Amelioration of age-related cognitive decline and anxiety in mice by Centella asiatica extract varies by sex, dose and mode of administration.

Background: A water extract (CAW) of the Ayurvedic plant Centella asiatica administered in drinking water has been shown to improve cognitive deficits in mouse models of aging and neurodegenerative diseases. Here the effects of CAW administered in drinking water or the diet on cognition, measures of anxiety and depression-like behavior in healthy aged mice are compared. Methods: Three- and eighteen-month-old male and female C57BL6 mice were administered rodent AIN-93M diet containing CAW (0, 0.2, 0.5 or 1% w/w) to provide 0, 200 mg/kg/d, 500 mg/kg/d or 1,000 mg/kg/d CAW for a total of 5 weeks. An additional group of eighteen-month-old mice were treated with CAW (10 mg/mL) in their drinking water CAW for a total of 5 weeks to deliver the same exposure of CAW as the highest dietary dose (1,000 mg/kg/d). CAW doses delivered were calculated based on food and water consumption measured in previous experiments. In the fourth and fifth weeks, mice underwent behavioral testing of cognition, anxiety and depression (n = 12 of each sex per treatment group in each test). Results: Aged mice of both sexes showed cognitive deficits relative to young mice while only female aged mice showed increased anxiety compared to the young female mice and no differences in depression were observed between the different ages. CAW (1,000 mg/kg/d) in the drinking water improved deficits in aged mice in learning, executive function and recognition memory in both sexes and attenuated the increased measures of anxiety observed in the aged female mice. However, CAW in the diet only improved executive function in aged mice at the highest dose (1,000 mg/kg/d) in both sexes and did so less robustly than when given in the water. There were no effects of CAW on depression-like behavior in aged animals regardless of whether it was administered in the diet or the water. Conclusions: These results suggest that CAW can ameliorate age-related changes in measures of anxiety and cognition and that the mode of administration is important for the effects of CAW on resilience to these age-related changes.

Nurse-sensitive quality and benchmarking in hospitals striving for Magnet® or Pathway® designation: A qualitative study.

AIM: To examine if and how selected German hospitals use nurse-sensitive clinical indicators and perspectives on national/international benchmarking. DESIGN: Qualitative study. METHODS: In 2020, 18 expert interviews were conducted with key informants from five purposively selected hospitals, being the first in Germany implementing Magnet® or Pathway®. Interviews were analyzed using content analysis with deductive-inductive coding. The study followed the COREQ guideline. RESULTS: Three major themes emerged: first, limited pre-existence of and necessity for nurse-sensitive data. Although most interviewees reported data collection for hospital-acquired pressure ulcers and falls with injuries, implementation varied and interviewees highlighted the necessity to develop additional nurse-sensitive indicators for the German context. Second, the theme creating an enabling data environment comprised building clinicians' acceptance, establishing a data culture, and reducing workload by using electronic health records. Third, challenges and opportunities in establishing benchmarking were identified but most interviewees called for a national or European benchmarking system. CONCLUSION: The need for further development of nurse-sensitive clinical indicators and its implementation in practice was highlighted. Several actions were suggested at hospital level to establish an enabling data environment in clinical care, including a nationwide or European benchmarking system. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Involving nurses in data collection, comparison and benchmarking of nurse-sensitive indicators and their use in practice can improve quality of patient care. IMPACT: Nurse-sensitive indicators were rarely collected, and a need for action was identified. The study results show research needs on nurse-sensitive indicators for Germany and Europe. Measures were identified to create an enabling data environment in hospitals. An initiative was started in Germany to establish a nurse-sensitive benchmarking capacity. PATIENT OR PUBLIC CONTRIBUTION: Clinical practitioners and nurse/clinical managers were interviewed.

Transformational nurse leadership attributes in German hospitals pursuing organization-wide change via Magnet® or Pathway® principles: results from a qualitative study.

