Digital health literacy among primary and secondary school teachers-a quantitative study.

Introduction: Digital health literacy (DHL) is a key competency for individuals' daily decisions toward their health behavior and wellbeing. While there is much focus on health literacy (HL) among the general population, teachers have been rarely addressed. Given the shortages in the teaching workforce in Europe and the impact of demanding working conditions on their health, it is important to address DHL in teachers. This paper examines the DHL of primary and secondary teachers and its associations with sociodemographic and school-related factors. Methods: An online cross-sectional study was conducted with 1,600 German primary and secondary school teachers between October and December 2022. To assess DHL, the Digital Health Literacy Instrument (DHLI) including seven subscales was used. Statistical analyses were conducted on item and subscale level and an overall DHL score was calculated. Next to descriptive analyses, bivariate and regression analyses were conducted to explore potential associations with sociodemographic and school-related factors. Results: The frequency of difficulty in using digital health information varied across DHL dimensions and was greatest for protecting privacy (70.9%) and evaluating reliability (40.0%). In multivariate analysis, females more often reported a sufficient ability of adding content (OR = 1.61, CI = 1.05-2.48), while males more often reported a sufficient ability to protect their privacy (OR = 0.45, CI = 0.27-0.75). Teachers with leadership positions more often reported a sufficient ability in adding content (OR = 1.78, CI = 1.07-2.98). Regarding the ability to determine the relevance of online health-related information, no associations with a predictor variable were found. Discussion: The results suggest that it is important to examine the individual dimensions of DHL and their distinct associations with sociodemographic and school-level factors, rather than just to rely on the overall level of DHL. The differential patterns identified in this study suggest a greater intervention need for teachers from higher age groups, primary and secondary general schools, and those without leadership roles. However, based on the limited predictive power of the variables included, further individual and school-level factors and their potential association with DHL should be investigated in the future. The promotion of DHL should be integrated into both teacher education and in-service training.

Management of adult patients with podocytopathies: an update from the ERA Immunonephrology Working Group.

The histopathological lesions, minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are entities without immune complex deposits which can cause podocyte injury, thus are frequently grouped under the umbrella of podocytopathies. Whether MCD and FSGS may represent a spectrum of the same disease remains a matter of conjecture. Both frequently require repeated high-dose glucocorticoid therapy with alternative immunosuppressive treatments reserved for relapsing or resistant cases and response rates are variable. There is an unmet need to identify patients who should receive immunosuppressive therapies as opposed to those who would benefit from supportive strategies. Therapeutic trials focusing on MCD are scarce, and the evidence used for the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guideline for the management of glomerular diseases largely stems from observational and pediatric trials. In FSGS, the differentiation between primary forms and those with underlying genetic variants or secondary forms further complicates trial design. This article provides a perspective of the Immunonephrology Working Group (IWG) of the European Renal Association (ERA) and discusses the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases focusing on the management of MCD and primary forms of FSGS in the context of recently published evidence, with a special emphasis on the role of rituximab, cyclophosphamide, supportive treatment options and ongoing clinical trials in the field.

CONNECTing Concussion Care with Research Across Ontario.

Common data elements (CDEs) for concussion, as established by international bodies, are not being widely used in Ontario, resulting in significant variability in the data being assessed and collected across clinics. CDEs support standardization of care as well as large-scale data sharing for high impact research. A collaborative network - Concussion Ontario Network: Neuroinformatics to Enhance Clinical care and Translation (CONNECT) - comprised of health care professionals, researchers, members from advocacy groups, and patients was formed to establish and implement CDEs for concussion care and research. While the seeds have been planted and initial effectiveness demonstrated, future challenges exist.

Sex-related differences in gait characteristics and their associations with symptoms in individuals with patellofemoral osteoarthritis.

