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Exposure to mycotoxins through the dietary route occurs on a daily basis while their deleterious effects are exhibited in the form of ailments, such as inflammation, cancer, and hormonal imbalance. The negative impact of mycotoxins can be attributed to their interaction with various biomolecules and their interference in metabolic pathways. The activity of biomolecules, such as enzymes/receptors, which engage the intricate mechanism of endogenous metabolism, is more susceptible to disruption by metabolites of high toxicity, which gives rise to adverse health effects. Metabolomics is a useful analytical approach that can assist in unraveling such information. It can simultaneously and comprehensively analyze a large number of endogenous and exogenous molecules present in biofluids and can, thus, reveal biologically relevant perturbations following mycotoxin exposure. Information provided by genome, transcriptome and proteome analyses, which have been utilized for the elucidation of biological mechanisms so far, are further complemented by the addition of metabolomics in the available bioanalytics toolbox. Metabolomics can offer insight into complex biological processes and their respective response to several (co-)exposures. This review focuses on the most extensively studied mycotoxins reported in literature and their respective impact on the metabolome upon exposure. [ABSTRACT FROM AUTHOR]

Natural toxins produced by Alternaria fungi include the mycotoxins alternariol, tenuazonic acid and altertoxins I and II. Several of these toxins have shown high toxicity even at low levels including genotoxic, mutagenic, and estrogenic effects. However, the metabolic effects of toxin exposure from Alternaria are understudied, especially in the liver as a key target. To gain insight into the impact of Alternaria toxin exposure on the liver metabolome, rats (n = 21) were exposed to either (1) a complex culture extract with defined toxin profiles from Alternaria alternata (50 mg/kg body weight), (2) the isolated, highly genotoxic altertoxin-II (ATX-II) (0.7 mg/kg of body weight) or (3) a solvent control. The complex mixture contained a spectrum of Alternaria toxins including a controlled dose of ATX-II, matching the concentration of the isolated ATX-II. Liver samples were collected after 24 h and analyzed via liquid chromatography–high-resolution mass spectrometry (LC-HRMS). Authentic reference standards (> 100) were used to identify endogenous metabolites and exogenous compounds from the administered exposures in tandem with SWATH-acquired MS/MS data which was used for non-targeted analysis/screening. Screening for metabolites produced by Alternaria revealed several compounds solely isolated in the liver of rats exposed to the complex culture, confirming results from a previously performed targeted biomonitoring study. This included the altersetin and altercrasin A that were tentatively identified. An untargeted metabolomics analysis found upregulation of acylcarnitines in rats receiving the complex Alternaria extract as well as downregulation of riboflavin in rats exposed to both ATX-II and the complex mixture. Taken together, this work provides a mechanistic view of Alternari toxin exposure and new suspect screening insights into hardly characterized Alternaria toxins. [ABSTRACT FROM AUTHOR]

Children and adolescents with chronic health conditions are faced with ongoing challenges, making self-regulation crucial. As children grow up, they gradually develop differentiated beliefs about illness and treatment. While research indicates treatment beliefs as relevant factor on outcomes like adherence, the specific contents and dimensions of children's and adolescents' treatment beliefs remained unclear. This scoping review therefore aimed at the identification of treatment beliefs dimensions in children and adolescents with chronic health conditions, the underlying theoretical frameworks, and methodological operationalisation. Published literature was examined by applying systematic searches in electronic databases (Medline, PsycINFO, CINAHL) and comprehensive selection criteria, resulting in 49 included studies. The predominant treatment beliefs dimensions were necessity, concerns, perceived benefits and costs/barriers, and expectations. The latter can be differentiated into outcome, social, process, and structural expectations, and expectations of one's own role in the treatment process. In addition, dimensions that cover emotions and reasons for treatment were identified. The results are related to the methods and theoretical models applied, which were often adapted from adult research. However, additional and possibly more child-specific dimensions such as social expectations and emotions were found. This scoping review indicates several research gaps and discusses practical implications. [ABSTRACT FROM AUTHOR]

Humans are exposed to a cocktail of food-related and environmental contaminants, potentially contributing to the etiology of chronic diseases. Better characterizing the "exposome" is a challenging task and requires broad human biomonitoring (HBM). Veterinary drugs (VDs)/antibiotics, widely used and regulated in food and animal production, however, are typically not yet included in exposomics workflows. Therefore, in this work, a previously established multianalyte liquid chromatography-tandem mass spectrometry (LC-MS/MS) method covering >80 diverse xenobiotics was expanded by >40 VDs/antibiotics and pesticides. It was investigated if the generic workflow allowed for the successful integration of a high number of new analytes in a proof-of-principle study. The expanded method was successfully in-house validated and specificity, matrix effects, linearity, intra- and inter-day precision, accuracy, limits of quantification, and detection were evaluated. The optimized method demonstrated satisfactory recovery (81–120%) for most of the added analytes with acceptable RSDs (<20%) at three spiking levels. The majority of VDs/antibiotics and pesticides (69%) showed matrix effects within a range of 50–140%. Moreover, sensitivity was excellent with median LODs and LOQs of 0.10 ng/mL and 0.31 ng/mL, respectively. In total, the expanded method can be used to detect and quantify more than 120 highly diverse analytes in a single analytical run. To the best of the authors' knowledge, this work represents the first targeted biomonitoring method integrating VDs with various other classes of pollutants including plasticizers, PFAS, bisphenols, mycotoxins, and personal care products. It demonstrates the potential to expand targeted multianalyte methods towards additional groups of potentially toxic chemicals. [ABSTRACT FROM AUTHOR]

Background: Increased posterior tibial slope (PTS) has been identified as a risk factor for failure after anterior cruciate ligament (ACL) reconstruction. Correction of PTS may improve outcomes after revision ACL reconstruction. There are conflicting reports demonstrating the measurement of the PTS on standard short knee (SSK) radiographs versus full-length lateral (FLL) radiographs including the entire tibia. Purpose/Hypothesis: To compare PTS measurements between SSK and FLL radiographs in patients who failed primary ACL reconstruction. It was hypothesized that there would be high variability between the SSK and FLL radiographic measurements. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: The medial and lateral PTS were measured on the SSK and FLL radiographs of 33 patients with failed primary ACL reconstructions. All measurements were performed by 2 trained independent observers (A.A.M., J.S.), and inter- and intraobserver reliability were calculated using the intraclass correlation coefficient (ICC). Measurements recorded by the observer with the higher intraobserver ICC were used for comparison of the PTS on SSK versus FLL radiographs. Results: Both the inter- and the intraobserver reliability values of the PTS measurements were excellent. There was a significant difference in mean PTS on the medial plateau as measured on the SSK and FLL radiographs (11.2°± 5.3° vs 12.5°± 4.6°; P =.03), with the FLL radiographs demonstrating higher PTS. There was also a significant difference in the mean PTS on the lateral plateau as measured on SSK versus FLL radiographs (10.7°± 4.3° vs 12.2°± 4°, respectively; P =.01), with the FLL radiographs demonstrating higher PTS. Notably, 66.67% of the absolute measurements for PTS on the medial plateau differed by ≥2°, with variability as high as 8.5°. Conclusion: Results indicated that FLL and SSK radiographs are not interchangeable measurements for PTS associated with failed ACL reconstruction. Because FLL radiographs demonstrate less variability than SSK radiographs, we recommend obtaining them to evaluate these complex patients. [ABSTRACT FROM AUTHOR]

