producers and carried genes belonging to blaCTX-M group 1 or blaSHV-12. The remaining three isolates carried the AmpC-β-lactamase gene blaCMY-2. Several isolates showed additional antimicrobial resistances. All four major phylogenetic groups were represented with group B1 being the most common. This study demonstrates that wild boars can serve as a reservoir for ESBL-/AmpC-producing and multidrug-resistant E. coli.

Using glycosaminoglycan Chemical Exchange Saturation Transfer (gagCEST) magnetic resonance imaging (MRI), this study comparatively evaluated the GAG contents of lumbar intervertebral disks (IVDs) of patients with non-specific low back pain (nsLBP), radiculopathy, and asymptomatic volunteers to elucidate the association of clinical manifestation and compositional correlate. A total of 18 patients (mean age 57.5 ± 22.5 years) with radiculopathy, 16 age-matched patients with chronic nsLBP and 20 age-matched volunteers underwent standard morphologic and compositional gagCEST MRI on a 3T scanner. In all cohorts, GAG contents of lumbar IVDs were determined using gagCEST MRI. An assessment of morphologic IVD degeneration based on the Pfirrmann classification and T2-weighted sequences served as a reference. A linear mixed model adjusted for multiple confounders was used for statistical evaluation. IVDs of patients with nsLBP showed lower gagCEST values than those of volunteers (nsLBP: 1.3% [99% confidence intervals (CI): 1.0; 1.6] vs. volunteers: 1.9% [99% CI: 1.6; 2.2]). Yet, IVDs of patients with radiculopathy (1.8% [99% CI: 1.4; 2.1]) were not different from patients with nsLBP or volunteers. In patients with radiculopathy, IVDs directly adjacent to IVD extrusions demonstrated lower gagCEST values than distant IVDs (adjacent: 0.9% [99% CI: 0.3; 1.5], distant: 2.1% [99% CI: 1.7; 2.5]). Advanced GAG depletion in nsLBP and directly adjacent to IVD extrusions in radiculopathy indicates close interrelatedness of clinical pathology and compositional degeneration.

Purpose: The present study assessed the effects of the GABAA receptor (R) agonist muscimol (MUS), and the GABAAR antagonist bicuculline (BIC) on neocortical and subcortical radioligand binding to dopamine D2/3Rs in relation to motor and exploratory behaviors in the rat.Methods: D2/3R binding was measured with small animal SPECT in baseline and after challenge with either 1 mg/kg MUS or 1 mg/kg BIC, using [123I]IBZM as radioligand. Motor/exploratory behaviors were assessed for 30 min in an open field prior to radioligand administration. Anatomical information was gained with a dedicated small animal MRI tomograph. Based on the Paxinos rat brain atlas, regions of interest were defined on SPECT-MRI overlays. Estimations of the binding potentials in baseline and after challenges were obtained by computing ratios of the specifically bound compartments to the cerebellar reference region.Results: After MUS, D2/3R binding was significantly reduced in caudateputamen, nucleus accumbens, thalamus, substania nigra/ventral tegmental area, and posterior hippocampus relative to baseline (0.005 ≤ p ≤ 0.012). In all these areas, except for the thalamus, D2/3R binding was negatively correlated with grooming in the first half and positively correlated with various motor/exploratory behaviors in the second half of the testing session. After BIC, D2/3R binding was significantly elevated in caudateputamen (p = 0.022) and thalamus (p = 0.047) relative to baseline. D2/3R binding in caudateputamen and thalamus was correlated negatively with sitting duration and sitting frequency and positively with motor/exploratory behaviors in the first half of the testing time.Conclusions: Findings indicate direct GABAergic control over nigrostriatal and mesolimbic dopamine levels in relation to behavioral action. This may be of relevance for neuropsychiatric conditions such as anxiety disorder and schizophrenia, which are characterized by both dopaminergic and GABAergic dysfunction.

Though imports of products of animal origin into the European Union (EU) have to comply with legal requirements and quality standards of the community, food consignment rejections at external EU borders have been increasing in recent years. This study explored microbiological metrics according to national target and critical values valid for samples at consumer level of 498 fresh poultry meat and 136 fresh pork filets from consignments subjected to physical checks during clearing at the border inspection post Hamburg harbour between January 2014 and December 2015 with ISO standard methods. Quantitative results indicated that critical thresholds for aerobic counts, Enterobacteriaceae, and E. coli were never surpassed. Merely for staphylococci, one poultry sample (0.2%) and 10 pork samples (9.3%) exceeded the critical limit (3.7 log cfu/g). However, qualitative analyses revealed that, Staphylococcus aureus was present in 16% and 10% of all poultry and pork samples, respectively, though no methicillin-resistant Staphylococcus aureus could be confirmed. Moreover, E. coli was present in 50% and 67% of all pork and poultry samples, respectively, and thereof 33 isolates were confirmed as extended-spectrum β-lactamase-producing E. coli. Only 1.2% of the poultry samples were unacceptable due to the presence of Salmonella spp., whereas they were not detected in any pork sample. Campylobacter spp. were not detected in any sample. Though imported pork and poultry meat complies mostly with national market requirements, it might pose a potential risk to public health, especially for a direct or indirect foodborne transmission of imported, uncommon strains of zoonotic bacteria.