BACKGROUND: Budget constraints, staff shortages and high workloads pose challenges for German hospitals. Magnet® and Pathway® are concepts for implementing organization-wide change and redesigning work environments. There is limited research on the key elements that characterize nurse leaders driving the implementation of Magnet®/Pathway® principles outside the U.S. We explored the key attributes of nurse leaders driving organization-wide change through Magnet®/Pathway® principles in German hospitals. METHODS: Using a qualitative study design, semi-structured interviews (n = 18) were conducted with nurse leaders, managers, and clinicians, in five German hospitals known as having started implementing Magnet® or Pathway® principles. The interviews were recorded and transcribed verbatim. Data were analyzed in Atlas.ti using content analysis. For the analysis, a category system was created using a deductive-inductive approach. RESULTS: Five leadership attributes and eleven sub-attributes were identified as main themes and sub-themes: Visionary leaders who possess and communicate a strong vision and serve as role models to inspire change. Strategic leaders who focus on strategic planning and securing top management support. Supportive leaders who empower, emphasizing employee motivation, individualized support, and team collaboration. Stamina highlights courage, assertiveness, and resilience in the face of challenges. Finally, agility which addresses a leader's presence, accessibility, and rapid responsiveness, fostering adaptability. CONCLUSIONS: The study demonstrates leadership attributes explicitly focusing on instigating and driving organization-wide change through Magnet®/Pathway® principles in five German hospitals. The findings suggest a need for comprehensive preparation and ongoing development of nurse leaders aimed at establishing and sustaining a positive hospital work environment.

Profiling of Oxylipins as Markers of Oxidative Stress in Biological Samples.

Oxylipins are oxidized metabolites of polyunsaturated fatty acids (PUFAs). They represent a class of risk markers and/or therapeutic targets for diseases associated with inflammation, including cardiovascular disease and brain disorders. Because the biological activities of free PUFAs and oxylipins depend on their chemical structures and concentrations, monitoring PUFAs and oxylipin levels in biological systems is critical for understanding their roles in health and disease. Traditionally, accurate quantification of free PUFAs and oxylipins in biological samples was performed separately, as PUFAs are often 1000-fold more abundant than the derived oxidized fatty acids (oxylipins). This article describes a liquid chromatography multiple reaction monitoring tandem mass spectrometry method for the quantitative analysis of five free PUFAs and 88 oxylipins in various biological fluids, including plasma, platelet supernatants, and tissues. The same approach can also be used in conjunction with an alkaline hydrolysis step to quantify total oxylipins in fish oils. We observed that in some samples, linoleic acid levels in plasma and eicosapentaenoic acid and arachidonic acid levels in brain tissue were above the upper limit of quantification. To address this issue, we developed a data analysis method to obtain PUFA and oxylipin concentrations in these samples without additional sample preparation, thus significantly saving time and labor. © 2024 Wiley Periodicals LLC. Basic Protocol: Quantification of polyunsaturated fatty acids (PUFAs) and oxylipins using liquid chromatography multiple reaction monitoring tandem mass spectrometry Support Protocol 1: Preparation of internal standard mixed working solution Support Protocol 2: Preparation of standard mixed stock solution Support Protocol 3: Preparation of standard mixed working solution Alternate Protocol 1: Extraction and quantitation of free PUFAs and oxylipins from mouse brain tissue Alternate Protocol 2: Extraction and quantitation of total PUFAs and oxylipins from fish oil.

Laying the foundations for implementing Magnet principles in hospitals in Europe: A qualitative analysis.