Aldosterone is a steroid hormone that is important for maintaining the volume and ionic composition of extracellular fluids and is produced in the zona glomerulosa of the adrenal cortex. The basic mechanisms controlling aldosterone secretion are known. However, more detailed studies on the regulation of aldosterone secretion often fail due to the lack of suitable models: although secretion can be studied in cultured adrenocortical cells under defined conditions, the differentiation status of the cells is difficult to control and the complex anatomy of the adrenal cortex is lost. In living animals, the physiological context is intact, but the influences are manifold and the examination conditions cannot be sufficiently controlled. One method that closes the gap between cell models and studies in living animals is the isolated perfused adrenal gland. In the past, this method has provided important data on the pathophysiology of adrenal glands from larger animals, but the technique was not used in mice. Here, we developed a method for isolation and perfusion of the mouse adrenal gland to study aldosterone secretion. This technique preserves the complex anatomical and functional context of the mouse adrenal cortex, to ensure defined experimental conditions and to minimize extra-adrenal influences. Initial series of experiments with the ex vivo perfused mouse adrenal gland show that this model offers the possibility for unique insights into pathophysiological regulatory principles and is suitable for the use of genetically modified mouse models. [ABSTRACT FROM AUTHOR]

The majority of transgender and gender-nonconforming people (TGNC) report negative experiences with doctors in the healthcare system. As there is little knowledge about the communication behaviour of doctors towards TGNC, this survey aimed to assess the self-reported trans-inclusive communication of doctors and their willingness to communicate trans-inclusively, as well as their self-perceived barriers to it. A mixed-methods survey was applied for this. Firstly, we measured self-reported trans-inclusive communication behaviour based on the CommTrans questionnaire. Based on this, the overall willingness, as well as self-perceived barriers (qualitative) to communication, were assessed. In total, N = 57 doctors took part in the survey. Most participants reported not introducing themselves using pronouns (79.4%). Of these, 61.4% said that they would not be able to do this in the future either. Perceived barriers were classified into the following eight categories: necessity, sample-dependency, habit, structural barriers in practice, uncertainties in dealing with the topic, limits of patient-centredness, gender as a binary concept, and transphobia. In summary, doctors in Germany show different degrees of trans-inclusive communication. It is likely that this has a negative effect on TGNC, their health and access to the healthcare system. [ABSTRACT FROM AUTHOR]

Exposure to polyphenols is relevant throughout critical windows of infant development, including the breastfeeding phase. However, the quantitative assessment of polyphenols in human breast milk has received limited attention so far, though polyphenols may positively influence infant health. Therefore, a targeted LC–MS/MS assay was developed to investigate 86 analytes representing different polyphenol classes in human breast milk. The sample preparation consisted of liquid extraction, salting out, freeze-out, and a dilution step. Overall, nearly 70% of the chemically diverse polyphenols fulfilled all strict validation criteria for full quantitative assessment. The remaining analytes did not fulfill all criteria at every concentration level, but can still provide useful semi-quantitative insights into nutritional and biomedical research questions. The limits of detection for all analyzed polyphenols were in the range of 0.0041–87 ng*mL−1, with a median of 0.17 ng*mL−1. Moreover, the mean recovery was determined to be 82% and the mean signal suppression and enhancement effect was 117%. The developed assay was applied in a proof-of-principle study to investigate polyphenols in breast milk samples provided by twelve Nigerian mothers at three distinct time points post-delivery. In total, 50 polyphenol analytes were detected with almost half being phenolic acids. Phase II metabolites, including genistein-7-β-D-glucuronide, genistein-7-sulfate, and daidzein-7-β-D-glucuronide, were also detected in several samples. In conclusion, the developed method was demonstrated to be fit-for-purpose to simultaneously (semi-) quantify a wide variety of polyphenols in breast milk. It also demonstrated that various polyphenols including their biotransformation products were present in breast milk and therefore likely transferred to infants where they might impact microbiome development and infant health. [ABSTRACT FROM AUTHOR]

Background: The Coordinated medical Care (CoCare) project aimed to improve the quality of medical care in nursing homes by optimizing collaboration between nurses and physicians. We analyze the impact of the CoCare intervention on overall survival. Methods: The effect of time-varying treatment on 3-year overall survival was analyzed with treatment as time-varying covariate within the entire cohort. To reduce bias due to non-random assignment to treatment groups, regression adjustment was applied. Therefore, age, sex, and level of care were used as potential confounders. Results: The study population consisted of 8,893 nursing home residents (NHRs), of which 1,330 participated in the CoCare intervention. The three-year overall survival was 49.8% in the entire cohort. NHRs receiving the intervention were associated with a higher survival probability compared to NHRs of the control group. In a univariable cox model with time-dependent treatment, the intervention was associated with a hazard ratio of 0.70 [95%CI 0.56–0.87, p = 0.002]. After adjustment for age, sex and level of care, the hazard ratio increased to 0.82 but was still significant [95%CI 0.71–0.96, p = 0.011]. Conclusion: The analysis shows that optimizing collaboration between nurses and physicians leads to better survival of NHRs in Germany. This adds to the already published favorable cost-benefit ratio of the CoCare intervention and shows that a routine implementation of optimized collaboration between nurses and physicians is highly recommended. [ABSTRACT FROM AUTHOR]

Introduction: To date, there has been little research on the general health literacy of trans and gender diverse individuals, even though previous research undermines the importance of good health literacy in this sample. The aim of the article is therefore to describe the general health literacy of trans and gender diverse individuals based on a German survey. Methods: In September 2022, a survey study was conducted in which health literacy was recorded using HLS-EU-16. Data will be presented descriptively; gender differences will be explored using a Χ2- test and a univariate analysis of variance (ANOVA). Results: Out of N = 223 participants, n = 129 individuals (57.8%) identified as non-binary; n = 49 (22.0%) identified themselves as male, while n = 45 (20.2%) identified as female. Mean age was 28.03 years. Overall, 26.4% of all the participants showed an inadequate health literacy, as proposed by the HLS-EU-16. In trend, health-related task related to media use were more often perceived as easy compared to the German general population. Conclusion: Individuals, who identify as trans and gender diverse may have a general health literacy below average compared to the German general population. However, tasks related to media use were perceived as easy, which might be a good starting point for health literacy related interventions. Trial registration: DRKS00026249, Date of registration: 15/03/2022. [ABSTRACT FROM AUTHOR]