Children's interpretations of sentences containing focus particles do not seem adult-like until school age. This study investigates how German 4-year-old children comprehend sentences with the focus particle 'nur' (only) by using different tasks and controlling for the impact of general cognitive abilities on performance measures. Two sentence types with 'only' in either pre-subject or pre-object position were presented. Eye gaze data and verbal responses were collected via the visual world paradigm combined with a sentence-picture verification task. While the eye tracking data revealed an adult-like pattern of focus particle processing, the sentence-picture verification replicated previous findings of poor comprehension, especially for 'only' in pre-subject position. A second study focused on the impact of general cognitive abilities on the outcomes of the verification task. Working memory was related to children's performance in both sentence types whereas inhibitory control was selectively related to the number of errors for sentences with 'only' in pre-subject position. These results suggest that children at the age of 4 years have the linguistic competence to correctly interpret sentences with focus particles, which--depending on specific task demands--may be masked by immature general cognitive abilities.

Food products of animal origin can serve as a vehicle for Staphylococcus (S.) aureus, a facultative pathogen involved in a variety of diseases. As a result, international trade and illegal transportation of foodstuffs can facilitate the distribution of S. aureus over long distances. In this study, we investigated S. aureus isolates recovered from meat products confiscated from passengers returning from non-EU countries at two German airports and from samples of legally imported meats from non-EU countries. The aim was to characterize isolates in regard to their genetic relatedness as well as their antimicrobial resistance profiles and major virulence factors in order to assess potential risks associated with these products. The isolates were characterized by spa typing, MLST, macrorestriction analysis, microarray analysis and antimicrobial susceptibility testing. MRSA isolates were further characterized by dru typing. The characteristics of the majority of the isolates indicated a human origin, rather than an association with livestock. The results further revealed a considerable heterogeneity among the MRSA isolates, despite their common origin. Overall, a plenitude of major virulence factors and antimicrobial resistances was detected among the isolates, highlighting the potential risks associated with contaminated meat products and the transportation of such products among different countries.

Recent studies have demonstrated that the chemokine receptor CXCR4 plays a crucial role in organ-specific metastasis formation. Although a variety of studies showed the expression of chemokine receptors, in particular, CXCR4, by gastrointestinal tumors, the precise mechanisms of chemokine receptor-mediated homing of cancer cells to specific sites of metastasis remained elusive. Here, we used liver metastatic human HEP-G2 hepatoma and HT-29LMM colon cancer cells expressing functional CXCR4 to dissect the metastatic cascade by intravital fluorescence microscopy. Immunohistochemistry revealed that the CXCR4 ligand CXCL12 is expressed by endothelial cells and likely Kupffer cells lining the liver sinusoids. Tumor cell adhesion and extravasation in vivo was quantitatively analyzed using intravital fluorescence microscopy. Treatment of cells with an anti-CXCR4 antibody did not affect cell adhesion but significantly impaired tumor cell extravasation (HEP-G2; isotype control: 22.3% ± 4.3% vs anti-CXCR4: 6.0% ± 5.0%, P < .001). In addition, pretreatment of tumor cells with the ligand CXCL12 enhanced the activation of the small GTPases Rho, Rac, and cdc42 as well as tumor cell extravasation without affecting tumor cell adhesion within liver sinusoids. Taken together, the findings of the present study provide first in vivo insights into the early events of chemokine ligand/receptor-mediated liver metastasis formation of tumor cells and define tumor cell extravasation rather than tumor cell arrest as the rate-limiting event.

Editorial for Vol. 2, issue 1 (2013).

The following mission statements by linguists and literary scholars working in different institutional and cultural contexts and at different stages of their careers are intended to map out the terrain covered by this journal. They tell similar stories about how these scholars came to cross the disciplinary boundary that too often divides their two fields, and they reveal a number of shared interests and emphases. But they also highlight the diversity of methodologies to which this journal is open – from metrics and stylistics to the cognitive sciences and Systemic Functional Grammar. The hopes and expectations voiced by the authors are partly pragmatic, expressing the wish that the journal’s Open Access format will have a broader reach than a journal published in the “traditional” way would, notably to colleagues outside of Western Europe. They also, however, emphasise the journal’s potential to shape our conception of “literary linguistics” and, therefore, to make an innovative contribution to shaping what continues to be a contested and often misunderstood “field”.

CD4 T-cell help is required for the induction of efficient CD8 T-cells responses and the generation of memory cells. Lack of CD4 T-cell help may contribute to an exhausted CD8 phenotype and viral persistence. Little is known about priming of CD4 T-cells by liver-derived antigen. We used TF-OVA mice expressing ovalbumin in hepatocytes to investigate CD4 T-cell priming by liver-derived antigen and the impact of CD4 T-cell help on CD8 T-cell function. Naïve and effector CD4 T-cells specific for ovalbumin were transferred into TF-OVA mice alone or together with naïve ovalbumin-specific CD8 T-cells. T-cell activation and function were analyzed. CD4 T-cells ignored antigen presented by liver antigen-presenting cells (APCs) in vitro and in vivo but were primed in the liver-draining lymph node and the spleen. No priming occurred in the absence of bone-marrow derived APCs capable of presenting ovalbumin in vivo. CD4 T-cells primed in TF-OVA mice displayed defective Th1-effector function and caused no liver damage. CD4 T-cells were not required for the induction of hepatitis by CD8 T-cells. Th1-effector but not naïve CD4 T-cells augmented the severity of liver injury caused by CD8 T-cells. Our data demonstrate that CD4 T-cells fail to respond to liver-derived antigen presented by liver APCs and develop defective effector function after priming in lymph nodes and spleen. The lack of CD4 T-cell help may be responsible for insufficient CD8 T-cell function against hepatic antigens.