BACKGROUND: Patellofemoral osteoarthritis (OA) is an important subgroup of knee OA. However, the influence of sex on gait characteristics in patients with patellofemoral OA is unknown. RESEARCH QUESTION: Compare gait characteristics in females and males with patellofemoral OA and investigate their associations with patellofemoral joint-related symptoms and limitations. METHODS: Mixed effects polynomial regression models compared knee flexion-extension and adduction moments, knee flexion angles, and vertical ground reaction forces over 100% of stance between 26 females and 22 males with patellofemoral OA, with and without adjustment for walking speed and body mass. Multivariable linear regression models were then used to investigate the associations of gait characteristics with symptoms and limitations measured with the Knee injury and Osteoarthritis Outcome Score Patellofemoral Pain and Osteoarthritis (KOOS-PF) Subscale. Models included a sex-by-gait interaction term, and if significant, separate models were built for females and males. RESULTS: While controlling for walking speed and body mass, females had lower knee flexion moment (6-19% and 97-100% of stance), knee extension moment (45-86% of stance), knee adduction moment (3-37% and 69-99% of stance), vertical ground reaction force (1-97% of stance) and knee flexion angle (90-100% of stance) compared with males, when fitted over 100% of stance. Lower cadence, lower knee flexion angular impulse, and higher peak knee flexion angle were associated with worse KOOS-PF scores. Associations were not modified by sex. SIGNIFICANCE: There are distinct sex-based differences in gait characteristics throughout stance with patellofemoral OA when adjusting for body mass and walking speed. Lower cadence and knee flexion angular impulse, and higher peak knee flexion angle were associated with more extreme patellofemoral joint-related symptoms and limitations.

Effectiveness of the holistic primary school-based intervention MindMatters: study protocol for a cluster-randomised controlled trial.

BACKGROUND: The prevalence of mental health problems in childhood and adolescence has increased significantly, not least due to the COVID-19 pandemic in Germany and other countries worldwide. Although holistic school interventions to promote mental health and prevent mental health problems are considered promising, there is currently uncertainty about their effectiveness due to evaluation studies with heterogeneous methodological quality. This paper presents the study protocol for the evaluation of the primary school module of MindMatters. METHODS: As part of a universal mental health intervention, the MindMatters primary school module 'Learning Together with Emotions' aims to promote social-emotional learning (SEL) in the classroom across five skill areas. In addition to classroom activities, the intervention includes a school development module to help primary schools create structures and processes to maintain and promote mental health. To evaluate the effectiveness of the intervention, a two-arm cluster-randomised controlled trial will be conducted, including schools implementing MindMatters over a 12-month period and a control group with no access to the intervention. Data will be collected before and 18 months after initiation of the intervention. Controlled for baseline conditions, multilevel regression analysis will be used to examine primary intervention outcomes at the pupil level (i.e. reductions in mental and behavioural problems). Further mediation and moderation analyses will examine whether proximal outcomes predict changes in mental health outcomes and whether school-level factors influence the effectiveness of the intervention. DISCUSSION: This study will contribute to strengthen the evidence base for holistic school (mental) health promotion interventions using a study design with high internal validity. Based on an intervention model, the results will not only provide insights into the relationship between proximal and distal outcomes, but will also allow conclusions to be drawn about how the implementation of the intervention affects its effectiveness. Finally, the findings also address the question of whether improved mental health has a positive effect on primary school pupils' academic performance. TRIAL REGISTRATION: German Clinical Trials Register DRKS00023762. Registered on 5 January 2021.

Computational drug repositioning of clopidogrel as a novel therapeutic option for focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a glomerular lesion often associated with nephrotic syndrome. It is also associated with a high risk of progression to end-stage kidney disease. Current treatment of FSGS is limited to systemic corticosteroids or calcineurin inhibition, along with inhibitors of the renin-angiotensin-aldosterone system. FSGS is heterogeneous in etiology, and novel therapies targeting specific, dysregulated molecular pathways represent a major unmet medical need. We have generated a network-based molecular model of FSGS pathophysiology using previously established systems biology workflows to allow computational evaluation of compounds for their predicted interference with molecular processes contributing to FSGS. We identified the anti-platelet drug clopidogrel as a therapeutic option to counterbalance dysregulated FSGS pathways. This prediction of our computational screen was validated by testing clopidogrel in the adriamycin FSGS mouse model. Clopidogrel improved key FSGS outcome parameters and significantly reduced urinary albumin to creatinine ratio (P < 0.01) and weight loss (P < 0.01), and ameliorated histopathological damage (P < 0.05). Clopidogrel is used to treat several cardiovascular diseases linked to chronic kidney disease. Clopidogrel's favorable safety profile and its efficacy in the adriamycin mouse FSGS model thus recommend it as an attractive drug repositioning candidate for clinical trial in FSGS.

[Advanced Nursing Practice as a concept of care for people with outpatient ventilation in Germany: Results of a demand- and curriculum analysis]. / Advanced Nursing Practice als Konzept für die Versorgung von Menschen mit außerklinischer Beatmung in Deutschland: Ergebnisse einer Bedarfs- und Curriculumanalyse.

