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Abstract Healthcare organisations worldwide are affected by the shortage of health professionals due to work-related stress and health professional leaders play an important role by implementing effective strategies. Therefore, this study aims to investigate whether the STRAIN intervention program (using evidence-based training for health professional leaders) can reduce work-related stress among health professionals. This study is based on a cluster randomised controlled trial, consists of three measurements and includes 165 participating hospitals, nursing homes and home care organisations. A total of 206 health professional leaders took part in the intervention programme and 19,340 health professionals participated in the study. Results showed no significant differences (p > 0.05) between the intervention and control group regarding the effort-reward imbalance ratio, quantitative demands, opportunities for development, bond with the organisation, quality of leadership, social community, role clarity, rewards, difficulties with demarcation and work–private life conflict. Pre-/post-test analysis revealed a tendency for significant positive results (p

Abstract Background The prognosis of patients with anaplastic thyroid cancer (ATC) remains dismal. A small portion of patients experience longterm survival and need to be identified before treatment allocation. Survival scores may guide clinicians making more informed decisions about treatment options and improve the understanding of patients’ prognosis. The aim of this study was to validate two prognostic scores using an independent dataset to analyze which prognostic index is superior in discriminating survival. Methods Thirty-four patients with histologically confirmed ATC diagnosed between January 2009 and December 2019 were consecutively treated at our department and evaluated. Next generation sequencing was performed in 7 (21%) patients, but no druggable mutation was found. 50% of all patients received surgery and 56% were treated with chemoradiotherapy. The median radiation dose in equivalent dose in 2 Gy fractions (EQD2) was 50 Gy (SD:21 Gy). The study compared the discrimination of the Sugitani Prognostic Index (SPI) and the Marchand-Crety Prognostic Score (MCPS) using concordance statistics, area under the receiver-operating characteristics curve (AUC), net reclassification index, and integrated discrimination improvement for 6-month survival. Results The median survival of the entire cohort was 5 months (range: 1-133). The AUC for 6-month survival was 0.85 (95% confidence interval [CI]:0.72–0.97) for SPI and 0.69 (95% CI: 0.56–0.83) for MCPS (p

Objective: Shared decision-making is one promising approach to promoting recovery and person-centred care but seems challenging for implementation in clinical practice. This study aimed to explore how patients and health professionals experience shared decision-making and its facilitators and barriers. Methods: A multiple qualitative case study design was chosen, using a constant comparative method. Multiple data sources were used, including individual interviews, observation, document analysis and a focus group. Results: Through first a within-case analysis and then second a cross-case analysis, four patient profiles and their potential for shared decision-making were constructed. The results indicate that in the daily routine of the psychiatric inpatient setting different forms of decision making are used, even though health professionals advocate shared decision-making as the favored approach. Patients also have varying expectations and perceptions regarding shared decision-making, which is reflected in the degree of their involvement. Conclusion: Shared decision-making could be enhanced in the future by a more proactive communication style and the proactive provision of information on the part of health professionals, in order to enhance patient participation in decision-making. Innovation: The study identified different forms of decision-making within the acute psychiatric inpatient setting, highlighting the gap between the advocated SDM approach and its practical implementation. This divergence is a key aspect, as it underlines the complexity of implementing SDM in real clinical settings.

Biomass gasification has increased due to its ability to provide high-temperature heat, making it promising for the decarbonisation of industrial processes. The economic and technical challenges of large-scale operations need to be addressed by focusing on small-sized gasifiers, while the use of low-grade biomass, is essential to increase the flexibility and sustainability of the plant. However, the utilisation of low-grade biomass is hindered by challenges stemming from variations in the particle distribution and shape, which significantly impact the fluidisation process and overall. In this research, the gasification of shredded municipal waste wood in a pilot-scale bubbling fluidised bed reactor was demonstrated, and the fluid-dynamics and gas production were assessed. The gasification process was yielding a gas with a lower heating value between 3.5MJNm−3 and 3.9MJNm−3 and a cold gas efficiency (CGE) of 46.4 %–48.6 %. Notably, these CGE values are consistent with pilot-scale setups, where CGE values above 50 % are typically not achievable because of poor insulation standards. The reactor's conical shape facilitated dynamic fluid regime transitions, ensuring efficient gas-solid interactions. This design allowed optimisation of fluidisation by accommodating particles of varying sizes throughout the reactor's height, thereby promoting efficient gasification suitable for industrial applications with diverse biomass feedstocks.

