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Abstract Background Coronary heart disease (CHD) is often associated with mental disorders (MDs). Comorbid MDs reduce the quality of life and increase cardiac morbidity and mortality. Nevertheless, there is little and inconsistent research on the management of MDs in CHD patients. To bridge this gap, this study aims to gain insight into the long-term course of MD-related health care for patients with CHD, in order to identify opportunities for care improvement. Methods In this prospective cohort study, we investigated whether CHD patients with or without expert-rated MD at baseline (N = 364) received different MD-related health care from either their general practitioner (GP) or cardiologist at follow-up, M = 2.7 [2.0–4.0] years later. In the follow-up assessment, N = 131 CHD patients participated and received questionnaires capturing sociodemographic, mental health, and MD-related health care characteristics. Descriptive statistics, t-tests and chi-squared tests were used for analyses. Results We found significant differences in MD-related health care. CHD patients with MD were more likely to be examined psychologically/psychiatrically (MD 55.9%, non-MD 16.7%, p =

Abstract Background The reasons for developing depression are not fully understood. However, it is known that the serotonergic system plays a role in the etiology, but the endocannabinoid system receives attention. Method In this study, 161 patients with a depressive disorder and 161 healthy participants were examined for the distribution of the CNR1 rs4940353, 5‐HT2A rs6311, and 5‐HT1A rs6295 by high‐resolution melting genotyping. The concentration of arachidonoyl ethanolamide (AEA) and 2‐arachidonoylglycerol (2‐AG) in the blood was measured by liquid chromatography–tandem mass spectrometry. Additionally, depression and anxiety symptoms were evaluated based on self‐questionnaires. Fifty‐nine patients participated in a second appointment to measure the concentration of AEA, 2‐AG, and symptoms of depression and anxiety. Results We observed higher AEA and decreased 2‐AG concentrations in patients with depression compared to healthy participants. During the treatment, the concentrations of AEA and 2‐AG did not change significantly. In patients higher symptoms of anxiety correlated with lower concentrations of 2‐AG. Gender differences were found concerning increased 2‐AG concentration in male patients and increased anxiety symptoms in female patients. Genotypic variations of 5‐HT1A rs6295 and 5‐HT2A rs6311 are associated with altered serotonergic activity and serotonin content in patients. Conclusion In conclusion, it seems that the endocannabinoid system, especially the endocannabinoids 2‐AG and AEA, and genetic variations of the 5‐HT1A and 5‐HT2A could play a role in patients with depression and may be involved in a depressive disorder.

Abstract Introduction This mixed‐method study explores psychological needs, access and barriers in coronary heart disease (CHD) patients with and without mental health issues (MHI) within the German healthcare system. Methods This study was conducted in three different healthcare settings: two hospitals, two rehabilitation clinics and three cardiology practices in Cologne, Germany. Patients were screened for angiographically documented CHD and other inclusion criteria. In total, 364 CHD patients took part in this study. It consisted of two parts: In the first part, participants filled in a newly developed questionnaire about their psychological needs, access and barriers within the healthcare system and their contact with their doctor in these matters. Then, patients were screened for MHIs with the help of the Hospital Anxiety and Depression Scale (HADS). When a score above seven was scored on the HADS, patients were additionally screened for specific MHIs using the Structured Clinical Interview for DSM‐IV Axis I Disorders. In the second part, 20 participants were subsequently interviewed in a semi‐structured interview to generate more in‐depth findings. Results The interviews show that CHD patients with and without MHI experienced a cardiac event as life‐changing and had an urgent need to talk about CHD with their doctor, mostly the general practitioner (GP). When the GP spoke to the patient shortly after the cardiac event, patients experienced relief and were better able to cope with their illness. Only 9.1% reported being aided in their search for psychotherapeutic treatment or drug treatment (4.1%). Conclusion The needs of CHD patients with and without MHI were not adequately satisfied within our sample. Psychological measures are necessary for sufficient improvement, such as training of doctors in doctor–patient communication (e.g., better support in coping with MHI/CHD), improvements in the procedure (more time for conversations during doctor contacts), and improvement of structural requirements (referring patients faster to psychotherapists). Patient or Public Contribution We received input from patients during pretests and used the feedback to tailor our questionnaire and the interview guidelines. Afterwards, we disseminated the main results for the patient and public involvement (e.g., public lectures, leaflets for self‐help groups, etc.).

