[Testosterone replacement therapy and possible side effects]. / Testosteronsubstitution und etwaige Nebenwirkungen.

The substitution of testosterone is basic andrological treatment. Beside the "when and how," knowledge of possible side effects is mandatory. Therefore, we highlight the effects of testosterone replacement therapy on bones, cardiac function, sexuality, gynacomatia, fertility, and contraception, but also areas of concern regarding prostate carcinoma and testosterone replacement therapy.

Transoral laser microsurgery for supraglottic carcinomas: results of a prospective multicenter trial (SUPRATOL).

Background: A limited number of single institutions have published retrospective cohort studies on transoral laser microsurgery for supraglottic laryngectomy (TLM-SGL). These studies have shown that the oncologic outcomes of TLM-SGL are comparable to those of open SGL. However, there is limited information available regarding swallowing rehabilitation and quality of life (QoL). Patients and methods: SUPRATOL is a prospective, multicenter trial assessing the functional outcomes of TLM-SGL +/- adjuvant radio-(chemo)-therapy. The primary endpoint was aspiration-free swallowing at 12 months, as established using fibreoptic endoscopic evaluation of swallowing (FEES) and defined as a grade < 6 on the penetration-aspiration scale. Secondary endpoints were swallowing- and voice-related QoL, the prevalence of temporary and permanent tracheostomy and percutaneous gastrostomy, local control, laryngectomy-free survival, overall survival, and disease-free survival, as well as the influence of treatment centers on outcomes. Results: From April 2015 to February 2018, 102 patients were recruited from 26 German Otorhinolaryngology (ORL) hospitals. All patients had TLM-SGL and 96.1% underwent uni- or bilateral, mostly selective neck dissection. To 47.0% of patients, adjuvant radio-(chemo)-therapy (R(C)T) was administered. The median follow-up period was 24.1 months. At 12-month follow-up, completed by 84.3% of patients, 98.2%, 95.5%, and 98.8% were free of aspiration when tested with saliva, liquid, or pulp. Adjuvant R(C)T, pT category, and type of resection had no significant influence on swallowing rehabilitation. A total of 40.2% of patients had been tracheotomized, and in 46.1% of patients, a PEG tube was inserted. At the 24-month follow-up, 5.3% of patients still required a tracheostomy, and 8.0% continued to use a percutaneous endoscopic gastrostomy (PEG) tube. Deterioration of swallowing- and voice-related QoL was observed immediately after treatment, but patients recovered, and baseline values were reached again. The Kaplan-Meier 2-year rates for local control, laryngectomy-free survival, overall survival, and disease-free survival were 88%, 92%, 93%, and 82%, respectively. Conclusions: Our prospective multicenter trial shows that, at 12 months post-TLM-SGL +/- R(C)T, 95.5%-98.8% of patients achieved aspiration-free swallowing. Morbidity was higher than previously reported. The rates of permanent tracheostomy and gastrostomy tube placement correspond to previous cohort studies. The 2-year oncologic outcomes are within the reported range. Clinical trial registration: https://drks.de/search/en/trial/DRKS00004641, identifier (DRKS00004641).

Aridity drives the response of soil total and particulate organic carbon to drought in temperate grasslands and shrublands.

The increasing prevalence of drought events in grasslands and shrublands worldwide potentially has impacts on soil organic carbon (SOC). We leveraged the International Drought Experiment to study how SOC, including particulate organic carbon (POC) and mineral-associated organic carbon (MAOC) concentrations, responds to extreme drought treatments (1-in-100-year) for 1 to 5 years at 19 sites worldwide. In more mesic areas (aridity index > 0.65), SOC and POC concentrations decreased by 7.9% (±3.9) and 15.9% (±6.2) with drought, respectively, but there were no impacts on MAOC concentrations. However, drought had no impact on SOC, POC, or MAOC concentrations in drylands (aridity index < 0.65). The response of SOC to drought varied along an aridity gradient, concomitant with interannual precipitation variability and standing SOC concentration gradients. These findings highlight the differing response magnitudes of POC and MAOC concentrations to drought and the key regulating role of aridity.

