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Abstract For time-sensitive treatment of a patient with malignant melanoma, physicians must obtain a rapid overview of the patient’s status. This study aimed to analyze context-specific features and processes at the point of care to derive requirements for a dashboard granting more straightforward access to information. The Think-Aloud method, contextual inquiries, and interviews were performed with physicians from the Department of Dermatology at the University Hospital Essen in Germany. The user statements and observations that were obtained were grouped and categorized using an affinity diagram. Based on the derived subjects, requirements were defined, confirmed, and prioritized. The resulting affinity diagram revealed four topics of importance at the point of care. These topics are “Identifying and Processing the Important”, a comprehensive “Patient Record”, tasks and challenges in the “Clinical Routine”, and interactions and experiences with the available “Systems”. All aspects have been reflected in 135 requirements for developing context- and indication-specific patient dashboards. Our work has elucidated the most important aspects to consider when designing a dashboard that improves patient care by enabling physicians to focus on the relevant information. Furthermore, it has been demonstrated that the aspects most often mentioned are not context-specific and can be generalized to other medical contexts.

IntroductionAcetabular fractures are among the most challenging injuries in traumatology. The complex anatomy usually requires extensive surgical approaches baring the risk for iatrogenic damage to surrounding neurovascular structures. As a viable alternative, minimally invasive endoscopic techniques have emerged during the recent years. This paper reports on the feasibility of different coupling mechanisms for a novel suprapectineal plate especially designed for minimally invasive acetabular surgery.MethodsA total number of 34 participants contributed to the present study, who differed in their arthroscopic and surgical experience. A laparoscopic model was used to compare four different coupling mechanisms by the number of failed attempts, the time required for plate fixation, the influence of surgical experience as well as the learning success for each individual coupling mechanism. Moreover, the feasibility of each mechanism was evaluated by a questionnaire.ResultsThe results demonstrate that plates employing grooved and pressure-sliding coupling mechanisms exhibit fewer failed attempts and reduce trial times, especially in contrast to sole sliding mechanisms. Furthermore, our study revealed that proficiency in endoscopic procedures significantly influenced the outcome. Notably, the subjective evaluation of the participants show that the pressure base and pressure-slide base plate designs are the most supportive and feasible designs.ConclusionsIn summary, the present study evaluates for the first-time different plate and coupling designs for minimal-invasive surgery, indicating a superior feasibility for plates with a grooved and pressure-sliding mechanism.

In contrast to other common anticoagulants such as citrate and low-molecular-weight heparin (LMWH), high-molecular-weight heparin (HMWH) induces the expression of matrix metalloproteinase (MMP)-9, which is also measured as a biomarker for stroke in blood samples. Mechanistically, HMWH-stimulated T cells produce cytokines that induce monocytic MMP-9 expression. Here, the influence of further anticoagulants (Fondaparinux, Hirudin, and Alteplase) and the heparin-contaminating glycosaminoglycans (GAG) hyaluronic acid (HA), dermatan sulfate (DS), chondroitin sulfate (CS), and over-sulfated CS (OSCS) on MMP-9 was analyzed to assess its suitability as a biomarker under various conditions. Therefore, starved Jurkat T cells were stimulated with anticoagulants/contaminants. Subsequently, starved monocytic THP-1 cells were incubated with the conditioned Jurkat supernatant, and MMP-9 mRNA levels were monitored (quantitative (q)PCR). Jurkat-derived mediators secreted in response to anticoagulants/contaminants were also assessed (proteome profiler array). The supernatants of HMWH-, Hirudin-, CS-, and OSCS-treated Jurkat cells comprised combinations of activating mediators and led to a significant (in the case of OSCS, dramatic) MMP-9 induction in THP-1. HA induced MMP-9 only in high concentrations, while LMWH, Fondaparinux, Alteplase, and DS had no effect. This indicates that depending on molecular weight and charge (but independent of anticoagulant activity), anticoagulants/contaminants provoke the expression of T-cell-derived cytokines/chemokines that induce monocytic MMP-9 expression, thus potentially impairing the diagnostic validity of MMP-9.

Vision: Potential therapeutic target for corneal blindness A protein called nuclear factor of activated T cells 5 (NFAT5) plays a significant role in maintaining fluid balance in the cornea, the anterior part of the eye. Disturbances in corneal fluid balance and pathological swelling known as edema potentially lead to loss of corneal transparency and blindness. Deniz Hos and colleagues at the University of Cologne, Germany, studied the functional role of NFAT5 in a mouse model of corneal injury. They found that corneal injury induced significantly increased NFAT5 activity. Furthermore, NFAT5 in macrophages was crucial for controlling corneal fluid balance and the extent of and recovery from corneal edema. These results suggest that drugs able to modify NFAT5 activity could offer a novel way to combat edema-induced corneal blindness.