Abstract Background Personal last wishes of people facing a life-limiting illness may change closer to death and may vary across different forms of specialist palliative care (SPC). Aims To explore the presence and common themes of last wishes over time and according to the SPC settings (inpatient vs. home-based SPC), and to identify factors associated to having a last wish. Methods Patients enrolled in a longitudinal study completed questionnaires at the onset (baseline, t0) and within the first 6 weeks (follow-up, t1) of SPC including an open-ended question on their personal last wishes. Last wishes were content analyzed, and all wishes were coded for presence or absence of each of the identified themes. Changes of last wishes (t0-t1) were analyzed by a McNemar test. The chi-square-test was used to compare the two SPC settings. Predictors for the presence of a last wish were identified by logistic regression analysis. Results Three hundred sixty-one patients (mean age, 69.5 years; 49% female) answered at t0, and 130 at t1. In cross-sectional analyses, the presence of last wishes was higher at t0 (67%) than at t1 (59%). Comparisons revealed a higher presence of last wishes among inpatients than those in home-based SPC at t0 (78% vs. 62%; p = .002), but not at t1. Inpatient SPC (OR = 1.987, p = .011) and greater physical symptom burden over the past week (OR = 1.168, p

Being able to accurately control the interaction of spin waves is a crucial challenge for magnonics in order to offer an alternative wave-based computing scheme for certain technological applications. Especially in neural networks and neuromorphic computing, wave-based approaches can offer significant advantages over traditional CMOS-based binary computing schemes with regard to performance and power consumption. In this work, we demonstrate precise modulation of phase- and amplitude-sensitive interference of coherent spin waves in a yttrium–iron–garnet based magnonic analog adder device, while also showing the feasibility of frequency-division multiplexing. Using time-resolved scanning transmission x-ray microscopy, the interference was directly observed, giving an important proof of concept for this kind of analog computing device and its underlying working principle. This constitutes a step toward wave-based analog computing using magnons as an information carrier.

Abstract Background We investigated the need for additional professional support and associated factors in patients (pts) at initiation and in the course of in- and outpatient specialist palliative care (I-SPC/O-SPC). Methods Pts entering an urban SPC network consecutively completed questionnaires on psychosocial/spiritual problems and support needs within 72 h (T0) as well as within the first 6 weeks (T1) of SPC. Hierarchical linear regression analysis was used to investigate the impact of sociodemographic / disease-related variables, psychological / physical burden, social support, and SPC setting on the extent of support needs. Results Four hundred twenty-five pts (70 years, 48% female, 91% cancer, 67% O-SPC) answered at T0, and 167 at T1. At T0, main problems related to transportation, usual activities, and dependency (83–89%). At T1, most prevalent problems also related to transportation and usual activities and additionally to light housework (82–86%). At T0, support needs were highest for transportation, light housework, and usual activities (35–41%). Cross-sectional comparisons of SPC settings revealed higher problem scores in O-SPC compared to I-SPC at T0 (p = .039), but not at T1. Support need scores were higher in O-SPC at T0 (p