INTRODUCTION: Outpatient intensive care for people on home mechanical ventilation (HMV) is a complex area of care with high demands on the nurses specialised in this field. Internationally, academic qualification as an Advanced Practice Nurse (APN) has become established in these fields of specialised care. Despite the large number of further training opportunities, there is no university qualification for home mechanical ventilation in Germany. Based on a demand- and curriculum analysis, this study therefore defines the role of an APN for home mechanical ventilation (APN-HMV). METHODS: The study structure is based on the PEPPA framework (Participatory, Evidence-based and Patient-focused Process for the Development, Implementation and Evaluation of Advanced Practice Nursing). The need for a new model of care was determined with a qualitative secondary analysis based on interviews with health care professionals (n = 87) and a curriculum analysis (n = 5). Analyses were conducted using the Hamric model with a deductive-inductive approach. Subsequently, the main problems and objectives to improve the model of care were agreed upon in the research group, and the APN-HMV role was defined. RESULTS: The qualitative secondary data analysis illustrates the need for APN core competencies, especially in the psychosocial area and in family-centred care. The curriculum analysis resulted in a total of 1,375 coded segments. The focus of the curricula was on the central competency "direct clinical practice" (1,116 coded segments) and thus on ventilatory and critical care measures. Based on the results, the profile of APN-HMV could be defined. CONCLUSIONS: The introduction of an APN-HMV can usefully complement the skill and grade mix in outpatient intensive care and counteract care problems in this highly specialised area. The study provides a basis for the development of appropriate academic programmes or advanced training courses at universities.

An inosine triphosphate pyrophosphatase safeguards plant nucleic acids from aberrant purine nucleotides.

In plants, inosine is enzymatically introduced in some tRNAs, but not in other RNAs or DNA. Nonetheless, our data show that RNA and DNA from Arabidopsis thaliana contain (deoxy)inosine, probably derived from nonenzymatic adenosine deamination in nucleic acids and usage of (deoxy)inosine triphosphate (dITP and ITP) during nucleic acid synthesis. We combined biochemical approaches, LC-MS, as well as RNA-Seq to characterize a plant INOSINE TRIPHOSPHATE PYROPHOSPHATASE (ITPA) from A. thaliana, which is conserved in many organisms, and investigated the sources of deaminated purine nucleotides in plants. Inosine triphosphate pyrophosphatase dephosphorylates deaminated nucleoside di- and triphosphates to the respective monophosphates. ITPA loss-of-function causes inosine di- and triphosphate accumulation in vivo and an elevated inosine and deoxyinosine content in RNA and DNA, respectively, as well as salicylic acid (SA) accumulation, early senescence, and upregulation of transcripts associated with immunity and senescence. Cadmium-induced oxidative stress and biochemical inhibition of the INOSINE MONOPHOSPHATE DEHYDROGENASE leads to more IDP and ITP in the wild-type (WT), and this effect is enhanced in itpa mutants, suggesting that ITP originates from ATP deamination and IMP phosphorylation. Inosine triphosphate pyrophosphatase is part of a molecular protection system in plants, preventing the accumulation of (d)ITP and its usage for nucleic acid synthesis.

Crystal structure analysis of N-acetylated proline and ring size analogs.

Crystal structures of N-acetylated proline and homologs with four- and six-membered rings (azetidine carboxylic acid and piperidine carboxylic acid) were obtained and compared. The distinctly different conformations of the four-, five-, and six-membered rings reflect Bayer strain, n → π* interaction, and allylic strain, and result in crystal lattices with a zigzag structure.

Walk Smarter, Not Harder: Effects of Cadence Manipulation on Gait Biomechanics in Patients with Patellofemoral Osteoarthritis.

