Probing the glioma micro-environment: Analysis using biopsy in combination with ultra-fast cyclic immunolabeling.

The interaction between gliomas and the immune system is poorly understood and thus hindering development of effective immunotherapies for glioma patients. The immune response is highly variable during tumor development, and affected by therapies such as surgery, radiation, and chemotherapy. Currently, analysis of these local changes is difficult due to poor accessibility of the tumor and high-morbidity of sampling. In this study, we developed a model for repeat-biopsy in mice to study these local immunological changes over time. Using fine needle biopsy we were able to safely and repeatedly collect cells from intracranial tumors in mice. Ultra-fast cycling technology (FAST) was used for multi-cycle immunofluorescence of retrieved cells, and provided insights in the changing immune response over time. The combination of these techniques can be utilized to study changes in the immune response in glioma or other intracranial diseases over time, and in response to treatment within the same animal.

Probing the glioma micro-environment: analysis using biopsy in combination with ultra-fast cyclic immunolabeling.

The interaction between gliomas and the immune system is poorly understood and thus hindering development of effective immunotherapies for glioma patients. The immune response is highly variable during tumor development, and affected by therapies such as surgery, radiation, and chemotherapy. Currently, analysis of these local changes is difficult due to poor accessibility of the tumor and high-morbidity of sampling. In this study, we developed a model for repeat-biopsy in mice to study these local immunological changes over time. Using fine needle biopsy we were able to safely and repeatedly collect cells from intracranial tumors in mice. Ultra-fast cycling technology (FAST) was used for multi-cycle immunofluorescence of retrieved cells, and provided insights in the changing immune response over time. The combination of these techniques can be utilized to study changes in the immune response in glioma or other intracranial diseases over time, and in response to treatment within the same animal.

Subjective Health Status, Health-Related Behavior, and Health Literacy of Health Professional Students: Results from a Cross-Sectional Study.

The importance of health promotion for health professional students is increasingly crucial, as the rising requirements for those students can have a negative impact on their health. Despite this awareness, there is still limited knowledge in Germany about the specific health needs of this group of students. This study's aim was, therefore, to assess the subjective health of first-year students and to identify health needs. Thus, this study is based on an online survey using standardized measurement instruments. First-year students from three degree programs were included. The data were analyzed descriptively. A total of n = 98 (72.6%) participated in the survey. The results showed that a major proportion of participants (80.3%) rated their health positively, but a significant proportion reported weight disorders (24%) and pre-existing health conditions (62.1%) at baseline. Interestingly, a high proportion (59%) reported a high level of mental well-being at the time of the survey. However, worrying findings regarding lifestyle behaviors, including physical inactivity (40.6%), smoking (20%), risky alcohol use (24%), and unhealthy eating habits (37%) were determined. In terms of health literacy, around 45% of students rated their health competencies as problematic. Furthermore, it was found that students with low health literacy had a significantly higher prevalence of low mental well-being (53.3% vs. 30.8%, p = 0.036) and unhealthy eating habits (48.8% vs. 26.5%, p = 0.027) compared to students with sufficient health literacy. Health professional students should be considered a relevant target group for health and health competence promotion from the beginning of their studies. The identified fields of action should be addressed in the context of health promotion. This is of particular importance as they are not only aimed at improving the students' well-being but also will later work directly with patients and, therefore, have a direct influence on the health of others.

Health of (dual) health professional students in German-speaking countries: a scoping review.

University education marks a new stage in life, which is associated with unknown demands and challenges and can have a negative impact on students' health. Therefore, health promotion in the university setting is becoming increasingly important. In this context, scientific data on the health situation play a crucial role in improving students' health. Thus, the aim of the scoping review was to highlight the current scope of research on the health of health professional students. It also explored problems and outlined key future challenges and solutions. The review was conducted using the Joanna Briggs Institute (JBI) methodology for a scoping review. A total of nine databases (PubMed, CINAHL, CareLit, LIVIVO, Scopus, Psyndex, PEDro, OTseeker, Google Scholar) were systematically searched. The following search criteria were defined: health professional students, health, Germany, German-speaking countries, all types of sources from 2012 to present are selected. The research studies were mapped in a table and health evidence of included studies was summarized narratively. The initial search resulted in 23,938 records. Seven records met the inclusion criteria and were included in the review. Six cross-sectional studies were conducted in Germany, and one cross-sectional study was conducted in Switzerland. In fact, one study included a representative population. Qualitative studies were not found. The most studies investigated health status, health behavior, and personal resources. Most of the studies examined female nursing students. The included studies indicated that the young students reported physical or mental health conditions. In addition, the studies also identified health resources of the students that need to be improved. In summary, there is currently limited health evidence on this group of students in German-speaking countries. Therefore, further research is needed to generate knowledge and comprehensively describe the health situation.

Monitoring a cohort of trainees: changes over time and associations between health literacy, health behaviour and health.