Abstract Background Pelvic fractures are often associated with spine injury in polytrauma patients. This study aimed to determine whether concomitant spine injury influence the surgical outcome of pelvic fracture. Methods We performed a retrospective analysis of data of patients registered in the German Pelvic Registry between January 2003 and December 2017. Clinical characteristics, surgical parameters, and outcomes were compared between patients with isolated pelvic fracture (group A) and patients with pelvic fracture plus spine injury (group B). We also compared apart patients with isolated acetabular fracture (group C) versus patients with acetabular fracture plus spine injury (group D). Results Surgery for pelvic fracture was significantly more common in group B than in group A (38.3% vs. 36.6%; p = 0.0002), as also emergency pelvic stabilizations (9.5% vs. 6.7%; p

Integrity of epithelial and endothelial cell barriers is of critical importance for health, barrier disruption is a hallmark of numerous diseases, of which many are driven by carbonyl stressors such as methylglyoxal (MG). Carnosine and anserine exert some MG-quenching activity, but the impact of these and of other histidine containing dipeptides on cell barrier integrity has not been explored in detail. In human proximal tubular (HK-2) and umbilical vein endothelial (HUVEC) cells, exposure to 200 µM MG decreased transepithelial resistance (TER), i.e. increased ionic permeability and permeability for 4-, 10- and 70-kDa dextran, membrane zonula occludens (ZO-1) abundance was reduced, methylglyoxal 5-hydro-5-methylimidazolones (MG-H1) formation was increased. Carnosine, balenine (ß-ala-1methyl-histidine) and anserine (ß-ala-3-methyl-histidine) ameliorated MG-induced reduction of TER in both cell types. Incubation with histidine, 1-/3-methylhistidine, but not with ß-alanine alone, restored TER, although to a lower extent than the corresponding dipeptides. Carnosine and anserine normalized transport and membrane ZO-1 abundance. Aminoguanidine, a well-described MG-quencher, did not mitigate MG-induced loss of TER. Our results show that the effects of the dipeptides on epithelial and endothelial resistance and junction function depend on the methylation status of histidine and are not exclusively explained by their quenching activity. [ABSTRACT FROM AUTHOR]

In contrast to other common anticoagulants such as citrate and low-molecular-weight heparin (LMWH), high-molecular-weight heparin (HMWH) induces the expression of matrix metalloproteinase (MMP)-9, which is also measured as a biomarker for stroke in blood samples. Mechanistically, HMWH-stimulated T cells produce cytokines that induce monocytic MMP-9 expression. Here, the influence of further anticoagulants (Fondaparinux, Hirudin, and Alteplase) and the heparin-contaminating glycosaminoglycans (GAG) hyaluronic acid (HA), dermatan sulfate (DS), chondroitin sulfate (CS), and over-sulfated CS (OSCS) on MMP-9 was analyzed to assess its suitability as a biomarker under various conditions. Therefore, starved Jurkat T cells were stimulated with anticoagulants/contaminants. Subsequently, starved monocytic THP-1 cells were incubated with the conditioned Jurkat supernatant, and MMP-9 mRNA levels were monitored (quantitative (q)PCR). Jurkat-derived mediators secreted in response to anticoagulants/contaminants were also assessed (proteome profiler array). The supernatants of HMWH-, Hirudin-, CS-, and OSCS-treated Jurkat cells comprised combinations of activating mediators and led to a significant (in the case of OSCS, dramatic) MMP-9 induction in THP-1. HA induced MMP-9 only in high concentrations, while LMWH, Fondaparinux, Alteplase, and DS had no effect. This indicates that depending on molecular weight and charge (but independent of anticoagulant activity), anticoagulants/contaminants provoke the expression of T-cell-derived cytokines/chemokines that induce monocytic MMP-9 expression, thus potentially impairing the diagnostic validity of MMP-9. [ABSTRACT FROM AUTHOR]

Abstract As Russia’s invasion of Ukraine continues, more and more people are calling for a ban on Russian energy imports. The proponents argue that abstaining from importing billions worth of coal, oil and gas will further increase the pressure on the Kremlin. Critics, however, including German Chancellor Olaf Scholz, warn of what they believe to be incalculable consequences, with the gas supply being particularly at risk. This article outlines the different options for substituting Russian coal, oil, and especially gas and explains why the wait-and-see attitude of the German government towards a complete import ban is understandable.

The regulatory T cell master transcription factor, Forkhead box P3 (Foxp3), has been detected in cancer cells; however, its role in breast tumor pathogenesis remains controversial. Here we assessed Foxp3 tumor intrinsic effects in experimental breast cancer using a Foxp3 binder peptide (P60) that impairs Foxp3 nuclear translocation. Cisplatin upregulated Foxp3 expression in HER2+ and triple-negative breast cancer (TNBC) cells. Foxp3 inhibition with P60 enhanced chemosensitivity and reduced cell survival and migration in human and murine breast tumor cells. We also developed an adenoviral vector encoding P60 (Ad.P60) that efficiently transduced breast tumor cells, reduced cell viability and migration, and improved the cytotoxic response to cisplatin. Conditioned medium from transduced breast tumor cells contained lower levels of IL-10 and improved the activation of splenic lymphocytes. Intratumoral administration of Ad.P60 in breast-tumor-bearing mice significantly reduced tumor infiltration of Tregs, delayed tumor growth, and inhibited the development of spontaneous lung metastases. Our results suggest that Foxp3 exerts protumoral intrinsic effects in breast cancer cells and that gene-therapy-mediated blockade of Foxp3 could constitute a therapeutic strategy to improve the response of these tumors to standard treatment.

Bias in clinical reasoning has been identified as one of the main sources of diagnostic errors. Clinical Decision Support Systems that suggest possible diagnoses and provide information to mitigate cognitive bias could support physicians in finding a less biased diagnosis. We examine the influence of confidence and experience on the probability to adjust the decision after receiving decision aid and whether forming a first opinion beforehand or immediately receiving decision support makes a difference. 103 physicians and medical students participated in an online experiment built on decision tasks formulated to trigger availability and representativeness bias. The analysis showed that the presentation of prevalence data to mitigate availability bias changed the final probability estimate of the diagnosis significantly. Prototypical data to counteract representativeness bias showed no significant change. Medical experience, confidence in the decision, and timing of support had no significant influence on the probability to change the estimate. [ABSTRACT FROM AUTHOR]