Short QT intervals in African lions.

The cardiac conduction system in large carnivores, such as the African lion (Panthera leo), represents a significant knowledge gap in both veterinary science and in cardiac electrophysiology. Short QT intervals have been reported from zoo-kept, anaesthetized lions, and our goal was to record the first ECGs from wild, conscious lions roaming freely, and compare them to zoo-kept lions under the hypothesis that short QT is unique to zoo-kept lions. Macroscopic and histological examinations were performed on heart tissue removed from nine healthy zoo lions. ECGs were recorded from the nine anaesthetized zoo-kept lions, and from 15 anaesthetized and conscious wild lions in Africa. Our histological and topographical description of the lion's heart matched what has previously been published. In conscious lions, the ECG recordings revealed a mean heart rate of 70 ± 4 beats/min, with faster heart rates during the night. PQ and QT intervals were heart rate dependent in the conscious lions. Interestingly, QT intervals recorded in wild lions were markedly longer than QT intervals from zoo lions (398 ± 40 vs. 297 ± 9 ms, respectively; P < 0.0001). Anaesthesia or heart rate did not account for this difference. We provide a comprehensive description of the cardiac anatomy and electrophysiology of wild and zoo-kept lions. QT intervals were significantly shorter in zoo lions, suggesting functional disparities in cardiac electrophysiology between wild and zoo-kept lions, potentially related to physical fitness. These findings underscore the plasticity of cardiac electrophysiology and may be of value when reintroducing endangered species into the wild and when managing lions in human care.

Enteric methane emissions from zebu cattle are influenced by seasonal variations in rangeland fodder quality and intake.

Rangeland fodder resources used to feed ruminants in the Sahel decline considerably in both quantity and quality from the wet to dry seasons. While it is widely assumed worldwide that this seasonality of fodder supply impacts intake levels and therefore enteric methane (eCH4) emissions, there are very few references based on in vivo measurements of eCH4 in this region. The purpose of this study was to test the assumption that the seasonality of fodder supply impacts intake levels and consequently eCH4 in ruminants. Thus, eCH4 was measured in vivo in Sudanese Fulani zebu cattle during three main seasons of the year (wet season: WS, cold dry season: CDS, and hot dry season: HDS). The experiment was carried out on 10 steers aged 32 months with an average (± SD) initial BW of 138 ± 5.8 kg (i.e. 0.55 Tropical Livestock Unit - TLU) and kept in individual pens. Animals were fed with natural rangeland fodder harvested each season following herders' practices, i.e. green fodder in the WS and dry fodder hay in the CDS and HDS. Different levels of fodder were offered to the animals to reproduce the gradient of fodder availability on rangelands over the year (six trials): 3.3% BW during the CDS; 3.3, 2.3, and 1.4% BW successively during the HDS; and 2.3% in two sequential studies in the WS. Each trial lasted 3 weeks, split into 2 weeks of fodder adaptation and 1 week of data collection. The BW, quantity of voluntary DM intake, digestibility of DM digestibility and of OM digestibility, and eCH4 (GreenFeed® system) were measured for each animal. Fodder composition varied considerably between seasons (P < 0.05). The DM intake (g/kg BW per day) varied from 23.9 in CDS to 15.7 in HDS and 22.3 in WS (P < 0.001). The DM digestibility varied from 0.50 in CDS to 0.46 in HDS and 0.57 in WS. The eCH4 yields (g/kg DM intake per day) varied significantly from 25.2 in the CDS to 31.8 in the HDS and 20.5 in the WS. When extrapolated over a full year and irrespective of season, eCH4 emissions for steers amounted to 68.1 g/d (24.6 g/kg DM intake per day, 46.7 ± 3.34 kg of eCH4/TLU per year). Variations in the various parameters recorded in different areas and during the main seasons must therefore be accounted for in national inventories to refine eCH4 data for ruminants in Sub-Saharan Africa.

Machine learning to attribute the source of Campylobacter infections in the United States: A retrospective analysis of national surveillance data.