BACKGROUND: For many entrants, the initial stages of professional training are a challenge. Demands at work can lead to new physical and psychological stress, as well as new social requirements. These new requirements can influence the health behaviour and the state of health of young employees. In recent years, there have been many studies on health literacy (HL). HL represents resources and potentials that allow individuals to achieve improved control of their health and of factors that influence health. Thus, HL can influence both well-being and health. In the present study, the health of trainees in different branches (health and welfare services, office, sales, technology) is monitored over time ending in the period of the COVID-19 pandemic. Furthermore, the association between health literacy and health or health behaviour has been examined. METHODS: In 2017/18, a baseline survey (T0) was performed on trainees in various sectors (office, sales, teaching, nursing and social welfare, engineering, hairdressers), who had been contacted through vocational colleges in four federal states in north Germany. The trainees were surveyed again in the in the first year after training in 2021 (T3). Demographic data were collected, as well as information on health literacy (HLS-EU-16), health behaviour (physical exercise, nutrition, smoking and alcohol) and state of health (BMI, psychological well-being and subjective state of health). Recognition, satisfaction at work and thoughts of leaving the profession were surveyed with the Copenhagen Psychosocial Questionnaire (COPSOQ). Statistical analysis was performed with tests for paired samples and multivariate regression analysis in SPSS 26. RESULTS: 129 data sets were evaluated, with a follow-up rate of 10.2%. 85% of the trainees were female. The mean age at follow-up was 25.6 years. 56% were employed in the health service or social welfare. 35% worked in the office, sales or engineering. At T3, 47% of the employees exhibited limited health literacy, 67% low levels of exercise and 30% risky alcohol use. 42% exhibited overweight and 42% poor psychological well-being. An association between health literacy (HL) and psychological well-being was only observed in cross-section (HL inadequate vs. HL adequate OR: 3.2 95% CI: 1.07-9.49, p = 0.037). The odds ratio relative to subjective state of health was also increased, although the association was not statistically significant (HL inadequate vs. HL adequate OR: 2.7 95% CI: 0.72-9.78, p = 0.143). In the sector for health service and social welfare, there was statistically significant deterioration over time in all COPSOQ variables (recognition, satisfaction at work, thoughts of leaving the profession). CONCLUSIONS: For a group of trainees in the first year of work during the covid-19 epidemic, the present findings show that there is a need to prevent risky health behaviour, overweight and poor psychological well-being. Health literacy was shown to be a modifiable parameter, that apparently is associated in cross - but not in longitudinal section with the health of young employees. It would appear to be reasonable to modify developing health literacy in the setting of work and school.

What's the Harm in Cardiopulmonary Resuscitation?

In clinical ethics, there remains a great deal of uncertainty regarding the appropriateness of attempting cardiopulmonary resuscitation (CPR) for certain patients. Although the issue continues to receive ample attention and various frameworks have been proposed for navigating such cases, most discussions draw heavily on the notion of harm as a central consideration. In the following, I use emerging philosophical literature on the notion of harm to argue that the ambiguities and disagreement about harm create important and oft-overlooked challenges for the ethics of CPR. I begin by elucidating the standard account of harm, called the Counterfactual Comparative Account (CCA). I then show that three challenges to the CCA-preemptive harms, the harm of death, and non-experiential harms-are particularly salient when assessing potential harms for candidates of CPR and likely impact-related decision-making and communication. I extend this argument to explore how the ambiguities of harm might extend to other realms of clinical decision-making, such as the use and limitations of life-sustaining treatments. To address these challenges, I propose two strategies for identifying and minimizing the impact of such uncertainty: first, clinicians and ethicists ought to promote pluralistic conversations that account for different understandings of harm; second, they ought to invoke harm-independent considerations when discussing the ethics of CPR in order to reflect the nuances of such conversations. These strategies, coupled with a richer philosophical understanding of harm, promise to help clinicians and ethicists navigate the prevalent and difficult cases involving patient resuscitation and many other harm-based decisions in the clinical setting.

Effects of TP63 mutations on keratinocyte adhesion and migration.

The goal of this study was to investigate the molecular mechanisms responsible for the formation of skin erosions in patients affected by Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC). This ectodermal dysplasia is caused by mutations in the TP63 gene, which encodes several transcription factors that control epidermal development and homeostasis. We generated induced pluripotent stem cells (iPSC) from AEC patients and corrected the TP63 mutations using genome editing tools. Three pairs of the resulting conisogenic iPSC lines were differentiated into keratinocytes (iPSC-K). We identified a significant downregulation of key components of hemidesmosomes and focal adhesions in AEC iPSC-K compared to their gene-corrected counterparts. Further, we demonstrated reduced AEC iPSC-K migration, suggesting the possibility that a process critical for cutaneous wound healing might be impaired in AEC patients. Next, we generated chimeric mice expressing a TP63-AEC transgene and confirmed a downregulation of these genes in transgene-expressing cells in vivo. Finally, we also observed these abnormalities in AEC patient skin. Our findings suggest that integrin defects in AEC patients might weaken the adhesion of keratinocytes to the basement membrane. We propose that reduced expression of extracellular matrix adhesion receptors, potentially in conjunction with previously identified desmosomal protein defects, contribute to skin erosions in AEC.

