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Martin Adam,1 Cornelia Ganz,1 Weiguo Xu,1 Hamid-Reza Sarajian,2 Werner Götz,3 Thomas Gerber1 1Institute of Physics, Rostock University, Rostock, Germany; 2Department of Oral and Maxillofacial Plastic Surgery, Rostock University, Rostock, Germany; 3Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, Faculty of Medicine, University of Bonn, Bonn, Germany Abstract: Immediate loading of dental implants is only possible if a firm bone-implant anchorage at early stages is developed. This implies early and high bone apposition onto the implant surface. A nanostructured coating material based on an osseoinductive bone grafting is investigated in relation to the osseointegration at early stages. The goal is to transmit the structure (silica matrix with embedded hydroxyapatite) and the properties of the bone grafting into a coating material. The bone grafting substitute offers an osseoinductive potential caused by an exchange of the silica matrix in vivo accompanied by vascularization. X-ray diffraction and transmission electron microscopy analysis show that the coating material consists of a high porous silica matrix with embedded nanocrystalline hydroxyapatite with the same morphology as human hydroxyapatite. An in vitro investigation shows the early interaction between coating and human blood. Energy-dispersive X-ray analysis showed that the silica matrix was replaced by an organic matrix within a few minutes. Uncoated and coated titanium implants were inserted into the femora of New Zealand White rabbits. The bone-to-implant contact (BIC) was measured after 2, 4, and 6 weeks. The BIC of the coated implants was increased significantly at 2 and 4 weeks. After 6 weeks, the BIC was decreased to the level of the control group. A histological analysis revealed high bone apposition on the coated implant surface after 2 and 4 weeks. Osteoblastic and osteoclastic activities on the coating material indicated that the coating participates in the bone-remodeling process. The nanostructure of the coating material led to an exchange of the silica matrix by an autologous, organic matrix without delamination of the coating. This is the key issue in understanding initial bone formation on a coated surface. Keywords: silica, hydroxyapatite, dental implants, matrix change, osseointegration, in vivo

Abstract Background Whereas the antimicrobial peptides hBD-2 and -3 are related to inflammation, the constitutively expressed hBD-1 might function as 8p tumour suppressor gene and thus play a key role in control of transcription and induction of apoptosis in malignant epithelial tumours. Therefore this study was conducted to characterise proteins involved in cell cycle control and host defence in different benign and malignant salivary gland tumours in comparison with healthy salivary gland tissue. Methods 21 paraffin-embedded tissue samples of benign (n = 7), and malignant (n = 7) salivary gland tumours as well as healthy (n = 7) salivary glands were examined immunohistochemically for the expression of p53, bcl-2, and hBD-1, -2, -3. Results HBD-1 was distributed in the cytoplasm of healthy salivary glands and benign salivary gland tumours but seems to migrate into the nucleus of malignant salivary gland tumours. Pleomorphic adenomas showed cytoplasmic as well as weak nuclear hBD-1 staining. Conclusion HBD-1, 2 and 3 are traceable in healthy salivary gland tissue as well as in benign and malignant salivary gland tumours. As hBD-1 is shifted from the cytoplasm to the nucleus in malignant salivary gland tumours, we hypothesize that it might play a role in the oncogenesis of these tumours. In pleomorphic adenomas hBD-1 might be connected to their biologic behaviour of recurrence and malignant transformation.

Abstract Background Inhalation of biopersistent fibers like asbestos can cause strong chronic inflammatory effects, often resulting in fibrosis or even cancer. The interplay between fiber shape, fiber size and the resulting biological effects is still poorly understood due to the lack of reference materials. Results We investigated how length, diameter, aspect ratio, and shape of synthetic silica fibers influence inflammatory effects at doses up to 250 µg cm-2. Silica nanofibers were prepared with different diameter and shape. Straight (length ca. 6 to 8 µm, thickness ca. 0.25 to 0.35 µm, aspect ratio ca. 17:1 to 32:1) and curly fibers (length ca. 9 µm, thickness ca. 0.13 µm, radius of curvature ca. 0.5 µm, aspect ratio ca. 70:1) were dispersed in water with no apparent change in the fiber shape during up to 28 days. Upon immersion in aqueous saline (DPBS), the fibers released about 5 wt% silica after 7 days irrespectively of their shape. The uptake of the fibers by macrophages (human THP-1 and rat NR8383) was studied by scanning electron microscopy and confocal laser scanning microscopy. Some fibers were completely taken up whereas others were only partially internalized, leading to visual damage of the cell wall. The biological effects were assessed by determining cell toxicity, particle-induced chemotaxis, and the induction of gene expression of inflammatory mediators. Conclusions Straight fibers were only slightly cytotoxic and caused weak cell migration, regardless of their thickness, while the curly fibers were more toxic and caused significantly stronger chemotaxis. Curly fibers also had the strongest effect on the expression of cytokines and chemokines. This may be due to the different aspect ratio or its twisted shape.