PURPOSE: This study aimed to investigate the effect of walking cadence on knee flexion angular impulse and peak external flexion moment in patients with patellofemoral osteoarthritis (OA). METHODS: Forty-eight patients with patellofemoral OA underwent repeated quantitative gait analyses on an instrumented treadmill using a randomized crossover design. Walking trials were conducted at a fixed gait speed, under three cadence conditions: (i) preferred cadence, (ii) +10% increased cadence, and (iii) -10% decreased cadence, completed in random order. Using a linear mixed model, we tested the association of cadence conditions with surrogate measures of patellofemoral load (primary outcome measure: knee flexion angular impulse) while controlling for body mass. We then repeated the analyses while sequentially replacing the dependent variable with secondary outcome measures. RESULTS: Walking with increased cadence decreased (adjusted mean difference [95% confidence interval]) the knee flexion angular impulse (-0.85 N·m·s -1 [-1.52 to -0.18], d = 0.20) and peak knee flexion moment (-4.11 N·m [-7.35 to -0.86], d = 0.24), whereas walking with decreased cadence increased the knee flexion angular impulse (1.83 N·m·s -1 [1.15 to 2.49], d = 0.42) and peak knee flexion moment (3.55 N·m [0.30 to 6.78], d = 0.21). Similar decreases and increases were observed for secondary outcome measures. CONCLUSIONS: Walking with increased cadence, while maintaining a fixed gait speed, reduces knee flexion angular impulse as well as other surrogate measures of knee loading in patients with patellofemoral OA.

In-Depth Analysis of the Extracorporeal Proteome Adsorbed to Dialysis Membranes during Hemodialysis.

Used hemodialysis membranes (HD-M) are a valuable reservoir of biological information. Proteins bind to HD-M, but whether this process depends on the type of membrane or patient factors or selectively affects specific protein classes has not been adequately elucidated. State-of-the-art proteomics techniques are capable of identifying and quantifying this therapy-specific subproteome to enable the analysis of disease- or membrane-induced pathophysiologies. We demonstrate the feasibility of the deep proteomic characterization of the extracorporeal proteome adsorbed to HD-M. A shotgun proteomics approach using nano-flow liquid chromatography coupled to mass-spectrometry identified 1648 unique proteins eluted by a chaotropic buffer from the HD-M of eight patients. In total, 995 proteins were present in all eluates; a more stringent approach showed that a core proteome of 310 proteins could be identified independently in all samples. Stability of the dialyzer proteome was demonstrated by a >90% re-identification rate on longitudinal samples of a single patient. The core proteome showed an overrepresentation of pathways of hemostasis and the immune system, and showed differences in membrane materials (polysulfone vs. helixone). This study demonstrates that optimized conditions combined with high-performance proteomics enable the in-depth exploration of the subproteome bound to HD-M, yielding a stable core proteome that can be exploited to study patient-specific factors and improve hemodialysis therapy.

Protocol for a living systematic review for the management of concussion in adults.

INTRODUCTION: Concussion/mild traumatic brain injury (mTBI) often presents initially with disabling symptoms that resolve, but for an unfortunate minority some of these symptoms may become prolonged. Although research into diagnosis and interventions for concussion is increasing, study quality overall remains low. A living systematic review that is updated as evidence becomes available is the ideal research activity to inform a living guideline targeting clinicians and patients. The purpose of this paper is to present the protocol of an ongoing living systematic review for the management of adult concussion that will inform living guidelines building off the Guideline for Concussion/Mild Traumatic Brain Injury and Persistent Symptoms: third Edition. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol guidelines were followed in the reporting of this systematic review protocol. We are including English peer-reviewed observational studies, trials, qualitative studies, systematic reviews and clinical practice guidelines related to diagnosis/assessment or treatment of adult concussion. Future searches will be conducted at minimum every 6 months using the following databases: MEDLINE ALL, EMBASE, Cochrane, PsycInfo and CINAHL. The data are managed in the Covidence website. Screening, data extraction and risk-of-bias assessments are being done through multiple raters working independently. Multiple validated tools are being used to assess risk of bias, and the tool applied matches the document or study design (eg, Downs and Black Scale for healthcare interventions). Many concussion experts in various clinical disciplines from across North America have volunteered to examine the evidence in order to make recommendations for the living guidelines. ETHICS AND DISSEMINATION: No ethical approval is necessary because primary data are not collected. The results will be disseminated through peer-reviewed publications and on the living guidelines website once built. PROSPERO REGISTRATION NUMBER: CRD42022301786.

Targeted Training for Subspecialist Care in Children With Medical Complexity.