Effects of TP63 Mutations on Keratinocyte Adhesion and Migration.

The goal of this study was to investigate the molecular mechanisms responsible for the formation of skin erosions in patients affected by Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC). This ectodermal dysplasia is caused by mutations in the TP63 gene, which encodes several transcription factors that control epidermal development and homeostasis. We generated induced pluripotent stem cells (iPSC) from AEC patients and corrected the TP63 mutations using genome editing tools. Three pairs of the resulting conisogenic iPSC lines were differentiated into keratinocytes (iPSC-K). We identified a significant downregulation of key components of hemidesmosomes and focal adhesions in AEC iPSC-K compared to their gene-corrected counterparts. Further, we demonstrated reduced iPSC-K migration, suggesting the possibility that a process critical for cutaneous wound healing might be impaired in AEC patients. Next, we generated chimeric mice expressing a TP63-AEC transgene and confirmed a downregulation of these genes in transgene-expressing cells in vivo. Finally, we also observed these abnormalities in AEC patient skin. Our findings suggest that integrin defects in AEC patients might weaken the adhesion of keratinocytes to the basement membrane. We propose that reduced expression of extracellular matrix adhesion receptors, potentially in conjunction with previously identified desmosomal protein defects, contribute to skin erosions in AEC.

A neutrophil response linked to tumor control in immunotherapy.

Neutrophils accumulate in solid tumors, and their abundance correlates with poor prognosis. Neutrophils are not homogeneous, however, and could play different roles in cancer therapy. Here, we investigate the role of neutrophils in immunotherapy, leading to tumor control. We show that successful therapies acutely expanded tumor neutrophil numbers. This expansion could be attributed to a Sellhi state rather than to other neutrophils that accelerate tumor progression. Therapy-elicited neutrophils acquired an interferon gene signature, also seen in human patients, and appeared essential for successful therapy, as loss of the interferon-responsive transcription factor IRF1 in neutrophils led to failure of immunotherapy. The neutrophil response depended on key components of anti-tumor immunity, including BATF3-dependent DCs, IL-12, and IFNγ. In addition, we found that a therapy-elicited systemic neutrophil response positively correlated with disease outcome in lung cancer patients. Thus, we establish a crucial role of a neutrophil state in mediating effective cancer therapy.

Biomechanical Comparison of Anterior Cruciate Ligament Reconstruction Using a Single-Bundle Round or Ribbon-like Hamstring Tendon Graft.

BACKGROUND: Persistent instability of the knee is reported in up to 30% of patients after anterior cruciate ligament (ACL) reconstruction. Based on anatomic findings showing that ACL is a flat ribbon-like structure that twists during knee flexion, a new surgical ACL reconstruction technique using a ribbon-like graft has been developed. However the effect of this surgical technique on knee kinematics has not yet been evaluated. PURPOSE: To compare the anteroposterior and rotational stability of the knee after ACL reconstruction using single-bundle (SB) round and ribbon-like grafts in anterolateral-intact/deficient knees. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve human fresh-frozen cadaveric knees were tested with a 6 degrees of freedom robotic system. Internal rotation and anterior translation of the knee were recorded from 0° to 90° of flexion. A full kinematic assessment was performed in each of the following conditions: (1) intact knee, (2) after sectioning of the ACL, (3) after ACL reconstruction using a SB hamstring tendon graft in a round configuration and a ribbon-like configuration, and (4) after sectioning of the anterolateral structures. One-way analysis of variance and post hoc Tukey tests were used for statistical analyses. RESULTS: When compared with the intact knee, the ACL-deficient knee demonstrated a mean ± SD increase in anterior translation and internal rotation of 6.3 ± 2.5 mm (P < .01) and 5.8°± 2.3° (P < .01), respectively. After ACL reconstruction using a SB ribbon-like graft, the mean difference in anterior translation and internal rotation as compared with the intact knee was -0.1 ± 1.5 mm (P = .842) and 0.0°± 1.1° (P = .999). These differences from the intact knee were also not significant after ACL reconstruction using a round graft (-0.1 ± 1.3 mm, P = .999; -0.5°± 1.5°, P = .401). In the ACL-reconstructed knee using either a ribbon-like or round graft, sectioning of the anterolateral structures did not induce a significant increase of anterior translation and internal rotation of the knee. CONCLUSION: ACL reconstruction using a SB ribbon-like or round graft restored the kinematics of the intact knee at time zero. Secondary sectioning of the anterolateral structures in the ACL-reconstructed knee using both types of graft did not significantly affect the anterior translation and internal rotation of the knee. CLINICAL RELEVANCE: This is the first biomechanical study on the new ACL reconstruction technique using a ribbon-like graft.