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Purpose Delayed diagnosed injuries (DDI) in severely injured patients are an essential problem faced by emergency staff. Aim of the current study was to analyse incidence and type of DDI in a large trauma cohort. Furthermore, factors predicting DDI were investigated to create a score to identify patients at risk for DDI. Methods Multiply injured patients admitted between 2011 and 2020 and documented in the TraumaRegister DGU® were analysed. Primary admitted patients with severe injuries and/or intensive care who survived at least 24 h were included. The prevalence, type and severity of DDI were described. Through multivariate logistic regression analysis, risk factors for DDI were identified. Results were used to create a ‘Risk for Delayed Diagnoses’ (RIDD) score. Results Of 99,754 multiply injured patients, 9,175 (9.2%) had 13,226 injuries first diagnosed on ICU. Most common DDI were head injuries (35.8%), extremity injuries (33.3%) and thoracic injuries (19.7%). Patients with DDI had a higher ISS, were more frequently unconscious, in shock, required more blood transfusions, and stayed longer on ICU and in hospital. Multivariate analysis identified seven factors indicating a higher risk for DDI (OR from 1.2 to 1.9). The sum of these factors gives the RIDD score, which expresses the individual risk for a DDI ranging from 3.6% (0 points) to 24.8% (6 + points). Conclusion DDI are present in a sounding number of trauma patients. The reported results highlight the importance of a highly suspicious and thorough physical examination in the trauma room. The introduced RIDD score might help to identify patients at high risk for DDI. A tertiary survey should be implemented to minimise delayed diagnosed or even missed injuries.

Background/Objective: This prospective, multicenter observational cohort study was carried out in 12 trauma centers in Germany and Switzerland. Its purpose was to evaluate the rate of undertriage, as well as potential consequences, and relate these with different Trauma Team Activation Protocols (TTA-Protocols), as this has not been done before in Germany. Methods: Each trauma center collected the data during a three-month period between December 2019 and February 2021. All 12 participating hospitals are certified as supra-regional trauma centers. Here, we report a subgroup analysis of undertriaged patients. Those included in the study were all consecutive adult patients (age ≥ 18 years) with acute trauma admitted to the emergency department of one of the participating hospitals by the prehospital emergency medical service (EMS) within 6 h after trauma. The data contained information on age, sex, trauma mechanism, pre- and in-hospital physiology, emergency interventions, emergency surgical interventions, intensive care unit (ICU) stay, and death within 48 h. Trauma team activation (TTA) was initiated by the emergency medical services. This should follow the national guidelines for severe trauma using established field triage criteria. We used various denominators, such as ISS, and criteria for the appropriateness of TTA to evaluate the undertriage in four groups. Results: This study included a total of 3754 patients. The average injury severity score was 5.1 points, and 7.0% of cases (n = 261) presented with an injury severity score (ISS) of 16+. TTA was initiated for a total of 974 (26%) patients. In group 1, we evaluated how successful the actual practice in the EMS was in identifying patients with ISS 16+. The undertriage rate was 15.3%, but mortality was lower in the undertriage cohort compared to those with a TTA (5% vs. 10%). In group 2, we evaluated the actual practice of EMS in terms of identifying patients meeting the appropriateness of TTA criteria; this showed a higher undertriage rate of 35.9%, but as seen in group 1, the mortality was lower (5.9% vs. 3.3%). In group 3, we showed that, if the EMS were to strictly follow guideline criteria, the rate of undertriage would be even higher (26.2%) regarding ISS 16+. Using the appropriateness of TTA criteria to define the gold standard for TTA (group 4), 764 cases (20.4%) fulfilled at least one condition for retrospective definition of TTA requirement. Conclusions: Regarding ISS 16+, the rate of undertriage in actual practice was 15.3%, but those patients did not have a higher mortality.

In mammalian genomes, differentially methylated regions (DMRs) and histone marks including trimethylation of histone 3 lysine 27 (H3K27me3) at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. However, neither parent-of-origin-specific transcription nor imprints have been comprehensively mapped at the blastocyst stage of preimplantation development. Here, we address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos. We find that seventy-one genes exhibit previously unreported parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expressed). Uniparental expression of nBiX genes disappears soon after implantation. Micro-whole-genome bisulfite sequencing (µWGBS) of individual uniparental blastocysts detects 859 DMRs. We further find that 16% of nBiX genes are associated with a DMR, whereas most are associated with parentally-biased H3K27me3, suggesting a role for Polycomb-mediated imprinting in blastocysts. nBiX genes are clustered: five clusters contained at least one published imprinted gene, and five clusters exclusively contained nBiX genes. These data suggest that early development undergoes a complex program of stage-specific imprinting involving different tiers of regulation. In most mammals, imprinted genes contain epigenetic marks that differ in each parental genome and control their parent-of-origin-specific expression. Here, the authors map imprinted genes in mouse preimplantation embryos and find that imprinted gene expression in blastocysts is mainly dependent on Polycomb-mediated H3K27me3-associated gene silencing.