IntroductionThe FOXC2 transcription factor has been tied to a wide range of disease states, serving as a promising prognostic biomarker associated with aggressive basal-like human breast cancers (increased cancer invasion and metastasis). Dysregulation of FOXC2 expression has also been found to promote defects in lymphatic remodeling and hyperplastic lymphedema-distichiasis (LD). Since chronic lymphedema is a forerunner of several malignancies and cancers have been known to arise from poorly healing chronic wounds (e.g., Marjolin ulcers), we examined the effect of Foxc2 dysfunction on skin wound healing.MethodsWe used our splinted excisional wounding model that mimics human-like wound healing on wildtype and Foxc2+/− mice (n = 4), which demonstrate incomplete lymphatic vasculature and lymphatic dysfunction. Wound size was measured over the course of 18 days. Tissue was explanted from both groups at post-operative day (POD) 14 and 18 and stained with Masson’s Trichrome to assess scar formation, Picrosirius Red for dermal integrity, or immunofluorescence to assess lymphatic (LYVE1) cell populations.ResultsWildtype mice completely healed by POD 14, while Foxc2+/−mice did not completely heal until POD18. Scar area of healed Foxc2+/−mice (POD 18) was larger than that of healed wild-type mice (POD 14; p = 0.0294). At POD 14, collagen "bers in the scars of Foxc2+/−mice to be narrower (p = 0.0117) and more highly aligned (p = 0.0110), indicating signi"cantly more "brosis in these mice. Collagen "bers in both groups became longer (p = 0.0116) and wider (p = 0.0020) from POD 14 to 18, indicating a temporal evolution of "brosis. Foxc2+/−mice also had lower numbers of LYVE1+, F4/80+ and CD4+ cells compared to wildtype mice.DiscussionIndividuals over 65 years old are more likely to develop cancer and are highly susceptible to developing chronic wounds. Here, we found that FOXC2, which is tied to cancer metastasis and lymphatic dysregulation, also impairs wound healing and promotes "brotic tissue architecture. With FOXC2 proposed as a potential therapeutic target for cancer metastasis, its downstream systemic effects should be considered against the increased chance of developing nonhealing wounds. Further delineation of the microenvironment, cellular events, and molecular signals during normal and Foxc2-associated abnormal wound healing will improve clinical therapies targeting this important marker.

BackgroundSupporting individuals in managing their suicidality can prevent suicidal behavior. This study evaluated the suicide prevention project SERO, which was launched in Central Switzerland in 2021. SERO comprises four components: the suicide risk assessment technique PRISM-S, a personal safety plan, mental health first aid courses for relatives, and a self-management app. We assessed the mental health of individuals at increased suicide risk after hospital discharge and evaluated the usage and usefulness of SERO components.MethodsA cross-sectional study targeted former patients of Lucerne Psychiatry with an increased suicide risk. Between March 2023 and March 2024, we collected data from 24 individuals through a questionnaire administered six months post-discharge. Descriptive statistics characterized sociodemographics, assessed self-efficacy, self-management, and health literacy, and analyzed the usage and usefulness of SERO components. Associations between the usage of SERO components and mental health outcomes were investigated using Wilcoxon rank sum tests.ResultsMental health assessments indicated, on average, low to moderate levels of self-efficacy, self-management, and health literacy, with substantial variations across individuals. Participants’ exposure to SERO components varied: 83% used PRISM-S for suicide risk assessment, 67% developed a personal safety plan, 38% used the SERO app, and 8% reported that their relatives participated in a mental health first aid course. 50% of safety plan users and 44% of SERO app users found the tools helpful before or during a suicidal crisis. 78% of SERO app users would recommend the app to others.ConclusionLow to moderate levels of self-efficacy, self-management, and health literacy underscore the need for targeted interventions to support individuals at suicide risk. Positive feedback on the personal safety plan and the SERO app suggests their potential effectiveness in helping individuals manage their suicidality. Therefore, integrating structured measures for promoting self-management into standard care protocols in psychiatric hospitals and into patients’ lives may contribute to preventing suicides. The main limitation of our study is its small sample size. Future larger-scale studies should investigate user experiences in detail, assess the causal effects of SERO components on specific mental health and suicide outcomes, and evaluate the cost-effectiveness of each component separately and in combination.