BACKGROUND: Magnet hospitals, a concept developed in the U.S., have been associated with improved nurse recruitment and retention, and better patient outcomes. Magnet principles may be useful to address workforce challenges in European hospitals, but they have not been implemented or evaluated on a large scale in the European hospital context. OBJECTIVE: This study aims to explore the initial phase of implementing Magnet principles in 11 acute care hospitals in six European countries. The specific objectives of the study were to investigate the type of work that characterises the early phase of implementation and how implementation leaders engage with their context. METHODS: A multinational qualitative study was conducted, with data from 23 semi-structured, one-to-one interviews with implementation leaders in 11 acute care hospitals in six European countries. Thematic analyses guided the analysis of data. FINDINGS: Three themes of core work processes during the early phase of implementing Magnet principles in European hospitals were identified. The first theme, 'Creating space for Magnet', describes how work was directed towards creating both political and organisational space for the project. The second theme, 'Framing to fit: understanding and interpreting Magnet principles', describes the translational work to understand what the Magnet model entails and how it relates to the local hospital context. Finally, the third theme, 'Calibrating speed and dose', describes the strategic work of considering internal and external factors to adjust the process of implementation. CONCLUSIONS: The first phase of implementation was characterised by conceptual and relational work; translating the Magnet concepts, considering the fit into existing structures and practices and making space for Magnet in the local context. Understanding the local context played an important role in shaping and guiding the navigation of professional and organisational tensions. Hospitals employed diverse strategies to either emphasise or downplay the role of nurses and nursing to facilitate progress in the implementation.

Physician and nurse well-being, patient safety and recommendations for interventions: cross-sectional survey in hospitals in six European countries.

OBJECTIVES: To determine the well-being of physicians and nurses in hospital practice in Europe, and to identify interventions that hold promise for reducing adverse clinician outcomes and improving patient safety. DESIGN: Baseline cross-sectional survey of 2187 physicians and 6643 nurses practicing in 64 hospitals in six European countries participating in the EU-funded Magnet4Europe intervention to improve clinicians' well-being. SETTING: Acute general hospitals with 150 or more beds in six European countries: Belgium, England, Germany, Ireland, Sweden and Norway. PARTICIPANTS: Physicians and nurses with direct patient contact working in adult medical and surgical inpatient units, including intensive care and emergency departments. MAIN OUTCOME MEASURES: Burnout, job dissatisfaction, physical and mental health, intent to leave job, quality of care and patient safety and interventions clinicians believe would improve their well-being. RESULTS: Poor work/life balance (57% physicians, 40% nurses), intent to leave (29% physicians, 33% nurses) and high burnout (25% physicians, 26% nurses) were prevalent. Rates varied by hospitals within countries and between countries. Better work environments and staffing were associated with lower percentages of clinicians reporting unfavourable health indicators, quality of care and patient safety. The effect of a 1 IQR improvement in work environments was associated with 7.2% fewer physicians and 5.3% fewer nurses reporting high burnout, and 14.2% fewer physicians and 8.6% fewer nurses giving their hospital an unfavourable rating of quality of care. Improving nurse staffing levels (79% nurses) and reducing bureaucracy and red tape (44% physicians) were interventions clinicians reported would be most effective in improving their own well-being, whereas individual mental health interventions were less frequently prioritised. CONCLUSIONS: Burnout, mental health morbidities, job dissatisfaction and concerns about patient safety and care quality are prevalent among European hospital physicians and nurses. Interventions to improve hospital work environments and staffing are more important to clinicians than mental health interventions to improve personal resilience.

Gut enterotype-dependent modulation of gut microbiota and their metabolism in response to xanthohumol supplementation in healthy adults.