Treatment beliefs play a crucial role for patient satisfaction and the treatment outcome in psychosomatic rehabilitation. The aim of this study was the development and the psychometric evaluation of an indication-specific questionnaire of beliefs about psychosomatic rehabilitation. The study was conducted at a psychosomatic rehabilitation clinic. The primary item list comprised k = 125 items. After a descriptive item analysis, we conducted an exploratory factor analysis. Furthermore, we tested reliability via McDonald's Omega and construct validity by analyzing correlations of the scales with related constructs. Of the N = 264 participants, 50% were female and the mean age was 50.4 (SD = 9.8) years. K = 85 items were suitable for factor analysis, which resulted in k = 30 items constituting six scales, explaining of 57% the overall variance. The corrected item-total correlations were between r = 0.48 and r = 0.83. Internal consistency ranged from ω = 0.81 to ω = 0.86. The newly developed questionnaire assesses specific treatment beliefs about inpatient psychosomatic rehabilitation. The psychometric properties of the six scales are acceptable. Further studies should confirm the psychometric results, such as the factorial structure of the questionnaire. Treatment beliefs are known to play an important role for the adherence, therapy outcome and satisfaction in psychosomatic rehabilitation. We developed and tested a indication-specific questionnaire assessing treatment beliefs in psychosomatic rehabilitation. The questionnaire can be used to explore patient's rehabilitation-related treatment beliefs, predict treatment outcomes, and to develop interventions attempting to modify these. [ABSTRACT FROM AUTHOR]

While meditation is commonly practiced by individuals on their own, several programmes have incorporated dyadic forms, too. However, the setting – meditating alone or in dyads – and its impact on the effects of meditation have not yet been examined. We expected that dyadic compassion meditation (CM) may improve perceived social closeness more compared to closely-matched individual CM. N = 50 couples were randomly assigned to do a brief 15-min CM induction either together with their partner or individually. Social closeness was rated by both partners. Secondary outcomes were positive and negative affect as well as parasympathetic response, indicated by heart rate variability (HRV). Due to the dyadic data structure, multilevel models were tested. We found no difference between dyadic and individual CM in self-report. After both forms social closeness and positive affect were improved, while negative affect decreased. Only HRV differed between the two conditions over time: while HRV significantly decreased in the individual condition, there was no such change in the dyadic condition. The accompanying physiological profile suggests that CM may involve effort at least in the individual CM. Done individually or with a partner, brief CM can foster social closeness and improve affect and can be employed to improve socio-emotional well-being. [ABSTRACT FROM AUTHOR]

Background: Providing adequate medical care to nursing home residents is challenging. Transfers to emergency departments are frequent, although often avoidable. We conducted the complex CoCare intervention with the aim to optimize nursing staff–physician collaboration to reduce avoidable hospital admissions and ambulance transportations, thereby reducing costs. Methods: This prospective, non-randomized study, based on German insurance data, includes residents in nursing homes. Health care cost from a payer perspective and cost–savings of such a complex intervention were investigated. The utilisation of services after implementation of the intervention was compared with services in previous quarters as well as services in the control group. To compensate for remaining differences in resident characteristics between intervention and control group, a propensity score was determined and adjusted for in the regression analyses. Results: The study population included 1240 residents in the intervention and 7552 in the control group. Total costs of medical services utilisation were reduced by €468.56 (p < 0.001) per resident and quarter in the intervention group. Hospital stays were reduced by 0.08 (p = 0.001) and patient transports by 0.19 (p = 0.049). This led to 1.66 (p < 0.001) avoided hospital days or €621.37 (p < 0.001) in costs–savings of inpatient services. More services were billed by general practitioners in the intervention group, which led to additional costs of €97.89 (p < 0.001). Conclusion: The benefits of our intervention clearly exceed its costs. In the intervention group, avoided hospital admissions led to additional outpatient billing. This indicates that such a multifactorial intervention program can be cost-saving and improve medical care in long-term care homes. [ABSTRACT FROM AUTHOR]

In the face of growing 21st-century urban challenges, this study emphasizes the role of remote sensing data in objectively defining urban structure types (USTs) based on morphology. While numerous UST delineation approaches exist, few are universally applicable due to data constraints or impractical class schemes. This article attempts to tackle this challenge by summarizing important approaches dealing with the computation of USTs and to condense their contributions to the field of research within a single comprehensive framework. Hereby, this framework not only serves as a conjunctive reference for currently existing implementations, but is also independent regarding the input data, spatial scale, or targeted purpose of the mapping. It consists of four major steps: (1) the collection of suitable data sources to describe the building morphology as a key input, (2) the definition of a spatial mapping unit, (3) the parameterization of the mapping units, and (4) the final classification of the mapping units into urban structure types. We outline how these tasks can lead to a UST classification which fits the users' needs based on their available input data. At the same time, the framework can serve as a protocol for future studies where USTs are mapped, or new approaches are presented. This article closes with an application example for three different cities to underline the flexibility and applicability of the proposed framework while maintaining maximized objectivity and comparability. We recommend this framework as a guideline for the use-specific mapping of USTs and hope to contribute to past and future research on this topic by fostering the implementation of this concept for the spatial analysis and a better understanding of complex urban environments. [ABSTRACT FROM AUTHOR]

Dermatophytosis is a superficial cutaneous infection, most commonly caused by fungal species such as Microsporum canis, Nannizzia gypsea (Microsporum gypseum), and Trichophyton mentagrophytes in dogs and cats. The zoonotic potential of these species is concerning, as companion animals are increasingly close to their owners. Therefore, the objectives of the study were to evaluate the current prevalence of Nannizzia -causing canine and feline dermatophytosis in Curitiba and Metropolitan Region, as well as perform phenotypic and phylogenetic characterizations of these isolates. Thus, 241 skin and fur samples from 163 dogs and 78 cats were analyzed from 2020 to 2021. The samples were obtained from animals of three sources: Veterinary Hospital of the Federal University of Paraná, animal shelters, and private clinics. The diagnosis was performed through phenotypic characterization and sequencing ITS rDNA region. Among 97 positive samples for dermatophytes, Nannizzia was identified in 14 (14.4%) samples, while other dermatophyte genera were found in the remaining 83 (85.6%) samples. Among the canine samples, nine (90%) were N. gypsea , and one (10%) was N. incurvata. Whereas in feline samples, three (75%) were N. gypsea , and one (25%) was N. incurvata. It was concluded that among 97 animals infected with dermatophytes, dogs (24.4%; 10/41) were significantly more affected by Nannizzia than cats (7.1%; 4/56) (P  < .05). According to molecular analyses, the ITS rDNA region provided satisfactory results for species-level identification of Nannizzia , confirming the first report of N. incurvata as an etiological agent of canine and feline dermatophytosis in Brazil. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with kidney function. By combining these findings with post-GWAS information (e.g., statistical fine-mapping to identify independent association signals and to narrow down signals to causal variants; or different sources of annotation data), new hypotheses regarding physiology and disease aetiology can be obtained. These hypotheses need to be tested in laboratory experiments, for example, to identify new therapeutic targets. For this purpose, the evidence obtained from GWAS and post-GWAS analyses must be processed and presented in a way that they are easily accessible to kidney researchers without specific GWAS expertise. Main: Here we present KidneyGPS, a user-friendly web-application that combines genetic variant association for estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease Genetics consortium with annotation of (i) genetic variants with functional or regulatory effects ("SNP-to-gene" mapping), (ii) genes with kidney phenotypes in mice or human ("gene-to-phenotype"), and (iii) drugability of genes (to support re-purposing). KidneyGPS adopts a comprehensive approach summarizing evidence for all 5906 genes in the 424 GWAS loci for eGFR identified previously and the 35,885 variants in the 99% credible sets of 594 independent signals. KidneyGPS enables user-friendly access to the abundance of information by search functions for genes, variants, and regions. KidneyGPS also provides a function ("GPS tab") to generate lists of genes with specific characteristics thus enabling customizable Gene Prioritisation (GPS). These specific characteristics can be as broad as any gene in the 424 loci with a known kidney phenotype in mice or human; or they can be highly focussed on genes mapping to genetic variants or signals with particularly with high statistical support. KidneyGPS is implemented with RShiny in a modularized fashion to facilitate update of input data (https://kidneygps.ur.de/gps/). Conclusion: With the focus on kidney function related evidence, KidneyGPS fills a gap between large general platforms for accessing GWAS and post-GWAS results and the specific needs of the kidney research community. This makes KidneyGPS an important platform for kidney researchers to help translate in silico research results into in vitro or in vivo research. [ABSTRACT FROM AUTHOR]