BackgroundDespite the evidence of beneficial effects of physical activity (PA), people with multiple sclerosis (pwMS) are less physically active than the general population. To increase PA in pwMS, we developed a structured individually tailored PA promotion program which is conducted within clinical practice in a university-based outpatient clinic since 2016. This study serves as retrospective quality control of this program.ObjectiveIn a retrospective cohort study, we assessed the physical fitness of pwMS and the impact of the program on short- and long-term PA changes and behavioral determinants.MethodsThe program consisted of four appointments each 2–4 weeks apart. Spiroergometric test results of female pwMS were compared to female non-MS controls who underwent a voluntary physical fitness analysis. The short version of the Freiburger questionnaire, self-developed questions and the modified Physical activity screening questionnaire (PASQ) were sent to all participants assessing the PA levels before the program, 3 months after the program (short-term), and at the time of the survey (long-term). Additionally, established questionnaires assessed behavioral determinants before the program and long-term.ResultsA total of 166 participants [mean age 38.32 (± 10.61 SD), mean EDSS 2.30 (±1.29 SD)] and mostly females (63.3%, n = 105) were included in the study and started the program. A total of 136 participants completed the program. Out of these 63.9% (n = 87) answered the questionnaires in 12.38 (±11.34 SD) months after finishing the program. At baseline female pwMS (n = 100) showed a lower physical fitness in comparison to non-MS controls (n = 26) (maximal workload (Watts): 138.86 ± 37.85 vs. 191.73 ± 45.25, p

Objective Nurses’ and doctors’ health at work is crucial for their overall performance and the quality of care they provide. The Jobs Demands Resources (JD-R) model offers a framework for health at work, encompassing ‘job demands’, ‘job resources’, ‘personal resources’, ‘leadership’, ‘well-being’ and ‘outcomes’. While various instruments exist to measure health, an overview of instruments specifically designed for assessing nurses and doctors health is currently missing. This study provides a comprehensive overview of available health instruments specifically developed and validated for healthcare professionals in hospital care.Design Scoping review.Data sources MEDLINE, Embase and CINAHL.Eligibility criteria Studies assessing the health of nurses and/or doctors in hospitals using or evaluating instruments based on the JD-R model, published between January 2011 and January 2024, excluding student-exclusive samples.Data extraction and synthesis We extracted data on study and sample characteristics, as well as details of the measurement instruments, including main and subconstructs. Instruments were categorised based on the JD-R model domains. Descriptive analysis and data visualisation were performed using Excel and Python.Results We included 1204 studies, reporting 986 unique instruments. We identified 32 comprehensive instruments suitable for broad health screening, measuring four or more of the JD-R model domains. Additionally, we identified instruments focusing on specific domains for targeted screening needs. Furthermore, we present frequently reported instruments assumed to be extensively evaluated, user-friendly, accessible and available in multiple languages.Conclusions Health at work cannot be determined by a single instrument alone, underscoring the multidimensional nature of workplace health. Alternatively, organisations should select instruments based on domains most relevant and applicable to their context. This approach ensures a more comprehensive assessment of health at work.