Xanthohumol (XN), a polyphenol found in the hop plant (Humulus lupulus), has antioxidant, anti-inflammatory, prebiotic, and anti-hyperlipidemic activity. Preclinical evidence suggests the gut microbiome is essential in mediating these bioactivities; however, relatively little is known about XN's impact on human gut microbiota in vivo. We conducted a randomized, triple-blinded, placebo-controlled clinical trial (ClinicalTrials.gov NCT03735420) to determine safety and tolerability of XN in healthy adults. Thirty healthy participants were randomized to 24 mg/day XN or placebo for 8 weeks. As secondary outcomes, quantification of bacterial metabolites and 16S rRNA gene sequencing were utilized to explore the relationships between XN supplementation, gut microbiota, and biomarkers of gut health. Although XN did not significantly change gut microbiota composition, it did re-shape individual taxa in an enterotype-dependent manner. High levels of inter-individual variation in metabolic profiles and bioavailability of XN metabolites were observed. Moreover, reductions in microbiota-derived bile acid metabolism were observed, which were specific to Prevotella and Ruminococcus enterotypes. These results suggest interactions between XN and gut microbiota in healthy adults are highly inter-individualized and potentially indicate that XN elicits effects on gut health in an enterotype-dependent manner.

Integrating High-Resolution Mass Spectral Data, Bioassays and Computational Models to Annotate Bioactives in Botanical Extracts: Case Study Analysis of C. asiatica Extract Associates Dicaffeoylquinic Acids with Protection against Amyloid-ß Toxicity.

Rapid screening of botanical extracts for the discovery of bioactive natural products was performed using a fractionation approach in conjunction with flow-injection high-resolution mass spectrometry for obtaining chemical fingerprints of each fraction, enabling the correlation of the relative abundance of molecular features (representing individual phytochemicals) with the read-outs of bioassays. We applied this strategy for discovering and identifying constituents of Centella asiatica (C. asiatica) that protect against Aß cytotoxicity in vitro. C. asiatica has been associated with improving mental health and cognitive function, with potential use in Alzheimer's disease. Human neuroblastoma MC65 cells were exposed to subfractions of an aqueous extract of C. asiatica to evaluate the protective benefit derived from these subfractions against amyloid ß-cytotoxicity. The % viability score of the cells exposed to each subfraction was used in conjunction with the intensity of the molecular features in two computational models, namely Elastic Net and selectivity ratio, to determine the relationship of the peak intensity of molecular features with % viability. Finally, the correlation of mass spectral features with MC65 protection and their abundance in different sub-fractions were visualized using GNPS molecular networking. Both computational methods unequivocally identified dicaffeoylquinic acids as providing strong protection against Aß-toxicity in MC65 cells, in agreement with the protective effects observed for these compounds in previous preclinical model studies.

Amelioration of age-related cognitive decline and anxiety in mice by Centella asiatica extract varies by sex, dose and mode of administration.

We have previously reported that a water extract (CAW) of the Ayurvedic plant Centella asiatica administered in drinking water can improve cognitive deficits in mouse models of aging and neurodegenerative diseases. Here we compared the effects of CAW administered in drinking water or the diet on cognition, measures of anxiety and depression-like behavior in healthy aged mice. Three- and eighteen-month-old male and female C57BL6 mice were administered rodent AIN-93M diet containing CAW (0, 0.2, 0.5 or 1% w/w) to provide 0, 200 mg/kg/d, 500 mg/kg/d or 1000 mg/kg/d for a total of 5 weeks. An additional group of eighteen-month-old mice were treated with CAW (10 mg/mL) in their drinking water for a total of five weeks to deliver the same exposure of CAW as the highest dietary dose (1000 mg/kg/d). CAW doses delivered were calculated based on food and water consumption measured in previous experiments. In the fourth and fifth weeks, mice underwent behavioral testing of cognition, anxiety and depression (n=12 of each sex per treatment group in each test). Aged mice of both sexes showed cognitive deficits relative to young mice while only female aged mice showed increased anxiety compared to the young female mice and no differences in depression were observed between the different ages. CAW (1000 mg/kg/d) in the drinking water improved deficits in aged mice in learning, executive function and recognition memory in both sexes and attenuated the increased measures of anxiety observed in the aged female mice. However, CAW in the diet only improved executive function in aged mice at the highest dose (1000 mg/kg/d) in both sexes and did so less robustly than when given in the water. There were no effects of CAW on depression-like behavior in aged animals regardless of whether it was administered in the diet or the water. These results suggest that CAW can ameliorate age-related changes in measures of anxiety and cognition and that the mode of administration is important for the effects of CAW on resilience to these age-related changes.