Background: Children with medical complexity (CMC) are prone to medical errors and longer hospital stays, while residents do not feel prepared to provide adequate medical care for this vulnerable population. No educational guidance for the training of future pediatric tertiary care specialists outside their field of expertise involving the multidisciplinary care of CMC exists. We investigated pediatric residents past educational needs and challenges to identify key learning content for future training involving care for CMC. Methods: This was a prospective mixed-methods study at a single pediatric tertiary care center. Qualitative semi-structured interviews with residents were conducted, submitted to thematic content analysis, linked to the American Board of Pediatrics (ABP) general pediatrics content outline, and analyzed with importance performance analysis (IPA). Quantitative validation was focused on key themes of pediatric nephrology within the scope of an online survey among pediatric residents and specialists. Results: A total of 16 interviews, median duration 69 min [interquartile range IQR 35], were conducted. The 280 listed themes of the ABP general pediatrics content outline were reduced to 165 themes, with 86% (theoretical) knowledge, 12% practical skills, and 2% soft skills. IPA identified 23 knowledge themes to be of high importance where improvement is necessary and deemed fruitful. Quantitative validation among 84 residents and specialists (response rate 55%) of key themes in nephrology yielded high agreement among specialists in pediatric nephrology but low interrater agreement among trainees and "trained" non-nephrologists. The occurrence of themes in the qualitative interviews and their calculated importance in the quantitative survey were highly correlated (tau = 0.57, p = 0.001). Two clusters of high importance for other pediatric specialties emerged together with a contextual cluster of frequent encounters in both in- and outpatient care. Conclusion: Regarding patient safety, this study revealed the heterogeneous aspects and the importance of training future pediatric tertiary care specialists outside their field of expertise involving the multidisciplinary care of CMC. Our results may lay the groundwork for future detailed analysis and development of training boot camps that might be able to aid the improvement of patient safety by decreasing preventable harm by medical errors, especially for vulnerable patient groups, such as CMC in tertiary care pediatrics.

The relationship between empathy and the quality of the educational environment in Canadian emergency medicine residents.

PURPOSE: Empathy and quality of educational environment appear to be inversely correlated with burnout but the relationship between the two is largely unknown. Our primary objective was to examine the relationship between postgraduate educational environment and empathy. Secondary objectives included impact of gender, residency year and on- versus off-service context on levels of empathy and educational environment. METHODS: A modified Dillman approach was used to conduct an email survey of Canadian Royal College Emergency Medicine residents in June 2020. The survey instrument included: demographic data, Toronto Empathy Questionnaire (TEQ) and Scan of Postgraduate Educational Environment Domains (SPEED). Logistic and linear regressions evaluated the association between TEQ and SPEED, and mean SPEED scores and covariates, respectively. RESULTS: Response rate was 38% (138/363) with representation from all programs. Respondents were mean 30 years of age, 59% men and 25%, 20%, 18%, 24%, and 13% in postgraduate year (PGY) 1-5, respectively. There was no statistically significant association between high/low TEQ scores and mean SPEED score (p = 0.97). There were no statistically significant associations between any of the covariates and high/low TEQ scores (gender, p = 0.21; PGY, p = 0.58; on-versus off-service, p = 0.46) or mean SPEED score (gender, p = 0.95; PGY, p = 0.48; on- versus off-service, p = 0.07). Emergency medicine residents rated their educational environment on average 3.44 (+/- 0.43) out of four. 39 of 134 residents were found to have low empathy. CONCLUSION: There was no association between empathy and educational environment. Further research is needed to elucidate modifiable factors contributing to the development of low empathy in emergency medicine residents.

RéSUMé: OBJECTIF: L'empathie et la qualite de l'environnement educatif semblent etre inversement correlees a l'epuisement professionnel, mais la relation entre les deux est largement inconnue. Notre objectif principal etait d'examiner la relation entre l'environnement educatif de troisieme cycle et l'empathie. Les objectifs secondaires comprenaient l'impact du sexe, de l'annee de residence et du contexte en service ou hors service sur les niveaux d'empathie et l'environnement educatif. MéTHODES: Une approche Dillman modiiee a ete utilisee pour mener une enquete par courriel aupres des residents du College royal canadien de medecine d'urgence en juin 2020. L'instrument d'enquete comprenait : des donnees demographiques, le Toronto Empathy Questionnaire (TEQ) et le Scan of Postgraduate Educational Environment Domains (SPEED). Des regressions logistiques et lineaires ont evalue l'association entre TEQ et SPEED, et les scores SPEED moyens et les covariables, respectivement. RéSULTATS: Le taux de reponse etait de 38 % (138/363) avec une representation de tous les programmes. Les repondants etaient ages en moyenne de 30 ans, 59 % d'hommes et 25%, 20%, 18%, 24% et 13% de la 1re a la 5e annee de troisieme cycle, respectivement. Il n'y avait pas d'association statistiquement signiicative entre les scores TEQ eleves/bas et le score SPEED moyen (p = 0.97). Il n'y avait pas d'association statistiquement signiicative entre l'une des covariables et les scores TEQ eleves/faibles (sexe, p = 0,21 ; annee de troisieme cycle, p = 0.58 ; en service contre hors service, p = 0.46) ou le score SPEED moyen (sexe, p = 0.95 ; annee de troisieme cycle, p = 0.48 ; en service contre hors service, p = 0.07). Les residents en medecine d'urgence ont evalue leur environnement educatif a une moyenne de 3.44 ± 0.43. 4.39 des 134 residents se sont averes avoir une faible empathie. CONCLUSION: Il n'y avait pas d'association entre l'empathie et l'environnement educatif. Des recherches supplementaires sont necessaires pour elucider les facteurs modiiables contribuant au developpement d'une faible empathie chez les residents en medecine d'urgence.