The gadolinium-based contrast agent DOTA-Gd is clinically used in combination with local anesthetics for direct magnetic resonance arthrography. It remains unclear whether gadolinium uptake into cartilage is influenced by co-administration of bupivacaine or ropivacaine and whether DOTA-Gd alters their chondrotoxicity. Gadolinium quantification of chondrogenic spheroids revealed enhanced gadolinium uptake after simultaneous exposure to local anesthetics. Analyses of the spatial gadolinium distribution using synchrotron X-ray-fluorescence scanning indicates gadolinium exposed chondrocytes. In vitro exposure to DOTA-Gd does not alter viability and proliferation of human chondrocytes and the chondrotoxic potential of the anesthetics. Reduced viability induced by ropivacaine was found to be reversible, while exposure to bupivacaine leads to irreversible cell death. Our data suggest that ropivacaine is more tolerable than bupivacaine and that DOTA-Gd exposure does not alter the cytotoxicity of both anesthetics. Enhanced gadolinium uptake into cartilage due to co-administration of anesthetics should find attention.

Abstract Background Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are used in regenerative medicine and related research involving immunomodulatory, anti-inflammatory, anti-fibrotic and regenerative functions. Isolation of BM-MSCs from samples obtained during total hip arthroplasty (THA) is routinely possible. Advanced age and comorbidities of the majority of patients undergoing THA limit their applicability. Our study aimed to evaluate the potential of bone marrow obtained during periacetabular osteotomy (PAO) as a novel source of BM-MSCs from young donors by analyzing cell yield and cell characteristics. Methods Bone samples were obtained from the anterior Os ilium or superior Os pubis during PAO and from the femoral cavity during primary THA. Isolation of bone marrow-derived mononuclear cells (BM-MNCs) was performed by density gradient centrifugation. The samples from PAO and THA patients were compared in terms of BM-MSC yield, colony formation and the proportion of BM-MSCs within the BM-MNC population using flow cytometry analysis. The cells were characterized based on the expression of BM-MSC-specific surface markers. The functionality of the cells was compared by quantifying post-thaw viability, metabolic activity, proliferation capacity, senescence-associated beta galactosidase (SA-β-gal) expression, trilineage differentiation potential and major secretome proteins. Results Isolation of BM-MNCs was possible in a reliable and reproducible manner when using bone from PAO containing more than 0.24 g bone marrow. PAO patients were younger than patients of the THA group. Bone obtained during PAO contained less bone marrow and led to a lower BM-MSC number after the first cell culture passage compared to BM-MSCs obtained during THA. BM-MSCs from PAO samples are characterized by a higher proliferation capacity. This results in a higher yield in cell culture passage two, when normalized to the sample weight. BM-MSCs from PAO patients showed increased secretion of TGF-β1, TIMP2, and VEGF upon osteogenic differentiation. BM-MSCs from PAO and THA patients revealed similar results regarding the onset of SA-β-gal expression and trilineage differentiation capacity. Conclusions We suggest that bone obtained during PAO is a promising novel source for BM-MSCs from young donors. Limited absolute cell yield due to low sample weight must be considered in early cell culture passages and might be critical for the range of clinical applications possible for BM-MSCs from this source. The higher proliferation capacity and increased growth factor secretion of BM-MSCs from young donors may be beneficial for future regenerative cell therapies, in vitro models, and tissue engineering.

Chondrosarcoma (CS) is a rare malignant bone sarcoma that primarily affects cartilage cells in the femur and pelvis. While most subtypes exhibit slow growth with a very good prognosis, some aggressive subtypes have a poorer overall survival. CS is known for its resistance to chemotherapy and radiotherapy, leaving surgery as the sole effective therapeutic option. Cold physical plasma (CPP) has been explored in vitro as a potential therapy, demonstrating positive anti-tumor effects on CS cells. This study investigated the synergistic effects of combining CPP with cytostatics on CS cells. The chemotherapeutic agents cisplatin, doxorubicin, and vincristine were applied to two CS cell lines (CAL-78 and SW1353). After determining their IC20 and IC50, they were combined with CPP in both cell lines to assess their impact on the cell proliferation, viability, metabolism, and apoptosis. This combined approach significantly reduced the cell proliferation and viability while increasing the apoptosis signals compared to cytostatic therapy alone. The combination of CPP and chemotherapeutic drugs shows promise in targeting chemoresistant CS cells, potentially improving the prognosis for patients in clinical settings.