Members of the Wnt/wingless family of secreted proteins act as short-range inducers and long-range organizers during axis formation, organogenesis and tumorigenesis in many developing tissues 1 . Wnt signalling pathways are conserved in nematodes, insects and vertebrates 2 . Despite its developmental significance, the evolutionary origin of Wnt signalling is unclear. Here we describe the molecular characterization of members of the Wnt signalling pathway—Wnt, Dishevelled, GSK3, β-Catenin and Tcf/Lef—in Hydra , a member of the evolutionarily old metazoan phylum Cnidaria. Wnt and Tcf are expressed in the putative Hydra head organizer, the upper part of the hypostome. Wnt, β-Catenin and Tcf are transcriptionally upregulated when head organizers are established early in bud formation and head regeneration. Wnt and Tcf expression domains also define head organizers created by de novo pattern formation in aggregates. Our results indicate that Wnt signalling may be involved in axis formation in Hydra and support the idea that it was central in the evolution of axial differentiation in early multicellular animals.

Purpose The purpose was to compare two approaches for the acquisition and analysis of dynamic-contrast-enhanced MRI data with respect to differences in the modelling of the arterial input-function (AIF), the dependency of the model parameters on physiological parameters and their numerical stability. Eight hundred tissue concentration curves were simulated for different combinations of perfusion, permeability, interstitial volume and plasma volume based on two measured AIFs and analysed according to the two commonly used approaches. The transfer constants (Approach 1) K trans and (Approach 2) k ep were correlated with all tissue parameters. K trans showed a stronger dependency on perfusion, and k ep on permeability. The volume parameters (Approach 1) v e and (Approach 2) A were mainly influenced by the interstitial and plasma volume. Both approaches allow only rough characterisation of tissue microcirculation and microvasculature. Approach 2 seems to be somewhat more robust than 1, mainly due to the different methods of CA administration.

Self-organization has been demonstrated in a variety of systems ranging from chemical-molecular to ecosystem levels, and evidence is accumulating that it is also fundamental for animal development. Yet, self-organization can be approached experimentally in only a few animal systems. Cells isolated from the simple metazoan Hydra can aggregate and form a complete animal by self-organization. By using this experimental system, we found that clusters of 5-15 epithelial cells are necessary and sufficient to form de novo head-organizing centers in an aggregate. Such organizers presumably arise by a community effect from a small number of cells that express the conserved HyBra1 and HyWnt genes. These local sources then act to pattern and instruct the surrounding cells as well as generate a field of lateral inhibition that ranges up to 1,000 μ m. We propose that conserved patterning systems in higher animals originate from extremely robust and flexible molecular self-organizing systems that were selected for during early metazoan evolution.

Objectives To determine the prevalence of pharyngeal and rectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections among men who have sex with men (MSM) in Germany and describe associations between these infections, sexual practices and other factors to provide an evidence base for screening recommendations. Methods We conducted a cross-sectional study in 22 sentinel sites of sexually transmitted infections across Germany. Pharyngeal and rectal swabs were collected and tested for CT and NG with a nucleic acid amplification test (NAAT). Information on HIV status, number of sex partners and sexual practices was collected and linked to NAAT results. Results Overall, 2247 MSM were screened for pharyngeal or rectal CT and NG infections; median age was 34 years (range 16–83). Prevalence of CT was 1.5% in pharyngeal and 8.0% in rectal specimens. Prevalence of NG was 5.5% in pharyngeal and 4.6% in rectal specimens. Local symptoms were reported in 5.1% of pharyngeal and 11.9% of rectal infections. Altogether 90.8% of rectal or pharyngeal infections would remain undetected if only symptomatic cases were tested. Rectal infection was significantly more likely in men reporting multiple partners (2–5 partners, OR=1.85; 6–10 partners, OR=2.10; >11 partners, OR=2.95), men diagnosed with HIV (OR=1.60) and men practising receptive anal intercourse without a condom (OR=1.54). Pharyngeal infection was more likely in men reporting multiple partners (6–10 partners, OR=2.88; >11 partners, OR=4.96), and men diagnosed with HIV (OR=1.78). Conclusions Pharyngeal and rectal infections in sexually active MSM can remain undetected and thus transmissible if swabbing is not offered routinely. Screening should be offered particularly to MSM diagnosed with HIV and MSM reporting multiple partners.

ABSTRACT In mammals, chromatin marks at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. This control is thought predominantly to involve parent-specific differentially methylated regions (DMR) in genomic DNA. However, neither parent-of-origin-specific transcription nor DMRs have been comprehensively mapped. We here address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos (blastocysts). Transcriptome-analysis identified 71 genes expressed with previously unknown parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expression). Uniparental expression of nBiX genes disappeared soon after implantation. Micro-whole-genome bisulfite sequencing (μWGBS) of individual uniparental blastocysts detected 859 DMRs. Only 18% of nBiXs were associated with a DMR, whereas 60% were associated with parentally-biased H3K27me3. This suggests a major role for Polycomb-mediated imprinting in blastocysts. Five nBiX-clusters contained at least one known imprinted gene, and five novel clusters contained exclusively nBiX-genes. These data suggest a complex program of stage-specific imprinting involving different tiers of regulation. Competing Interest Statement The authors have declared no competing interest.