Two Symptoms to Triage Acute Concussions: Using Decision Tree Modeling to Predict Prolonged Recovery After a Concussion.

OBJECTIVE: The objective was to examine the 22 variables from the Sport Concussion Assessment Tool's 5th Edition Symptom Evaluation using a decision tree analysis to identify those most likely to predict prolonged recovery after a sport-related concussion. DESIGN: A cross-sectional design was used in this study. A total of 273 patients (52% men; mean age, 21 ± 7.6 yrs) initially assessed by either an emergency medicine or sport medicine physician within 14 days of concussion (mean, 6 ± 4 days) were included. The 22 symptoms from the Sport Concussion Assessment Tool's 5th Edition were included in a decision tree analysis performed using RStudio and the R package rpart. The decision tree was generated using a complexity parameter of 0.045, post hoc pruning was conducted with rpart, and the package carat was used to assess the final decision tree's accuracy, sensitivity and specificity. RESULTS: Of the 22 variables, only 2 contributed toward the predictive splits: Feeling like "in a fog" and Sadness. The confusion matrix yielded a statistically significant accuracy of 0.7636 (P [accuracy > no information rate] = 0.00009678), sensitivity of 0.6429, specificity of 0.8889, positive predictive value of 0.8571, and negative predictive value of 0.7059. CONCLUSIONS: Decision tree analysis yielded a statistically significant decision tree model that can be used clinically to identify patients at initial presentation who are at a higher risk of having prolonged symptoms lasting 28 days or more postconcussion.

Determination of Background Concentrations of Ag, Pd, Pt and Au in Highly Mineralized Ground Waters at Sub-ng L-1 Concentrations by Online Matrix Separation/Pre-Concentration Coupled to ICP-SFMS.

Though not regulated in directives such as the Water Framework Directive of the European Union, the investigation of geogenic background concentrations of certain elements such as precious metals is of increasing interest, in particular for the early detection of a potential environmental pollution due to the increased use in various industrial and technological applications and in medicine. However, the precise and accurate quantification of precious metals in natural waters is challenging due to the complex matrices and the ultra-low concentrations in the (sub-) ng L-1 range. A methodological approach, based on matrix separation and pre-concentration on the strong anion exchange resin TEVA® Resin in an online mode directly coupled to ICP-SFMS, has been developed for the determination of Ag, Pt, Pd and Au in ground water. Membrane desolvation sample introduction was used to reduce oxide-based spectral interferences, which complicate the quantification of these metals with high accuracy. To overcome errors arising from matrix effects-in particular, the highly varying major ion composition of the investigated ground water samples-an isotope dilution analysis and quantification based on standard additions, respectively, were performed. The method allowed to process four samples per hour in a fully automated mode. With a sample volume of only 8 mL, enrichment factors of 6-9 could be achieved, yielding detection limits <1 ng L-1. Validation of the trueness was performed based on the reference samples. This method has been used for the analysis of the total concentrations of Ag, Pt, Pd and Au in highly mineralized ground waters collected from springs located in important geological fault zones of Austria's territory. Concentrations ranges of 0.21-64.2 ng L-1 for Ag, 0.65-6.26 ng L-1 for Pd, 0.07-1.55 ng L-1 for Pt and 0.26-1.95 ng L-1 for Au were found.

Lithium preserves peritoneal membrane integrity by suppressing mesothelial cell αB-crystallin.