OBJECTIVES: Integrating pathogen genomic surveillance with bioinformatics can enhance public health responses by identifying risk and guiding interventions. This study focusses on the two predominant Campylobacter species, which are commonly found in the gut of birds and mammals and often infect humans via contaminated food. Rising incidence and antimicrobial resistance (AMR) are a global concern, and there is an urgent need to quantify the main routes to human infection. METHODS: During routine US national surveillance (2009-2019), 8856 Campylobacter genomes from human infections and 16,703 from possible sources were sequenced. Using machine learning and probabilistic models, we target genetic variation associated with host adaptation to attribute the source of human infections and estimate the importance of different disease reservoirs. RESULTS: Poultry was identified as the primary source of human infections, responsible for an estimated 68% of cases, followed by cattle (28%), and only a small contribution from wild birds (3%) and pork sources (1%). There was also evidence of an increase in multidrug resistance, particularly among isolates attributed to chickens. CONCLUSIONS: National surveillance and source attribution can guide policy, and our study suggests that interventions targeting poultry will yield the greatest reductions in campylobacteriosis and spread of AMR in the US. DATA AVAILABILITY: All sequence reads were uploaded and shared on NCBI's Sequence Read Archive (SRA) associated with BioProjects; PRJNA239251 (CDC / PulseNet surveillance), PRJNA287430 (FSIS surveillance), PRJNA292668 & PRJNA292664 (NARMS) and PRJNA258022 (FDA surveillance). Publicly available genomes, including reference genomes and isolates sampled worldwide from wild birds are associated with BioProject accessions: PRJNA176480, PRJNA177352, PRJNA342755, PRJNA345429, PRJNA312235, PRJNA415188, PRJNA524300, PRJNA528879, PRJNA529798, PRJNA575343, PRJNA524315 and PRJNA689604. Contiguous assemblies of all genome sequences compared are available at Mendeley data (assembled C. coli genomes doi: 10.17632/gxswjvxyh3.1; assembled C. jejuni genomes doi: 10.17632/6ngsz3dtbd.1) and individual project and accession numbers can be found in Supplementary tables S1 and S2, which also includes pubMLST identifiers for assembled genomes. Figshare (10.6084/m9.figshare.20279928). Interactive phylogenies are hosted on microreact separately for C. jejuni (https://microreact.org/project/pascoe-us-cjejuni) and C. coli (https://microreact.org/project/pascoe-us-ccoli).

Local adaptation to climate facilitates a global invasion.

Local adaptation may facilitate range expansion during invasions, but the mechanisms promoting destructive invasions remain unclear. Cheatgrass (Bromus tectorum), native to Eurasia and Africa, has invaded globally, with particularly severe impacts in western North America. We sequenced 307 genotypes and conducted controlled experiments. We found that diverse lineages invaded North America, where long-distance gene flow is common. Ancestry and phenotypic clines in the native range predicted those in the invaded range, indicating pre-adapted genotypes colonized different regions. Common gardens showed directional selection on flowering time that reversed between warm and cold sites, potentially maintaining clines. In the Great Basin, genomic predictions of strong local adaptation identified sites where cheatgrass is most dominant. Preventing new introductions that may fuel adaptation is critical for managing ongoing invasions.

SARS-CoV-2-specific plasma cells are not durably established in the bone marrow long-lived compartment after mRNA vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines are effective at protecting from severe disease, but the protective antibodies wane rapidly even though SARS-CoV-2-specific plasma cells can be found in the bone marrow (BM). Here, to explore this paradox, we enrolled 19 healthy adults at 2.5-33 months after receipt of a SARS-CoV-2 mRNA vaccine and measured influenza-, tetanus- or SARS-CoV-2-specific antibody-secreting cells (ASCs) in long-lived plasma cell (LLPC) and non-LLPC subsets within the BM. Only influenza- and tetanus-specific ASCs were readily detected in the LLPCs, whereas SARS-CoV-2 specificities were mostly absent. The ratios of non-LLPC:LLPC for influenza, tetanus and SARS-CoV-2 were 0.61, 0.44 and 29.07, respectively. In five patients with known PCR-proven history of recent infection and vaccination, SARS-CoV-2-specific ASCs were mostly absent from the LLPCs. We show similar results with measurement for secreted antibodies from BM ASC culture supernatant. While serum IgG titers specific for influenza and tetanus correlated with IgG LLPCs, serum IgG levels for SARS-CoV-2, which waned within 3-6 months after vaccination, were associated with IgG non-LLPCs. In all, our studies suggest that rapid waning of SARS-CoV-2-specific serum antibodies could be accounted for by the absence of BM LLPCs after these mRNA vaccines.