Taurine-respiring gut bacteria produce H2S with ambivalent impact on host health. We report the isolation and ecophysiological characterization of a taurine-respiring mouse gut bacterium. Taurinivorans muris strain LT0009 represents a new widespread species that differs from the human gut sulfidogen Bilophila wadsworthia in its sulfur metabolism pathways and host distribution. T. muris specializes in taurine respiration in vivo, seemingly unaffected by mouse diet and genotype, but is dependent on other bacteria for release of taurine from bile acids. Colonization of T. muris in gnotobiotic mice increased deconjugation of taurine-conjugated bile acids and transcriptional activity of a sulfur metabolism gene-encoding prophage in other commensals, and slightly decreased the abundance of Salmonella enterica, which showed reduced expression of galactonate catabolism genes. Re-analysis of metagenome data from a previous study further suggested that T. muris can contribute to protection against pathogens by the commensal mouse gut microbiota. Together, we show the realized physiological niche of a key murine gut sulfidogen and its interactions with selected gut microbiota members. Authors utilise a multi-omics approach for the ecophysiological characterization of a taurine-respiring mouse gut bacterium. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) affects a significant proportion of the population over the age of 60 years, and its prevalence is increasing. While symptomatic treatment is available for motor symptoms of PD, non‐motor complications such as dementia result in diminished life quality for patients and are far more difficult to treat. In this study, we analyzed PD‐associated alterations in the hippocampus of PD patients, since this brain region is strongly affected by PD dementia. We focused on synapses, analyzing the proteome of post‐mortal hippocampal tissue from 16 PD cases and 14 control subjects by mass spectrometry. Whole tissue lysates and synaptosomal fractions were analyzed in parallel. Differential analysis combined with bioinformatic network analyses identified neuronal pentraxin 1 (NPTX1) to be significantly dysregulated in PD and interacting with proteins of the synaptic compartment. Modulation of NPTX1 protein levels in primary hippocampal neuron cultures validated its role in synapse morphology. Our analysis suggests that NPTX1 contributes to synaptic pathology in late‐stage PD and represents a putative target for novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Trans and gender-diverse individuals experience adverse health outcomes that might be due, in addition to other factors, to stigma and discrimination in the health care sector. At the same time, the concept of person-centred care acknowledges the role of patient-physician communication in health care outcomes. This study aims to explore patient-physician communication preferences in trans and gender-diverse individuals. Method: A qualitative interview study was conducted, including N = 10 participants between February and March 2022. Participants were interviewed using a semi-structured interview guideline, based on previous knowledge in person-centred care and sample specific communication. Participants were asked about their experiences and wishes in patient-physician centeredness. Analyses were conducting using a qualitative content analysis strategy. Results: Mean age was 29.3 years; n = 6 participants identified themselves within the binary gender concept, while n = 4 identified themselves with a non-binary gender. Communication preferences for patient-physician communication were categorised into four themes: general communication aspects (e.g. active listening); the role of gender during appointments (e.g. appropriate/inappropriate addressing); gender-neutral language (e.g. experiences use of gender neutral language by physicians); own communication style (e.g. early outing and justification). Furthermore, possible contextual factors of patient-physician communication where found (e.g. trusting relationship). Conclusion: Adding knowledge to communication preferences of trans and gender-diverse individuals, this study was able to identify preferences that are specific to the sample as well as preferences that differ from the cis-gendered population. However, it remains unclear how the patient-physician communication preferences affects health care utilization and outcomes. Trial registration: German Clinical Trial Register (DRKS00026249). [ABSTRACT FROM AUTHOR]

The Microsporum canis complex consists of one zoophilic species, M. canis, and two anthropophilic species, M. audouinii and M. ferrugineum. These species are the most widespread zoonotic pathogens causing dermatophytosis in cats and humans worldwide. To clarify the evolutionary relationship between the three species and explore the potential host shift process, this study used phylogenetic analysis, population structure analysis, multispecies coalescent analyses, determination of MAT idiomorph distribution, sexual crosses, and macromorphology and physicochemical features to address the above questions. The complex of Microsporum canis, M. audouinii and M. ferrugineum comprises 12 genotypes. MAT1-1 was present only in M. canis, while the anthropophilic entities contained MAT1-2. The pseudocleistothecia were yielded by the mating behaviour of M. canis and M. audouinii. Growth rates and lipase, keratinolysis and urea hydrolytic capacities of zoophilic M. canis isolates were all higher than those of anthropophilic strains; DNase activity of M. ferrugineum exceeded that of M. canis. The optimum growth temperature was 28 °C, but 22 °C favoured the development of macroconidia. Molecular data, physicochemical properties and phenotypes suggest the adaptation of zoophilic M. canis to anthropophilic M. ferrugineum, with M. audouinii in an intermediate position. [ABSTRACT FROM AUTHOR]