Web-Based Public Reporting as a Decision-Making Tool for Consumers of Long-Term Care in the United States and the United Kingdom: Systematic Analysis of Report Cards.

BACKGROUND: Report cards can help consumers make an informed decision when searching for a long-term care facility. OBJECTIVE: This study aims to examine the current state of web-based public reporting on long-term care facilities in the United States and the United Kingdom. METHODS: We conducted an internet search for report cards, which allowed for a nationwide search for long-term care facilities and provided freely accessible quality information. On the included report cards, we drew a sample of 1320 facility profiles by searching for long-term care facilities in 4 US and 2 UK cities. Based on those profiles, we analyzed the information provided by the included report cards descriptively. RESULTS: We found 40 report cards (26 in the United States and 14 in the United Kingdom). In total, 11 of them did not state the source of information. Additionally, 7 report cards had an advanced search field, 24 provided simplification tools, and only 3 had a comparison function. Structural quality information was always provided, followed by consumer feedback on 27 websites, process quality on 15 websites, prices on 12 websites, and outcome quality on 8 websites. Inspection results were always displayed as composite measures. CONCLUSIONS: Apparently, the identified report cards have deficits. To make them more helpful for users and to bring public reporting a bit closer to its goal of improving the quality of health care services, both countries are advised to concentrate on optimizing the existing report cards. Those should become more transparent and improve the reporting of prices and consumer feedback. Advanced search, simplification tools, and comparison functions should be integrated more widely.

Quantification of Caffeoylquinic Acids and Triterpenes as Targeted Bioactive Compounds of Centella asiatica in Extracts and Formulations by Liquid Chromatography Mass Spectrometry.

Centella asiatica (CA) is a culinary vegetable and well-known functional food that is widely used as a medicinal herb and dietary supplement. CA is rich in pentacyclic triterpenes (TTs), including asiaticoside (AS), madecassoside (MS) and the related aglycones asiatic acid (AA), madecassic acid (MA). Traditionally, TTs have been associated with the bioactivity and health promoting effect of CA. Recently, mono-caffeoylquinic acids (MonoCQAs) and di-caffeoylquinic acids (DiCQAs) have been found to contribute to the bioactivity of CA as well. This work reports an analytical strategy based on liquid chromatography coupled to multiple reaction monitoring mass spectrometry (LC-MRM-MS) for the simultaneous rapid and accurate quantification of 12 bioactive compounds in CA, namely AS, MS, AA, MA, 5-CQA, 4-CQA, 3-CQA, 1,3-DiCQA, 3,4-DiCQA, 1,5-DiCQA, 3,5-DiCQA, 4,5-DiCQA. Method selectivity, accuracy, precision, repeatability, robustness, linearity range, limit of detection (LOD), and limit of quantitation (LOQ) were validated. The validated LC-MRM-MS method has been successfully applied to quantify the 12 bioactive compounds in CA aqueous extracts and two related formulations: a standardized CA product (CAP) used in a phase I clinical trial and formulated CA rodent diets used in preclinical studies. The validated method allows us to support the standardization of CA products used for clinical trials and conduct routine LC-MRM-MS analyses of formulated preclinical diets to confirm correct levels of CA phytochemical markers.

Top-down mass spectrometry for characterizing the low molecular weight proteome of canine osteosarcoma cell phenotypes.