# Background Lateral ankle sprain (LAS) is one of the most common types of injury in football (soccer). Normative baseline data of performance tests for Return to Play (RTP) decision are still lacking. # Purpose The primary aim of this study was to generate baseline values for uninjured elite youth football players for a multifactorial RTP assessment and compare with previously published data. A secondary aim was to investigate the use of the Limb Symmetry Index (LSI) as a method to determine whether an athlete passes a performance test or not. # Study Design Observational Cohort study # Methods Baseline data of performance tests (Y-Balance \[YBT-LQ], Heel Rise \[HRT]; Singe Leg Squat \[SLST]; Single Leg Drop Jump \[SLDJ]; Side Hop \[SHT]; Figure of 8 Hop \[F-8]; Modified Agility T-Test \[MAT]) were assessed in 20 elite youth football players, aged 16-21 years. Additionally, the traditional LSI (dividing the result of the non-dominant leg by the result of the dominant leg and multiplying by 100) and directionally corrected LSI (the worst value is divided by the better value and multiplied by 100) were calculated. The test values were compared to previously reported study results. LSI and side-to-side comparisons between dominant and non-dominant leg sides were analyzed using the Wilcoxon test. # Results Male elite youth football players achieved better results in the dynamic performance tests (SHT, F-8, and MAT) compared to reference values of the cohorts previously described in the literature: YBT-LQ total score (cm) dominant (dom) 99.3±8.3, non-dominant (ND) 99.5±10.4; HRT (average number) dom. 27.1±5.4, ND 25.2±5.1); SLDJ height (cm) dom 15±5, ND 15±5 and contact time (sec) dom 0.29±0.08, ND 0.29±0.07, Reactive Strength Index (RSI) dom 0.52±0.12, ND 0.50±0.13); SHT (sec) dom 7.12±0.73, ND 7.39±0.93; F-8 (sec) dom 10.52±1.02, ND 10.37±1.04; and MAT (sec) 5.82±0.22. Directionally corrected LSI differed significantly from the traditional calculated LSI (p

Lateral ankle sprain (LAS) is one of the most common types of injury in professional football (soccer) players with high risk of recurrence. The rehabilitation after LAS in professional football players is often still time-based and relies on anecdotal experience of clinicans. There is still a lack of utilization of criteria-based rehabilitation concepts after LAS in professional football. The aims of this clinical commentary are (1) to critically discuss the need for criteria-based rehabilitation concepts after LAS in professional football players, (2) to highlight the current lack of these approaches and (3) to present a novel clinical guideline-based rehabilitation algorithm. Short time-loss (15 days) and high recurrence rate (17%) raise the question of trivialization of LAS in professional football. Despite consequences for many stakeholders involved (players, teams, clubs, insurers), there is still a lack of of criteria-based, step-by-step approaches. The use of a criteria-based rehabilitation approach might reduce the high recurrence rate after LAS in professional football players and will lead, in turn, to increased long-term player availability. Practical experiences of he authors demonstrate the feasibility of such an approach. The effectiveness of this novel rehabilitation algorithm remains to be evaluated in future studies. Level of Evidence: 5

BackgroundWell-being at work can be defined as “creating an environment to promote a state of contentment which allows an employee to flourish and achieve their full potential for the benefit of themselves and their organisation.” In the health care context, well-being at work of nurses and doctors is important for good patient care. Moreover, it is strongly associated with individual- and organization-level consequences. Relevant literature presents models and concepts of physical, mental, and social well-being. This study uses the 6 elements of the job demands-resources (JD-R) model to interpret well-being at work (job demands, job resources, personal resources, leadership, well-being, and outcomes) as part of a Netherlands Federation of University Medical Hospitals program to find ways to improve and monitor health care professionals’ well-being in Dutch hospitals. Many instruments exist to measure well-being at work in terms of population, setting, and other aspects. An overview of available and eligible instruments assessing and monitoring the well-being of nurses and doctors is currently missing. ObjectiveWe will perform a scoping review aiming to provide an overview of validated instruments assessing and monitoring the well-being of nurses and doctors at work. MethodsWe will perform a search of published literature in the following databases: Medline, Embase, and CINAHL. Studies will be eligible if they (1) assess well-being at work of nurses and doctors employed in hospitals; (2) describe an evaluation of an instrument or review an instrument; (3) measure well-being at work or aspects of well-being at work according to the elements of the JD-R model, and (4) were published in English from 2011 onwards. Title/abstract screening according to the eligibility criteria will be followed by full-text screening. Data extraction of included studies will be conducted by 3 reviewers independently. Reviewers will use standardized data extraction forms that include study characteristics, sample characteristics, measurement instrument details, and psychometric properties. The analysis will be descriptive. When synthesizing the data, a distinction will be made between comprehensive instruments and common instruments. ResultsThis scoping review identifies instruments that have been developed and validated for monitoring the well-being of nurses and doctors at work. Studies were searched between September and December 2021 and screened between December 2021 and May 2022. A total of 739 studies were included. ConclusionsTimely screening of well-being at work may be beneficial for individual health care workers, the organization, and patients. There is often a substantial gap and mismatch between employer perceptions of well-being and well-being interventions. It is important to develop and implement suitable interventions adapted to the needs of nurses and doctors and their health or other problems. Well-being screening should be timely to gain insight into these needs and problems. Moreover, to determine the effectiveness of well-being interventions, measurement is mandatory. The results will be critical for organizations to select a monitoring instrument that best fits the needs of employees and organizations. International Registered Report Identifier (IRRID)DERR1-10.2196/43692