Patients with chronic obstructive pulmonary disease (COPD) are still waiting for curative treatments. Considering its environmental cause, we hypothesized that COPD will be associated with altered epigenetic signaling in lung cells. We generated genome‐wide DNA methylation maps at single CpG resolution of primary human lung fibroblasts (HLFs) across COPD stages. We show that the epigenetic landscape is changed early in COPD, with DNA methylation changes occurring predominantly in regulatory regions. RNA sequencing of matched fibroblasts demonstrated dysregulation of genes involved in proliferation, DNA repair, and extracellular matrix organization. Data integration identified 110 candidate regulators of disease phenotypes that were linked to fibroblast repair processes using phenotypic screens. Our study provides high‐resolution multi‐omic maps of HLFs across COPD stages. We reveal novel transcriptomic and epigenetic signatures associated with COPD onset and progression and identify new candidate regulators involved in the pathogenesis of chronic lung diseases. The presence of various epigenetic factors among the candidates demonstrates that epigenetic regulation in COPD is an exciting research field that holds promise for novel therapeutic avenues for patients. Synopsis: New therapeutic targets are required for patients suffering from chronic obstructive pulmonary disease (COPD). Here, single CpG‐resolution DNA methylation maps of primary lung fibroblasts across disease stages reveal novel transcriptomic and epigenetic signatures associated with COPD onset and progression. DNA methylation and gene expression dynamics in lung fibroblasts from COPD patients were analyzedAberrant methylation was observed at enhancer and promoter elements in COPD fibroblastsDNA methylation patterns are changed early in COPD fibroblastsNovel regulators of fibroblast proliferation and differentiation in COPD were identified [ABSTRACT FROM AUTHOR]

Medicines are important for well-being. Thus, medication errors can have severe consequences, even death. Transfers between professionals and levels of care are a challenge in terms of medicines management. Norwegian governmental strategies encourage communication and collaboration between levels of care, and several initiatives are invested in to improve digital medicine management. In the project Electronic Medicines Management (eMM), we established an arena for inter-professional discussions about medicines management. This paper provides an example of how the eMM arena contributed to knowledge sharing and development in current medicines management practices at a nursing home. Building on communities of practice as a method we carried out the first of several sessions, with nine inter-professional participants. The results illustrate how discussion and agreement were reached on a common practice across different levels of care, and how the knowledge required bringing this knowledge back to the local practices. [ABSTRACT FROM AUTHOR]

This project sought to develop evidence-based guidelines for the administration of analgesics for moderate to severe pain by Emergency Medical Services (EMS) clinicians based on a separate, previously published, systematic review of the comparative effectiveness of analgesics in the prehospital setting prepared by the University of Connecticut Evidence-Based Practice Center for the Agency for Healthcare Research and Quality (AHRQ). A technical expert panel (TEP) was assembled consisting of subject matter experts in prehospital and emergency care, and the development of evidence-based guidelines and patient care guidelines. A series of nine "patient/population-intervention-comparison-outcome" (PICO) questions were developed based on the Key Questions identified in the AHRQ systematic review, and an additional PICO question was developed to specifically address analgesia in pediatric patients. The panel made a strong recommendation for the use of intranasal fentanyl over intravenous (IV) opioids for pediatric patients without intravenous access given the supporting evidence, its effectiveness, ease of administration, and acceptance by patients and providers. The panel made a conditional recommendation for the use of IV non-steroidal anti-inflammatory drugs (NSAIDs) over IV acetaminophen (APAP). The panel made conditional recommendations for the use of either IV ketamine or IV opioids; for either IV NSAIDs or IV opioids; for either IV fentanyl or IV morphine; and for either IV ketamine or IV NSAIDs. A conditional recommendation was made for IV APAP over IV opioids. The panel made a conditional recommendation against the use of weight-based IV ketamine in combination with weight-based IV opioids versus weight–based IV opioids alone. The panel considered the use of oral analgesics and a conditional recommendation was made for either oral APAP or oral NSAIDs when the oral route of administration was preferred. Given the lack of a supporting evidence base, the panel was unable to make recommendations for the use of nitrous oxide versus IV opioids, or for IV ketamine in combination with IV opioids versus IV ketamine alone. Taken together, the recommendations emphasize that EMS medical directors and EMS clinicians have a variety of effective options for the management of moderate to severe pain in addition to opioids when designing patient care guidelines and caring for patients suffering from acute pain. [ABSTRACT FROM AUTHOR]

Early human life is considered a critical window of susceptibility to external exposures. Infants are exposed to a multitude of environmental factors, collectively referred to as the exposome. The chemical exposome can be summarized as the sum of all xenobiotics that humans are exposed to throughout a lifetime. We review different exposure classes and routes that impact fetal and infant metabolism and the potential toxicological role of mixture effects. We also discuss the progress in human biomonitoring and present possiblemodels for studying maternal–fetal transfer. Data gaps on prenatal and infant exposure to xenobiotic mixtures are identified and include natural biotoxins, in addition to commonly reported synthetic toxicants, to obtain a more holistic assessment of the chemical exposome. We highlight the lack of large-scale studies covering a broad range of xenobiotics. Several recommendations to advance our understanding of the early-life chemical exposome and the subsequent impact on health outcomes are proposed. [ABSTRACT FROM AUTHOR]

Background: Psychosocial interventions are rapidly emerging in palliative care. However, randomized trials often fail to provide evidence for their effectiveness with regard to patient-reported outcomes. Stress biomarkers could complement self-report data, but little is known about their feasibility, acceptance, and interpretability. Methods: Therefore, we designed a randomized crossover trial in which 42 patients in a palliative care unit participated in both a brief mindfulness intervention (MI) and a resting state control condition (CC) on two consecutive afternoons. On each day, we collected four saliva samples in 20-min intervals using Salivettes© to determine salivary cortisol (sCort) and alpha-amylase (sAA) concentration levels. At all measurement points, self-rated well-being and stress as well as cardiovascular markers were assessed. Baseline measurements further included self-rated quality of life and clinician-rated functional status. Results: 78.6% of the patients provided the maximum number of 8 saliva samples and 62.2% reported no subjective difficulties with the sampling procedures. 66.6% (sCort) and 69.6% (sAA) of all possible samples were finally included in the analysis. Xerostomia and nausea were the main reasons for missing data. Higher sCort levels were associated with higher heart rate and lower quality of life, functional status, and heart rate variability. Corticosteroid and sedative medication as well as time since last meal were identified as potential confounders. Regarding reactivity to the MI, we found an overall decrease in sCort levels over time (b = -.03, p =.01), but this effect did not differ significantly between the study conditions (b =.03, p =.21). sAA levels were higher in men than in women. Trajectories over time did not significantly differ between the two conditions (b = -.02, p =.80) and associations with other stress and health-related constructs were weak. Conclusions: Findings indicate that sCort might serve as a psychobiological outcome in future palliative care trials. However, future research should refine the exact measurement and conceptualization strategies for sCort in palliative care research. High attrition rates should be expected in patients with xerostomia or nausea. Trial Registration: Registered at the German Clinical Trials Registry (DRKS00013135) at 04/12/2017. [ABSTRACT FROM AUTHOR]