Abstract Chronic non-healing wounds significantly strain modern healthcare systems, affecting 1–2% of the population in developed countries with costs ranging between $28.1 and $96.8 billion annually. Additionally, it has been established that chronic wounds resulting from comorbidities, such as peripheral vascular disease and diabetes mellitus, tend to be polymicrobial in nature. Treatment of polymicrobial chronic wounds with oral and IV antibiotics can result in antimicrobial resistance, leading to more difficult-to-treat wounds. Ideally, chronic ulcers would be topically treated with antibiotic combinations tailored to the microbiome of a patient’s wound. We have previously shown that a topical collagen-rich hydrogel (cHG) can elute single antibiotics to inhibit bacterial growth in a manner that is nontoxic to mammalian cells. Here, we analyzed the microbiology of cultures taken from human patients diagnosed with diabetes mellitus suffering from chronic wounds present for more than 6 weeks. Additionally, we examined the safety of the elution of multiple antibiotics from collagen-rich hydrogel in mammalian cells in vivo. Finally, we aimed to create tailored combinations of antibiotics impregnated into cHG to successfully target and treat infections and eradicate biofilms cultured from human chronic diabetic wound tissue. We found that the majority of human chronic wounds in our study were polymicrobial in nature. The elution of multiple antibiotics from cHG was well-tolerated in mammalian cells, making it a potential topical treatment of the polymicrobial chronic wound. Finally, combinations of antibiotics tailored to each patient’s microbiome eluted from a collagen-rich hydrogel successfully treated bacterial cultures isolated from patient samples via an in vitro assay.

Abstract The aim of this study is to identify (1) the extent of work-related stress and (2) stressors associated with cognitive and behavioral stress reactions, burnout symptoms, health status, quality of sleep, job satisfaction, and intention to leave the organization and the profession among health professionals working in acute care /rehabilitation hospitals, psychiatric hospitals, nursing homes, and home care organizations. Background Health professionals are faced with various stressors at work and as a consequence are leaving their profession prematurely. This study aimed to identify the extent of work-related stress and stressors associated with stress reactions, job satisfaction, and intention to leave and health-related outcomes among health professionals working in different healthcare sectors (acute care, rehabilitation and psychiatric hospitals, nursing homes and home care organizations). Methods This study is based on a repeated cross-sectional design, which includes three data measures between 2017 and 2020 and 19,340 participating health professionals from 26 acute care / rehabilitation hospitals, 12 psychiatric hospitals, 86 nursing homes and 41 home care organizations in Switzerland. For data analysis, hierarchical multilevel models (using AIC) were calculated separately for hospitals, nursing homes, and home care organizations, regarding health professionals’ stress symptoms, job satisfaction, intention to leave the organization / profession, general health status, burnout symptoms, and quality of sleep. Results The main findings reveal that the incompatibility of health professionals’ work and private life was significantly associated (p

Abstract Glioblastoma (GBM) is the most frequent and lethal brain tumor, whose therapeutic outcome - only partially effective with current schemes - places this disease among the unmet medical needs, and effective therapeutic approaches are urgently required. In our attempts to identify repositionable drugs in glioblastoma therapy, we identified the neuroleptic drug chlorpromazine (CPZ) as a very promising compound. Here we aimed to further unveil the mode of action of this drug. We performed a supervised recognition of the signal transduction pathways potentially influenced by CPZ via Reverse-Phase Protein microArrays (RPPA) and carried out an Activity-Based Protein Profiling (ABPP) followed by Mass Spectrometry (MS) analysis to possibly identify cellular factors targeted by the drug. Indeed, the glycolytic enzyme PKM2 was identified as one of the major targets of CPZ. Furthermore, using the Seahorse platform, we analyzed the bioenergetics changes induced by the drug. Consistent with the ability of CPZ to target PKM2, we detected relevant changes in GBM energy metabolism, possibly attributable to the drug’s ability to inhibit the oncogenic properties of PKM2. RPE-1 non-cancer neuroepithelial cells appeared less responsive to the drug. PKM2 silencing reduced the effects of CPZ. 3D modeling showed that CPZ interacts with PKM2 tetramer in the same region involved in binding other known activators. The effect of CPZ can be epitomized as an inhibition of the Warburg effect and thus malignancy in GBM cells, while sparing RPE-1 cells. These preclinical data enforce the rationale that allowed us to investigate the role of CPZ in GBM treatment in a recent multicenter Phase II clinical trial.