Oscillatory-Quality of sleep spindles links brain state with sleep regulation and function.

Here, we characterized the dynamics of sleep spindles, focusing on their damping, which we estimated using a metric called oscillatory-Quality (o-Quality), derived by fitting an autoregressive model to electrophysiological signals, recorded from the cortex in mice. The o-Quality of sleep spindles correlates weakly with their amplitude, shows marked laminar differences and regional topography across cortical regions, reflects the level of synchrony within and between cortical networks, is strongly modulated by sleep-wake history, reflects the degree of sensory disconnection, and correlates with the strength of coupling between spindles and slow waves. As most spindle events are highly localized and not detectable with conventional low-density recording approaches, o-Quality thus emerges as a valuable metric that allows us to infer the spread and dynamics of spindle activity across the brain and directly links their spatiotemporal dynamics with local and global regulation of brain states, sleep regulation, and function.

What every paediatrician needs to know about mechanical ventilation.

Invasive mechanical ventilation (MV) is one of the most practiced interventions in the intensive care unit (ICU) and is unmistakably lifesaving for children with acute respiratory failure (ARF). However, if delivered inappropriately (i.e. ignoring the respiratory system mechanics and not targeted to the need of the individual patient at a specific time point in the disease trajectory), the side effects will outweigh the benefits. Decades of experimental and clinical investigations have resulted in a better understanding of three important detrimental effects of MV. These are ventilation-induced lung injury (VILI), patient self-inflicted lung injury (P-SILI), and ventilation-induced diaphragmatic injury (VIDD). VILI, P-SILI, and VIDD have in common that they occur when there is either too much or too little ventilatory assistance.Conclusion: The purpose of this review is to give the paediatrician an overview of the challenges to prevent these detrimental effects and titrate MV to the individual patient needs.

Monitoring macroplastics in aquatic and terrestrial ecosystems: Expert survey reveals visual and drone-based census as most effective techniques.

Anthropogenic litter, such as plastic, is investigated by the global scientific community from various fields employing diverse techniques. The goal is to assess and finally mitigate the pollutants' impacts on the natural environment. Plastic litter can accumulate in different matrices of aquatic and terrestrial ecosystems, impacting both biota and ecosystem functioning. Detection and quantification of macroplastics, and other litter, can be realized by jointly using visual census and remote sensing techniques. The primary objective of this research was to identify the most effective approach for monitoring macroplastic litter in riverine and marine environments through a comprehensive survey based on the experiences of the scientific community. Researchers involved in plastic pollution evaluated four litter occurrence and flux investigation methods (visual census, drone-based surveys, satellite imagery, and GPS/GNSS trackers) through a questionnaire. Traditional visual census and drone deployment were deemed as the most popular approaches among the 46 surveyed researchers, while satellite imagery and GPS/GNSS trackers received lower scores due to limited field validation and short performance ranges, respectively. On a scale from 0 to 5, visual census and drone-based surveys obtained 3.5 and 2.0, respectively, whereas satellite imagery and alternative solutions received scores lower than 1.2. Visual and drone censuses were used in high, medium and low-income countries, while satellite census and GPS/GNSS trackers were mostly used in high-income countries. This work provides an overview of the advantages and drawbacks of litter investigation techniques, contributing i) to the global harmonization of macroplastic litter monitoring and ii) providing a starting point for researchers and water managers approaching this topic. This work supports the selection and design of reliable and cost-effective monitoring approaches to mitigate the ambiguity in macroplastic data collection, contributing to the global harmonization of macroplastic litter monitoring protocols.