Background: Psychosocial interventions are rapidly emerging in palliative care. However, randomized trials often fail to provide evidence for their effectiveness with regard to patient-reported outcomes. Stress biomarkers could complement self-report data, but little is known about their feasibility, acceptance, and interpretability. Methods: Therefore, we designed a randomized crossover trial in which 42 patients in a palliative care unit participated in both a brief mindfulness intervention (MI) and a resting state control condition (CC) on two consecutive afternoons. On each day, we collected four saliva samples in 20-min intervals using Salivettes© to determine salivary cortisol (sCort) and alpha-amylase (sAA) concentration levels. At all measurement points, self-rated well-being and stress as well as cardiovascular markers were assessed. Baseline measurements further included self-rated quality of life and clinician-rated functional status. Results: 78.6% of the patients provided the maximum number of 8 saliva samples and 62.2% reported no subjective difficulties with the sampling procedures. 66.6% (sCort) and 69.6% (sAA) of all possible samples were finally included in the analysis. Xerostomia and nausea were the main reasons for missing data. Higher sCort levels were associated with higher heart rate and lower quality of life, functional status, and heart rate variability. Corticosteroid and sedative medication as well as time since last meal were identified as potential confounders. Regarding reactivity to the MI, we found an overall decrease in sCort levels over time (b = -.03, p =.01), but this effect did not differ significantly between the study conditions (b =.03, p =.21). sAA levels were higher in men than in women. Trajectories over time did not significantly differ between the two conditions (b = -.02, p =.80) and associations with other stress and health-related constructs were weak. Conclusions: Findings indicate that sCort might serve as a psychobiological outcome in future palliative care trials. However, future research should refine the exact measurement and conceptualization strategies for sCort in palliative care research. High attrition rates should be expected in patients with xerostomia or nausea. Trial Registration: Registered at the German Clinical Trials Registry (DRKS00013135) at 04/12/2017. [ABSTRACT FROM AUTHOR]

Purpose: Patients' illness and treatment beliefs have been shown to predict health outcomes in many health care settings. However, information about their impact on patient satisfaction is scarce. The aim of this study was to investigate illness- and rehabilitation-related treatment beliefs and met rehabilitation-related treatment expectations and their relationship with patient satisfaction in psychosomatic rehabilitation. Methods: In a repeated measures study design, patients filled out questionnaires 2 to 3 weeks before the start of rehabilitation and at the end of an inpatient rehabilitation 6 to 7 weeks later. The predictive value of illness beliefs, treatment beliefs, and fulfilled treatment expectations regarding patient satisfaction was analyzed with multiple hierarchical regression analyses controlling for sociodemographic and clinical variables. Results: Two hundred sixty-four patients participated. The sample was composed of equal numbers of men and women (n = 129 each). The mean age was 50.4 years. Most patients had diagnoses from the ICD– 10 diagnostic group F3 (affective disorders; n = 145) or F4 (neurotic, stress-related and somatoform disorders; n = 94). Sociodemographic and clinical variables were not associated with patient satisfaction. The explained variance of patient satisfaction increased to 10% by adding illness beliefs (namely personal control and coherence) (p = 0.006), to 5% by adding rehabilitation-related treatment beliefs (namely concerns) (p = 0.063), and to 49% by adding fulfilled expectations (namely a positive discrepancy between expectations and experiences related to outcome expectations and related to participation and treatment structure, and a negative discrepancy between expectations and experiences related to concerns) (p < 0.001) as predictor variables. Conclusion: This study highlights the relationship of fulfilled (rehabilitation-related) treatment expectations with patient satisfaction in psychosomatic rehabilitation. Given the evidence underlining the importance of patients' illness and treatment beliefs and expectations, it is vital that these constructs are addressed in corresponding interventions. [ABSTRACT FROM AUTHOR]

We report a case of long-term complete response to selective intra-arterial radiation therapy in a 48-year-old female patient with metastatic liver disease from undifferentiated uterine sarcoma. [ABSTRACT FROM AUTHOR]

Some studies suggest a bi-directional association between low relationship quality and depression. However, the social impact of depression and the potential preventative effects of healthy relationships are not yet sufficiently understood, as studies have shown heterogenous results for effects in both directions. Therefore, the main aim of this study was to differentiate the actor and partner effects of this association more comprehensively using two measures to capture characteristics of relationship quality–firstly regarding general aspects of social system quality and secondly considering specific aspects of the romantic relationship. 110 different-sex couples were included, being separated in partners with highly pronounced depressive symptoms in women (Cw/DW) versus partners with low depressive symptoms (LDCs). We investigated effects cross-sectionally using multi-group analyses to predict relationship (couple specific questionnaire: PFB) versus system quality (general system quality questionnaire: EVOS) in a step-by-step approach, modelling actor and partner effects with variation within and across both groups and then comparing the results to models with equal actor and partner effects. Depression was measured with the PHQ-9. With regard to the relationship between depressive symptoms and system quality, the model that constrained actor and partner effects to be equal across both groups was preferred and showed negative significant actor effects across gender and groups. Concerning the association between depressive symptoms and relationship quality, the model constraining actor and partner effects to be equal within groups had the best fit to the data and revealed a negative partner effect in LDCs. Conclusions Controlling for the moderating variable of clinically relevant depressive symptoms, we found evidence for actor and partner effects, which differed between the two relationship measures. This underlines the importance to reflect how relationship quality is operationalized. The negative partner effect on relationship quality in LDCs emphasizes that even in a non-clinical context, depressive symptoms negatively impact the perceived relationship quality of both women and men. This suggests that addressing the relationship is important in non-clinical preventive contexts and calls for integrating the partner into counselling or trainings. [ABSTRACT FROM AUTHOR]

Grading of squamous cell carcinomas (SCCs) based on tumour budding and cell nest size has been termed cellular dissociation grading (CDG) and was suggested as a robust outcome predictor when assessed in biopsies and resections of various extrapulmonary SCCs. In pulmonary SCC (pSCC), this has so far been shown only for resected cancers. As most lung cancers are inoperable, it is of utmost importance to clarify whether the prognostic impact of CDG is retained in the biopsy setting. Two independent pSCC biopsy cohorts from Munich (n = 134, non‐resected) and Heidelberg (n = 135, resected) were assessed. Tumour budding and cell nest size measures were assembled into the three‐tiered CDG system (G1–G3). Data were correlated with clinicopathological parameters and overall‐ (OS), disease‐specific‐ (DSS), and disease‐free survival (DFS). Interobserver variability and concordance between biopsy and resection specimen were also investigated. CDG was highly congruent between biopsy and resection specimens (κ = 0.77, p < 0.001). In both pSCC cohorts, biopsy‐derived CDG strongly impacted on OS, DSS, and DFS (e.g. DFS: p < 0.001). In multivariate survival analyses, CDG remained a stage independent predictor of survival in both cohorts (DFS: p < 0.001 respectively; hazard ratio Munich cohort: CDG‐G2: 4.31, CDG‐G3; 5.14; Heidelberg cohort: CDG‐G2: 5.87, CDG‐G3: 9.07). Interobserver agreement for CDG was almost perfect (κ = 0.84, p < 0.001). We conclude that assessment of CDG based on tumour budding and cell nest size is feasible on pSCC biopsies and harbours stage independent prognostic information in resectable as well as non‐resectable pSCC. Integration of this grading approach into clinicopathological routine should be considered. [ABSTRACT FROM AUTHOR]