Abstract Background Most threshold limit values are based on animal experiments. Often, the question remains whether these data reflect the situation in humans. As part of a series of investigations in our exposure lab, this study investigates whether the results on the inflammatory effects of particles that have been demonstrated in animal models can be confirmed in acute inhalation studies in humans. Such studies have not been conducted so far for barium sulfate particles (BaSO4), a substance with very low solubility and without known substance-specific toxicity. Previous inhalation studies with zinc oxide (ZnO), which has a substance-specific toxicity, have shown local and systemic inflammatory respones. The design of these human ZnO inhalation studies was adopted for BaSO4 to compare the effects of particles with known inflammatory activity and supposedly inert particles. For further comparison, in vitro investigations on inflammatory processes were carried out. Methods Sixteen healthy volunteers were exposed to filtered air and BaSO4 particles (4.0 mg/m3) for two hours including one hour of ergometric cycling at moderate workload. Effect parameters were clinical signs, body temperature, and inflammatory markers in blood and induced sputum. In addition, particle-induced in vitro-chemotaxis of BaSO4 was investigated with regard to mode of action and differences between in vivo and in vitro effects. Results No local or systemic clinical signs were observed after acute BaSO4 inhalation and, in contrast to our previous human exposure studies with ZnO, no elevated values of biomarkers of inflammation were measured after the challenge. The in vitro chemotaxis induced by BaSO4 particles was minimal and 15-fold lower compared to ZnO. Conclusion The results of this study indicate that BaSO4 as a representative of granular biopersistent particles without specific toxicity does not induce inflammatory effects in humans after acute inhalation. Moreover, the in vitro data fit in with these in vivo results. Despite the careful and complex investigations, limitations must be admitted because the number of local effect parameters were limited and chronic toxicity could not be studied.

Abstract Background Many residents experience their transitions, such as from medical student to resident, as demanding and stressful. The challenges they face are twofold: coping with changes in tasks or responsibilities and performing (new) social roles. This process of ‘learning the ropes’ is known as Organizational Socialization (OS). Although there is substantial literature on transitions from the perspective of residents, the voices of program directors (PDs) who facilitate and guide residents through the organizational socialization process have not yet been explored. PDs’ perspectives are important, since PDs are formally responsible for Postgraduate Medical Education (PGME) and contribute, directly or indirectly, to residents’ socialization process. Using the lens of OS, we explored what strategies PDs use to facilitate organizational socialization of newcomer residents. Methods We conducted semi-structured interviews with 17 PDs of different specialties. We used a theory-informing inductive data analysis study design, comprising an inductive thematic analysis, a deductive interpretation of the results through the lens of OS and, subsequently, an inductive analysis to identify overarching insights. Results We identified six strategies PDs used to facilitate organizational socialization of newcomer residents and uncovered two overarching insights. First, PDs varied in the extent to which they planned their guidance. Some PDs planned socialization as an explicit learning objective and assigned residents’ tasks and responsibilities accordingly, making it an intended program outcome. However, socialization was also facilitated by social interactions in the workplace, making it an unintended program outcome. Second, PDs varied in the extent to which they adapted their strategies to the newcomer residents. Some PDs used individualized strategies tailored to individual residents’ needs and skills, particularly in cases of poor performance, by broaching and discussing the issue or adjusting tasks and responsibilities. However, PDs also used workplace strategies requiring residents to adjust to the workplace without much intervention, which was often viewed as an implicit expectation. Conclusions PDs’ used both intentional and unintentional strategies to facilitate socialization in residents, which may imply that socialization can occur irrespective of the PD’s strategy. PDs’ strategies varied from an individual-centered to a workplace-centered approach to socialization. Further research is needed to gain a deeper understanding of residents’ perceptions of PD’s efforts to facilitate their socialization process during transitions.