In Silico Decoding of Parkinson's: Speech & Writing Analysis.

Background: Parkinson's disease (PD) has transitioned from a rare condition in 1817 to the fastest-growing neurological disorder globally. The significant increase in cases from 2.5 million in 1990 to 6.1 million in 2016, coupled with predictions of a further doubling by 2040, underscores an impending healthcare challenge. This escalation aligns with global demographic shifts, including rising life expectancy and a growing global population. The economic impact, notably in the U.S., reached $51.9 billion in 2017, with projections suggesting a 46% increase by 2037, emphasizing the substantial socio-economic implications for both patients and caregivers. Coupled with a worldwide demand for health workers that is expected to rise to 80 million by 2030, we have fertile ground for a pandemic. Methods: Our transdisciplinary research focused on early PD detection through running speech and continuous handwriting analysis, incorporating medical, biomedical engineering, AI, and linguistic expertise. The cohort comprised 30 participants, including 20 PD patients at stages 1-4 on the Hoehn and Yahr scale and 10 healthy controls. We employed advanced AI techniques to analyze correlation plots generated from speech and handwriting features, aiming to identify prodromal PD biomarkers. Results: The study revealed distinct speech and handwriting patterns in PD patients compared to controls. Our ParkinsonNet model demonstrated high predictive accuracy, with F1 scores of 95.74% for speech and 96.72% for handwriting analyses. These findings highlight the potential of speech and handwriting as effective early biomarkers for PD. Conclusions: The integration of AI as a decision support system in analyzing speech and handwriting presents a promising approach for early PD detection. This methodology not only offers a novel diagnostic tool but also contributes to the broader understanding of PD's early manifestations. Further research is required to validate these findings in larger, diverse cohorts and to integrate these tools into clinical practice for timely PD pre-diagnosis and management.

Improving Triage Accuracy in Prehospital Emergency Telemedicine: Scoping Review of Machine Learning-Enhanced Approaches.

BACKGROUND: Prehospital telemedicine triage systems combined with machine learning (ML) methods have the potential to improve triage accuracy and safely redirect low-acuity patients from attending the emergency department. However, research in prehospital settings is limited but needed; emergency department overcrowding and adverse patient outcomes are increasingly common. OBJECTIVE: In this scoping review, we sought to characterize the existing methods for ML-enhanced telemedicine emergency triage. In order to support future research, we aimed to delineate what data sources, predictors, labels, ML models, and performance metrics were used, and in which telemedicine triage systems these methods were applied. METHODS: A scoping review was conducted, querying multiple databases (MEDLINE, PubMed, Scopus, and IEEE Xplore) through February 24, 2023, to identify potential ML-enhanced methods, and for those eligible, relevant study characteristics were extracted, including prehospital triage setting, types of predictors, ground truth labeling method, ML models used, and performance metrics. Inclusion criteria were restricted to the triage of emergency telemedicine services using ML methods on an undifferentiated (disease nonspecific) population. Only primary research studies in English were considered. Furthermore, only those studies using data collected remotely (as opposed to derived from physical assessments) were included. In order to limit bias, we exclusively included articles identified through our predefined search criteria and had 3 researchers (DR, JS, and KS) independently screen the resulting studies. We conducted a narrative synthesis of findings to establish a knowledge base in this domain and identify potential gaps to be addressed in forthcoming ML-enhanced methods. RESULTS: A total of 165 unique records were screened for eligibility and 15 were included in the review. Most studies applied ML methods during emergency medical dispatch (7/15, 47%) or used chatbot applications (5/15, 33%). Patient demographics and health status variables were the most common predictors, with a notable absence of social variables. Frequently used ML models included support vector machines and tree-based methods. ML-enhanced models typically outperformed conventional triage algorithms, and we found a wide range of methods used to establish ground truth labels. CONCLUSIONS: This scoping review observed heterogeneity in dataset size, predictors, clinical setting (triage process), and reported performance metrics. Standard structured predictors, including age, sex, and comorbidities, across articles suggest the importance of these inputs; however, there was a notable absence of other potentially useful data, including medications, social variables, and health system exposure. Ground truth labeling practices should be reported in a standard fashion as the true model performance hinges on these labels. This review calls for future work to form a standardized framework, thereby supporting consistent reporting and performance comparisons across ML-enhanced prehospital triage systems.