Abstract Background Prostatic carcinoma (PCA) is a rare but severe condition in dogs that is similar to the androgen-independent form of PCA in men. In contrast to humans, PCA is difficult to diagnose in dogs as reliable biomarkers, available for PCA screening in human medicine, are currently lacking in small animal oncology. Calprotectin (S100A8/A9) and S100A12 are Ca2+-binding proteins of the innate immune system with promising potential to distinguish malignant from benign urogenital tract conditions, similar to the blood neutrophil-to-lymphocyte-ratio (NLR). However, both have not yet been extensively investigated in dogs with PCA. Thus, this study aimed to evaluate the expression of the S100/calgranulins (calprotectin, S100A12, and their ratio [Cal-ratio]) in prostatic biopsies from nine dogs with PCA and compare them to those in dogs with benign prostatic lesions (eight dogs with prostatitis and ten dogs with benign prostatic hyperplasia [BPH]) as well as five healthy controls. In addition, blood NLRs were investigated in twelve dogs with PCA and 22 dogs with benign prostatic conditions. Results Tissue S100A8/A9+ cell counts did not differ significantly between tissue from PCA and prostatitis cases (P = 0.0659) but were significantly higher in dogs with prostatitis than BPH (P = 0.0013) or controls (P = 0.0033). S100A12+ cell counts were significantly lower in PCA tissues than in prostatitis tissue (P = 0.0458) but did not differ compared to BPH tissue (P = 0.6499) or tissue from controls (P = 0.0622). Cal-ratios did not differ significantly among the groups but were highest in prostatitis tissues and significantly higher in those dogs with poor prostatitis outcomes than in patients that were still alive at the end of the study (P = 0.0455). Blood NLR strongly correlated with prostatic tissue S100A8/A9+ cell counts in dogs with PCA (ρ = 0.81, P = 0.0499) but did not differ among the disease groups of dogs. Conclusions This study suggests that the S100/calgranulins play a role in malignant (PCA) and benign (prostatic inflammation) prostatic conditions and supports previous results in lower urinary tract conditions in dogs. These molecules might be linked to the inflammatory environment with potential effects on the inflammasome. The blood NLR does not appear to aid in distinguishing prostatic conditions in dogs. Further investigation of the S100/calgranulin pathways and their role in modulation of tumor development, progression, and metastasis in PCA is warranted.

Abstract Background A recessive form of MOCOS‐associated xanthinuria type II is described in Tyrolean grey cattle. A similar case was identified in a 5‐month‐old Brown Swiss calf with hoof overgrowth, rough coat, urine sediment, and pneumonia. Hypothesis/Objectives To characterize the disease phenotype, to evaluate its genetic etiology, and to determine the prevalence of the deleterious allele in the Brown Swiss population. Animals An affected calf, its parents, and 65 441 Swiss dairy cattle. Methods The affected animal was clinically examined and necropsied. Microarray genotyping was used to determine the genotypes and to assess the frequency of the MOCOS allele in a Brown Swiss control cohort. Results Ultrasonography revealed hyperechoic renal pyramids with multifocal distal shadowing and echogenic sediment in the urinary bladder. Necropsy revealed suppurative bronchopneumonia and urolithiasis. Histology revealed numerous nephroliths with multifocal chronic lymphohistiocytic interstitial infiltrates, fibrosis, tubular degeneration, chronic multifocal glomerulonephritis with sclerosis, and bilateral hydronephrosis. Dysplastic changes were observed in the corium of the claw and the cornea. Genetic testing identified the homozygous presence of a known MOCOS frameshift variant in the case. Both parents were heterozygous and the prevalence of carriers in genotyped Brown Swiss cattle was 1.4% (342/24337). Conclusions and Clinical Importance The findings were consistent with the diagnosis of a recessive renal syndrome similar to xanthinuria type II described in Tyrolean grey cattle. The prevalence of the deleterious MOCOS allele is low in the Brown Swiss breed. However, mating of carriers should be avoided to prevent further losses.