Background: Digitalization in the health system is a topic that is rapidly gaining popularity, and not only because of the current pandemic. As in many areas of daily life, digitalization is becoming increasingly important in the medical field amid the exponential rise in the use of computers and smartphones. This opens up new possibilities for optimizing patient education in the context of anesthesia. The main aim of this study was to assess the implementation of remote consent in Europe. Methods: An online survey entitled “Digital online Patient Informed Consent for Anesthesia before Elective Surgery. Recent practice in Europe,” with a total of 27 questions, was sent by the European Society of Anesthesiology and Intensive Care (ESAIC) to their members in 47 European countries. To assess the effect of the economy on digitalization and legal status with regard to anesthesia consent, data were stratified based on gross domestic product per capita (GDPPC). Results: In total, 23.1% and 37.2% of the 930 participants indicated that it was possible to obtain consent online or via telephone, respectively. This observation was more often reported in countries with high GDPPC levels than in countries with low GDPPC levels. Furthermore, 27.3% of the responses for simple anesthesia, 18.7% of the responses for complex anesthesia, and 32.2% of the responses for repeated anesthesia indicated that remote consent was in accordance with the law, and this was especially prevalent in countries with high GDPPC. Concerning the timing of consent, patients were informed at least one day before in 67.1% of cases for simple procedures and in 85.2% of cases for complex procedures. Conclusion: Even European countries with high GDPPC use remote informed consent only in a minority of cases, and most of the time for repeated anesthetic procedures. This might reflect the inconsistent legal situation and inhomogeneous medical technical structures across Europe.

Six types of titanium dioxide particles with defined size, shape, and crystal structure (polymorphic form) were prepared: nanorods (70 × 25 nm2), rutile sub-microrods (190 × 40 nm2), rutile microspheres (620 nm), anatase nanospheres (100 nm), anatase microspheres (510 nm), and amorphous titania microspheres (620 nm). All particles were characterized by scanning electron microscopy, X-ray powder diffraction, dynamic light scattering, infrared spectroscopy, and UV spectroscopy. The sub-toxic cell-biological response to these particles by NR8383 macrophages was assessed. All particle types were taken up well by the cells. The cytotoxicity and the induction of reactive oxygen species (ROS) were negligible for all particles up to a dose of 100 µg mL−1, except for rutile microspheres which had a very rough surface in contrast to anatase and amorphous titania microspheres. The particle-induced cell migration assay (PICMA; based on chemotaxis) of all titanium dioxide particles was comparable to the effect of control silica nanoparticles (50 nm, uncoated, agglomerated) but did not show a trend with respect to particle size, shape, or crystal structure. The coating with carboxymethylcellulose (CMC) had no significant biological effect. However, the rough surface of rutile microspheres clearly induced pro-inflammatory cell reactions that were not predictable by the primary particle size alone.

Abstract Health risks from particles are a priority challenge to health protection at work. Despite the ubiquitous exposure to a wide range of particles and the many years of research in this field, there are fundamental unresolved questions regarding the prevention of particle-related respiratory diseases. Here, the highly relevant particulate material silicon dioxide was analyzed with emphasis on defined size and shape. Silica particles were prepared with different size and shape: Spheres (NS nanospheres 60 nm; SMS submicrospheres 230 nm; MS microspheres 430 nm) and rods (SMR submicrorods with d = 125 nm, L = 230 nm; aspect ratio 1:1.8; MR microrods with d = 100 nm, L = 600 nm; aspect ratio 1:6). After an in-depth physicochemical characterization, their effects on NR8383 alveolar macrophages were investigated. The particles were X-ray amorphous, well dispersed, and not agglomerated. Toxic effects were only observed at high concentrations, i.e. ≥ 200 µg mL−1, with the microparticles showing a stronger significant effect on toxicity (MS≈MR > SMR≈SMS≈NS) than the nanoparticles. Special attention was directed to effects in the subtoxic range (less than 50% cell death compared to untreated cells), i.e. below 100 µg mL−1 where chronic health effects may be expected. All particles were readily taken up by NR8383 cells within a few hours and mainly found associated with endolysosomes. At subtoxic levels, neither particle type induced strongly adverse effects, as probed by viability tests, detection of reactive oxygen species (ROS), protein microarrays, and cytokine release (IL-1β, GDF-15, TNF-α, CXCL1). In the particle-induced cell migration assay (PICMA) with leukocytes (dHL-60 cells) and in cytokine release assays, only small effects were seen. In conclusion, at subtoxic concentrations, where chronic health effects may be expected, neither size and nor shape of the synthesized chemically identical silica particles showed harmful cell-biological effects.