A 3D Epithelial-Mesenchymal Co-Culture Model of the Airway Wall Using Native Lung Extracellular Matrix.

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by ongoing inflammation, impaired tissue repair, and aberrant interplay between airway epithelium and fibroblasts, resulting in an altered extracellular matrix (ECM) composition. The ECM is the three-dimensional (3D) scaffold that provides mechanical support and biochemical signals to cells, now recognized not only as a consequence but as a potential driver of disease progression. To elucidate how the ECM influences pathophysiological changes occurring in COPD, in vitro models are needed that incorporate the ECM. ECM hydrogels are a novel experimental tool for incorporating the ECM in experimental setups. We developed an airway wall model by combining lung-derived ECM hydrogels with a co-culture of primary human fibroblasts and epithelial cells at an air-liquid interface. Collagen IV and a mixture of collagen I, fibronectin, and bovine serum albumin were used as basement membrane-mimicking coatings. The model was initially assembled using porcine lung-derived ECM hydrogels and subsequently with COPD and non-COPD human lung-derived ECM hydrogels. The resulting 3D construct exhibited considerable contraction and supported co-culture, resulting in a differentiated epithelial layer. This multi-component 3D model allows the investigation of remodelling mechanisms, exploring ECM involvement in cellular crosstalk, and holds promise as a model for drug discovery studies exploring ECM involvement in cellular interactions.

Spinal laser interstitial thermal therapy and radiotherapy for thoracic metastatic epidural spinal cord compression.

PURPOSE: Spinal laser interstitial thermal therapy (sLITT) is a less invasive alternative to surgery for metastatic epidural spinal cord compression. Here, we analyze outcomes of patients treated with sLITT either in conjunction with radiotherapy or as a standalone salvage therapy. METHODS: We included patients with thoracic vertebral metastatic cord compression treated with sLITT. Outcomes included freedom from local failure (FFLF) and overall survival (OS). Factors associated with FFLF were identified with univariable and multivariable analyses via a Cox proportional hazards model. RESULTS: Between 2013-2022, 129 patients received sLITT to 144 vertebral segments; 69% were radiotherapy naïve, 81% were radioresistant histologies, and 74% were centered in the vertebral body. Median age was 61 years. Pre-sLITT Bilsky score was 3 in 28%, 2 in 33%, and 1c in 37%. Radiotherapy was delivered in conjunction with sLITT for 80% of cases, including 68% that received stereotactic radiotherapy, at a median of 5 days after sLITT. Median follow-up was 9.1 months. One-year FFLF and OS was 80% and 78%, respectively. On multivariable analysis, variables independently associated with adverse FFLF included paraspinal/foraminal disease location (p = 0.001), and post-sLITT imaging Bilsky score of 2 (p = 0.073) or 3 (p = 0.011). Prior radiotherapy, technique of radiotherapy, and time between radiotherapy and sLITT were not associated with FFLF. CONCLUSION: sLITT with radiotherapy is an effective minimally invasive treatment approach for thoracic metastatic epidural spinal cord compression. Early treatment response may serve as a prognostic imaging biomarker.

Orthoflaviviral Inhibitors in Clinical Trials, Preclinical In Vivo Efficacy Targeting NS2B-NS3 and Cellular Antiviral Activity via Competitive Protease Inhibition.