Context: Discovering visual languages across professions is a complex task since it entails discovering a communication system composed of information in image or textual form called representations and also including various kinds of annotations such as notes. Such a task has been previously scarcely considered within research, and basically only investigating in white collar professions (e.g., doctors). This leaves us wondering about all the possible shapes of these vocational visual languages and the potential of using these images to foster learning. For this reason, the current research aims to investigate commonalities and differences of visual languages across vocational professions with the goal of using the outcomes to design educational activities for vocational education and training (VET). Approach: 55 semi-structured interviews have been conducted within eleven professions from the areas of Craftsmanship, Industry, Health and Services such a plumber and fashion designers. The interviews were audio-recorded and analyzed with NVivo through a coding scheme which served as the main reference for the analysis. Findings Results showed that, in terms of visual representations, professionals use different types of drawings such as technical drawings (e.g., woodworkers), evaluation forms (e.g., dental assistants) and illustrations (e.g., gardeners). For sketches, participants indicate the practice of creating sketches depicting objects to produce (e.g. goldsmiths). For photos, they portrayed things to remember or pay attention to (e.g., chemical technologists). Participants across professions use annotations such as notes to specify details of their job. On the other side, they also report profession-specific annotations such as mathematical symbols like the surface roughness (e.g., polymechanics) and diagrammatic elements like different type of lines to indicate the status of the bones and muscles (e.g., massage therapists) or where to cut textiles (e.g., fashion designers). In terms of communalities, participants within technical professions indicated a shared use of both representations and annotations. Conversely, other professions had very specific visual languages hardly shareable across professions. Conclusion: These results helped in discovering the visual languages of different professions and this knowledge will be used to implement educational activities based on specific skills needed in different professions such as observation skills with the use of VET-specific educational technologies.

Abstract Chronic wounds impose a significant healthcare burden to a broad patient population. Cell-based therapies, while having shown benefits for the treatment of chronic wounds, have not yet achieved widespread adoption into clinical practice. We developed a CRISPR/Cas9 approach to precisely edit murine dendritic cells to enhance their therapeutic potential for healing chronic wounds. Using single-cell RNA sequencing of tolerogenic dendritic cells, we identified N-myc downregulated gene 2 (Ndrg2), which marks a specific population of dendritic cell progenitors, as a promising target for CRISPR knockout. Ndrg2-knockout alters the transcriptomic profile of dendritic cells and preserves an immature cell state with a strong pro-angiogenic and regenerative capacity. We then incorporated our CRISPR-based cell engineering within a therapeutic hydrogel for in vivo cell delivery and developed an effective translational approach for dendritic cell-based immunotherapy that accelerated healing of full-thickness wounds in both non-diabetic and diabetic mouse models. These findings could open the door to future clinical trials using safe gene editing in dendritic cells for treating various types of chronic wounds.

Abstract Mandibular distraction osteogenesis (DO) is mediated by skeletal stem cells (SSCs) in mice, which enact bone regeneration via neural crest re-activation. As peripheral nerves are essential to progenitor function during development and in response to injury, we questioned if denervation impairs mandibular DO. C57Bl6 mice were divided into two groups: DO with a segmental defect in the inferior alveolar nerve (IAN) at the time of mandibular osteotomy (“DO Den”) and DO with IAN intact (“DO Inn”). DO Den demonstrated significantly reduced histological and radiological osteogenesis relative to DO Inn. Denervation preceding DO results in reduced SSC amplification and osteogenic potential in mice. Single cell RNA sequencing analysis revealed that there was a predominance of innervated SSCs in clusters dominated by pathways related to bone formation. A rare human patient specimen was also analyzed and suggested that histological, radiological, and transcriptional alterations seen in mouse DO may be conserved in the setting of denervated human mandible distraction. Fibromodulin (FMOD) transcriptional and protein expression were reduced in denervated relative to innervated mouse and human mandible regenerate. Finally, when exogenous FMOD was added to DO-Den and DO-Inn SSCs undergoing in vitro osteogenic differentiation, the osteogenic potential of DO-Den SSCs was increased in comparison to control untreated DO-Den SSCs, modeling the superior osteogenic potential of DO-Inn SSCs.

Conventional synthetic vascular grafts are associated with significant failure rates due to their mismatched mechanical properties with the native vessel and poor regenerative potential. Though different tissue engineering approaches have been used to improve the biocompatibility of synthetic vascular grafts, it is still crucial to develop a new generation of synthetic grafts that can match the dynamics of native vessel and direct the host response to achieve robust vascular regeneration. The size of pores within implanted biomaterials has shown significant effects on macrophage polarization, which has been further confirmed as necessary for efficient vascular formation and remodeling. Here, we developed biodegradable, autoclavable synthetic vascular grafts from a new polyurethane elastomer and tailored the grafts' interconnected pore sizes to promote macrophage populations with a pro-regenerative phenotype and improve vascular regeneration and patency rate. The synthetic vascular grafts showed similar mechanical properties to native blood vessels, encouraged macrophage populations with varying M2 to M1 phenotypic expression, and maintained patency and vascular regeneration in a one-month rat carotid interposition model and in a four-month rat aortic interposition model. This innovative bioactive synthetic vascular graft holds promise to treat clinical vascular diseases.