Life-saving renal replacement therapy by peritoneal dialysis (PD) is limited in use and duration by progressive impairment of peritoneal membrane integrity and homeostasis. Preservation of peritoneal membrane integrity during chronic PD remains an urgent but long unmet medical need. PD therapy failure results from peritoneal fibrosis and angiogenesis caused by hypertonic PD fluid (PDF)-induced mesothelial cytotoxicity. However, the pathophysiological mechanisms involved are incompletely understood, limiting identification of therapeutic targets. We report that addition of lithium chloride (LiCl) to PDF is a translatable intervention to counteract PDF-induced mesothelial cell death, peritoneal membrane fibrosis, and angiogenesis. LiCl improved mesothelial cell survival in a dose-dependent manner. Combined transcriptomic and proteomic characterization of icodextrin-based PDF-induced mesothelial cell injury identified αB-crystallin as the mesothelial cell protein most consistently counter-regulated by LiCl. In vitro and in vivo overexpression of αB-crystallin triggered a fibrotic phenotype and PDF-like up-regulation of vascular endothelial growth factor (VEGF), CD31-positive cells, and TGF-ß-independent activation of TGF-ß-regulated targets. In contrast, αB-crystallin knockdown decreased VEGF expression and early mesothelial-to-mesenchymal transition. LiCl reduced VEGF release and counteracted fibrosis- and angiogenesis-associated processes. αB-crystallin in patient-derived mesothelial cells was specifically up-regulated in response to PDF and increased in peritoneal mesothelial cells from biopsies from pediatric patients undergoing PD, correlating with markers of angiogenesis and fibrosis. LiCl-supplemented PDF promoted morphological preservation of mesothelial cells and the submesothelial zone in a mouse model of chronic PD. Thus, repurposing LiCl as a cytoprotective PDF additive may offer a translatable therapeutic strategy to combat peritoneal membrane deterioration during PD therapy.

Peptide-PAINT Enables Investigation of Endogenous Talin with Molecular Scale Resolution in Cells and Tissues.

Talin is a cell adhesion molecule that is indispensable for the development and function of multicellular organisms. Despite its central role for many cell biological processes, suitable methods to investigate the nanoscale organization of talin in its native environment are missing. Here, we overcome this limitation by combining single-molecule resolved PAINT (points accumulation in nanoscale topography) imaging with the IRIS (image reconstruction by integrating exchangeable single-molecule localization) approach, enabling the quantitative analysis of genetically unmodified talin molecules in cells. We demonstrate that a previously reported peptide can be utilized to specifically label the two major talin isoforms expressed in mammalian tissues with a localization precision of <10 nm. Our experiments show that the methodology performs equally well as state-of-the-art single-molecule localization techniques, and the first applications reveal a thus far undescribed cell adhesion structure in differentiating stem cells. Furthermore, we demonstrate the applicability of this peptide-PAINT technique to mouse tissues paving the way to single-protein imaging of endogenous talin proteins under physiologically relevant conditions.

Complement in Renal Disease as a Potential Contributor to Arterial Hypertension.

OBJECTIVE: Complement deposition is prevalent in kidney biopsies of patients with arterial hypertension and hypertensive nephropathy, but an association of hypertension and complement deposition or involvement of complement in the pathogenesis of hypertensive nephropathy has not been shown to date. METHODS: In this study, we analyzed complement C1q and C3c deposition in a rat model of overload and hypertension by subtotal nephrectomy (SNX) and in archival human renal biopsies from 217 patients with known hypertension and 91 control patients with no history of hypertension using semiquantitative scoring of C1q and C3c immunohistochemistry and correlation with parameters of renal function. To address whether complement was only passively deposited or actively expressed by renal cells, C1q and C3 mRNA expression were additionally analyzed. RESULTS: Glomerular C1q and C3c complement deposition were significantly higher in kidneys of hypertensive SNX rats and hypertensive compared to nonhypertensive patients. Mean arterial blood pressure (BP) in SNX rats correlated well with the amount of glomerular C1q and C3c deposition and with left ventricular weight, as an indirect parameter of high BP. Quantitative mRNA analysis showed that C3 was not only deposited but also actively produced by glomerular cells of hypertensive SNX rats and in human renal biopsies. Of note, in patients CKD-stage correlated significantly with the intensity of glomerular C3c staining, but not with that of C1q. CONCLUSION: Renal complement deposition correlated with experimental hypertension as well as the presence of hypertension in a variety of renal diseases. To answer the question, if and how exactly renal complement is causative for the pathogenesis of arterial hypertension in men, further studies are needed.