Osteosarcoma (OS) is the most common primary malignant tumor of bone, which occupying about 20% of all bone cancers. To increase understanding of the biology of OS, we developed and evaluated a top-down mass spectrometry approach to detect, identify and quantify low molecular weight (MW) proteins (i.e., 1 kDa < MW < 30 kDa) in osteosarcoma cells. Top-down proteomic (TDP) data was acquired using reversed phase nano-liquid chromatography in conjunction with high-resolution mass spectrometry and resulted in the assignment of 328 proteins and 820 proteoforms or degradation products with high confidence. Eight post-translational modifications (PTMs) were identified in the present study, including N-terminal acetylation, lysine acetylation, succinylation, malonylation, serine/tyrosine phosphorylation, histidine methylation and N-acetylleucine. We confirmed that a truncated N-terminal proteoform lost 73 Da of mass through removal of the N-terminal Met (-131 Da), acetylation of the second amino acid (+42 Da), and Met oxidation (+16 Da). The results showed that the levels of proteoforms/biodegradable peptides correlated with the metastatic phenotypes of osteosarcoma cell lines. This study demonstrates the benefits of TDP for the characterization and relative quantification of proteoforms with relevance to OS biology and the potential of small molecular weight proteoforms to serve as a still underappreciated source of biomarkers.

Bioanalytical method validation and application to a phase 1, double-blind, randomized pharmacokinetic trial of a standardized Centella asiatica (L.) Urban water extract product in healthy older adults.

Introduction: Centella asiatica is an herbaceous plant reputed in Eastern medicine to improve memory. Preclinical studies have shown that C. asiatica aqueous extract (CAW) improves neuronal health, reduces oxidative stress, and positively impacts learning and cognition. This study aimed to develop and validate bioanalytical methods for detecting known bioactive compounds from C. asiatica in human biological matrices and apply them to a human pharmacokinetic trial in healthy older adults. Methods: High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used for detecting triterpenes and caffeoylquinic acids from C. asiatica, or their metabolites, in human plasma and urine. Validation parameters including linearity, precision, accuracy, recovery and thermal stability were evaluated. The method was applied to a Phase I, randomized, double-blind, crossover trial of two doses (2 or 4 g) of a standardized C. asiatica water extract product (CAP) in eight healthy older adults. Pharmacokinetic parameters were measured over a 12-h post administration period and acute safety was assessed. Results: The method satisfied US Food & Drug Administration criteria for linearity and recovery of the analytes of interest in human plasma and urine. The method also satisfied criteria for precision and accuracy at medium and high concentrations. Single administration of 2 and 4 g of CAP was well tolerated and safe in healthy older adults. The parent triterpene glycosides, asiaticoside and madecassoside, were not detected in plasma and in minimal amounts in urinary excretion analyses, while the aglycones, asiatic acid and madecassic acid, showed readily detectable pharmacokinetic profiles. Similarly, the di-caffeoylquinic acids and mono-caffeoylquinic acids were detected in low quantities, while their putative metabolites showed readily detectable pharmacokinetic profiles and urinary excretion. Discussion: This method was able to identify and calculate the concentration of triterpenes and caffeoylquinic acids from C. asiatica, or their metabolites, in human plasma and urine. The oral absorption of these key compounds from CAP, and its acute safety in healthy older adults, support the use of this C. asiatica product in future clinical trials.

Chlorogenic Acids, Acting via Calcineurin, Are the Main Compounds in Centella asiatica Extracts That Mediate Resilience to Chronic Stress in Drosophila melanogaster.

Common symptoms of depressive disorders include anhedonia, sleep problems, and reduced physical activity. Drugs used to treat depression mostly aim to increase serotonin signaling but these can have unwanted side effects. Depression has also been treated by traditional medicine using plants like Centella asiatica (CA) and this has been found to be well tolerated. However, very few controlled studies have addressed CA's protective role in depression, nor have the active compounds or mechanisms that mediate this function been identified. To address this issue, we used Drosophila melanogaster to investigate whether CA can improve depression-associated symptoms like anhedonia and decreased climbing activity. We found that a water extract of CA provides resilience to stress induced phenotypes and that this effect is primarily due to mono-caffeoylquinic acids found in CA. Furthermore, we describe that the protective function of CA is due to a synergy between chlorogenic acid and one of its isomers also present in CA. However, increasing the concentration of chlorogenic acid can overcome the requirement for the second isomer. Lastly, we found that chlorogenic acid acts via calcineurin, a multifunctional phosphatase that can regulate synaptic transmission and plasticity and is also involved in neuronal maintenance.