In order to substitute fossil resources in activated carbon (AC) production, recent efforts have focused on the utilization of renewable raw materials. Regions with important wood industries offer two potentially underestimated resource types: forestry residue biomass (FRB) and waste wood (WW). Although these materials are widely available (approx. 130 mio. m3a-1 FRB, approx. 50 mio. ta-1 WW in the EU), they are mostly valorised through energy production, as they are high in ashes and may be contaminated with organics and heavy metals. In this study, both FRB and WW were treated via one-step pyrolysis for AC production. ZnCl2 was applied as activating agent at pyrolysis temperatures varying from 400 to 600 °C and residence times between 1 and 3 h. Overall, 76 samples were prepared and characterized thoroughly via elemental analysis, N2/CO2 ad/-desorption, thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and infrared spectroscopy (FTIR). The produced carbons showed specific surface areas of up to 1430 m2g−1 and a pore size distribution with a micropore share of up to 80 %. The presence of oxygen-containing functional groups was confirmed via FTIR. Potential feedstock contamination can be mitigated, as minerals and heavy metals could be leached out (up to –99.15 %) by an additional wash step and organic contamination undergoes thermal cracking during pyrolysis. The presented study could be a next step in upcycling considerable waste streams from the wood sector through localised and non-fossil-based AC production.

Abstract Background Urothelial carcinoma (UC) is the most common neoplasm of the canine lower urinary tract, affecting approximately 2% of dogs. Elderly female patients of certain breeds are predisposed, and clinical signs of UC can easily be confused with urinary tract infection or urolithiasis. Diagnosis and treatment are challenging given the lack of disease-specific markers and treatments. The S100A8/A9 complex and S100A12 protein are Ca2+-binding proteins expressed by cells of the innate immune system and have shown promise as urinary screening markers for UC. The neutrophil-to-lymphocyte ratio (NLR) can also aid in distinguishing certain neoplastic from inflammatory conditions. Our study aimed to evaluate the tissue expression of S100/calgranulins and the blood NLR in dogs with UC. Urinary bladder and/or urethral tissue samples from dogs with UC (n = 10), non-neoplastic inflammatory lesions (NNUTD; n = 6), and no histologic changes (n = 11) were evaluated using immunohistochemistry. Blood NLRs were analyzed in dogs with UC (n = 22) or NNUTD (n = 26). Results Tissue S100A12-positive cell counts were significantly higher in dogs with lower urinary tract disease than healthy controls (P = 0.0267 for UC, P = 0.0049 for NNUTD), with no significant difference between UC and NNUTD patients. Tissue S100A8/A9-positivity appeared to be higher with NNUTD than UC, but this difference did not reach statistical significance. The S100A8/A9+-to-S100A12+ ratio was significantly decreased in neoplastic and inflamed lower urinary tract tissue compared to histologically normal specimens (P = 0.0062 for UC, P = 0.0030 for NNUTD). NLRs were significantly higher in dogs with UC than in dogs with NNUTD, and a cut-off NLR of ≤ 2.83 distinguished UC from NNUTD with 41% sensitivity and 100% specificity. Higher NLRs were also associated with a poor overall survival time (P = 0.0417). Conclusions These results confirm that the S100/calgranulins play a role in the immune response to inflammatory and neoplastic lower urinary tract diseases in dogs, but the tissue expression of these proteins appears to differ from their concentrations reported in urine samples. Further investigations of the S100/calgranulin pathways in UC and their potential as diagnostic or prognostic tools and potential therapeutic targets are warranted. The NLR as a routinely available marker might be a useful surrogate to distinguish UC from inflammatory conditions.

Abstract In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in Saudi Arabia and was mostly associated with severe respiratory illness in humans. Dromedary camels are the zoonotic reservoir for MERS-CoV. To investigate the biology of MERS-CoV in camelids, we developed a well-differentiated airway epithelial cell (AEC) culture model for Llama glama and Camelus bactrianus. Histological characterization revealed progressive epithelial cellular differentiation with well-resemblance to autologous ex vivo tissues. We demonstrate that MERS-CoV displays a divergent cell tropism and replication kinetics profile in both AEC models. Furthermore, we observed that in the camelid AEC models MERS-CoV replication can be inhibited by both type I and III interferons (IFNs). In conclusion, we successfully established camelid AEC cultures that recapitulate the in vivo airway epithelium and reflect MERS-CoV infection in vivo. In combination with human AEC cultures, this system allows detailed characterization of the molecular basis of MERS-CoV cross-species transmission in respiratory epithelium.