A microfluidic platform for continuous synthesis of hydrogel microparticles with superparamagnetic colloids (SPCs) embedded at prescribed positions is described. The shape of the cross‐linked microparticle is independently controlled by stop–flow lithography, whereas the position of trapped SPCs are dictated by virtual magnetic moulds made of 2D nickel patches facilitating magnetic trapping. The spatial positions of trapped SPCs collectively function as a binary code matrix for product authentication. Analytical and finite element methods are combined to optimize the trapping efficiency of SPCs by systematically investigating magnetic field microgradients produced by nickel patches. It is envisioned that the proposed magnetic microparticles will contribute to the development of soft matter inspired product quality control, tracking and anti‐counterfeiting technologies. [ABSTRACT FROM AUTHOR]

Depression occurs in an interpersonal dynamic and living with a depressed person can lead to a significant burden on the partner. Instruments measuring burden do not address couples and often measure caregiving for individuals with schizophrenic disorders. The partner burden in depression (PBD) questionnaire is a new instrument measuring PBD by asking individuals, (1) which symptoms they can observe in their depressed partners and (2) to which degree this burdens them. Hence, PBD combines measuring the awareness of observed depressive symptoms and the resulting burden. Additionally, it addresses aspects unique to couple relationships. Our German validation confirmed a one‐factor model with 12 items. The PBD had good psychometric properties and was sensitive to change. Partner burden predicted self‐reported depressive symptoms (PHQ‐9) over time. PBD is short, easily applicable in research and practice and can add to the understanding of partner effects in depression. [ABSTRACT FROM AUTHOR]

Additives and inoculants are the focus of silage research, as new additives and their combinations can improve fermentation and silage quality. We performed two trials evaluating two doses (4 and 8 g/t, wet weight) of natamycin as an additive to maize silage compared to a control without supplementation. In the first trial, we assessed fermentation losses, yeast count, chemical composition, and aerobic stability of maize silages stored in pilot-scale silos using four replicates per treatment. The second trial was designed to evaluate the voluntary intake and performance of lambs fed the treated silages prepared in bunker silos. The lambs (10 lambs/treatment) were kept in individual pens and fed twice daily a total-mixed ration containing one of the treated silages. The highest dose of natamycin decreased dry matter and gas losses. The yeast count in the silages from the bunker silos tended to increase (r = 0.92) over the weeks. There was no significant difference in voluntary feed intake or average daily gain of lambs fed natamycin silages compared to the control silage. Since high natamycin doses caused a decrease in fermentation losses in maize silage and exerted no deleterious effects on animal performance, this bacteriocin may soon be considered a potential component of silage additives. [ABSTRACT FROM AUTHOR]

Infants are sensitive to negative effects caused by food contaminants such as mycotoxins. To date, analytical methods assessing mycotoxin mixture exposure in infant stool are absent. Herein, we present a novel multi-mycotoxin LC-MS/MS assay capable of detecting 30+ analytes including the regulated mycotoxin classes (aflatoxins, trichothecenes, ochratoxins, zearalenone, citrinin), emerging Alternaria and Fusarium toxins, and several key metabolites. Sample preparation consisted of a 'dilute, filter, and shoot' approach. The method was in-house validated and demonstrated that 25 analytes fulfilled all required criteria despite the high diversity of chemical structures included. Extraction recoveries for most of the analytes were in the range of 65–114% with standard deviations below 30% and limits of detection between 0.03 and 11.3 ng/g dry weight. To prove the methods' applicability, 22 human stool samples from premature Austrian infants (n = 12) and 12-month-old Nigerian infants (n = 10) were analyzed. The majority of the Nigerian samples were contaminated with alternariol monomethyl ether (8/10) and fumonisin B1 (8/10), while fumonisin B2 and citrinin were quantified in some samples. No mycotoxins were detected in any of the Austrian samples. The method can be used for sensitive human biomonitoring (HBM) purposes and to support exposure and, potentially, risk assessment of mycotoxins. Moreover, it allows for investigating potential associations between toxicant exposure and the infants' developing gut microbiome. [ABSTRACT FROM AUTHOR]

Changes in DNA methylation identified by epigenome-wide association studies (EWAS) have been recently linked to increased lung cancer risk. However, the cellular effects of these differentially methylated positions (DMPs) are often unclear. Therefore, we investigated top differentially methylated positions identified from an EWAS study. This included a putative regulatory region of NHLRC1. Hypomethylation of this gene was recently linked with decreased survival rates in lung cancer patients. HumanMethylation450 BeadChip array (450K) analysis was performed on 66 lung cancer case-control pairs from the European Prospective Investigation into Cancer and Nutrition Heidelberg lung cancer EWAS (EPIC HD) cohort. DMPs identified in these pre-diagnostic blood samples were then investigated for differential DNA methylation in lung tumor versus adjacent normal lung tissue from The Cancer Genome Atlas (TCGA) and replicated in two independent lung tumor versus adjacent normal tissue replication sets with MassARRAY. The EPIC HD top hypermethylated DMP cg06646708 was found to be a hypomethylated region in multiple data sets of lung tumor versus adjacent normal tissue. Hypomethylation within this region caused increased mRNA transcription of the closest gene NHLRC1 in lung tumors. In functional assays, we demonstrate attenuated proliferation, viability, migration, and invasion upon NHLRC1 knock-down in lung cancer cells. Furthermore, diminished AKT phosphorylation at serine 473 causing expression of pro-apoptotic AKT-repressed genes was detected in these knock-down experiments. In conclusion, this study demonstrates the powerful potential for discovery of novel functional mechanisms in oncogenesis based on EWAS DNA methylation data. NHLRC1 holds promise as a new prognostic biomarker for lung cancer survival and prognosis, as well as a target for novel treatment strategies in lung cancer patients. [ABSTRACT FROM AUTHOR]

Digital medicines management is a high priority in Norwegian e-health strategies. A key challenge is the existence of multiple electronic information sources and systems, which require multi-professional cooperation. Lack of communication, understanding and collaboration between pharmacies, hospitals and community caregivers is also a challenge. Communities of practices (CoPs) have been used to establish arenas for discussing issues challenging the workflow to reach a common agreement on successful work practices for electronic medicines management. The purpose of this paper is to explore: How can we establish communities of practice (CoPs) to gather new knowledge on the facilitators and challenges for electronic medicines management practices in Norway? The results show engagement in establishing the CoPs and a willingness for joint enterprise. The establishment of the CoPs was performed simply based on established forms of collaboration. For CoPs to be effective, established alliances need to be expanded and renewed to form new group dynamics and thus a basis for new knowledge about electronic medicines management. [ABSTRACT FROM AUTHOR]