Orthoflaviviruses, including zika (ZIKV), West Nile (WNV), and dengue (DENV) virus, induce severely debilitating infections and contribute significantly to the global disease burden, yet no clinically approved antiviral treatments exist. This review offers a comprehensive analysis of small-molecule drug development targeting orthoflaviviral infections, with a focus on NS2B-NS3 inhibition. We systematically examined clinical trials, preclinical efficacy studies, and modes of action for various viral replication inhibitors, emphasizing allosteric and orthosteric drugs inhibiting NS2B-NS3 protease with in vivo efficacy and in vitro-tested competitive NS2B-NS3 inhibitors with cellular efficacy. Our findings revealed that several compounds with in vivo preclinical efficacy failed to show clinical antiviral efficacy. NS3-NS4B inhibitors, such as JNJ-64281802 and EYU688, show promise, recently entering clinical trials, underscoring the importance of developing novel viral replication inhibitors targeting viral machinery. To date, the only NS2B-NS3 inhibitor that has undergone clinical trials is doxycycline, however, its mechanism of action and clinical efficacy as viral growth inhibitor require additional investigation. SYC-1307, an allosteric inhibitor, exhibits high in vivo efficacy, while temoporfin and methylene blue represent promising orthosteric non-competitive inhibitors. Compound 71, a competitive NS2B-NS3 inhibitor, emerges as a leading preclinical candidate due to its high cellular antiviral efficacy, minimal cytotoxicity, and favorable in vitro pharmacokinetic parameters. Challenges remain in developing competitive NS2B-NS3 inhibitors, including appropriate biochemical inhibition assays as well as the selectivity and conformational flexibility of the protease, complicating effective antiviral treatment design.

Comparative study of the antiproliferative activity of heterometallic carbene gold(i)-platinum(ii) and gold(i)-palladium(ii) complexes in cancer cell lines.

The stepwise, one-pot synthesis of heterobimetallic carbene gold(i) platinum(ii) complexes from readily available starting materials is presented. The protecting group free methodology is based on the graduated nucleophilicities of aliphatic and aromatic amines as linkers between both metal centers. This enables the selective, sequential installation of the metal fragments. In addition, the obtained complexes were tested as potential anticancer agents and directly compared to their gold(i) palladium(ii) counterparts.

Immersive medical training: a comprehensive longitudinal study of extended reality in emergency scenarios for large student groups.

Young healthcare professionals and medical graduates often fall short in the practical experience necessary for handling medical emergencies. This can not only lead to strained feelings of inadequacy and insecurity among future physicians and less experienced healthcare providers in general, but also to detrimental outcomes for patients as emergency medicine demands rapid decision-making with low tolerance for errors. New didactic modalities and approaches may be needed to effectively address this shortcoming. Immersive technologies are powerful novel educational tools with untapped potential in medical training, and may be particularly suitable for simulation trainings in the high-stakes field of emergency medicine.Herein, we systematically explored the educational potential of extended reality (XR) technology, particularly virtual reality (VR), in the management of patients presenting as medical emergencies, combining the use of the STEP-VR application with an untethered hardware setup.Importantly, we aimed at studying multiple, large cohorts of senior medical students involving a total of 529 participants and collecting data over a period of two years. We assessed students' acceptance of the training through a modified questionnaire measuring device handling, content complexity, degree of immersion, learning success, and seminar design.Our results show high, sustained acceptance and ease of use across different student cohorts and subgroups, with most students finding XR/VR engaging and beneficial for acquiring emergency medicine skills. Importantly, the prevalence of simulation sickness was minimal. Moreover, no major effect of the head-mounted displays (HMDs) price range was noted with regard to the learning experience. The results underscore the potential of XR/VR capabilities in effectively enhancing medical education, particularly in areas of high-stakes clinical scenarios and emergency care, by providing realistic and reproducible immersive training environments.In summary, our findings suggest that XR/VR-based training approaches could significantly contribute to preparing future physicians for the complexities of emergency medical care, encouraging the integration of such technologies into medical curricula. However, careful consideration must be given to its suitability for all students and the practical challenges of its implementation, highlighting the need for further research to harness its full potential for medical education.

Construction of a Theoretical Model of Chronic Disease Self-Management: Self-Management Within a Syndemic.

The purpose of this article is to describe a model of chronic disease self-management that incorporates the complexity of social and environmental interactions experienced by people who self-manage chronic conditions. This study combines quantitative data from a large national research cohort and qualitative interviews to test and refine a self-management model. The self-management within a syndemic model depicts the contextual, psychological, and social factors that predict self-management behaviors and clinical and long-term outcomes.