Abstract Background Virtual communities played an important role in mental health and well-being during the Covid-19 pandemic by providing access to others and thereby preventing loneliness. The pandemic has accelerated the urge for digital solutions for people with pre-existing mental health problems. So far, it remains unclear how the people concerned communicate with each other and benefit from peer-to-peer support on a moderated digital platform. Objective The aim of the project was to identify and describe the communication patterns and verbal expression of users on the inCLOUsiv platform during the first lockdown in 2020. Methods Discussions in forums and live chats on inCLOUsiv were analysed using text mining, which included frequency, correlation, n-gram and sentiment analyses. Results The communication behaviour of users on inCLOUsiv was benevolent and supportive; and 72% of the identified sentiments were positive. Users addressed the topics of ‘corona’, ‘anxiety’ and ‘crisis’ and shared coping strategies. Conclusions The benevolent interaction between users on inCLOUsiv is in line with other virtual communities for Covid-19 and the potential for peer-to-peer support. Users can benefit from each other’s experiences and support each other. Virtual communities can be used as an adjuvant to existing therapy, particularly in times of reduced access to local health services.

Abstract Background Radiation-induced skin injury is a well-known risk factor for impaired wound healing. Over time, the deleterious effects of radiation on skin produce a fibrotic, hypovascular dermis poorly suited to wound healing. Despite increasing understanding of the underlying pathophysiology, therapeutic options remain elusive. Deferoxamine (DFO), an iron-chelating drug, has been shown in prior murine studies to ameliorate radiation-induced skin injury as well as improve wound healing outcomes in various pathologic conditions when administered transdermally. In this preclinical study, we evaluated the effects of deferoxamine on wound healing outcomes in chronically irradiated murine skin. Methods Wild-type mice received 30 Gy of irradiation to their dorsal skin and were left to develop chronic fibrosis. Stented excisional wounds were created on their dorsal skin. Wound healing outcomes were compared across 4 experimental conditions: DFO patch treatment, vehicle-only patch treatment, untreated irradiated wound, and untreated nonirradiated wounds. Gross closure rate, wound perfusion, scar elasticity, histology, and nitric oxide assays were compared across the conditions. Results Relative to vehicle and untreated irradiated wounds, DFO accelerated wound closure and reduced the frequency of healing failure in irradiated wounds. DFO augmented wound perfusion throughout healing and upregulated angiogenesis to levels observed in nonirradiated wounds. Histology revealed DFO increased wound thickness, collagen density, and improved collagen fiber organization to more closely resemble nonirradiated wounds, likely contributing to the observed improved scar elasticity. Lastly, DFO upregulated inducible nitric oxide synthase and increased nitric oxide production in early healing wounds. Conclusion Deferoxamine treatment presents a potential therapeutic avenue through which to target impaired wound healing in patients following radiotherapy.

Abstract Background Cancer mortality is mainly caused by organ failure and thrombotic events. It has been demonstrated that NETosis, a chromatin release mechanism implemented by neutrophils, may contribute to these lethal systemic effects. Our aim was to investigate NETosis biomarkers in endometrial cancer (EC). Methods The experiments were conducted on 21 healthy subjects (HS) with no gynecological conditions, and on 63 EC patients. To assess the presence of NETosis features, IHC and IF was performed using antibodies against citrullinated histone H3 (citH3), neutrophil elastase (NE) and histone 2B. Serum levels of cell free DNA (cfDNA), cell free mitochondrial DNA (cfmtDNA) and citH3 were measured by qPCR using one microliter of deactivated serum, and by ELISA assay respectively. Fragmentation pattern of serum cfDNA was analyzed using the Agilent 2100 Bioanalyzer and High Sensitivity DNA Chips. Receiver operating characteristic (ROC) analysis was used to identify a cut off for cfDNA and cfmtDNA values able to discriminate between ECs and HSs. Correlation analysis and multiple correspondence analysis (MCA) between cfDNA, mtcfDNA, citH3 and blood parameters were used to identify the potential association among serum parameters in EC grades. Results We demonstrated the presence of NETosis features in tissues from all EC grades. Serum cfDNA and cfmtDNA levels discriminate ECs from HSs and a direct correlation between citH3 and cfDNA content and an inverse correlation between cfmtDNA and citH3 in EC sera was observed, not detectable in HSs. MCA indicates cfDNA, cfmtDNA and citH3 as features associated to G1 and G2 grades. A correlation between increased levels of cfDNA, citH3 and inflammation features was found. Finally, serum nucleosomal cfDNA fragmentation pattern varies in EC sera and correlates with increased levels of cfDNA, citH3, lymphocytes and fibrinogen. Conclusion Our data highlight the occurrence of NETosis in EC and indicate serum cfDNA and citH3 as noninvasive biomarkers of tumor-induced systemic effects in endometrial cancer.