Objective: Compassion training seems to be a promising intervention for couples to improve individual psychopathology and relationship quality. Beyond studying the efficacy of training such as Cognitively-Based Compassion Training for Couples (CBCT-fC), it is important to gain insights into the putative mechanisms along the process. Methods: Theoretically derived presumed mechanisms of compassion training (clarification of values, self- regulation, decentering, and exposure) and additional therapeutic factors (emotional bond, social learning, and clarification of meaning) were studied over the course of a 10-session-long group-based CBCT-fC among women with depressive disorders. Results: Dyadic growth curve models indicated that emotional bond, social learning, and clarification of meaning increase over time in both partners. In decentering and clarification of values, women who suffered from depression showed a larger increase than men, while men had higher values at the start of the training. Conclusions: Women with depression seem to benefit from CBCT-fC in terms of an increase in decentering and value clarification, important mechanisms of compassion training. This study is the first to show that theoretically derived mechanisms of compassion and additional therapeutic factors can describe the process along secular contemplative training sessions, which are increasingly implemented in the health care system. Future studies should explore the relationship of mechanisms and the outcome along the process of the training. Study Registration: Trial registration number NCT03080025. [ABSTRACT FROM AUTHOR]

Motivation Chromatographic peak picking is among the first steps in data processing workflows of raw LC-HRMS datasets in untargeted metabolomics applications. Its performance is crucial for the holistic detection of all metabolic features as well as their relative quantification for statistical analysis and metabolite identification. Random noise, non-baseline separated compounds and unspecific background signals complicate this task. Results A machine-learning-based approach entitled PeakBot was developed for detecting chromatographic peaks in LC-HRMS profile-mode data. It first detects all local signal maxima in a chromatogram, which are then extracted as super-sampled standardized areas (retention-time versus m/z). These are subsequently inspected by a custom-trained convolutional neural network that forms the basis of PeakBot's architecture. The model reports if the respective local maximum is the apex of a chromatographic peak or not as well as its peak center and bounding box. In training and independent validation datasets used for development, PeakBot achieved a high performance with respect to discriminating between chromatographic peaks and background signals (accuracy of 0.99). For training the machine-learning model a minimum of 100 reference features are needed to learn their characteristics to achieve high-quality peak-picking results for detecting such chromatographic peaks in an untargeted fashion. PeakBot is implemented in python (3.8) and uses the TensorFlow (2.5.0) package for machine-learning related tasks. It has been tested on Linux and Windows OSs. Availability and implementation The package is available free of charge for non-commercial use (CC BY-NC-SA). It is available at https://github.com/christophuv/PeakBot. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Exposure to synthetic and natural chemicals is a major environmental risk factor in the etiology of many chronic diseases. Investigating complex co-exposures is necessary for a holistic assessment in exposome-wide association studies. In this work, a sensitive liquid chromatography-tandem mass spectrometry approach was developed and validated. The assay enables the analysis of more than 80 highly-diverse xenobiotics in urine, serum/plasma, and breast milk; with detection limits generally in the pg-ng mL−1 range. In plasma of extremely-premature infants, 27 xenobiotics are identified; including contamination with plasticizers, perfluorinated alkylated substances and parabens. In breast milk samples collected longitudinally over the first 211 days post-partum, 29 analytes are detected, including pyrrolizidine- and tropane alkaloids which have not been identified in this matrix before. A preliminary estimation of daily toxicant intake via breast milk is conducted. In conclusion, we observe significant early-life co-exposure to multiple toxicants, and demonstrate the method's applicability for large-scale exposomics-type cohort studies. Exposure to synthetic and natural toxicants is a major risk factor in the etiology of disease. Here, authors describe the development of a method to quantify >80 xenobiotics and apply it to assess early-life exposure in vulnerable infants. [ABSTRACT FROM AUTHOR]

In 2009, two groups independently linked human mutations in the inwardly rectifying K+ channel Kir4.1 (gene name KCNJ10) to a syndrome affecting the central nervous system (CNS), hearing, and renal tubular salt reabsorption. The autosomal recessive syndrome has been named EAST (epilepsy, ataxia, sensorineural deafness, and renal tubulopathy) or SeSAME syndrome (seizures, sensorineural deafness, ataxia, intellectual disability, and electrolyte imbalance), accordingly. Renal dysfunction in EAST/SeSAME patients results in loss of Na+, K+, and Mg2+ with urine, activation of the renin–angiotensin–aldosterone system, and hypokalemic metabolic alkalosis. Kir4.1 is highly expressed in affected organs: the CNS, inner ear, and kidney. In the kidney, it mostly forms heteromeric channels with Kir5.1 (KCNJ16). Biallelic loss-of-function mutations of Kir5.1 can also have disease significance, but the clinical symptoms differ substantially from those of EAST/SeSAME syndrome: although sensorineural hearing loss and hypokalemia are replicated, there is no alkalosis, but rather acidosis of variable severity; in contrast to EAST/SeSAME syndrome, the CNS is unaffected. This review provides a framework for understanding some of these differences and will guide the reader through the growing literature on Kir4.1 and Kir5.1, discussing the complex disease mechanisms and the variable expression of disease symptoms from a molecular and systems physiology perspective. Knowledge of the pathophysiology of these diseases and their multifaceted clinical spectrum is an important prerequisite for making the correct diagnosis and forms the basis for personalized therapies. [ABSTRACT FROM AUTHOR]

Purpose: Although research on psychosocial interventions in palliative care provided evidence for their effectiveness regarding patient-reported outcomes, few studies have examined their psychobiological effects yet. Therefore, the purpose of the present work as part of an overarching study was to investigate differential effects of music therapy versus mindfulness on subjective distress and both neuroendocrine and autonomic stress biomarkers. Methods: A total of 104 patients from two palliative care units were randomly assigned to three sessions of either music therapy or mindfulness. Before and after the second session (completed by 89 patients), participants rated their momentary distress and provided three saliva samples for cortisol and α-amylase analysis. Furthermore, photoplethysmography recordings were continuously assessed to calculate mean heart rate and heart rate variability. Data were analyzed using multilevel modeling of all available data and sensitivity analysis with multiply imputed data. Results: Between 67 and 75% of the maximally available data points were included in the primary analyses of psychobiological outcomes. Results showed a significant time*treatment effect on distress (b = − 0.83, p =.02) indicating a greater reduction in the music therapy group. No interaction effects were found in psychobiological outcomes (all p >.05), but multilevel models revealed a significant reduction in cortisol (b = − 0.06, p =.01) and mean heart rate (b = − 7.89, p =.05) over time following either intervention. Conclusion: Findings suggest a beneficial effect music therapy on distress while no differential psychobiological treatment effects were found. Future studies should continue to investigate optimal stress biomarkers for psychosocial palliative care research. Trial Registration: German Clinical Trials Register (DRKS)—DRKS00015308 (date of registration: September 7, 2018) [ABSTRACT FROM AUTHOR]