Cold physical plasma (CPP) technology is of high promise for various medical applications. The interplay of specific components of physical plasma with living cells, tissues and organs on a structural and functional level is of paramount interest with the aim to induce therapeutic effects in a controlled and replicable fashion. In contrast to other medical disciplines such as dermatology and oromaxillofacial surgery, research reports on CPP application in orthopaedics are scarce. The present implementation of CPP in orthopaedics involves surface modifications of orthopaedic materials and biomaterials to optimize osseointegration. In addition, the influence of CPP on musculoskeletal cells and tissues is a focus of research, including possible adverse reactions and side effects. Its bactericidal aspects make CPP an attractive supplement to current treatment regimens in case of microbial inflammations such as periprosthetic joint infections. Attributed anticancerogenic and pro-apoptotic effects underline the clinical relevance of CPP as an additive in treating malignant bone lesions. The present review outlines ongoing research in orthopaedics involving CPP; it distinguishes considerations for safe application and the need for more evidence-based research to facilitate robust clinical implementation.

In musculoskeletal surgery, the treatment of large bone defects is challenging and can require the use of bone graft substitutes to restore mechanical stability and promote host-mediated regeneration. The use of bone allografts is well-established in many bone regenerative procedures, but is associated with low rates of ingrowth due to pre-therapeutic graft processing. Cold physical plasma (CPP), a partially ionized gas that simultaneously generates reactive oxygen (O2) and nitrogen (N2) species, is suggested to be advantageous in biomedical implant processing. CPP is a promising tool in allograft processing for improving surface characteristics of bone allografts towards enhanced cellularization and osteoconduction. However, a preclinical assessment regarding the feasibility of pre-therapeutic processing of allogeneic bone grafts with CPP has not yet been performed. Thus, this pilot study aimed to analyze the bone morphology of CPP processed allografts using synchrotron radiation-based microcomputed tomography (SR-µCT) and to analyze the effects of CPP processing on human bone cell viability and function. The analyzes, including co-registration of pre- and post-treatment SR-µCT scans, revealed that the main bone morphological properties (total volume, mineralized volume, surface area, and porosity) remained unaffected by CPP treatment if compared to allografts not treated with CPP. Varying effects on cellular metabolic activity and alkaline phosphatase activity were found in response to different gas mixtures and treatment durations employed for CPP application. It was found that 3 min CPP treatment using a He + 0.1% N2 gas mixture led to the most favourable outcome regarding a significant increase in bone cell viability and alkaline phosphatase activity. This study highlights the promising potential of pre-therapeuthic bone allograft processing by CPP prior to intraoperative application and emphasizes the need for gas source and treatment time optimization for specific applications.

Bone generally displays a high intrinsic capacity to regenerate. Nonetheless, large osseous defects sometimes fail to heal. The treatment of such large segmental defects still represents a considerable clinical challenge. The regeneration of large bone defects often proves difficult, since it relies on the formation of large amounts of bone within an environment impedimental to osteogenesis, characterized by soft tissue damage and hampered vascularization. Consequently, research efforts have concentrated on tissue engineering and regenerative medical strategies to resolve this multifaceted challenge. In this review, we summarize, critically evaluate, and discuss present approaches in light of their clinical relevance; we also present future advanced techniques for bone tissue engineering, outlining the steps to realize for their translation from bench to bedside. The discussion includes the physiology of bone healing, requirements and properties of natural and synthetic biomaterials for bone reconstruction, their use in conjunction with cellular components and suitable growth factors, and strategies to improve vascularization and the translation of these regenerative concepts to in vivo applications. We conclude that the ideal all-purpose material for scaffold-guided bone regeneration is currently not available. It seems that a variety of different solutions will be employed, according to the clinical treatment necessary.