Stress and poor working conditions can affect the health and satisfaction of health professionals. Until now, the perspective of the staff has not been sufficiently considered in the development of solutions. The aim was to capture the wishes and recommendations of health professionals that could contribute to an improvement of the work situation from their perspective.

IntroductionAccording to the American Diabetes Association (ADA), 9–12 million patients suffer from chronic ulceration each year, costing the healthcare system over USD $25 billion annually. There is a significant unmet need for new and efficacious therapies to accelerate closure of non-healing wounds. Nitric Oxide (NO) levels typically increase rapidly after skin injury in the inflammatory phase and gradually diminish as wound healing progresses. The effect of increased NO concentration on promoting re-epithelization and wound closure has yet to be described in the context of diabetic wound healing.MethodsIn this study, we investigated the effects of local administration of an NO-releasing gel on excisional wound healing in diabetic mice. The excisional wounds of each mouse received either NO-releasing gel or a control phosphate-buffered saline (PBS)-releasing gel treatment twice daily until complete wound closure.ResultsTopical administration of NO-gel significantly accelerated the rate of wound healing as compared with PBS-gel-treated mice during the later stages of healing. The treatment also promoted a more regenerative ECM architecture resulting in shorter, less dense, and more randomly aligned collagen fibers within the healed scars, similar to that of unwounded skin. Wound healing promoting factors fibronectin, TGF-β1, CD31, and VEGF were significantly elevated in NO vs. PBS-gel-treated wounds.DiscussionThe results of this work may have important clinical implications for the management of patients with non-healing wounds.

Summary: Despite its rapidly increased availability for the study of complex tissue, single-cell RNA sequencing remains prohibitively expensive for large studies. Here, we present a protocol using oligonucleotide barcoding for the tagging and pooling of multiple samples from healing wounds, which are among the most challenging tissue types for this application. We describe steps to generate skin wounds in mice, followed by tissue harvest and oligonucleotide barcoding. This protocol is also applicable to other species including rats, pigs, and humans.For complete details on the use and execution of this protocol, please refer to Stoeckius et al. (2018),1 Galiano et al. (2004),2 and Mascharak et al. (2022).3 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

While wound healing in humans occurs primarily through re-epithelization, in rodents it also occurs through contraction of the panniculus carnosus, an underlying muscle layer that humans do not possess. Murine experimental models are by far the most convenient and inexpensive research model to study wound healing, as they offer great variability in genetic alterations and disease models. To overcome the obstacle of contraction biasing wound healing kinetics, our group invented the splinted excisional wound model. While other rodent wound healing models have been used in the past, the splinted excisional wound model has persisted as the most used model in the field of wound healing. Here, we present a detailed protocol of updated and refined techniques necessary to utilize this model, generate results with high validity, and accurately analyze the collected data. This model is simple to conduct and provides an easy, standardizable, and replicable model of human-like wound healing.

There is undisputable benefit in translating basic science research concretely into clinical practice, and yet, the vast majority of therapies and treatments fail to achieve approval. The rift between basic research and approved treatment continues to grow, and in cases where a drug is granted approval, the average time from initiation of human trials to regulatory marketing authorization spans almost a decade. Albeit with these hurdles, recent research with deferoxamine (DFO) bodes significant promise as a potential treatment for chronic, radiation-induced soft tissue injury. DFO was originally approved by the Food and Drug Administration (FDA) in 1968 for the treatment of iron overload. However, investigators more recently have posited that its angiogenic and antioxidant properties could be beneficial in treating the hypovascular and reactive-oxygen species-rich tissues seen in chronic wounds and radiation-induced fibrosis (RIF). Small animal experiments of various chronic wound and RIF models confirmed that treatment with DFO improved blood flow and collagen ultrastructure. With a well-established safety profile, and now a strong foundation of basic scientific research that supports its potential use in chronic wounds and RIF, we believe that the next steps required for DFO to achieve FDA marketing approval will include large animal studies and, if those prove successful, human clinical trials. Though these milestones remain, the extensive research thus far leaves hope for DFO to bridge the gap between bench and wound clinic in the near future.