Advancement of research on nurse practitioners: Setting a research agenda.

BACKGROUND: Primary care delivered by nurse practitioners (NPs) helps to meet the United States' growing demand for care and improves patient outcomes. Yet, barriers impede NP practice. Knowledge of these barriers is limited, hindering opportunities to eliminate them. PURPOSE: We convened a 1.5-day conference to develop a research agenda to advance evidence on the primary care NP workforce. METHODS: Thirty experts gathered in New York City for a conference in 2022. The conference included plenary sessions, small group discussions, and a prioritization process to identify areas for future research and research questions. DISCUSSION: The research agenda includes top-ranked research questions within five categories: (a) policy regulations and implications for care, quality, and access; (b) systems affecting NP practice; (c) health equity and the NP workforce; (d) NP education and workforce dynamics, and (e) international perspectives. CONCLUSION: The agenda can advance evidence on the NP workforce to guide policy and practice.

Recruiting and retaining bachelor qualified nurses in German hospitals (BSN4Hospital): protocol of a mixed-methods design.

INTRODUCTION: Many countries in Europe are facing a shortage of nurses and seek effective recruitment and retention strategies. The nursing workforce is increasingly diverse in its educational background, ranging from 3-year vocational training (diploma) to bachelor and master educated nurses. This study analyses recruitment and retention strategies for academically educated nurses (minimum bachelor), including intention to leave, job satisfaction and work engagement compared with diploma nurses in innovative German hospitals; it explores recruitment and retention challenges and opportunities, and identifies lessons on recruitment and retention taking an international perspective. METHODS AND ANALYSIS: The study will apply a convergent mixed-methods design, including qualitative and quantitative methods. The qualitative study will include semistructured interviews among hospital managers, nurses, students and stakeholders in Germany. In addition, expert interviews will be conducted internationally in countries with a higher proportion of bachelor/master nurses in hospitals. The quantitative, cross-sectional study will consist of a survey among professional nurses (bachelor/master, diploma nurses) in German hospitals. Study settings are hospitals with a higher-than-average proportion of bachelor nurses or relevant recruitment, work environment or retention strategies in place. Analyses will be conducted in several phases, first in parallel, then combined via triangulation: the parallel analysis technique will analyse the qualitative and quantitative data separately via content analyses (interviews) and descriptive, bivariate and multivariate analyses (survey). Subsequently, data sources will be collectively analysed via a triangulation matrix focusing on developing thematic exploratory clusters at three systemic levels: microlevel, mesolevel and macrolevel. The analyses will be relevant for generating lessons for clinical nursing, management and policy in Germany and internationally. ETHICS AND DISSEMINATION: Ethics approval was obtained by the Charité Ethics Committee.Several dissemination channels will be used, including publications and presentations, for the scientific community, nursing management, clinical nurses and the wider public in Germany and internationally.

Skill-Mix Changes Targeting Health Promotion and Prevention Interventions and Effects on Outcomes in all Settings (Except Hospitals): Overview of Reviews.

Objectives: Skill-mix changes to step up health promotion and prevention are increasing, but there is limited evidence on their effects. Methods: Overview of reviews, based on a protocol. The search was carried out in six databases, screening was performed ensuring high interrater reliability. All countries, health professions and lay workers in all settings (except hospitals) were included, quality appraisals performed. Results: A total of 31 systematic reviews were included. Expanded roles performing outreach (e.g., home visits) had mostly positive effects on access and health outcomes, primarily for hard-to-reach groups. Task-shifting in colorectal or skin cancer screenings (performed by advanced practice nurses) were suggested effective; supporting roles (by community health workers) increased uptake in screenings, but based on limited evidence. Expanded roles of various professions focusing on lifestyle modification showed promising effects in most reviews, including weight, diet, smoking cessation and physical activity. Reviews on cost-effectiveness were based on limited evidence. Conclusion: Promising skill-mix changes included expanded roles providing lifestyle modifying interventions, task-shifting, and outreach roles for hard-to-reach groups, whereas evidence on costs was limited.

Simultaneous Chemical Mapping of Live Biofilm Microenvironmental pH and Hydrogen Peroxide in Real Time with a Triple Scanning Electrochemical Microscopy Tip.

Dental plaque biofilm is a complex ecosystem. The distribution of microbial species in the biofilm is heavily influenced by local chemical interactions that result from diverse metabolic activities and the nature of the released molecules. As a relevant example, H2O2-producing bacteria can antagonize disease-associated bacteria, leading to the maintenance of a healthy oral microbiome. Herein, we report the development of a triple-sensor (redox, pH, and H2O2) scanning electrochemical microscopy (SECM) tip capable of simultaneously mapping the pH and H2O2 concentration produced by a dental plaque-derived multispecies biofilm grown on hydroxyapatite. The pH sensor of the triple SECM tip showed a near Nernstian slope of -71.1 ± 2 mV/pH (N = 3), whereas the H2O2 sensor showed a slope of -0.052 ± 0.002 nA/µM H2O2 at pH 7.2 and a detection limit of 1.0 ± 0.2 µM (N = 7). There is no significant difference in the sensitivities of H2O2 sensors at pH 6.2, 7.2, and 8.2 at 95% CI (N = 7). The pH and H2O2 sensors demonstrated excellent reversibility with response times of 3 and 5 s, respectively, along with reliable stability over 4 h at 37 °C. The sensors did not show any cross talk between pH and H2O2 concentration ([H2O2]) measurements, highlighting the accuracy and versatility of the SECM tip. Simultaneous chemical imaging of pH and [H2O2] across the biofilm revealed a clustered distribution of local H2O2 concentrations, ranging from 0 to 17 µM. Conversely, the local pH remained constant at 7.2. The relation of local chemical profiles and the distribution of bacterial species within the oral microbiome was experimentally investigated in the context of bacterial H2O2 antagonism. The benefit of clustered H2O2 production was that the total area of H2O2 produced by smaller clusters was 67% more than that of a single cluster with the same starting number of bacteria. Thus, this triple SECM tip can potentially be used to study local molecular mechanisms that result in dysbiosis of the oral microbiome.

Xanthohumol improves cognition in farnesoid X receptor-deficient mice on a high-fat diet.

Xanthohumol (XN) improves cognition of wild-type rodents on a high-fat diet (HFD). Bile acids and ceramide levels in the liver and hippocampus might be linked to these effects. XN modulates activity of the nuclear farnesoid X receptor (FXR; also known as NR1H4), the primary receptor for bile acids. To determine the role of FXR in the liver and intestine in mediating the effects of XN on cognitive performance, mice with intestine- and liver-specific FXR ablation (FXRIntestine-/- and FXRLiver-/-, respectively) on an HFD or an HFD containing XN were cognitively tested. XN improved cognitive performance in a genotype- and sex-dependent manner, with improved task learning in females (specifically wild-type), reversal learning in males (specifically wild-type and FXRIntestine-/- mutant) and spatial learning (both sexes). XN increased hippocampal diacylglycerol and sphingomyelin levels in females but decreased them in males. XN increased the ratio of shorter-chain to longer-chain ceramides and hexaceramides. Higher diacylglycerol and lower longer-chain ceramide and hexaceramide levels were linked to improved cognitive performance. Thus, the beneficial sex-dependent cognitive effects of XN are linked to changes in hippocampal diacylglycerol and ceramide levels. This article has an associated First Person interview with the first author of the paper.